A developmental approach to public health focuses attention on better nourishing girls and young women, especially those of low socio-economic status, to improve mothers’ nutrition and thereby the health of future generations. There have been significant advances in the behavioural sciences that may allow us to understand and support dietary change in young women and their children in ways that have not previously been possible. This paper describes some of these advances and aims to show how they inform this new approach to public health. The first of these has been to work out what is effective in supporting behaviour change, which has been achieved by careful and detailed analysis of behaviour change techniques used by practitioners in intervention, and of the effectiveness of these in supporting change. There is also a new understanding of the role that social and physical environments play in shaping our behaviours, and that behaviour is influenced by automatic processes and ‘habits’ as much as by reflective processes and rational decisions. To be maximally effective, interventions therefore have to address both influences on behaviour. An approach developed in Southampton aims to motivate, support and empower young women to make better food choices, but also to change the culture in which those choices are being made. Empowerment is the basis of the new public health. An empowered public demand for better access to better food can go a long way towards improving maternal, infant and family nutrition, and therefore the health of generations to come.

Uteroplacental insufficiency resulting in intrauterine growth restriction has been associated with the development of cardiovascular disease, coronary heart disease and increased blood pressure, particularly in males. The molecular mechanisms that result in the programming of these phenotypes are not clear. This study investigated the expression of cardiac JAK/STAT signalling genes in growth restricted offspring born small due to uteroplacental insufficiency. Bilateral uterine vessel ligation was performed on day 18 of pregnancy to induce growth restriction (Restricted) or sham surgery (Control). Cardiac tissue at embryonic day (E) 20, postnatal day (PN) 1, PN7 and PN35 in male and female Wistar (WKY) rats (n=7–10 per group per age) was isolated and mRNA extracted. In the heart, there was an effect of age for males for all genes examined there was a decrease in expression after PN1. With females, JAK2 expression was significantly reduced after E20, while PI3K in females was increased at E30 and PN35. Further, mRNA expression was significantly altered in JAK/STAT signalling targets in Restricteds in a sex-specific manner. Compared with Controls, in males, JAK2 and STAT3 were significantly reduced in the Restricted, while in females SOCS3 was significantly increased and PI3K significantly decreased in the Restricted offspring. Finally, there were specific differences in the levels of gene expression within the JAK/STAT pathway when comparing males to females. Thus, growth restriction alters specific targets in the JAK/STAT signalling pathway, with altered JAK2 and STAT3 potentially contributing to the increased risk of cardiovascular disease in the growth restricted males.

Fetal growth restriction (FGR) is a pregnancy condition in which fetal growth is suboptimal for gestation, and this population is at increased risk for type 2 diabetes as adults. In humans, maternal malnutrition and placental insufficiency are the most common causes of FGR, and both result in fetal undernutrition. We hypothesized that maternal nutrient restriction (MNR) in mice will cause FGR and alter glucose metabolism in adult offspring. Pregnant CD-1 mice were subjected to MNR (70% of average ad libitum) or control (ad libitum) from E6.5 to birth. Following birth, mice were fostered by mothers on ad libitum feeds. Weight, blood glucose, glucose tolerance and tissue-specific insulin sensitivity were assessed in male offspring. MNR resulted in reduced fetal sizes but caught up to controls by 3 days postnatal age. As adults, glucose intolerance was detected in 19% of male MNR offspring. At 6 months, liver size was reduced (P = 0.01), but pAkt-to-Akt ratios in response to insulin were increased 2.5-fold relative to controls (P = 0.004). These data suggest that MNR causes FGR and long-term glucose intolerance in a population of male offspring similar to human populations. This mouse model can be used to investigate the impacts of FGR on tissues of importance in glucose metabolism.

