Steegers, E.A.P.

First-trimester crown-rump length and embryonic volume of aneuploid fetuses measured in virtual reality (Article)

2013-05-01T00:00:00Z

Objectives To examine whether embryonic volume (EV), as measured using three-dimensional (3D) ultrasound and a virtual reality approach, is a better measure of growth restriction than is crown-rump length (CRL) in aneuploid fetuses. Methods We retrospectively measured CRL and EV in prospectively collected 3D ultrasound volumes of 55 aneuploid fetuses using the Barco I-Space VR system. The gestational age ranged from 11 + 2 to 14 + 4 weeks. We compared our measured data with previously published reference curves for euploid fetuses. Delta-values were calculated by subtracting the expected mean for euploid fetuses of the same gestational age from observed values. The one-sample t-test was used to test the significance of differences observed. Results The CRL measurements of fetuses with trisomy 21 (n = 26), trisomy 13 (n = 5) and monosomy X (n = 5) were comparable with those of euploid fetuses, but in fetuses with trisomy 18 (n = 19) the CRL was 14.5% smaller (P < 0.001). The EV in fetuses with trisomies 21, 18 and 13 and monosomy X was smaller than in euploid fetuses (-27.8%, P < 0.001; -39.4%, P < 0.001; -40.9%, P = 0.004; and -27.3%, P = 0.055, respectively). Conclusions When relying on CRL measurements alone, first-trimester growth restriction is especially manifest in trisomy 18. Using EV, growth restriction is also evident in trisomies 21 and 13 and monosomy X. EV seems to be a more effective measurement for the assessment of first-trimester growth restriction in aneuploid fetuses. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd. Copyright

Social deprivation and adverse perinatal outcomes among Western and non-Western pregnant women in a Dutch urban population (Article)

2013-04-01T00:00:00Z

Social deprivation is considered a key factor in adverse perinatal outcomes. Rotterdam, the second largest city in The Netherlands, has large inequalities in perinatal health and a high number of deprived neighbourhoods. Social deprivation is measured here through a composite variable: 'Social Index' (SI). We studied the impact of the SI (2008-2009; 5 categories) in terms of perinatal mortality, congenital anomalies, preterm birth, small for gestational age (SGA) and low 5-minute Apgar score as registered in The Netherlands Perinatal Registry (Rotterdam 2000-2007, n = 56,443 singleton pregnancies). We applied ethnic dichotomisation as Western (European/North-American/Australian) vs. Non-Western (all others) ethnicity was expected to interact with the impact of SI. Tests for trend and multilevel regression analysis were applied. Gradually decreasing prevalence of adverse perinatal outcomes was observed in Western women from the lowest SI category (low social quality) to the highest SI category (high social quality). In Western women the low-high SI gradient for prevalence of spontaneous preterm birth (per 1000) changed from 57.2 to 34.1, for iatrogenic preterm birth from 35.2 to 19.0, for SGA from 119.6 to 59.4, for low Apgar score from 10.9 to 8.2, and for perinatal mortality from 14.9 to 7.6. These trends were statistically confirmed by Chi2-tests for trend (p < 0.001). For non-Western women such trends were absent. These strong effects for Western women were confirmed by significant odds ratios for almost all adverse perinatal outcomes estimated from multilevel regression analysis. We conclude social deprivation to play a different role among Western vs. non-Western women. Our results suggest that improvements in social quality may improve perinatal outcomes in Western women, but alternative approaches may be necessary for non-Western groups. Suggested explanations for non-Western 'migrant' groups include the presence of 'protective' effects through knowledge systems or intrinsic resilience. Implications concern both general and targeted policies. © 2013 Elsevier Ltd.

Levels of antibodies against tissue transglutaminase during pregnancy are associated with reduced fetal weight and birth weight (Article)

2013-04-01T00:00:00Z

Background & Aims: Celiac disease in pregnant women has been associated with poor growth of the fetus, but little is known about how the level of celiac disease affects fetal growth or birth outcomes. We assessed the associations between levels of antibodies against tissue transglutaminase (anti-tTG, a marker of celiac disease) and fetal growth and birth outcomes for pregnant women. Methods: We performed a population-based prospective birth cohort study of 7046 pregnant women. Serum samples were collected during the second trimester of pregnancy and analyzed for levels of anti-tTG. Based on these levels, the women were categorized into 3 groups: negative anti-tTG (≤0.79 U/mL; n = 6702), intermediate anti-tTG (0.8 to ≤6 U/mL; n = 308), or positive anti-tTG (>6 U/mL; n = 36). Data on fetal growth and birth outcomes were collected from ultrasound measurements and medical records. Results: Fetuses of women in the positive anti-tTG group weighed 16 g less than those of women in the negative anti-tTG group (95% confidence interval [CI], -32 to -1 g) during the second trimester and weighed 74 g less (95% CI, -140 to -8 g) during the third trimester. Newborns of women in the intermediate and positive anti-tTG groups weighed 53 g (95% CI, -106 to -1 g) and 159 g (95% CI, -316 to -1 g) less at birth, respectively, than those of women in the negative anti-tTG group. The reduction in birth weight in offspring of mothers in the intermediate anti-tTG group was 2-fold greater among mothers who carried HLA-DQ2 or -DQ8 than among those without HLA-DQ2 or -DQ8. Conclusions: Levels of anti-tTG in pregnant women are inversely associated with fetal growth. Growth was reduced to the greatest extent in fetuses of women with the highest levels of anti-tTG (>6 U/mL). Birth weight was also reduced in women with intermediate levels of anti-tTG (0.8 to ≤6 U/mL) and further reduced in those carrying HLA-DQ2 and -DQ8. © 2013 AGA Institute.

Chorionic villous vascularization related to phenotype and genotype in first trimester miscarriages in a recurrent pregnancy loss cohort (Article)

2013-04-01T00:00:00Z

STUDY QUESTION: Is there an association between chorionic villous vascularization, ultrasound findings and corresponding chromosome results in early miscarriage specimens from a cohort of recurrent pregnancy loss patients?SUMMARY ANSWERWe did not find a significant difference in vascularization scores of chorionic villi between embryonic, yolk sac or empty sac miscarriages, or between euploid and noneuploid miscarriages.WHAT IS KNOWN ALREADYAt least half of first trimester miscarriages are due to embryopathogenesis associated with chromosome errors and/or major congenital anomalies, resulting in an empty sac, a yolk sac or an embryonic miscarriage. Absent and decreased chorionic villous vascularization is usually present in these pregnancies.STUDY DESIGN, SIZE, DURATIONFor this retrospective study, 60 hematoxylin and eosin slides of miscarriage tissue of less than 10 weeks gestational age were collected from an academic institution. All patients were seen in consultation between July 2004 and October 2009.PARTICIPANTS, SETTING, METHODSChorionic villous vascularization was determined using a previously published classification. The results were validated and compared with the ultrasound findings and corresponding chromosome results. MAIN RESULTS AND THE ROLE OF CHANCE: There were 53 embryonic miscarriages, 5 yolk sac miscarriages and 2 empty sac miscarriages. Chromosome results were obtained in 59 of the 60 miscarriages; 37.3% were euploid and 62.7% were noneuploid. Validation of the vascularization score between observers was reasonable to good (Kappa 0.47-0.76), and 59% of the cases were classified as avascular. The vascularization score did not differ between euploid or noneuploid miscarriages, or between embryonic, yolk sac or empty sac miscarriages. Avascular villi were seen more frequently in miscarriages trisomic for chromosome 16, when compared with miscarriages with other trisomies (6 out of 7 versus 8 out of 22, P = 0.04). LIMITATIONS, REASONS FOR CAUTION: Unfortunately, the number of samples in the study was limited. WIDER IMPLICATIONS OF THE FINDINGS: Avascular villi may indicate abnormal early placentation as a part of embryopathogenesis. Further study is warranted to determine whether a genetic cause can be found to explain these results. © 2013 The Author.

Living in deprived urban districts increases perinatal health inequalities (Article)

2013-03-01T00:00:00Z

Objective: Analyses of the effects of place of residence, socioeconomic status and ethnicity on perinatal mortality and morbidity in the Netherlands. Methods: Epidemiological analysis of all singleton deliveries > 22 gestational weeks (871,889 live born and 5927 stillborn) from the Dutch National Perinatal Registry 2002-2006. Multiple logistic regression analysis was used to determine whether place of residence (deprived neighborhood, or not) contributed to the adverse perinatal outcome (defined as perinatal mortality, preterm birth, small for gestational age, congenital abnormalities or Apgar score <7, 5min after birth), additional to individual pregnancy characteristics, demographic characteristics, ethnic background and socioeconomic class. Results: Incidence of adverse perinatal outcome was 16.7%. After adjustment the excess risk for perinatal mortality in deprived districts was 21%, for preterm birth 16%, for small-for-gestational age 11%, and for Apgar score <7 after 5min 11%. Conclusions: Perinatal inequalities appear impressive in both urban and nonurban areas, with a significant additive risk of living in a deprived neighborhood. Excess risk for perinatal mortality generally outranges that for morbidity, suggesting both an etiological and prognostic pathway for neighborhood effects. A distinct pattern exists for congenital anomalies, for which first trimester adverse selection effects may be responsible.

A periconceptional energy-rich dietary pattern is associated with early fetal growth: The Generation R study (Article)

2012-12-04T00:00:00Z

Objective: To identify periconceptional maternal dietary patterns associated with crown-rump length (CRL), estimated fetal weight (EFW) and birthweight. Design: Population-based prospective birth cohort study. Setting: Rotterdam, the Netherlands. Participants: For this study, 847 pregnant Dutch women were eligible. Women were included between 2001 and 2005. Methods: Information on nutritional intake was collected by a semiquantitative food frequency questionnaire. For extracting dietary patterns, principal component factor analysis was used. Fetal growth was assessed using ultrasound measurements. Information on birth outcomes was retrieved from medical records. Multivariate regression analyses were used. Main outcome measures: Crown-to-rump length, estimated fetal weight in second and third trimester and birthweight. Results: An 'energy-rich dietary pattern' was identified, characterised by high intakes of bread, margarine and nuts. A significant association was shown between a high adherence to this dietary pattern (difference, mm: 2.15, 95% confidence interval 0.79-3.50) and CRL (linear trend analyses P = 0.015). No association was revealed between increasing adherence to this dietary pattern and EFW in second or third trimester, or birthweight. Conclusion: This study suggests that increasing adherence to an energy-rich dietary pattern is associated with increased CRL in the first trimester.

Differences in Quality of Antenatal Care Provided by Midwives to Low-Risk Pregnant Dutch Women in Different Ethnic Groups (Article)

2012-09-01T00:00:00Z

Introduction: The objective of this study was to evaluate whether differences existed in the adherence to the Dutch national guidelines regarding basic antenatal care by Dutch midwives for low-risk women of different ethnic groups. Methods: This was an observational study using data from electronic antenatal charts of 7 midwife practices (23 midwives), participating in the Generation R Study. The Generation R Study is a multiethnic, population-based, prospective, cohort study that is investigating the growth, development, and health of urban children from fetal life until young adulthood. The study is conducted in Rotterdam, The Netherlands. The antenatal charts of 2093 low-risk pregnant women with an expected birthing date in 2002 through 2004 were used to determine the mean quality of antenatal care scores for 7 ethnic groups. These scores reflected the degree of adherence to the guidelines regarding 10 tests and examinations. Results: Few differences between ethnic groups were found in adherence to the guidelines that addressed the obstetric-technical quality of antenatal care. This finding applied more to nulliparous than to multiparous women. Adherence to guidelines was not always better in the antenatal care provided to native Dutch multiparous women when compared to other ethnic groups. Midwives adhered well to the guidelines regarding most tests. For all women, irrespective of ethnic background, hemoglobin was not measured as often as recommended, and this was especially the case for Moroccan, Surinamese-Creole, and Dutch-Antillean multiparous women. Discussion: The poorer adherence regarding screening for hemoglobin needs further investigation, as women with African or Mediterranean heritage are more at risk for hemoglobinopathies. However, in general, midwives adhered well to the clinical guidelines regarding most tests irrespective of the ethnic background of the pregnant women. When differences were present, these were not systematically less favorable for non-Dutch pregnant women.

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2012-01-01T00:00:00Z

Mede vanwege de hoge Rotterdamse perinatale sterfte en -morbiditeit is in 2008 het meerjarig programma Klaar voor een Kind van start gegaan. Hiermee wil de Gemeente Rotterdam in samenwerking met het Erasmus MC en de GGD Rotterdam Rijnmond de perinatale sterfte en -morbiditeit binnen Rotterdam verminderen. Gebruik makend van de Perinatale Registratie Nederland 2000-2007 (n=56.443 eenling zwangerschappen) is gekeken naar het voorkomen van perinatale sterfte en ziekte in de verschillende Rotterdamse deelgemeenten, zowel absoluut als gestandaardiseerd. Hierbij lag het accent op de zogenoemde ‘Big4’ aandoeningen: aangeboren afwijkingen, vroeggeboorte, laag geboortegewicht gelet op de zwangerschapsduur en een lage Apgar score. Daarnaast zijn ook enkele kenmerken met betrekking tot de zwangere en haar zwangerschap bekeken. Binnen Rotterdam blijken er grote verschillen te bestaan in perinatale sterfte en -morbiditeit tussen verschillende deelgemeenten. De achtergrond verschilt hoogstwaarschijnlijk per deelgemeente. Waar het in de ene deelgemeente veelal een gecombineerd probleem is van zorgfactoren en omgevingsfactoren zal het in de andere deelgemeente voornamelijk een kwestie zijn van kenmerken van de zwangere zelf (bijvoorbeeld leefstijl, leeftijd of etniciteit). Deze gegevens zijn van groot belang bij het ontwikkelen van beleid gericht op deelgemeente specifieke problemen ter vermindering van de perinatale sterfte en -morbiditeit binnen de stad Rotterdam.

Planned Home Compared With Planned Hospital Births in the Netherlands: Intrapartum and Early Neonatal Death in Low-Risk Pregnancies (Letter To Editor)

2012-01-01T00:00:00Z

We read with interest the article by van der Kooy et al reporting on planned home compared with planned hospital births.1 We previously have reported on the same question in the same cohort and found no difference between the two groups. 2 The authors state that previous studies have compared outcomes after exclusion of pregnant women who, in view of the delivery guidelines, should not deliver at home. Second, they state that previous studies did not apply case-mix analysis, assuming risk equivalence of the home and hospital groups.

Amino acid metabolism in the human fetus at term: Leucine, valine, and methionine kinetics (Article)

2011-12-01T00:00:00Z

Human fetal metabolism is largely unexplored. Understanding how a healthy fetus achieves its fast growth rates could eventually play a pivotal role in improving future nutritional strategies for premature infants. To quantify specific fetal amino acid kinetics, eight healthy pregnant women received before elective cesarean section at term, continuous stable isotope infusions of the essential amino acids [1-13C,15N]leucine, [U-13C5]valine, and [1-13C]methionine. Umbilical blood was collected after birth and analyzed for enrichments and concentrations using mass spectrometry techniques. Fetuses showed considerable leucine, valine, and methionine uptake and high turnover rates. α-Ketoisocaproate, but not α-ketoisovalerate (the leucine and valine ketoacids, respectively), was transported at net rate from the fetus to the placenta. Especially, leucine and valine data suggested high oxidation rates, up to half of net uptake. This was supported by relatively low α-ketoisocaproate reamination rates to leucine. Our data suggest high protein breakdown and synthesis rates, comparable with, or even slightly higher than in premature infants. The relatively large uptakes of total leucine and valine carbon also suggest high fetal oxidation rates of these essential branched chain amino acids.

Blood pressure tracking during pregnancy and the risk of gestational hypertensive disorders: The Generation R Study (Article)

2011-12-01T00:00:00Z

Aims Blood pressure tracking can be used to examine the predictability of future values by early measurements. In a population-based prospective cohort study, among 8482 pregnant women, we examined whether blood pressure in early pregnancy tracks to third trimester and whether this tracking is influenced by maternal characteristics and is associated with the risk of gestational hypertensive disorders. Methods and resultsBlood pressure was measured in each trimester of pregnancy. Information about doctor-diagnosed pregnancy-induced hypertension and preeclampsia was obtained from medical records. Correlation coefficients between first and third trimester for systolic and diastolic blood pressure were 0.47 and 0.46, respectively. The odds ratio for staying in the highest tertile from first to third trimester for systolic blood pressure was 3.09 [95 confidence interval (CI): 2.73, 3.50] and for diastolic blood pressure 3.28 (95 CI: 2.90, 3.69). Blood pressure tracking coefficients were lower in younger, shorter, and non-European women and in women with higher gestational weight gain. Systolic and diastolic blood pressure changes from second to third trimester, but not from first to second trimester, were positively associated with the risks of pregnancy-induced hypertension and preeclampsia. ConclusionBlood pressure tracks moderately during pregnancy and is influenced by maternal characteristics. Second to third trimester increases in systolic and diastolic blood pressure are associated with an increased risk of gestational hypertensive disorders. Published on behalf of the European Society of Cardiology.

C-reactive protein levels, blood pressure and the risks of gestational hypertensive complications: The Generation R Study (Article)

2011-12-01T00:00:00Z

OBJECTIVES: Aim of this study was to investigate the associations of C-reactive protein levels, as marker of low-grade inflammation, with blood pressure development during pregnancy and the risks of gestational hypertensive complications. We also explored the role of maternal BMI in these associations. METHODS: High-sensitivity C-reactive protein levels were measured in early pregnancy (median 13.2 weeks, 95% range 9.6-17.6) in 5816 mothers participating in a population-based prospective cohort study in the Netherlands. Blood pressure measurements were performed in each trimester. Information about pregnancy-induced hypertension and preeclampsia was retrieved from hospital charts of the women. RESULTS: Longitudinal analyses showed that C-reactive protein levels were not associated with SBP and DBP patterns throughout pregnancy. Trimester-specific multivariate linear regression models showed that as compared to low C-reactive protein levels (<5.0 mg/l), elevated levels (≥20.0 mg/l) were associated with maternal SBP and DBP. Elevated C-reactive protein levels in early pregnancy were associated with the risks of pregnancy-induced hypertension [odds ratio (OR) 2.78, 95% confidence interval (CI) 1.66-4.66]. After adjustment for maternal BMI, all associations attenuated. CONCLUSION: Our results suggest that first-trimester C-reactive protein levels are associated with SBP and DBP levels throughout pregnancy and with gestational hypertensive complications, but these associations are largely explained by maternal BMI.

