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.

Dietary protein restriction in pregnant females reduces offspring birth weight and increases the risk of developing obesity, type 2 diabetes and cardiovascular disease. Despite these grave consequences, few studies have addressed the effects of preconceptional maternal malnutrition. Here we investigate how a preconceptional low-protein (LP) diet affects offspring body mass and insulin-regulated glucose metabolism. Ten-week-old female mice (C57BL/6JBom) received either an LP or isocaloric control diet (8% and 22% crude protein, respectively) for 10 weeks before conception, but were thereafter fed standard laboratory chow (22.5% crude protein) during pregnancy, lactation and offspring growth. When the offspring were 10 weeks old, they were subjected to an intraperitoneal glucose tolerance test (GTT), and sacrificed after a 5-day recovery period to determine visceral organ mass. Body mass of LP male offspring was significantly lower at weaning compared with controls. A similar, nonsignificant, tendency was observed for LP female offspring. These differences in body mass disappeared within 1 week after weaning, a consequence of catch-up growth in LP offspring. GTTs of 10-week-old offspring revealed enhanced insulin sensitivity in LP offspring of both sexes. No differences were found in body mass, food intake or absolute size of visceral organs of adult offspring. Our results indicate that maternal protein restriction imposed before pregnancy produces effects similar to postconceptional malnutrition, namely, low birth weight, catch-up growth and enhanced insulin sensitivity at young adulthood. This could imply an increased risk of offspring developing lifestyle-acquired diseases during adulthood.

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.

While birth cohorts are shaped by underpinning life course frameworks, few if any report how they select them. This review aimed to (1) summarise publicly available frameworks relevant to planning and communicating large new early-life cohorts and (2) help select frameworks to guide and communicate Generation Victoria (GenV), a whole-of-state birth and parent cohort in planning in the state of Victoria, Australia. We identified potential frameworks from prior knowledge, networks and a pragmatic literature search in 2019. We considered for inclusion only frameworks with an existing visual graphic. We summarised each framework’s concept, then judged it on a seven-item matrix (Scope, Dimensions, Outcomes, Life course, Mechanisms, Multi-age, and Visual Clarity) to be of high, intermediate or low relevance to GenV. We presented and evaluated 14 life course frameworks across research and policy. Two, nine and three frameworks, respectively, were ranked as high, intermediate and low relevance to GenV, although none totally communicated its scope and intent. Shonkoff’s biodevelopmental framework was selected as GenV’s primary framework, adapted to include ongoing feedback loops through the life course and influence of an individual’s outcomes on the next generation. Because conceptual simplicity precluded the primary framework from capturing the wide range of relevant exposures, we selected the Australian Institute of Health and Welfare’s person-centred model as a secondary framework. This summary of existing life course frameworks may prove helpful to other cohorts in planning. Our transparent process and focus on visual communication are already assisting in explaining and selecting measures for GenV. The feasibility, comprehension and validity of these frameworks could be further tested at implementation.

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.

Although the association between stress and poor reproductive health is well established, this association has not been examined from a life course perspective. Using data from the National Longitudinal Survey of Youth 1997 cohort (N = 1652), we fit logistic regression models to test the association between stressful life events (SLEs) (e.g., death of a close relative, victim of a violent crime) during childhood, adolescence, and early adulthood and later experiences of infertility (inability to achieve pregnancy after 12 months of intercourse without contraception) reported by female respondents. Because reactions to SLEs may be moderated by different family life experiences, we stratified responses by maternal responsiveness (based on the Conger and Elder Parent-Youth Relationship scale) in adolescence. After adjusting for demographic and environmental factors, in comparison to respondents with one or zero SLEs, those with 3 SLEs and ≥ 4 SLEs had 1.68 (1.16, 2.42) and 1.88 (1.38, 2.57) times higher odds of infertility, respectively. Respondents with low maternal responsiveness had higher odds of infertility that increased in a dose–response manner. Among respondents with high maternal responsiveness, only those experiencing four or more SLEs had an elevated risk of infertility (aOR = 1.53; 1.05, 2.25). In this novel investigation, we demonstrate a temporal association between the experience of SLEs and self-reported infertility. This association varies by maternal responsiveness in adolescence, highlighting the importance of maternal behavior toward children in mitigating harms associated with stress over the life course.

