Understanding the role and importance of nutrition in early postnatal life, as an influence on lifelong vulnerability to poor health, is an important part of current research. We need to be able to define optimal patterns of infant feeding, not just to support growth and development in infancy, but also as determinants of later health. To date, much of the focus on the long-term effects of infant nutrition has been on milk feeding, to compare breast and formula feeding and to evaluate the effects of exclusivity, timing and duration of feeding different types of milk in infancy; other aspects of infant feeding such as age at introduction of solid foods and type of weaning diet have received less attention, and relatively little is known about their links to later health. Contemporary data are needed to enable us to move beyond explanation of historical infant feeding data in order to understand and predict health outcomes in future generations. Ongoing and new population studies, that include infants from diverse settings, will be key to providing generalizable data that can be used to define optimal feeding practice. There are some methodological challenges ahead, although significant progress has already been made, and further progress is envisaged in the future. In particular, the opportunity to bring together epidemiological studies and new mechanistic insights that will help identify key aspects of infant nutrition and their causal effects offer great promise both in moving this field forward as well as the potential for health benefits for future generations.

Early nutrition may have long-lasting metabolic impacts in adulthood. Even though breast milk is the gold standard, most infants are at least partly formula-fed. Despite obvious improvements, infant formulas remain perfectible to reduce the gap between breastfed and formula-fed infants. Improvements such as reducing the protein content, modulating the lipid matrix and adding prebiotics, probiotics and synbiotics, are discussed regarding metabolic health. Numerous questions remain to be answered on how impacting the infant formula composition may modulate the host metabolism and exert long-term benefits. Interactions between early nutrition (composition of human milk and infant formula) and the gut microbiota profile, as well as mechanisms connecting gut microbiota to metabolic health, are highlighted. Gut microbiota stands as a key actor in the nutritional programming but additional well-designed longitudinal human studies are needed.

Maternal diet-induced obesity can cause detrimental developmental origins of health and disease in offspring. Perinatal exposure to a high-fat diet (HFD) can lead to later behavioral and metabolic disturbances, but it is not clear which behaviors and metabolic parameters are most vulnerable. To address this critical gap, biparental and monogamous oldfield mice (Peromyscus polionotus), which may better replicate most human societies, were used in the current study. About 2 weeks before breeding, adult females were placed on a control or HFD and maintained on the diets throughout gestation and lactation. F1 offspring were placed at weaning (30 days of age) on the control diet and spatial learning and memory, anxiety, exploratory, voluntary physical activity, and metabolic parameters were tested when they reached adulthood (90 days of age). Surprisingly, maternal HFD caused decreased latency in initial and reverse Barnes maze trials in male, but not female, offspring. Both male and female HFD-fed offspring showed increased anxiogenic behaviors, but decreased exploratory and voluntary physical activity. Moreover, HFD offspring demonstrated lower resting energy expenditure (EE) compared with controls. Accordingly, HFD offspring weighed more at adulthood than those from control fed dams, likely the result of reduced physical activity and EE. Current findings indicate a maternal HFD may increase obesity susceptibility in offspring due to prenatal programming resulting in reduced physical activity and EE later in life. Further work is needed to determine the underpinning neural and metabolic mechanisms by which a maternal HFD adversely affects neurobehavioral and metabolic pathways in offspring.

The Chinese Famine of 1959–1961 caused up to 30 million deaths. It varied in intensity across China and affected rural areas disproportionately. Data from the China–U.S. Collaborative Project for Neural Tube Defect Prevention on 31, 449 women (born 1957–1963) and their offspring birth size were recorded in 1993–1996. We used a measure of famine intensity at county level based on the size of famine-born cohorts relative to cohorts preceding and following the famine in a difference-in-difference model that compared offspring birth size of pre-famine (1957–1958; exposed between 0.5 and 4.5 years), famine (1959–1961; prenatal and up to 2.5 years) and post-famine (1962; some exposed in early pregnancy) cohort groups to that of the unexposed 1963 cohort. The model corrected for age and cohort trends and estimated associations between maternal famine exposure and offspring birth size for the average level of famine intensity across counties, and included adjustment for clustering. In rural areas and in pre-famine and famine cohorts, exposure to famine was associated with larger weight (69 g; 95% CI 30, 108), length (0.3 cm; 95% CI −0.0, 0.5) and birth body mass index (0.1 kg/m2; 95% CI 0.0, 0.2). In urban areas, however, exposure to famine was not associated with offspring birth size. Our findings in rural areas suggest that severe and prolonged famine leads to larger newborn size in the offspring of mothers exposed to famine in utero and during the first few years of life; less severe famine in urban areas however, appeared to have no impact. The markedly increased mortality in rural areas may have resulted in the selection of hardier mothers with greater growth potential, which becomes expressed in their offspring.