Several studies have shown that South Asian neonates have a characteristic thin–fat insulin-resistant phenotype. The aim of our study was to determine whether this phenotype is also present in South Asians who have migrated to a Western country (the Netherlands). South Asian and white Dutch pregnant women were included in our study. After delivery, cord blood was collected and neonatal anthropometry was measured within 72 h. Compared with white Dutch mothers, South Asian mothers were younger (28.5 v. 32.2 years, P<0.001) and had a higher prepregnancy body mass index (25.1 v. 23.0, P=0.001). Gestational age at delivery was on average 4 days shorter in South Asians (274.9 v. 278.8, P=0.001). To compare the two groups of neonates, we calculated sex- and gestation-specific s.d. scores using the values for mean and s.d. obtained from the white Dutch subjects as a reference. All measurements were smaller in South Asian neonates, except for those of the skinfolds. The largest difference was found in abdominal circumference (s.d. score 1.39, 95% CI −1.76 to −1.01). Triceps and subscapular skinfolds were similar in both groups (triceps s.d. score −0.34, 95% CI −0.88 to +0.20 and subscapular s.d. score −0.03, 95% CI −0.31 to +0.25). South Asian neonates had higher cord plasma levels of triglycerides (0.40 v. 0.36, P=0.614), glucose (5.4 v. 4.8, P=0.079) and insulin (6.3 v. 4.0, P=0.051). However, these differences were not statistically significant. After adjustment for birth weight, the difference in insulin became statistically significant (P=0.001). We therefore conclude that the thin–fat insulin-resistant phenotype is also present in South Asian neonates in the Netherlands.

Stimulating the maternal immune system before or during pregnancy can dramatically improve morphologic outcome in mice that have been exposed to teratogens. For example, maternal immune stimulation in mice reduced craniofacial and palate defects, heart defects, digit and limb defects, tail malformations and neural tube defects caused by diverse teratogens that included chemical agents, hyperthermia, X-rays and diabetes mellitus. Several different procedures of immune stimulation were effective and included footpad injection with Freund's Complete Adjuvant, intraperitoneal (IP) injection with inert particles or attenuated Bacillus Calmette–Guerin, intrauterine injection with allogenic or xenogenic lymphocytes, or intravascular, intrauterine or IP injection with immunomodulatory cytokines. Limited information is available regarding mechanisms by which such immune stimulation reduces fetal dysmorphogenesis; however, cytokines of maternal origin have been suggested as effector molecules that act on the placenta or fetus to improve development. These collective data raise novel questions about the possibility of unrecognized maternal immune system regulatory activity in normal fetal development. This manuscript reviews the literature showing maternal immune protection against morphologic birth defects. Potential operating mechanisms are discussed, and the possibility is considered that a suppressed maternal immune system may negatively impact fetal development.

Maternal obesity (MO) during pregnancy and lactation leads to maternal and offspring metabolic dysfunction. Recent research has suggested that probiotics might be a novel approach to counteract these unwanted MO effects. The aim of this research was to analyze the impact of Leuconostoc SD23, a probiotic isolated from aguamiel (traditional Mexican drink), on MO metabolism in rats at the end of lactation (21 days). From weaning through lactation, control female Wistar rats (C) ate chow (5% fat) or high-energy obesogenic diet (MO; 25% fat). Half the C and MO mothers received a daily dose (1 × 1010 CFU/ml) of probiotic orally, control with probiotic (CP) and MO with probiotic (MOP), 1 month before mating and through pregnancy and lactation. Histological analyses of the liver, white adipose tissue and small intestine, body composition, glucose, insulin, triglycerides, and leptin were determined in mothers at the end of lactation. Maternal weight during pregnancy was greater in MO than C mothers, but similar at the end of lactation. Probiotic intervention had no effect on maternal weight. However, at the end of lactation, percentage of body fat was higher in MO than C, CP, and MOP. Serum glucose, homeostasis model assessment of insulin resistance, and triglycerides were higher in MO versus C, CP, and MOP. MO small intestine villus height was higher versus MOP, C, and CP. Leuconostoc SD23 did not present adverse effects in C. Conclusions: maternal administration of Leuconostoc SD23 has beneficial effects on maternal metabolism, which holds possibilities for preventing adverse offspring metabolic programming.

Hypertension (HTN) remains a common complication after kidney transplantation among paediatric patients. Although low birth weight (LBW) has been implicated as an important risk factor for cardiovascular diseases, its effect on transplantation patients has not yet been addressed. It is essential to determine whether children with LBW who undergo transplantation are more likely to develop post-transplantation HTN. For this study, the medical records of 96 kidney recipients were retrospectively examined. A total of 83 patients fulfilled the inclusion criteria. Overall, post-transplantation HTN was observed in 54% of the recipients. Multivariate logistic regression revealed that time from transplantation >14 months (odds ratio (OR) 3.6; 95% confidence interval (CI) 1.31–10.06; P = 0.013), current CKD (OR 2.6; 95% CI 1.01–7.20; P = 0.045), presence of LBW (OR 3.6; 95% CI 1.04–12.32; P = 0.044) and current overweight/obesity (OR 3.7; 95% CI 1.02–13.91; P = 0.047) were associated with post-transplantation HTN. In conclusion, our data provide evidence for the first time that LBW is a significant predictive factor in the development of post-transplantation HTN. This finding has important clinical implications as it serves to alert clinicians about this additional risk factor in paediatric patients undergoing kidney transplant.

