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Prenatal dexamethasone has been shown to increase blood pressure in male offspring but the mechanism for the increase in blood pressure is unclear. The present study examined if prenatal programming by maternal injection of dexamethasone on days 15 and 16 of gestation affected the blood pressure comparably in female and male offspring. Our hypothesis was that males would be affected by prenatal dexamethasone to a greater extent than females and that either an increase in renal tubular transporter abundance or an increase in renin or aldosterone system would be associated with hypertension with prenatal programming. Prenatal dexamethasone increased blood pressure at two months and six months of age and resulted in proteinuria and albuminuria at six months in male but not female rat offspring. There was no effect of prenatal dexamethasone on blood pressure and proteinuria at one month in male and in female offspring. While prenatal dexamethasone increased male renal thick ascending limb sodium potassium two chloride cotransporter protein abundance at two months, prenatal dexamethasone on days 15 and 16 of gestation did not affect transporter abundance in males at other ages, nor did it affect proximal tubule sodium/hydrogen exchanger or distal convoluted tubule sodium chloride cotransporter protein abundance at any age. There was no difference in systemic renin or aldosterone in the prenatal dexamethasone group compared to same sex controls. In conclusion, male but not female offspring have an increase in blood pressure and urinary protein excretion with prenatal dexamethasone. The increase in blood pressure with prenatal programming was not associated with a consistent increase in renal tubular transporter protein abundance, nor plasma renin activity and serum aldosterone.

Becoming a mother is a fundamental life-transforming event characterized by high psychosocial distress. Most prenatal programming leaves women feeling unprepared for the realities of early parenthood. The purpose of this study was to design, implement, and evaluate a brief enhancement to existing prenatal programming, Welcome to Parenthood® (W2P). Using a single-group, longitudinal design, we implemented W2P with a community sample of 454 primiparous women via 11 Parent Link Centres in Alberta, Canada. The women completed questionnaires during late pregnancy, and 2 and 6 months postpartum to capture adverse childhood experiences (ACE), depressive symptoms (Edinburgh Postpartum Depression Scale; EPDS), and infant development (Ages and Stages Questionnaires; ASQs). Outcomes were compared with the naturalistic values from All Our Families community cohort from the same province and to the ASQ reference samples. By the end of W2P, depressive symptoms decreased significantly (p

Maternal mental health problems during pregnancy, especially mood and anxiety disorders and symptoms, are common. They not only hinder maternal well-being and health during pregnancy but also are associated with physical and mental health adversities in the offspring. We provide here a review of the studies published between 2017 and 2019, which reported on the associations between maternal mental health problems during pregnancy and child neurocognitive outcomes. We identified eight studies, which reported a mixed pattern of findings. While the balance of evidence favors lack of associations, small sample sizes and heterogeneity in study designs, exposures, outcomes, and covariate adjustments between the studies preclude firm conclusions. The reviewed studies encourage further research filling in the knowledge gaps we identified.

This study is part of a coordinated-multicentre Project, funded by the Ministerio deEconomia y Competitividad (PI08/0208; PI11/00325; PI14/00612), Instituto de Salud Car-los III–Fondo Europeo de Desarrollo Regional, Union Europea, Una manera de hacer Eu-ropa, Centro de Investigacion Biomedica en Red de salud Mental, CIBERSAM, by theCERCA Programme/Generalitat de Catalunya and Secretaria d’Universitats i Recerca delDepartament d’Economia I Coneixement (2017SGR1355), Departament de Salut de laGeneralitat de Catalunya, en la convocatoria corresponent a l’any 2017 de concessio desubvencions del Pla Estrategic de Recerca i Innovacio en Salut (PERIS) 2016-2020,modalitat Projectes de recerca orientats a l’atencio primaria, amb el codi d’expedientSLT006/17/00345

