This issue of the Journal features collaborative follow-up studies of two unique pregnancy cohorts recruited during 1959–1966 in the United States. Here we introduce the Early Determinants of Adult Health (EDAH) study. EDAH was designed to compare health outcomes in midlife (age 40s) for same-sex siblings discordant on birthweight for gestational age. A sufficient sample of discordant siblings could only be obtained by combining these two cohorts in a single follow-up study. All of the subsequent six papers are either based upon the EDAH sample or are related to it in various ways. For example, three papers report results from studies that significantly extended the ‘core’ EDAH sample to address specific questions.

We first present the overall design of and rationale for the EDAH study. Then we offer a synopsis of past work with the two cohorts to provide a context for both EDAH and the related studies. Next, we describe the recruitment and assessment procedures for the core EDAH sample. This includes the process of sampling and recruitment of potential participants; a comparison of those who were assessed and not assessed based on archived data; the methods used in the adult follow-up assessment; and the characteristics at follow-up of those who were assessed. We provide online supplementary tables with much further detail. Finally, we note further work in progress on EDAH and related studies, and draw attention to the broader implications of this endeavor.

Growth trajectories play a central role in life course epidemiology, often providing fundamental indicators of prenatal or childhood development, as well as an array of potential determinants of adult health outcomes. Statistical methods for the analysis of growth trajectories have been widely studied, but many challenging problems remain. Repeated measurements of length, weight and head circumference, for example, may be available on most subjects in a study, but usually only sparse temporal sampling of such variables is feasible. It can thus be challenging to gain a detailed understanding of growth patterns, and smoothing techniques are inevitably needed. Moreover, the problem is exacerbated by the presence of large fluctuations in growth velocity during early infancy, and high variability between subjects. Existing approaches, however, can be inflexible because of a reliance on parametric models, require computationally intensive methods that are unsuitable for exploratory analyses, or are only capable of examining each variable separately. This article proposes some new nonparametric approaches to analyzing sparse data on growth trajectories, with flexibility and ease of implementation being key features. The methods are illustrated using data on participants in the Collaborative Perinatal Project.

We report on life course stress determinants of overweight in children, using data from the longitudinal follow-up of the nested case–control arm of the SAGE (study of asthma genes and the environment) birth cohort in Manitoba, Canada. Waist and hip measurements were obtained during a clinic visit at age 9–11 years. Multiple linear regression was conducted to determine the relationship between the waist-to-hip ratio and maternal smoking during pregnancy, postpartum maternal distress and stress reactivity in children (cortisol, cortisol-DHEA [dihydroepiandrostrenone] ratio quartiles) following a clinic stressor at age 8–10 years. We found waist-to-hip risk at age 9–11 years to be elevated among boys and girls whose mothers had experienced distress in the postnatal period. This association varied by gender and asthma status. In healthy girls, postpartum distress increased waist-to-hip ratio by a factor of 0.034 (P < 0.01), independent of the child's stage of puberty and adrenarche, cortisol-DHEA ratio and duration of exclusive breastfeeding. Among girls with asthma, maternal smoking during pregnancy was associated with an increased waist-to-hip ratio, if the mother also experienced distress in the postpartum period (0.072, P = 0.038). Among asthmatic boys, an association between maternal distress and waist-to-hip ratio was evident at the highest cortisol-DHEA ratios. Stress-induced changes to leptin and infant over-eating pathways were proposed to explain the postnatal maternal distress effects. Drawing on the theories of evolutionary biology, our findings underscore the significance of postnatal stress in disrupting hypothalamic–pituitary–adrenal axis function in infants and increasing risk for child overweight.

Recent advances in epigenetics have enhanced our knowledge of how environmental factors (UV radiation, drugs, infections, etc.) contribute to the development of autoimmune diseases (AID) in genetically predisposed individuals. Studies conducted in monozygotic twins discordant for AID and spontaneous autoimmune animal models have highlighted the importance of DNA methylation changes and histone modifications. Alterations in the epigenetic pattern seem to be cell specific, as CD4+ T cells and B cells are dysregulated in systemic lupus erythematosus, synovial fibroblasts in rheumatoid arthritis and cerebral cells in multiple sclerosis. With regard to lymphocytes, the control of tolerance is affected, leading to the development of autoreactive cells. Other epigenetic processes, such as the newly described miRNAs, and post-translational protein modifications may also be suspected. Altogether, a conceptual revolution is in progress, in AID, with potential new therapeutic strategies targeting epigenetic patterns.

Evidence from previous studies suggests an association between prenatal exposure to famine and increased risk for depression. The aim of this study was to investigate whether prenatal exposure to the Dutch famine is associated with self-reported depression/anxiety and whether a potential association is mediated by the presence of cardio-metabolic disease. A total of 819 persons, born as term singletons around the 1944–1945 Dutch famine, filled out the Hospital Anxiety and Depression Scale (HADS) and were asked about their medical history. As indicators of cardio-metabolic disease we included type 2 diabetes (T2D), hypertension and coronary heart disease (CHD). In the total study population, exposure to famine during early gestation was associated with the presence of self-reported mild-to-severe anxiety. Evidence was found for several interactions between exposure in early gestation and sex. Subsequent analyses according to sex showed that men exposed to famine during early gestation scored higher on the HADS depression scale. Self-reported mild-to-severe anxiety symptoms were more prevalent among early exposed men. No such differences were found in women. T2D and hypertension were not correlated with any of the depression and anxiety measures. Adjusting for the presence of CHD did minimally attenuate the size of the reported associations. In conclusion, the present results do not match those previously reported in prenatally famine-exposed individuals. We found only weak evidence for an association between prenatal famine exposure and symptoms of depression and anxiety, which was shown exclusively in men exposed during early gestation.

