Intrauterine growth restriction (IUGR) and fetal growth restriction (FGR) are pregnancy complications associated with morbidity in later life. Despite a growing body of evidence from current research on developmental origins of health and disease (DOHaD), little information is currently provided to parents on long-term metabolic, cardiovascular and neurologic consequences. As parents strongly rely on internet-based health-related information, we examined the quality of information on IUGR/FGR sequelae and DOHaD in webpages used by laypersons. Simulating non-clinicians experience, we entered the terms ‘IUGR consequences’ and ‘FGR consequences’ into Google and Yahoo search engines. The quality of the top search-hits was analyzed with regard to the certification through the Health On the Net Foundation (HON), currentness of cited references, while reliability of information and DOHaD-related consequences were assessed via the DISCERN Plus score (DPS). Overall the citation status was not up-to-date and only a few websites were HON-certified. The results of our analysis showed a dichotomy between the growing body of evidence regarding IUGR/FGR-related sequelae and lack of current guidelines, leaving parents without clear directions. Furthermore, detailed information on the concept of DOHaD is not provided. These findings emphasize the responsibility of the individual physician for providing advice on IUGR/FGR-related sequelae, monitoring and follow-up.

There is some evidence that perinatal factors, specifically birth weight (BW), may be related to the onset of prostate cancer (PRCA). This case–control study, nested within the Malmö Diet and Cancer Cohort Study, used archived birth record data from 308 incident PRCA cases diagnosed between 1991 and 2005, and 637 age-matched controls among 4781 men born (1923–1945) in Malmö and Lund, Sweden. We applied conditional logistic regression to examine the birth size–PRCA association, including tumour subtypes, adjusting for perinatal and adult factors. Compared with controls, cases had a non-significantly higher mean BW and were more likely to have high (>4000 g) BW (21% v. 18%), but did not differ in other birth size measures, nor in mean adult body mass index . We observed a non-linear association between BW and PRCA risk. Compared with BWs between 3000 and 3500 g (reference), the fully adjusted odds ratios (OR, 95% CI) were 0.55 (0.33–0.91) for <3000 g, 0.86 (0.61–1.22) for 3500–4000 g and 0.98 (0.64–1.50) for >4000 g. Among men with aggressive tumours, the reduction in risk for those with BWs <3000 g (OR 0.26, 95% CI 0.09–0.72) was stronger than the rate of risk for PRCA overall. Crude risk estimates were minimally attenuated when adjusted for gestational age, maternal age, birth order and adult factors. Birth length, head circumference and placental weight were not associated with prostate cancer. Our results indicate a protective effect of lower BW on risk of total and aggressive prostate cancer, rather than any direct effect of larger birth size.

We examined the association between life course body weight percentile trajectories and risk for preterm delivery (PTD). Data about women’s weight at birth, age 18, and before pregnancy were obtained by retrospective self-report in a cohort of 1410 black women in metropolitan Detroit. Growth mixture models were used to categorize women with similar weight percentile trajectories across these time points. Log-Poisson models were used to examine the association between the trajectory groups and PTD. Four trajectory groups with different beginning and endpoints of their weight percentiles (high-high, high-low, low-high and low-low) best fit the data. The groups with the highest prevalence of PTD were those that started low (low-high, 21%; low-low, 18%). The low-high group had a higher prevalence of PTD than the high-high trajectory group in unadjusted models (prevalence ratio=1.49 [95% confidence interval (CI) 1.11, 2.00]). The association became not significant after adjusting for maternal age at delivery, income, diabetes and hypertension. When compared with the high-high trajectory group, the low-low trajectory seemed to also have a higher prevalence of PTD after adjusting for maternal age at delivery, income, diabetes and hypertension (prevalence ratio=1.35 [95% CI 1.00, 1.83]). Results suggest that a woman’s risk for PTD is influenced by her body weight trajectory across the life course.

