Heijden, A.J. van der

Extending prednisolone treatment does not reduce relapses in childhood nephrotic syndrome (Article)

2013-12-28T00:00:00Z

Prolonged prednisolone treatment for the initial episode of childhood nephrotic syndrome may reduce relapse rate, butwhether this results fromthe increased duration of treatment or a higher cumulative dose remains unclear.We conducted a randomized, double-blind, placebo-controlled trial in 69 hospitals in The Netherlands. We randomly assigned 150 children (9 months to 17 years) presenting with nephrotic syndrome to either 3 months of prednisolone followed by 3 months of placebo ( n=74) or 6 months of prednisolone (n=76), and median follow-up was 47 months. Both groups received equal cumulative doses of prednisolone (approximately 3360 mg/m2). Among the 126 children who started trial medication, relapses occurred in 48 (77%) of 62 patients who received 3 months of prednisolone and 51 (80%) of 64 patients who received 6 months of prednisolone. Frequent relapses, according to international criteria, occurred with similar frequency between groups as well (45% versus 50%). In addition, there were no statistically significant differences between groups with respect to the eventual initiation of prednisolone maintenance and/or other immunosuppressive therapy (50% versus 59%), steroid dependence, or adverse effects. In conclusion, in this trial, extending initial prednisolone treatment from 3 to 6 months without increasing cumulative dose did not bene fit clinical outcome in children with nephrotic syndrome. Previous findings indicating that prolonged treatment regimens reduce relapses most likely resulted from increased cumulative dose rather than the treatment duration. Copyright

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.

The Generation R Study: Design and cohort update 2010 (Article)

2010-11-01T00:00:00Z

The Generation R Study is a population-based prospective cohort study from fetal life until young adulthood. The study is designed to identify early environmental and genetic causes of normal and abnormal growth, development and health during fetal life, childhood and adulthood. The study focuses on four primary areas of research: (1) growth and physical development; (2) behavioural and cognitive development; (3) diseases in childhood; and (4) health and healthcare for pregnant women and children. In total, 9,778 mothers with a delivery date from April 2002 until January 2006 were enrolled in the study. General follow-up rates until the age of 4 years exceed 75%. Data collection in mothers, fathers and preschool children included questionnaires, detailed physical and ultrasound examinations, behavioural observations, and biological samples. A genome wide association screen is available in the participating children. Regular detailed hands on assessment are performed from the age of 5 years onwards. Eventually, results forthcoming from the Generation R Study have to contribute to the development of strategies for optimizing health and healthcare for pregnant women and children.

Reduced renal length and volume 20 years after very preterm birth (Article)

2010-03-01T00:00:00Z

Intrauterine growth retardation is presumed to be associated with decreased renal size and impaired renal function as a result of stunted kidney development and nephron deficit. To study whether very preterm birth also affects renal size at young adulthood, we sonographically measured bipolar kidney length and volume in 51 very premature individuals (<32 weeks of gestation), either small (SGA) or appropriate (AGA) for gestational age (22 SGA and 29 AGA), and 30 full-term controls 20 years after birth. Relative kidney length and volume were calculated. Both absolute and relative left kidney length and volume were significantly lower in SGA and AGA individuals, otably in women. Renal size did not differ between SGA and AGA individuals. In 70% of controls, the left kidney was larger than the right one compared with 40.9% in SGA [relative risk (RR) 1.7; 95% confidence interval (CI) 1.0 -3.0] and 48.3% in AGA (RR 1.5; 95% CI 0.9-2.3) individuals. Renal structural anomalies were present in eight prematurely born participants only. Our data suggest that kidney growth is stunted after preterm birth, especially on the left side, and in the female gender.

Very preterm birth is a risk factor for increased systolic blood pressure at a young adult age (Article)

2010-03-01T00:00:00Z

Children born very prematurely who show intrauterine growth retardation (IUGR) are suggested to be at risk of developing high blood pressure as adults. Renal function may already be impaired by young adult age. To study whether very preterm birth affects blood pressure in young adults, we measured 24-h ambulatory blood pressure (SpacelabsTM90207 device) and renin concentration in 50 very premature individuals (<32 weeks of gestation), either small (SGA) or appropriate (AGA) for gestational age (21 SGA, 29 AGA), and 30 full-term controls who all were aged 20 years at time of measurement. The mean (standard deviation) daytime systolic blood pressure in SGA and AGA prematurely born individuals, respectively, was 122.7 (8.7) and 123.1 (8.5) mmHg. These values were, respectively, 3.6 mmHg [95% confidence interval (CI) -0.9 to 8.0] and 4.2 mmHg (95% CI 0.4-8.0) higher than in controls [119.6 (7.6)]. Daytime diastolic blood pressure and nighttime blood pressure did not differ between groups. We conclude that individuals born very preterm have higher daytime systolic blood pressure and higher risk of hypertension at a young adult age.

