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Altered maternal haemoglobin levels during pregnancy are associated with pre-clinical and clinical conditions affecting the fetus. Evidence from animal models suggests that these associations may be partially explained by differential DNA methylation in the newborn with possible long-term consequences. To test this in humans, we meta-analyzed the epigenome-wide associations of maternal haemoglobin levels during pregnancy with offspring DNA methylation in 3,967 newborn cord blood and 1,534 children and 1,962 adolescent whole-blood samples derived from 10 cohorts. DNA methylation was measured using Illumina Infinium Methylation 450K or MethylationEPIC arrays covering 450,000 and 850,000 methylation sites, respectively. There was no statistical support for the association of maternal haemoglobin levels with offspring DNA methylation either at individual methylation sites or clustered in regions. For most participants, maternal haemoglobin levels were within the normal range in the current study, whereas adverse perinatal outcomes often arise at the extremes. Thus, this study does not rule out the possibility that associations with offspring DNA methylation might be seen in studies with more extreme maternal haemoglobin levels.

While studies suggest potential influences of childhood adversities on obesity development in adulthood, less is known about the short-term association in children. We examined the association between a wide range of life events experienced in the first ten years of life (including maltreatment and milder adversities) and body composition in 5333 ten-year old Dutch children. In structured interviews, mothers retrospectively reported on their children's experience of 24 events. BMI was calculated, and fat mass index and fat free mass index were determined by dual-x-ray absorptiometry scanning. Linear regressions showed that, unadjusted, a higher number of life events was associated with higher BMI and body composition. However, associations attenuated to non-significance after adjustment for covariates. Similar findings were observed for maltreatment and milder life events. Thus, the number of experienced life events was not associated with body composition in middle childhood. Rather, other factors, like socioeconomic conditions, accounted for the relationship between life events and weight development in children., (© 2021. The Author(s).)

Context: Biological stress is related to cardiovascular disease in adults. The associations of stress with cardiovascular and metabolic diseases may originate in childhood., Objective: This work aims to examine the associations of hair cortisol concentrations at age 6 years with cardiometabolic risk factors at ages 6 and 10 years., Methods: Cortisol concentrations were measured in hair of 6-year-old children (n = 2598) participating in the Generation R Study, a population-based prospective cohort study in Rotterdam, the Netherlands. Main outcome measures included blood pressure, heart rate, concentrations of insulin, glucose, lipids, and C-reactive protein in blood at ages 6 and 10 years., Results: Higher hair cortisol concentrations at age 6 years were associated with higher systolic blood pressure at age 10 years (difference 0.17 SD score; 95% CI, 0.03-0.31). The association attenuated into nonsignificance after adjustment for childhood body mass index (BMI) at age 6 years. Higher hair cortisol concentrations at age 6 years were associated with an increase in total and low-density lipoprotein cholesterol between ages 6 and 10 years but not with those measurements at age 6 or 10 years. Hair cortisol concentrations were not associated with other cardiometabolic risk factors at age 6 or 10 years., Conclusion: Hair cortisol concentrations were not independent of BMI associated with cardiometabolic risk factors at 6 or 10 years. The associations of biological stress with cardiometabolic risk factors may develop at later ages., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)

