Intrauterine growth restriction (IUGR) and maternal stress during pregnancy are two compromises that negatively impact neurodevelopment and increase the risk of developing later life neuropsychiatric disorders such as schizophrenia, depression and behavioural disorders. Neurosteroids, particularly allopregnanolone, are important in protecting the developing brain and promoting many essential neurodevelopmental processes. Individually, IUGR and prenatal stress (PS) reduce myelination and neurogenesis within affected fetal brains, however less information is available on the combined effects of these two disorders on the term fetal brain. This study aimed to investigate how IUGR and PS impairs the neurosteroid pathway when combined using a guinea pig model, and how these then disrupt the neurodevelopment of the fetus. Uterine artery blood flow restriction was performed at GA30-35 to induce growth restriction, whilst PS was induced by exposure of the dam to a strobe light during gestation commencing GA40 and repeated every 5 days. Exposure in this model caused reductions in hippocampal CA1 MBP immunostaining of male fetuses in both IUGR alone and IUGR+PS paradigms but only by IUGR in the subcortical white mater, compared with control males. Plasma allopregnanolone was reduced by both stressors irrespective of sex, whereas GFAP or MAP2 expression were not affected by either stressor. Female neurodevelopment, as assessed by these markers, was unimpeded by these compromises. The addition of prenatal stress did not further compound these deficits.

From 1949 to 1962, residents of several villages in Kazakhstan received substantial doses of radiation to the thyroid gland resulting from nuclear tests conducted at the Semipalatinsk Nuclear Test Site. The primary source of radiation was internal from an intake of radioactive iodine by consumption of contaminated dairy products. A previous research study of childhood exposure and thyroid disease in this region gathered limited data on study participants’ dairy intake at the time of the fallout for the purpose of estimating past radiation doses. As many participants were too young at the time of the nuclear tests to recall dietary consumption and existing sources of archival data are limited, it was necessary to interview parents and other village residents who cared for children during this time – older adults ranging in age from 75 to 90 years. Results from 11 focus group interviews conducted in 2007 with 82 women from 4 villages in Kazakhstan yielded group-level estimates of age-, gender-, ethnicity- and village-specific dairy consumption patterns in rural Kazakhstan during the 1950s. Children typically consumed cow’s milk with limited consumption of mare, goat and sheep milk; and consumed dairy products such as sour milk (airan), soft cottage cheese (tvorog) and fermented mare milk (koumiss) with the greatest amounts of koumiss reported at ages 15–21 years. The consumption patterns differed by age, and between Kazakh and Russian children, which should lead to different estimates of radiation exposure to the thyroid. This study showed the utility of focus groups to obtain quantitative estimates for dietary intake in the distant past.

Evidence in support of the Developmental Origins of Health and Disease (DOHaD) hypothesis has reached the level where it can appropriately be used to inform practice. DOHaD informed interventions supporting primary noncommunicable disease risk reduction should target the pre- and periconceptional periods, pregnancy, lactation, childhood and adolescence. Such interventions are dependent on a health workforce (including dietitians, nurses, midwives, doctors, and nutrition teachers), that has a deep understanding of DOHaD concepts. This study assessed development of awareness of DOHaD concepts during undergraduate health professional training programs. Using a cross-sectional design, a standardized questionnaire was completed by Year 1–4 undergraduate students studying nutrition in Japan (n=309) and Year 1–3 nursing students in New Zealand (n=151). On entry to undergraduate study, most students had no awareness of the terms ‘DOHaD’ or ‘First 1000 Days’. While awareness reached 60% by Year 3 in courses that included DOHaD-related teaching, this remains inadequate. More than 95% of Year 1 undergraduates in both countries demonstrated an appreciation of associations between maternal nutrition and fetal health. However, awareness of associations between parental health status and/or nutritional environment and later-life health was low. While levels of awareness increased across program years, overall awareness was less than optimal. These results indicate evidence of some focus on DOHaD-related content in curricula. We argue that DOHaD principles should be one pillar around which health training curricula are built. This study indicates a need for the DOHaD community to engage with faculties in curriculum development.