First experience with enzyme replacement therapy during pregnancy and lactation in Pompe disease (Article)

2011-12-01T00:00:00Z

Enzyme replacement therapy (ERT) with alglucosidase alfa was registered as a treatment for Pompe disease in 2006. It is as yet unknown whether ERT can be safely applied during pregnancy and lactation.A primiparous 40-year-old woman diagnosed with Pompe disease continued receiving ERT during pregnancy and lactation. Before pregnancy, she had moderate limb-girdle weakness and used nocturnal ventilation. During pregnancy, her clinical condition remained fairly stable until the 25th gestational week. Thereafter she experienced more problems with mobility and respiration. Fetal growth was normal as monitored by regular ultrasound investigations. A healthy boy was born at a gestational age of 37. weeks and 5. days by elective Cesarean section. There were no maternal complications and the child developed normally. One year after delivery the mother's physical condition was similar as prior to her pregnancy. Pharmacokinetic studies following enzyme infusion showed that alglucosidase alfa was secreted into the breast milk. Activity levels in the milk (245. nmol/ml.h) peaked at 2.5. h after the end of the infusion; which was 2. h later than in the plasma (80 μmol/ml.h). Twenty-four hours after start of the infusion, the enzyme activity in the breast milk was back to the pre-infusion level.In this case report, the continuation of treatment with alglucosidase alfa during pregnancy and lactation has been safe for the mother and the child.

Assessment of maternal smoking status during pregnancy and the associations with neonatal outcomes (Article)

2011-12-01T00:00:00Z

Introduction: Single assessment of smoking during pregnancy may lead to misclassification due to underreporting or failure of smoking cessation. We examined the percentage of mothers who were misclassified in smoking status based on single assessment, as compared with repeated assessment, and whether this misclassification leads to altered effect estimates for the associations between maternal smoking and neonatal complications. Methods: This study was performed in 5,389 mothers participating in a prospective population-based cohort study in the Netherlands. Smoking status was assessed 3 times during pregnancy using questionnaires. Information on birth weight and neonatal complications was obtained from hospital records. Results: For categorizing mothers per smoking status, Cohen's Kappa coefficient was .86 (p < .001) between single and repeated assessments. Of all mothers who reported nonsmoking or first trimester-only smoking in early pregnancy, 1.7% (70 of 4,141) and 33.7% (217 of 643), respectively, were reclassified to continued smoking based on repeated assessment. Younger, shorter lower educated mothers who had non-European ethnicity experienced more stress, consumed more alcohol, and did not use folic acid supplements had higher risk of underreporting their smoking status or failure of smoking cessation. Marginal differences were found on the associations of maternal smoking with neonatal complications between single or repeated assessment. Conclusions: Our results suggest that single assessment of smoking during pregnancy leads to underestimation of the continued smoking prevalence, especially among mothers who reported quitting smoking in first trimester. However, this underestimation does not materially change the effect estimates for the associations between maternal smoking and neonatal outcomes.

Individually customised fetal weight charts derived from ultrasound measurements: the Generation R Study (Article)

2011-11-24T00:00:00Z

Maternal and fetal characteristics are important determinants of fetal growth potential, and should ideally be taken into consideration when evaluating fetal growth variation. We developed a model for individually customised growth charts for estimated fetal weight, which takes into account physiological maternal and fetal characteristics known at the start of pregnancy. We used fetal ultrasound data of 8,162 pregnant women participating in the Generation R Study, a prospective, population-based cohort study from early pregnancy onwards. A repeated measurements regression model was constructed, using backward selection procedures for identifying relevant maternal and fetal characteristics. The final model for estimating expected fetal weight included gestational age, fetal sex, parity, ethnicity, maternal age, height and weight. Using this model, we developed individually customised growth charts, and their corresponding standard deviations, for fetal weight from 18 weeks onwards. Of the total of 495 fetuses who were classified as small size for gestational age (<10th percentile) when fetal weight was evaluated using the normal population growth chart, 80 (16%) were in the normal range when individually customised growth charts were used. 550 fetuses were classified as small size for gestational age using individually customised growth charts, and 135 of them (25%) were classified as normal if the unadjusted reference chart was used. In conclusion, this is the first study using ultrasound measurements in a large population-based study to fit a model to construct individually customised growth charts, taking into account physiological maternal and fetal characteristics. These charts might be useful for use in epidemiological studies and in clinical practice.

Planned home compared with planned hospital births in the netherlands: Intrapartum and early neonatal death in low-risk pregnancies (Article)

2011-11-01T00:00:00Z

Objective: The purpose of our study was to compare the intrapartum and early neonatal mortality rate of planned home birth with planned hospital birth in community midwife-led deliveries after case mix adjustment. Methods: The perinatal outcome of 679,952 low-risk women was obtained from the Netherlands Perinatal Registry (2000-2007). This group represents all women who had a choice between home and hospital birth. Two different analyses were performed: natural prospective approach (intention-to-treat-like analysis) and perfect guideline approach (per-protocol-like analysis). Unadjusted and adjusted odds ratios (ORs) were calculated. Case mix was based on the presence of at least one of the following: congenital abnormalities, small for gestational age, preterm birth, or low Apgar score. We also investigated the potential risk role of intended place of birth. Multivariate stepwise logistic regression was used to investigate the potential risk role of intended place of birth. Results: Intrapartum and neonatal death at 0-7 days was observed in 0.15% of planned home compared with 0.18% in planned hospital births (crude relative risk 0.80, 95% confidence interval [CI] 0.71-0.91). After case mix adjustment, the relation is reversed, showing nonsignificant increased mortality risk of home birth (OR 1.05, 95% CI 0.91-1.21). In certain subgroups, additional mortality may arise at home if risk conditions emerge at birth (up to 20% increase). Conclusion: Home birth, under routine conditions, is generally not associated with increased intrapartum and early neonatal death, yet in subgroups, additional risk cannot be excluded.

Intrauterine cannabis exposure leads to more aggressive behavior and attention problems in 18-month-old girls (Article)

2011-11-01T00:00:00Z

Background: The development of the fetal endocannabinoid receptor system may be vulnerable to maternal cannabis use during pregnancy and may produce long-term consequences in children. In this study, we aimed to determine the relationship between gestational cannabis use and childhood attention problems and aggressive behavior. Methods: Using a large general population birth cohort, we examined the associations between parental prenatal cannabis and tobacco use and childhood behavior problems at 18 months measured using the Child Behavior Checklist in N= 4077 children. Substance use was measured in early pregnancy. Results: Linear regression analyses demonstrated that gestational exposure to cannabis is associated with behavioral problems in early childhood but only in girls and only in the area of increased aggressive behavior (B= 2.02; 95% CI: 0.30-3.73; p= 0.02) and attention problems (B= 1.04; 95% CI: 0.46-1.62; p< 0.001). Furthermore, this study showed that long-term (but not short term) tobacco exposure was associated with behavioral problems in girls (B= 1.16; 95% CI: 0.20-2.12; p= 0.02). There was no association between cannabis use of the father and child behavior problems. Conclusions: Our results suggest that intrauterine exposure to cannabis is associated with an increased risk for aggressive behavior and attention problems as early as 18 months of age in girls, but not boys. Further research is needed to explore the association between prenatal cannabis exposure and child behavior at later ages. Our data support educating future mothers about the risk to their babies should they smoke cannabis during pregnancy.

Blood pressure in different gestational trimesters, fetal growth, and the risk of adverse birth outcomes (Article)

2011-10-01T00:00:00Z

Researchers have suggested that maternal hypertensive disorders during pregnancy affect fetal growth. The authors examined the associations between systolic and diastolic blood pressures in different trimesters of pregnancy and both repeatedly measured fetal growth characteristics and the risks of adverse birth outcomes. The present study (2001-2005) was performed in 8,623 women who were participating in a population-based prospective cohort study from fetal life onwards. Blood pressure and fetal growth characteristics were assessed in each trimester of pregnancy. Information on hypertensive complications and adverse birth outcomes was obtained from medical records. The results suggested that higher blood pressure was associated with smaller fetal head circumference and femur length, as well as lower fetal weight from the third trimester onward. An increase in blood pressure from the second trimester to the third trimester was associated with an increased risk of adverse birth outcomes. Compared with women who did not experience hypertension during pregnancy, women with preeclampsia had increased risks of having children who were preterm (odds ratio = 5.89, 95% confidence interval: 2.63, 13.14), had a low birth weight (odds ratio = 8.94, 95% confidence interval: 6.19, 12.90), or were small for their gestational age (odds ratio = 5.03, 95% confidence interval: 3.31, 7.62). The present results suggest that higher maternal blood pressure is associated with impaired fetal growth during the third trimester of pregnancy and increased risks of adverse birth outcomes.

Fetal and infant growth and the risk of obesity during early childhood: The generation R study (Article)

2011-10-01T00:00:00Z

Objective: To examine whether infant growth rates are influenced by fetal growth characteristics and are associated with the risks of overweight and obesity in early childhood. Design: This study was embedded in the Generation R Study, a population-based prospective cohort study from fetal life onward. Methods: Fetal growth characteristics (femur length (FL) and estimated fetal weight (EFW)) were assessed in the second and third trimesters and at birth (length and weight). Infant peak weight velocity (PWV), peak height velocity (PHV), and body mass index at adiposity peak (BMIAP) were derived for 6267 infants with multiple height and weight measurements. Results: EFW measured during the second trimester was positively associated with PWV and BMIAP during infancy. Subjects with a smaller weight gain between the third trimester and birth had a higher PWV. FL measured during the second trimester was positively associated with PHV. Gradual length gain between the second and third trimesters and between the third trimester and birth were associated with higher PHV. Compared with infants in the lowest quintile, the infants in the highest quintile of PWV had strongly increased risks of overweight/obesity at the age of 4 years (odds ratio (95% confidence interval): 15.01 (9.63, 23.38)). Conclusion: Fetal growth characteristics strongly influence infant growth rates. A higher PWV, which generally occurs in the first month after birth, was associated with an increased risk of overweight and obesity at 4 years of age. Longer follow-up studies are necessary to determine how fetal and infant growth patterns affect the risk of disease in later life.

Postpartum fepression after mild and severe preeclampsia (Article)

2011-10-01T00:00:00Z

Objective: To describe the prevalence of postpartum depressive symptoms after preeclampsia, to assess the extent to which the prevalence of postpartum depressive symptoms differs after mild and severe preeclampsia, and to investigate which factors contribute to such differences. Methods: Women diagnosed with preeclampsia (n=161) completed the Edinburgh Postnatal Depression Scale (EPDS) at 6, 12, or 26 weeks postpartum. Multiple logistic regression analysis was used to investigate the association between severity of preeclampsia, contributing factors and postpartum depression (PPD) (1) at any time during the first 26 weeks postpartum and (2) accounting for longitudinal observations at three time points. Results: After mild preeclampsia, 23% reported postpartum depressive symptoms at any time up to 26 weeks postpartum compared to 44% after severe preeclampsia (unadjusted odds ratio [OR] 2.65, 95% confidence interval [CI] 1.16-6.05) for depression at any time up to 26 weeks postpartum (unadjusted OR 2.57, 95% CI, 1.14-5.76) while accounting for longitudinal observations. Admission to the neonatal intensive care unit (NICU) (adjusted OR 3.19, 95% CI 1.15-8.89) and perinatal death (adjusted OR 2.96, 95% CI 1.09-8.03) contributed to this difference. Conclusions: It appears that not the severity of preeclampsia itself but rather the consequences of the severity of the disease (especially admission to the NICU and perinatal death) cause postpartum depressive symptoms. Obstetricians should be aware of the high risk of postpartum depressive symptoms after severe preeclampsia, particularly among women whose infant has been admitted to the NICU or has died.

Poor Health-related Quality of Life After Severe Preeclampsia (Article)

2011-09-01T00:00:00Z

Background: Preeclampsia is a major complication of pregnancy associated with increased maternal morbidity and mortality, and adverse birth outcomes. The objective of this study was to describe changes in all domains of health-related quality of life between 6 and 12weeks postpartum after mild and severe preeclampsia; to assess the extent to which it differs after mild and severe preeclampsia; and to assess which factors contribute to such differences. Methods: We conducted a prospective multicenter cohort study of 174 postpartum women who experienced preeclampsia, and who gave birth between February 2007 and June 2009. Health-related quality of life was measured at 6 and 12weeks postpartum by the RAND 36-item Short-Form Health Survey (SF-36). The population for analysis comprised women (74%) who obtained scores on the questionnaire at both time points. Results: Women who experienced severe preeclampsia had a lower postpartum health-related quality of life than those who had mild preeclampsia (all p<0.05 at 6wk postpartum). Quality of life improved on almost all SF-36 scales from 6 to 12weeks postpartum (p<0.05). Compared with women who had mild preeclampsia, those who experienced severe preeclampsia had a poorer mental quality of life at 12weeks postpartum (p<0.05). Neonatal intensive care unit admission and perinatal death were contributing factors to this poorer mental quality of life. Conclusions: Obstetric caregivers should be aware of poor health-related quality of life, particularly mental health quality of life in women who have experienced severe preeclampsia (especially those confronted with perinatal death or their child's admission to a neonatal intensive care unit), and should consider referral for postpartum psychological care. (BIRTH 38:3 September 2011) © 2011, the Authors. Journal compilation

Tailored preconceptional dietary and lifestyle counselling in a tertiary outpatient clinic in the Netherlands (Article)

2011-09-01T00:00:00Z

Background Adverse reproductive performance has been linked to unhealthy dietary intake and lifestyles. Our objectives were to investigate the prevalence of unhealthy dietary intake and lifestyles before conception and to evaluate whether tailored preconception counselling modifies these behaviours. Methods Between October 2007 and April 2009, 419 couples received tailored preconception dietary and lifestyle counselling at the outpatient clinic of Obstetrics and Gynaecology of the Erasmus University Medical Center Rotterdam, the Netherlands. A subgroup (n = 110 couples) was counselled twice with a fixed time interval of 3 months. Self-administered questionnaires were used for tailored dietary and lifestyle counselling. A cumulative score based on six Dutch dietary guidelines was displayed in the personal Preconception Dietary Risk score (PDR score). In a similar manner, the Rotterdam Reproduction Risk score (R3 score) was calculated from lifestyle factors (women: 13 items, men: 10 items). Univariate and paired tests were used. Results Most couples (93.8) were subfertile. At the second counselling, the percentage consuming the recommended intake of fruit had increased from 65 to 80 in women and from 49 to 68 in men and the percentage of women getting the recommended intake of fish increased from 39 to 52. As a consequence, the median PDR score was decreased [women: 2.6 (95 CI 2.4-2.9) to 2.4 (95 CI 2.1-2.6), men: 2.5 (95 CI 2.3-2.7) to 2.2 (95 CI 1.9-2.4), both P < 0.05]. The median R3 scores were also lower [women: 4.7 (95 CI 4.3-5.0) to 3.1 (95 CI 2.8-3.4), men: 3.0 (95 CI 2.8-3.3) to 2.0 (95 CI 1.7-2.3), both P < 0.01] due to less alcohol use (-14.6), more physical exercise and folic acid use in women, and less alcohol use in men (-19.4) (all P < 0.01). The R3 scores in women and men were decreased in all ethnicity, educational level, neighbourhood and BMI categories. However, low educated women appeared to show a larger reduction than better educated women and men with a normal BMI to show a larger decrease than overweight men. The reduction in the PDR score of women was similar in both ethnic groups. More than 85 women and men found the counselling useful and around 70 would recommend it to others. Conclusions Tailored preconception counselling about unhealthy dietary and lifestyle behaviours of subfertile couples in an outpatient tertiary clinic is feasible and seems to decrease the prevalence of harmful behaviours in the short term. These Results with subfertile couples are promising and illustrate their opportunities to contribute to reproductive performance and pregnancy outcome.

A maternal dietary pattern characterised by fish and seafood in association with the risk of congenital heart defects in the offspring (Article)

2011-09-01T00:00:00Z

Objective To identify maternal dietary patterns related to biomarkers of methylation and to investigate associations between these dietary patterns and the risk of congenital heart defects (CHDs) in the offspring. Design Case-control study. Setting Western part of the Netherlands, 2003-08. Population One hundred and seventy-nine mothers of children with CHD and 231 mothers of children without a congenital malformation. Methods Food intake was obtained by food frequency questionnaires. The reduced rank regression method was used to identify dietary patterns related to the biomarker concentrations of methylation in blood. Main outcome measures Dietary patterns, vitamin B and homocysteine concentrations, biomarkers of methylation (S-adenosylmethionine [SAM] and S-adenosylhomocysteine [SAH]) and the risk of CHD estimated by odds ratios and 95% confidence intervals. Results The one-carbon-poor dietary pattern, comprising a high intake of snacks, sugar-rich products and beverages, was associated with SAH (β = 0.92, P < 0.001). The one-carbon-rich dietary pattern with high fish and seafood intake was associated with SAM (β = 0.44, P < 0.001) and inversely with SAH (β = -0.08, P < 0.001). Strong adherence to this dietary pattern resulted in higher serum (P < 0.05) and red blood cell (P < 0.01) folate and a reduced risk of CHD in offspring: odds ratio, 0.3 (95% confidence interval, 0.2-0.6). Conclusions The one-carbon-rich dietary pattern, characterised by the high intake of fish and seafood, is associated with a reduced risk of CHD. This finding warrants further investigation in a randomised intervention trial. © 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology

Maternal age during pregnancy is associated with third trimester blood pressure level: The generation R study (Article)

2011-09-01T00:00:00Z

BACKGROUND: We hypothesized that hemodynamic adaptations related to pregnancy and ageing might be associated with differences in blood pressure levels during pregnancy between younger and older women. This might partly explain the increased risk of gestational hypertensive disorders with advanced maternal age. We examined the associations of maternal age with systolic and diastolic blood pressure in each trimester of pregnancy and the risks of gestational hypertensive disorders. METHODS: The study was conducted among 8,623 women participating in a population-based prospective cohort study from early pregnancy onwards. Age was assessed at enrolment. Blood pressure was measured in each trimester. Information about gestational hypertensive disorders was available from medical records. RESULTS: In second and third trimester, older maternal age was associated with lower systolic blood pressure (-0.9mmHg (95% confidence interval: -1.4, -0.3) and -0.6mmHg (95% confidence interval: -1.1, -0.02) per additional 10 maternal years, respectively). Older maternal age was associated with higher third trimester diastolic blood pressure (0.5mmHg (95% confidence interval: 0.04, 0.9) per additional 10 maternal years). Maternal age was associated with pregnancy-induced hypertension among overweight and obese women. CONCLUSION: Older maternal age is associated with lower second and third trimester systolic blood pressure, but higher third trimester diastolic blood pressure. These blood pressure differences seem to be small and within the physiological range. Maternal age is not consistently associated with the risks of gestational hypertensive disorders. Maternal body mass index might influence the association between maternal age and the risk of pregnancy-induced hypertension.