In humans, obesity before and during pregnancy is associated with both fetal macrosomia and growth restriction, and long-term cardiovascular risk in the offspring. We aimed to determine whether overweighted pregnant guinea pig sows results in an increased fetal weight at term and the effects on the vascular reactivity in fetal systemic and umbilical arteries. Pregnant guinea pigs were classified as control (n=4) or high weight (HWS, n=5) according to their pre-mating weight, and their fetuses extracted at 0.9 gestation (~60 days). Segments of fetal femoral and umbilical arteries were mounted in a wire myograph, where the contractile response to KCl (5–125 mM), and the relaxation to nitric oxide synthase-dependent agents (insulin, 10−10–10−7 and acetylcholine, 10−10–10−5) and nitric oxide [sodium nitroprusside (SNP), 10−10–10−5] were determined. Fetuses from HWS (HWSF) were grouped according to their body weight as low (<76 g) or high (>85 g) fetal weight, based on the confidence interval (76.5–84.9 g) of the control group. No HWSF were observed in the normal range. Umbilical arteries from HWSF showed a lower response to KCl and insulin compared with controls, but a comparable response with SNP. Conversely, femoral arteries from HWSF showed an increased response to KCl and acetylcholine, along with a decreased sensitivity to SNP. These data show that overweight sows have altered fetal growth along gestation. Further, large and small fetuses from obese guinea pig sows showed altered vascular reactivity at umbilical and systemic vessels, which potentially associates with long-term cardiovascular risk.

Maternal prenatal psychological distress, which includes depression and anxiety, affects the onset of autism spectrum disorder (ASD). However, there is no consistent knowledge regarding at which term during pregnancy psychological distress affects the risk of ASD among children. We used a dataset obtained from the Japan Environment and Children’s Study, which is a nationwide prospective birth cohort study, to evaluate the association between the six-item Kessler Psychological Distress Scale (K6) and ASD among 3-year-old children. A total of 78,745 children were analyzed, and 355 of them were diagnosed with ASD (0.45%). The maternal K6 was administered twice during pregnancy: at a median of 15.1 weeks (M-T1) and at that of 27.4 weeks (M-T2) of gestation. Multivariate logistic regression analyses demonstrated that the group with a maternal K6 score of ≥5 at both M-T1 and M-T2 was significantly associated with ASD among the children (adjusted odds ratio, 1.440; 95% confidence interval, 1.104–1.877) compared to the group with a score of ≤4 at both M-T1 and M-T2. There was no significant difference between the group with a score of ≥5 only at M-T1 or M-T2 and that with a score of ≤4 at both M-T1 and M-T2. In conclusion, from the first to the second half of pregnancy, continuous maternal psychological distress was associated with ASD among 3-year-old children. Contrarily, in the group without persistent maternal psychological distress during pregnancy, there was no significant association.

Fetal hepatic calcifications can be caused by infections, chromosomal disorders, thrombotic events, ischemic hepatic necrosis and subcapsular hematomas among others events. Its features and clinical significance are still not well known. We performed an observational study to describe fetal hepatic calcifications and its association with main clinical and histopathological findings from the fetal autopsy database, between 2007 and 2014. Raw odds ratio analysis was performed. We reviewed 591 fetal autopsies: 14 cases with hepatic calcifications, 102 fetuses with chromosomal disorders; 13 with diagnosis of TORSCH (toxoplasma, rubella, syphilis, cytomegalovirus, herpes virus 1 and 2, and others) and 207 with any abnormality in the umbilical cord (UC). The relation between hepatic calcifications and chromosomal disorders in our series had significance. It is known that hepatic calcifications are common in chromosomal disorders, transplacental infections and UC abnormalities, those conditions are risk factor for hepatic calcifications formation; we suggest hepatic calcifications should alert the pathologists in order to consider these etiologies in first instance.

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.