Nephrocalcinosis in preterm neonates (Article)

2010-02-01T00:00:00Z

The prevalence of nephrocalcinosis (NC) in preterm neonates in recent reports is 7-41%. The wide range in prevalence is a consequence of different study populations and ultrasound equipment and criteria, in addition to a moderate interobserver variation. NC in preterm neonates has a multifactorial aetiology, consisting of low gestational age and birth weight, often in combination with severe respiratory disease, and occurs as a result of an imbalance between stone-promoting and stoneinhibiting factors. A limited number of histological studies suggest that calcium oxalate crystals play an important role in NC in premature neonates. In 85% of children resolution of NC occurs in the first years of life. Prematurity, per se, is associated with high blood pressure, relatively small kidneys, and (distal) tubular dysfunction. In addition, NC in preterm neonates can have long-term sequelae for glomerular and tubular function. Long-term follow-up of blood pressure and renal function of prematurely born children, especially with neonatal NC, is recommended. Prevention of NC with (low) oral doses of citrate has not resulted in a significant decrease in the prevalence of NC; a higher citrate dosage deserves further study. Future research pertaining to prevention of NC in preterm neonates is crucial.

Kidney growth curves in healthy children from the third trimester of pregnancy until the age of two years. The Generation R Study (Article)

2010-02-01T00:00:00Z

Information about growth of kidney structures in early life is limited. In a population-based prospective cohort study, from foetal life onwards, we constructed reference curves for kidney growth from the third trimester of pregnancy until early childhood, using data from 1,158 healthy children. Kidney size, defined as length, width, depth and volume, was measured in the third trimester of pregnancy and at the postnatal ages of 6 months and 24 months. Analyses were based on more than 2,500 kidney measurements. In the third trimester of pregnancy and at 6 months of age all kidney measurements were larger in boys than in girls. At 24 months of age, these gender differences were only significant for left kidney structures and right kidney length. Both groups showed trends towards smaller left kidney measurements than right kidney measurements at all ages. Gender-specific reference curves based on post-conceptional and postnatal ages were constructed for left and right kidney length, width, depth and volume. We concluded that kidney size is influenced by age and gender. Left kidney size tended to be smaller than right kidney size, except for kidney length. The reference curves can be used for assessing kidney structures by ultrasound in foetal life and early childhood.

Cardiac structures track during the first 2 years of life and are associated with fetal growth and hemodynamics. The Generation R Study (Article)

2009-07-01T00:00:00Z

Background: The aim of this study is to examine whether cardiac size and function track in early childhood and are associated with fetal and early postnatal growth and blood flow characteristics. Methods: This study was embedded in a population-based prospective cohort study from fetal life onward. Fetal growth and fetal and placental blood flow parameters in second and third trimester of pregnancy were measured by ultrasound and Doppler. Left cardiac structures and shortening fraction were measured postnatally at the ages of 1.5, 6, and 24 months. Analyses were based on 1,001 children. Results: Left ventricular mass tended to remain in the lowest and highest quartiles from the age of 1.5 to 24 months (odds ratio 1.70, 95% confidence interval [CI] 1.10-2.63) and 2.15 (95% CI 1.41-3.30), respectively. Similar results were found for aortic root diameter and left atrial diameter. Birth weight was positively associated with aortic root diameter (0.08 mm, 95% CI 0.01-0.17; per SD increase) and left ventricular mass (0.65 g, 95% CI 0.09-1.21; per SD increase). Resistance indices of the umbilical and uterine arteries showed weak tendencies toward inverse associations with left cardiac structures. Fetal cardiac output was positively associated with both left atrial diameter (increase of 1.96 mm, 95% CI 1.28-2.64; per mL/min increase) and left ventricular mass (increase of 1.79 g, 95% CI 0.35-3.22; per mL/min increase). Conclusions: This study suggest moderate tracking of left cardiac structures during the first 2 years and that small size and hemodynamic variations in fetal life have consequences for postnatal cardiac size and function.