Inflammation is associated with preterm premature rupture of membranes (PPROM) and adverse neonatal outcomes. Subchorionic thrombi, with or without inflammation, may also be a significant pathological finding in PPROM. Patterns of inflammation and thrombosis may give insight into mechanisms of adverse neonatal outcomes associated with PPROM. To characterize histologic findings of placentas from pregnancies complicated by PPROM at altitude, 44 placentas were evaluated for gross and histological indicators of inflammation and thrombosis. Student's t-test (or Mann–Whitney U-test), χ2 analysis (or Fisher's exact test), mean square contingency and logistic regression were used when appropriate. The prevalence of histologic acute chorioamnionitis (HCA) was 59%. Fetal-derived inflammation (funisitis and chorionic plate vasculitis) was seen at lower frequency (30% and 45%, respectively) and not always in association with HCA. There was a trend for Hispanic women to have higher odds of funisitis (OR = 5.9; P = 0.05). Subchorionic thrombi were seen in 34% of all placentas. The odds of subchorionic thrombi without HCA was 6.3 times greater that the odds of subchorionic thrombi with HCA (P = 0.02). There was no difference in gestational age or rupture-to-delivery interval, with the presence or absence of inflammatory or thrombotic lesions. These findings suggest that PPROM is caused by or can result in fetal inflammation, placental malperfusion, or both, independent of gestational age or rupture-to-delivery interval; maternal ethnicity and altitude may contribute to these findings. Future studies focused on this constellation of PPROM placental findings, genetic polymorphisms and neonatal outcomes are needed.

Foetal development may permanently affect muscle function. Indian newborns have a low mean birthweight, predominantly due to low lean tissue and muscle mass. We aimed to examine the relationship of birthweight, and arm muscle area (AMA) at birth and post-natal growth to handgrip strength in Indian children. Grip strength was measured in 574 children aged 9 years, who had detailed anthropometry at birth and every 6–12 months post-natally. Mean (standard deviation (s.d.)) birthweight was 2863 (446) g. At 9 years, the children were short (mean height s.d. −0.6) and light (mean weight s.d. −1.1) compared with the World Health Organization growth reference. Mean (s.d.) grip strength was 12.7 (2.2) kg (boys) and 11.0 (2.0) kg (girls). Weight, length and AMA at birth, but not skinfold measurements at birth, were positively related to 9-year grip strength (β = 0.40 kg/s.d. increase in birthweight, P < 0.001; and β = 0.41 kg/s.d. increase in AMA, P < 0.001). Grip strength was positively related to 9-year height, body mass index and AMA and to gains in these measurements from birth to 2 years, 2–5 years and 5–9 years (P < 0.001 for all). The associations between birth size and grip strength were attenuated but remained statistically significant for AMA after adjusting for 9-year size. We conclude that larger overall size and muscle mass at birth are associated with greater muscle strength in childhood, and that this is mediated mainly through greater post-natal size. Poorer muscle development in utero is associated with reduced childhood muscle strength.

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.

Increased fat and carbohydrate intakes based on the Western diet are important lifestyle modifications that lead to hypercaloric inputs, obesity, and male fertility negative effects. Epigenetic transmission may also predispose descended generations to chronic diseases, such as obesity, type 2 diabetes, behavioral, and reproductive disorders. The present study sought to evaluate the influence of a high-fat-high-sugar (HFHS) diet supplied to Wistar rats from 25 to 90 days of life on reproductive and metabolic parameters in male generations F0, F1, and F2. The standard group received the normocaloric – Nuvilab Quimtia® –3.86 kcal/kg. The hypercaloric diet (HD) group received the HFHS diet – PragSoluções® –4.77 kcal/kg. Body weight, adiposity, F1 and F2 prepubertal age evaluations, oral glucose tolerance test, insulin tolerance test, organ weights, sperm count and morphology assessments, and histometric testicular analyses were performed. The HFHS diet promoted dyslipidemia, higher adiposity, lower relative organ weights, and higher mean kidney weight, decreased mean testicle and parenchyma weights and lower height of seminiferous epithelium (HE) for the F0 generation. F1 and F2 offspring of HD group displayed early preprepubertal development, although did not alter the metabolic parameters. Decreased HE and tubular testicular compartment volumetric density and increased intertubular testicular compartment volumetric density and volume in the F1 generation of HD group were observed. Alterations in histometry of intertubular testicular compartment were also noted. It is concluded that the HFHS experimental model altered only paternal metabolic parameters. However, reproductive parameters of the three generations were affected.