The aim of this study was to compare physical growth from birth to 2 years of age of babies born to women with or without gestational diabetes mellitus (GDM), among the subjects of the 2004 Pelotas Birth Cohort. Mothers who gave birth in 2004 in any of the five maternity wards in the city of Pelotas, Southern Brazil, were interviewed shortly after delivery by trained interviewers, using tested, pre-coded questionnaires. GDM diagnosis was self-reported. Child weight, length and abdominal circumference were measured, and adjusted weight-for-age, height-for-age and weight-for-height Z-scores were calculated at birth, 3, 12 and 24 months. We studied 4239 children. Offspring of GDM mothers (OGDM; n = 125) had lower gestational age (GA; P = 0.004), greater weight (P = 0.002) and greater abdominal circumference (P < 0.001) at birth. Prevalence of large for GA (LGA) was threefold higher among OGDM (18.4% v. 6.8%). Mean weight-for-age (0.48 v. −0.07; P < 0.001) and weight-for-height (0.94 v. 0.51; P < 0.001) Z-scores were also higher among OGDM. During the first 3 months, there was an abrupt catch-down among OGDM babies, who remained lighter than non-GDM offspring until the 24th month. LGA OGDM were heavier than LGA offspring of non-GDM mothers at birth, but had caught down with babies born with adequate weight for GA to non-GDM by 3 months, and showed similar growth patterns from thereon. OGDM show different growth patterns when compared to offspring of non-GDM mothers, which may be part of a causal pathway or constitute a risk marker for future obesity, impaired glucose tolerance and diabetes mellitus.

The critical period during which maternal hyperglycemia predisposes offspring to develop reproductive disorders in adult life is not known. The relationship between maternal hyperglycemia at different stages and reproductive functions of male offspring was investigated. A single intraperitoneal injection of alloxan (90 mg/kg body weight) was administered at gestation days (GD) 1, 8 and 15. Animals were subsequently given 10% glucose solution daily as drinking water until parturition. All male pups were sacrificed on the 63rd day of postnatal life. Birth weight, anogenital distance index (AGDi), testes descent day, preputial separation day, sperm profile, serum testosterone, luteinizing hormone and follicle-stimulating hormone levels and the histology of the testis were assessed. Data significance test was based on 95% confidence interval. GD1 pups showed a significant increase in mean birth weight, whereas GD8 pups and GD15 pups had significantly reduced birth weight as compared with control. AGDi was significantly increased in GD8 and GD15 pups. Testes descent and preputial separation in all the experimental groups were significantly earlier. There was a significant reduction in sperm count and viability in GD8 offspring. Sperm motility was reduced in all test groups. Testosterone level was reduced in all test groups. Histology of the testis showed varying degrees of pathologies. It was deduced from this study that maternal hyperglycemia caused alterations in reproductive functions in male offspring of Wistar rats irrespective of the period of gestation involved, although GD8 pups were most severely affected.

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.

There is increasing evidence linking maternal diet and physical activity before and during pregnancy with offspring’s cardiovascular health. Although many studies examined this association, the evidence has not been reviewed systematically. We therefore undertook a systematic review to synthesize evidence examining the association of maternal diet and physical activity before and during pregnancy with offspring’s blood pressure and vascular health. We systematically searched the databases MEDLINE and EMBASE from inception to June 30, 2017. Eligibility screening, data extraction and quality assessment were performed by two independent reviewers. A total of 19 articles were included comprising three randomized controlled trials and 16 observational studies. Of the studies that examined the association of interest, 60% (three out of five studies) showed that high maternal carbohydrate intake was associated with higher offspring’s blood pressure. Maternal protein intake during pregnancy was negatively associated with offspring carotid intima-media thickness in two out of two studies. No consistent findings for maternal fatty acid intake were found. There were too few studies to draw conclusions on energy intake, fibre intake, protein/carbohydrate ratio, specific foods, dietary patterns and maternal physical activity. Heterogeneity in exposure and outcome assessment hampered pooling. Also, owing to the observational nature of most studies, causality cannot be established. Harmonization of valid exposure and outcome measurements, and the development of core outcome sets are needed to enable more robust conclusions.