Early weaning (EW) is associated with obesity later in life. Here, using an EW model in rats, we investigated changes in feeding behavior and the dopaminergic and endocannabinoid systems (ECS) in the adult offspring. Lactating Wistar rats were divided into two groups: EW, dams were wrapped with a bandage to interrupt suckling during the last 3 days of breastfeeding; CONT; dams fed the pups throughout the period without hindrances. EW animals were compared with CONT animals of the same sex. At PN175, male and female offspring of both groups could freely self-select between high-fat and high-sugar diets (food challenge test). EW males preferred the high-fat diet at 30 min and more of the high-sugar diet after 12 h compared to CONT males. EW females did not show differences in their preference for the palatable diets compared to CONT females. Total intake of standard diet from PN30-PN180 was higher in both male and female EW animals, indicating hyperphagia. At PN180, EW males showed lower type 2 dopamine receptor (D2r) in the nucleus accumbens (NAc) and dorsal striatum, while EW females had lower tyrosine hydroxylase in the ventral tegmental area and NAc, D1r in the NAc, and D2r in the prefrontal cortex. In the lateral hypothalamus, EW males had lower fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase, whereas EW females showed lower N-arachidonoyl-phosphatidylethanolamine phospholipase-D and increased FAAH. Early weaning altered both the dopaminergic and ECS parameters at adulthood, contributing to the eating behavior changes of the progeny in a sex-dependent manner.

This study aimed to assess the association between maternal-isolated oligohydramnios (IO) and offspring long-term neurological complications. A population-based retrospective cohort study was conducted, including all births at a single tertiary medical center in Israel between the years 1991 and 2014. Multiple pregnancies and potential pregnancy complications associated with oligohydramnios were excluded. The computerized obstetrical database was linked with the computerized dataset of all pediatric hospitalizations of the same medical center. Evaluation of cumulative neurological-associated hospitalizations rate over time was compared using a Kaplan–Meier survival curve. The Weibull survival parametric model was conducted to assess the neurological-associated hospitalization risk in the presence of IO, while accounting for potential confounders. A total of 190,259 pregnancies were included in the study, of which 4063 (2.13%) pregnancies were complicated with IO. Total neurological-related hospitalizations were significantly more common in the IO group (3.7% in the IO group and 3.0% in the comparison group, p = 0.005). Pervasive developmental disorder, movement disorders, developmental disorders, and degenerative and demyelization disorders were all specific neurological diagnoses significantly more common in the exposed group. The survival curve demonstrated a significantly higher cumulative hospitalization rate in the exposed group (log-rank p = 0.001). Using a multivariate model adjusting for gestational age, maternal age, and labor induction, an independent association between IO and long-term neurological morbidity of the offspring was observed (adjusted hazard ratio 1.203; 95% CI 1.02–1.42). In summary, a significant association was found between pregnancies complicated by IO and long-term neurological morbidity of the offspring.

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.

With type 2 diabetes presenting at younger ages, there is a growing need to identify biomarkers of future glucose intolerance. A high (20%) prevalence of glucose intolerance at 18 years was seen in women from the Pune Maternal Nutrition Study (PMNS) birth cohort. We investigated the potential of circulating microRNAs in risk stratification for future pre-diabetes in these women. Here, we provide preliminary longitudinal analyses of circulating microRNAs in normal glucose tolerant (NGT@18y, N = 10) and glucose intolerant (N = 8) women (ADA criteria) at 6, 12 and 17 years of their age using discovery analysis (OpenArray™ platform). Machine-learning workflows involving Lasso with bootstrapping/leave-one-out cross-validation identified microRNAs associated with glucose intolerance at 18 years of age. Several microRNAs, including miR-212-3p, miR-30e-3p and miR-638, stratified glucose-intolerant women from NGT at childhood. Our results suggest that circulating microRNAs, longitudinally assessed over 17 years of life, are dynamic biomarkers associated with and predictive of pre-diabetes at 18 years of age. Validation of these findings in males and remaining participants from the PMNS birth cohort will provide a unique opportunity to study novel epigenetic mechanisms in the life-course progression of glucose intolerance and enhance current clinical risk prediction of pre-diabetes and progression to type 2 diabetes.