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.

Endocrine disrupting chemicals (EDC) have received considerable attention as potential obesogens. Past studies examining obesogenic potential of one widespread EDC, bisphenol A (BPA), have generally focused on metabolic and adipose tissue effects. However, physical inactivity has been proposed to be a leading cause of obesity. A paucity of studies has considered whether EDC, including BPA, affects this behavior. To test whether early exposure to BPA and ethinyl estradiol (EE, estrogen present in birth control pills) results in metabolic and such behavioral disruptions, California mice developmentally exposed to BPA and EE were tested as adults for energy expenditure (indirect calorimetry), body composition (echoMRI) and physical activity (measured by beam breaks and voluntary wheel running). Serum glucose and metabolic hormones were measured. No differences in body weight or food consumption were detected. BPA-exposed females exhibited greater variation in weight than females in control and EE groups. During the dark and light cycles, BPA females exhibited a higher average respiratory quotient than control females, indicative of metabolizing carbohydrates rather than fats. Various assessments of voluntary physical activity in the home cage confirmed that during the dark cycle, BPA and EE-exposed females were significantly less active in this setting than control females. Similar effects were not observed in BPA or EE-exposed males. No significant differences were detected in serum glucose, insulin, adiponectin and leptin concentrations. Results suggest that females developmentally exposed to BPA exhibit decreased motivation to engage in voluntary physical activity and altered metabolism of carbohydrates v. fats, which could have important health implications.

A primary challenge for nutrition policy in low-income settings is to position nutrition as an investment rather than simply as a form of social spending that governments grant poor people to the degree that governments prioritize equity. Various economic models have produced estimates of the economic costs of malnutrition as a combination of the impact of malnutrition on mortality, on health care costs for the survivors, including those that manifest in adult years, and on the lost productivity attributable to malnutrition. However, these estimates often center on the costs of early mortality and are sensitive to assumptions on how to place a dollar cost on mortality. This study argues that even when focusing only on the productivity impact of malnutrition – clearly a lower bound of the full costs – the economic consequences of malnutrition are substantial. Stating this somewhat differently, the economic returns to preventing malnutrition are on a par with those investments generally considered at the heart of economic development strategies. Moreover, the body of evidence that has been accumulated to indicate these productivity gains is both substantial and robust.

In pregnancies complicated by placental insufficiency (PI), fetal hypoglycemia and hypoxemia progressively worsen during the third trimester, which increases circulating norepinephrine (NE). Pharmacological adrenergic blockade (ADR-block) at 0.9 gestation revealed that NE inhibits insulin secretion and enhanced β-cell responsiveness in fetuses with PI-induced intrauterine growth restriction (IUGR). NE concentrations in PI fetuses at 0.7 gestation were threefold greater compared with age-matched controls, but the levels were similar to near-term controls. Therefore, our objective was to determine whether elevations in plasma NE concentrations inhibit insulin secretion and produce compensatory β-cell responsiveness in PI fetuses at 0.7 gestation. Fetal insulin was measured under basal, glucose-stimulated insulin secretion (GSIS) and glucose-potentiated arginine-stimulated insulin secretion (GPAIS) conditions in the absence and presence of an ADR-block. Placental weights were 38% lower (P < 0.05) in PI fetus than in controls, but fetal weights were not different. PI fetuses had lower (P < 0.05) basal blood oxygen content, plasma glucose, insulin-like growth factor-1 and insulin concentrations and greater plasma NE concentrations (891 ± 211 v. 292 ± 65 pg/ml; P < 0.05) than controls. GSIS was lower in PI fetuses than in controls (0.34 ± 0.03 v. 1.08 ± 0.06 ng/ml; P < 0.05). ADR-block increased GSIS in PI fetuses (1.19 ± 0.11 ng/ml; P < 0.05) but decreased GSIS in controls (0.86 ± 0.02 ng/ml; P < 0.05). Similarly, GPAIS was 44% lower (P < 0.05) in PI fetuses than in controls, and ADR-block increased (P < 0.05) GPAIS in PI fetuses but not in controls. Insulin content per islet was not different between treatments. We conclude that elevations in fetal plasma NE suppress insulin concentrations, and that compensatory β-cell stimulus-secretion responsiveness is present before IUGR.

