The ‘DOHaD’ literature argues that stressors encountered at age t ‘program’ individual health at age t+n, and that this programming appears strongest when t defines critical developmental periods including gestation. Accordingly, children of ill-nourished pregnant women suffer greater later life morbidity than do offspring of well-nourished mothers. The possibility that circumstances other than access to nutritious food drive both a mother’s diet and fetal development remains, however, a threat to the inference of programming in utero. Attempts to rule out this threat include tests of the hypothesis that birth cohorts in gestation during famines exhibit shorter life spans than other cohorts. The tests produce conflicting results attributed to confounding by autocorrelation, selective migration and introduction of modern medicine. We offer a test in which neither medicine nor migration nor autocorrelation could obscure the presumed effect. We apply time-series regression methods to the life span of Swedes born between 1751 and 1800 to test the hypothesis that cohorts exposed in utero to the Swedish Famine of 1773 lived shorter lives than expected from trends and other forms of autocorrelation. We use these 50 birth cohorts not only because they included those exposed to severe famine but also because they may well be the only human birth cohorts that completed life unaffected by selective migration and unaided by modern medicine and for which we know life span. We find that the cohort born in 1773 live 4.2 years longer than expected from trends over the last half of the 18th century.

Since its debut in a ground-breaking report by Barker and Osmond in 1986, the concept of the Developmental Origins of Health and Disease (DOHaD) has been further developed in several aspects. Its methodology and conclusions relating to proposed origins and outcomes of early life events have been developing and spreading internationally. Indeed, the DOHaD concept now seems to have influenced many fields of research. This article aims to briefly review why the DOHaD concept is important in biomedical science, how it has developed, is currently developing, and how it should develop in future.

The prenatal environment is now recognized as a key driver of non-communicable disease risk later in life. Within the developmental origins of health and disease (DOHaD) paradigm, studies are increasingly identifying links between maternal morbidity during pregnancy and disease later in life for offspring. Nutrient restriction, metabolic disorders during gestation, such as diabetes or obesity, and maternal immune activation provoked by infection have been linked to adverse health outcomes for offspring later in life. These factors frequently co-occur, but the potential for compounding effects of multiple morbidities on DOHaD-related outcomes has not received adequate attention. This is of particular importance in low- or middle-income countries (LMICs), which have ongoing high rates of infectious diseases and are now experiencing transitions from undernutrition to excess adiposity. The purpose of this scoping review is to summarize studies examining the effect and interaction of co-occurring metabolic or nutritional stressors and infectious diseases during gestation on DOHaD-related health outcomes. We identified nine studies in humans – four performed in the United States and five in LMICs. The most common outcome, also in seven of nine studies, was premature birth or low birth weight. We identified nine animal studies, six in mice, two in rats and one in sheep. The interaction between metabolic/nutritional exposures and infectious exposures had varying effects including synergism, inhibition and independent actions. No human studies were specifically designed to assess the interaction of metabolic/nutritional exposures and infectious diseases. Future studies of neonatal outcomes should measure these exposures and explicitly examine their concerted effect.

The brain is highly susceptible to adverse effects of drugs of abuse during early phases of life. Prenatal nicotine exposure (PNE), a preventable cause of gestational and infant mortality, can alter neuron wiring and induce sustained deficits in attention and learning. Here, a rat model of PNE (embryonic days 7–21) was used to examine the maturing hippocampus, which encodes new memories and processes emotional memory. Components of synaptic signaling were evaluated at postnatal day 14 (P14), a period of prolific synaptogenesis in rats, to determine if glutamatergic transmission-associated molecules are regulated in subregions of hippocampus as early as P14. PNE resulted in reduced expression of GluN2B, GluA2 and CaMKIIα, but elevated SNAP25 proteins specifically in the CA3 but not CA1. Only CaMKIIα was regulated in dentate gyrus at this age. These results suggest that glutamatergic and synaptic dysregulation of learning and memory may occur in hippocampus in a temporally and subregionally specific manner.

Epidemiology formed the basis of ‘the Barker hypothesis’, the concept of ‘developmental programming’ and today’s discipline of the Developmental Origins of Health and Disease (DOHaD). Animal experimentation provided proof of the underlying concepts, and continues to generate knowledge of underlying mechanisms. Interventions in humans, based on DOHaD principles, will be informed by experiments in animals. As knowledge in this discipline has accumulated, from studies of humans and other animals, the complexity of interactions between genome, environment and epigenetics, has been revealed. The vast nature of programming stimuli and breadth of effects is becoming known. As a result of our accumulating knowledge we now appreciate the impact of many variables that contribute to programmed outcomes. To guide further animal research in this field, the Australia and New Zealand DOHaD society (ANZ DOHaD) Animals Models of DOHaD Research Working Group convened at the 2nd Annual ANZ DOHaD Congress in Melbourne, Australia in April 2015. This review summarizes the contributions of animal research to the understanding of DOHaD, and makes recommendations for the design and conduct of animal experiments to maximize relevance, reproducibility and translation of knowledge into improving health and well-being.

Prenatal and early-life environmental exposures play a key role in the development of atopy and allergic disease. The Family Atherosclerosis Monitoring In earLY life Study is a general, population-based Canadian birth cohort that prospectively evaluated prenatal and early-life traits and their association with atopy and/or allergic disease. The study population included 901 babies, 857 mothers and 530 fathers. Prenatal and postnatal risk factors were evaluated through questionnaires collected during the antenatal period and at 1 year. The end points of atopy and allergic diseases in infants were evaluated through questionnaires and skin prick testing. Key outcomes included atopy (24.5%), food allergy (17.5%), cow’s milk allergy (4.8%), wheezing (18.6%) and eczema (16%). The association between infant antibiotic exposure [odds ratio (OR): 2.04, 95% confidence interval (CI): 1.45–2.88] and increased atopy was noted in the multivariate analysis, whereas prenatal maternal exposure to dogs (OR: 0.60, 95% CI: 0.42–0.84) and acetaminophen (OR: 0.68, 95% CI: 0.51–0.92) was associated with decreased atopy. This population-based birth cohort in Canada demonstrated high rates of atopy, food allergy, wheezing and eczema. Several previously reported and some novel prenatal and postnatal exposures were associated with atopy and allergic diseases at 1 year of age.

Mitochondria play a regulatory role in several essential cell processes including cell metabolism, calcium balance and cell viability. In recent years, it has been postulated that mitochondria participate in the pathogenesis of a number of chronic diseases, including central nervous system disorders. Thus, the concept of mitochondrial function now extends far beyond the common view of this organelle as the ‘powerhouse’ of the cell to a new appreciation of the mitochondrion as a transducer of early metabolic insult into chronic disease in later life. In this review, we have attempted to describe some of the associations between nutritional status and mitochondrial function (and dysfunction) during embryonic development with the occurrence of neural oxidative imbalance and neurogenic disease in adulthood.

Recently, large-scale trials of behavioural interventions have failed to show improvements in pregnancy outcomes. They have, however, shown that lifestyle support improves maternal diet and physical activity during pregnancy, and can reduce weight gain. This suggests that pregnancy, and possibly the whole periconceptional period, represents a ‘teachable moment’ for changes in diet and lifestyle, an idea that was made much of in the recent report of the Chief Medical Officer for England. The greatest challenge with all trials of diet and lifestyle interventions is to engage people and to sustain this engagement. With this in mind, we propose a design of intervention that aims simultaneously to engage women through motivational conversations and to offer access to a digital platform that provides structured support for diet and lifestyle change. This intervention design therefore makes best use of learning from the trials described above and from recent advances in digital intervention design.