Reliability of renal ultrasound measurements in children (Article)

2009-03-12T00:00:00Z

The aim of the investigation reported here was to assess the intraobserver and interobserver variability of renal measurements in children. The study comprised 56 paired measurements in 28 children (median age 7.5 years, range 3.0-15.0 years) without renal or ureterovesical anomalies. Intraobserver and interobserver reproducibility was assessed by repeated measurements of the left and right renal length, width, and thickness. Intraclass correlation coefficients (ICCs) with the corresponding 95% confidence interval (CI) were calculated. Bland and Altman plots were computed to assess the agreement of the measurements. Limits of agreement ± 2 standard deviations (SD) for the mean differences in renal measurements were derived. Intraobserver ICCs ranged from 0.93 (left and right renal width and right renal thickness) to 0.99 (left renal length), and interobserver ICCs ranged from 0.64 (right renal thickness) to 0.90 (right renal length). Limits of agreement in the Bland and Altman plots ranged from -8.0 to 9.2% (intraobserver left renal width) to the widest limit from -18.0 to 19.2% (interobserver left renal length). Overall, this study demonstrated the good reproducibility and agreement of most renal dimensions in children measured by ultrasound (US). Based on these results, we conclude that US is an appropriate measure to assess renal dimensions in both clinical and epidemiological studies.

Tracking and Determinants of Kidney Size From Fetal Life Until the Age of 2 Years: The Generation R Study (Article)

2009-02-01T00:00:00Z

Background: An adverse fetal environment may lead to smaller kidneys and subsequently kidney disease and hypertension in adulthood. The aims of this study are to examine whether kidney size tracks from fetal life to childhood and whether maternal and fetal characteristics are associated with kidney size at the age of 2 years. Study Design: Prospective cohort study from fetal life onward. Setting & Participants: The study was conducted in a group of 688 infants in Rotterdam, The Netherlands. Entry criteria were singleton, noncomplicated pregnancies, and Dutch ethnicity. Predictors: The maternal characteristics age, height, and prepregnancy weight were measured in early pregnancy. Fetal growth, head circumference, abdominal circumference, femur length and estimated fetal weight, and placental characteristics were assessed in the second and third trimesters. Outcomes & Measurements: Kidney size, defined as length, width, depth, and volume, was measured in the third trimester of pregnancy and at postnatal ages 6 and 24 months. Results: Overall median gestational age was 40.3 weeks (95% range, 36.0 to 42.3 weeks), and mean birth weight was 3,536 ± 524 (SD) g. Children tended to remain in the lowest and highest quartiles of kidney volume from the third trimester to the age of 2 years (odds ratio, 2.05; 95% confidence interval, 1.38 to 3.06; odds ratio, 3.29; 95% confidence interval, 2.22 to 4.87, respectively). Maternal height and prepregnancy weight were associated positively with kidney volume at the age of 2 years. Third-trimester fetal head circumference, abdominal circumference, and estimated weight and postnatal length were associated positively with kidney volume at the age of 2 years. Preferential fetal blood flow to the brain was associated with smaller kidneys. Limitations: Kidney measurements successfully performed in only 86% of children. Conclusions: Small kidney size in fetal life tends to persist in early childhood. Maternal anthropometrics and fetal biometrics and blood flow patterns are associated with kidney size in childhood. Follow-up studies are needed to examine whether these variations in kidney size are related to kidney function and blood pressure in later life.

The generation R study: Design and cohort update until the age of 4 years (Article)

2008-12-01T00:00:00Z

The Generation R Study is a population-based prospective cohort study from fetal life until young adulthood. The study is designed to identify early environmental and genetic causes of normal and abnormal growth, development and health from fetal life until young adulthood. The study focuses on four primary areas of research: (1) growth and physical development; (2) behavioural and cognitive development; (3) diseases in childhood; and (4) health and healthcare for pregnant women and children. In total, 9,778 mothers with a delivery date from April 2002 until January 2006 were enrolled in the study. Of all eligible children at birth, 61% participate in the study. In addition, more detailed assessments are conducted in a subgroup of 1,232 pregnant women and their children. Data collection in the prenatal phase and postnatal phase until the age of 4 years includes questionnaires, detailed physical and ultrasound examinations, behavioural observations and biological samples. This paper gives an update of the study design and cohort profile until the children's age of 4 years. Eventually, results forthcoming from the Generation R Study have to contribute to the development of strategies for optimizing health and healthcare for pregnant women and children.

