Layla L. de Jonge

First trimester fetal growth restriction and cardiovascular risk factors in school age children: population based cohort study

Objective To examine whether first trimester fetal growth restriction correlates with cardiovascular outcomes in childhood. Design Population based prospective cohort study. Setting City of Rotterdam, the Netherlands. Participants 1184 children with first trimester fetal crown to rump length measurements, whose mothers had a reliable first day of their last menstrual period and a regular menstrual cycle. Main outcomes measures Body mass index, total and abdominal fat distribution, blood pressure, and blood concentrations of cholesterol, triglycerides, insulin, and C peptide at the median age of 6.0 (90% range 5.7-6.8) years. Clustering of cardiovascular risk factors was defined as having three or more of: high android fat mass; high systolic or diastolic blood pressure; low high density lipoprotein cholesterol or high triglycerides concentrations; and high insulin concentrations. Results One standard deviation score greater first trimester fetal crown to rump length was associated with a lower total fat mass (−0.30%, 95% confidence interval −0.57% to −0.03%), android fat mass (−0.07%, −0.12% to −0.02%), android/gynoid fat mass ratio (−0.53, −0.89 to −0.17), diastolic blood pressure (−0.43, −0.84 to −0.01, mm Hg), total cholesterol (−0.05, −0.10 to 0, mmol/L), low density lipoprotein cholesterol (−0.04, −0.09 to 0, mmol/L), and risk of clustering of cardiovascular risk factors (relative risk 0.81, 0.66 to 1.00) in childhood. Additional adjustment for gestational age and weight at birth changed these effect estimates only slightly. Childhood body mass index fully explained the associations of first trimester fetal crown to rump length with childhood total fat mass. First trimester fetal growth was not associated with other cardiovascular outcomes. Longitudinal growth analyses showed that compared with school age children without clustering of cardiovascular risk factors, those with clustering had a smaller first trimester fetal crown to rump length and lower second and third trimester estimated fetal weight but higher weight growth from the age of 6 months onwards. Conclusions Impaired first trimester fetal growth is associated with an adverse cardiovascular risk profile in school age children. Early fetal life might be a critical period for cardiovascular health in later life.

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

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, 1.61-5.36). CONCLUSION Maternal CRP levels in early pregnancy are associated with fetal growth restriction and increased risks of neonatal complications.

BMI, total and abdominal fat distribution, and cardiovascular risk factors in school-age children.

Background:More specific total body and abdominal fat mass measures might be stronger associated with cardiovascular risk factors in childhood, than BMI. We examined the independent associations of total and abdominal fat measures with cardiovascular risk factors in school age children.Methods:We performed a population-based cohort study among 6,523 children. At the age of 6 y, we measured childhood BMI, and general and abdominal fat mass, using dual-energy X-ray absorptiometry, and ultrasound and cardiovascular risk factors.Results:Conditional on BMI, higher fat mass percentage and abdominal fat mass were associated with higher blood pressure, total- and low-density lipoprotein (LDL)-cholesterol, insulin and c-peptide levels, but with lower left ventricular mass and high-density lipoprotein (HDL)-cholesterol (P values < 0.05). These associations differed between underweight, normal weight, overweight, and obese children. Higher childhood adiposity measures were associated with increased odds of cardiovascular risk factors clustering, with the strongest effect for fat mass percentage (odds ratios: 3.01 (95% confidence interval: 2.67, 3.9).Conclusion:Our results suggest that general and abdominal fat measures are associated with cardiovascular risk factors in childhood, independent from BMI. These measures may provide additional information for identification of children with an adverse cardiovascular profile.

Growth, obesity, and cardiac structures in early childhood: the Generation R Study.

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.

Fetal Exposure to Parental Smoking and the Risk of Type 2 Diabetes in Adult Women

OBJECTIVE We evaluated the associations of both maternal and paternal smoking during pregnancy with the risk of type 2 diabetes in daughters and explored whether any association was explained by weight at birth or BMI throughout life. RESEARCH DESIGN AND METHODS We used data from 34,453 participants of the Nurses’ Health Study II. We used Cox proportional hazards models to examine the associations of maternal and paternal smoking during pregnancy with incidence of type 2 diabetes in daughters between 1989 and 2009. RESULTS Maternal smoking during the first trimester only was associated with the risk of type 2 diabetes in the offspring, independent of confounders, birth weight, and later-life BMI (fully adjusted hazard ratio 1.34 [95% CI 1.01, 1.76]). In the age-adjusted models, both continued maternal smoking during pregnancy and paternal smoking tended to be associated with an increased risk of type 2 diabetes in daughters. Perinatal and adult life variables did not explain these associations, but additional adjustment for current BMI fully attenuated the effect estimates. CONCLUSIONS The associations of maternal and paternal smoking during pregnancy with the risk of type 2 diabetes in daughters were largely explained by BMI throughout the life course. Further studies are needed to explore the role of first-trimester-only maternal smoking on insulin resistance in the offspring. Also, similar effect estimates for maternal and paternal smoking suggest that the associations reflect shared family-based or lifestyle-related factors.

