Associations between different forms of malnutrition and environmental conditions, including water, sanitation and hygiene (WASH), may contribute towards persistently poor child health, growth and cognitive development. Experiencing poor nutrition in utero or during early childhood is furthermore associated with chronic diseases later in life. The primary responsibility for provision of water and sanitation, as a basic service and human right, lies with the State; however, a number of stakeholders are involved. The situation is most critical in sub-Saharan Africa (SSA), where, in 2015, 311 million people lacked a safe water source, and >70% of SSA populations were living without adequate sanitation. The aim of this paper was to conduct a systematic review to investigate the state of literature concerned with WASH and its association with nutritional status, and governance in children from birth to 5 years of age in SSA. Articles were sourced from PubMed Central, Science Direct and ProQuest Social Science databases published between 1990 and 2017. The PRISMA Statement was utilised and this systematic review is registered with PROSPERO (CRD42017071700). The search terms returned 15,351 articles for screening, with 46 articles included. This is indicative of a limited body of knowledge; however, the number of publications on this topic has been increasing, suggesting burgeoning field of interest. Targeted research on the governance of WASH through the identification of the various role players and stakeholders at various levels, while understanding the policy environment in relation to particular health-related outcomes is imperative to address the burden of child undernutrition.

Disruption of physiological aging of the placenta can lead to pregnancy complications and increased risk for cardiometabolic diseases during childhood and adulthood. Maternal metabolic and genetic factors need to operate in concert with placental development for optimal pregnancy outcome. However, it is unknown whether maternal cardiometabolic status and genetic ancestry contribute to differences in placental epigenetic age acceleration (PAA). We investigated whether maternal prepregnancy obesity, gestational weight gain (GWG), blood pressure, and genetic ancestry influence PAA. Among 301 pregnant women from 4 race/ethnic groups who provided placenta samples at delivery as part of the National Institute of Child Health and Human Development Fetal Growth Studies, placental DNA methylation age was estimated using 62 CpGs known to predict placental aging. PAA was defined to be the difference between placental DNA methylation age and gestational age at birth. Percentage of genetic ancestries was estimated using genotype data. We found that a 1 kg/week increase in GWG was associated with up to 1.71 (95% CI: −3.11, −0.32) week lower PAA. Offspring Native American ancestry and African ancestry were associated, respectively, with higher and lower PAA among Hispanics, and maternal East Asian ancestry was associated with lower PAA among Asians (p < 0.05). Among mothers with a male offspring, blood pressure was associated with lower PAA across all three trimesters (p < 0.05), prepregnancy obesity compared to normal weight was associated with 1.24 (95% CI: −2.24, −0.25) week lower PAA. In summary, we observed that maternal cardiometabolic factors and genetic ancestry influence placental epigenetic aging and some of these influences may be male offspring-specific.

Muscle and bone have been considered a functional unit that grows together early in life, deteriorates with aging, and can cause osteosarcopenia. Due to its importance in public health, detecting risk factors in early life is desirable. This study examined whether birth weight (BW) was associated with muscle–bone unit using dual energy X-ray absorptiometry (DXA) parameters in young women from the Nutritionists’ Health Study (NutriHS), a cohort study of undergraduates and Nutrition graduates. This cross-sectional analysis included 170 young healthy women who answered early life events-questionnaire, and had anthropometric, muscle tests and DXA-determined body composition and bone densitometry (iDXA-Lunar®). A blood sample was obtained for a subsample of 148 participants. Appendicular skeletal muscle mass index (ASMI) was calculated. BW was categorized in quartiles (BWq) and variables of interest compared by ANOVA. Associations of BWq with calf circumference (CC), handgrip, muscle performance tests, ASMI, bone mineral density and content (BMD and BMC), and plasma glucose, lipids, insulin, and 25-hydroxyvitamin D were performed using multiple linear regression and directed acyclic graph-recommended adjustments. Mean values of age, body mass index, and BW were 23.0 years (20.0–28.0), 22.9 ± 2.9 kg/m2, and 3199 ± 424 g, respectively. Comparing variables across BWq, significant differences in CC, handgrip, ASMI, and total body BMC were detected. Regression models adjusted for confounders showed associations of BWq with CC (β = 0.72, p = 0.005), handgrip (β = 1.53, p = 0.001), ASMI (β = 0.16, p = 0.022), total body BMC (β = 64.8, p = 0.005), total femur BMC (β = 0.70, p = 0.041), total body BMD (β = 0.02, p = 0.043), and lumbar spine BMD (β = 0.03, p = 0.028). We conclude that BW is associated with muscle–bone unit using DXA-parameters in Brazilian young healthy women from the NutriHS, suggesting a role for intrauterine environment for musculoskeletal health.