Maternal smoking during pregnancy and kidney volume in the offspring: the Generation R Study (Article)

2011-08-01T00:00:00Z

An adverse fetal environment leads to smaller kidneys, with fewer nephrons, which might predispose an individual to the development of kidney disease and hypertension in adult life. In a prospective cohort study among 1,072 children followed from early fetal life onward, we examined whether maternal smoking during pregnancy, as a significant adverse fetal exposure, is associated with fetal (third trimester of pregnancy, n = 1,031) and infant kidney volume (2 years of age, n = 538) measured by ultrasound. Analyses were adjusted for various potential confounders. Among mothers who continued smoking, we observed dose-dependent associations between the number of cigarettes smoked during pregnancy and kidney volume in fetal life. Smoking less than five cigarettes per day was associated with larger fetal combined kidney volume, while smoking more than ten cigarettes per day tended to be associated with smaller fetal combined kidney volume (p for trend: 0.002). This pattern was not significant for kidney volume at the age of 2 years. Our results suggest that smoking during pregnancy might affect kidney development in fetal life with a dose-dependent relationship. Further studies are needed to assess the underlying mechanisms and whether these differences in fetal kidney volume have postnatal consequences for kidney function and blood pressure.

Maternal milk consumption, fetal growth, and the risks of neonatal complications: The Generation R Study (Article)

2011-08-01T00:00:00Z

Background: Maternal cow-milk consumption may increase birth weight. Previous studies did not assess the association of maternal milk consumption with trimester-specific fetal growth. Objective: The objective was to assess associations of first-trimester maternal milk consumption with fetal growth characteristics in different trimesters and the risk of neonatal complications. Design: In total, 3405 mothers participating in a prospective cohort study completed a 293-item semiquantitative food-frequency questionnaire to obtain information about dairy consumption during the first trimester of pregnancy. Fetal head circumference, femur length, and weight were estimated in the second and third trimesters by ultrasonography. Results: Maternal milk consumption of >3 glasses/d was associated with greater fetal weight gain in the third trimester of pregnancy, which led to an 88-g (95% CI: 39, 135 g) higher birth weight than that with milk consumption of 0 to 1 glass/d. In addition, head circumference tended to be 2.3 cm (95% CI: -0.0, 4.6 cm) larger when mothers consumed >3 glasses/d. Maternal milk consumption was not associated with length growth. Maternal protein intake (P for trend = 0.01), but not fat or carbohydrate intake, from dairy products was associated with higher birth weight. This association appeared to be limited to milk (P for trend < 0.01), whereas protein intake from nondairy food or cheese was not associated with birth weight. Conclusions: Maternal milk consumption is associated with greater fetal weight gain. The association seems to be due to milk protein, or milk components closely associated with protein, rather than to the fat or carbohydrate fraction of milk.

Parental smoking during pregnancy, early growth, and risk of obesity in preschool children: The Generation R Study (Article)

2011-07-01T00:00:00Z

Background: Maternal smoking during pregnancy seems to be associated with obesity in offspring. Not much is known about the specific critical exposure periods or underlying mechanisms for this association. Objective: We assessed the associations of active maternal and paternal smoking during pregnancy with early growth characteristics and risks of overweight and obesity in preschool children. Design: This study was a population-based, prospective cohort study from early fetal life until the age of 4 y in 5342 mothers and fathers and their children. Growth characteristics [head circumference, length, weight, and body mass index (BMI; in kg/m2)] and overweight and obesity were repeatedly measured at the ages of 1, 2, 3, and 4 y. Results: In comparison with children from nonsmoking mothers, children from mothers who continued smoking during pregnancy had persistently smaller head circumferences and heights until the age of 4 y, whereas their weights were lower only until the age of 3 mo. This smaller length and normal to higher weight led to an increased BMI [SD score difference: 0.11; 95% CI: 0.02, 0.20; P < 0.05)] and an increased risk of obesity (odds ratio: 1.61; 95% CI: 1.03, 2.53; P < 0.05) at the age of 4 y. In nonsmoking mothers, paternal smoking was not associated with postnatal growth characteristics or risk of obesity in offspring. Maternal smoking during pregnancy was associated with a higher BMI at the age of 4 y in children with a normal birth weight and in those who were small for gestational age at birth. Conclusion: Our findings suggest that direct intrauterine exposure to smoke until late pregnancy leads to different height and weight growth adaptations and increased risks of overweight and obesity in preschool children.

Multiple reaction monitoring assay for pre-eclampsia related calcyclin peptides in formalin fixed paraffin embedded placenta (Article)

2011-07-01T00:00:00Z

Although the cause of pre-eclampsia during pregnancy has not been elucidated yet, it is evident that placental and maternal endothelial dysfunction is involved. We previously demonstrated that in early onset pre-eclampsia placental calcyclin (S100A6) expression is significantly higher compared to controls (De Groot, C. J.; Clin. Proteomics 2007, 1, 325). In the current study, the results were confirmed and relatively quantified by using multiple reaction monitoring (MRM) on two peptide fragments of calcyclin. Cells were obtained from control (n = 5) and pre-eclamptic placental (n = 5) tissue collected by laser capture microdissection from formalin-fixed paraffin-embedded (FFPE) material treated with a solution to reverse formalin fixation. Two calcyclin peptides with an extra glycine inserted in the middle of the amino acid sequence were synthesized and used as an internal reference. Data presented show that MRM on laser microdissected material from FFPE tissue material is possible. The developed MRM assay to study quantitative levels of proteins in FFPE laser microdissected cells using nonisotopic-labeled chemical analogs of mass tagged internal references showed that in pre-eclamptic patients elevated levels of calcyclin is observed in placental trophoblast cells compared to normal trophoblast cells. By immunohistochemistry, we were able to confirm this observation in a qualitative manner.

Breast-feeding and growth in children until the age of 3 years: The Generation R Study (Article)

2011-06-14T00:00:00Z

Breast-feeding has been suggested to be associated with lower risks of obesity in older children and adults. We assessed whether the duration and exclusiveness of breast-feeding are associated with early postnatal growth rates and the risks of overweight and obesity in preschool children. The present study was embedded in a population-based prospective cohort study from early fetal life onwards, among 5047 children and their mothers in The Netherlands. Compared with children who were breast-fed, those who were never breast-fed had a lower weight at birth (difference 134 (95 % CI ' 190,' 77) g). No associations between breast-feeding duration and exclusivity with growth rates before the age of 3 months were observed. Shorter breast-feeding duration was associated with an increased gain in age- and sex-adjusted standard deviation scores for length, weight and BMI (P for trend < 0•05) between 3 and 6 months of age. Similar tendencies were observed for the associations of breast-feeding exclusivity with change in length, weight and BMI. Breast-feeding duration and exclusivity were not consistently associated with the risks of overweight and obesity at the ages of 1, 2 and 3 years. In conclusion, shorter breast-feeding duration and exclusivity during the first 6 months tended to be associated with increased growth rates for length, weight and BMI between the age of 3 and 6 months but not with the risks of overweight and obesity until the age of 3 years.

Variants near CCNL1/LEKR1 and in ADCY5 and fetal growth characteristics in different trimesters (Article)

2011-05-01T00:00:00Z

Context: A recent genome-wide association study identified variants near CCNL1/LEKR1 (rs900400) and in ADCY5 (rs9883204) to be associated with birth weight. We examined the associations of these variants with fetal growth characteristics in different trimesters, with a main interest in the timing of the associations and the affected body proportions. Methods: We used data from two prospective cohort studies from fetal life onward in The Netherlands and Australia. Repeated fetal ultrasound examinations were performed to measure head circumference (HC), abdominal circumference (AC), femur length (FL), and estimated fetal weight (EFW). Analyses were based on a total group of 3909 subjects. Results: The C-allele of rs900400 was associated in second trimester with smaller fetal HC and FL, and in third trimester with smaller HC, AC, FL, and EFW. For each C-allele, the combined effect estimate for EFW in third trimester was - 18.6 g (95% confidence interval, -27.5, -9.7 g; P = 4.2 x 10-5). The C-allele of rs9883204 was not associated with fetal growth characteristics in second trimester but was associated with restriction of all growth characteristics, except HC, in third trimesterandat birth. For each C-allele, thecombinedeffect estimatewas-16.9g(95%confidence interval, -26.8, -7.0 g; P = 8.4 x 10-4) for EFW in third trimester. Both genetic variants were associated with lower birth and placenta weight. Conclusions: Our results suggest that a genetic variant of rs900400 leads to symmetric growth restriction from early pregnancy onward, whereas a genetic variant of rs9883204 leads to asymmetric growth restriction, characterized by a relatively larger HC, from third trimester. Copyright

Maternal smoking during pregnancy, fetal arterial resistance adaptations and cardiovascular function in childhood (Article)

2011-05-01T00:00:00Z

Objective To unravel the mechanisms underlying the previously demonstrated associations between low birthweight and cardiovascular disease in adulthood, we examined whether maternal smoking during pregnancy leads to fetal arterial resistance adaptations, and subsequently to fetal growth retardation and changes in postnatal blood pressure and cardiac development. Design Prospective cohort study from early fetal life onwards. Setting Academic hospital. Population Analyses were based on 1120 children aged 2 years. Methods Maternal smoking during pregnancy [non-smoking, first trimester smoking, continued smoking (<5 and ≥5 cigarettes/day)] was assessed by questionnaire. Main outcome measures Third trimester placental and fetal arterial resistance indices and fetal growth were assessed by ultrasound and Doppler measurements. Postnatal blood pressure and cardiac structures (aortic root diameter, left atrial diameter, left ventricular mass) were measured at 2 years of age. Results First trimester smoking was not associated with third trimester placental and fetal blood flow adaptations. Continued smoking of ≥5 cigarettes/day was associated with an increased resistance in uterine, umbilical and middle cerebral arteries, and with a decreased flow and diameter of the ascending aorta. Among mothers who continued to smoke, the third trimester estimated fetal weights and birthweights were most affected in children with the highest umbilical artery resistance. Fetal arterial resistance indices were also associated with aortic root diameter and left atrial diameter. Conclusions Fetal arterial resistance adaptations may be involved in the pathways leading from maternal smoking during pregnancy to low birthweight and cardiovascular developmental changes in childhood in the offspring.

Maternal fish consumption, fetal growth and the risks of neonatal complications: The Generation R Study (Article)

2011-03-28T00:00:00Z

Maternal fish consumption during pregnancy has been suggested to affect birth outcomes. Previous studies mainly focused on birth outcomes and did not study fetal growth during pregnancy. In a prospective cohort study from early pregnancy onwards in The Netherlands, we assessed the associations of first-trimester maternal total-fish, lean-fish, fatty-fish and shellfish consumption with fetal growth characteristics in the second and third trimesters, growth characteristics at birth and the risks of neonatal complications, including pre-term birth, low birth weight and small for gestational age. In total, 3380 mothers completed a 293-item semi-quantitative FFQ to obtain information about fish consumption during the first trimester of pregnancy. Head circumference, femur length and fetal weight were estimated in the second and third trimesters by ultrasound. Information about birth anthropometrics and neonatal complications was available from hospital and midwife registries. Maternal older age, higher educational level, folic acid supplement use, alcohol use and not smoking were associated with higher fish consumption (P < 0.01). After adjustment, we observed no consistent associations of maternal total-fish consumption or specific consumption of lean fish, fatty fish or shellfish with fetal growth characteristics in the second and third trimesters and at birth. Likewise, total-fish consumption or specific consumption of any type of fish was not consistently associated with the risks of neonatal complications. These findings suggest that in a population with a relatively low fish intake, consumption of lean fish, fatty fish or shellfish in the first trimester is not associated with fetal growth or the risks of neonatal complications.

Maternal and fetal haemodynamic effects of nifedipine in normotensive pregnant women (Article)

2011-03-01T00:00:00Z

While nifedipine is commonly used for tocolysis, the controversy on its safety remains. So far, the haemodynamic effects on maternal and fetal circulations have not been well documented. Fifteen normotensive women who received 20 mg nifedipine were included in this prospective observational study. The maternal and fetal haemodynamic effects were analysed using maternal echocardiography and fetal Doppler ultrasonography. Nifedipine induced a significant afterload reduction in all women. It triggered a compensatory increase in cardiac output, which maintained blood pressure. These maternal changes had no influence on the uteroplacental and fetal circulations.

Explaining differences in birth outcomes in relation to maternal age: The generation R study (Article)

2011-03-01T00:00:00Z

Please cite this paper as: Bakker R, Steegers E, Biharie A, Mackenbach J, Hofman A, Jaddoe V. Explaining differences in birth outcomes in relation to maternal age: the Generation R Study. BJOG 2011;118:500-509. Objective To examine the association between maternal age and birth outcomes, and to investigate the role of sociodemographic and lifestyle-related determinants. Design Population-based prospective cohort study from early pregnancy onwards. Setting Rotterdam, the Netherlands. Population A cohort of 8568 mothers and their children. Methods Maternal age was assessed at enrolment. Information about sociodemographic (height, weight, educational level, ethnicity, parity) and lifestyle-related determinants (alcohol consumption, smoking habits, folic acid supplement use, caffeine intake, daily energy intake) and birth outcomes was obtained from questionnaires and hospital records. Multivariate linear and logistic regression analyses were used. Main outcomes measures Birthweight, preterm delivery, small-for-gestational-age, and large-for-gestational-age. Results As compared with mothers aged 30-34.9 years, no differences in risk of preterm delivery were found. Mothers younger than 20 years had the highest risk of delivering small-for-gestational-age babies(OR 1.6, 95% CI: 1.1-2.5); however, this increased risk disappeared after adjustment for sociodemographic and lifestyle-related determinants. Mothers older than 40 years had the highest risk of delivering large-for-gestational-age babies (OR 1.3, 95% CI: 0.8-2.4). The associations of maternal age with the risks of delivering large-for-gestational-age babies could not be explained by sociodemographic and lifestyle-related determinants. Conclusions As compared with mothers aged 30-34.9 years, younger mothers have an increased risk of small-for-gestational- age babies, whereas older mothers have an increased risk of large-for- gestational-age babies. Sociodemographic and lifestyle-related determinants cannot fully explain these differences.

The effects of work-related maternal risk factors on time to pregnancy, preterm birth and birth weight: The seneration R study (Article)

2011-03-01T00:00:00Z

Objective: To investigate the influence of maternal working conditions on fertility and pregnancy outcomes. Methods: 8880 women were enrolled in a large prospective birth cohort during early (76%), mid (21%) or late pregnancy (3%) (61% participation). Complete questionnaire information was available for 6302 women (71% response). Outcomes were prolonged time to pregnancy (TTP) (>6 months), preterm birth (<37 weeks) and decreased birth weight (<3000 g). Self-reported exposure to chemical agents was based on a limited list of chemicals. Physical load questions concerned manual materials handling, prolonged sitting and long periods of standing. A job-exposure matrix (JEM) linked reported job title to workplace chemical exposure within jobs according to expert judgement. Associations between maternal occupational exposure and fertility and pregnancy outcomes, adjusted for age, education, minority, parity, smoking and alcohol use, were studied using logistic regression analysis. Results: Women in jobs with regular handling of loads ≥5 kg had better fertility and pregnancy outcomes. No self-reported exposure to chemicals was associated with any outcomes and self-assessments had very low reliability compared with JEM-based assessments. JEM-based maternal occupational exposure to phthalates was associated with prolonged TTP (OR 2.16, 95% CI 1.02 to 4.57) and exposure to pesticides was associated with decreased birth weight (OR 2.42, 95% CI 1.10 to 5.34). The population attributable fractions were small at 0.7% for phthalates and 0.7% for pesticides. Conclusion: This birth cohort study presents evidence of health-based selection into the workforce and adverse effects of maternal occupational exposure to phthalates and pesticides on fertility and pregnancy outcomes.

Virtual reality for embryonic measurements requiring depth perception (Article)

2011-02-01T00:00:00Z

Two real-time three-dimensional images of first-trimester pregnancies visualized using virtual reality (VR) are presented. Inherently three-dimensional structures, like the umbilical cord and limbs, can be efficiently and accurately measured using VR.

Glucocorticoid receptor-9beta polymorphism is associated with systolic blood pressure and heart growth during early childhood. The Generation R Study (Article)

2011-02-01T00:00:00Z

Background: Glucocorticoid receptor-9β polymorphism (rs6198) is associated with the susceptibility for cardiovascular disease. Aim: To examine whether the GR-9β variant is also associated with blood pressure and heart growth in early childhood. Study design: This study was embedded in a population-based prospective cohort study from fetal life onwards. Analyses were based on 857 children. Outcome measures: Left cardiac structures (aortic root diameter, left atrial diameter and left ventricular mass), shortening fraction and heart beat were measured postnatally at the ages of 1.5, 6 and 24 months. Blood pressure was measured at 24 months of age. Results: The distribution of the GR-9β genotype showed 75.1% homozygous reference, 23.5% heterozygous and 1.4% homozygous variant subjects. No differences in cardiovascular outcomes were observed at the ages of 1.5 and 6 months. At the age of 24 months, homozygous variants showed an increased systolic blood pressure of 2.65 mm. Hg (95% CI: 0.16, 5.14), an increased heart rate of 9.10 beats per minute (95% CI: 1.28, 16.7) and an increased left ventricular mass of 4.99 g (95% CI: 1.33, 8.65) compared to homozygous references. This means an increase of 2.6%, 8.6% and 16%, respectively. GR-9β polymorphism was significantly associated with left ventricular mass growth during the first 2 years. Conclusion: Our findings suggest that genetically determined differences in cortisol exposure affect cardiovascular development in early life.

