Romy Gaillard

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.

Maternal obesity during pregnancy and cardiovascular development and disease in the offspring

AbstractnMaternal obesity during pregnancy is an important public health problem in Western countries. Currently, obesity prevalence rates in pregnant women are estimated to be as high as 30xa0%. In addition, approximately 40xa0% of women gain an excessive amount of weight during pregnancy in Western countries. An accumulating body of evidence suggests a long-term impact of maternal obesity and excessive weight gain during pregnancy on adiposity, cardiovascular and metabolic related health outcomes in the offspring in fetal life, childhood and adulthood. In this review, we discuss results from recent studies, potential underlying mechanisms and challenges for future epidemiological studies.

OS021. Risk factors and outcomes of maternal obesity and excessive weight gain during pregnancy

INTRODUCTIONnThe prevalence of overweight and obesity among women of reproductive age is increasing. Maternal obesity seems to be associated with short-term and long-term adverse outcomes. Excessive gestational weight gain might also influence the risk of adverse pregnancy outcomes. Not much is known about risk factors of maternal obesity and excessive gestational weight gain. Also, little is known about critical periods of gestational weight gain in relation to adverse pregnancy outcomes.nnnOBJECTIVESnWe aimed to determine risk factors and maternal, fetal and childhood consequences of maternal obesity and excessive gestational weight gain. Furthermore, we examined the associations of trimester-specific weight gain with the risk of adverse pregnancy outcomes.nnnMETHODSnThe study was embedded in a population-based prospective cohort study among 6959 mothers and their children. Maternal anthropometrics were measured in each trimester of pregnancy. Information about maternal weight just before pregnancy, maximum weight during pregnancy and potential socio-demographic and lifestyle related determinants was obtained from questionnaire. Information about gestational hypertensive disorders and birth outcomes was obtained from medical records. Multivariate linear and logistic regression analyses were used.nnnRESULTSnMaternal lower educational level, lower household income, multiparity, and FTO risk allel were associated with an increased risk of maternal obesity, whereas maternal European ethnicity, nulliparity, higher total energy intake, and smoking during pregnancy were associated with an increased risk of excessive gestational weight gain (all p-values <0.05). As compared to normal weight, maternal obesity was associated with increased risks of gestational hypertension (OR 6.31 (95% CI 4.30,9.26)), preeclampsia (OR (3.61 (95% CI 2.04,6.39)), gestational diabetes (OR 6.28 (95%CI 3.01,13.06)), caesarean delivery (OR 1.91 (95% CI 1.46,2.50)), delivering large size for gestational age infants (OR 2.97 (95% CI 2.16,4.08)), and childhood obesity (OR 5.02 (95% CI:2.97,8.45)). Weaker associations of excessive gestational weight gain with these outcomes were observed, with the strongest effects for first trimester weight gain. Weight gain in first and third trimester was associated with the risk of gestational hypertension (OR 1.24 (95% CI 1.12,1.39) and OR 1.27 (95% CI 1.06,1.51) per standard deviation of change in gestational weight gain per week, respectively), whereas weight gain in third trimester was associated with the risk of preeclampsia (OR 1.35 (95% CI 1.08,1.69), per standard deviation of change in gestational weight gain per week).nnnCONCLUSIONnOur study shows that maternal obesity and excessive weight gain during pregnancy are associated with socio-demographic, lifestyle, and genetic factors and with increased risks of adverse maternal, fetal and childhood health outcomes. As compared to prepregnancy overweight and obesity, excessive gestational weight gain has a limited influence on adverse pregnancy outcomes.

Foetal and infant growth patterns, airway resistance and school-age asthma.

Preterm birth, low birth weight and rapid infant weight gain are associated with increased risks of asthma symptoms in childhood. The underlying mechanism may include persistently higher airway resistance (Rint). The aim of our study was to examine the associations of longitudinally measured foetal and infant growth characteristics with Rint and asthma outcomes in school‐age children.

Body fat distribution, metabolic and inflammatory markers and retinal microvasculature in school-age children. The Generation R Study

Objective:To examine the associations of body fatness, metabolic and inflammatory markers with retinal vessel calibers among children.Design:We performed a population-based cohort study among 4145 school-age children. At the median age of 6.0 years (95% range 5.8, 8.0 years), we measured body mass index, total and abdominal fat mass, metabolic and inflammatory markers (blood levels of lipids, insulin and C-peptide and C-reactive protein) and retinal vascular calibers from retinal photographs.Results:We observed that compared with normal weight children, obese children had narrower retinal arteriolar caliber (difference −0.21 s.d. score (SDS; 95% confidence interval (CI) −0.35, −0.06)), but not venular caliber. Continuous analyses showed that higher body mass index and total body fat mass, but not android/gynoid fat mass ratio and pre-peritoneal fat mass, were associated with narrower retinal arteriolar caliber (P<0.05 for body mass index and total body fat mass), but not with retinal venular caliber. Lipid and insulin levels were not associated with retinal vessel calibers. Higher C-reactive protein was associated with only wider retinal venular caliber (difference 0.10 SDS (95% CI 0.06, 0.14) per SDS increase in C-reactive protein). This latter association was not influenced by body mass index.Conclusions:Higher body fatness is associated with narrower retinal arteriolar caliber, whereas increased C-reactive protein levels are associated with wider retinal venular caliber. Increased fat mass and inflammation correlate with microvascular development from school-age onwards.