Asthma is a chronic respiratory disease with complex etiology. Adverse childhood experiences (ACEs) have been linked to asthma in adulthood. Underlying potential mechanisms for the ACE-asthma relationship include stress-induced inflammatory pathways and immune dysregulation. We conducted a cross-sectional secondary data analysis of the 2013 Alberta ACE Survey to explore the relationship between latent ACE factors and self-reported adult asthma. We evaluated the underlying correlation structure among eight different ACEs using exploratory factor analysis. We conducted a logistic regression model to evaluate whether ACE factors retained from the factor analysis predicted self-reported asthma in adulthood. Results were reported as odds ratios (ORs) with 95% confidence intervals (CIs). We analyzed ACE survey results from 1207 participants. Factor analysis yielded four ACE latent factors: factor 1/relational violence, factor 2/negative home environment, factor 3/illness at home, and factor 4/sexual abuse. Results of the logistic regression showed that experiencing sexual abuse (OR: 3.23; 95% CI: 1.89, 5.23), relational violence (OR: 1.99; 95% CI: 1.17, 3.38), and being exposed to a negative home environment (OR: 1.86; 95% CI: 1.03, 3.35) were predictive of a diagnosis of asthma in adulthood, whereas living in a household with someone experiencing illness did not show an effect (OR: 1.38; 95% CI: 0.75, 2.56). Factor analysis provides an effectual approach to understand the long-term impact of ACEs on respiratory health. Our findings have important implications to understand the developmental origins of asthma in adulthood and inform interventions aimed at reducing the lasting negative impact of childhood adversities on future respiratory health.

Antenatal exogenous glucocorticoids (ANG) are standard management for women at risk of preterm birth but are reputed to impair glucose tolerance in preterm offspring. We compared lambs born preterm (137 days gestation) following labour induced with exogenous glucocorticoids (G-Prem, glucocorticoid-induced preterm group), or with a progesterone synthesis inhibitor (NG-Prem, non-glucocorticoid-induced preterm group), with term-born lambs (Term; 149 days). We assessed glucose tolerance, insulin secretion and sensitivity at 4 and 10 months n = 11–14/group) and pancreatic and hepatic gene and protein expression at 4 weeks post-term (4 weeks; n = 6/group) and 12 months (12 months; n = 12–13/group). NG-Prem had higher plasma glucose concentrations than G-Prem, but not Term, at 4 months (Mean[SEM] mM: NG-Prem = 4.1[0.1]; G-Prem = 3.4[0.1]; Term = 3.7[0.1]; p = 0.003) and 10 months (NG-Prem = 3.9[0.1]; G-Prem = 3.5[0.1]; Term = 3.7[0.1]; p = 0.01). Insulin sensitivity decreased from 4 to 10 months, in NG-Prem but not in Term (Mean[SEM] µmol·ml−1·kg−1·min−1·ng−1, 4 vs. 10 months: NG-Prem = 18.7[2.5] vs. 9.5[1.5], p < 0.01; Term: 12.1[2.8] vs. 10.4[1.5], p = 0.44). At 12 months, β-cell mass in NG-Prem was reduced by 30% vs. G-Prem (p < 0.01) and 75% vs. Term (p < 0.01) and was accompanied by an increased β-cell apoptosis: proliferation ratio at 12 months. At 12 months, pancreatic glucokinase, igf2 and insulin mRNA levels were reduced 21%–71% in NG-Prem vs. G-Prem and 42%–80% vs. Term. Hepatic glut2 mRNA levels in NG-Prem were 250% of those in G-Prem and Term. Thus, induction of preterm birth without exogenous glucocorticoids more adversely affected pancreas and liver than induction with exogenous glucocorticoids. These findings do not support that ANG lead to long-term adverse metabolic effects, but support an effect of preterm birth itself.

