A Priori and a Posteriori dietary patterns during pregnancy and gestational weight gain: The generation R study

Abnormal gestational weight gain (GWG) is associated with adverse pregnancy outcomes. We examined whether dietary patterns are associated with GWG. Participants included 3374 pregnant women from a population-based cohort in the Netherlands. Dietary intake during pregnancy was assessed with food-frequency questionnaires. Three a posteriori-derived dietary patterns were identified using principal component analysis: a “Vegetable, oil and fish”, a “Nuts, high-fiber cereals and soy”, and a “Margarine, sugar and snacks” pattern. The a priori-defined dietary pattern was based on national dietary recommendations. Weight was repeatedly measured around 13, 20 and 30 weeks of pregnancy; pre-pregnancy and maximum weight were self-reported. Normal weight women with high adherence to the “Vegetable, oil and fish” pattern had higher early-pregnancy GWG than those with low adherence (43 g/week (95% CI 16; 69) for highest vs. lowest quartile (Q)). Adherence to the “Margarine, sugar and snacks” pattern was associated with a higher prevalence of excessive GWG (OR 1.45 (95% CI 1.06; 1.99) Q4 vs. Q1). Normal weight women with higher scores on the “Nuts, high-fiber cereals and soy” pattern had more moderate GWG than women with lower scores (-0.01 (95% CI 0.02; -0.00) per SD). The a priori-defined pattern was not associated with GWG. To conclude, specific dietary patterns may play a role in early pregnancy but are not consistently associated with GWG

Critical periods and growth patterns from fetal life onwards associated with childhood insulin levels

Aims/hypothesis: We aimed to identify critical periods and specific longitudinal growth patterns from fetal life onwards associated with childhood insulin and C-peptide levels. Methods: In a prospective population-based cohort study of 4328 children, we repeatedly measured (femur) length and (estimated fetal) weight from the second trimester of fetal life until 6 years of age. BMI was calculated from 6 months onwards. Insulin and C-peptide levels were measured at 6 years of age. Results: Preterm birth and small or large size for gestational age at birth were not associated with childhood insulin levels. Conditional growth modelling showed that, independent of growth in other time intervals, weight growth in each time interval from birth onwards, length growth from 6 months onwards and BMI growth from 12 months onwards were positively associated with childhood insulin levels. The strongest associations were present for weight and BMI growth between 48 and 72 months of age. Repeated measurement analyses showed that, compared with children in the lowest quartile of childhood insulin, those in the highest quartile had a higher length from birth onwards and a higher weight and BMI from 24 months onwards. These differences increased with age. No associations were observed for fetal growth characteristics. Similar results were observed for C-peptide levels. Conclusions/interpretation: Our results suggest that rapid length, weight and BMI growth from birth onwards, but not during fetal life, is associated with higher insulin levels in childhood

Maternal fish consumption, fatty acid levels and angiogenic factors: The Generation R Study

Introduction Angiogenic factors, such as placental growth factor (PlGF) and soluble Flt-1 (sFlt-1), are key regulators of placental vascular development. Evidence from in vitro studies indicates that fatty acids can affect angiogenesis. We investigated the associations of maternal fish consumption and fatty acids levels with angiogenic factors during pregnancy, and in cord blood in a large population-based prospective cohort. Methods First trimester fish consumption was assessed among 3134 pregnant women using a food-frequency questionnaire. Plasma fatty acid levels were measured in second trimester. Plasma PlGF and sFlt-1 were measured in first and second trimester and in cord blood. Associations of fish consumption or fatty acid levels with angiogenic factors were assessed by multivariable linear regression analyses. Results There were no consistent associations of total fish or lean fish consumption with levels of PlGF, sFlt-1, or sFlt-1/PlGF ratio. Neither fatty fish nor shellfish were associated with angiogenic factors. Plasma omega-3 polyunsaturated fatty acids, which are the main type of fatty acids in fish, were inconsistently associated with angiogenic factors in second trimester and cord blood. Yet, higher levels of arachidonic acid, an omega-6 polyunsaturated fatty acid, were associated with lower levels of PlGF and sFlt-1. Discussion We found no consistent associations of fish consumption or fatty acids levels with angiogenic factors in a population with low fish consumption. Studies including populations with higher fish consumption are required to fully grasp the potential effects of maternal fish consumption on placental angiogenesis

Maternal vomiting during early pregnancy and cardiovascular risk factors at school age: the Generation R Study