BACKGROUND Many pregnant women are consuming diets of poor overall quality. Although many studies have linked poor prenatal diet quality to an increased risk of specific diseases in offspring, it is not known if exposure to poor prenatal diet affects core neurophysiological regulatory systems in offspring known to lie upstream of multiple diseases. OBJECTIVE We aimed to examine the association between prenatal diet quality and autonomic nervous system (ANS) function in infants at 6 mo of age. METHODS Data from 400 women (aged >18 y, with uncomplicated pregnancies) and their infants participating in the Maternal-Infant Research on Environmental Chemicals-Infant Development cohort were used to investigate links between prenatal diet quality and infant ANS function at 6 mo of age. Prenatal diet quality was assessed using the Healthy Eating Index (2010), calculated from a validated FFQ completed by women during the first trimester. Infant ANS function was measured using 2 assessments of heart rate variability (HRV) including root mean square of successive differences (RMSSD) and SD of N-N intervals (SDNN). Associations were analyzed before and after adjustment for socioeconomic status, maternal depression symptoms, maternal cardiometabolic dysfunction, breastfeeding, and prenatal smoking. RESULTS Poorer prenatal diet quality was associated with lower infant HRV assessed using RMSSD (B: 0.07; 95% CI: 0.01, 0.13; R2 = 0.013) and SDNN (B: 0.18; 95% CI: 0.02, 0.35; R2 = 0.011). These associations remained significant after adjustment for confounding variables [RMSSD: B: 0.09; 95% CI: 0.003, 0.18; squared semipartial correlation (sp2) = 0.14 and SDNN B: 0.24; 95% CI: 0.0, 0.49; sp2 = 0.13]. CONCLUSIONS In a large cohort study, poorer prenatal diet quality was associated with lower offspring HRV, a marker of decreased capacity of the ANS to respond adaptively to challenge. Therefore, poor prenatal diet may play a significant role in the programming of multiple organ systems and could increase general susceptibility to disease in offspring.

BackgroundThe prenatal exposure to maternal n-6 and n-3 polyunsaturated fatty acids (PUFAs) might influence the development of social competence and internalizing and externalizing behaviours of the child, because of the numerous functions of PUFAs within the nervous system.MethodsTo analyse the association of selected maternal PUFAs (i.e., AA, EPA, DHA, total n-6, total n-3, and the n-6:n-3 ratio) measured during gestation with childhood social competence and problem behaviours, we examined 311 mother-child pairs from the Maastricht Essential Fatty Acid Birth (MEFAB) cohort. For each woman, PUFA-specific changes in relative concentrations were calculated by identifying the best-fitting curve of PUFA concentration by linear splines of gestational age. The associations of changes in maternal PUFAs in early and late pregnancy with childhood social competence, total problems, internalizing and externalizing behaviours, measured with the Child Behaviour Checklist 4/18 at age 7, were investigated with linear regression analyses adjusted for maternal and children's socio-demographic characteristics.ResultsIn late gestation (i.e., from gestational week 30), an increase in AA was associated with higher social competence, while a decrease in total n-6 was associated with lower externalizing behaviours. No other significant associations were found.DiscussionIn this prospective study, increasing maternal AA and decreasing total n-6 were associated with improved social competence and externalizing behaviours, respectively, in 7-year old children. Nonetheless, the clinical significance of the identified associations is modest and further investigations are warranted to clarify the relationship between maternal AA and total n-6 during pregnancy and childhood social and behavioural development.

Background Altered hypothalamic-pituitary-adrenal axis (HPA) functioning is one of the potential mechanisms bridging exposure to maternal prenatal psychological distress (PPD) and later risk for offspring psychiatric illness. Research on infant cortisol stress reactivity, on scarcely studied recovery and their associations with maternal PPD is needed to clarify these mechanisms. Knowledge on sex differences in prospective settings is largely lacking. We aimed at filling these gaps by building upon our previous report showing that exposure to maternal prenatal depressive and anxiety symptoms associates with slower cortisol recovery among 10-week-old female infants. Methods In all, 363, 205 and 263 infants at 10 weeks, six and 14 months of age from the FinnBrain Birth Cohort Study participated in a stress test comprising of venipuncture and nasopharynx sampling. Five saliva cortisol samples were collected during each visit to measure cortisol reactivity and recovery. PPD was assessed from maternal self-reports for depressive, anxiety and pregnancy-related anxiety symptoms at gestational weeks 14, 24 and 34. Results An 11% enhanced recovery among 14-month-old females was associated with higher depressive and anxiety symptoms (95% CI=1-23%) and pregnancy-related anxiety symptoms (2-21%). No alterations in the female cortisol reactivity or male cortisol stress responses were observed. Conclusions The opposite directions in the associations between the PPD exposure and infant cortisol recovery among 10-week-old and 14-month-old females suggest sex- and age-dependent associations between HPA axis functioning and PPD exposure among healthy infants. Follow-up is needed to characterize the impact of this altered negative feedback mechanism on later health.