Ethnic differences in antenatal care use in a large multi-ethnic urban population in the Netherlands (Article)

2011-02-01T00:00:00Z

Objective: to determine differences in antenatal care use between the native population and different ethnic minority groups in the Netherlands. Design: the Generation R Study is a multi-ethnic population-based prospective cohort study. Setting: seven midwife practices participating in the Generation R Study conducted in the city of Rotterdam. Participants: in total 2093 pregnant women with a Dutch, Moroccan, Turkish, Cape Verdean, Antillean, Surinamese-Creole and Surinamese-Hindustani background were included in this study. Measurements: to assess adequate antenatal care use, we constructed an index, including two indicators; gestational age at first visit and total number of antenatal care visits.Logistic regression analysis was used to assess differences in adequate antenatal care use between different ethnic groups and a Dutch reference group, taking into account differences in maternal age, gravidity and parity. Findings: overall, the percentages of women making adequate use are higher in nulliparae than in multiparae, except in Dutch women where no differences are present.Except for the Surinamese-Hindustani, all women from ethnic minority groups make less adequate use as compared to the native Dutch women, especially because of late entry in antenatal care. When taking into account potential explanatory factors such as maternal age, gravidity and parity, differences remain significant, except for Cape-Verdian women. Dutch-Antillean, Moroccan and Surinamese-Creole women exhibit most inadequate use of antenatal care. Key conclusions: this study shows that there are ethnic differences in the frequency of adequate use of antenatal care, which cannot be attributed to differences in maternal age, gravidity and parity. Future research is necessary to investigate whether these differences can be explained by socio-economic and cultural factors. Implications for practise: clinicians should inform primiparous women, and especially those from ethnic minority groups, on the importance of timely antenatal care entry.

Congenital heart defects and biomarkers of methylation in children: A case-control study (Article)

2011-02-01T00:00:00Z

Eur J Clin Invest 2011; 41 (2): 143-150Background Derangements in the maternal methylation pathway, expressed by global hypomethylation and hyperhomocysteinemia, are associated with the risk of having a child with a congenital heart defect (CHD). It is not known whether periconception exposure to these metabolic derangements contributes to chromosome segregation and metabolic programming of this pathway in the foetus.Design In a Dutch population-based case-control study of 143 children with CHD and 186 healthy children, we investigated S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), total homocysteine (tHcy), the vitamins folate and B12 and the functional single nucleotide polymorphisms in the folate gene MTHFR 677C>T and 1298A>C. Comparisons were made between cases and controls adjusting for age, medication, vitamin use and CHD family history.Results In the overall CHD group, the median concentrations of SAM (P = 0.011), folate in serum (P = 0.021) and RBC (P = 0.030) were significantly higher than in the controls. Subgroup analysis showed that this was mainly attributable to complex CHD with higher SAM (P < 0.001), SAH (P = 0.012) and serum folate (P = 0.010) independent of carriership of MTHFR polymorphisms. Highest concentrations of SAM, SAH and folate RBC were observed in complex syndromic CHD. The subgroup of children with Down syndrome, however, showed significantly higher SAH (P = 0.037) and significantly lower SAM:SAH ratio (P = 0.034) compared with other complex CHD, suggesting a state of global hypomethylation.Conclusion High concentrations of methylation biomarkers in very young children are associated with complex CHD. Down syndrome and CHD may be associated with a global hypomethylation status, which has to be confirmed in tissues and global DNA methylation in future studies.

Maternal and fetal haemodynamic effects of nifedipine in normotensive pregnant women (Article)

2011-01-01T00:00:00Z

First trimester umbilical cord and vitelline duct measurements using virtual reality (Article)

2011-01-01T00:00:00Z

Background: The umbilical cord and vitelline duct are of vital importance to the fetus, but they are rarely the subject of first trimester two-dimensional (2D) ultrasound evaluation due to the complexity of their shape and morphology. Virtual reality (VR) allows efficient visualisation and measurement of complex structures like the umbilical cord and vitelline duct. Aim: To measure normal first trimester human growth of the umbilical cord length (UCL) and vitelline duct length (VDL) using a VR system; and to correlate both measurements with the gestational age (GA) and crown-rump length (CRL) and the VDL with the yolk sac volume (YSV). Study design: Prospective cohort study. Serial three-dimensional (3D) ultrasound measurements were performed from six to 14 weeks GA, resulting in 125 3D volumes. These volumes were analysed using an I-Space VR system. Subjects: Thirty-two healthy pregnant women with an ongoing, normal pregnancy. Outcome measures: The UCL, VDL, YSV and other related structures were measured. Results: The UCL, measurable in 55% of cases, was positively correlated to advancing GA and CRL (p<0.001). The VDL could be measured in 42% of cases and showed a positive relationship with GA and CRL (p<0.001). There was a significant (p<0.001) relationship between YSV and VDL. Conclusions: The present study, facilitated by a VR system, is the first to provide an in-vivo longitudinal description of normal first trimester growth of the human umbilical cord and vitelline duct. Further studies will reveal whether these parameters can be used in detection of abnormal fetal development.

Perinatale gezondheid in Rotterdam; nulmeting periode 2000-2007 (Research Report)

2011-01-01T00:00:00Z

Inleiding Rotterdam heeft binnen Nederland een relatief hoog perinataal sterftecijfer. Onder perinatale sterfte verstaan we sterfte vanaf 22 weken zwangerschapsduur tot en met de eerste 7 dagen na de geboorte. Dit bleek reeds in 2008 toen De Graaf et al. beschreven dat vrouwen in de vier grote steden een sterk verhoogde kans hebben op perinatale sterfte en daarmee samenhangende perinatale ziekte. De belangrijkste vier perinatale ziekten, die vaak voorlopers zijn van perinatale sterfte, zijn aangeboren afwijkingen, vroeggeboorte, laag geboortegewicht gelet op de zwangerschapsduur, en een lage Apgar score (een slechte start bij de geboorte). In vervolg op de bevindingen voor Rotterdam is in 2008 het Aanvalsplan Perinatale Sterfte Rotterdam van start gegaan. Dit is een meerjarig programma waarin de Gemeente Rotterdam in samenwerking met het Erasmus MC en de GGD Rotterdam Rijnmond tot doel heeft de perinatale sterfte en perinatale ziekte binnen Rotterdam te verminderen. Een eerste stap hierbij is het nauwkeurig in kaart brengen van perinatale ziekten en sterfte, en de factoren die mogelijk hiervoor verantwoordelijk zijn. Deze factoren kunnen gebonden zijn aan zwangeren zelf, met hun omgeving te maken hebben of met de zorg te maken hebben.

Perinatale gezondheid in Rotterdam; nulmeting periode 2000-2007 (Research Report)

2011-01-01T00:00:00Z

Perinatale gezondheid in Rotterdam; nulmeting periode 2000-2007 (Research Report)

2011-01-01T00:00:00Z

Well being of obstetric patients on minimal blood transfusions (WOMB trial) (Article)

2010-12-16T00:00:00Z

Background: Primary postpartum haemorrhage is an obstetrical emergency often causing acute anaemia that may require immediate red blood cell (RBC) transfusion. This anaemia results in symptoms such as fatigue, which may have major impact on the health-related quality of life. RBC transfusion is generally thought to alleviate these undesirable effects although it may cause transfusion reactions. Moreover, the postpartum haemoglobin level seems to influence fatigue only for a short period of time. At present, there are no strict transfusion criteria for this specific indication, resulting in a wide variation in postpartum policy of RBC transfusion in the Netherlands.Methods/Design: The WOMB trial is a multicentre randomised non-inferiority trial. Women with acute anaemia due to postpartum haemorrhage, 12-24 hours after delivery and not initially treated with RBC transfusion, are eligible for randomisation. Patients with severe physical complaints are excluded. Patients are randomised for either RBC transfusion or expectant management. Health related quality of life (HRQoL) will be assessed at inclusion, at three days and one, three and six weeks postpartum with three validated measures (Multi-dimensional Fatigue Inventory, ShortForm-36, EuroQol-5D). Primary outcome of the study is physical fatigue three days postpartum. Secondary outcome measures are general and mental fatigue scores and generic health related quality of life scores, the number of RBC transfusions, length of hospital stay, complications and health-care costs.The primary analysis will be by intention-to-treat. The various longitudinal scores will be evaluated using Repeated Measurements ANOVA. A costs benefit analysis will also be performed. The power calculation is based on the exclusion of a difference in means of 1.3 points or greater in favour of RBC transfusion arm regarding physical fatigue subscale. With missing data not exceeding 20%, 250 patients per arm have to be randomised (one-sided alpha = 0.025, power = 80%).Discussion: This study will provide evidence for a guideline regarding RBC transfusion in the postpartum patient suffering from acute anaemia. Equivalence in fatigue score, remaining HRQoL scores and physical complications between both groups is assumed, in which case an expectant management would be preferred to minimise transfusion reactions and costs.Trial registration: ClinicalTrials.gov NCT00335023, Nederlands Trial Register NTR335.

The preconception nutritional status of women undergoing fertility treatment: Use of a one-year post-delivery assessment (Article)

2010-12-01T00:00:00Z

Background&Aims: A poor maternal nutritional status in the preconception period is associated with adverse pregnancy outcomes. A valid standardized assessment period after pregnancy reflecting the preconception nutritional status is missing. Therefore, this study aimed to validate the assessment period at around 1 year after delivery in women undergoing fertility treatment. Methods: In a prospective study including 30 women with a fertility problem, we compared nutrient intakes from a food frequency questionnaire and biomarkers related to the homocysteine pathway in blood, at two assessment periods, i.e., preconceptionally and 1 year after delivery. We used a linear mixed model and adjusted for possible confounders, such as body mass index and folic acid supplement use. Results: The energy-adjusted nutrient intakes were not significantly different between the two assessment periods, except for higher retinol, alcohol and vitamin B2 and lower carbohydrate intakes at around 1 year after delivery. The intraclass correlation coefficients of the nutrients ranged from 0.3 to 0.7. After adjustment, none of the biomarkers was significantly different between the two assessment periods. The intraclass correlation coefficients of the biomarkers were all ≥0.5. Conclusions: An assessment at around 1 year after delivery seems to adequately reflect the preconception nutritional status of women with a fertility problem, however larger confirmatory studies are required.

Breastfeeding patterns among ethnic minorities: The Generation R Study (Article)

2010-12-01T00:00:00Z

Background Because breastfeeding is the best method of infant feeding, groups at risk of low breastfeeding rates should be identified. Therefore, this study compared breastfeeding patterns of ethnic minority groups in The Netherlands with those of native mothers and established how they were influenced by generational status and socio-demographic determinants of breastfeeding. Methods We used data on 2914 Dutch, 366 Mediterranean first-generation, 143 Mediterranean second-generation, 285 Caribbean first-generation and 140 Caribbean second-generation mothers. Information on starting breastfeeding and breastfeeding at 2 and 6 months after birth were obtained from questionnaires during the first year after birth. Results Overall, 90.6% of women started breastfeeding after delivery. This percentage was lowest among the native Dutch (89.1%) and highest among the Mediterranean second-generation women (98.6%; p≤0.001). At 6 months postpartum, 30.6% of mothers were still breastfeeding, ranging from 19.3% in the Caribbean second-generation mothers to 42.6% in first-generation Mediterranean mothers. After adjustment for covariates, more non-native mothers started breastfeeding than native Dutch mothers. While Mediterranean first-generation mothers had higher breastfeeding rates at 6 months (OR: 2.71, 95% CI: 2.09 to 3.51), there were no differences in Mediterranean second-generation and Caribbean mothers compared to native Dutch mothers. Conclusion More non-native mothers started breastfeeding than native mothers, but relative fewer continued. Although both native Dutch and non-native mothers had low continuation rates, ethnic minorities may face other difficulties in continuing breastfeeding than native women.

The preconception nutritional status of women undergoing fertility treatment: Use of a one-year post-delivery assessment (Article)

2010-12-01T00:00:00Z

Paroxysmal disorders in infancy and their risk factors in a population-based cohort: The Generation R Study (Article)

2010-11-01T00:00:00Z

Aim To examine the incidence of paroxysmal epileptic and non-epileptic disorders and the associated prenatal and perinatal factors that might predict them in the first year of life in a population-based cohort.Method This study was embedded in the Generation R Study, a population-based prospective cohort study from early fetal life onwards. Information about the occurrence of paroxysmal events, defined as suddenly occurring episodes with an altered consciousness, altered behaviour, involuntary movements, altered muscle tone, and/or a changed breathing pattern, was collected by questionnaires at the ages of 2, 6, and 12 months. Information on possible prenatal and perinatal determinants was obtained by measurements and questionnaires during pregnancy and after birth.Results Information about paroxysmal events in the first year of life was available in 2860 participants (1410 males, 1450 females). We found an incidence of paroxysmal disorders of 8.9% (n=255) in the first year of life. Of these participants, 17 were diagnosed with febrile seizures and two with epilepsy. Non-epileptic events included physiological events, apnoeic spells, loss of consciousness by causes other than epileptic seizures or apnoeic spells, parasomnias, and other events. Preterm birth (p<0.001) and low Apgar score at 1 minute (p<0.05) were significantly associated with paroxysmal disorders in the first year of life. Continued maternal smoking during pregnancy and preterm birth were significantly associated with febrile seizures in the first year of life (p<0.05).Interpretation Paroxysmal disorders are frequent in infancy. They are associated with preterm birth and a low Apgar score. Epileptic seizures only form a minority of the paroxysmal events in infancy. In this study, children whose mothers continued smoking during pregnancy had a higher reported incidence of febrile seizures in the first year of life. These findings may generate various hypotheses for further investigations.

Ethnic differences in participation in prenatal screening for Down syndrome: A register-based study (Article)

2010-10-01T00:00:00Z

Objective: To assess ethnic differences in participation in prenatal screening for Down syndrome in the Netherlands. Methods: Participation in prenatal screening was assessed for the period 1 January 2009 to 1 July 2009 in a defined postal code area in the southwest of the Netherlands. Data on ethnic origin, socio-economic background and age of participants in prenatal screening were obtained from the Medical Diagnostic Centre and the Department of Clinical Genetics. Population data were obtained from Statistics Netherlands. Logistic regression models were used to assess ethnic differences in participation, adjusted for socio-economic and age differences. Results: The overall participation in prenatal screening was 3865 out of 15 093 (26%). Participation was 28% among Dutch women, 15% among those from Turkish ethnic origin, 8% among those from North-African origin, 15% among those from Aruban/Antillean origin and 26% among women from Surinamese origin. Conclusions: Compared to Dutch women, those from Turkish, North-African, Aruban/Antillean and other non-Western ethnic origin were less likely to participate in screening. It was unexpected that women from Surinamese origin equally participated. It should be further investigated to what extent participation and non-participation in these various ethnic groups was based on informed decision-making.

Fetal growth retardation and risk of febrile seizures (Article)

2010-10-01T00:00:00Z

OBJECTIVE: The goal was to examine the associations between fetal growth characteristics in different trimesters of pregnancy and the occurrence of febrile seizures in early childhood. METHODS: This study was embedded in a population-based, prospective, cohort study from early fetal life onward. Fetal growth characteristics (femur length, abdominal circumference, estimated fetal weight, head circumference, biparietal diameter, and transverse cerebellar diameter [TCD]) were measured with ultrasonography in the second and third trimesters of pregnancy. Information on the occurrence of febrile seizures was collected with questionnaires at the ages of 12 and 24 months. Analyses were based on data for 3372 subjects. RESULTS: In the second trimester, children in the lowest tertile of TCDs were at increased risk of developing febrile seizures, compared with children in the highest tertile (odds ratio 2.87 [95% confidence interval: 1.31-6.28]). In the third trimester, children in the lowest tertile of all general growth characteristics (femur length, abdominal circumference, and estimated fetal weight) were at increased risk of developing febrile seizures. This association was strongest for children in the lowest tertile of estimated fetal weight (odds ratio: 2.57 [95% confidence interval: 1.34-4.96]). Children in the lowest tertile of biparietal diameter in the third trimester also were at increased risk of febrile seizures. Similar but not statistically significant tendencies were observed for head circumference and TCD. CONCLUSIONS: Fetal growth retardation is associated with increased risk of febrile seizures in the first 2 years of life. Adverse environmental and genetic factors during pregnancy may be important in the development of febrile seizures.

An innovative virtual reality technique for automated human embryonic volume measurements (Article)

2010-09-01T00:00:00Z

Background: The recent introduction of virtual reality (VR) enables us to use all three dimensions in a three-dimensional (3D) image. The aim of this prospective study was to evaluate an innovative VR technique for automated 3D volume measurements of the human embryo and yolk sac in first trimester pregnancies. Methods: We analysed 180 3D first trimester ultrasound scans of 42 pregnancies. Scans were transferred to an I-Space VR system and visualized as 3D 'holograms' with the V-Scope volume-rendering software. A semi-automatic segmentation algorithm was used to calculate the volumes. The logarithmically transformed outcomes were analysed using repeated measurements ANOVA. Interobserver and intraobserver agreement was established by calculating intraclass correlation coefficients (ICCs). Results:Eighty-eight embryonic volumes (EVs) and 118 yolk sac volumes (YSVs) were selected and measured between 5+5 and 12+6 weeks of gestational age (GA). EV ranged from 14 to 29 877 mm3 and YSV ranged from 33 to 424 mm3. ANOVA calculations showed that when the crown-rump length (CRL) doubles, the mean EV increases 6.5-fold and when the GA doubles, the mean EV increases 500-fold (P < 0.001). Furthermore, it was found that a doubling in GA results in a 3.8-fold increase of the YSV and when the CRL doubles, the YSV increases 1.5-fold (P < 0.001). Interobserver and intraobserver agreement were both excellent with ICCs of 0.99. Conclusion: We measured the human EV and YSV in early pregnancy using a VR system. This innovative technique allows us to obtain unique information about the size of the embryo using all dimensions, which may be used to differentiate between normal and abnormal human development.

Compromised chorionic villous vascularization in idiopathic second trimester fetal loss (Article)

2010-08-01T00:00:00Z

Background: For normal fetal growth and development a well-developed chorionic villous vascularization is essential. Aim: The aim of this study is to investigate whether idiopathic second trimester fetal loss is associated with an underdeveloped chorionic villous vascularization. Methods: 38 placentas after late miscarriage, classified as idiopathic fetal loss (IFL, n = 16) or as fetal loss due to intrauterine infection (IUI, n = 22) were collected. After CD34 immunohistochemical staining the villous stromal area, number of villous vessels, vascular area and vascular area density (central, peripheral and total) were measured in randomly selected immature intermediate villi. Results: The mean gestational age was 19 + 4 weeks for the IFL group and 20 + 6 weeks for the IUI group. After controlling for gestational age, we found no differences in fetal weight, placental weight, villous stromal area, number of vessels and central vascular features. The mean peripheral vascular area and peripheral vascular area density were, after adjusting for gestational age, reduced in the IFL group. Conclusion: Idiopathic second trimester fetal loss is associated with a reduced peripheral chorionic villous vascularization. We hypothesize that in these cases, placentation is already disturbed in first trimester of pregnancy, leading to a reduced materno-fetal interface in second trimester, thus to early postplacental fetal hypoxia and fetal death.