The mechanism through which developmental programming of offspring overweight/obesity following in utero exposure to maternal overweight/obesity operates is unknown but may operate through biologic pathways involving offspring anthropometry at birth. Thus, we sought to examine to what extent the association between in utero exposure to maternal overweight/obesity and childhood overweight/obesity is mediated by birth anthropometry. Analyses were conducted on a retrospective cohort with data obtained from one hospital system. A natural effects model framework was used to estimate the natural direct effect and natural indirect effect of birth anthropometry (weight, length, head circumference, ponderal index, and small-for-gestational age [SGA] or large-for-gestational age [LGA]) for the association between pre-pregnancy maternal body mass index (BMI) category (overweight/obese vs normal weight) and offspring overweight/obesity in childhood. Models were adjusted for maternal and child socio-demographics. Three thousand nine hundred and fifty mother–child dyads were included in analyses (1467 [57.8%] of mothers and 913 [34.4%] of children were overweight/obese). Results suggest that a small percentage of the effect of maternal pre-pregnancy BMI overweight/obesity on offspring overweight/obesity operated through offspring anthropometry at birth (weight: 15.5%, length: 5.2%, head circumference: 8.5%, ponderal index: 2.2%, SGA: 2.9%, and LGA: 4.2%). There was a small increase in the percentage mediated when gestational diabetes or hypertensive disorders were added to the models. Our study suggests that some measures of birth anthropometry mediate the association between maternal pre-pregnancy overweight/obesity and offspring overweight/obesity in childhood and that the size of this mediated effect is small.

The aim of this study was to identify social and biological drivers of fetal growth by examining associations with household, preconception, and pregnancy factors in a cohort from Soweto, South Africa. Complete data and ultrasound scans were collected on 519 women between 2013 and 2016 at 6 time points during pregnancy (<14, 14–18, 19–23, 24–28, 29–33 weeks, and 34–38 weeks). Household-level factors, preconception health, baseline body mass index (BMI), and demographic data were collected at the first visit. During pregnancy, gestational weight gain (GWG; kg/week) was calculated. At 24–28 weeks of gestation, oral glucose tolerance test was used to determine gestational diabetes mellitus (GDM) status, and hypertension status was characterised. Longitudinal growth in head circumference, abdominal circumference, biparietal diameter, and femur length were modelled using the Superimposition by Translation and Rotation, a shape-invariant model which produces growth curves against gestational age. A priori identified exposure variables were then included in a series of sex-stratified hierarchical regression models for each fetal growth outcome. No household-level factors were associated with fetal growth. Maternal BMI at baseline was positively associated with all outcome parameters in males and females. Both GWG (in males and females) and GDM (in males) were significant positive predictors of abdominal growth. Males showed more responsiveness to abdominal growth, while females were more responsive to linear growth. Thus, fetal growth was largely predicted by maternal biological factors, and sexual dimorphism in the responsiveness of fetal biometry to biological exposures was evident.

Major obstetrics and gynecology societies offer inconsistent recommendation regarding optimal delivery timing in uncomplicated dizygotic twins. We sought to investigate the impact of delivery timing within term gestation, in dizygotic twins, on the short- and long-term offspring morbidity. A prospectively analyzed cohort of dizygotic twin deliveries was conducted. All women delivered at a regional tertiary medical center, at term (≥37 0/7), between the years 1991 and 2014, were included. The primary exposure was delivery at 37 0/7–37 + 6/7 weeks, while delivery at ≥38 0/7 weeks’ gestation was considered the reference. Neonatal short- and long-term outcomes according to hospitalizations of offspring up to 18 years of age due to cardiac, respiratory, hematological, neurological, and infectious morbidity were compared. Kaplan–Meier survival curves were used to compare cumulative incidences per each major-system hospitalization. Cox regression models were used to estimate the adjusted hazard ratios, while adjusting for variables with clinical importance. During the study period, 612 dizygotic twin deliveries met the inclusion criteria. Of them, 200 (31.3%) occurred at 37–37 6/7 weeks, and 412 (68.7%) occurred at ≥38 0/7 weeks’ gestation. In the long-term analysis, rates of hospitalizations involving several major morbidity categories exhibited comparable rates in both groups. The Cox regression models did not demonstrate an independent association between gestational age within term and later major pediatric morbidity in offspring (total long-term morbidity: adjusted hazard ratio 1.33, 95% confidence interval 0.77–2.29). Dizygotic twin deliveries occurring at different gestational ages within term do not appear to significantly impact on major short- and long-term outcomes.