Background: Evidence suggests that low birth weight and fetal exposure to extreme maternal undernutrition is associated with cardiovascular disease in adulthood. Hyperemesis gravidarum, a clinical entity characterized by severe nausea and excess vomiting leading to a suboptimal maternal nutritional status during early pregnancy, is associated with an increased risk of adverse pregnancy outcomes. Several studies also showed that different measures related to hyperemesis gravidarum, such as maternal daily vomiting or severe weight loss, are associated with increased risks of adverse fetal pregnancy outcomes. Not much is known about long-term offspring consequences of maternal hyperemesis gravidarum and related measures during pregnancy. We examined the associations of maternal daily vomiting during early pregnancy, as a measure related to hyperemesis gravidarum, with childhood cardiovascular risk factors. Methods: In a population-based prospective cohort study from early pregnancy onwards among 4,769 mothers and their children in Rotterdam, the Netherlands, we measured childhood body mass index, total fat mass percentage, android/gynoid fat mass ratio, preperitoneal fat mass area, blood pressure, lipids, and insulin levels. We used multiple regression analyses to assess the associations of maternal vomiting during early pregnancy with childhood cardiovascular outcomes. Results: Compared with the children of mothers without daily vomiting during early pregnancy, the children of mothers with daily vomiting during early pregnancy had a higher childhood total body fat mass (difference 0.12 standard deviation score [SDS]; 95% confidence interval [CI] 0.03–0.20), android/gynoid fat mass ratio (difference 0.13 SDS; 95% CI 0.04– 0.23), and preperitoneal fat mass area (difference 0.10 SDS; 95% CI 0–0.20). These associations were not explained by birth characteristics but partly explained by higher infant growth. Maternal daily vomiting during early pregnancy was not associated with childhood blood pressure, lipids, and insulin levels. Conclusions: Maternal daily vomiting during early pregnancy is associated with higher childhood total body fat mass and abdominal fat mass levels, but not with other cardiovascular risk factors. Further studies are needed to replicate these findings, to explore the underlying mechanisms and to ass

Fetal sex and maternal pregnancy outcomes: a systematic review and meta-analysis

BACKGROUND: Since the placenta also has a sex, fetal sex-specific differences in the occurrence of placenta-mediated complications could exist. OBJECTIVE: To determine the association of fetal sex with multiple maternal pregnancy complications. SEARCH STRATEGY: Six electronic databases Ovid MEDLINE, EMBASE, Cochrane Central, Web-of-Science, PubMed, and Google Scholar were systematically searched to identify eligible studies. Reference lists of the included studies and contact with experts were also used for identification of studies. SELECTION CRITERIA: Observational studies that assessed fetal sex and the presence of maternal pregnancy complications within singleton pregnancies. DATA COLLECTION AND ANALYSES: Data were extracted by 2 independent reviewers using a predesigned data collection form. MAIN RESULTS: From 6522 original references, 74 studies were selected, including over 12,5 million women. Male fetal sex was associated with term pre-eclampsia (pooled OR 1.07 [95%CI 1.06 to 1.09]) and gestational diabetes (pooled OR 1.04 [1.02 to 1.07]). All other pregnancy complications (i.e., gestational hypertension, total pre-eclampsia, eclampsia, placental abruption, and post-partum hemorrhage) tended to be associated with male fetal sex, except for preterm pre-eclampsia, which was more associated with female fetal sex. Overall quality of the included studies was good. Between-study heterogeneity was high due to differences in study population and outcome definition. CONCLUSION: This meta-analysis suggests that the occurrence of pregnancy complications differ according to fetal sex with a higher cardiovascular an

The Generation R Study: design and cohort update 2017

The Generation R Study is a population-based prospective cohort study from fetal life until adulthood. The study is designed to identify early environmental and genetic causes and causal pathways leading to normal and abnormal growth, development and health from fetal life, childhood and young adulthood. This multidisciplinary study focuses on several health outcomes including behaviour and cognition, body composition, eye development, growth, hearing, heart and vascular development, infectious disease and immunity, oral health and facial growth, respiratory health, allergy and skin disorders of children and their parents. Main exposures of interest include environmental, endocrine, genomic (genetic, epigenetic, microbiome), lifestyle related, nutritional and socio-demographic determinants. In total, 9778 mothers with a delivery date from April 2002 until January 2006 were enrolled in the study. Response at baseline was 61%, and general follow-up rates until the age of 10 years were around 80%. Data collection in children and their parents includes questionnaires, interviews, detailed physical and ultrasound examinations, behavioural observations, lung function, Magnetic Resonance Imaging and biological sampling. Genome and epigenome wide association screens are available. Eventually, results from the Generation R Study contribute to the deve

Maternal plasma folate impacts differential DNA methylation in an epigenome-wide meta-analysis of newborns

Folate is vital for fetal development. Periconceptional folic acid supplementation and food fortification are recommended to prevent neural tube defects. Mechanisms whereby periconceptional folate influences normal development and disease are poorly understood: epigenetics may be involved. We examine the association between maternal plasma folate during pregnancy and epigenome-wide DNA methylation using Illumina" s HumanMethyl450 Beadchip in 1,988 newborns from two European cohorts. Here we report the combined covariate-adjusted results using meta-analysis and employ pathway and gene expression analyses. Four-hundred forty-three CpGs (320 genes) are significantly associated with maternal plasma folate levels during pregnancy (false discovery rate 5%); 48 are significant after Bonferroni correction. Most genes are not known for folate biology, including APC2, GRM8, SLC16A12, OPCML, PRPH, LHX1, KLK4 and PRSS21. Some relate to birth defects other than neural tube defects, neurological functions or varied aspects of embryonic development. These findings may inform how maternal folate impacts the developing epigenome and health outcomes in offspring