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In this paper, meant to stimulate debate, we argue that there is considerable benefit in approaching together the implementation of two seemingly separate recent developments. First, on the global development agenda, we have the United Nations General Assembly’s 2015 finalized list of 17 Sustainable Development Goals (SDGs). Several of the SDGs are related to health. Second, the field of Developmental Origins of Health and Disease (DOHaD) has garnered enough compelling evidence demonstrating that early exposures in life affect not only future health, but that the effects of that exposure can be transmitted across generations – necessitating that we begin to focus on prevention. We argue that implementing the SDGs and DOHaD together will be beneficial in several ways; and will require attending to multiple, complex and multidisciplinary approaches as we reach the point of translating science to policy to impact. Here, we begin by providing the context for our work and making the case for a mutually reinforcing, synergistic approach to implementing SDGs and DOHaD, particularly in Africa. To do this, we initiate discussion via an early mapping of some of the overlapping considerations between SDGs and DOHaD.
Pregnant women, children under 2 and the first thousand days of life have been principal targets for Developmental Origins of Health and Disease interventions. This paradigm has been criticized for laying responsibility for health outcomes on pregnant women and mothers and through the thousand days focus inadvertently deflecting attention from other windows for intervention. Drawing on insights from the South African context, this commentary argues for integrated and inclusive interventions that encompass broader social framings. First, future interventions should include a wider range of actors. Second, broader action frameworks should encompass life-course approaches that identify multiple windows of opportunity for intervention. Using two examples – the inclusion of men, and engagement with adolescents – this commentary offers strategies for producing more inclusive interventions by using a broader social framework.
Footprints in Time: The Longitudinal Study of Indigenous Children (LSIC) is a national study of 1759 Australian Aboriginal and Torres Strait Islander children living across urban, regional and remote areas of Australia. The study is in its 11th wave of annual data collection, having collected extensive data on topics including birth and early life influences, parental health and well-being, identity, cultural engagement, language use, housing, racism, school engagement and academic achievement, and social and emotional well-being. The current paper reviews a selection of major findings from Footprints in Time relating to the developmental origins of health and disease for Australian Aboriginal and Torres Strait Islander peoples. Opportunities for new researchers to conduct further research utilizing the LSIC data set are also presented.
Studies in urban informal settlements show widespread inappropriate infant and young child feeding (IYCF) practices and high rates of food insecurity. This study assessed the association between household food security and IYCF practices in two urban informal settlements in Nairobi, Kenya. The study adopted a longitudinal design that involved a census sample of 1110 children less than 12 months of age and their mothers aged between 12 and 49 years. A questionnaire was used to collect information on: IYCF practices and household food security. Logistic regression was used to determine the association between food insecurity and IYFC practices. The findings showed high household food insecurity; only 19.5% of the households were food secure based on Household Insecurity Access Score. Infant feeding practices were inappropriate: 76% attained minimum meal frequency; 41% of the children attained a minimum dietary diversity; and 27% attained minimum acceptable diet. With the exception of the minimum meal frequency, infants living in food secure households were significantly more likely to achieve appropriate infant feeding practices than those in food insecure households: minimum meal frequency (adjusted odds ratio (AOR)=1.26, P=0.530); minimum dietary diversity (AOR=1.84, P=0.046) and minimum acceptable diet (AOR=2.35, P=0.008). The study adds to the existing body of knowledge by demonstrating an association between household food security and infant feeding practices in low-income settings. The findings imply that interventions aimed at improving infant feeding practices and ultimately nutritional status need to also focus on improving household food security.
