First-trimester maternal haemodynamic adaptation to pregnancy and placental, embryonic and fetal development: the prospective observational Rotterdam Periconception cohort.

OBJECTIVE: To investigate whether first-trimester maternal haemodynamic adaptation impacts placental, embryonic and fetal development as well as birth outcomes in pregnancies with and without placenta-related complications. DESIGN: Prospective observational cohort. SETTING: A Dutch tertiary hospital. POPULATION: Two hundred and fourteen ongoing pregnancies. METHODS: At 7, 9 and 11 weeks of gestation, we assessed maternal haemodynamic adaptation (mean arterial blood pressure [MAP], uterine artery [UtA] blood flow) and placental development (placental volume [PV], uteroplacental vascular volume [uPVV]) using three-dimensional power Doppler ultrasound volumes, and embryonic development (crown-rump length, embryonic volume). At 22 and 32 weeks of gestation, fetal development was assessed by estimated fetal weight. Birth outcomes (birthweight, placental weight) were extracted from medical records. Linear mixed modelling and linear regression analyses were applied. MAIN OUTCOME MEASURES: Birthweight centile and placental weight. RESULTS: In placenta-related complications (n= 55, 25.7%), reduced haemodynamic adaptation, i.e. higher UtA pulsatility index (PI) and resistance index (RI) trajectories, was associated with smaller increase in PV (ß = -0.559, 95% CI -0.841 to -0.278, P< 0.001; ß = -0.579, 95% CI -0.878 to -0.280, P< 0.001) and uPVV trajectories (UtA PI: ß = -0.301, 95% CI -0.578 to -0.023, P= 0.034). At birth, reduced haemodynamic adaptation was associated with lower placental weight (UtA PI: ß = -0.502, 95% CI -0.922 to -0.082, P= 0.022; UtA RI: ß = -0.435, 95% CI -0.839 to -0.032, P= 0.036). In pregnancies without placenta-related complications, higher MAP trajectories were positively associated with birthweight centile (ß = 0.398, 95% CI 0.049-0.748, P= 0.025). CONCLUSIONS: Reduced first-trimester maternal haemodynamic adaptation impacts both placental size and vascularisation and birthweight centile, in particular in pregnancies with placenta-related complications. TWEETABLE ABSTRACT: Reduced first-trimester maternal haemodynamic adaptation to pregnancy impairs early placental development.

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.

Determinants of number-specific recall error of last menstrual period: a retrospective cohort study.

OBJECTIVE: To assess the digit preference for last menstrual period (LMP) dates, associated determinants and impact on obstetric outcome. DESIGN: Retrospective cohort study. SETTING: University medical centre (the Netherlands). POPULATION: Cohort of 24 665 LMP records and a subgroup of 4630 cases with known crown-rump length (CRL) measurement, and obstetric outcome. METHODS: Digit preference was determined by comparing the observed to expected counts of each day. Associated determinants were identified by multivariate regression analysis. Differences in obstetric outcome between LMP and CRL dating were analysed. MAIN OUTCOME MEASURES: (Non)deprived neighbourhood, cycle irregularity, certainty of LMP date, maternal age, smoking, body mass index, parity and ultrasound investigator. Preterm and post-term delivery. RESULTS: LMP digit preference for the first [odds ratio (OR), 1.28; 95% confidence interval (95% CI), 1.20-1.36], fifth (OR, 1.10; 95% CI, 1.03-1.17), 10th (OR, 1.17; 95% CI, 1.09-1.25), 15th (OR, 1.31; 95% CI, 1.23-1.40), 20th (OR, 1.22; 95% CI, 1.15-1.30) and 25th (OR, 1.08; 95% CI, 1.01-1.15) days of the month occurred more often than expected. Digit preference occurred more frequently in women living in a deprived neighbourhood (OR, 1.21; 95% CI, 1.06-1.39), with uncertain LMP (OR, 2.03; 95% CI, 1.63-2.52) or irregular cycle (OR, 1.24; 95% CI, 1.06-1.44). More post-term (≥42 weeks) deliveries (OR, 1.27; 95% CI, 1.05-1.54) were observed in LMP dating. This effect was larger in women with a digit preference (OR, 1.56; 95% CI, 1.03-2.37). CONCLUSIONS: LMP digit preference occurs more often in women living in deprived neighbourhoods, with uncertain LMP or an irregular cycle. LMP-dated pregnancies are associated with more post-term pregnancies.

Fertility treatment, twin births, and unplanned pregnancies in women with eating disorders: findings from a population-based birth cohort.

OBJECTIVE: To investigate fertility treatment, twin births, and unplanned pregnancies in pregnant women with eating disorders in a population-based sample. DESIGN: A longitudinal population-based birth cohort (Generation R). SETTING: Rotterdam, the Netherlands. SAMPLE: Women from the Generation R study who reported a history of (recent or past) anorexia nervosa (n = 160), bulimia nervosa (n = 265), or both (n = 130), and a history of psychiatric disorders other than eating disorders (n = 1396) were compared with women without psychiatric disorders (n = 4367). METHODS: Women were compared on the studied outcomes using logistic regression. We performed crude and adjusted analyses (adjusting for relevant confounding factors). MAIN OUTCOME MEASURES: Fertility treatment, twin births, unplanned pregnancies, and women's feelings towards unplanned pregnancies. RESULTS: Relative to women without psychiatric disorders, women with bulimia nervosa had increased odds (odds ratio, OR, 2.3; 95% confidence interval, 95% CI, 1.1-5.2) of having undergone fertility treatment. Women with all eating disorders had increased odds of twin births (anorexia nervosa, OR 2.7, 95% CI 1.0-7.7; bulimia nervosa, OR 2.7, 95% CI 1.1-6.6; anorexia and bulimia nervosa, OR 3.795% CI 1.3-10.7). Anorexia nervosa was associated with increased odds of unplanned pregnancies (OR 1.8, 95% CI 1.2-2.6) and mixed feelings about these pregnancies (adjusted OR 5.0, 95% CI 1.7-14.4). Pre-pregnancy body mass index did not explain the observed associations. CONCLUSIONS: Eating disorders are associated with increased odds of receiving fertility treatment and twin births. Women with anorexia nervosa were more likely to have an unplanned pregnancy and have mixed feelings about the unplanned pregnancy. Fertility treatment specialists should be aware that both active and past eating disorders (both anorexia nervosa and bulimia nervosa) might underlie fertility problems.

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.