Clinical depression is accompanied by changes in sleep patterning, which is controlled in a circadian fashion. It is thus desirable that animal models of depression mirror such diurnally-specific state alterations, along with other behavioral and physiological changes. We previously found several changes in behavior indicative of a depression-like phenotype in offspring of rats subjected to repeated, variable prenatal stress (PNS), including increased locomotor activity during specific periods of the circadian cycle. We, therefore, investigated whether PNS rats also exhibit alterations in sleep/wakefulness behavior around the change from light-to-dark phase. Control and PNS Sprague–Dawley rats were implanted with electrodes for continuous monitoring of electroencephalic activity used to determine behavioral state. The distribution of slow-wave sleep (SWS), rapid eye movement sleep (REMS) and wakefulness was compared for periods before and after lights were turned off, between baseline conditions and after exposure to an acute stressor. Both REMS and SWS amounts were increased in PNS rats relative to control animals in the beginning of the dark phase. REMS changes were due to an increase in REMS bout number, rather than in bout duration. During this circadian time period, we did not find any sex differences in the state changes. These results indicate that PNS affects baseline sleep patterning in both male and female rats around active-phase onset.

The objective of this study was to determine the association between birthweight and risk of thyroid and autoimmune conditions in a large sample of postmenopausal women. Baseline data from the Women’s Health Initiative (n = 80,806) were used to examine the associations between birthweight category (<6 lbs., 6–7 lbs. 15 oz, 8–9 lbs. 15 oz, and ≥10 lbs.) and prevalent thyroid (underactive and overactive thyroid and goiter) and autoimmune (lupus, rheumatoid arthritis (RA), multiple sclerosis, ulcerative colitis/Crohn’s disease) conditions. Follow-up questionnaire data were used to examine the associations between birthweight and incident underactive and overactive thyroid, lupus, and RA. Logistic and Cox proportional hazards regression models were used to estimate crude and adjusted odds (OR) and hazards ratios (HR), respectively. Overall, women born weighing ≥10 lbs. had an increased risk for underactive thyroid [OR 1.14 (95% CI 1.02, 1.28)] and incident lupus [HR 1.51 (95% CI 1.12, 2.03)] and a decreased risk for overactive thyroid [OR 0.67 (95% CI 0.50, 0.92)] compared to women born weighing 6–7.99 lbs., after adjustment for adult BMI, demographic variables, and lifestyle factors. Further, women born weighing <6 lbs. were at increased risk for underactive thyroid [OR 1.13 (95% CI 1.04, 1.22)]. Birthweight was not associated with other thyroid or autoimmune disorders. High birthweight was associated with later-life thyroid and autoimmune conditions while low birthweight was associated with underactive thyroid. Preconception and prenatal interventions aimed at reducing the risk of both high and low birthweights may reduce the burden of later-life thyroid and autoimmune conditions.