Depression and anxiety in the antenatal period are of public health concern given potential adverse effects for both mother and infant. Both are under-researched in the first trimester of pregnancy, especially in Africa. We examine the prevalence of first trimester antenatal depression and anxiety in a cohort of South African women and investigate associated risk factors. Data were collected from 946 women (2014–2016) in the Soweto First 1000 Days Cohort, a prospective pregnancy cohort in Soweto, South Africa. Antenatal depression was assessed using the Edinburgh Postnatal Depression Scale with a score of ⩾13 indicating probable depression. Anxiety was assessed using the short form of the State-Trait Anxiety Index with a score ⩾12 indicating probable anxiety. Prevalence of antenatal depression was 27% [95% confidence interval (CI) 24.2–29.8] and anxiety 15.2% (95% CI 12.9–17.5). Factors associated with antenatal depression and anxiety were predominantly relationship- and family-centred. Women who perceived that their partner made life harder for them had three-fold increased odds for depression [(odds ratio (OR) 3.33 [2.28–4.85] P<0.001], whereas those with family stressors had almost double the odds for depression (OR 1.78 [1.22–2.59] P=0.003) and anxiety (OR 1.75 [1.44–2.69] P=0.0011). Antenatal depression and anxiety are common in the first trimester of pregnancy, and partner and family relationship stressors are central. Longitudinal analysis is needed to determine if this is a phase of adjustment to pregnancy or onset of persistent symptomology. Early intervention may have secondary preventative effects and should involve the partner and family.
Barker et al. proposed that low birth weight predisposes to higher death rates in adult life. We previously confirmed this fact in a cohort of young adults who were born in a remote Australian Aboriginal community between 1956 and 1985. We now present data in these same people with four more years of follow-up and a greater number of deaths. The fates of participants were documented from age 15 years until death, start of dialysis, or until the end of 2010 and causes of death were derived from clinic narratives and dialysis records. Rates of natural deaths were compared by birth cohorts and birth weight, and hazard ratios were calculated using Cox proportional hazards methods, by birth weight and adjusted for birth cohort and sex. Over follow-up of 19,661 person-years, 61 people died of natural causes between age 15 and the censor date. Low birth weights (<2.5 kg) were associated with higher rates of natural death, with HR (95% CI) 1.76 (1.1–2.9, P=0.03), after adjustment for year of birth and sex. The effect was particularly prominent for deaths at <41 years of age, and with deaths from respiratory conditions/sepsis and unusual causes. A predisposing effect of low birth weight on adult deaths was confirmed. This phenomenon, occurring in the context of dramatically improved survivals of lower birth weight infants and children since the early 1960s, helps explain the current epidemic of chronic disease in Aboriginal people. Birth weights continue to improve, so excess deaths from this source should progressively be minimized.
Maternal adversity and fetal glucocorticoid exposure has long-term effects on cardiovascular, metabolic and behavioral systems in offspring that can persist throughout the lifespan. These data, along with other environmental exposure data, implicate epigenetic modifications as potential mechanisms for long-term effects of maternal exposures on adverse health outcomes in offspring. Advances in microarray, sequencing and bioinformatic approaches have enabled recent studies to examine the genome-wide epigenetic response to maternal adversity. Studies of maternal exposures to xenobiotics such as arsenic and smoking have been performed at birth to examine fetal epigenomic signatures in cord blood relating to adult health outcomes. However, there have been no epigenomic studies examining these effects in animal models. On the other hand, to date, only a few studies of the effects of maternal psychosocial stress have been performed in human infants, and the majority of animal studies have examined epigenomic outcomes in adulthood. In terms of maternal exposure to excess glucocorticoids by synthetic glucocorticoid treatment, there has been no epigenetic study performed in humans and only a few studies undertaken in animal models. This review emphasizes the importance of examining biomarkers of exposure to adversity throughout development to identify individuals at risk and to target interventions. Thus, research performed at birth will be reviewed. In addition, potential subject characteristics associated with epigenetic modifications, technical considerations, the selection of target tissues and combining human studies with animal models will be discussed in relation to the design of experiments in this field of study.
Children of parents with major mood and psychotic disorders are at increased risk of psychopathology, including psychotic symptoms. It has been suggested that the risk of psychosis may be more often transmitted from parent to opposite-sex offspring (e.g., from father to daughter) than to same-sex offspring (e.g., from father to son). To test whether sex-specific transmission extends to early manifestations of psychosis, we examined sex-specific contributions to psychotic symptoms among offspring of mothers and fathers with depression, bipolar disorder and schizophrenia. We assessed psychotic symptoms in 309 offspring (160 daughters and 149 sons) aged 8–24 years (mean=13.1, s.d.=4.3), of whom 113 had a mother with schizophrenia, bipolar disorder or major depression and 43 had a father with schizophrenia, bipolar disorder or major depression. In semi-structured interviews, 130 (42%) offspring had definite psychotic symptoms established and confirmed by psychiatrists on one or more assessments. We tested the effects of mental illness in parents on same-sex and opposite-sex offspring psychotic symptoms in mixed-effect logistic regression models. Psychotic symptoms were more prevalent among daughters of affected fathers and sons of affected mothers than among offspring of the same sex as their affected parent. Mental illness in the opposite-sex parent increased the odds of psychotic symptoms (odds ratio (OR)=2.65, 95% confidence interval (CI) 1.43–4.91, P=0.002), but mental illness in the same-sex parent did not have a significant effect on psychotic symptoms in offspring (OR=1.13, 95% CI 0.61–2.07, P=0.697). The opposite-sex-specific parent-of-origin effects may suggest X chromosome-linked genetic transmission or inherited chromosomal modifications in the etiology of psychotic symptoms.