Linoleic acid and α-linolenic acid are essential fatty acids (eFAs) and have to be acquired from the diet. eFAs are the precursors for long-chain polyunsaturated fatty acids (lcPUFAs), which are important immune-modulating compounds. lcPUFAs can be converted into eicosanoids and other mediators. They affect membrane structure and fluidity and can alter gene expression. There has been a marked change in dietary fatty acid intake over the last several decades. Since eFAs are acquired from the diet and immune development occurs mainly perinatally, the maternal diet may influence fetal and neonatal eFA levels, and thereby lcPUFA status, and thus immune development and function. To study whether early exposure to eFAs can program immune function, mice were fed diets varying in the ratio of ω-3 to ω-6-eFAs during pregnancy and/or lactation. After weaning, pups received a Western-style diet. At 11 weeks of age, the effects of maternal diet on the offspring's allergic and vaccination responses were examined using the T-helper 2 driven ovalbumin-induced allergy model and the T-helper 1 driven influenza-vaccination model, respectively. Offspring of dams fed a high α-linolenic acid diet during lactation showed an enhanced vaccination response. As diets with either low or high ω-3/ω-6-eFA ratio attenuated the T-helper 2 allergic response, the high α-linolenic acid diet fed during lactation had the most pronounced effect. These results indicate that there is a programming effect of maternal diet on the offspring's immune response and that in mice the window of greatest susceptibility to maternal dietary intervention is the lactation/suckling period.

There is limited evidence on the association between maternal preconception body mass index (BMI) trajectories and pregnancy complications and child development. This study examined the relationships of maternal BMI trajectories, diabetes and hypertensive disorders during pregnancy and offspring’s childhood physical and cognitive development. Data were from the Australian Longitudinal Study on Women’s Health and the Mothers and their Children’s Health study (n=771). Women’s preconception BMI trajectories were identified using group-based trajectory modelling. Children’s physical and cognitive development (up to the average age of 5 years) were obtained from the Ages and Stages Questionnaire (suspected gross motor delay) and the Australian Early Development Census (AEDC). Generalized estimating equation models, adjusted for maternal sociodemographic and lifestyle factors, were used for analyses. Three distinct BMI trajectories were identified (normative, chronically overweight and chronically obese). Children born to chronically obese women were more likely to be classified as developmentally vulnerable/at-risk on AEDC domains; gross and fine motor skills [risk ratio (RR)=1.64, 95% confidence interval (CI): 1.04, 2.61] and communication skills and general knowledge (RR=1.71, 95% CI: 1.09, 2.68). They also had an elevated risk of suspected gross motor delay (RR=2.62, 95% CI: 1.26, 5.44) compared with children born to women with a normative BMI trajectory. Maternal diabetes or hypertensive disorders during pregnancy were not associated with child outcomes. Maternal preconception BMI trajectories were associated with poorer childhood development. This study finding underscores the importance of excessive weight gain prevention throughout the reproductive stage of life.

Poor maternal nutrition during pregnancy can result in increased disease risk in adult offspring. Many of these effects are proposed to be mediated via altered hypothalamo–pituitary–adrenal axis (HPAA) function, and are sex and age specific. Maternal undernutrition around the time of conception alters HPAA function in foetal and early postnatal life, but there are limited conflicting data about later effects. The aim of this study was to investigate the effect of moderate periconceptional undernutrition on HPAA function of offspring of both sexes longitudinally, from juvenile to adult life. Ewes were undernourished from 61 days before until 30 days after conception or fed ad libitum. HPAA function in offspring was assessed by arginine vasopressin plus corticotropin-releasing hormone challenge at 4, 10 and 18 months. Plasma cortisol response was lower in males than in females, and was not different between singles and twins. Periconceptional undernutrition suppressed offspring plasma cortisol but not adrenocorticotropic hormone responses. In males, this suppression was apparent by 4 months, and was more profound by 10 months, with no further change by 18 months. In females, suppression was first observed at 10 months and became more profound by 18 months. Maternal undernutrition limited to the periconceptional period has a prolonged, sex-dependent effect on adrenal function in the offspring.

Bisphenol A (BPA) is a chemical compound that has adverse health outcomes in adults when exposed during the perinatal period. However, its effect on cardiovascular function remains to be elucidated. In this study, we examined the effects of daily administration of BPA to pregnant mice from gestational days 11 to 19 on cardiometabolic outcomes in the adult offspring. Prenatal BPA exposure resulted in altered growth trajectory and organ size, increase adiposity and impaired glucose homeostasis in male and female offspring. In addition, these BPA offspring exhibited raised systolic blood pressure, and in the males this was accompanied by impaired vascular tone. The aortas in females, but not in males, from the BPA group also showed reduced estrogen receptor gene expression. These results indicate that prenatal exposure to BPA increased susceptibility of the offspring to developing cardiovascular and metabolic dysfunction later in life.

