Obesity and its related non-communicable diseases (NCDs), such as type 2 diabetes, heart disease and cancer, impose huge burdens on society, particularly the healthcare system. Until recently, public health and policy were primarily focused on secondary prevention and treatment of NCDs. However, epidemiological and experimental evidence indicates that early-life exposures influence the risk of childhood obesity and related diseases later in life, and has now focused attention on the health of both mother and child. During pregnancy and the early neonatal period, individuals respond to their environment by establishing anatomical, physiological and biochemical trajectories that shape their future health. This period of developmental plasticity provides an early window of opportunity to mitigate the environmental insults that may increase an individual’s sensitivity to, or risk of, developing obesity or related diseases later in life. Although much investigation has already occurred in the area of Developmental Origins of Health and Disease research, the science itself is still in its infancy. It remains for researchers to tackle the important outstanding questions and translate their knowledge into workable solutions for the public good. The challenge, however, is to decide which areas to focus on. With these opportunities and challenges in mind, the 2014 Gravida Summit convened to examine how its early-life research program can determine which areas of research into mechanisms, biomarkers and interventions could contribute to the international research strategy to fight childhood obesity and its related diseases.

Accumulating evidence suggest that the concept of programming can also be applied to reproductive development and function, representing an ever expanding research area. Recently issues such as peri- or even preconceptional nutrition, transgenerational effects and underlying mechanisms have received considerable attention. The present chapter presents the existed evidence and reviews the available data from numerous animal and human studies on the effects of early life nutritional environment on adult reproductive function. Specific outcomes depend on the severity, duration and stage of development when nutritional perturbations are imposed, while sex-specific effects are also manifested. Apart from undernutrition, effects of relative overnutrition as well as the complex interactions between pre- and postnatal nutrition is of high importance, especially in the context of our days obesity epidemic. Mechanisms underlying reproductive programming are yet unclear, but may include a role for epigenetic modifications. Epigenetic modulation of critical genes involved in the control of reproductive function and potential intergenerational effects represent an exciting area of interdisciplinary research toward the development of new nutritional approaches during pre- and postnatal periods to ensure reproductive health in later life.

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.

For heavy metals that have any degree of transfer though the placenta to the fetus, it is unlikely that there are safe limits for maternal blood levels. The only means of reducing fetal exposure is to minimise maternal exposure. There are few recommendations for levels of concern. With the exception of US recommendations for maternal Pb levels, but there are no international levels of concern or cut-off levels specifically for pregnancy for heavy metals, so that comparisons can generally only be made with national reference values relating to similar physiological statuses or age groups. These include recommendations for Cd levels by Germany (reference value for non-smoking adults aged 18–69 years, 1 µg/l) and for Hg by Germany (reference value for adults age 18–60 years with fish intake ⩽3 times per month, 2.0 µg/l) and the USA (cut-off level for women, 5.8 µg/dl). To illustrate the lack of cohesion, we present data on blood Pb, Cd and Hg levels from pregnant women enroled in the UK Avon Longitudinal Study of Parents and Children study and compare the values with present levels of concern and recommended cut-off values. We also compare the levels with those found in other groups of pregnant women worldwide to strengthen the database for the development of levels of concern in pregnancy. The need for clarity of terminology in describing levels of concern is discussed. There is a pressing need for international consensus on levels of concern for all age groups and physiological statuses, particularly for pregnancy.

Altered levels of selenium and copper have been linked with altered cardiovascular disease risk factors including changes in blood triglyceride and cholesterol levels. However, it is unclear whether this can be observed prenatally. This cross-sectional study includes 274 singleton births from 2004 to 2005 in Baltimore, Maryland. We measured umbilical cord serum selenium and copper using inductively coupled plasma mass spectrometry. We evaluated exposure levels vis-à-vis umbilical cord serum triglyceride and total cholesterol concentrations in multivariable regression models adjusted for gestational age, birth weight, maternal age, race, parity, smoking, prepregnancy body mass index, n-3 fatty acids and methyl mercury. The percent difference in triglycerides comparing those in the highest v. lowest quartile of selenium was 22.3% (95% confidence interval (CI): 7.1, 39.7). For copper this was 43.8% (95% CI: 25.9, 64.3). In multivariable models including both copper and selenium as covariates, copper, but not selenium, maintained a statistically significant association with increased triglycerides (percent difference: 40.7%, 95% CI: 22.1, 62.1). There was limited evidence of a relationship of increasing selenium with increasing total cholesterol. Our findings provide evidence that higher serum copper levels are associated with higher serum triglycerides in newborns, but should be confirmed in larger studies.

Studies on placental size and cardiovascular disease have shown inconsistent results. We followed 10,503 men and women born in Uppsala, Sweden, 1915–1929 from 1964 to 2008 to assess whether birth characteristics, including placental weight and placenta/birth weight ratio, were predictive of future ischaemic heart disease (IHD). Adjustments were made for birth cohort, age, sex, mother’s parity, birth weight, gestational age and social class at birth. Placental weight and birth weight were negatively associated with IHD. The effect of placental weight on IHD was stronger in individuals from medium social class at birth and in those with low education. Men and women from non-manual social class at birth had the lowest risk for IHD as adults. We conclude that low foetal growth rate rather than placental weight was more predictive of IHD in the Swedish cohort. However, the strong effect of social class at birth on risk for IHD did not appear to be mediated by foetal growth rate.