Exercise during pregnancy has beneficial effects on maternal and offspring’s health in humans and mice. The underlying mechanisms remain unclear. This comparative study aimed to determine the long-term effects of an exercise program on metabolism, weight gain, body composition and changes in hormones [insulin, leptin, brain-derived neurotrophic factor (BDNF)]. Pregnant women (n=34) and mouse dams (n=44) were subjected to an exercise program compared with matched controls (period I). Follow-up in the offspring was performed over 6 months in humans, corresponding to postnatal day (P) 21 in mice (period II). Half of the mouse offspring was challenged with a high-fat diet (HFD) for 6 weeks between P70 and P112 (period III). In period I, exercise during pregnancy led to 6% lower fat content, 40% lower leptin levels and an increase of 50% BDNF levels in humans compared with controls, which was not observed in mice. After period II in humans and mice, offspring body weight did not differ from that of the controls. Further differences were observed in period III. Offspring of exercising mouse dams had significantly lower fat mass and leptin levels compared with controls. In addition, at P112, BDNF levels in offspring were significantly higher from exercising mothers while this effect was completely blunted by HFD feeding. In this study, we found comparable effects on maternal and offspring’s weight gain in humans and mice but different effects in insulin, leptin and BDNF. The long-term potential protective effects of exercise on biomarkers should be examined in human studies.

Methyl donor supplementation has been reported to prevent obesity-induced liver fat accumulation in adult rats. We hypothesized that this protection could be mediated by perinatal nutrition. For this purpose, we assessed the response to an obesogenic diet (high-fat-sucrose, HFS) during adulthood depending on maternal diet during lactation. Female Wistar rats fed control diet during pregnancy were assigned to four postpartum dietary groups: control, control supplemented with methyl donors (choline, betaine, folic acid, vitamin B12), HFS and HFS supplemented with methyl donors. At weaning, the male offspring was transferred to a chow diet and at week 12th assigned to a control or a HFS diet during 8 weeks. The offspring whose mothers were fed HFS during lactation showed increased adiposity (19%, P<0.001). When fed the HFS diet as adults, offspring whose mothers were HFS supplemented had more body fat (23%, P<0.001) than those from HFS non-supplemented. However, they showed lower liver fat accumulation (−18%, P<0.001). Srebf1, Dnmt1 and Lepr liver mRNA levels increased after adulthood HFS feeding. In those animals HFS fed during adulthood, previous maternal HFS decreased Lepr and Dnmt1 expression levels when compared with c-HFS offspring, while the supplementation of control and HFS-fed dams, respectively, induced higher hepatic Mme and Lepr mRNA levels after adult HFS intake compared with hfs-HFS offspring. In conclusion, maternal HFS diet during lactation influenced the response to an obesogenic diet in the adult progeny. Interestingly, dietary methyl donor supplementation in lactating mothers fed an obesogenic diet reduced liver fat accumulation, but increased adipose tissue storage in adult HFS-fed offspring.