Experimental data have suggested that some contaminants in the environment may increase the risk of obesity. Infants can be exposed to chemicals either prenatally, by trans-placental passage of chemicals, or postnatally by their own diet and by other external pathways (air inhalation, dust, hand-to-mouth exposure) after birth. To provide a review of epidemiological evidence on the association between prenatal exposure to chemicals and prenatal and postnatal growth, we present the literature from systematic review articles and international meta-analyses, when available, or recent research articles when summarizing articles were not available. The most studied contaminants in this field were persistent organic pollutants (e.g. organochlorinated pesticides, polychlorinated biphenyls), non-persistent pollutants (e.g. phthalates, bisphenol A), toxic heavy metals (i.e. cadmium, lead and mercury), arsenic, mycotoxins and acrylamide. Mounting evidence suggests that child’s growth may be associated with prenatal or postnatal exposures to environmental contaminants. Improving exposure assessment and studying the contaminants as mixtures should allow to gain knowledge about the environmental determinants of growth and obesity.

Early pubertal timing is known to put women at greater risk for adverse physiological and psychological health outcomes. Of the factors that influence girls’ pubertal timing, stress experienced during childhood has been found to advance age at menarche (AAM). However, it is not known if stress experienced by mothers during or in the months before conception can be similarly associated with earlier pubertal timing. Prenatal maternal stress (PNMS) is associated with metabolic changes, such as increased childhood adiposity and risk of obesity, that have been associated with earlier menarchal age. Using a prospective longitudinal design, the present study tested whether PNMS induced by a natural disaster is either directly associated with earlier AAM, or whether there is an indirect association mediated through increased girls’ body mass index (BMI) during childhood. A total of 31 girls, whose mothers were exposed to the Quebec’s January 1998 ice storm during pregnancy were followed from 6 months to 5 1/2 to 5.5 years of age. Mother’s stress was measured within 6 months of the storm. BMI was measured at 5.5 years, and AAM was assessed through teen’s self-report at 13.5 and 15.5 years of age. Results revealed that greater BMI at 5.5 years mediated the effect of PNMS on decreasing AAM [B=−0.059, 95% confidence intervals (−0.18, −0.0035)]. The present study is the first to demonstrate that maternal experience of stressful conditions during pregnancy reduces AAM in the offspring through its effects on childhood BMI. Future research should consider the impact of AAM on other measures of reproductive ability.

Preterm birth is common and the associated short-term morbidity well described. The adult-onset consequences of preterm birth are less clear, but cardiovascular and metabolic health may be adversely affected. Although large animal models of preterm birth addressing important short-term issues exist, long-term studies are hampered by significant logistical constraints. Current small animal models of prematurity require terminal caesarean section of the mother; both caesarean birth and early maternal care modify offspring adult cardio-metabolic function.

We describe a novel method for inducing preterm labour in guinea pigs. With support comparable to that received by moderately preterm human infants, preterm pups are viable. Growth trajectories between preterm and term-born pups differ significantly; between term equivalent age and weaning ex-preterm animals demonstrate increased weight and ponderal index.

We believe this novel paradigm will significantly improve our ability to investigate the cardio-metabolic sequelae of preterm birth throughout the life course and into the second generation.

Health before conception, and periconceptional nutritional environments, contribute to conditioning of later-life health and disease. Health behaviors developed during adolescence continue into adulthood. Thus, even when the gap between pregnancy and adolescence is substantial, behaviors developed during adolescence influence later-life non-communicable disease (NCD) vulnerability in offspring. Consequently, adolescence is an important life phase where development of positive health behaviors can contribute to disruption of transgenerational cycles of NCD risk. Schooling is a core activity during adolescence. Modern curricula focus on development of capabilities associated with critical, engaged citizenship, empowering learning that supports action-based engagement in complex issues. Contexts relevant to adolescents and their communities, such as the NCD epidemic, are used to facilitate learning. Thus, engaging the education sector as participants in the work of the Developmental Origins of Health and Disease community offers an important strategy to capture the potential of adolescence as a life stage for transgenerational primary prevention of obesity and NCD risk.

The purpose of this investigation was to test the hypothesis that maternal exercise training during pregnancy enhances endothelial function in offspring at birth. Six-month-old gilts (n = 8) were artificially inseminated and randomized into exercise-trained (n = 4) and sedentary groups (n = 4). Exercise training consisted of 15 weeks of treadmill exercise. The thoracic aorta of offspring were harvested within 48 h after birth and vascular responsiveness to cumulative doses of endothelium-dependent (bradykinin: 10−11–10−6 M) and independent (sodium nitroprusside: 10−10–10−4 M) vasodilators were assessed using in vitro wire myography. Female offspring from the exercised-trained gilts had a significantly greater endothelium-dependent relaxation response in the thoracic aorta when compared with the male offspring and female offspring from the sedentary gilts. The results of this investigation demonstrate for the first time that maternal exercise during pregnancy produces an enhanced endothelium-dependent vasorelaxation response in the thoracic aortas of female offspring at birth.