Parental smoking during pregnancy and total and abdominal fat distribution in school-age children: the Generation R Study

Objective:Fetal smoke exposure may influence growth and body composition later in life. We examined the associations of maternal and paternal smoking during pregnancy with total and abdominal fat distribution in school-age children.Methods:We performed a population-based prospective cohort study among 5243 children followed from early pregnancy onward in the Netherlands. Information about parental smoking was obtained by questionnaires during pregnancy. At the median age of 6.0 years (90% range: 5.7–7.4), we measured anthropometrics, total fat and android/gynoid fat ratio by dual-energy X-ray absorptiometry, and preperitoneal and subcutaneous abdominal fat were measured by ultrasound.Results:The associations of maternal smoking during pregnancy were only present among girls (P-value for sex interaction<0.05). Compared with girls from mothers who did not smoke during pregnancy, those from mothers who smoked during the first trimester only had a higher android/gynoid fat ratio (difference 0.23 (95% confidence interval (CI): 0.09–0.37) s.d. scores (SDS). Girls from mothers who continued smoking throughout pregnancy had a higher body mass index (difference: 0.24 (95% CI: 0.14–0.35) SDS), total fat mass (difference: 0.23 (95% CI: 0.14–0.33) SDS), android/gynoid fat ratio (difference: 0.34 (95% CI: 0.22–0.46) SDS), subcutaneous abdominal fat (difference: 0.22 (95% CI: 0.11–0.33) SDS) and preperitoneal abdominal fat (difference: 0.20 (95% CI: 0.08–0.31) SDS). Similar associations with body fat distribution outcomes were observed for paternal smoking during pregnancy. Both continued maternal and paternal smoking during pregnancy may be associated with an increased risk of childhood overweight. The corresponding odds ratios were 1.19 (95% CI: 0.98–1.46) and 1.32 (1.10–1.58), respectively.Conclusions:Maternal and paternal smoking during pregnancy are associated with an adverse body and abdominal fat distribution and increased risk of overweight in children. Similar effects of maternal and paternal smoking suggest that direct intrauterine mechanisms and common family-based lifestyle-related factors explain the associations.

Maternal obesity, gestational weight gain and childhood cardiac outcomes: role of childhood body mass index

Background:Maternal obesity may affect cardiovascular outcomes in the offspring. We examined the associations of maternal prepregnancy body mass index and gestational weight gain with childhood cardiac outcomes and explored whether these associations were explained by parental characteristics, infant characteristics or childhood body mass index.Methods:In a population-based prospective cohort study among 4852 parents and their children, we obtained maternal weight before pregnancy and in early, mid- and late pregnancy. At age 6 years, we measured aortic root diameter (cm) and left ventricular dimensions. We calculated left ventricular mass (g), left ventricular mass index (gu2009m−2.7), relative wall thickness ((2 × left ventricular posterior wall thickness)/left ventricular diameter), fractional shorting (%), eccentric left ventricular hypertrophy and concentric remodeling.Results:A one standard deviation score (SDS) higher maternal prepregnancy body mass index was associated with higher left ventricular mass (0.10 SDS (95% confidence interval (CI) 0.08, 0.13)), left ventricular mass index (0.06 SDS (95% CI 0.03, 0.09)) and aortic root diameter (0.09 SDS (95% CI 0.06, 0.12)), but not with relative wall thickness or fractional shortening. A one SDS higher maternal prepregnancy body mass index was associated with an increased risk of eccentric left ventricular hypertrophy (odds ratio 1.21 (95% CI 1.03, 1.41)), but not of concentric remodeling. When analyzing the effects of maternal weight in different periods simultaneously, only maternal prepregnancy weight and early pregnancy weight were associated with left ventricular mass, left ventricular mass index and aortic root diameter (P-values<0.05), independent of weight in other pregnancy periods. All observed associations were independent of parental and infant characteristics, but attenuated to non-significance after adjustment for childhood body mass index.Conclusion:Maternal prepregnancy body mass index and weight gain in early pregnancy are both associated with offspring cardiac structure in childhood, but these associations seem to be fully explained by childhood body mass index.