Exposure to glucocorticoid levels higher than appropriate for current developmental stages induces offspring metabolic dysfunction. Overfed/obese (OB) ewes and their fetuses display elevated blood cortisol, while fetal Adrenocorticotropic hormone (ACTH) remains unchanged. We hypothesized that OB pregnancies would show increased placental 11β hydroxysteroid dehydrogenase 2 (11β-HSD2) that converts maternal cortisol to fetal cortisone as it crosses the placenta and increased 11β-HSD system components responsible for peripheral tissue cortisol production, providing a mechanism for ACTH-independent increase in circulating fetal cortisol. Control ewes ate 100% National Research Council recommendations (CON) and OB ewes ate 150% CON diet from 60 days before conception until necropsy at day 135 gestation. At necropsy, maternal jugular and umbilical venous blood, fetal liver, perirenal fat, and cotyledonary tissues were harvested. Maternal plasma cortisol and fetal cortisol and cortisone were measured. Fetal liver, perirenal fat, cotyledonary 11β-HSD1, hexose-6-phosphate dehydrogenase (H6PD), and 11β-HSD2 protein abundance were determined by Western blot. Maternal plasma cortisol, fetal plasma cortisol, and cortisone were higher in OB vs. CON (p < 0.01). 11β-HSD2 protein was greater (p < 0.05) in OB cotyledonary tissue than CON. 11β-HSD1 abundance increased (p < 0.05) in OB vs. CON fetal liver and perirenal fat. Fetal H6PD, an 11β-HSD1 cofactor, also increased (p < 0.05) in OB vs. CON perirenal fat and tended to be elevated in OB liver (p < 0.10). Our data provide evidence for increased 11β-HSD system components responsible for peripheral tissue cortisol production in fetal liver and adipose tissue, thereby providing a mechanism for an ACTH-independent increase in circulating fetal cortisol in OB fetuses.

Overconsumption of fructose time dependently induces the development of non-alcoholic fatty liver disease (NAFLD). We investigated whether ursolic acid (UA) intake by new-born rats would protect against fructose-induced NAFLD. One hundred and seven male and female Sprague Dawley rat pups were randomly grouped and gavaged (10 ml/kg body weight) with either 0.5% dimethylsulphoxide (vehicle control), 0.05% UA, 50% fructose mixed with UA (0.05%) or 50% fructose alone, from postnatal day 6 (P6) to P20. Post-weaning (P21–P69), the rats received normal rat chow (NRC) and water to drink. On P70, the rats in each group were continued on water or 20% fructose to drink, as a secondary high fructose diet during adulthood. After 8 weeks, body mass, food and fluid intake, circulating metabolites, visceral adiposity, surrogate markers of liver function and indices of NAFLD were determined. Food intake was reduced as a result of fructose feeding in both male and female rats (p < 0.0001). Fructose consumption in adulthood significantly increased fluid intake and visceral adiposity in female rats (p < 0.05) and had no apparent effects in male rats (p > 0.05). In both sexes of rats, fructose had no significant (p > 0.05) effects on body mass, circulating metabolites, total calorie intake and surrogate markers of hepatic function. Fructose consumption in both early life and adulthood in female rats promoted hepatic lipid accumulation (p < 0.001), hypertrophy, microvesicular and macrovesicular steatosis (p < 0.05). Early-life UA intake significantly (p < 0.001) reduced fructose-induced hepatic lipid accumulation in both male and female rats. Administration of UA during periods of developmental plasticity shows prophylactic potential against dietary fructose-induced NAFLD.