The aim of this study was to compare physical growth from birth to 2 years of age of babies born to women with or without gestational diabetes mellitus (GDM), among the subjects of the 2004 Pelotas Birth Cohort. Mothers who gave birth in 2004 in any of the five maternity wards in the city of Pelotas, Southern Brazil, were interviewed shortly after delivery by trained interviewers, using tested, pre-coded questionnaires. GDM diagnosis was self-reported. Child weight, length and abdominal circumference were measured, and adjusted weight-for-age, height-for-age and weight-for-height Z-scores were calculated at birth, 3, 12 and 24 months. We studied 4239 children. Offspring of GDM mothers (OGDM; n = 125) had lower gestational age (GA; P = 0.004), greater weight (P = 0.002) and greater abdominal circumference (P < 0.001) at birth. Prevalence of large for GA (LGA) was threefold higher among OGDM (18.4% v. 6.8%). Mean weight-for-age (0.48 v. −0.07; P < 0.001) and weight-for-height (0.94 v. 0.51; P < 0.001) Z-scores were also higher among OGDM. During the first 3 months, there was an abrupt catch-down among OGDM babies, who remained lighter than non-GDM offspring until the 24th month. LGA OGDM were heavier than LGA offspring of non-GDM mothers at birth, but had caught down with babies born with adequate weight for GA to non-GDM by 3 months, and showed similar growth patterns from thereon. OGDM show different growth patterns when compared to offspring of non-GDM mothers, which may be part of a causal pathway or constitute a risk marker for future obesity, impaired glucose tolerance and diabetes mellitus.

Many studies have reported on relations between birth size and adult size but the findings to date are hard to compare due to the lack of uniform measures across studies. Interpretation of findings is also hampered by potential confounding by ethnic, socioeconomic and family factors. The purpose of this study is to explore these relationships in a comprehensive fashion, with multiple measures of birth size and adult size, using same-sex sibling controls discordant in birth weight to address potential confounding at the family level. Study subjects include pregnant women enrolled during 1959–1966 in the Child Health and Development Study in Oakland, CA and the Boston, MA, and providence, RI, sites of the Collaborative Perinatal Project in New England, currently combined into the New England Family Study. We assessed 392 offspring (mean age 43 years), the great majority as sibships as available. Our analyses confirm the positive association between birth weight and adult length reported in other studies, with a change in adult height of 1.25 cm (95% CI: 0.79 to 1.70 cm) for each quintile change in standardized birth weight. No associations were seen between birth weight and adult fatness for which findings in other studies are highly variable. As adult weight is likely to reflect recent variations in the adult nutritional environment rather than the early environment, it may be more useful for studies of birth size and adult size to focus on adult length rather than weight measures in evaluating the role of early influences on adult health.

Undernutrition during pregnancy is associated with detrimental pregnancy and neonatal outcomes, which can have long-term implications for the infant. Hyperemesis gravidarum may severely limit nutritional intake. The aim of this study was to investigate the effect of hyperemesis on pregnancy and neonatal outcome, particularly gestation length and infant size at birth. Seventy-five prospectively recruited women admitted to a tertiary level hospital in Auckland, with hyperemesis gravidarum between March 2003 and October 2005, were compared to 142 controls matched for age, parity, ethnicity and expected date of delivery. Data were obtained from electronic records and analysed by Student's t-test, χ2, Wilcoxon, Fisher's exact tests and linear regression. Length of gestation, birth weight and crown-heel length were not different between participants and controls. Infants born to women with hyperemesis gravidarum had smaller head circumferences (Z-score mean (s.d.) 0.02 (0.16) v. 0.43 (0.11), P = 0.04 in all infants and −0.02 (1.24) v. 0.48 (1.29), P = 0.01 in-term infants). This study found hyperemesis gravidarum to be associated with smaller head circumferences in offspring. Given the reported associations between smaller head circumference at birth and lower cognitive ability and higher risk of cardiovascular disease in later life, further study is necessary to confirm these results and to determine whether there are any long-term implications for the offspring.

Offspring of diabetic mothers experience an increased risk for type 2 diabetes but it is not known whether diabetic pregnancies also confer a higher inter-generational risk for diabetic complications. Because microalbuminuria is a sensitive indicator of glomerular damage, we compared the urine albumin:creatinine ratios (ACRs) between 65 infants of diabetic mothers (InfDM+) and 59 infants of non-diabetic mothers (InfDM−), and repeated the comparisons in 21 InfDM+ and 19 InfDM− when children were 5–19 months old. ACRs were higher among neonates compared with normal reference values for adults, but declined with increasing age. The only independent predictor of higher ACRs in a logistic regression model (⩾13 mg/mmol v. <13 mg/mmol) was the presence of delivery complications (odds ratio 2.95; P = 0.015). Neither high nor low birth weight was associated with higher neonatal ACRs. The most unique finding of the study was that InfDM+ had significantly lower ACRs than InfDM− [mean = 12.9 (median = 6.0) v. mean = 16.6 (median = 11.5), respectively at P = 0.05] even after adjusting for other variables using logistic regression (odds ratio 0.25; P = 0.001). In contrast, by 5–19 months, there was a trend toward higher ACRs among InfDM+ compared with InfDM− [mean = 6.3 mg/mmol (median = 1.9) v. mean = 3.0 mg/mmol (median = 2.5), respectively at P = 0.25]. Lower ACRs in InfDM+ may be due to developmental changes in fetal kidneys induced by hyperinsulinemia. Although the implications of this observation are unclear, it is possible that exposure to a diabetic intrauterine environment might influence the later risk for renal disease.