Emerging evidence suggests that parents’ nutritional status before and at the time of conception influences the lifelong physical and mental health of their child. Yet little is known about the relationship between diet in adolescence and the health of the next generation at birth. This study examined data from Norwegian cohorts to assess the relationship between dietary patterns in adolescence and neonatal outcomes. Data from adolescents who participated in the Nord-Trøndelag Health Study (Young-HUNT) were merged with birth data for their offspring through the Medical Birth Registry of Norway. Young-HUNT1 collected data from 8980 adolescents between 1995 and 1997. Linear regression was used to assess associations between adolescents’ diet and later neonatal outcomes of their offspring adjusting for sociodemographic factors. Analyses were replicated with data from the Young-HUNT3 cohort (dietary data collected from 2006 to 2008) and combined with Young-HUNT1 for pooled analyses. In Young-HUNT1, there was evidence of associations between dietary choices, meal patterns, and neonatal outcomes, these were similar in the pooled analyses but were attenuated to the point of nonsignificance in the smaller Young-HUNT3 cohort. Overall, energy-dense food products were associated with a small detrimental impact on some neonatal outcomes, whereas healthier food choices appeared protective. Our study suggests that there are causal links between consumption of healthy and unhealthy food and meal patterns in adolescence with neonatal outcomes for offspring some years later. The effects seen are small and will require even larger studies with more state-of-the-art dietary assessment to estimate these robustly.

According to the World Health Organization, smoking is the most important risk factor for adverse pregnancy outcomes in industrialized nations. We aimed to establish how fetal gender and smoking interact with regard to perinatal outcomes, especially preterm delivery. Data from 220,339 singleton pregnancies, obtained from the German Perinatal Survey in Schleswig-Holstein and registered between 2004 and 2017 were analyzed in regard to smoking behavior, fetal gender, and preterm delivery. The rate of preterm births was directly proportional to the women’s consumption of nicotine. The rate of preterm deliveries was 6.8% among nonsmokers, and 13.2% in women who were very heavy smokers (≥22 cigarettes/day). Very heavy smoking (≥22 cigarettes/day) had a marked impact on extremely preterm births (<28 weeks of gestation) and very preterm births (28–31 weeks of gestation). Preterm births increased by 1.2% from heavy smokers to very heavy smokers; the differences between the other groups ranged between 0.1% and 0.4%. Fetal gender also had an impact on preterm birth: male infants were predominant in nearly all groups of women who delivered preterm infants. Smoking during pregnancy and male gender are both risk factors for preterm delivery. Fetal gender should be given greater attention as one of the several risk factors of preterm birth. Due to the high rate of morbidity among preterm infants and enormous costs for the healthcare system, women should be encouraged to cease or at least reduce smoking during pregnancy.

Globally, mortality of Indigenous persons is greater than that of their non-Indigenous counterparts, which has been shown to be disproportionately attributable to non-communicable diseases. The historically subordinate position that Indigenous Knowledge (IK) held in comparison to Western science has shifted over the last several decades, with the credibility and importance of IK now being internationally recognized. Herein, we examine how Marsahall’s (2014) Two-Eyed Seeing can foster collaborative and culturally relevant Developmental Origins of Health and Disease (DOHaD) studies for health and well-being by using ‘..the best in Indigenous ways of knowing…[and] the best in Western (or mainstream) ways of knowing…and learn to use both these eyes for the benefit of all.’ At its core, Two-Eyed Seeing also includes the principles of ownership, control, access and possession, and Community-Based Participatory Research, which further reinforces the critical role of Indigenous peoples taking active roles in DOHaD research. Additionally, we also present a partnership model for working with Indigenous communities that includes the principles of respect, equity and empowerment. As researchers begin to fill the gap in Indigenous health, we outline how Two-Eyed Seeing should form the basis of DOHaD studies involving Indigenous communities. This model can be used to develop and guide projects that result in robust and meaningful participatory partnerships that have impactful uptake of research findings.