Context Parabens are used as preservatives in consumer products but are suspected of having endocrine-disrupting properties. A recent study reported an association between in utero exposure to butyl paraben and overweight in childhood, with a stronger trend in girls. Objective We therefore studied the association between parabens in maternal urine in third trimester and fat percentage in children aged 7 years. Design, Setting, and Participants We used data from the Odense Child Cohort, a mother-child cohort with enrollment from 2010 to 2012, in which the children are followed. Paraben concentration was assessed in maternal urine at median gestational week 28.7 and body composition measured as total, gynoid, and android fat percentages assessed by dual X-ray absorptiometry in their children at age 7 years. Main Outcome Measurements Total, gynoid, and android fat percentages and z-score for body mass index. Interventions None. Results Paraben exposure was low. In multivariate linear regressions, detection of butylparaben in maternal urine was associated with an increase of 17% [95% confidence intervals (CI) 3.0%, 32%] in total body fat percentage and an increase of 23% (95% CI 5.1%, 43%) in android fat percentage in boys, compared to boys whose mother had no detectable butylparaben in urine. No significant associations between in utero exposure to methyl-, ethyl- or propyl parabens and body composition were found, and no significant associations were seen in girls. Conclusion Our findings suggest that parabens, which are believed to have low toxicity, may affect obesity development at vulnerable time periods during development.

To improve care for the estimated 17.1 million children with psychiatric disorders in the United States (1), it is critical to explore all possible connections to better understand these disorders' origins. The onset of neurodevelopmental/psychiatric disorders varies person-to-person. However, even for disorders diagnosed after infancy, there is a growing appreciation that the origins of these disorders are at the earliest stages of brain development—prenatally. Furthermore, not only is it crucial to understand what is unusual during development, but also why this occurs. A significant contributor to abnormal prenatal brain development is physiological stress during pregnancy (2–6). Physiological stress induces a significant shift from homeostasis, and may arise from chemical exposures, psychological stress, infections, and illnesses such as preeclampsia or gestational diabetes. Epidemiological studies link maternal stress with offspring neurodevelopmental impairments (2), and animal studies have demonstrated causality of this relationship. For example, preeclampsia—a disorder with disrupted maternal vascular and immune biology—increases risk of neuropsychiatric problems among children (3). Evidence has come from human and non-human preeclampsia studies implicating what in the offspring brain has changed: its morphology, white matter, and vasculature. When we ask the further question of why these changes occur with preeclampsia or any maternal stress, it is critical to consider the biology of not only mother and offspring but also their link—the placenta. Changes in placenta may be a critical factor for offspring neurodevelopment (Figure 1). Open in a separate window Figure 1 Examples of placental mechanisms as the link between maternal physiological stressors and offspring brain outcomes.

Natural disasters have detrimental effects not only on local infrastructure in an affected population but may also have an impact on the human biological condition, particularly during critical periods of life. This study aimed to assess the nutritional and weight status of women and their children who had experienced cyclone Aila prenatally and postnatally in comparison with a non‐affected neighbouring group. The study sample involved N = 597 dyads consisting of mothers and their prepubertal children prenatally or postnatally (during infancy) exposed to a natural disaster and a control group from a neighbouring region (West Bengal, India). The analysed anthropometric indices involved body mass index (BMI) and mid‐upper arm circumference (MUAC). Moreover, several socioeconomic characteristics were collected (mother's and father's education, family size and family income). Analyses revealed that the group factor (Aila‐exposed or non‐exposed groups) had the highest impact on both children's and their mothers' BMI and MUAC (p