Breastfeeding is not associated with left cardiac structures and blood pressure during the first two years of life. The Generation R Study (Article)

2010-08-01T00:00:00Z

Background: Shorter duration of breastfeeding in infancy has been suggested to be associated with an increased risk of cardiovascular disease in adulthood. Early cardiovascular adaptations due to breastfeeding may explain these associations. Aim: To investigate whether breastfeeding affects left cardiac structures and blood pressure development in early childhood. Study design: Prospective cohort study from fetal life until the age of two years. Subjects: Information about the duration and exclusivity of breastfeeding was collected by questionnaires at the ages of 2, 6 and 12 months in 933 children. Outcome measures: Left cardiac structures (left atrial diameter, aortic root diameter and left ventricular mass), fractional shortening and blood pressure at the ages of 1.5, 6 and 24 months. Results: No differences in cardiac structures, fractional shortening and blood pressure were observed between breastfed and non-breastfed children. Duration and exclusivity of breastfeeding were not consistently associated with any cardiac structure, fractional shortening, or blood pressure until the age of 24 months. Also, there was no association of breastfeeding with cardiac growth between 6 months and 24 months. All analyses were adjusted for child age and sex. Additional adjustment for child anthropometrics, maternal age, anthropometrics, family history, maternal cardiovascular risk factors, pregnancy or delivery complications, parity, socio-economic status, smoking status and alcohol consumption during pregnancy did not materially change the effect estimates. Conclusions: Our results do not support the hypothesis that early postnatal cardiovascular adaptations underlie the previously shown associations between breastfeeding and cardiovascular disease in adulthood. Further studies are needed to investigate whether and at what age the associations appear.

Pre-eclampsia (Article)

2010-08-01T00:00:00Z

Pre-eclampsia remains a leading cause of maternal and perinatal mortality and morbidity. It is a pregnancy-specific disease characterised by de-novo development of concurrent hypertension and proteinuria, sometimes progressing into a multiorgan cluster of varying clinical features. Poor early placentation is especially associated with early onset disease. Predisposing cardiovascular or metabolic risks for endothelial dysfunction, as part of an exaggerated systemic inflammatory response, might dominate in the origins of late onset pre-eclampsia. Because the multifactorial pathogenesis of different pre-eclampsia phenotypes has not been fully elucidated, prevention and prediction are still not possible, and symptomatic clinical management should be mainly directed to prevent maternal morbidity (eg, eclampsia) and mortality. Expectant management of women with early onset disease to improve perinatal outcome should not preclude timely delivery-the only definitive cure. Pre-eclampsia foretells raised rates of cardiovascular and metabolic disease in later life, which could be reason for subsequent lifestyle education and intervention.

Increased adverse perinatal outcome of hospital delivery at night (Article)

2010-08-01T00:00:00Z

Objective To determine whether delivery in the evening or at night and some organisational features of maternity units are related to perinatal adverse outcome. Design A 7-year national registry-based cohort study. Setting All 99 Dutch hospitals. Population From nontertiary hospitals (n = 88), 655 961 singleton deliveries from 32 gestational weeks onwards, and, from tertiary centres (n = 10), 108 445 singleton deliveries from 22 gestational weeks onwards. Methods Multiple logistic regression analysis of national perinatal registration data over the period 2000-2006. In addition, multilevel analysis was applied to investigate whether the effects of time of delivery and other variables systematically vary across different hospitals. Main outcome measures Delivery-related perinatal mortality (intrapartum or early neonatal mortality) and combined delivery-related perinatal adverse outcome (any of the following: intrapartum or early neonatal mortality, 5-minute Apgar score below 7, or admission to neonatal intensive care). Results After case mix adjustment, relative to daytime, increased perinatal mortality was found in nontertiary hospitals during the evening (OR, 1.32; 95% CI, 1.15-1.52) and at night (OR, 1.47; 95% CI, 1.28-1.69) and, in tertiary centres, at night only (OR, 1.20; 95% CI, 1.06-1.37). Similar significant effects were observed using the combined perinatal adverse outcome measure. Multilevel analysis was unsuccessful; extending the initial analysis with nominal hospital effects and hospital-delivery time interaction effects confirmed the significant effect of night in nontertiary hospitals, whereas other organisational effects (nontertiary, tertiary) were taken up by the hospital terms. Conclusion Hospital deliveries at night are associated with increased perinatal mortality and adverse perinatal outcome. The time of delivery and other organisational features representing experience (seniority of staff, volume) explain hospital-to-hospital variation.

Compromised chorionic villous vascularization in idiopathic second trimester fetal loss (Article)

2010-08-01T00:00:00Z

Background: For normal fetal growth and development a well-developed chorionic villous vascularization is essential. Aim: The aim of this study is to investigate whether idiopathic second trimester fetal loss is associated with an underdeveloped chorionic villous vascularization. Methods: 38 placentas after late miscarriage, classified as idiopathic fetal loss (IFL, n=16) or as fetal loss due to intrauterine infection (IUI, n=22) were collected. After CD34 immunohistochemical staining the villous stromal area, number of villous vessels, vascular area and vascular area density (central, peripheral and total) were measured in randomly selected immature intermediate villi. Results: The mean gestational age was 19 + 4. weeks for the IFL group and 20 + 6. weeks for the IUI group. After controlling for gestational age, we found no differences in fetal weight, placental weight, villous stromal area, number of vessels and central vascular features. The mean peripheral vascular area and peripheral vascular area density were, after adjusting for gestational age, reduced in the IFL group. Conclusion: Idiopathic second trimester fetal loss is associated with a reduced peripheral chorionic villous vascularization. We hypothesize that in these cases, placentation is already disturbed in first trimester of pregnancy, leading to a reduced materno-fetal interface in second trimester, thus to early postplacental fetal hypoxia and fetal death.

Breastfeeding is not associated with left cardiac structures and blood pressure during the first two years of life. The Generation R Study (Article)

2010-08-01T00:00:00Z

Background: Shorter duration of breastfeeding in infancy has been suggested to be associated with an increased risk of cardiovascular disease in adulthood. Early cardiovascular adaptations due to breastfeeding may explain these associations. Aim: To investigate whether breastfeeding affects left cardiac structures and blood pressure development in early childhood. Study design: Prospective cohort study from fetal life until the age of two years. Subjects: Information about the duration and exclusivity of breastfeeding was collected by questionnaires at the ages of 2, 6 and 12. months in 933 children. Outcome measures: Left cardiac structures (left atrial diameter, aortic root diameter and left ventricular mass), fractional shortening and blood pressure at the ages of 1.5, 6 and 24. months. Results: No differences in cardiac structures, fractional shortening and blood pressure were observed between breastfed and non-breastfed children. Duration and exclusivity of breastfeeding were not consistently associated with any cardiac structure, fractional shortening, or blood pressure until the age of 24. months. Also, there was no association of breastfeeding with cardiac growth between 6. months and 24. months. All analyses were adjusted for child age and sex. Additional adjustment for child anthropometrics, maternal age, anthropometrics, family history, maternal cardiovascular risk factors, pregnancy or delivery complications, parity, socio-economic status, smoking status and alcohol consumption during pregnancy did not materially change the effect estimates. Conclusions: Our results do not support the hypothesis that early postnatal cardiovascular adaptations underlie the previously shown associations between breastfeeding and cardiovascular disease in adulthood. Further studies are needed to investigate whether and at what age the associations appear.

Ethnic and socio-economic differences in uptake of prenatal diagnostic tests for Down's syndrome (Article)

2010-08-01T00:00:00Z

Objective: The objective of this study was to assess ethnic and socio-economic differences in the uptake of maternal age-based prenatal diagnostic testing for Down's syndrome by amniocentesis or chorionic villus sampling. Study design: The study population consisted of 12,340 women aged 36 years or over, who lived in a geographically defined region in the Southwest of The Netherlands and who gave birth to a live born infant in the period 2000-2004. Data were obtained from the Department of Clinical Genetics Erasmus MC and Statistics Netherlands. Logistic regression analyses were done to assess ethnic and socio-economic differences in uptake. Results: The overall uptake of prenatal diagnostic tests was 28.5%. Women of Turkish and Caribbean origin participated in prenatal diagnostic tests equally or more often than Dutch women. Women of North-African origin and women from low socio-economic background had a lower uptake than others. Ethnic differences in uptake could not be attributed to differences in socio-economic background. Conclusions: Uptake of prenatal diagnostic tests for Down's syndrome in The Netherlands was low and varied among ethnic and socio-economic groups of advanced maternal age. The finding that women of Turkish and Caribbean origin participated in prenatal diagnostic tests equally or more often than Dutch women was unexpected. The low uptake among Dutch women may be related to the Dutch pregnancy culture. The finding that women of North-African origin and women from low socio-economic background had a lower uptake may be related to barriers in access to prenatal diagnostic tests.

Fetal growth from mid- to late pregnancy is associated with infant development: The Generation R Study (Article)

2010-07-01T00:00:00Z

Aim: The aim of this study was to investigate within a population-based cohort of 4384 infants (2182 males, 2202 females) whether fetal growth from early pregnancy onwards is related to infant development and whether this potential relationship is independent of postnatal growth. Method: Ultrasound measurements were performed in early, mid-, and late pregnancy. Estimated fetal weight was calculated using head and abdominal circumference and femur length. Infant development was measured with the Minnesota Infant Development Inventory at 12 months (SD 1.1mo, range 10-17mo). Information on postnatal head size and body weight at 7 months was obtained from medical records. Results: After adjusting for potential confounders and for postnatal growth, faster fetal weight gain from mid- to late pregnancy predicted a reduced risk of delayed social development (odds ratio [OR] 0.82; 95% confidence interval [CI] 0.71-0.95, p=0.008), self-help abilities (OR 0.84; 95% CI 0.73-0.98, p=0.023), and overall infant development (OR 0.65; 95% CI 0.49-0.87, p=0.003). Similar findings were observed for fetal head growth from mid- to late pregnancy. Interpretation: Faster fetal growth predicts a lower risk of delayed infant development independent of postnatal growth. These results suggest that reduced fetal growth between mid- and late pregnancy may determine subsequent developmental outcomes.

Explaining Ethnic Differences in Late Antenatal Care Entry by Predisposing, Enabling and Need Factors in the Netherlands. The Generation R Study (Article)

2010-06-09T00:00:00Z

Despite compulsory health insurance in Europe, ethnic differences in access to health care exist. The objective of this study is to investigate how ethnic differences between Dutch and non-Dutch women with respect to late entry into antenatal care provided by community midwifes can be explained by need, predisposing and enabling factors. Data were obtained from the Generation R Study. The Generation R Study is a multi-ethnic population-based prospective cohort study conducted in the city of Rotterdam. In total, 2,093 pregnant women with a Dutch, Moroccan, Turkish, Cape Verdean, Antillean, Surinamese Creole and Surinamese Hindustani background were included in this study. We examined whether ethnic differences in late antenatal care entry could be explained by need, predisposing and enabling factors. Subsequently, logistic regression analysis was used to assess the independent role of explanatory variables in the timing of antenatal care entry. The main outcome measure was late entry into antenatal care (gestational age at first visit after 14 weeks). With the exception of Surinamese-Hindustani women, the percentage of mothers entering antenatal care late was higher in all non-Dutch compared to Dutch mothers. We could explain differences between Turkish (OR = 0.95, CI: 0.57-1.58), Cape Verdean (OR = 1.65. CI: 0.96-2.82) and Dutch women. Other differences diminished but remained significant (Moroccan: OR = 1,74, CI: 1.07-2.85; Dutch Antillean OR 1.80, CI: 1.04-3.13). We found that non-Dutch mothers were more likely to enter antenatal care later than Dutch mothers. Because we are unable to explain fully the differences regarding Moroccan, Surinamese-Creole and Antillean women, future research should focus on differences between 1st and 2nd generation migrants, as well as on language barriers that may hinder access to adequate information about the Dutch obstetric system.

Employment status and the risk of pregnancy complications: The Generation R Study (Article)

2010-06-01T00:00:00Z

Objectives: This study explored the relationships of employment status, type of unemployment and number of weekly working hours, with a wide range of pregnancy outcomes. Methods: Information on employment characteristics and pregnancy outcomes was available for 6111 pregnant women enrolled in a population-based cohort study in the Netherlands. Results: After adjustment for confounders, there were no statistically significant differences in risks of pregnancy complications between employed and unemployed women. Among unemployed women, women receiving disability benefit had an increased risk of preterm ruptured membranes (OR 3.16, 95% CI 1.49 to 6.70), elective caesarean section (OR 2.98, 95% CI 1.21 to 7.34) and preterm birth (OR 2.64, 95% CI 1.32 to 5.28) compared to housewives. Offspring of students and women receiving disability benefit had a significantly lower mean birth weight than offspring of housewives (difference: -93, 95% CI -174 to -12; and -97, 95% CI -190 to -5, respectively). In employed women, long working hours (≥40 h/week) were associated with a decrease of 45 g in offspring's mean birth weight (adjusted analysis; 95% CI -89 to -1) compared with 1-24 h/weekly working hours. Conclusions: We found no indications that paid employment during pregnancy effects the health of the mother and child. However, among unemployed and employed women, women receiving disability benefit, students and women with long working hours during pregnancy were at risk for some adverse pregnancy outcomes. More research is needed to replicate these results and explain these findings. Meanwhile, prenatal care providers should be made aware of the risks associated with specific types of unemployment and long working hours.

Estimating the effect of gestational age on test performance of combined first-trimester screening for down syndrome: A preliminary study (Article)

2010-05-01T00:00:00Z

Objective: To establish how different methods of estimating gestational age (GA) affect reliability of first-trimester screening for Down syndrome. Methods: Retrospective single-center study of 100 women with a viable singleton pregnancy, who had first-trimester screening. We calculated multiples of the median (MoM) for maternal-serum free beta human chorionic gonadotropin (free b-hCG) and pregnancy associated plasma protein-A (PAPP-A), derived from either last menstrual period (LMP) or ultrasound-dating scans. Results: In women with a regular cycle, LMP-derived estimates of GA were two days longer (range -11 to 18), than crown-rump length (CRL)-derived estimates of GA whereas this discrepancy was more pronounced in women who reported to have an irregular cycle, i.e., six days (range -7 to 32). Except for PAPP-A in the regular-cycle group, all differences were significant. Consequently, risk estimates are affected by the mode of estimating GA. In fact, LMP-based estimates revealed ten "screen-positive" cases compared to five "screen-positive" cases where GA was derived from dating-scans. Conclusion: Provided fixed values for nuchal translucency are applied, dating-scans reduce the number of screen-positive findings on the basis of biochemical screening. We recommend implementation of guidelines for Down syndrome creening based on CRL-dependent rather than LMPdependent parameters of GA.

Maternal psychological distress and fetal growth trajectories: the Generation R Study (Article)

2010-04-01T00:00:00Z

Abstract BACKGROUND: Previous research suggests, though not consistently, that maternal psychological distress during pregnancy leads to adverse birth outcomes. We investigated whether maternal psychological distress affects fetal growth during the period of mid-pregnancy until birth. METHOD: Pregnant women (n=6313) reported levels of psychological distress using the Brief Symptom Inventory (anxious and depressive symptoms) and the Family Assessment Device (family stress) at 20.6 weeks pregnancy and had fetal ultrasound measurements in mid- and late pregnancy. Estimated fetal weight was calculated using head circumference, abdominal circumference and femur length. RESULTS: In mid-pregnancy, maternal distress was not linked to fetal size. In late pregnancy, however, anxious symptoms were related to fetal size after controlling for potential confounders. Anxious symptoms were also associated with a 37.73 g [95% confidence interval (CI) -69.22 to -6.25, p=0.019] lower birth weight. When we related maternal distress to fetal growth curves using multilevel models, more consistent results emerged. Maternal symptoms of anxiety or depression were associated with impaired fetal weight gain and impaired fetal head and abdominal growth. For example, depressive symptoms reduced fetal weight gain by 2.86 g (95% CI -4.48 to -1.23, p<0.001) per week. CONCLUSIONS: The study suggests that, starting in mid-pregnancy, fetal growth can be affected by different aspects of maternal distress. In particular, children of prenatally anxious mothers seem to display impaired fetal growth patterns during pregnancy. Future work should address the biological mechanisms underlying the association of maternal distress with fetal development and focus on the effects of reducing psychological distress in pregnancy.

Associations of light and moderate maternal alcohol consumption with fetal growth characteristics in different periods of pregnancy: The generation R study (Article)

2010-03-01T00:00:00Z

Background: Excessive alcohol consumption during pregnancy has adverse effects on fetal growth and development. Less consistent associations have been shown for the associations of light-to-moderate maternal alcohol consumption during pregnancy with health outcomes in the offspring. Therefore, we examined the associations of light-to-moderate maternal alcohol consumption with various fetal growth characteristics measured in different periods of pregnancy. Methods: This study was based on 7333 pregnant women participating in a population-based cohort study. Alcohol consumption habits and fetal growth were assessed in early (gestational age <17.9 weeks), mid- (gestational age 18-24.9 weeks) and late pregnancy (gestational age ≥25 weeks). We assessed the effects of different categories of alcohol consumption (no; less than one drink per week; one to three drinks per week; four to six drinks per week; one drink per day and two to three drinks per day) on repeatedly measured fetal head circumference, abdominal circumference and femur length. Results: In total, 37% of all mothers continued alcohol consumption during pregnancy, of whom the majority used less than three drinks per week. We observed no differences in growth rates of fetal head circumference, abdominal circumference or femur length between mothers with and without continued alcohol consumption during pregnancy. Compared with mothers without alcohol consumption, mothers with continued alcohol consumption during pregnancy had an increased fetal weight gain [difference 0.61 g (95% confidence interval: 0.18, 1.04) per week]. Cross-sectional analyses in mid- and late pregnancy showed no consistent associations between the number of alcoholic consumptions and fetal growth characteristics. All analyses were adjusted for potential confounders. Conclusions: Light-to-moderate maternal alcohol consumption during pregnancy does not adversely affect fetal growth characteristics. Further studies are needed to assess whether moderate alcohol consumption during pregnancy influences organ growth and function in postnatal life.