Antenatal glucocorticoid treatment is not associated with long-term metabolic risks in individuals born before 32 weeks of gestation (Article)

2008-11-01T00:00:00Z

Background: A single course of maternal glucocorticoid treatment is effective in reducing neonatal mortality after preterm birth. However, in animals, maternal glucocorticoid treatment is associated with lifelong hyperglycemia and hypertension, and impaired nephrogenesis in offspring. Findings from studies in humans on this topic are highly contradictory due to a number of methodological flaws, and renal function after glucocorticoid exposure has never been assessed. Objectives: To assess in individuals born <32 gestational weeks whether antenatal glucocorticoid treatment for preterm birth is associated with long-term metabolical risks, including renal function, in adulthood. Design: Birth cohort study. Setting: Multicentre study. Patients: 412 19 year olds born <32 gestational weeks from the Project On Preterm and Small-for-gestational-age infants (POPS) cohort. Interventions: Maternal betamethasone 12 mg administered twice with a 24 h interval. Main outcome measures: Body composition, insulin resistance, the serum lipid profile, blood pressure and estimated renal function. Results: We did not find any long-term adverse effects of antenatal betamethasone, with the exception of an effect on glomerular filtration rate (GFR). In 19-year-old survivors, GFR was lower after betamethasone: -5.2 ml/min (95% CI -8.9 to -1.4) per 1.73 m2. Conclusions: The reduction in neonatal mortality associated with a single course of maternal betamethasone is not accompanied by long-term metabolical risks in survivors of preterm birth. The only adverse effect found was lower GFR. Although this difference was not clinically relevant at 19 years, it might predict an increased risk of chronic renal failure in prematurely born individuals who were exposed antenatally to betamethasone.

Mycophenolate mofetil versus cyclosporine for remission maintenance in nephrotic syndrome (Article)

2008-11-01T00:00:00Z

We performed a multi-centre randomized controlled trial to compare the efficacy of mycophenolate mofetil (MMF) to that of cyclosporine A (CsA) in treating children with frequently relapsing nephrotic syndrome and biopsy-proven minimal change disease. Of the 31 randomized initially selected patients, seven were excluded. The remaining 24 children received either MMF 1200 mg/m2per day (n = 12) or CsA 4-5 mg/kg per day (n = 12) during a 12-month period. Of the 12 patients in the MMF group, two discontinued the study medication. Evaluation of the changes from the baseline glomerular filtration rate showed an overall significant difference in favour of MMF over the treatment period (p = 0.03). Seven of the 12 patients in the MMF group and 11 of the 12 patients in the CsA group remained in complete remission during the entire study period. Relapse rate in the MMF group was 0.83/year compared to 0.08/year in the CsA group (p = 0.08). None of the patients reported diarrhea. Pharmacokinetic profiles of mycophenolic acid were performed in seven patients. The patient with the lowest area under the curve had three relapses within 6 months. In children with frequently relapsing minimal change nephrotic syndrome, MMF has a favourable side effect profile compared to CsA; however, there is a tendency towards a higher relapse risk in patients treated with MMF.

Absence of tolerance and toxicity to high-dose continuous intravenous furosemide in haemodynamically unstable infants after cardiac surgery (Article)

2007-12-01T00:00:00Z

Aim: To evaluate a high-dose continuous furosemide regimen in infants after cardiac surgery. Methods: Fifteen haemodynamically unstable infants with volume overload admitted to a paediatric intensive care unit were treated with an aggressive furosemide regimen consisting of a loading bolus (1-2 mg kg-1) followed by a continuous infusion at 0.2 mg kg-1h-1which was adjusted according to a target urine output of 4 ml kg-1h-1. Frequent sampling for furosemide concentrations in blood and urine was done for 3 days with simultaneous assessment of sodium excretion and urine output. Results: The mean furosemide dose was 0.22 (± 0.06), 0.25 (± 0.10) and 0.22 (± 0.11) mg kg-1h-1on the first, second and third day, respectively. Median urine production was 3.0 (0.6-5.3), 4.2 (1.7-6.6) and 3.9 (2.0-8.5) ml kg-1h-1, respectively, on the first, second and third day of the study. The target urine production was reached at a median time of 24 (6-60) h and this was maintained during the study period. The regimen did not result in toxic serum concentrations and was haemodynamically well tolerated. Conclusion: High-dose continuous furosemide infusion for 72 h in haemodynamically unstable infants after cardiac surgery appears to be a safe and effective treatment for volume overload. Development of tolerance against the effects of furosemide and ototoxic furosemide concentrations were not observed.

