Jonge, L.L. de

Early Growth and Cardiovascular Development in Childhood. The Generation R Study (Doctoral Thesis)

2013-04-18T00:00:00Z

The developmental plasticity hypothesis proposes that environmental exposures, acting at different stages of fetal and early postnatal development, lead to permanent adaptations in the structure, physiology and function of various organ systems.This early programming contributes to short-term survival, but increases the susceptibility of cardiovascular disease in adulthood.1 This hypothesis is supported by observational studies demonstrating that low birth weight, as a measure of reduced growth in utero, is associated with an increased risk of the development of cardiovascular disease in later life. Low birth weight has also been related to cardiovascular risk factors such as hypertension and cholesterol levels, although systematic reviews suggest small effects. Birth weight is merely a marker of fetal growth and environment, and does not account for the influence of postnatal growth. Retrospective follow up studies have shown that individuals with a low birth weight and high rates of childhood weight gain have increased risks of cardiovascular disease, suggesting that fetal and childhood growth are both related to cardiovascular health and disease in later life. The exact growth patterns and underlying biological mechanisms linking fetal and childhood growth with disease in later life are not fully understood.

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.

C-reactive protein levels in early pregnancy, fetal growth patterns, and the risk for neonatal complications: The Generation R Study (Article)

2011-08-01T00:00:00Z

Objective: We sought to examine the associations of maternal C-reactive protein (CRP) levels with fetal growth and the risks of neonatal complications. Study Design: CRP levels were measured in early pregnancy in 6016 women. Main outcome measures were fetal growth in each trimester and neonatal complications. Results: As compared to the reference group (CRP levels <5 mg/L), elevated maternal CRP levels (<25 mg/L) were associated with lower estimated fetal weight in third trimester and lower weight at birth (differences: -29 g, 95% confidence interval [CI], -58 to 0 and -128 g, 95% CI, -195 to -60, respectively). Elevated maternal CRP levels were also associated with an increased risk of a small size for gestational age in the offspring (adjusted odds ratio, 2.94; 95% CI, 1.615.36). Conclusion: Maternal CRP levels in early pregnancy are associated with fetal growth restriction and increased risks of neonatal complications.

Growth, obesity, and cardiac structures in early childhood: The generation r study (Article)

2011-05-01T00:00:00Z

Cardiac structural adaptations in response to physical growth and obesity in older children have been identified and might have long-term consequences. We examined the associations of growth and obesity with cardiac structures during the first 2 years of life. In a population-based prospective cohort study among 974 children, left atrial diameter, left ventricular diastolic diameter, left ventricular mass, aortic root diameter, and fractional shortening were repeatedly measured by ultrasound at the ages of 1.5, 6, and 24 months. Height, weight, and subcutaneous fat mass were measured at the same visits, and blood pressure was measured at the age of 24 months. Height, weight, body mass index, and body surface area were positively associated with all of the cardiac structures during the first 2 years of life. At the age of 24 months, as compared with normal weight children, obese children had a greater left ventricular mass (1.04 SD score [95% CI: 0.20 to 1.89]) and a higher fractional shortening (0.91 SD score [95% CI: 0.02 to 1.80]). Nonsignificant tendencies were found for left atrial diameter, left ventricular diastolic diameter, and aortic root diameter. Our results suggest that normal variation in growth affects cardiac structures in early life. Overweight and obese children show cardiac adaptations already at the age of 2 years. Further studies are needed to assess whether these structural adaptations influence the risk of cardiovascular disease in later life.

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.

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.

Indirect maternal mortality increases in the Netherlands (Article)

2010-06-01T00:00:00Z

Objective. To assess causes, trends, and substandard care in indirect maternal mortality in the Netherlands. Design. Confidential enquiry into causes of maternal death. Setting. Nationwide in the Netherlands. Population. A total of 2,557,208 live births. Methods. Data analysis of indirect maternal deaths in the period 1993-2005. Main outcome measures. Indirect maternal mortality. Results. Of the study subjects, 97 were classified as indirect deaths, representing a maternal mortality ratio of 3.3/100,000 live births, a significant increase compared to the preceding enquiry in the period 1983-1992 (MMR 2.4, OR 1.5, 95%CI 1.0-2.1). The percentage of cases not directly reported to the Maternal Mortality Committee decreased from 15 to 5%. Cardiovascular disorders were the leading cause of indirect maternal mortality, followed by cerebrovascular disorders. Vascular dissection (n=19) was the most frequent specified cause of death. Risk factors were advanced maternal age, non-indigenous origin (Surinam and Dutch Antilles), and medical health risks before pregnancy. Substandard care was present in 35%, mainly being misjudgment of the severity of the condition and delay in initiating therapy. Conclusion. The rise of mortality due to indirect causes is considered a reflection of the change in risk profile of women of childbearing age and the result of demographic alterations concerning ethnicity and maternal age. The identification of high risk groups, preferably by programs of preconception care, should lead to improved care for these women, with a multidisciplinary approach when needed.