Early influences on cardiovascular and renal development

The hypothesis that a developmental component plays a role in subsequent disease initially arose from epidemiological studies relating birth size to both risk factors for cardiovascular disease and actual cardiovascular disease prevalence in later life. The findings that small size at birth is associated with an increased risk of cardiovascular disease have led to concerns about the effect size and the causality of the associations. However, recent studies have overcome most methodological flaws and suggested small effect sizes for these associations for the individual, but an potential important effect size on a population level. Various mechanisms underlying these associations have been hypothesized, including fetal undernutrition, genetic susceptibility and postnatal accelerated growth. The specific adverse exposures in fetal and early postnatal life leading to cardiovascular disease in adult life are not yet fully understood. Current studies suggest that both environmental and genetic factors in various periods of life may underlie the complex associations of fetal growth retardation and low birth weight with cardiovascular disease in later life. To estimate the population effect size and to identify the underlying mechanisms, well-designed epidemiological studies are needed. This review is focused on specific adverse fetal exposures, cardiovascular adaptations and perspectives for new studies. Copyrigh

Associations of maternal early-pregnancy dietary glycemic index with childhood general, abdominal and ectopic fat accumulation

BACKGROUND & AIMS: Maternal hyperglycemia during pregnancy is an important risk factor for childhood adiposity. Maternal dietary glycemic index during pregnancy directly influences maternal and fetal glucose concentrations. We examined the associations of maternal early-pregnancy dietary glycemic index with offspring general, abdominal and ectopic fat accumulation among normal weight and overweight or obese pregnant women and their offspring. METHODS: In a population-based cohort study among 2488 Dutch pregnant women and their children, we assessed maternal dietary glycemic index by food frequency questionnaire at median 13.4 (95% range 10.7; 21.1) weeks gestation. Dietary glycemic index was used continuously and categorized into low (≤55), normal (56–69) and high (≥70) glycemic index diet. We measured offspring BMI, total fat mass and android/gynoid fat mass ratio by DXA, and visceral fat mass and liver fat fraction by MRI at 10 years. RESULTS: No associations of maternal early-pregnancy dietary glycemic index with offspring adiposity were present among normal weight women and their children. Among overweight and obese women and their children, 1-Standard Deviation Score (SDS) increase in maternal early-pregnancy dietary glycemic index was associated with higher childhood BMI (0.10 SDS, 95% Confidence Interval (CI) 0.01; 0.19), total fat mass index (0.13 SDS, 95% CI 0.05; 0.22), visceral fat mass index (0.19 SDS, 95% CI 0.07; 0.32) and tended to be associated with a higher android/gynoid fat mass ratio (0.09 SDS, 95% CI −0.01; 0.19) and higher risk of childhood overweight (Odds Ratio (OR) 1.20, 95% CI 0.97; 1.48). Overweight and obese women consuming an early-pregnancy low-glycemic index diet, as compared to an early-pregnancy normal-glycemic index diet, had children with lower BMI, total fat mass index, visceral fat mass index and android/gynoid fat mass ratio at 10 years (p-values<0.05). No women consumed a high-glycemic index diet. No associations were explained by maternal socio-economic, lifestyle and dietary characteristics, birth or childhood characteristics. No associations with liver fat fraction were present. CONCLUSIONS: In overweight or obese women and their children, a higher maternal early-pregnancy dietary glycemic index is associated with childhood general, abdominal and visceral fat accumulation, but not with liver fat. Intervention studies among overweight and obese pregnant women may need to target the dietary glycemic index to prevent childhood adiposity

Intrauterine exposure to mild analgesics during pregnancy and the occurrence of cryptorchidism and hypospadia in the offspring: The Generation R Study