Fructose (C6H12O6) is acutely obesogenic and is a risk factor for hypertension, cardiovascular disease, and nonalcoholic fatty liver disease. However, the possible long-lasting effects of early-life fructose consumption have not been studied. We tested for effects of early-life fructose and/or wheel access (voluntary exercise) in a line of selectively bred High Runner (HR) mice and a non-selected Control (C) line. Exposures began at weaning and continued for 3 weeks to sexual maturity, followed by a 23-week "washout" period (equivalent to ∼17 human years). Fructose increased total caloric intake, body mass, and body fat during juvenile exposure, but had no effect on juvenile wheel running and no important lasting effects on adult physical activity or body weight/composition. Interestingly, adult maximal aerobic capacity (VO2max) was reduced in mice that had early-life fructose and wheel access. Consistent with previous studies, early-life exercise promoted adult wheel running. In a 3-way interaction, C mice that had early-life fructose and no wheel access gained body mass in response to 2 weeks of adult wheel access, while all other groups lost mass. Overall, we found some long-lasting positive effects of early-life exercise, but minimal effects of early-life fructose, regardless of the mouse line.

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.

Maternal prenatal diet can exert a powerful influence on the health of children when they reach adulthood – an orienting phenomenon in the Developmental Origins of Health and Disease research paradigm. Similar to other subsistence-based communities experiencing a rapid nutrition transition, obesity is increasing among Yup’ik Alaskans. Diabetes prevalence, however, remains relatively low and may reflect developmental nutritional processes that have yet to be thoroughly considered. Here we investigate recall of Yup’ik women’s diets during a past pregnancy using a mixed-methods approach as a critical first step in exploring such alternative developmental hypotheses. For certain populations, retrospective dietary reports might be the only source of information on factors relevant to understanding developmental pathways to health and disease. Our analysis identified community-specific factors that will likely improve the accuracy of future retrospective dietary analyses investigating the role of prenatal nutrition in the developmental origins of metabolic disease, especially among Alaska Natives.

The early-life origins of disease hypothesis has been applied to obesity research and modeled through overnutrition, usually with a high-fat diet (HFD). Since the obesity epidemic coincided with societal change in dietary fat consumption, rather than amount, manipulation of fatty acid (FA) profile is an under-investigated area of study. Additionally, the binding of FAs to nuclear receptors may have persistent intergenerational, extranutritive endocrinological effects that interact with the actions of reproductive steroids causing sex-dependent effects. To determine the role of FA type in the effects underlying maternal HFD, we fed wild-type C57BL6/J mating pairs, from preconception through lactation, a HFD with high saturated fat levels from coconut oil or high linoleic acid (LA) levels from vegetable oil. Male and female offspring body weight and food intake were measured weekly for 25 weeks. Assays for glucose metabolism, body composition, and calorimetry were performed at 25 weeks. Plasma metabolic peptides and liver mRNA were measured terminally. Obesity was primarily affected by adult rather than maternal diet in males, yet in females, maternal HFD potentiated the effects of adult HFD. Maternal HFD high in LA impaired glucose disposal in males weaned onto HFD and insulin sensitivity of females. Plasma leptin correlated with adiposity, but insulin and insulin receptor expression in the liver were altered by maternal LA in males. Our results suggest that maternal FA profile is most influential on offspring glucose metabolism and that adult diet is more important than maternal diet for obesity and other parameters of metabolic syndrome.