Risk factors and outcomes associated with first-trimester fetal growth restriction (Article)

2010-02-10T00:00:00Z

Context: Adverse environmental exposures lead to developmental adaptations in fetal life. The influences of maternal physical characteristics and lifestyle habits on first-trimester fetal adaptations and the postnatal consequences are not known. Objective: To determine the risk factors and outcomes associated with firsttrimester growth restriction. Design, Setting, and Participants: Prospective evaluation of the associations of maternal physical characteristics and lifestyle habits with first-trimester fetal crown to rump length in 1631 mothers with a known and reliable first day of their last menstrual period and a regular menstrual cycle. Subsequently, we assessed the associations of first-trimester fetal growth restriction with the risks of adverse birth outcomes and postnatal growth acceleration until the age of 2 years. The study was based in Rotterdam, the Netherlands. Mothers were enrolled between 2001 and 2005. Main Outcome Measures: First-trimester fetal growth was measured as fetal crown to rump length by ultrasound between the gestational age of 10 weeks 0 days and 13 weeks 6 days. Main birth outcomes were preterm birth (gestational age <37 weeks), low birth weight (<2500 g), and small size for gestational age (lowest fifth birth centile). Postnatal growth was measured until the age of 2 years. Results In the multivariate analysis, maternal age was positively associated with firsttrimester fetal crown to rump length (difference per maternal year of age, 0.79 mm; 95% confidence interval [CI], 0.41 to 1.18 per standard deviation score increase). Higher diastolic blood pressure and higher hematocrit levels were associated with a shorter crown to rump length (differences, -0.40 mm; 95% CI, -0.74 to -0.06 and -0.52 mm; 95% CI, -0.90 to -0.14 per standard deviation increase, respectively). Compared with mothers who were nonsmokers and optimal users of folic acid supplements, those who both smoked and did not use folic acid supplements had shorter fetal crown to rump lengths (difference, -3.84 mm; 95% CI, -5.71 to -1.98). Compared with normal first-trimester fetal growth, first-trimester growth restriction was associated with increased risks of preterm birth (4.0% vs 7.2%; adjusted odds ratio [OR], 2.12; 95% CI, 1.24 to 3.61), low birth weight (3.5% vs 7.5%; adjusted OR, 2.42; 95% CI, 1.41 to 4.16), and small size for gestational age at birth (4.0% vs 10.6%; adjusted OR, 2.64; 95% CI, 1.64 to 4.25). Each standard deviation decrease in firsttrimester fetal crown to rump length was associated with a postnatal growth acceleration until the age of 2 years (standard deviation score increase, 0.139 per 2 years; 95% CI, 0.097 to 0.181). Conclusions Maternal physical characteristics and lifestyle habits were independently associated with early fetal growth. First-trimester fetal growth restriction was associated with an increased risk of adverse birth outcomes and growth acceleration in early childhood.

Fetal programming of infant neuromotor development: The generation R study (Article)

2010-02-01T00:00:00Z

The objective of the study was to examine whether infant neuromotor development is determined by fetal size and body symmetry in the general population. This study was embedded within the Generation R Study, a population-based cohort in Rotterdam. In 2965 fetuses, growth parameters were measured in mid-pregnancy and late pregnancy. After birth, at age 9 to 15 wks, neuromotor development was assessed with an adapted version of Touwen's Neurodevelopmental Examination. Less optimal neuromotor development was defined as a score in the highest tertile. We found that higher fetal weight was beneficial to infant neurodevelopment. A fetus with a 1-SD score higher weight in mid-pregnancy had an 11% lower risk of less optimal neuromotor development (OR: 0.89; 95% CI: 0.82-0.97). Similarly, a fetus with a 1-SD score larger abdominal-to-head circumference (AC/HC) ratio had a 13% lower risk of less optimal neuromotor development (OR: 0.87; 95% CI: 0.79-0.96). These associations were also present in late pregnancy. Our findings show that fetal size and body symmetry in pregnancy are associated with infant neuromotor development. These results suggest that differences in infant neuromotor development, a marker of behavioral and cognitive problems, are at least partly caused by processes occurring early in fetal life.

Forensic pregnancy diagnostics with placental mRNA markers (Article)

2010-01-01T00:00:00Z

Current methods for pregnancy diagnostics are based on immunodetection of pregnancy-specific proteins and in a forensic context suffer from sensitivity and specificity issues. Here, we applied reverse transcriptase polymerase chain reaction (RT-PCR) technology to 11 genes previously reported with placental mRNA circulating in maternal blood. We found two genes, hPL and βhCG, with pregnancy-specific expression in whole blood samples. RT-PCR detection of hPL was positive in all samples tested throughout the pregnancy, whereas βhCG was detectable until half of the second trimester but not at later gestation ages. For hPL, in vitro stability of the transcript was demonstrated until 2 months of age, and the hPL-specific RT-PCR assay applied was highly sensitive with reliable detection from down to 0.25 cm2 dried bloodstain. We therefore suggest hPL-specific RT-PCR as a new molecular tool for forensic pregnancy diagnostics from dried blood stains. Moreover, our results indicate that the time-wise reverse expression of hPL and βhCG during pregnancy may allow an RT-PCR-based estimation of the gestational age from blood stains, adding to the value of forensic pregnancy diagnosis for crime scene investigations.

First trimester umbilical cord and vitelline duct measurements using virtual reality (Article)

2010-01-01T00:00:00Z

Background: The umbilical cord and vitelline duct are of vital importance to the fetus, but they are rarely the subject of first trimester two-dimensional (2D) ultrasound evaluation due to the complexity of their shape and morphology. Virtual reality (VR) allows efficient visualisation and measurement of complex structures like the umbilical cord and vitelline duct. Aim: To measure normal first trimester human growth of the umbilical cord length (UCL) and vitelline duct length (VDL) using a VR system; and to correlate both measurements with the gestational age (GA) and crown-rump length (CRL) and the VDL with the yolk sac volume (YSV). Study design: Prospective cohort study. Serial three-dimensional (3D) ultrasound measurements were performed from six to 14 weeks GA, resulting in 125 3D volumes. These volumes were analysed using an I-Space VR system. Subjects: Thirty-two healthy pregnant women with an ongoing, normal pregnancy. Outcome measures: The UCL, VDL, YSV and other related structures were measured. Results: The UCL, measurable in 55% of cases, was positively correlated to advancing GA and CRL (p < 0.001). The VDL could be measured in 42% of cases and showed a positive relationship with GA and CRL (p < 0.001). There was a significant (p < 0.001) relationship between YSV and VDL. Conclusions: The present study, facilitated by a VR system, is the first to provide an in-vivo longitudinal description of normal first trimester growth of the human umbilical cord and vitelline duct. Further studies will reveal whether these parameters can be used in detection of abnormal fetal development.

Lijnen in de Perinatale Sterfte (Research Report)

2010-01-01T00:00:00Z

Voorwoord: De laatste jaren is er groeiende aandacht voor de gezondheid van zwangere vrouwen en hun pasgeboren kinderen. Een belangrijke aanleiding is geweest dat de sterfte van kinderen rondom de geboorte -perinatale sterfte- in Nederland hoger blijkt dan in de ons omringende landen en ook minder snel dan daar daalt. De betrokken beroepsgroepen, de overheid en daarnaast ook de media hebben in de discussie over de mogelijke oorzaken geparticipeerd. Zowel het functioneren van de typisch Nederlandse verloskundige ketenzorg, de risico’s van vrouwen door ziekte, leefstijl en sociaal-maatschappelijke status waaronder de woonomgeving, als de relatief grote verschillen in perinatale gezondheid tussen bevolkingsgroepen waren daarbij onderwerp van gesprek

Rapportage eerste jaar pilotstudie preconceptiezorg in deelgemeente Noord (Research Report)

2010-01-01T00:00:00Z

Inleiding: Nederland kent hoge perinatale sterftecijfers met grote verschillen tussen etnische, sociaaleconomische en tussen mensen al dan niet wonen in een grote stad of in een zogenoemde prachtwijk (De Graaf et al.; NTVG 2008;152:2734). Zwangere vrouwen die in een grote stad wonen hebben vaker een slechte zwangerschapsuitkomst. Verklaringen hiervoor zijn dat in grote steden meer allochtone ouders en ouders met een lage sociaaleconomische status wonen, meer ouders woonachtig zijn in een prachtwijk, en in de grote steden meer sprake is van cumulatie van diverse risico’s. Ongunstige perinatale uitkomsten komen binnen de vier grote steden in Rotterdam het meest voor. In Rotterdam vormt het wonen in een prachtwijk een extra risico, vooral voor autochtone ouders. De Nederlandse situatie gaf de minister aanleiding tot de installatie van de Stuurgroep Zwangerschap en Geboorte die binnen het huidige kader verbeteringsvoorstellen voorbereidt met de beroepsgroepen. Hij kondigde verder in 2008 aan dat - in dit verband - meer voorlichting aan toekomstige ouders speerpunt van beleid werd. In Rotterdam werd op grond van de cijfers in 2008 het Aanvalsplan Perinatale Sterfte (Denktas et al, TSG 2009;87:199; www.klaarvooreenkind.nl) ontwikkeld en omgedoopt tot het programma Klaar voor een Kind dat op 1 januari 2009 van start is gegaan. De gemeente Rotterdam investeert in de ontwikkeling en start-up van nieuwe preventieprogramma’s. De GGD Rotterdam-Rijnmond en het Erasmus MC coördineren het programma via het KveK-programmabureau. Dit regisseert de activiteiten (ontwikkeling, onderzoek, implementatie, afstemming, beleid). Het programma Klaar voor een Kind voorziet in verschillende projecten en de Pilotstudie Preconceptiezorg in deelgemeente Noord is de eerste die in uitvoering is genomen.

Human Placenta Is a Potent Hematopoietic Niche Containing Hematopoietic Stem and Progenitor Cells throughout Development (Article)

2009-10-02T00:00:00Z

Hematopoietic stem cells (HSCs) are responsible for the life-long production of the blood system and are pivotal cells in hematologic transplantation therapies. During mouse and human development, the first HSCs are produced in the aorta-gonad-mesonephros region. Subsequent to this emergence, HSCs are found in other anatomical sites of the mouse conceptus. While the mouse placenta contains abundant HSCs at midgestation, little is known concerning whether HSCs or hematopoietic progenitors are present and supported in the human placenta during development. In this study we show, over a range of developmental times including term, that the human placenta contains hematopoietic progenitors and HSCs. Moreover, stromal cell lines generated from human placenta at several developmental time points are pericyte-like cells and support human hematopoiesis. Immunostaining of placenta sections during development localizes hematopoietic cells in close contact with pericytes/perivascular cells. Thus, the human placenta is a potent hematopoietic niche throughout development.

Maternal medication use, carriership of the ABCB1 3435C > T polymorphism and the risk of a child with cleft lip with or without cleft palate (Article)

2009-10-01T00:00:00Z

Gene-environment interactions in the periconceptional period play an increasing role in the pathogenesis of birth defects, including cleft lip and/or cleft palate (CL/P). The P-glycoprotein, encoded by the ABCB1 gene, is suggested to protect the developing embryo from medication and other xenobiotic exposures. Furthermore, maternal medication use during early pregnancy is a significant risk factor for CL/P offspring. Therefore, the aim of this study is to investigate the association between the maternal and child's functional ABCB1 3435C > T polymorphism, periconceptional medication exposure, and the risk of a child with CL/P. A case-control study was performed among 175 mothers and 98 of their children with CL/P and 83 control mothers and their 65 children. Information on medication and folic acid use was collected. Mothers carrying the 3435TT genotype and using medication showed a 6.2-fold (95% CI = 1.6-24.2) increased risk of having a child with CL/P compared to mothers carrying the 3435CC genotype and not using medication. Periconceptional folic acid use reduced this risk by approximately 30% (OR = 3.9, 95% CI = 0.9-18.0). Mothers carrying the 3435TT genotype, using medication and not taking folic acid showed the highest risk estimate (OR = 19.2, 95% CI = 1.0-369.2). These data suggest that mothers who carry the ABCB1 3435C > T polymorphism are at significantly increased risk for having offspring with CL/P, especially mothers using medication in the periconceptional period.

Decreasing perinatal mortality in the Netherlands, 2000-2006: A record linkage study (Article)

2009-09-01T00:00:00Z

Background: The European PERISTAT-1 study showed that, in 1999, perinatal mortality, especially fetal mortality, was substantially higher in The Netherlands than in other European countries. The aim of this study was to analyse the recent trend in Dutch perinatal mortality and the influence of risk factors. Methods: A nationwide retrospective cohort study of 1 246 440 singleton births in 2000-2006 in The Netherlands. The source data were available from three linked registries: the midwifery registry, the obstetrics registry and the neonatology/paediatrics registry. The outcome measure was perinatal mortality (fetal and early neonatal mortality). The trend was studied with and without risk adjustment. Five clinical distinct groups with different perinatal mortality risks were used to gain further insight. Results: Perinatal mortality among singletons declined from 10.5 to 9.1 per 1000 total births in the period 2000-2006. This trend remained significant after full adjustment (odds ratio 0.97; 95% CI 0.96 to 0.98) and was present in both fetal and neonatal mortality. The decline was most prominent among births complicated by congenital anomalies, among premature births (32.0-36.6 weeks) and among term births. Home births showed the lowest mortality risk. Conclusions: Dutch perinatal mortality declined steadily over this period, which could not be explained by changes in known risk factors including high maternal age and nonwestern ethnicity. The decline was present in all risk groups except in very premature births. The mortality level is still high compared with European standards.

Fetal size in mid- and late pregnancy is related to infant alertness: The generation R study (Article)

2009-06-03T00:00:00Z

The vulnerability for behavioral problems is partly shaped in fetal life. Numerous studies have related indicators of intrauterine growth, for example, birth weight and body size, to behavioral development. We investigated whether fetal size in mid- and late pregnancy is related to infant irritability and alertness. In a population-based birth cohort of 4,255 singleton full-term infants ultrasound measurements of fetal head and abdominal circumference in mid- and late pregnancy were performed. Infant irritability and alertness scores were obtained by the Mother and Baby Scales at 3 months and z-standardized. Multiple linear regression analyses revealed curvilinear associations (inverted J-shape) of measures of fetal size in both mid- and late pregnancy with infant alertness. Fetal size characteristics were not associated with infant irritability. These results suggest that alterations of intrauterine growth affecting infant alertness are already detectable from mid-pregnancy onwards.

Explaining educational inequalities in birthweight: The Generation R Study (Article)

2009-05-01T00:00:00Z

Although low socio-economic status has consistently been associated with lower birthweight, little is known about the factors whereby socio-economic disadvantage influences birthweight. We therefore examined explanatory mechanisms that may underlie the association between the educational level of pregnant women, as an indicator of socio-economic status, and birthweight. The study was embedded within a population-based cohort study in the Netherlands. Information on maternal education, offspring's birthweight and several determinants of birthweight was available for 3546 pregnant women of Dutch origin. Infants of the lowest educated women had a statistically significantly lower birthweight than infants of the highest educated women [difference adjusted for gender and gestational age: -123 g (95% CI -167, -79)]. Parity, age of the pregnant women, hypertension, parental height and parental birthweight, marital status, pregnancy planning, financial concerns, number of people in household, weight gain and smoking habits individually explained part of the differences in birthweight, while adjustment for working hours and body mass index resulted in increases in birthweight differences between the educational levels. After full adjustment, the difference in birthweight between lowest and highest education was reduced by 66%. Our study confirmed remarkable educational inequalities in birthweight, a large part of which was explained by pregnancy characteristics, anthropometrics, the psychosocial and material situation, and lifestyle-related factors. Altering smoking habits may be an option to reduce educational differences in birthweight, as many lower-educated women tend to continue smoking during pregnancy. In order to tackle inequalities in birthweight, it is important that interventions are accessible for pregnant women in lower socio-economic strata.

Pharmacokinetics of amoxicillin in maternal, umbilical cord, and neonatal sera (Article)

2009-04-01T00:00:00Z

The pharmacokinetics of amoxicillin were studied in umbilical cord and neonatal sera relative to maternal concentrations in prevention of neonatal group B streptococcus infection. The subjects were 44 pregnant women receiving amoxicillin as 1 or 2 g as an intravenous infusion. To measure the concentrations, blood samples were obtained from the mother, the arterial and venous umbilical cord, and the neonate. The pharmacokinetics were characterized by a five-compartment model by using nonlinear mixed-effects (population) modeling. The population estimates for the clearance, central volume of distribution, and the two peripheral maternal volumes of distribution were 19.7 ± 0.99 liters/h, 6.40 ± 0.61 liters, and 5.88 ± 0.83 liters (mean ± standard error), respectively. The volume of distribution of the venous umbilical cord and the neonatal volume of distribution were 3.40 liters and 11.9 liters, respectively. The pharmacokinetic parameter estimates were used to simulate the concentration-time profiles in maternal, venous umbilical cord, and neonatal sera. The peak concentration in the venous umbilical cord serum was 18% of the maternal peak concentration. It was reached 3.3 min after the maternal peak concentration. The concentration-time profile in neonatal serum was determined by the profile in venous umbilical cord serum, which in turn depended on the profile in maternal serum. Furthermore, the simulated concentrations in maternal, venous umbilical cord, and neonatal sera exceeded the MIC for group B streptococcus for more than 90% of the 4-h dosing interval. In a first approximation, the 2-g infusion to the mother appears to be adequate for the prevention of group B streptococcal disease. However, to Investigate the efficacy of the prophylaxis, further studies of the interlndi-vidual variability in pharmacokinetics are indicated.

Information about prenatal screening for Down syndrome Ethnic differences in knowledge. (Article)

2009-04-01T00:00:00Z

OBJECTIVE: To evaluate the provision of information about prenatal screening for Down syndrome to women of Dutch, Turkish and Surinamese origins, and to examine the effects of this provision on ethnic differences in knowledge about Down syndrome and prenatal screening. METHODS: The study population consisted of 105 Dutch, 100 Turkish and 65 Surinamese pregnant women attending midwifery or obstetrical practices in The Netherlands. Each woman was personally interviewed for 3 weeks (mean) after booking for prenatal care. RESULTS: Most women reported to have received oral and/or written information about prenatal screening by their midwife or obstetrician at booking for prenatal care. Turkish and Surinamese women less often read the information than Dutch women, more often reported difficulties in understanding the information, and had less knowledge about Down syndrome, prenatal screening and amniocentesis. Language skills and educational level contributed most to the explanation of these ethnic variations. CONCLUSION: Although most Dutch, Turkish and Surinamese women reported to have received information from their midwife or obstetrician, ethnic differences in knowledge about Down syndrome and prenatal screening are substantial. PRACTICE IMPLICATIONS: Interventions to improve the provision of information to women from ethnic minority groups should especially be aimed at overcoming language barriers, and targeting information to the women's abilities to comprehend the information about prenatal screening for Down syndrome.