The purpose of this study was to investigate the effects of maternal gestational diabetes mellitus (GDM) and breast feeding on childhood overweight and obesity in a mainland Chinese population. The incidence of and factors associated with overweight and obesity were compared between children of mothers with (n=1068) and without (n=1756) GDM. The independent roles of the associated factors were examined by multiple logistic regression analysis. The incidence of overweight was higher (16.6 v. 12.6%, P=0.002) in the GDM group, but that of obesity was not different (10.7 v. 12.0%, P=0.315). At age 1–2 and 2–5 years, no difference in overweight (11.0 v. 12.0%, P=0.917, and 15.7 v. 14.6%, P=0.693, respectively) was found, while obesity (8.0 v. 13.6%, P=0.019, and 8.4 v. 13.4%, P=0.014, respectively) was less frequent in the GDM offspring. At age 5–10 years, increased overweight (22.2 v. 12.1%, P<0.001) and obesity (15.9 v. 9.0%, P=0.001) were found in the GDM group, which was associated with maternal obesity, being born large-for-gestational age, male gender and formula feeding. After adjusting for confounding factors, GDM remained an independent determinant of offspring overweight and obesity (aOR 2.28, 95% CI 1.61–3.22), suggesting that the effects of GDM were independent of breast feeding, as well as of maternal obesity and birth size.

Childhood obesity rates are higher among Indigenous compared with non-Indigenous Australian children. It has been hypothesized that early-life influences beginning with the intrauterine environment predict the development of obesity in the offspring. The aim of this paper was to assess, in 227 mother–child dyads from the Gomeroi gaaynggal cohort, associations between prematurity, Gestation Related-Optimal Weight (GROW) centiles, maternal adiposity (percentage body fat, visceral fat area), maternal non-fasting plasma glucose levels (measured at mean gestational age of 23.1 weeks) and offspring BMI and adiposity (abdominal circumference, subscapular skinfold thickness) in early childhood (mean age 23.4 months). Maternal non-fasting plasma glucose concentrations were positively associated with infant birth weight (P=0.005) and GROW customized birth weight centiles (P=0.008). There was a significant association between maternal percentage body fat (P=0.02) and visceral fat area (P=0.00) with infant body weight in early childhood. Body mass index (BMI) in early childhood was significantly higher in offspring born preterm compared with those born at term (P=0.03). GROW customized birth weight centiles was significantly associated with body weight (P=0.01), BMI (P=0.007) and abdominal circumference (P=0.039) at early childhood. Our findings suggest that being born preterm, large for gestational age or exposed to an obesogenic intrauterine environment and higher maternal non-fasting plasma glucose concentrations are associated with increased obesity risk in early childhood. Future strategies should aim to reduce the prevalence of overweight/obesity in women of child-bearing age and emphasize the importance of optimal glycemia during pregnancy, particularly in Indigenous women.

Developmental plasticity is the property of a given genotype to produce different phenotypes in response to the environmental conditions experienced during development. Chordates have two basic modes of development, direct and indirect. Direct development (mode of humans) was derived evolutionarily from indirect development (mode of many amphibians), the major difference being the presence of a larval stage with indirect development; larvae undergo metamorphosis to the juvenile adult. In amphibians, environmental conditions experienced during the larval stage can lead to extreme plasticity in behaviour, morphology and the timing of metamorphosis and can cause variation in adult phenotypic expression (carry-over effects, or developmental programming). Hormones of the neuroendocrine stress axis play pivotal roles in mediating environmental effects on animal development. Stress hormones, produced in response to a deteriorating larval habitat, accelerate amphibian metamorphosis; in mammals, stress hormones hasten the onset of parturition and play an important role in pre-term birth caused by intra-uterine stress. While stress hormones can promote survival in a deteriorating larval or intra-uterine habitat, costs may be incurred, such as reduced growth and size at metamorphosis or birth. Furthermore, exposure to elevated stress hormones during the tadpole or foetal stage can cause permanent neurological changes, leading to altered physiology and behaviour later in life. The actions of stress hormones in animal development are evolutionarily conserved, and therefore amphibians can serve as important model organisms for research on the mechanisms of developmental plasticity.