Studies in urban informal settlements show widespread inappropriate infant and young child feeding (IYCF) practices and high rates of food insecurity. This study assessed the association between household food security and IYCF practices in two urban informal settlements in Nairobi, Kenya. The study adopted a longitudinal design that involved a census sample of 1110 children less than 12 months of age and their mothers aged between 12 and 49 years. A questionnaire was used to collect information on: IYCF practices and household food security. Logistic regression was used to determine the association between food insecurity and IYFC practices. The findings showed high household food insecurity; only 19.5% of the households were food secure based on Household Insecurity Access Score. Infant feeding practices were inappropriate: 76% attained minimum meal frequency; 41% of the children attained a minimum dietary diversity; and 27% attained minimum acceptable diet. With the exception of the minimum meal frequency, infants living in food secure households were significantly more likely to achieve appropriate infant feeding practices than those in food insecure households: minimum meal frequency (adjusted odds ratio (AOR)=1.26, P=0.530); minimum dietary diversity (AOR=1.84, P=0.046) and minimum acceptable diet (AOR=2.35, P=0.008). The study adds to the existing body of knowledge by demonstrating an association between household food security and infant feeding practices in low-income settings. The findings imply that interventions aimed at improving infant feeding practices and ultimately nutritional status need to also focus on improving household food security.

Stress experienced early in life exerts a powerful, lasting influence on development. Converging empirical findings show that stressful experiences become deeply embedded in the child’s neurobiology, with an astonishing range of long-term effects on cognition, emotion, and behavior. In contrast with the prevailing view that such effects are the maladaptive outcomes of ‘toxic’ stress, adaptive models regard them as manifestations of evolved developmental plasticity. In this paper, I offer a brief introduction to adaptive models of early stress and human behavioral development, with emphasis on recent theoretical contributions and emerging concepts in the field. I begin by contrasting dysregulation models of early stress with their adaptive counterparts; I then introduce life history theory as a unifying framework, and review recent work on predictive adaptive responses (PARs) in human life history development. In particular, I discuss the distinction between forecasting the future state of the environment (external prediction) and forecasting the future state of the organism (internal prediction). Next, I present the adaptive calibration model, an integrative model of individual differences in stress responsivity based on life history concepts. I conclude by examining how maternal–fetal conflict may shape the physiology of prenatal stress and its adaptive and maladaptive effects on postnatal development. In total, I aim to show how theoretical work from evolutionary biology is reshaping the way we think about the role of stress in human development, and provide researchers with an up-to-date conceptual map of this fascinating and rapidly evolving field.

Developmental exposure to phthalates has been implicated as a risk for obesity; however, epidemiological studies have yielded conflicting results and mechanisms are poorly understood. An additional layer of complexity in epidemiological studies is that humans are exposed to mixtures of many different phthalates. Here, we utilize an established mouse model of perinatal exposure to investigate the effects of three phthalates, diethylhexyl phthalate (DEHP), diisononyl phthalate (DINP) and dibutyl phthalate (DBP), on body weight and organ weights in weanling mice. In addition to individual phthalate exposures, we employed two mixture exposures: DEHP+DINP and DEHP+DINP+DBP. Phthalates were administered through phytoestrogen-free chow at the following exposure levels: 25 mg DEHP/kg chow, 25 mg DBP/kg chow and 75 mg DINP/kg chow. The viable yellow agouti (Avy) mouse strain, along with measurement of tail DNA methylation, was used as a biosensor to examine effects of phthalates and phthalate mixtures on the DNA methylome. We found that female and male mice perinatally exposed to DINP alone had increased body weights at postnatal day 21 (PND21), and that exposure to mixtures did not exaggerate these effects. Females exposed to DINP and DEHP+DINP had increased relative liver weights at PND21, and females exposed to a mixture of DEHP+DINP+DBP had increased relative gonadal fat weight. Phthalate-exposed Avy/a offspring exhibited altered coat color distributions and altered DNA methylation at intracisternal A-particles (IAPs), repetitive elements in the mouse genome. These findings provide evidence that developmental exposures to phthalates influence body weight and organ weight changes in early life, and are associated with altered DNA methylation at IAPs.