The content of omega-3 long-chain polyunsaturated fatty acids (n−3 LCPUFA) in chicken meat can be boosted by feeding broilers a diet containing α-linolenic acid (ALA, from flaxseed oil), some of which is converted by hepatic enzymes to n−3 LCPUFA. However, most of the accumulated n−3 polyunsaturated fatty acid (PUFA) in meat tissues is still in the form of ALA. Despite this, the levels of chicken diets are being enhanced by the inclusion of vegetable and marine sources of omega-3 fats. This study investigated whether the capacity of chicken for n−3 LCPUFA accumulation could be enhanced or inhibited by exposure to an increased supply of ALA or n−3 LCPUFA in ovo. Breeder hens were fed either flaxseed oil (High-ALA), fish oil (high n−3 LCPUFA) or tallow- (low n−3 PUFA, Control) based diets. The newly hatched chicks in each group were fed either the High-ALA or the Control diets until harvest at 42 days’ post-hatch. The n−3 PUFA content of egg yolk and day-old chick meat closely matched the n−3 PUFA composition of the maternal diet. In contrast, the n−3 PUFA composition of breast and leg meat tissues of the 42-day-old offspring closely matched the diet fed post-hatch, with no significant effect of maternal diet. Indeed, there was an inhibition of n−3 LCPUFA accumulation in meat of the broilers from the maternal Fish-Oil diet group when fed the post-hatch High-ALA diet. Therefore, this approach is not valid to elevate n-3 LCPUFA in chicken meat.

Risk factors associated with intrauterine growth restriction (IUGR) have previously been identified, but few studies have described the relationship between IUGR and maternal stress caused by exposure to civil unrest. Here, we investigate this relationship during the Mount Elgon crisis in western Kenya between 2006 and 2008, following a period of violence. Birth weight data were compared between three hospitals in an exposed area, Mount Elgon (n=570), and one hospital in a control area, Kimilili (n=530). In a sub-analysis, the most stress exposed hospital, Bungoma West (n=211), was compared with the control hospital in Kimilili. Adjustments were made for offspring sex, gestational age and parity. The difference in mean birth weight between the most stress-exposed hospital (Bungoma West) and the control hospital (Kimilili) was 91 g after full adjustment (P=0.041). In conclusion, epidemiological data suggest a significant relationship between exposure to civil unrest and IUGR causing lower birth weight.

The availability of clinically feasible infant body composition assessment can inform current questions regarding the developmental origins of chronic disease. A strategic approach will facilitate more rapid advancement in knowledge. The objective of this study was to summarize published evidence and ongoing research activity in infant body composition using the PEA POD® infant body composition system. All published studies using the PEA POD® were identified and grouped according to study population and question. All centers with PEA POD® units were invited to participate in an online survey regarding past, current and future PEA POD® use, and results were analyzed using descriptive statistics. The resulting information was used to identify gaps or limitations in existing knowledge, thus highlighting potential research priorities. Twenty-seven published articles were identified and grouped into six research themes. Although the number of infants studied is significant in some areas, interpretation of data is limited by methodological differences. Survey responses were received from 16 of ∼60 centers. Research themes echoed those identified from the published literature. Controlling for or reporting potential confounding variables is essential for understanding infant body composition data. Measurement of health outcome variables would be helpful in identifying associations.

Several studies have reported association of altered levels of lipids and some trace elements with risk factors for cardiovascular disease development in adulthood. Accordingly, the present study aimed to determine the relationship among the serum levels of copper (Cu), zinc (Zn), lipids, lipoproteins and apolipoproteins in preterm infants through an assessment of atherogenic indices shortly after birth. Blood samples were collected within 20 min of birth from 45 preterm infants with gestational ages ranging from 32 to 35 weeks. Serum Cu, Zn, total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc), apolipoprotein-A1 (apoA1) and apolipoprotein-B (apoB) levels were measured, and the TC/HDLc, LDLc/HDLc and apoB/apoA1 ratios were calculated. Upon determining the correlation between the levels of Cu, Zn and these indices of lipid metabolism, triglyceride (TG) and Cu were found to correlate negatively with birth weight (BW) and the standard deviation (s.d.) score for body weight. Furthermore, Cu levels correlated positively with the TG level and TC/HDLc, LDLc/HDLc and apoB/apoA1 ratios and negatively with the HDLc level and HDLc/apoA1 ratios. However, a stepwise multiple regression analysis indicated that the s.d. score for BW and TG level were significant independent determinants of the Cu level. In contrast, Zn did not correlate with any of these indices. In conclusion, intrauterine growth restriction and the TG level at birth influence Cu levels in preterm infants, whereas atherogenic indices do not affect this parameter.