Despite progress in gender equality, women continue to be disadvantaged compared with men. Worldwide, women are more often confronted with poverty, violence, and mental health problems, and they have less access to food and education. All these factors do not only affect women themselves, but also have a negative impact on the child’s early environment and impair its early development, thereby reducing the health and well-being of future generations. Framing gender equality as a women’s issue fails to highlight the importance of gender equality for the health and well-being of the next generation. As a scientific community investigating early human development and health, we have failed to fully recognize and underscore the importance of gender equality in achieving the best possible start for every child. If women and men had equal rights and opportunities, their children would be more likely to reach their full potential which would improve the health and well-being of future generations. Our studies and interventions have not fully taken into account the complexity of gender inequality and women’s disadvantaged positions in society. We need better insight into the complex adaptive interactions between various societal and human factors contributing to gender inequality and find approaches that take this complexity into account. If we want DOHaD science to have societal impact, we should strive beyond gender equality for gender equity and help women achieve equal rights and opportunities. We need to work with public health professionals, human rights activists, and policymakers to gauge the importance of gender equality. After all, gender equality is not only a fundamental human right, but also a necessary foundation for healthier future generations.
Maternal physical activity induces brain functional changes and neuroplasticity, leading to an improvement of cognitive functions, such as learning and memory in the offspring. This study investigated the effects of voluntary maternal physical activity on the gene expression of the neurotrophic factors (NTFs): BDNF, NTF4, NTRK2, IGF-1 and IGF-1r in the different areas of mother’s brain, placenta and foetus brain of rats. Female Wistar rats (n = 15) were individually housed in voluntary physical activity cages, containing a running wheel, for 4 weeks (period of adaptation) before gestation. Rats were classified as inactive (I, n = 6); active (A, n = 4) and very active (VA, n = 5) according to daily distance spontaneously travelled. During gestation, the dams continued to have access to the running wheel. At the 20th day of gestation, gene expression of NTFs was analysed in different areas of mother’s brain (cerebellum, hypothalamus, hippocampus and cortex), placenta and the offspring’s brain. NTFs gene expression was evaluated using quantitative PCR. Very active mothers showed upregulation of IGF-1 mRNA in the cerebellum (36.8%) and NTF4 mRNA expression in the placenta (24.3%). In the cortex, there was a tendency of up-regulation of NTRK2 mRNA (p = 0.06) in the A and VA groups when compared to I group. There were no noticeable changes in the gene expression of NTFs in the offspring’s brain. Our findings suggest the existence of a developmental plasticity induced by maternal physical activity in specific areas of the brain and placenta representing the first investment for offspring during development.
Evidence suggests that low birth weight and fetal exposure to extreme maternal undernutrition is associated with cardiovascular disease in adulthood. Hyperemesis gravidarum, a clinical entity characterized by severe nausea and excess vomiting leading to a suboptimal maternal nutritional status during early pregnancy, is associated with an increased risk of adverse pregnancy outcomes. Several studies also showed that different measures related to hyperemesis gravidarum, such as maternal daily vomiting or severe weight loss, are associated with increased risks of adverse fetal pregnancy outcomes. Not much is known about long-term offspring consequences of maternal hyperemesis gravidarum and related measures during pregnancy. We examined the associations of maternal daily vomiting during early pregnancy, as a measure related to hyperemesis gravidarum, with childhood cardiovascular risk factors.