Placental 5α-reductase (5αR) is influenced by in utero compromises and has a role in regulating neuroactive steroid concentrations in the fetus. The objective of this study was to determine if changes in placental 5αR were associated with neonatal outcome after birth. Guinea pigs were delivered by cesarean section at term (GA69, n=22) or preterm (GA62, n=36) and the placenta collected. Preterm neonates were maintained for 24 h unless their condition deteriorated before this time. Enzyme mRNA expression of 5αR type-1 and 5αR type-2 were determined using real-time PCR. All preterm neonates had significantly higher 5αR2 expression in their placenta compared with placentae from term neonates (P<0.0001). Expression was also markedly higher in the placentae from neonates that did not survive until 24 h, compared with surviving preterm neonates (P=0.04). These findings suggest differences of in utero neurosteroidogenic capacity between surviving and non-surviving preterm guinea pig neonates. The increased 5αR2 mRNA expression in the placenta of non-survivors suggests an induction of the neurosteroid pathway due to prior exposure to an in utero compromise, with such exposure possibly a predisposing factor that contributed to their poor ex utero outcome.

Some studies have found a significant relationship between birth weight (BW) and the risk of coronary heart disease (CHD) in adulthood, but results were inconsistent. The purpose of this study was to characterize the association between BW and the risk of CHD in adults. Among 144 papers detected by our search, 27 papers provided data on the relationship between BW and CHD, of which 23 papers considered BW as a continuous variable, and 14 articles considered BW as a categorical variable for this meta-analysis. Based on 23 papers, the mean weighted estimate for the association between BW and the combined outcome of non-fatal and fatal CHD was 0.83 [95% confidence interval (CI), 0.80–0.86] per kilogram of BW (P<0.0001). Low birth weight (LBW<2500 g) was associated with increased risk of CHD [odds ratio (OR), 1.19; 95% confidence interval (CI), 1.11–1.27] compared with subjects with BW⩾2500 g. LBW, as compared with normal BW (2500–4000 g), was associated with increased risk of CHD (OR, 1.16; 95% CI, 1.08–1.25). High birth weight (HBW⩾4000 g) was associated with decreased risk of CHD (OR, 0.89; 95% CI, 0.81–0.98) compared with subjects with BW<4000 g. In addition, there was an indication (not quite significant) that HBW was associated with a lower risk of CHD (OR, 0.89; 95% CI, 0.79–1.01), as compared with normal BW. No significant evidence of publication bias was present. These results suggest that LBW is significantly associated with increased risk of CHD and a 1 kg higher BW is associated with a 10–20% lower risk of CHD.

Available data from both experimental and epidemiological studies suggest that inadequate diet in early life can permanently change the structure and function of specific organs or homoeostatic pathways, thereby ‘programming’ the individual’s health status and longevity. Sufficient evidence has accumulated showing significant impact of epigenetic regulation mechanisms in nutritional programming phenomenon. The essential role of early-life diet in the development of aging-related chronic diseases is well established and described in many scientific publications. However, the programming effects on lifespan have not been extensively reviewed systematically. The aim of the review is to provide a summary of research findings and theoretical explanations that indicate that longevity can be influenced by early nutrition.

Maternal periconceptional undernutrition is associated with altered development and increased risks of adverse outcomes in the offspring. This circumstance is normal in flocks under extensive farming systems, which depend on natural forage resources. The aim of this study was to determine the effect of periconceptional undernutrition in sheep on behavioral and reproductive aspects of the offspring. Eighty ewes were synchronized in estrus and allocated to two groups (n=40) to be fed diets that provided 1.5 (C) or 0.5 (L) times the requirements for maintenance. Ewes were mated and 7 days later fed the control diet until lambing. One month after lambing, 32 lambs were exposed to tests to determine their cognitive and emotional responses. Six ewe lambs were euthanized and in vitro maturation and fertilization procedures were performed. L ewes presented a significant reduction in prolificacy and fecundity (P<0.05) in comparison with C ewes. Mean LW at lambing of L lambs was significantly higher than C lambs (C: 3.80±0.11; L: 4.24±0.15 kg, P<0.05). Lambs born from C ewes spent more time walking than L lambs (P<0.05) in the isolation test, revealing a decrease in the locomotor activity of lambs born from undernourished ewes around conception. Ewe lambs from the undernourished ewes presented a total population of oocytes 2.3 times higher than ovaries from control ewe lambs (60.0±7.8 v. 140.0±18.5 oocytes; P<0.05). In conclusion, periconceptional undernutrition is able to produce an increment in the body weight and the oocyte population, and an alteration of the locomotor activity of the offspring.

Rates of chronic kidney disease (CKD) among Indigenous groups in Australia exceed non-Indigenous rates eight-fold. Using kidney volume as a surrogate for nephron number, we carried out a study to determine if Indigenous neonates have a smaller kidney volume (and thus a reduced nephron number) from birth compared with non-Indigenous neonates. We recruited term and preterm neonates (<32 weeks) at a tertiary care neonatal unit over a 12 months period. Preterm neonates were assessed (renal sonography and renal function measurement) at 32 weeks corrected age (CA) and again at 38 weeks CA when blood pressure was also measured. All term neonates were assessed in the first post-natal week, including renal sonography, renal function and blood pressure measurement. The primary outcome measured was total kidney volume (TKV) and estimated glomerular filtration rate (eGFR) was a secondary outcome. Data was available for 44 preterm (11 Indigenous) and 39 term (13 Indigenous) neonates. TKV of Indigenous neonates was significantly lower at 32 weeks [12.0 (2.0) v. 15.4 (5.1) ml; P=0.03] and 38 weeks CA [18.6 (4.0) v. 22.6 (5.9) ml; P=0.04] respectively. Term Indigenous neonates also had smaller kidney volumes compared with non-Indigenous neonates. Despite a smaller kidney volume (and reduced nephron number), Indigenous neonates did not have a significantly lower eGFR. Indigenous neonates achieve similar eGFRs to Non-Indigenous neonates, presumably through a higher single nephron filtration rate. This places Indigenous neonates at a greater risk of long-term kidney damage later in life.