Previous studies have suggested that maternal active smoking can increase the risk of birth defects, but evidence on second-hand tobacco smoke (SHS) is limited. We aimed to assess the association between maternal exposure to SHS and birth defects in a Chinese population. The data were based on a large-scale cross-sectional survey conducted in Shaanxi Province, China. Considering the characteristics of survey design and the potential impact of confounding factors, we adopted propensity score matching (PSM) to match the SHS exposure group and the non-exposure group to attain a balance of the confounders between the two groups. Subsequently, conditional logistic regression was employed to estimate the effect of SHS exposure on birth defects. Furthermore, sensitivity analyses were conducted to verify the key findings. After nearest neighbor matching of PSM with a ratio of 2 and a caliper width of 0.03, there were 6,205 and 12,410 participants in the exposure and control group, respectively. Pregnant women exposed to SHS were estimated to be 58% more likely to have infants with overall birth defects (OR = 1.58, 95% CI: 1.30–1.91) and 75% more likely to have infants with circulatory system defects (OR = 1.75, 95% CI: 1.26–2.44). We also observed that the risk effect of overall birth defects had an increasing trend as the frequency of exposure increased. Additionally, sensitivity analyses suggested that our results had good robustness. These results indicate that maternal exposure to SHS likely increases the risk of overall birth defects, especially circulatory system defects, in Chinese offspring.

It is estimated that 80% of the world population trusts traditional medicine. A large number of Americans use infusions of Bocconia frutescens L. leaves to treat cough and gastrointestinal disorders. However, phytochemical studies reveal that this plant contains alkaloids and other potentially harmful substances. This study aimed to evaluate the teratogenic effects of B. frutescens L. in an experimental model. Pregnant Wistar rats were administered lyophilized B. frutescens L. extract at 300 mg/kg/day or vehicle by orogastric route during the organogenesis period (gestation days 7–13), and external and internal congenital malformations were analyzed on the progeny on gestational day 20. Bocconia frutescens L. produced a significant increase in the number of different malformations, relative to the control group. We conclude that the consumption of B. frutescens L. during pregnancy at a dose equivalent to that consumed by humans increases the risk of teratogenic effects.

There is an accumulating data that shows relation between childhood adversity and vulnerability to chronic diseases as well as epigenetic influences that in turn give rise to these diseases. Asthma is one of the chronic diseases that is influenced from genetic regulation of the inflammatory biomolecules and therefore the hypothesis in this research was childhood adversity might have caused epigenetic differentiation in the asthma-related genes in the population who had childhood trauma. To test this hypothesis, the literature was systematically reviewed to extract epigenetically modified gene data of the adults who had childhood adversity, and affected genes were further evaluated for their association with asthma. PRISMA guidelines were adopted and PubMed and Google Scholar were included in the searched databases, to evaluate epigenetic modifications in asthma-related genes of physically, emotionally or sexually abused children. After retrieving a total of 5245 articles, 36 of them were included in the study. Several genes and pathways that may contribute to pathogenesis of asthma development, increased inflammation, or response to asthma treatment were found epigenetically affected by childhood traumas. Childhood adversity, causing epigenetic changes in DNA, may lead to asthma development or influence the course of the disease and therefore should be taken into account for the prolonged health consequences.

The in utero and immediate postnatal environments are recognized as critical windows of developmental plasticity where offspring are highly susceptible to changes in the maternal metabolic milieu. Maternal hypercholesterolemia (MHC) is a pathological condition characterized by an exaggerated rise in maternal serum cholesterol during pregnancy which can program metabolic dysfunction in offspring, including dysregulation of hepatic lipid metabolism. Although there is currently no established reference range MHC, a loosely defined cutoff point for total cholesterol >280 mg/dL in the third trimester has been suggested. There are several unanswered questions regarding this condition particularly with regard to how the timing of cholesterol exposure influences hepatic lipid dysfunction and the mechanisms through which these adaptations manifest in adulthood. Gestational hypercholesterolemia increased fetal hepatic lipid concentrations and altered lipid regulatory mRNA and protein content. These early changes in hepatic lipid metabolism are evident in the postweaning environment and persist into adulthood. Further, changes to hepatic epigenetic signatures including microRNA (miR) and DNA methylation are observed in utero, at weaning, and are evident in adult offspring. In conclusion, early exposure to cholesterol during critical developmental periods can predispose offspring to the early development of nonalcoholic fatty liver disease (NAFLD) which is characterized by altered regulatory function beginning in utero and persisting throughout the life cycle.

