Influence of fetal blood flow redistribution on fetal and childhood growth and fat distribution: the Generation R Study.

OBJECTIVE: A suboptimal intrauterine environment leads to fetal blood flow redistribution and fetal growth restriction. Not much is known about childhood growth consequences. We examined the associations of fetal blood flow redistribution with birth outcomes, and repeatedly measured fetal and childhood growth and fat mass measures. DESIGN: Prospective cohort study. SETTING: Population-based. POPULATION: One thousand one hundred and ninety-five pregnant women and their children. METHODS: We measured umbilical and cerebral artery blood flow at a gestational age of 30.3 weeks (95% range, 28.5-32.6 weeks). A higher umbilical/cerebral (U/C) pulsatility index ratio is an indicator of preferential blood flow to the brain cerebral circulation at the expense of the lower body parts. MAIN OUTCOME MEASURES: Fetal and childhood growth were repeatedly measured from the third trimester until childhood. We measured the total body fat mass, lean fat mass and android/gynoid fat mass ratio by dual-energy X-ray absorptiometry and preperitoneal fat by ultrasound at 6 years. RESULTS: A higher fetal U/C ratio was associated with increased risks of preterm birth and small size for gestational age at birth [odds ratios, 1.41 (95% confidence interval, 1.08-1.85) and 1.63 (95% confidence interval, 1.21-2.19), respectively, per SDS increase in U/C ratio]. Longitudinal growth analyses showed that a higher fetal U/C ratio was associated with persistently lower head circumference, length and weight from third trimester fetal life until childhood (all P < 0.05). The fetal U/C ratio was not associated with total body and abdominal fat measures at 6 years. CONCLUSION: Our results suggest that fetal blood flow redistribution affects fetal development and has persistent consequences for childhood growth. TWEETABLE ABSTRACT: Fetal blood flow redistribution affects fetal development and has persistent consequences for childhood growth.

Fetal sex dependency of maternal vascular adaptation to pregnancy: a prospective population-based cohort study.

OBJECTIVE: To investigate fetal sex dependency of maternal vascular adaptation to pregnancy as assessed by uteroplacental vascular resistance and maternal blood pressure. DESIGN: Prospective population-based cohort study. SETTING: Rotterdam, the Netherlands. POPULATION: In total, 8224 liveborn singleton pregnancies were included. METHODS: Maternal vascular adaptation was assessed in all trimesters of pregnancy. Pregnancies were stratified into being either complicated by the placental syndrome (i.e. pre-eclampsia, fetal growth restriction or preterm birth, n = 1229) or uncomplicated (n = 6995). MAIN OUTCOME MEASURES: First trimester: blood pressures. Second trimester: blood pressures, pulsatility index of the uterine artery (PI-UtA). Third trimester: blood pressures, PI-UtA, presence of notching in the uterine artery. RESULTS: In women carrying a male fetus PI-UtA was higher than in women with a female fetus in the total group (second trimester P < 0.001, third trimester P = 0.005). Effect estimates differed between women with or without the placental syndrome. In the total group, women with a male fetus more often showed notching in the Doppler resistance pattern (odds ratio 1.42, 95% confidence interval 1.17-1.72). Different blood pressure patterns were observed between pregnant women with a male fetus and pregnant women with a female fetus and between complicated pregnancies and uncomplicated pregnancies. CONCLUSION: Fetal sex is significantly associated with maternal vascular adaptation to pregnancy with differential effects in uncomplicated pregnancies and in pregnancies complicated by the placental syndrome. TWEETABLE ABSTRACT: Fetal sex is significantly associated with maternal vascular adaptation to pregnancy.

Maternal haemoglobin levels and cardio-metabolic risk factors in childhood: the Generation R study.

OBJECTIVE: To assess whether variations in maternal haemoglobin levels during pregnancy are associated with cardio-metabolic risk factors in school age children. DESIGN: Population-based prospective cohort study. SETTING: Rotterdam, The Netherlands, 2002-2012. POPULATION: Mothers and children (n = 5002) participating in the Generation R Study. METHODS: We obtained maternal haemoglobin levels during early pregnancy (median gestational age 14.6 weeks [95% range 10.3, 25.3]) from venous blood samples. Maternal anaemia and elevated haemoglobin levels were based on World Health Organization criteria. We measured childhood cardio-metabolic risk factors at age 6 years. MAIN OUTCOME MEASURES: Cardio-metabolic risk factors included body mass index, total fat mass percentage, android/gynoid fat mass ratio, systolic and diastolic blood pressure, left ventricular mass, and blood levels of cholesterol, insulin and C-peptide. RESULTS: Maternal haemoglobin levels were not associated with childhood body mass index, total fat mass percentage, android/gynoid fat mass ratio, systolic blood pressure, cholesterol or insulin levels. Compared with children with normal maternal haemoglobin levels, children from anaemic mothers had slightly higher diastolic blood pressures (difference 0.70 mmHg, 95% CI 0.12, 1.29) and lower C-peptide levels (difference factor 0.93, 95% CI 0.88, 0.98), and children of mothers with elevated haemoglobin levels had lower left ventricular masses (difference -1.08 g, 95% CI -1.88, -0.29). These associations attenuated after adjustment for multiple testing and were not consistent within linear models. CONCLUSION: These results do not strongly support the hypothesis that variations in maternal haemoglobin levels during pregnancy influence cardio-metabolic risk factors in childhood.

Maternal educational level and risk of gestational hypertension: the Generation R Study.

We examined whether maternal educational level as an indicator of socioeconomic status is associated with gestational hypertension. We also examined the extent to which the effect of education is mediated by maternal substance use (that is smoking, alcohol consumption and illegal drug use), pre-existing diabetes, anthropometrics (that is height and body mass index (BMI)) and blood pressure at enrollment. This was studied in 3262 Dutch pregnant women participating in the Generation R Study, a population-based cohort study. Level of maternal education was established by questionnaire at enrollment, and categorized into high, mid-high, mid-low and low. Diagnosis of gestational hypertension was retrieved from medical records using standard criteria. Odds ratios (OR) of gestational hypertension for educational levels were calculated, adjusted for potential confounders and additionally adjusted for potential mediators. Adjusted for age and gravidity, women with mid-low (OR: 1.52; 95% CI: 1.02, 2.27) and low education (OR: 1.30; 95% CI: 0.80, 2.12) had a higher risk of gestational hypertension than women with high education. Additional adjustment for substance use, pre-existing diabetes, anthropometrics and blood pressure at enrollment attenuated these ORs to 1.09 (95% CI: 0.70, 1.69) and 0.89 (95% CI: 0.50, 1.58), respectively. These attenuations were largely due to the effects of BMI and blood pressure at enrollment. Women with relatively low educational levels have a higher risk of gestational hypertension, which is largely due to higher BMI and blood pressure levels from early pregnancy. The higher risk of gestational hypertension in these women is probably caused by pre-existing hypertensive tendencies that manifested themselves during pregnancy.