The field of Developmental Origins of Health and Disease (DOHaD) seeks to understand the relationships between early-life environmental exposures and long-term health and disease. Until recently, the molecular mechanisms underlying these phenomena were poorly understood; however, epigenetics has been proposed to bridge the gap between the environment and phenotype. Epigenetics involves the study of heritable changes in gene expression, which occur without changes to the underlying DNA sequence. Different types of epigenetic modifications include DNA methylation, post-translational histone modifications and non-coding RNAs. Increasingly, changes to the epigenome have been associated with early-life exposures in both humans and animal models, offering both an explanation for how the environment may programme long-term health, as well as molecular changes that could be developed as biomarkers of exposure and/or future disease. As such, epigenetic studies in DOHaD hold much promise; however, there are a number of factors which should be considered when designing and interpreting such studies. These include the impact of the genome on the epigenome, the tissue-specificity of epigenetic marks, the stability (or lack thereof) of epigenetic changes over time and the importance of associating epigenetic changes with changes in transcription or translation to demonstrate functional consequences. In this review, we discuss each of these key concepts and provide practical strategies to mitigate some common pitfalls with the aim of providing a useful guide for future epigenetic studies in DOHaD.

Low birth weight is associated with adverse health outcomes. If birth weight records are not available, studies may use recalled birth weight. It is unclear whether this is reliable. We performed a systematic review and meta-analysis of studies comparing recalled with recorded birth weights. We followed the Meta-Analyses of Observational Studies in Epidemiology (MOOSE) statement and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched MEDLINE, EMBASE and Cumulative Index to Nursing and Allied Health Literature (CINAHL) to May 2015. We included studies that reported recalled birth weight and recorded birth weight. We excluded studies investigating a clinical population. Two reviewers independently reviewed citations, extracted data, assessed risk of bias. Data were pooled in a random effects meta-analysis for correlation and mean difference. In total, 40 studies were eligible for qualitative synthesis (n=78,997 births from 78,196 parents). Agreement between recalled and recorded birth weight was high: pooled estimate of correlation in 23 samples from 19 studies (n=7406) was 0.90 [95% confidence interval (CI) 0.87–0.93]. The difference between recalled and recorded birth weight in 29 samples from 26 studies (n=29,293) was small [range −86–129 g; random effects estimate 1.4 g (95% CI −4.0–6.9 g)]. Studies were heterogeneous, with no evidence for an effect of time since birth, person reporting, recall bias, or birth order. In post-hoc subgroup analysis, recall was higher than recorded birth weight by 80 g (95% CI 57–103 g) in low and middle income countries. In conclusion, there is high agreement between recalled and recorded birth weight. If birth weight is recalled, it is suitable for use in epidemiological studies, at least in high income countries.

Epigenetic changes represent a potential mechanism underlying associations of early-life exposures and later life health outcomes. Population-based cohort studies starting in early life are an attractive framework to study the role of such changes. DNA methylation is the most studied epigenetic mechanism in population research. We discuss the application of DNA methylation in early-life population studies, some recent findings, key challenges and recommendations for future research. Studies into DNA methylation within the Developmental Origins of Health and Disease framework generally either explore associations between prenatal exposures and offspring DNA methylation or associations between offspring DNA methylation in early life and later health outcomes. Only a few studies to date have integrated prospective exposure, epigenetic and phenotypic data in order to explicitly test the role of DNA methylation as a potential biological mediator of environmental effects on health outcomes. Population epigenetics is an emerging field which has challenges in terms of methodology and interpretation of the data. Key challenges include tissue specificity, cell type adjustment, issues of power and comparability of findings, genetic influences, and exploring causality and functional consequences. Ongoing studies are working on addressing these issues. Large collaborative efforts of prospective cohorts are emerging, with clear benefits in terms of optimizing power and use of resources, and in advancing methodology. In the future, multidisciplinary approaches, within and beyond longitudinal birth and preconception cohorts will advance this complex, but highly promising, the field of research.