In a population-based prospective cohort study from early pregnancy onwards among 4,769 mothers and their children in Rotterdam, the Netherlands, we measured childhood body mass index, total fat mass percentage, android/gynoid fat mass ratio, preperitoneal fat mass area, blood pressure, lipids, and insulin levels. We used multiple regression analyses to assess the associations of maternal vomiting during early pregnancy with childhood cardiovascular outcomes.
Compared with the children of mothers without daily vomiting during early pregnancy, the children of mothers with daily vomiting during early pregnancy had a higher childhood total body fat mass (difference 0.12 standard deviation score [SDS]; 95% confidence interval [CI] 0.03–0.20), android/gynoid fat mass ratio (difference 0.13 SDS; 95% CI 0.04–0.23), and preperitoneal fat mass area (difference 0.10 SDS; 95% CI 0–0.20). These associations were not explained by birth characteristics but partly explained by higher infant growth. Maternal daily vomiting during early pregnancy was not associated with childhood blood pressure, lipids, and insulin levels.
Maternal daily vomiting during early pregnancy is associated with higher childhood total body fat mass and abdominal fat mass levels, but not with other cardiovascular risk factors. Further studies are needed to replicate these findings, to explore the underlying mechanisms and to assess the long-term consequences.
The Indian residential school (IRS) system in Canada ran for over a century until the last school closed in 1996. Conditions in the IRSs resulted in generations of Indigenous children being exposed to chronic childhood adversity. The current investigation used data from the 2008–2010 First Nations Regional Health Survey to explore whether parental IRS attendance was associated with suicidal thoughts and attempts in childhood, adolescence and in adulthood among a representative sample of First Nations peoples living on-reserve across Canada. Analyses of the adult sample in Study 1 (unweighted n=7716; weighted n=186,830) revealed that having a parent who attended IRS was linked with increased risk for suicidal thoughts and attempts in adolescence and adulthood. Although females were negatively affected by having a parent who attended IRS, the link with suicidal ideation in adulthood was greater for males. Analyses of the youth sample in Study 2 (unweighted n=2883; weighted n=30,190) confirmed that parental IRS attendance was associated with an increased risk for suicidal ideation and attempts. In contrast to the adult sample, parental IRS attendance had a significantly greater relation with suicidal ideation among female youth. A significant interaction also emerged between parental IRS attendance and age in the youth sample, with the influence of parental attendance being particularly strong among youth ages 12–14, compared with those 15–17 years. These results underscore the need for culturally relevant early interventions for the large proportions of Indigenous children and youth intergenerationally affected by IRSs and other collective traumas.
The thymus undergoes a critical period of growth and development early in gestation and, by mid-gestation, immature thymocytes are subject to positive and negative selection. Exposure to undernutrition during these periods may permanently affect phenotype. We measured thymulin concentrations, as a proxy for thymic size and function, in children (n = 290; aged 9–13 years) born to participants in a cluster-randomized trial of maternal vitamin A or β-carotene supplementation in rural Nepal (1994–1997). The geometric mean (95% confidence interval) thymulin concentration was 1.37 ng/ml (1.27, 1.47). A multivariate model of early-life exposures revealed a positive association with gestational age at delivery (β = 0.02; P = 0.05) and higher concentrations among children born to β-carotene-supplemented mothers (β = 0.19; P < 0.05). At ∼9–12 years of age, thymulin was positively associated with all anthropometric measures, with height retained in our multivariate model (β = 0.02; P < 0.001). There was significant seasonal variation: concentrations tended to be lower pre-monsoon (β = −0.13; P = 0.15), during the monsoon (β = −0.22; P = 0.04), and pre-harvest (β = −0.34; P = 0.01), relative to the post-harvest season. All early-life associations, except supplementation, were mediated in part by nutritional status at follow-up. Our findings underscore the known sensitivity of the thymus to nutrition, including potentially lasting effects of early nutritional exposures. The relevance of these findings to later disease risk remains to be explored, particularly given the role of thymulin in the neuroendocrine regulation of inflammation.