Early origins of ethnic disparities in cardiovascular risk factors

BACKGROUNDnNot much is known about the ethnic differences in cardiovascular risk factors during childhood in European countries. We examined the ethnic differences in childhood cardiovascular risk factors in the Netherlands.nnnMETHODSnIn a multi-ethnic population-based prospective cohort study, we measured blood pressure, left ventricular mass, and levels of cholesterol, triglyceride and insulin at the median age of 6.2years.nnnRESULTSnAs compared to Dutch children, Cape Verdean and Turkish children had a higher blood pressure, whereas Cape Verdean, Surinamese-Creole and Turkish children had higher total-cholesterol levels (p-values<0.05). Turkish children had higher triglyceride levels, but lower insulin levels than Dutch children (p-values<0.05). As compared to Dutch children, only Turkish children had an increased risk of clustering of cardiovascular risk factors (odds ratio: 2.45 (95% confidence interval 1.18, 3.37)). Parental pre-pregnancy factors explained up to 50% of the ethnic differences in childhood risk factors. In addition to these factors, pregnancy and childhood factors and childhood BMI explained up to 50%, 12.5% and 61.1%, respectively.nnnCONCLUSIONSnOur results suggest that compared to Dutch children, Cape Verdean, Surinamese-Creole and Turkish children have an adverse cardiovascular profile. These differences are largely explained by parental pre-pregnancy factors, pregnancy factors and childhood BMI.

Associations of Maternal and Paternal Blood Pressure Patterns and Hypertensive Disorders during Pregnancy with Childhood Blood Pressure

Background Hypertensive disorders in pregnancy may affect the cardiovascular risk of offspring. We examined the associations of maternal blood pressure throughout pregnancy and hypertensive disorders in pregnancy with childhood blood pressure of offspring. Specific focus was on the comparison with paternal blood pressure effects, the identification of critical periods, and the role of birth outcomes and childhood body mass index in the observed associations. Methods and Results This study was embedded in a population‐based prospective cohort study among 5310 mothers and fathers and their children. We measured maternal blood pressure in each trimester of pregnancy and paternal blood pressure once. Information about hypertensive disorders in pregnancy was obtained from medical records. We measured childhood blood pressure at the median age of 6.0 years (95% range 5.7–8.0 years). Both maternal and paternal blood pressure were positively associated with childhood blood pressure (all P<0.05), with similar effect estimates. Conditional regression analyses showed that early, mid‐, and late‐pregnancy maternal blood pressure levels were all independent and positively associated with childhood blood pressure, with the strongest effect estimates for early pregnancy. Compared with children of mothers without hypertensive disorders in pregnancy, children of mothers with hypertensive disorders in pregnancy had higher diastolic blood pressure by a standard deviation score of 0.13 (95% CI 0.05–0.21). The observed associations were not materially affected by birth outcomes and childhood body mass index. Conclusions Both maternal and paternal blood pressure affects childhood blood pressure, independent of fetal and childhood growth measures, with the strongest effect of maternal blood pressure in early pregnancy.

Tracking of abdominal subcutaneous and preperitoneal fat mass during childhood. The Generation R Study

Background:Overweight and obesity in early life tends to track into later life. Not much is known about tracking of abdominal fat. Our objective was to examine the extent of tracking of abdominal fat measures during the first six years of life.Design:We performed a prospective cohort study among 393 Dutch children followed from the age of 2 years (90% range 1.9; 2.3) until the age of 6 years (90% range 5.7; 6.2). At both ages, we performed abdominal ultrasound to measure abdominal subcutaneous and preperitoneal fat distances and areas, and we calculated the preperitoneal/subcutaneous fat distance ratio. High abdominal fat measures were defined as values in the upper 15%.Results:Abdominal subcutaneous fat distance and area, and preperitoneal fat area at 2 years were correlated with their corresponding measures at 6 years (all P-values <0.01), with the strongest coefficients for abdominal subcutaneous fat measures. Preperitoneal fat distance at the age of 2 years was not correlated with the corresponding measure at 6 years. The tracking coefficient for preperitoneal/subcutaneous fat distance ratio from 2 to 6 years was r=0.36 (P<0.01). Children with high abdominal subcutaneous fat measures at 2 years had increased risk of having high abdominal subcutaneous fat measures at 6 years (odds ratios 9.2 (95% confidence interval (CI) 4.1–20.8) and 12.4 (95% CI 5.4–28.6) for subcutaneous fat distance and area, respectively). These associations were not observed for preperitoneal fat measures.Conclusions:Our findings suggest that both abdominal subcutaneous and preperitoneal fat mass measures track during childhood, but with stronger tracking for abdominal subcutaneous fat measures. An adverse abdominal fat distribution in early life may have long-term consequences.