Vasculogenesis and Angiogenesis in the First Trimester Human Placenta: An Innovative 3D Study Using an Immersive Virtual Reality System (Article)

2009-03-01T00:00:00Z

First trimester human villous vascularization is mainly studied by conventional two-dimensional (2D) microscopy. With this (2D) technique it is not possible to observe the spatial arrangement of the haemangioblastic cords and vessels, transition of cords into vessels and the transition of vasculogenesis to angiogenesis. The Confocal Laser Scanning Microscopy (CLSM) allows for a three-dimensional (3D) reconstruction of images of early pregnancy villous vascularization. These 3D reconstructions, however, are normally analyzed on a 2D medium, lacking depth perception. We performed a descriptive morphologic study, using an immersive Virtual Reality system to utilize the full third dimension completely. This innovative 3D technique visualizes 3D datasets as enlarged 3D holograms and provided detailed insight in the spatial arrangement of first trimester villous vascularization, the beginning of lumen formation within various junctions of haemangioblastic cords between 5 and 7 weeks gestational age and in the gradual transition of vasculogenesis to angiogenesis. This innovative immersive Virtual Reality system enables new perspectives for vascular research and will be implemented for future investigation.

The maternal Mediterranean dietary pattern is associated with a reduced risk of spina bifida in the offspring (Article)

2009-02-01T00:00:00Z

Objective: The objective of this study was to test the hypothesis whether a maternal dietary pattern is associated with the risk of spina bifida (SB) in the offspring. Design: Case-control study. Setting: Eight clinic sites in the Netherlands, 1999-2001. Sample: A total of 50 mothers of children with SB and 81 control mothers. Methods: Maternal food intakes were obtained by food frequency questionnaires at the standardised study moment of 14 months after the birth of the index child. Principal component factor analysis (PCA) and reduced rank regression (RRR) were used to identify dietary patterns. Main outcome measures: Maternal biomarkers were used as response measures in the RRR analysis and composed of serum and red blood cell (RBC) folate, serum vitamin B12 and total plasma homocysteine. The strength of the use of the dietary pattern in association with SB risk was estimated by odds ratios and 95% CI with the highest quartiles of the dietary pattern as reference. Results: A predominantly Mediterranean dietary pattern was identified by both PCA and RRR. Those dietary patterns were highly correlated (r = 0.51, P < 0.001) and characterised by joint intakes of fruit, vegetables, vegetable oil, alcohol, fish, legumes and cereals and low intakes of potatoes and sweets. We observed a significantly increased risk of SB offspring in mothers with a weak use of the Mediterranean dietary pattern, OR 2.7 (95% CI 1.2-6.1) and OR 3.5 (95% CI 1.5-7.9). The Mediterranean dietary pattern was correlated with higher levels of serum and RBC folate, serum vitamin B12 and lower plasma homocysteine. Conclusion: The Mediterranean dietary pattern seems to be associated with reduction in the risk of offspring being affected by SB.

Body composition by dual-energy X-ray absorptiometry in women with previous pre-eclampsia or small-for-gestational-age offspring (Article)

2009-02-01T00:00:00Z

Objective: To investigate differences in body composition and fat distribution between women with previous pre-eclampsia or small-for-gestational- age (SGA) offspring and those with uncomplicated pregnancies. Design: Cohort study. Setting: Population-based study in a genetically isolated population in the southwest of the Netherlands. Population: Women after pregnancies complicated by pre-eclampsia (n=45), SGA offspring (n=53) and uncomplicated pregnancies (n=106). Methods: Women were compared for body composition and fat distribution variables, assessed by dual-energy X-ray absorptiometry (DXA) and anthropometrics at a mean follow-up time of 10.8 (SD ±5.9) years after pregnancy. Main outcome measures: Total lean and fat mass, android fat mass, gynoid fat mass, android-to-gynoid fat ratio, waist and hip circumference, waist-to-hip ratio. Results: Women with previous pre-eclampsia compared with controls had higher mean total fat mass index (11.5 ± 0.6 versus 9.7 ± 0.4 kg/m2; P = 0.03), lean mass index (15.8 ± 0.3 versus 14.5 ± 0.2 kg/m2; P = 0.001) and body mass index ([BMI]; 28.4 ± 0.8 versus 25.4 ± 0.5 kg/m2; P = 0.005). Their waist circumferences (90.7 ± 2.0 versus 78.5 ± 1.3 cm; P < 0.001) and waist-to-hip ratios (0.86 ± 0.01 versus 0.77 ± 0.01; P < 0.001) were also higher as well as android fat mass (2.8 ± 0.2 versus 2.1 ± 0.1 kg; P = 0.01) and android-to-gynoid fat ratios (0.45 ± 0.02 versus 0.39 ± 0.01; P = 0.02). Mean total fat, lean and BMI was not significantly different between women with previous SGA offspring and controls, yet waist-to-hip ratios (0.83 ± 0.01; P < 0.001) were higher. The observed differences in waist and hip circumference, waist-to-hip ratio and gynoid fat mass could not be attributed to differences in BMI. Conclusion: Women with previous pre-eclampsia or SGA offspring pregnancies compared with those with uncomplicated pregnancies have a preferential fat accumulation in the abdominal over hip region, which may explain, at least partly, their increased cardiovascular risk.

High maternal vitamin E intake by diet or supplements is associated with congenital heart defects in the offspring (Article)

2009-02-01T00:00:00Z

Objective: To study associations between maternal dietary and supplement intake of antioxidants vitamin E, retinol and congenital heart defects (CHDs). Design: Case-control study. Setting: Erasmus MC, University Medical Center Rotterdam, the Netherlands. Population: Participants were 276 case mothers of a child with CHD and 324 control mothers with their children. Methods: Food frequency questionnaires covering the intake of the previous 4 weeks were filled out at 16 months after the index pregnancy. Data were compared between cases and controls using the Mann-Whitney U test. Risk estimates for the association between CHD and dietary intake of vitamin E and retinol were estimated in a multivariable logistic regression model. Main outcome measures: Medians (5-95th percentile) and odds ratios with 95% CI. Results: Dietary vitamin E intake was higher in case mothers than in controls, 13.3 (8.1-20.4) and 12.6 (8.5-19.8) mg/day (P = 0.05). CHD risk increased with rising dietary vitamin E intakes (P-trend = 0.01). Periconception use of vitamin E supplements in addition to a high dietary vitamin E intake above 14.9 mg/day up to nine-fold increased CHD risk. Retinol intakes were not significantly different between the groups and not associated with CHD risk. Conclusions: High maternal vitamin E by diet and supplements is associated with an increased risk of CHD offspring.

Maternal folic acid supplement use in early pregnancy and child behavioural problems: The Generation R Study (Article)

2009-01-01T00:00:00Z

Folate deficiency during embryogenesis is an established risk factor for neural tube defects in the fetus. An adequate folate nutritional status is also important for normal fetal growth and brain development. The aim of the present research was to study the association between folic acid use of the mother during pregnancy and child behavioural development. Within a population-based cohort, we prospectively assessed folic acid supplement use during the first trimester by questionnaire. Child behavioural and emotional problems were assessed with the Child Behaviour Checklist at the age of 18 months in 4214 toddlers. Results showed that children of mothers who did not use folic acid supplements in the first trimester had a higher risk of total problems (OR 1·44; 95 % CI 1·12, 1·86). Folic acid supplement use protected both from internalising (OR of no supplement use 1·65; 95 % CI 1·24, 2·19) and externalising problems (OR 1·45; 95 % CI 1·17, 1·80), even when adjusted for maternal characteristics. Birth weight and size of the fetal head did not mediate the association between folic acid use and child behaviour. In conclusion, inadequate use of folic acid supplements during early pregnancy may be associated with a higher risk of behavioural problems in the offspring. Folic acid supplementation in early pregnancy, aimed to prevent neural tube defects, may also reduce mental health problems in children.

Folic acid is positively associated with uteroplacental vascular resistance: The Generation R Study (Article)

2009-01-01T00:00:00Z

Background and aims: Periconception folic acid supplementation may influence early placentation processes and thereby the occurrence of hypertensive pregnancy disorders. For this reason we examined the associations between periconception folic acid supplementation and uteroplacental vascular resistance, blood pressure, and the risks of gestational hypertension and preeclampsia, in 5993 pregnant women, participating in a population-based cohort study. Methods and results: Folic acid supplementation was assessed by questionnaire. Mean pulsatility index (PI) and resistance index (RI) of the uterine (UtA) and umbilical arteries (UmA) were measured by Doppler ultrasound in mid- and late pregnancy. Systolic and diastolic blood pressures (SBP, DBP) were measured in early, mid- and late pregnancy. Compared to women who did not use folic acid, preconception folic acid users had a slightly lower UtA-RI in mid-pregnancy [β -0.02, 95% confidence interval (CI) -0.03, -0.01] and late pregnancy [β -0.02, 95% CI -0.03, -0.001], a lower UtA-PI in mid-pregnancy [β -0.06, 95% CI -0.1, -0.03] and late pregnancy [β -0.03, 95% CI -0.05, -0.01], as well as tendencies towards a lower UmA-PI in mid-pregnancy [β -0.02, 95% CI -0.04, -0.001] and late pregnancy [β -0.01, 95% CI -0.02, 0.01]. Additionally, these women had slightly higher SBP and DBP throughout pregnancy. Neither the patterns of blood-pressure change during pregnancy, nor the risk of gestational hypertension and preeclampsia differed between the folic acid categories. Conclusion: Periconception folic acid supplementation is associated with lower uteroplacental vascular resistance and higher blood pressures during pregnancy. The effects are small and within physiologic ranges and seem not associated with the risk of hypertensive pregnancy disorders.

Medical record validation of maternally reported history of preeclampsia (Article)

2009-01-01T00:00:00Z

Objective: In this study, we assessed the validity of maternally self-reported history of preeclampsia. Study Design and Setting: This study was embedded in the Generation R Study, a population-based prospective cohort study. Data were obtained from prenatal questionnaires and one questionnaire obtained 2 months postpartum from the mother. All women who delivered in hospital and returned a 2-month postpartum questionnaire (n = 4,330) were selected. Results: Of the 4,330 women, 76 out of 152 (50%) women who self-reported preeclampsia appeared not to have had the disease according to the definition (International Society for the Study of Hypertension in Pregnancy). From the women who self-reported not to have experienced preeclampsia, 11 out of 4,178 (0.3%) had suffered from preeclampsia. Sensitivity and specificity were 0.87 and 0.98, respectively. Higher maternal education level and parity were associated with a better self-reported diagnosis of preeclampsia. Conclusion: The validity of maternal-recall self-reported preeclampsia is moderate. The reduced self-reported preeclampsia might suggest a lack of accuracy in patient-doctor communication with regard to the diagnostic criteria of the disease. Therefore, doctors have to pay attention to make sure that women understand the nature of preeclampsia.

The preconception Mediterranean dietary pattern in couples undergoing in vitro fertilization/intracytoplasmic sperm injection treatment increases the chance of pregnancy (Article)

2009-01-01T00:00:00Z

Objective: To investigate associations between preconception dietary patterns and IVF/intracytoplasmic sperm injection (ICSI) outcomes validated by biomarkers of the homocysteine pathway. Design: Observational prospective study. Setting: A tertiary referral fertility clinic at the Erasmus University Medical Centre, Rotterdam, The Netherlands. Patient(s): One hundred sixty-one couples undergoing IVF/ICSI treatment. Intervention(s): No interventions other than the Dutch governmental recommendation of folic acid. Main Outcome Measure(s): Dietary patterns, blood and follicular fluid concentrations of folate, vitamin B12, vitamin B6, homocysteine, and fertilization rate, embryo quality, and pregnancy. Result(s): In women, two dietary patterns were identified. The "health conscious-low processed" dietary pattern (variation explained 12.1%) was characterized by high intakes of fruits, vegetables, fish, and whole grains and low intakes of snacks, meats, and mayonnaise, and positively correlated with red blood cell folate (β = 0.07). The "Mediterranean" dietary pattern (variation explained 9.1%), that is, high intakes of vegetable oils, vegetables, fish, and legumes and low intakes of snacks, was positively correlated with red blood cell folate (β = 0.13), and vitamin B6 in blood (β = 0.09) and follicular fluid (β = 0.18). High adherence by the couple to the "Mediterranean" diet increased the probability of pregnancy, odds ratio 1.4 (95% confidence interval 1.0-1.9). Conclusion(s): A preconception "Mediterranean" diet by couples undergoing IVF/ICSI treatment contributes to the success of achieving pregnancy. © 2010 American Society for Reproductive Medicine.

Perinatale uitkomsten in de vier grote steden en de prachtwijken in Nederland (Article)

2008-12-13T00:00:00Z

Doel. Het verband tussen woonwijk, etniciteit en ongunstige perinatale uitkomsten analyseren bij zwangeren in de 4 grootste steden (Amsterdam, Rotterdam, Den Haag en Utrecht; G4) en in de rest van Nederland. Opzet. Descriptief, retrospectief. Methode. De perinatale uitkomst van 877.816 eenlingzwangerschappen in Nederland in de periode 2002-2006, vastgelegd in de Perinatale Registratie Nederland, werd geanalyseerd op etniciteit van de zwangere (westers of niet-westers) en op woonwijk (achterstandswijk (‘prachtwijk’) of niet) in de G4-steden en daarbuiten. Een ongunstige perinatale uitkomst was gedefinieerd als perinatale sterfte, congenitale afwijkingen, dysmaturiteit, vroeggeboorte, een apgar-score na 5 minuten < 7 en/of opname op een neonatale intensivecareunit. Resultaten. Het perinatale sterftecijfer was in de G4-steden hoger dan in de rest van Nederland (11,1 versus 9,3‰; p < 0,001; 95%-BI van het verschil: 1,2-2,4‰). Hetzelfde gold voor het totaal van ongunstige perinatale uitkomsten (154,9 versus 138,9‰). In de G4-steden was de perinatale sterfte in de groep niet-westerse vrouwen hoger dan in de groep westerse vrouwen (13,2 versus 9,5‰). Het wonen in een prachtwijk gaat gepaard met een hogere perinatale sterfte dan in een niet-prachtwijk (13,5 versus 9,3‰). De relatieve risico’s van het wonen in een prachtwijk zijn groter bij westerse dan bij niet-westerse vrouwen. Conclusie. Vrouwen in de G4-steden hebben een sterk verhoogde kans op een ongunstige perinatale uitkomst. Wonen in een prachtwijk vormt een nog groter risico, vooral voor westerse zwangeren. Deze bevindingen zijn van belang voor het vaststellen van nieuwe strategieën ter verbetering van de perinatale uitkomst.

The influence of labour on the pharmacokinetics of intravenously administered amoxicillin in pregnant women (Article)

2008-12-01T00:00:00Z

AIMS: Many physiological changes take place during pregnancy and labour. These might change the pharmacokinetics of amoxicillin, necessitating adjustment of the dose for prevention of neonatal infections. We investigated the influence of labour on the pharmacokinetics of amoxicillin. METHODS: Pregnant women before and during labour were recruited and treated with amoxicillin intravenously. A postpartum dose was offered. Blood samples were obtained and amoxicillin concentrations were determined using high-pressure liquid chromatography. The pharmacokinetics were characterized by nonlinear mixed-effects modelling using NONMEM. RESULTS: The pharmacokinetics of amoxicillin in 34 patients was best described by a three-compartment model. Moderate interindividual variability was identified in CL, central and peripheral volumes of distribution. The volume of distribution (V) increased with an increasing amount of oedema. Labour influenced the parameter estimate of peripheral volume of distribution (V2). V2 was decreased during labour, and even more in the immediate postpartum period. For all patients the population estimates (mean ± SE) for CL and V were 21.1 ± 4.1 l h-1 (CL), 8.7 ± 6.6 l (V1), 11.8 ± 7.7 l (V2) and 20.5 ± 15.4 l (V3) respectively. CONCLUSIONS: The peripheral distribution volume of amoxicillin in pregnant women during labour and immediately postpartum is decreased. However, these changes are not clinically relevant and do not warrant deviations from the recommended dosing regimen for amoxicillin during labour in healthy pregnant patients.

Maternal death after oocyte donation at high maternal age: Case report (Article)

2008-12-01T00:00:00Z

Background. The percentage of women giving birth after the age of 35 increased in many western countries. The number of women remaining childless also increased, mostly due to aging oocytes. The method of oocyte donation offers the possibility for infertile older women to become pregnant. Gestation after oocyte-donation-IVF, however, is not without risks for the mother, especially at advanced age. Case presentation. An infertile woman went abroad for oocyte-donation-IVF, since this treatment is not offered in The Netherlands after the age of 45. The first oocyte donation treatment resulted in multiple gestation, but was ended by induced abortion: the woman could not cope with the idea of being pregnant with twins. During the second pregnancy after oocyte donation, at the age of 50, she was mentally more stable. The pregnancy, again a multiple gestation, was uneventful until delivery. Immediately after delivery the woman had hypertension with nausea and vomiting. A few hours later she had an eclamptic fit. HELLP-syndrome was diagnosed. She died due to cerebral haemorrhage. Conclusion. In The Netherlands, the age limit for women receiving donor oocytes is 45 years and commercial oocyte donation is forbidden by law. In other countries there is no age limit, the reason why some women are going abroad to receive the treatment of their choice. Advanced age, IVF and twin pregnancy are all risk factors for pre-eclampsia, the leading cause of maternal death in The Netherlands. Patient autonomy is an important ethical principle, but doctors are also bound to the principle of 'not doing harm', and do have the right to refuse medical treatment such as IVF-treatment. The discussion whether women above 50 should have children is still not closed. If the decision is made to offer this treatment to a woman at advanced age, the doctor should counsel her intensively about the risks before treatment is started.

What is spared by fetal brain-sparing? Fetal circulatory redistribution and behavioral problems in the general population (Article)

2008-11-01T00:00:00Z

Intrauterine growth restriction has been linked to infant behavioral problems. While typically only birth weight is examined, here the authors assessed fetal circulatory redistribution, also called the "brain-sparing effect," which is a fetal adaptive reaction to placental insufficiency. They aimed to investigate whether fetal circulatory redistribution protects against behavioral problems. Within the Generation R Study (Rotterdam, the Netherlands, 2003-2007), fetal circulation variables for the umbilical artery and the middle and anterior cerebral arteries were assessed with Doppler ultrasound in late pregnancy. Ratios between placental resistance and cerebral resistance were related to behavioral problems, as measured by the Child Behavior Checklist, in 935 toddlers aged 18 months. The umbilical/anterior cerebral ratio was associated with the Total Problems summary score from the Child Behavior Checklist (per standard-deviation increase, odds ratio = 1.2, 95% confidence interval: 1.0, 1.5). Children with higher umbilical/anterior cerebral ratios had higher risks of internalizing problems, emotional reactivity, somatic complaints, and attention problems. A high umbilical/middle cerebral ratio was related to higher scores on the Internalizing and Somatic Complaints scales. The authors conclude that infants with circulatory redistribution in gestation are more likely to have behavioral problems. This suggests that "brain-sparing" does not completely spare the brain and indicates underlying pathology with consequences for later behavior.