Little is known about the long-term effect of breastfeeding on dietary habits. We examined the association between breastfeeding duration and adherence to current dietary patterns of young women. This was a cross-sectional analysis of 587 healthy women aged ≤45 years, undergraduates or nutrition graduates. Maternal characteristics and breastfeeding duration [<6; 6–<12; ≥12 months (reference)] were recalled. Diet was assessed using a food frequency questionnaire and patterns were identified using factor analysis by principal component. Adherence to patterns was categorized in tertiles; the first (T1 = reference) was compared to T2 + T3 (moderate-to-high adherence). Logistic regression was performed considering the minimal sufficient adjustment recommended by the directed acyclic graph. Median age was 22 (interquartile range (IQR) 20; 27) years and body mass index (BMI) 22.2 (IQR 20.4; 25.0) kg/m2. The four dietary patterns identified (Processed, Prudent, Brazilian and Lacto-vegetarian) explained 27% of diet variance. Women breastfed for <6 months showed lower chance of moderate-to-high adherence to the Prudent pattern (odds ratio (OR) = 0.53, p = 0.04). Breastfeeding was not associated with the other patterns. Maternal pre-pregnancy BMI was directly associated with moderate-to-high adherence to the Processed pattern (OR = 2.01, p = 0.03) and inversely to the Prudent pattern (OR = 0.52, p = 0.02). Higher adherence to the Brazilian pattern was associated with proxies of low socioeconomic status and the Lacto-vegetarian pattern with the opposite. Confirmation in prospective studies of the association found in this study between breastfeeding with the Prudent pattern in adult offspring could suggest that early feeding practices influence long-term dietary habits, which could then affect the risk of nutrition-related diseases.
Low birth weight programs diseases in adulthood, including adverse bone health. These diseases can have intergenerational and transgenerational origins, whereby transmission to subsequent generations occurs via both parental lines. Uteroplacental insufficiency surgery (Restricted) or sham surgery (Control) was performed on gestational day 18, in F0 Wistar–Kyoto rats. F1 Restricted males and females mated with breeders in order to generate F2 offspring of maternal and paternal lineages. F2 males and females were randomly selected for breeding to generate F3 offspring. F2 and F3 offspring did not have differences in birth weight irrespective of F1 low birth weight and parental line. Maternal line females had minor alterations to trabecular content and density at 6 months, these differences were not sustained at 12 months. Maternal line males had changes to trabecular content at 6 and 12 months; however, differences were no longer present at 16 months. Despite altered bone geometry at 12 and 16 months, bending strength remained unaffected at both ages. Bone health of paternal line females was not affected at 6 and 12 months. Paternal line males at 6 months had changes to trabecular and cortical content; cortical thickness, periosteal circumference and bending strength; however, these differences were no longer sustained at 12 and 16 months. Our data demonstrate that there is no transgenerational transmission of adverse bone health in F2 and F3 offspring, derived from low F1 birth weight females and males. Our results are novel, as bone health across generations and both parental lines has not been investigated in a model of low birth weight due to uteroplacental insufficiency.
One of the most consumed pesticides in the world is glyphosate, the active ingredient in the herbicide ROUNDUP®. Studies demonstrate that glyphosate can act as an endocrine disruptor and that exposure to this substance at critical periods in the developmental period may program the fetus to induce reproductive damage in adulthood. Our hypothesis is that maternal exposure to glyphosate during pregnancy and lactation in mice will affect the development of male reproductive organs, impairing male fertility during adult life. Female mice consumed 0.5% glyphosate-ROUNDUP® in their drinking water [glyphosate-based herbicide (GBH) group] or filtered water [control (CTRL) group] from the fourth day of pregnancy until the end of the lactation period. Male F1 offspring were designated, according to their mother’s treatment, as CTRL-F1 and GBH-F1. Female mice that drank glyphosate displayed reduced body weight (BW) gain during gestation, but no alterations in litter size. Although GBH male F1 offspring did not exhibit modifications in BW, they demonstrated delayed testicular descent. Furthermore, at PND150, GBH-F1 mice presented a lower number of spermatozoa in the cauda epididymis and reduced epithelial height of the seminiferous epithelium. Notably, intratesticular testosterone concentrations were enhanced in GBH-F1 mice; we show that it is an effect associated with increased plasma and pituitary concentrations of luteinizing hormone. Therefore, data indicate that maternal exposure to glyphosate-ROUNDUP® during pregnancy and lactation may lead to decreased spermatogenesis and disruptions in hypothalamus–pituitary–testicular axis regulation in F1 offspring.