Context: Stress may lead to an adverse body fat distribution from childhood onwards., Objective: To examine the associations of hair cortisol concentration (HCC) at 6 years with general and organ fat measures, risk of overweight, and nonalcoholic fatty liver disease (NAFLD) at 10 years and to assess whether these were independent of adiposity measures at 6 years., Design, Setting and Participants: HCCs were measured in hair of 6-year-old children (n = 2042) participating in the Generation R Study, a population-based prospective cohort study., Main Outcome Measures: Body mass index (BMI), fat mass index measured by dual-energy X-ray absorptiometry scan, and visceral fat index, pericardial fat index, liver fat fraction measured by magnetic resonance imaging and risk of overweight and NAFLD were obtained at 10 years., Results: The associations of higher HCC at 6 years, with higher BMI, fat mass index, and increased risk of overweight at age 10 years are explained by the relationships observed at 6 years. HCCs at 6 years were associated with a higher liver fat fraction (difference 0.11 liver fat fraction standard deviation score; 95% confidence interval [CI] 0.03, 0.18) and a higher risk of NAFLD at 10 years (odds ratio 1.95; 95% CI 1.06, 3.56), independent of fat mass index at 6 years. HCCs were not associated with pericardial or visceral fat indices., Conclusions: Higher HCCs at 6 years were associated with higher BMI, fat mass index, liver fat fraction, and higher risks of overweight and NAFLD at 10 years. Only the associations for liver fat fraction and NAFLD were independent of fat mass index at 6 years., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: DNA methylation has been shown to be associated with adiposity in adulthood. However, whether similar DNA methylation patterns are associated with childhood and adolescent body mass index (BMI) is largely unknown. More insight into this relationship at younger ages may have implications for future prevention of obesity and its related traits., Methods: We examined whether DNA methylation in cord blood and whole blood in childhood and adolescence was associated with BMI in the age range from 2 to 18 years using both cross-sectional and longitudinal models. We performed meta-analyses of epigenome-wide association studies including up to 4133 children from 23 studies. We examined the overlap of findings reported in previous studies in children and adults with those in our analyses and calculated enrichment., Results: DNA methylation at three CpGs (cg05937453, cg25212453, and cg10040131), each in a different age range, was associated with BMI at Bonferroni significance, P < 1.06 × 10 -7 , with a 0.96 standard deviation score (SDS) (standard error (SE) 0.17), 0.32 SDS (SE 0.06), and 0.32 BMI SDS (SE 0.06) higher BMI per 10% increase in methylation, respectively. DNA methylation at nine additional CpGs in the cross-sectional childhood model was associated with BMI at false discovery rate significance. The strength of the associations of DNA methylation at the 187 CpGs previously identified to be associated with adult BMI, increased with advancing age across childhood and adolescence in our analyses. In addition, correlation coefficients between effect estimates for those CpGs in adults and in children and adolescents also increased. Among the top findings for each age range, we observed increasing enrichment for the CpGs that were previously identified in adults (birth P enrichment  = 1; childhood P enrichment  = 2.00 × 10 -4 ; adolescence P enrichment  = 2.10 × 10 -7 )., Conclusions: There were only minimal associations of DNA methylation with childhood and adolescent BMI. With the advancing age of the participants across childhood and adolescence, we observed increasing overlap with altered DNA methylation loci reported in association with adult BMI. These findings may be compatible with the hypothesis that DNA methylation differences are mostly a consequence rather than a cause of obesity.

Background: Psychological distress and inappropriate or excessive weight gain are common in pregnancy and are associated with adverse maternal and offspring outcomes. Psychological well-being and weight status of women during pregnancy might be interrelated. We aimed to examine whether psychological distress during pregnancy is associated with gestational weight gain., Method: In a population-based cohort of 3393 pregnant women, information about psychological distress, depressive and anxiety symptoms was assessed at 20 weeks of gestation using the Brief Symptom Inventory questionnaire. Weight was repeatedly measured during pregnancy and obtained by questionnaire before and after pregnancy. Linear regression and multinomial logistic regression models were used. Weight gain in the second half of pregnancy, total weight gain, and the risks of inadequate and excessive total weight gain were the main outcome measures., Results: In total, 7.0% of all women experienced psychological distress. Overall psychological distress and anxiety were associated with lower weight gain in the second half of pregnancy (differences - 1.00 kg (95% confidence interval (CI) - 1.62, - 0.37) and - 0.68 kg (95% CI - 1.24, -0.11), respectively). These associations fully attenuated into non-significance after taking account for socio-demographic variables. Similar results were observed for total weight gain. Only women with anxiety symptoms had, independently of potential confounders, a lower risk of excessive weight gain (odds ratio (OR) 0.61 (95% CI 0.48, 0.91))., Conclusions: In this large prospective cohort study, the observed associations of psychological distress with weight gain during pregnancy seem to be largely explained by common socio-demographic factors.