Many studies have reported on relations between birth size and adult size but the findings to date are hard to compare due to the lack of uniform measures across studies. Interpretation of findings is also hampered by potential confounding by ethnic, socioeconomic and family factors. The purpose of this study is to explore these relationships in a comprehensive fashion, with multiple measures of birth size and adult size, using same-sex sibling controls discordant in birth weight to address potential confounding at the family level. Study subjects include pregnant women enrolled during 1959–1966 in the Child Health and Development Study in Oakland, CA and the Boston, MA, and providence, RI, sites of the Collaborative Perinatal Project in New England, currently combined into the New England Family Study. We assessed 392 offspring (mean age 43 years), the great majority as sibships as available. Our analyses confirm the positive association between birth weight and adult length reported in other studies, with a change in adult height of 1.25 cm (95% CI: 0.79 to 1.70 cm) for each quintile change in standardized birth weight. No associations were seen between birth weight and adult fatness for which findings in other studies are highly variable. As adult weight is likely to reflect recent variations in the adult nutritional environment rather than the early environment, it may be more useful for studies of birth size and adult size to focus on adult length rather than weight measures in evaluating the role of early influences on adult health.

In the last decades, obesity and nonalcoholic fatty liver disease (NAFLD) have become increasingly prevalent in wide world. Fatty liver can be detrimental to liver regeneration (LR) and offspring of obese dams (HFD-O) are susceptible to NAFLD development. Here we evaluated LR capacity in HFD-O after partial hepatectomy (PHx). HFD-O re-exposed or not to HFD in later life were evaluated for metabolic parameters, inflammation, proliferation, tissue repair markers and survival rate after PHx. Increasing adiposity and fatty liver were observed in HFD-O. Despite lower IL-6 levels, Ki67 labeling, cells in S phase and Ciclin D1/PCNA protein content, a lower impact on survival rate was found after PHx, even when re-exposed to HFD. However, no difference was observed between offspring of control dams (SC-O) and HFD-O after surgery. Although LR impairment is dependent of steatosis development, offspring of obese dams are programmed to be protected from the damage promoted by HFD.

Cell-free fetal DNA in maternal circulation is higher during preeclampsia. It is unclear whether it is the cause or the consequence of the disease. The aim of this study was to prove whether injected rat fetal DNA induces preeclampsia-like symptoms in pregnant Wistar rats. They received daily i.p. injections of water or rat fetal DNA (400 μg) from gestation day 14 to 18. Blood pressure, proteinuria, placental and fetal weight were measured at gestation day 19. Plasma DNase activity, proteinuria and creatinine clearance were assessed. There was no significant difference in any of the measured parameters. The results of this study do not confirm the hypothesis that fetal DNA might induce preeclampsia. This is in contrast to others using human fetal DNA in mice. Further studies should be focused on the effects of fetal DNA from the same species protected from DNase activity.

Maternal prenatal psychological distress, including depression and anxiety, may affect offspring’s motor/cognitive development. However, research findings have been inconsistent. We used a dataset from the Japan Environment and Children’s Study to evaluate associations between maternal six-item Kessler Psychological Distress Scale (K6) scores and motor/cognitive development among offspring at two years of age. Their offspring’s motor/cognitive development was assessed using the Kyoto Scale of Psychological Development 2001. Records for 1859 male and 1817 female offspring were analyzed. The maternal K6 was administered twice during pregnancy: at a median of 14.6 weeks (M-T1) and 27.3 weeks (M-T2) of gestation. Multiple regression analysis was performed with the group with K6 scores ≤4 at both M-T1 and M-T2 as a reference. In the group with K6 scores ≥5 at both M-T1 and M-T2, male offspring had significantly lower developmental quotients (DQ) in the posture-motor area (partial regression coefficient [B]: −3.68, 95% confidence interval [CI]: −5.92 to −1.44) and language-social area (B: −1.93; 95%CI: −3.73 to −0.12), while female offspring had a lower DQ for the language-social area (B: −1.95; 95%CI: −3.73 to −0.17). In those with K6 scores ≥5 only at M-T1 or M-T2, male and female offspring did not differ significantly in DQ for any area. Continuous maternal psychological distress from the first to the second half of pregnancy was associated with lower motor and verbal cognitive development in male offspring and lower verbal cognitive development in female offspring at 2 years compared with the group without persistent maternal prenatal psychological distress.