The Generation R Study Biobank: A resource for epidemiological studies in children and their parents (Article)

2007-12-01T00:00:00Z

The Generation R Study is a population-based prospective cohort study from fetal life until young adulthood. The study is designed to identify early environmental and genetic causes of normal and abnormal growth, development and health from fetal life until young adulthood. In total, 9,778 mothers were enrolled in the study. Prenatal and postnatal data collection is conducted by physical examinations, questionnaires, interviews, ultrasound examinations and biological samples. Major efforts have been conducted for collecting biological specimens including DNA, blood for phenotypes and urine samples. In this paper, the collection, processing and storage of these biological specimens are described. Together with detailed phenotype measurements, these biological specimens form a unique resource for epidemiological studies focused on environmental exposures, genetic determinants and their interactions in relation to growth, health and development from fetal life onwards.

Renal Function and Size at Young Adult Age After Intrauterine Growth Restriction and Very Premature Birth (Article)

2007-10-01T00:00:00Z

Background: Premature birth and intrauterine growth restriction may increase the risk of developing renal disease at adult age. Renal function may already be impaired at young adult age. Study Design: Cross-sectional study. Setting & Participants: Very premature individuals (gestational age < 32 weeks) recruited from Project on Premature and Small for Gestational Age Infants and full-term-born controls (37 to 42 weeks) recruited from a children's hospital in Rotterdam, The Netherlands. All individuals were 20 years of age at the time of study. Predictors: Gestational age and birth weight: premature and small for gestational age (SGA; n = 23), premature and appropriate for gestational age (n = 29), and controls (n = 30). Outcomes & Measurements: Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and filtration fraction before and after renal stimulation with low-dose dopamine infusion and oral amino-acid intake. Urine albumin and renal ultrasound. Results: Height, weight, kidney length and volume, GFR, and ERPF were significantly lower in the SGA group than in controls. After adjustment for body surface area, GFR did not differ significantly among groups. Mean ERPF was 71 mL/min/1.73 m2(95% confidence interval [CI], 3 to 139) less, but filtration fraction was only 1.3% (95% CI, -0.3 to 3.0) greater, in the SGA group than controls. Renal stimulation significantly increased GFR and ERPF and decreased filtration fraction in all groups. After renal stimulation, ERPF was 130 mL/min/1.73 m2(95% CI, 21 to 238) greater in the SGA group than controls, but GFR and filtration fraction did not differ significantly among groups. Microalbuminuria was present in 2 patients (8.7%) in the SGA group, but none in the appropriate-for-gestational-age group or controls. Renal function correlated with renal size. Limitations: Small sample size. Conclusions: Our findings do not fully support the hypothesis that preterm birth in combination with intrauterine growth restriction contributes to renal function alterations at young adult age. Larger studies are needed to evaluate this hypothesis.

Is nephrocalcinosis in preterm neonates harmful for long-term blood pressure and renal function? (Article)

2007-03-01T00:00:00Z

OBJECTIVE. The aim of our study was to examine long-term effects of nephrocalcinosis in prematurely born children. PATIENTS AND METHODS. Preterm neonates (gestational age <32 weeks) with (n = 42) and without (n = 32) nephrocalcinosis were prospectively studied at a mean age of 7.5 (±1.0) years. RESULTS. Blood pressure did not differ in ex-preterm infants with and without nephrocalcinosis but was significantly higher than expected for healthy children. In comparison to healthy children, more ex-preterm infants with neonatal nephrocalcinosis had (mild) chronic renal insufficiency (glomerular filtration rate: <85 mL/min per 1.73 m2; 6 of 40); this is in contrast to ex-preterm infants without neonatal nephrocalcinosis (2 of 32). Tubular phosphate reabsorption and plasma bicarbonate were significantly lower in children with nephrocalcinosis compared with children without nephrocalcinosis. In addition, more ex-preterm infants with and without nephrocalcinosis than expected had low values for plasma bicarbonate and early-morning urine osmolality compared with healthy children. Kidney length of ex-preterm infants with and without nephrocalcinosis was significantly smaller than expected in healthy children of the same height. Nephrocalcinosis persisted long-term in 4 of 42 children but was not related to blood pressure, kidney length, or renal function. CONCLUSIONS. Nephrocalcinosis in preterm neonates can have long-term sequelae for glomerular and tubular function. Furthermore, prematurity per se is associated with high blood pressure, relatively small kidneys, and (distal) tubular dysfunction. Long-term follow-up of blood pressure and renal glomerular and tubular function of preterm neonates, especially with neonatal nephrocalcinosis, seems warranted. Copyright