Background: Psychological distress during pregnancy may influence offspring adiposity. No studies assessed the associations with organ fat measures. We examined the associations of maternal psychological distress, depression, and anxiety during pregnancy with child general and organ fat measures. Methods: In 4161 mother-offspring pairs, psychological distress was self-reported in pregnancy. We obtained general fat measures, including BMI and fat mass index by dual-energy X-ray absorptiometry, and organ fat measures (in a subsample of 2447 children), including subcutaneous, visceral, and pericardial fat indices and liver fat fraction by magnetic resonance imaging at 10 years. Linear and logistic regression models were used. Results: Children of mothers with psychological distress had higher fat mass index [difference 0.14 (95% confidence interval {CI} 0.04-0.24) standard deviation scores (SDS)] and higher risk of obesity [odds ratio (OR) 1.73 (95% CI 1.09-2.74)]. Maternal anxiety was associated with higher BMI [difference 0.16 (95% CI 0.05-0.26) SDS], fat mass index [difference 0.19 (95% CI 0.10-0.28) SDS], and higher risks of overweight and obesity [OR 1.36 (95% CI 1.03-1.81), 1.78 (95% CI 1.13-2.81)]. Maternal anxiety was associated with higher subcutaneous and visceral fat indices and liver fat fraction [differences 0.16 (95% CI 0.03-0.29), 0.15 (95% CI 0.01-0.29), and 0.16 (95% CI 0.02-0.29) SDS]. No associations were observed for maternal depression. Conclusions: Psychological distress and anxiety, but not depression, during pregnancy were associated with higher child general and organ fat measures. A healthy mental state during pregnancy may be important for preventing child adiposity.

Maternal psychological distress is common in pregnancy and may influence the risk of adverse outcomes in children. Psychological distress may cause a suboptimal intrauterine environment leading to growth and developmental adaptations of the fetus and child. In this narrative review, we examined the influence of maternal psychological distress during pregnancy on fetal outcomes and child cardiometabolic, respiratory, atopic and neurodevelopment-related health outcomes. We discussed these findings from an epidemiological and life course perspective and provided recommendations for future studies. The literature in the field of maternal psychological distress and child health outcomes is extensive and shows that exposure to stress during pregnancy is associated with multiple adverse child health outcomes. Because maternal psychological distress is an important and potential modifiable factor during pregnancy, it should be a target for prevention strategies in order to optimize fetal and child health. Future studies should use innovative designs and strategies in order to address the issue of causality.

Background and Aims: Previous studies suggest that psychological distress during pregnancy may lead to fetal developmental adaptations, which programme cardio-metabolic disease of the offspring. We examined the associations of maternal overall psychological distress, depression and anxiety during pregnancy with cardio-metabolic risk factors in 10-year-old children and explore potential sex-specific differences., Methods and Results: In a population-based prospective cohort study among 4,088 mothers and their children, information about overall psychological distress, including depression and anxiety was obtained through the Brief Symptom Inventory during pregnancy. We measured child blood pressure and heart rate and insulin, glucose, serum lipids and C-reactive protein blood concentrations at 10 years. Analyses were performed in the total group and in boys and girls separately. Psychological distress during pregnancy was associated with higher childhood heart rate among boys only (differences 0.34 (95% Confidence Interval (CI) 0.18, 0.50) standard deviation scores (SDS), 0.22 (95% CI 0.06, 0.38) SDS, 0.33 (95% CI 0.19, 0.48) SDS, for overall psychological distress, depression and anxiety, respectively). Maternal anxiety during pregnancy was associated with higher childhood triglycerides among girls (difference 0.35 (95% CI 0.17, 0.53) SDS). Maternal psychological distress was not associated with childhood blood pressure, cholesterol, insulin, glucose and C-reactive protein concentrations., Conclusions: Maternal psychological distress may influence their offspring heart rate and triglycerides concentrations. Further studies are needed to replicate these findings and assess the long-term cardio-metabolic consequences of maternal psychological distress., (Copyright © 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)