Obesity and osteoporosis may have their origins in early postnatal life. This study was designed to evaluate whether flaxseed flour use during lactation period bears effect on body adiposity and skeletal structure of male rat pups at weaning. At birth, male Wistar rats were randomly assigned to control and experimental (FF) groups, whose dams were treated with control or flaxseed flour diet, respectively, during lactation. At 21 days of age, pups were weaned to assess body mass, length and composition by dual-energy X-ray absorptiometry. The animals were then sacrificed to carry out analysis of serum profile, intra-abdominal adipocyte morphology and femur characteristics. Differences were considered significant when P<0.05. The FF group displayed the following characteristics (P<0.05): higher body mass, length, bone mineral content, bone area and concentrations of osteoprotegerin, osteocalcin and high-density lipoprotein cholesterol; higher levels of stearic, α-linolenic, eicosapentaenoic and docosapentaenoic acids and lower levels of arachidonic acid and cholesterol; smaller adipocyte area; and higher mass, epiphysis distance, diaphysis width, maximal load, break load, resilience and stiffness of femur. Flaxseed flour intake during lactation period promoted adipocyte hypertrophy down-regulation and contributed to pup bone quality at weaning.

The associations between fetal environment and diabetes risk are likely mediated by the offspring’s diminished pancreatic β-cell function or reduced insulin sensitivity. Our ability to distinguish between these mechanisms is impeded by the lack of markers describing an individual’s gestational environment. Fingerprints, however, are permanently fixed in the first half of gestation, and increased values of a dermatoglyphic marker that contrasts fingerprint ridge counts between the thumbs and fifth fingers (Md15) have been linked to type 2 diabetes. Among 763 adults without known diabetes from the Dutch Hunger Winter Families Study, we tested the associations of Md15 with homeostatic assessment indices of β-cell function (HOMA-b) and insulin sensitivity (QUICKI). For either outcome index, linear regression models included terms for Md15 tertiles and for maternal history of diabetes as reported by each participant. All models were corrected for sibling pairs and adjusted for age, sex and famine exposures. Increased Md15 was associated with decreased HOMA-b (P = 0.03 for Md15 tertile 3 v. 1) but not with QUICKI. In contrast, maternal history of diabetes was associated with decreased QUICKI (P < 0.001) but not with HOMA-b. Birth weight (available for 520 participants) was positively associated with increased QUICKI (P = 0.04 for birth weight tertile 3 v. 1) but not with HOMA-b. Fingerprint Md15, maternal history of diabetes and birth weight may help to identify specific defects in the control of adult glucose metabolism. Research into the environment associated with Md15 variation may suggest prenatal strategies for optimizing β-cell function in adult life.

The precocious interruption of lactation is a prime factor for developmental plasticity. Here we analyzed whether flour or flaxseed oil treatment contributes to body and brain mass in male rats subjected to early weaning. Pups were weaned for separation from their mother at 14 (early weaning, EW) and 21 days (control, C). At 21 days, some of the pups were evaluated (C21 v. EW21). After 21 days, control pups (C60) were fed a control diet. EW pups were divided into those fed a control diet (EWC60), those given flaxseed flour (EWFF60), and those given flaxseed oil (EWFO60) until 60 days. EW21 showed lower body and absolute brain mass and higher relative brain mass. At 60 days, EWC60 and EWFO60 had lower body mass. With regard to relative brain mass, EWC60 was heavier; EWFO60 had lower values compared with EWC60 and higher values compared with C60 and EWFF60. These results indicated that flaxseed flour, in comparison with flaxseed oil, contributes to brain development after EW.

Low birth weight (LBW) and macrosomia have been associated with later-in-life metabolic alterations. The aim of this study was to elucidate whether the expression levels of circulating microRNAs (c-miRNAs) associated with adult metabolic diseases are also dysregulated in newborns with LBW or macrosomia. The expression levels of five microRNAs (miRNAs) associated with metabolic diseases were quantified in dried blood spots of newborns with adequate birth weight, LBW and macrosomia by stem-loop real-time polymerase chain reaction. miR-29a-5p, miR-126-3p, miR-221-3p, and miR-486-5p were significantly overexpressed in newborns with macrosomia and showed no significant change in the LBW group compared to normal weight controls. miR-320a showed no statistical difference among groups. We predicted the putative target genes and pathways of the overexpressed miRNAs with bioinformatic tools. Bioinformatic analyses of overexpressed miRNAs predicted target genes involved in carbohydrate metabolism, participate in FoxO and PI3K/Akt signaling pathways, and are associated with diabetes, obesity, and cardiovascular diseases. The overexpression of circulating miR-29a-5p, miR-126-3p, miR-221-3p, and miR-486-5p may explain the increased risk of obesity and diabetes associated with macrosomia. The use of dried blood spots from newborn screening cards to quantify miRNAs expression levels could be an early and minimally invasive predictive tool for these metabolic alterations.