Infant Feeding Patterns Are Associated with Cardiovascular Structures and Function in Childhood

Nutrition in infancy seems to be associated with cardiovascular disease and its risk factors in adulthood. These associations may be explained by cardiovascular developmental adaptations in childhood in response to specific infant feeding patterns. The aim of this study was to assess whether duration and exclusivity of breastfeeding and timing of introduction of solid foods affect cardiovascular development in childhood. In a population-based prospective cohort study from fetal life onward, information about duration and exclusivity of breastfeeding and timing of introduction of solid foods was obtained from delivery reports and questionnaires. Blood pressure, carotid-femoral pulse wave velocity (PWV), left atrial diameter (LAD), aortic root diameter (AOD), left ventricular (LV) mass, and fractional shortening (FS) were measured at a median age of 6.0 y (95% range: 5.6-7.4 y). Analyses were based on 5003 children. Age at introduction of solid foods was negatively associated with systolic and diastolic blood pressure at the age of 6 y. Compared with children who had ever been breast-fed, never-breast-fed children had a higher carotid-femoral PWV (β: 0.13 m/s; 95% CI: 0.03, 0.24 m/s), a smaller LAD (β: -0.29 mm; 95% CI: -0.55, -0.03 mm), and less LV mass (β:-1.46 g; 95% CI: -2.41, -0.52 g) at the age of 6 y. Among breast-fed children, duration and exclusivity were not associated with cardiovascular structures or function. Breastfeeding pattern and age at introduction of solid foods were not associated with AOD or FS. Feeding patterns in infancy may influence cardiovascular development in childhood. Further research is required to replicate these findings and to investigate whether these changes contribute to an increased risk of cardiovascular disease in later life.

Parental Smoking in Pregnancy and the Risks of Adult-Onset Hypertension

Fetal exposure to parental smoking may lead to developmental adaptations and promote various diseases in later life. This study evaluated the associations of parental smoking during pregnancy with the risk of hypertension in the daughter in adulthood, and assessed whether these associations are explained by birth weight or body weight throughout life. We used data on 33 086 participants of the Nurses’ Health Study II and the Nurses’ Mothers’ Cohort. Cox proportional hazards models were used to examine the associations of maternal and paternal smoking during pregnancy with the nurse daughter, with self-reported physician-diagnosed hypertension from 1989 until 2007. Overall, 8575 (25.9%) mothers and 18 874 (57.0%) fathers smoked during pregnancy. During follow-up, 7825 incident cases of adult-onset hypertension were reported. Both maternal and paternal smoking of ≥15 cigarettes/d during pregnancy were associated with increased risks of hypertension (rate ratio, 1.19; 95% CI, 1.09–1.29; and rate ratio, 1.18; 95% CI, 1.12–1.25, respectively) in the age-adjusted models. Further adjustment for birth weight did not affect the effect estimates appreciably, whereas additional adjustment for body shape and weight until age 18, or current body mass index, attenuated the associations with both maternal and paternal smoking (rate ratio, 1.07; 95% CI, 0.98–1.16; and rate ratio, 1.06; 95% CI, 1.01–1.12, respectively). The associations of parental smoking during pregnancy with the risk of hypertension in the offspring were largely explained by body weight throughout life, suggesting that these associations may not reflect direct intrauterine mechanisms.

Parental smoking during pregnancy and cardiovascular structures and function in childhood: The Generation R Study

BACKGROUND Foetal smoke exposure might lead to foetal developmental adaptations that permanently affect the cardiovascular system. We assessed the associations of both maternal and paternal smoking during pregnancy with childhood cardiovascular structures and function. METHOD In a prospective cohort study among 5565 children, we examined whether maternal and paternal smoking during pregnancy are associated with blood pressure, carotid-femoral pulse wave velocity and left cardiac structures and function in 6-year-old children. RESULTS As compared with children from non-smoking mothers, children from mothers who smoked more than 10 cigarettes per day had a higher diastolic blood pressure [difference 1.43 mmHg (95% confidence interval: 0.22, 2.63)]. Maternal smoking during pregnancy was not associated with systolic blood pressure, childhood carotid-femoral pulse wave velocity or left cardiac structures. Maternal smoking of 10 or more cigarettes per day was associated with a higher fractional shortening in childhood [difference 1.01% (95% confidence interval: 0.18, 1.84)]. Among mothers who did not smoke during pregnancy, paternal smoking was associated with aortic root diameter but not with other cardiovascular outcomes. CONCLUSIONS Maternal smoking during pregnancy is associated with higher diastolic blood pressure and fractional shortening, although the effect estimates are small. The stronger effect estimates for maternal smoking compared with paternal smoking might suggest that direct intrauterine adaptive responses are involved as underlying mechanisms.

C-reactive protein levels, blood pressure and the risks of gestational hypertensive complications: the Generation R Study.

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.

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

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.