Experimental data on the effects of lifestyle interventions on fetal neurodevelopment in humans remain scarce. This study assessed the impact of a pregnancy nutrition+exercise intervention on offspring neurodevelopment at 12 months of age. The Be Healthy in Pregnancy (BHIP) randomized controlled trial (RCT) randomly assigned pregnant persons with stratification by site and body mass index (BMI) to bi-weekly nutrition counselling and high dairy protein diet, walking goal of 10,000 steps/day plus usual prenatal care (UPC; intervention group) or UPC alone (control group). This study examined a subset of these mothers (> 18 years, singleton pregnancy, BMI <40 kg/m2, and enrolled by ≤12 weeks gestation) and their infants (intervention = 42, control = 32), assessing cognition, language, motor, social-emotional, and adaptive functioning at 12 months using the Bayley Scales of Infant and Toddler Development third edition (BSID-III) as the outcome measure. We also examined if maternal factors (prepregnancy BMI, gestational weight gain (GWG)) moderated associations. Expressive language (MD = 9.62, 95% CI = (9.05–10.18), p = 0.03, ƞ2p = 0.07) and general adaptive composite (GAC) scores (MD = 103.97, 95% CI = (100.31–107.63), p = 0.04, ƞ2p = 0.06) were higher in infants of mothers in the intervention group. Effect sizes were medium. However, mean cognitive, receptive language, motor, and social-emotional scale scores did not differ between groups. A structured and monitored nutrition+exercise intervention during pregnancy led to improved expressive language and general adaptive behavior in 12-month-olds, but not cognitive, receptive language, motor, or socioemotional functioning. While these experimental data are promising, further research is needed to determine the clinical utility of nutrition+exercise interventions for optimizing infant neurodevelopment.

Preterm birth has been associated with insulin resistance and beta-cell dysfunction, a hallmark characteristic of type 2 diabetes. However, studies investigating the relationship between a personal history of being born preterm and type 2 diabetes are sparse. We sought to investigate the potential association between a personal history of being born preterm and risk for type 2 diabetes in a racially and ethnically diverse population. Baseline and incident data (>16 years of follow-up) from the Women’s Health Initiative (n = 85,356) were used to examine the association between personal history of being born preterm (born 1910–1940s) and prevalent (baseline enrollment; cross-sectional) or incident (prospective cohort) cases of type 2 diabetes. Logistic and Cox proportional hazards regression models were used to estimate odds and hazards ratios. Being born preterm was significantly, positively associated with odds for prevalent type 2 diabetes at enrollment (adjOR = 1.79, 95% CI 1.43–2.24; P < 0.0001). Stratified regression models suggested the positive associations at baseline were consistent across race and ethnicity groups. However, being born preterm was not significantly associated with risk for incident type 2 diabetes. Regression models stratified by age at enrollment suggest the relationship between being born preterm and type 2 diabetes persists only among younger age groups. Preterm birth was associated with higher risk of type 2 diabetes but only in those diagnosed with type 2 diabetes prior to study enrollment, suggesting the association between preterm birth and type 2 diabetes may exist at earlier age of diagnosis but wane over time.