Epigenetic programming is essential for lineage differentiation, embryogenesis and placentation in early pregnancy. In epigenetic association studies, DNA methylation is often examined in DNA derived from white blood cells, although its validity to other tissues of interest remains questionable. Therefore, we investigated the tissue specificity of epigenome-wide DNA methylation in newborn and placental tissues. Umbilical cord white blood cells (UC-WBC, n = 25), umbilical cord blood mononuclear cells (UC-MNC, n = 10), human umbilical vein endothelial cells (HUVEC, n = 25) and placental tissue (n = 25) were obtained from 36 uncomplicated pregnancies. Genome-wide DNA methylation was measured by the Illumina HumanMethylation450K BeadChip. Using UC-WBC as a reference tissue, we identified 3595 HUVEC tissue-specific differentially methylated regions (tDMRs) and 11,938 placental tDMRs. Functional enrichment analysis showed that HUVEC and placental tDMRs were involved in embryogenesis, vascular development and regulation of gene expression. No tDMRs were identified in UC-MNC. In conclusion, the extensive amount of genome-wide HUVEC and placental tDMRs underlines the relevance of tissue-specific approaches in future epigenetic association studies, or the use of validated representative tissues for a certain disease of interest, if available. To this purpose, we herewith provide a relevant dataset of paired, tissue-specific, genome-wide methylation measurements in newborn tissues.

Prenatal exposure to mercury in utero causes abnormal foetal growth and adverse outcomes. DNA methylation is currently considered a possible mechanism through which this occurs. However, few studies have investigated the association between prenatal exposure to mercury and DNA methylation in detail. This study aimed to clarify the relationship between prenatal exposure to total mercury (Hg) and DNA methylation and its associations with sex-specific characteristics in male and female offspring. In a birth cohort study known as the Chiba study of Mother and Child Health, the DNA methylation status in cord tissue and Hg concentrations in cord serum were examined. A total of 67 participants (27 males and 40 females) were analysed based on Spearmanʼs correlations, adjusted by a false discovery rate of the sex of each offspring. Only one methylated locus was positively correlated with Hg concentrations in cord serum in male offspring, but not in female offspring, and was annotated to the haloacid dehalogenase-like hydrolase domain-containing protein 1 (HDHD1) gene on chromosome X. This locus was located in the intron of the HDHD1 gene body and is a binding site for the zinc finger protein CCCTC-binding factor. One of the other loci, located in HDHD1, was highly methylated in the group with higher mercury concentrations, and this locus was in the gene body of HDHD1. Our results suggest that prenatal exposure to Hg might affect the epigenetic status of male foetuses.

Mono-2-ethylhexyl phthalate (MEHP) is the primary metabolite of the ubiquitous plasticizer and toxicant, di-2-ethylhexyl phthalate. MEHP exposure has been linked to abnormal development, increased oxidative stress, and metabolic syndrome in vertebrates. Nuclear factor, Erythroid 2 Like 2 (Nrf2), is a transcription factor that regulates gene expression in response to oxidative stress. We investigated the role of Nrf2a in larval steatosis following embryonic exposure to MEHP. Wild-type and nrf2a mutant (m) zebrafish embryos were exposed to 0 or 200 μg/l MEHP from 6 to either 96 (histology) or 120 hours post fertilization (hpf). At 120 hpf, exposures were ceased and fish were maintained in clean conditions until 15 days post fertilization (dpf). At 15 dpf, fish lengths and lipid content were examined, and the expression of genes involved in the antioxidant response and lipid processing was quantified. At 96 hpf, a subset of animals treated with MEHP had vacuolization in the liver. At 15 dpf, deficient Nrf2a signaling attenuated fish length by 7.7%. MEHP exposure increased hepatic steatosis and increased expression of peroxisome proliferator-activated receptor alpha target fabp1a1. Cumulatively, these data indicate that developmental exposure alone to MEHP may increase risk for hepatic steatosis and that Nrf2a does not play a major role in this phenotype.

Action to improve preconception nutrition is a collective, societal responsibility. We believe that the Developmental Origins of Health and Disease (DOHaD) society is ideally placed to facilitate the development of a global agenda for preconception nutrition which recognises the societal importance of nutrition for young women and men, and supports them in optimising their nutritional status for the benefit of the next generation. In this paper, we outline four key actions that can be taken by the members of DOHaDʼs international society located across 67 countries, and nine regional societies, to demonstrate this leadership role. The recommended actions to place preconception nutrition at the top of national and regional agendas include (i) continuing to build the scientific evidence, (ii) monitoring of progress made by governments and commercial companies, (iii) developing advocacy coalitions that unite individuals and organisations around common policy options and (iv) working with partners to develop an emotive and empowering preconception nutrition awareness campaign. Collectively, these actions hold the potential to develop into a preconception nutrition social movement to invoke high-level government support and across-sector policy action, while raising public demand for action and engaging corporate actors.