It is widely recognized that environmental insults during adulthood including smoking, lack of exercise and a poor diet increases an individual's risk of cardiovascular disease (CVD). However, research initiated over the last two decades has highlighted that our risk of CVD can be programmed following adverse exposures during early development. Such adverse exposures may include, undernutrition, placental insufficiency, hypoxia, overnutrition and obesity. This review aims to address the current Western obesity crisis by addressing the long-term impact of maternal overnutrition and obesity on the offspring's future risk of CVD. Although current human studies have observed the presence of adverse CVD markers in children born to obese mothers, animal models have proved vital in understanding the underlying mechanisms involved. Mechanisms suggested to be involved in the programming of CVD in the offspring include increased oxidative stress, inflammation, lipotoxicity and epigenetics. CVD remains the greatest cause of death worldwide, therefore further understanding of the mechanisms mediating these effects is important in the development of intervention strategies.

Exposures during the early life (periconceptional, prenatal and early postnatal) period are increasingly recognized as playing an important role in the aetiology of chronic non-communicable diseases (NCD), including coronary heart disease, stroke, hypertension, Type 2 diabetes and osteoporosis. The ‘Developmental Origins of Health and Disease’ (DOHaD) hypothesis states that these disorders originate through unbalanced nutrition early in life and risk is highest when there is a ‘mismatch’ between the early- and later-life environments. Thus, the DOHaD hypothesis would predict highest risk in countries where an excess of infants are born with low birth weight and where there is a rapid transition to nutritional adequacy or excess in adulthood. Here, I will review data from work conducted in rural Gambia, West Africa. Using demographic data dating back to the 1940s, the follow-up of randomized controlled trials of nutritional supplementation in pregnancy and the ‘experiment of nature’ that seasonality in this region provides, we have investigated the DOHaD hypothesis in a population with high rates of maternal and infant under-nutrition, a high burden from infectious disease, and an emerging risk of NCDs.

Pregestational obesity is a significant risk factor for adverse pregnancy outcomes. Maternal obesity is associated with a specific proinflammatory, endocrine and metabolic phenotype that may lead to higher supply of nutrients to the feto-placental unit and to excessive fetal fat accumulation. In particular, obesity may influence placental fatty acid (FA) transport in several ways, leading to increased diffusion driving force across the placenta, and to altered placental development, size and exchange surface area. Animal models show that maternal obesity is associated with increased expression of specific FA carriers and inflammatory signaling molecules in placental cotyledonary tissue, resulting in enhanced lipid transfer across the placenta, dislipidemia, fat accumulation and possibly altered development in fetuses. Cell culture experiments confirmed that inflammatory molecules, adipokines and FA, all significantly altered in obesity, are important regulators of placental lipid exchange. Expression studies in placentas of obese–diabetic women found a significant increase in FA binding protein-4 expression and in cellular triglyceride content, resulting in increased triglyceride cord blood concentrations. The expression and activity of carriers involved in placental lipid transport are influenced by the endocrine, inflammatory and metabolic milieu of obesity, and further studies are needed to elucidate the strong association between maternal obesity and fetal overgrowth.

A life-course approach to reduction of risk of non-communicable diseases (NCD) suggests that early-life interventions may be more effective than lifestyle modifications in middle age. Knowledge translation to develop understanding of the Developmental Origins of Health and Disease (DOHaD) within the community offers the potential to encourage informed diet and lifestyle choices supporting reduction of NCD risk in current and future generations. Many women do not make sustained dietary change before or during pregnancy, therefore appropriate nutritional behaviours need to be established prior to adulthood. This makes adolescence an appropriate stage for interventions to establish suitable dietary and lifestyle behaviours. Therefore, we engaged adolescents in a school-based educational intervention, and assessed the value of this in development of understanding of DOHaD concepts to support behaviour change that could lead to NCD risk reduction in the next generation. Modules of course work were written for 11–14 year olds and trialled in nine schools. Matched pre- and post-intervention questionnaire responses from 238 students and 99 parents, and post-intervention interviews evaluated the intervention. Understanding of a link between maternal diet during pregnancy and the health of the foetus in adulthood increased from 46% to 76% following intervention. Post-intervention evidence suggests the programme facilitated discussion of diet, lifestyle and DOHaD concepts in most families. The intervention was effective in improving understanding of DOHaD concepts and in some cases led to appropriate behaviour change. However, the sustainability of these changes remains to be determined through on-going evaluation of attitudes and behaviour within this cohort.