The prenatal environment may program health and disease susceptibility via epigenetic mechanisms. We evaluated associations of maternal trimester-specific intake of micronutrients with global DNA methylation (%5mC) and 5-hydroxymethylation (%5hmC) at birth in cord blood and tested for persistence into childhood. We quantified global %5mC and %5hmC in cord blood cells (n = 434) and in leukocytes collected in early (n = 108) and mid-childhood (n = 390) from children in Project Viva, a pre-birth cohort from Boston, MA. Validated food frequency questionnaires estimated maternal first- and second-trimester intakes of vitamin B2, vitamin B6, vitamin B12, folate, betaine, choline, methionine, iron, and zinc. Mean (SD) cord blood %5mC and %5hmC was 5.62% (2.04) and 0.25% (0.15), respectively. Each μg increase in first-trimester B12 intake was associated with 0.002 lower %5hmC in cord blood (95% CI: −0.005, −0.0003), and this association persisted in early childhood (β = −0.007; 95% CI: −0.01, −0.001) but not mid-childhood. Second-trimester iron (mg) was associated with 0.01 lower %5mC (95% CI: −0.02, −0.002) and 0.001 lower %5hmC (95% CI: −0.01, −0.00001) in cord blood only. Increased second-trimester zinc (mg) intake was associated with 0.003 greater %5hmC in early childhood (β = 0.003; 95% CI: 0.0004, 0.006). Second-trimester folate was positively associated with %5hmC in early childhood only (β = 0.08, 95% CI: 0.003, 0.16). Associations did not survive multiple testing adjustment; future replication is needed. Trimester-specific nutrients may impact various sensitive windows of epigenetic programming some with lasting effects in childhood. Further research is needed to understand the role of gene-specific epigenetic changes and how global DNA methylation measures relate to child health.

High-quality evidence from prospective longitudinal studies in humans is essential to testing hypotheses related to the developmental origins of health and disease. In this paper, the authors draw upon their own experiences leading birth cohorts with longitudinal follow-up into adulthood to describe specific challenges and lessons learned. Challenges are substantial and grow over time. Long-term funding is essential for study operations and critical to retaining study staff, who develop relationships with participants and hold important institutional knowledge and technical skill sets. To maintain contact, we recommend that cohorts apply multiple strategies for tracking and obtain as much high-quality contact information as possible before the child’s 18th birthday. To maximize engagement, we suggest that cohorts offer flexibility in visit timing, length, location, frequency, and type. Data collection may entail multiple modalities, even at a single collection timepoint, including measures that are self-reported, research-measured, and administrative with a mix of remote and in-person collection. Many topics highly relevant for adolescent and young adult health and well-being are considered to be private in nature, and their assessment requires sensitivity. To motivate ongoing participation, cohorts must work to understand participant barriers and motivators, share scientific findings, and provide appropriate compensation for participation. It is essential for cohorts to strive for broad representation including individuals from higher risk populations, not only among the participants but also the staff. Successful longitudinal follow-up of a study population ultimately requires flexibility, adaptability, appropriate incentives, and opportunities for feedback from participants.

Exposure to maternal hyperglycemia in utero has been associated with adverse metabolic outcomes in offspring. However, few studies have investigated the relationship between maternal hyperglycemia and offspring cortisol levels. We assessed associations of gestational diabetes mellitus (GDM) with cortisol biomarkers in two longitudinal prebirth cohorts: Project Viva included 928 mother–child pairs and Gen3G included 313 mother–child pairs. In Project Viva, GDM was diagnosed in N = 48 (5.2%) women using a two-step procedure (50 g glucose challenge test, if abnormal followed by 100 g oral glucose tolerance test [OGTT]), and in N = 29 (9.3%) women participating in Gen3G using one-step 75 g OGTT. In Project Viva, we measured cord blood glucocorticoids and child hair cortisol levels during mid-childhood (mean (SD) age: 7.8 (0.8) years) and early adolescence (mean (SD) age: 13.2 (0.9) years). In Gen3G, we measured hair cortisol at 5.4 (0.3) years. We used multivariable linear regression to examine associations of GDM with offspring cortisol, adjusting for child age and sex, maternal prepregnancy body mass index, education, and socioeconomic status. We additionally adjusted for child race/ethnicity in the cord blood analyses. In both Project Viva and Gen3G, we observed null associations of GDM and maternal glucose markers in pregnancy with cortisol biomarkers in cord blood at birth (β = 16.6 nmol/L, 95% CI −60.7, 94.0 in Project Viva) and in hair samples during childhood (β = −0.56 pg/mg, 95% CI −1.16, 0.04 in Project Viva; β = 0.09 pg/mg, 95% CI −0.38, 0.57 in Gen3G). Our findings do not support the hypothesis that maternal hyperglycemia is related to hypothalamic–pituitary–adrenal axis activity.

Maternal fish intake during pregnancy may influence the risk of child asthma and allergic rhinitis, yet evidence is conflicting on its association with these outcomes. We examined the associations of maternal fish intake during pregnancy with child asthma and allergic rhinitis. Mothers in the Danish National Birth Cohort (n 28 936) reported their fish intake at 12 and 30 weeks of gestation. Using multivariate logistic regression, we examined the associations of fish intake with child wheeze, asthma and rhinitis assessed at several time points: ever wheeze, recurrent wheeze (>3 episodes), ever asthma and allergic rhinitis, and current asthma, assessed at 18 months (n approximately 22 000) and 7 years (n approximately 17 000) using self-report and registry data on hospitalisations and prescribed medications. Compared with consistently high fish intake during pregnancy (fish as a sandwich or hot meal ≥ 2–3 times/week), never eating fish was associated with a higher risk of child asthma diagnosis at 18 months (OR 1·30, 95 % CI 1·05, 1·63, P= 0·02), and ever asthma by hospitalisation (OR 1·46, 95 % CI 0·99, 2·13, P= 0·05) and medication prescription (OR 1·37, 95 % CI 1·10, 1·71, P= 0·01). A dose–response was present for asthma at 18 months only (P for trend = 0·001). We found no associations with wheeze or recurrent wheeze at 18 months or with allergic rhinitis. The results suggest that high (v. no) maternal fish intake during pregnancy is protective against both early and ever asthma in 7-year-old children.