Microalbuminuria and lower glomerular filtration rate at young adult age in subjects born very premature and after intrauterine growth retardation. (Article)

2005-12-01T00:00:00Z

This prospective follow-up study of 422 19-yr-old subjects born very preterm in The Netherlands was performed to determine whether intrauterine growth retardation (IUGR) predisposes to abnormal GFR and microalbuminuria in adolescents. GFR (ml/min per 1.73 m2) was estimated using the Cockcroft-Gault equation, and albumin-creatinine ratio (mg/mmol) was calculated in a cohort of 19-yr-old subjects born very preterm (gestational age <32 wk) in 1983. Birth weights were adjusted for gestational age and expressed as standard deviation scores (sds) as a measure of IUGR. All subjects had normal renal function. Birth weight (sds) was associated negatively with serum creatinine concentration (micromol/L) (beta = -1.0 micromol/L, 95% confidence interval [CI]: -1.9 to -0.2), positively with GFR (beta = 3.0, 95% CI: 1.7 to 4.2), and negatively with the logarithm of albumin-creatinine ratio (beta = -0.05, 95% CI: -0.09 to -0.01) in young adults born very preterm. IUGR is associated with unfavorable renal functions at young adult age in subjects born very premature. These data suggest that intrauterine growth-retarded subjects born very premature have an increased risk to develop progressive renal failure in later life.

Is blood pressure increased 19 years after intrauterine growth restriction and preterm birth? A prospective follow-up study in The Netherlands. (Article)

2005-09-01T00:00:00Z

OBJECTIVE: To determine whether intrauterine growth restriction (IUGR) is a predisposing factor for high blood pressure (BP) in 19-year-olds who were born (very) preterm. METHODS: A prospective follow-up study was conducted at age 19 in individuals who born preterm in the Netherlands in 1983. Systolic, diastolic, and mean BP values and plasma renin activity concentration were obtained in 422 young adults who were born with a gestational age (GA) <32 weeks. BP values were also measured in 174 individuals who born with a GA of > or =32 weeks and a birth weight of <1500 g. RESULTS: An increased prevalence of hypertension and probably also of prehypertensive stage was found. IUGR, birth weight, GA, and plasma renin activity were not associated with BP. Current weight and BMI were the best predicting factors for systolic BP at the age of 19 years. CONCLUSIONS: The prevalence of hypertension is high in individuals who were born preterm when compared with the general population. In the individuals who were born very preterm, no support to the hypothesis that low birth weight is associated with increased BP at young adult age can be given.

Once-daily versus twice-daily administration of ceftazidime in the preterm infant (Article)

1995-01-01T00:00:00Z

Ceftazidime pharmacokinetics in 28 preterm infants (gestational ages, 25.6 to 31.9 weeks) were studied on day 3 of life. Patients with suspected septicemia were randomized on day 1 of life in two groups. One group (n = 13) was administered 25 mg of ceftazidime per kg of body weight once daily, and the other (n = 15) was given 25 mg of ceftazidime per kg twice daily. Both groups also received 25 mg of amoxicillin per kg twice daily. Blood samples were collected on day 3 of life with an arterial catheter at 0, 0.5, 1, 2, 4, 8, and 12 h after an intravenous bolus injection. An additional blood sample was taken at 24 h from the group dosed once a day. High-performance liquid chromatography was used to determine serum ceftazidime concentrations. The pharmacokinetics of ceftazidime were best described by using a one-compartment model. The half-life for the elimination of the drug from serum, apparent volume of distribution, total body clearance of ceftazidime, and inulin clearance were not significantly different for both groups. The ceftazidime/inulin clearance ratio was 0.72 for both groups. However, trough concentrations in serum for the twice-daily group were significantly (P < 0.001) higher (42.0 +/- 13.4 mg/liter) than those for the once-daily group (13.1 +/- 4.7 mg/liter). The latter concentrations were all still substantially higher than the MIC of ceftazidime for major neonatal pathogens. We conclude that the currently recommended dosage of 25 mg of ceftazidime per kg twice daily for preterm infants with gestational ages below 32 weeks may be adjusted during the first days of life to one daily dose at 25 mg/kg, provided that for the empirical treatment of septicemia, amoxicillin at 25 mg/kg is also given twice daily.