This article is available open access through the publisher’s website. Copyright @ 2012 The Authors.BACKGROUND - Recently, over-the-counter mild analgesic use during pregnancy has been suggested to influence the risk of reproductive disorders in the offspring. We examined the influence of maternal exposure to mild analgesics during pregnancy on the occurrence of cryptorchidism and hypospadia in their offspring. METHODS - Associations between maternal exposure to mild analgesics during pregnancy and cryptorchidism or hypospadia in the offspring were studied in 3184 women participating in a large population-based prospective birth cohort study from early pregnancy onwards in the Netherlands (2002–2006), the Generation R Study. Cryptorchidism and hypospadia were identified during routine screening assessments performed in child health care centres by trained physicians. The use of mild analgesics was assessed in three prenatal questionnaires in pregnancy, resulting in four periods of use, namely, periconception period, first 14 weeks of gestation, 14–22 weeks of gestation and 20–32 weeks of gestation. Logistic regression analyses were used to study the associations between maternal exposure to mild analgesics and cryptorchidism and hypospadia. RESULTS - The cumulative prevalence over 30 months of follow up was 2.1% for cryptorchidism and 0.7% for hypospadia. Use of mild analgesics in the second period of pregnancy (14–22 weeks) increased the risk of congenital cryptorchidism [adjusted odds ratio (OR) 2.12; 95% confidence interval (CI) 1.17–3.83], primarily due to the use of acetaminophen (paracetamol) (adjusted OR 1.89; 95% CI 1.01–3.51). Among mothers of cryptorchid sons, 33.8% reported (23 of 68) the use of mild analgesics during pregnancy, compared with 31.8% (7 of 22) of mothers with a boy with hypospadia and 29.9% (926 of 3094) of mothers with healthy boys. CONCLUSIONS - Our results suggest that intrauterine exposure to mild analgesics, primarily paracetamol, during the period in pregnancy when male sexual differentiation takes place, increases the risk of cryptorchidism.Erasmus University Rotterdam, School of Law and Faculty of Social Sciences, the Municipal Health Service Rotterdam area, Rotterdam, the Rotterdam Homecare Foundation, Rotterdam and the Stichting Trombosedienst & Artsenlaboratorium Rijnmond (STAR), Rotterdam

Associations of maternal angiogenic factors during pregnancy with childhood carotid intima-media thickness and blood pressure

BACKGROUND AND AIMS: Reduced maternal placental growth factor (PlGF) and higher soluble fms-like tyrosine kinase (sFlt-1) concentrations in pregnancy may have persistent effects on offspring vasculature. We hypothesized that suboptimal maternal angiogenic factors in pregnancy may adversely affect fetal vascular development, leading to an increased risk of adverse atheriosclerotic adaptations and higher blood pressure in offspring. METHODS: In a population-based prospective cohort among 4565 women and their offspring, we examined the associations of maternal serum PlGF and sFlt-1 concentrations in the first half of pregnancy with offspring vascular development. We measured childhood blood pressure and obtained childhood carotid intima media thickness and carotid distensibility through ultrasonography at 9 years. RESULTS: After adjustment for maternal sociodemographic and lifestyle characteristics, no associations were present of maternal first and second trimester angiogenic factors with childhood blood pressure, carotid intima media thickness (IMT) or distensibility in the total population. In preterm born children only, higher maternal second trimester PlGF concentrations, but not sFlt-1 concentrations, were associated with a lower childhood diastolic blood pressure (difference: -0.16 SDS (95% CI -0.30, –0.03) per SDS increase in maternal second trimester PlGF concentration). No associations among children born small-for-gestational age were present. CONCLUSIONS: In a low-risk population, maternal angiogenic factors in the first half of pregnancy are not associated with childhood blood pressure, carotid IMT or carotid distensibility after considering maternal socio-demographic and lifestyle factors. Only in children born preterm, lower maternal second trimester PlGF concentrations are associated with higher childhood diastolic blood pressure, but not with other vascular outcomes

Maternal milk consumption, fetal growth, and the risks of neonatal complications: The Generation R Study