Epidemiological studies suggest that glucocorticoid excess in the fetus may contribute to the pathophysiology of cardiovascular diseases in adulthood. However, the impact of maternal glucocorticoid on the cardiovascular system of the offspring has not been much explored in studies involving humans, especially in childhood. The objective of this study was to assess the influence of maternal cortisol concentrations on child arterial elasticity. One hundred and thirty pregnant women followed from 1997 to 2000, and respective children 5–7 years of age followed from 2004 to 2006 were included in the study. Maternal cortisol was determined in saliva by an enzyme immunoassay utilizing the mean concentration of nine samples of saliva. Arterial elasticity was assessed by the large artery elasticity index (LAEI; the capacitive elasticity of large arteries) by recording radial artery pulse wave, utilizing the equipment HDI/PulseWave CR-2000 Cardiovascular Profiling System®. The nutritional status of the children was determined by the body mass index (BMI). Insulin concentration was assessed by chemiluminescence, and insulin resistance by the homeostasis model assessment. Blood glucose, total cholesterol and fractions (LDL-c and HDL-c) and triglyceride concentrations were determined by automated enzymatic methods. The association between maternal cortisol and child arterial elasticity was assessed by multivariate linear regression analysis. There was a statistically significant association between maternal cortisol and LAEI (P = 0.02), controlling for birth weight, age, BMI and HDL-c of the children. This study suggests that exposure to higher glucocorticoid concentrations in the prenatal period is associated to lower arterial elasticity in childhood, an earlier cardiovascular risk marker.

There is little record of birth weight of Irish Travellers, a minority group in Ireland. Travellers are known to have higher rate of adult chronic disease and to be exposed to life-long disadvantage. The aim of this study was to establish whether the birth weight and infant mortality rate patterns in Ireland's Travellers were consistent with the developmental plasticity hypothesis. A 1-year follow-up birth cohort study was conducted with linkage data from maternity hospital records of Traveller infants born on the island of Ireland over a 12-month period to self-identifying Traveller and general Irish population mothers from the Lifeways Cross-Generation Cohort Study. The main outcome measure was the rate of birth weight <3000 g in a cohort of Traveller children. There were 987 confirmed Traveller births, 500 of whose mothers consented to linkage to their records. A social gradient was observed in the distribution of birth weight in the general population and Traveller infants constituted the highest proportion of all social classes in the birth weight range of 3 kg or less (16.3%). There was a high rate of persistent smoking among Traveller mothers (53%). After adjustment for smoking and alcohol consumption in pregnancy, the birth weight differential persisted (OR 3.5, 95% CI 1.4–8.1). Infant mortality rate at 12.0/1000 births (95% CI 5.5–19.7) was almost four times that of the general population. This analysis confirms Travellers had a greater than expected incidence of low birth weight and high infant mortality with high rates of premature adult chronic diseases from all causes already demonstrated previously.

Individuals born small have an increased risk for developing type 2 diabetes. Altered food preferences in these subjects seem to play a role; however, limited evidence is available on the association between being born small-for-gestational-age (SGA) at term and food intake in adolescence. Alterations in leptin, ghrelin and dopamine levels are suggested mechanisms linking SGA with later food intake. From a large prospective Danish National Birth Cohort, we compared dietary intake of adolescents being born SGA with normal-for-gestational-age (NGA) adolescents. Intake of foods and nutrients was assessed by a validated food frequency questionnaire in a subsample of 15,607 14-year-old individuals born at term. SGA was defined by birth weight (BW) <10th percentile (n = 1470) and NGA as BW between 10 and 90th percentile (n = 14,137) according to sex and gestational age-specific BW standard curves. Girls born SGA had a 7% (95% CI: 3–12%, P = 0.002) higher intake of added sugar and a 2–8% lower intake of dietary fibre, vegetables, polyunsaturated fatty acids, and total n−6, compared with NGA girls (P < 0.05). Adjusting for parental socio-occupational status, maternal smoking and diet in pregnancy did not substantially change the differences in dietary intake, except from dietary fibre, which were no longer statistically significant. No significant differences in dietary intake between SGA and NGA boys were found. In summary, girls born SGA had an unfavourable dietary intake compared with NGA girls. These differences persisted after controlling for potential confounders, thus supporting a fetal programming effect on dietary intake in girls born SGA at term. However, residual confounding by other factors operating early in childhood cannot be excluded.