Jugular lymphatic sacs in the first trimester of pregnancy: The prevalence and the potential value in screening for chromosomal abnormalities (Article)

2008-11-01T00:00:00Z

Objective: To investigate the prevalence of detectable jugular lymphatic sacs in a setting for first trimester screening for Down syndrome, and to evaluate the influence of jugular lymphatic sacs on the screening performance for chromosomal abnormalities. Methods: A prospective single center study (Erasmus University Medical Center, Rotterdam, The Netherlands) over a period of one year (January 2003-February 2004). First trimester nuchal translucency measurement was performed in a study population of 415 fetuses. Additionally, the transversal plane with the spine and mandible was visualized to verify the presence of jugular lymphatic sacs. The jugular lymphatic sacs were measured anterior-posterior. The association between nuchal translucency and jugular lymphatic sacs was tested. Results: Follow-up was complete in 406 cases (97.8%). Jugular lymphatic sacs could be visualized in 98 out of 415 (23.5%). The nuchal translucency thickness and the mean of the left and right jugular lymphatic sac were significantly correlated. Conclusion: The sonographic visualization of jugular lymphatic sacs significantly predicts chromosomal abnormalities, although nuchal translucency is a better predictor. Nuchal translucency and jugular lymphatic sacs are strongly correlated and therefore not applicable in a combination test.

Embryonic delay in growth and development related to confined placental trisomy 16 mosaicism, diagnosed by I-Space Virtual Reality (Article)

2008-11-01T00:00:00Z

Objective: To demonstrate the use of a novel three-dimensional (3D) virtual reality (VR) system in the visualization of first trimester growth and development in a case of confined placental trisomy 16 mosaicism (CPM+16). Design: Case report. Setting: Prospective study on first trimester growth using a 3D VR system. Patient(s): A 34-year-old gravida 1, para 0 was seen weekly in the first trimester for 3D ultrasound examinations. Intervention(s): Chorionic villus sampling was performed because of an enlarged nuchal translucency (NT) measurement and low pregnancy-associated plasma protein-A levels, followed by amniocentesis. Result(s): Amniocentesis revealed a CPM+16. On two-dimensional (2D) and 3D ultrasound no structural anomalies were found with normal fetal Dopplers. Growth remained below the 2.3 percentile. At 37 weeks, a female child of 2010 g (<2.5 percentile) was born. After birth, growth climbed to the 50th percentile in the first 2 months. Conclusion(s): The I-Space VR system provided information about phenotypes not obtainable by standard 2D ultrasound. In this case, the delay in growth and development could be observed very early in pregnancy. Since first trimester screening programs are still improving and becoming even more important, systems such as the I-Space open a new era for in vivo studies on the physiologic and pathologic processes involved in embryogenesis.

Homocysteine metabolism in the pre-ovulatory follicle during ovarian stimulation (Article)

2008-11-01T00:00:00Z

BACKGROUND: Ovarian stimulation gives rise to supraphysiological estradiol levels, which may affect oocyte quality. This study aims to investigate whether ovarian stimulation deranges the homocysteine pathway thereby affecting the pre-ovulatory follicle. METHODS: Blood samples were collected on cycle day 2 and the day of hCG administration in 181 women undergoing ovarian stimulation for IVF. In each subject, the diameter of the two leading follicles was measured and the corresponding follicular fluids were collected. In blood and follicular fluid samples, total homocysteine (tHcy), folate, cobalamin and pyridoxal'5-phosphate (PLP) were determined. According to the blood folate levels, women were classified as either folic acid supplemented (n = 113) or non-supplemented (n = 32). RESULTS: Ovarian stimulation resulted in a significant decrease in blood tHcy and cobalamin levels (both P ≤ 0.001). The blood concentrations of tHcy, folate, cobalamin and PLP were significantly correlated with the corresponding follicular fluid concentrations (all P ≤ 0.001). Follicular fluid tHcy concentrations were inversely correlated with follicular diameter (P ≤ 0.05). In folic acid supplemented women, follicular fluid folate was inversely correlated with follicular diameter (P ≤ 0.05). CONCLUSIONS: Ovarian stimulation deranges blood and follicular fluid biomarkers of the homocysteine pathway. High ovarian follicular fluid tHcy and folate levels may have detrimental effects on follicular development.

No midpregnancy fall in diastolic blood pressure in women with a low educational level: The generation R study (Article)

2008-10-01T00:00:00Z

Low socioeconomic status has been associated with preeclampsia. The underlying mechanism, however, is unknown. Preeclampsia is associated with relatively high blood pressure levels in early pregnancy and with an absent midpregnancy fall in blood pressure. At present, little is known about the associations among socioeconomic status, blood pressure level in early pregnancy, blood pressure change during pregnancy, and preeclampsia. We studied these associations in 3142 pregnant women participating in a population-based cohort study. Maternal educational level (high, midhigh, midlow, and low) was used as an indicator of socioeconomic status. Systolic and diastolic blood pressure was measured in early, mid-, and late pregnancy. Relative to women with high education, those with low and midlow education had higher mean systolic and diastolic blood pressure levels in early pregnancy; this was explained largely by a higher prepregnancy body mass index. Although women with high, midhigh, and midlow education had a significant midpregnancy fall in diastolic blood pressure, those with low education did not (change from early to midpregnancy: -0.38 mm Hg; 95% CI: -1.33 to 0.58). The latter could not be explained by prepregnancy body mass index, smoking, or alcohol consumption during pregnancy. The absence of a midpregnancy fall also tended to be related to the development of preeclampsia, especially among women with a low educational level (OR: 3.8; 95% CI: 0.80 to 18.19). The absence of a midpregnancy fall in diastolic blood pressure in women with a low education level may be a sign of endothelial dysfunction that is manifested during pregnancy. This might partly explain these women's susceptibility to preeclampsia.

Maternal intake of fat, riboflavin and nicotinamide and the risk of having offspring with congenital heart defects (Article)

2008-10-01T00:00:00Z

Background: With the exception of studies on folic acid, little evidence is available concerning other nutrients in the pathogenesis of congenital heart defects (CHDs). Fatty acids play a central role in embryonic development, and the B-vitamins riboflavin and nicotinamide are co-enzymes in lipid metabolism. Aim of the study: To investigate associations between the maternal dietary intake of fats, riboflavin and nicotinamide, and CHD risk in the offspring. Methods: A case-control family study was conducted in 276 mothers of a child with a CHD comprising of 190 outflow tract defects (OTD) and 86 non-outflow tract defects (non-OTD) and 324 control mothers of a non-malformed child. Mothers filled out general and food frequency questionnaires at 16 months after the index-pregnancy, as a proxy of the habitual food intake in the preconception period. Nutrient intakes (medians) were compared between cases and controls by Mann-Whitney U test. Odds ratios (OR) for the association between CHDs and nutrient intakes were estimated in a logistic regression model. Results: Case mothers, in particular mothers of a child with OTD, had higher dietary intakes of saturated fat, 30.9 vs. 29.8 g/d; P < 0.05. Dietary intakes of riboflavin and nicotinamide were lower in mothers of a child with an OTD than in controls (1.32 vs. 1.41 mg/d; P < 0.05 and 14.6 vs. 15.1 mg/d; P < 0.05, respectively). Energy, unsaturated fat, cholesterol and folate intakes were comparable between the groups. Low dietary intakes of both riboflavin (<1.20 mg/d) and nicotinamide (<13.5 mg/d) increased more than two-fold the risk of a child with an OTD, especially in mothers who did not use vitamin supplements in the periconceptional period (OR 2.4, 95%CI 1.4-4.0). Increasing intakes of nicotinamide (OR 0.8, 95%CI 0.7-1.001, per unit standard deviation increase) decreased CHD risk independent of dietary folate intake. Conclusions: A maternal diet high in saturated fats and low in riboflavin and nicotinamide seems to contribute to CHD risk, in particular OTDs.

Does gestational duration within the normal range predict infant neuromotor development? (Article)

2008-10-01T00:00:00Z

Aim: To examine the extent to which infant neuromotor development is determined by gestational duration and birth weight within the normal range. Methods: The study was embedded within the Generation R Study, a population-based cohort in Rotterdam, the Netherlands. An adapted version of Touwen's Neurodevelopmental Examination was used to assess 3224 infants (1576 males and 1648 females) at corrected ages between 9 and 15 weeks. Non-optimal neuromotor development was defined as a score in the highest tertile. Results: Infant neuromotor development was significantly affected by gestational duration (odds ratio 0.8, 95% confidence interval 0.7;0.8). Adding a quadratic term of gestational duration to the model revealed a highly significant curvilinear association between gestational duration and neuromotor development; after adjusting for post-conceptional age this was still significant. Although babies with a 1 kg lower birth weight had a 30% higher risk of non-optimal neuromotor development, this association disappeared after adjustment for post-conceptional age. Conclusions: Our findings indicate that differences in infant neuromotor development can be explained even by variations in gestational duration within the normal range. If an infant is found to have minor neuromotor delays, account should be taken of this.

Urinary metabolite concentrations of organophosphorous pesticides, bisphenol A, and phthalates among pregnant women in Rotterdam, the Netherlands: The Generation R study (Article)

2008-09-05T00:00:00Z

Concern about potential health impacts of low-level exposures to organophosphorus (OP) pesticides, bisphenol A (BPA), and phthalates among the general population is increasing. We measured levels of six dialkyl phosphate (DAP) metabolites of OP pesticides, a chlorpyrifos-specific metabolite (3,5,6-trichloro-2-pyridinol, TCPy), BPA, and 14 phthalate metabolites in urine samples of 100 pregnant women from the Generation R study, the Netherlands. The unadjusted and creatinine-adjusted concentrations were reported, and compared to National Health and Nutrition Examination Survey and other studies. In general, these metabolites were detectable in the urine of the women from the Generation R study and compared with other groups, they had relatively high-level exposures to OP pesticides and several phthalates but similar exposure to BPA. The median concentrations of total dimethyl (DM) metabolites was 264.0 nmol/g creatinine (Cr) and of total DAP was 316.0 nmol/g Cr. The median concentration of mono-ethyl phthalate (MEP) was 222.0 μg/g Cr; the median concentrations of mono-isobutyl phthalate (MiBP) and mono-n-butyl phthalate (MnBP) were above 50 μg/g Cr. The median concentrations of the three secondary metabolites of di-2-ethylhexyl phthalate (DEHP) were greater than 20 μg/g Cr. The data indicate that the Generation R study population provides a wide distribution of selected environmental exposures. Reasons for the relatively high levels and possible health effects need investigation.

Using virtual reality for evaluation of fetal ambiguous genitalia (Article)

2008-09-01T00:00:00Z

Objective The utility of a virtual reality system was examined in the visualization of three-dimensional (3D) ultrasound images of fetal ambiguous genitalia. Methods In 2005, fetal ambiguous genitalia were diagnosed in four patients referred to our department for prenatal ultrasound assessment. The patients were examined by two-dimensional (2D) and 3D ultrasound and, subsequently, the volumes obtained on 3D ultrasound were visualized in the BARCO I-Space virtual reality system. This system projects stereoscopic images on three walls and the floor of a small 'room', allowing several viewers to see a 3D 'hologram' of the data being visualized. The results of 2D and 3D ultrasound examination and the virtual reality images of the I-Space were compared with diagnoses made postpartum. Results In all cases, prenatal diagnosis was unclear based on 2D ultrasound alone. Surface rendering of 3D data provided an impression of ambiguity, but diagnosis based on these data proved incorrect at birth in three cases. Conclusions based on the evaluation of 3D volumes in virtual reality best fitted the postpartum diagnosis in all cases. Conclusions This study suggests that by evaluation of the genitals in the I-Space, a better impression of genital ambiguity can be established. Binocular depth perception appeared particularly useful in distinguishing either a micropenis or enlarged clitoris from labia minora, since it helps in the estimation of size and position. Therefore, we see potential for the application of virtual reality not only for the evaluation of fetal ambiguous genitalia, but in all those cases where depth perception would improve the visualization of anatomical structures.

Genome-wide pathway analysis of folate-responsive genes to unravel the pathogenesis of orofacial clefting in man (Article)

2008-09-01T00:00:00Z

BACKGROUND: A cleft of the lip with or without the palate (CLP) is a frequent congenital malformation with a heterogeneous etiology, for which folic acid supplementation has a protective effect. To gain more insight into the molecular pathways affected by natural folate, we examined gene expression profiles of cultured B-lymphoblasts from CLP patients before and after the addition of 5-methyltetrahydrofolate (5-mTHF) to the cultures. METHODS: Immortalized B-lymphoblasts from five children with CLP were cultured in folate-deficient medium for 5 days. 5-mTHF was added to a concentration of 30 nM. Gene expression patterns were then evaluated before and after supplementation using Human Genome U133 Plus 2.0 arrays. Data analysis was performed with Omniviz and the GEPAS analysis suite. Differential genes were categorized into biological pathways with Ingenuity Pathway systems. Differential expression was validated by quantitative RT-PCR. RESULTS: Using supervised clustering, with a false discovery rate <1%, we identified 144 and 409 significantly up-regulated and down-regulated probesets, respectively, after 5-mTHF addition. The regulated genes were involved in a variety of biological pathways, including one carbon pool and cell cycle regulation, biosynthesis of amino acids and DNA/RNA nucleotides, protein processing, apoptosis, and DNA repair. CONCLUSIONS: The large variety of the identified folate responsive pathways fits with the modifying role of folate via the methylation pathway. From the present data we may conclude that folate deficiency deranges normal cell development, which might contribute to the development of CLP. The role of these folate responsive genes in CLP development is intriguing and needs further investigation.

Author response to: Substandard care in maternal mortality due to hypertensive disease in pregnancy in the Netherlands (Article)

2008-09-01T00:00:00Z

Familial aggregation of preeclampsia and intrauterine growth restriction in a genetically isolated population in The Netherlands (Article)

2008-07-10T00:00:00Z

Preeclampsia and intrauterine growth restriction are related, pregnancy-specific disorders with a substantial genetic influence, which may have a joint genetic aetiology. We investigated familial aggregation, consanguinity and parent-of-origin effects for preeclampsia and IUGR. Fifty women with previous preeclampsia and 56 with previous pregnancies complicated by intrauterine growth restriction were recruited from a recent genetically isolated population in the Netherlands. Their relationships were estimated by means of a large genealogy database that contains information on more than 110000 individuals from the isolate over 23 generations. Relationships were quantified using kinship and inbreeding coefficients. Parent-of-origin effects were evaluated by comparing parental kinships. Eighty-six women (39 preeclampsia and 47 intrauterine growth restriction) could be linked to one common ancestor within 14 generations. The proportion of related women with previous preeclampsia (95.6%) or pregnancies complicated by intrauterine growth restriction (95.1%) was significantly greater than expected by chance (P<0.001). Combined analysis of both disorders did not change the magnitude of familial aggregation. The proportion of women born from consanguineous marriages was increased in women with previous preeclampsia (81.8%) and those with intrauterine growth restriction (78%) compared to a random sample (P<0.001). Maternal and paternal kinships were not significantly different in both disorders. We demonstrate cosegregation of preeclampsia and intrauterine growth restriction, supporting a common genetic aetiology. The high proportion of parental consanguineous marriages suggests the possibility of an underlying recessive mutation. No evidence was found for a parent-of-origin effect either in preeclampsia or in intrauterine growth restriction.

Explaining Educational Inequalities in Preterm Birth. The Generation R Study (Article)

2008-06-18T00:00:00Z

BACKGROUND: Although a low socioeconomic status has consistently been associated with an increased risk of preterm birth, little is known about the pathways through which socioeconomic disadvantage influences preterm birth. AIM: To examine mechanisms that might underlie the association between the educational level of pregnant women as an indicator of socioeconomic status, and preterm birth. METHODS: The study was nested in a population-based cohort study in the Netherlands. Information was available for 3830 pregnant women of Dutch origin. FINDINGS: The lowest-educated pregnant women had a statistically significant higher risk of preterm birth (odds ratio (OR) = 1.89 (95% CI 1.28 to 2.80)) than the highest educated women. This increased OR was reduced by up to 22% after separate adjustment for age, height, preeclampsia, intrauterine growth restriction, financial concerns, long-lasting difficulties, psychopathology, smoking habits, alcohol consumption, and body mass index (BMI) of the pregnant women. Joint adjustment for these variables resulted in a reduction of 89% of the increased risk of preterm birth among low-educated pregnant women (fully adjusted OR = 1.10 (95% CI 0.66 to 1.84)). CONCLUSIONS: Pregnant women with a low educational level have a nearly twofold higher risk of preterm birth than women with a high educational level. This elevated risk could largely be explained by pregnancy characteristics, indicators of psychosocial well-being, and lifestyle habits. Apparently, educational inequalities in preterm birth go together with an accumulation of multiple adverse circumstances among women with a low education. A number of explanatory mechanisms unravelled in the present study seem to be modifiable by intervention programmes.

Low folate in seminal plasma is associated with increased sperm DNA damage (Article)

2008-01-01T00:00:00Z

Objective: To determine associations between vitamin B status, homocysteine (tHcy), semen parameters, and sperm DNA damage. Design: Observational study. Setting: A tertiary referral fertility clinic. Patient(s): Two hundred fifty-one men of couples undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment, with subgroups of fertile (n = 70) and subfertile men (n = 63) defined according to semen concentration and proven fertility. Intervention(s): None. Main Outcome Measure(s): The DNA fragmentation index (DFI) as marker of sperm DNA damage determined using the sperm chromatin structure assay (SCSA), and semen parameters assessed according to World Health Organization criteria; tHcy, folate, cobalamin, and pyridoxine concentrations determined in seminal plasma and blood. Result(s): In the total group of fertile and subfertile men, all biomarkers in blood were statistically significantly correlated with those in seminal plasma. No correlation was found between the biomarkers in blood and the semen parameters. In seminal plasma, both tHcy and cobalamin positively correlated with sperm count. Folate, cobalamin, and pyridoxine were inversely correlated with ejaculate volume. In fertile men, seminal plasma folate showed an inverse correlation with the DNA fragmentation index. Conclusion(s): Low concentrations of folate in seminal plasma may be detrimental for sperm DNA stability.

Begin bij 't begin (Inaugural Lecture)

2005-03-11T00:00:00Z