Background: Maternal cow-milk consumption may increase birth weight. Previous studies did not assess the association of maternal milk consumption with trimester-specific fetal growth. Objective: The objective was to assess associations of first-trimester maternal milk consumption with fetal growth characteristics in different trimesters and the risk of neonatal complications. Design: In total, 3405 mothers participating in a prospective cohort study completed a 293-item semiquantitative food-frequency questionnaire to obtain information about dairy consumption during the first trimester of pregnancy. Fetal head circumference, femur length, and weight were estimated in the second and third trimesters by ultrasonography. Results: Maternal milk consumption of >3 glasses/d was associated with greater fetal weight gain in the third trimester of pregnancy, which led to an 88-g (95% CI: 39, 135 g) higher birth weight than that with milk consumption of 0 to 1 glass/d. In addition, head circumference tended to be 2.3 cm (95% CI: -0.0, 4.6 cm) larger when mothers consumed >3 glasses/d. Maternal milk consumption was not associated with length growth. Maternal protein intake (P for trend = 0.01), but not fat or carbohydrate intake, from dairy products was associated with higher birth weight. This association appeared to be limited to milk (P for trend < 0.01), whereas protein intake from nondairy food or cheese was not associated with birth weight. Conclusions: Maternal milk consumption is associated with greater fetal weight gain. The association seems to be due to milk protein, or milk components closely associated with protein, rather than to the fat or carbohydrate fraction of milk

Risk factors and cardio-metabolic outcomes associated with metabolic-associated fatty liver disease in childhood

Background Non-Alcoholic Fatty Liver Disease (NAFLD) is defined as increased liver fat percentage, and is the most common chronic liver disease in children. Rather than NAFLD, Metabolic-Associated Fatty Liver Disease (MAFLD), defined as increased liver fat with presence of adverse cardio-metabolic measures, might have more clinical relevance in children. We assessed the prevalence, risk-factors and cardio-metabolic outcomes of MAFLD at school-age. Methods This cross-sectional analysis was embedded in an ongoing population-based prospective cohort study started in 2001, in the Netherlands. In 1910 children of 10 years, we measured liver fat fraction by magnetic resonance imaging (MRI), body mass index (BMI), blood pressure, and lipids, insulin, and glucose concentrations. Childhood lifestyle factors were obtained through questionnaires. MAFLD was defined as ≥2% liver fat in addition to excess adiposity (BMI or visceral adiposity), presence of metabolic risk (blood pressure, triglycerides and HDL-concentrations) or prediabetes (glucose). Findings Of all children, 49.6% had ≥2% liver fat, and 25.2% fulfilled the criteria of MAFLD. Only non-European descent was associated with increased odds of MAFLD at nominal significance (Odds Ratio 1.38, 95% Confidence Interval 1.04, 1.82). Compared to children with <2% liver fat, those with MAFLD had increased odds of cardio-metabolic-risk-factor clustering (Odds Ratio 7.65, 95% Confidence Interval 5.04, 11.62). Interpretation In this study, no NAFLD-associated childhood risk factors were associated with increased odds of childhood MAFLD, yet the findings suggest that ethnicity could be, despite mostly explained by socio-economic factors. Use of MAFLD criteria, rather than NAFLD, may identify children at risk for impaired cardio-metabolic health. Funding Erasmus University MC, the Netherlands Organisation for Health Research and Development, the Ministry of Health, Welfare, and Sport, and the European Research Council.The general design of the Generation R Study was made possible by financial support from the Erasmus University Medical Center, the Netherlands Organisation for Health Research and Development, and the Ministry of Health, Welfare, and Sport. The study was supported by the European Research Council (Consolidator Grant ERC-2014-CoG-648916), and the European Union’s Horizon 2020 research and innovation program (Grant Agreement No. 733206 LifeCycle). We gratefully acknowledge the contribution of the participating children, their mothers, general practitioners, hospitals, midwives, and pharmacies in Rotterdam. We additionally would like to thank the staff of the data collection team and data-management team of Generation R for their work that resulted in the population data