Prenatal maternal stress is highly prevalent and predicts many child psychopathologies. Here, we apply the fetal programming hypothesis as an organizational framework to address the possibility that exposure to maternal stress during pregnancy affects fetal neurodevelopmental pathways that enhance risk for subsequent psychopathology. This chapter evaluates the empirical literature assessing the ontogenetic influences of prenatal maternal stress on child brain maturation. We conducted a systematic review investigating prenatal stress broadly defined and any direct measure of brain development including electroencephalography (EEG) and event-related potential (ERP), structural and functional magnetic resonance imaging (MRI), and diffusion tensor imaging (DTI). Lastly, we propose the following areas as promising avenues of future research to further elucidate the underlying etiology of such findings: investigation of sex/gender specific mechanisms, genetic interactions, pre- and postnatal effects, and opportunities for intervention.

Individual differences in risk for neuropsychiatric disorders are shaped before the individual is born. In this chapter, we summarize existing evidence from animal and human studies describing prenatal programming in the fetus and placenta in response to prenatal maternal stress, and associated outcomes seen in offspring neurobehavioral development and risk for psychopathology. First, we review fetal neurobehavioral development and assessment, including fetal physiological monitoring and fetal neuroimaging. We then highlight extant research on associations between fetal neurobehavior and later outcomes. Emerging research also points to the involvement of the placenta, which regulates the prenatal environment. We continue by describing how maternal stress can disrupt the placenta’s fundamental functions, highlighting the role of nutrient transfer, placental barrier permeability, serotonin signaling, and epigenetic changes to placental genes. We close by discussing the importance of sex differences in fetal and placental programming as well as developmental timing of exposures, and future directions for research.

For all lives regardless of sex, the longitudinal increase in blood pressure (BP) with age is attributed to lifestyle, internal environments like systemic brain-derived neurotrophic factor (BDNF) signaling, and external environments, allowing the individuals to better adapt to the developmental and environmental changes. Basic levels of renin-angiotensin-aldosterone system (RAAS) components in males and females define the fundamental sex difference in BP, which may be set by prenatal programming and the profound influence of BP after birth. The innate sex difference in BP is magnified during puberty growth and later on, affected and modified by menopause in women. At the age of 70 and older, blood pressure has been found to be similar for men and women. Understanding the prenatal setup and development of sexual dimorphism in BP may provide preventative therapeutic strategies, including timing and choice of drugs, for individuals with abnormal BP.

Polycystic ovary syndrome (PCOS) affects over 10% of women. Insulin resistance, elevated free fatty acids (FFAs) and increased adiposity are key factors contributing to metabolic dysfunction in PCOS. We hypothesised that aberrant adipogenesis during adolescence, and downstream metabolic perturbations, contributes to the metabolic phenotype of adult PCOS. We used prenatally androgenized (PA) sheep as a clinically realistic model of PCOS. During adolescence, but not during fetal or early life of PA sheep, adipogenesis was decreased in subcutaneous adipose tissue (SAT) accompanied by decreased leptin, adiponectin, and increased FFAs. In adulthood, PA sheep developed adipocyte hypertrophy in SAT paralleled by increased expression of inflammatory markers, elevated FFAs and increased expression of genes linked to fat accumulation in visceral adipose tissue. This study provides better understanding into the pathophysiology of PCOS from puberty to adulthood and identifies opportunity for early clinical intervention to normalise adipogenesis and ameliorate the metabolic phenotype.

Polygenic risk scores for major depressive disorder (PRS-MDD) have been identified in large genome-wide association studies, and recent findings suggest that PRS-MDD might interact with environmental risk factors to shape human limbic brain development as early as in the prenatal period. Striatal structures are crucially involved in depression; however, the association of PRS-MDD with infant striatal volumes is yet unknown. In this study, 105 Finnish mother-infant dyads (44 female, 11-54 days old) were investigated to reveal how infant PRS-MDD is associated with infant dorsal striatal volumes (caudate, putamen) and whether PRS-MDD interacts with prenatal maternal depressive symptoms (Edinburgh Postnatal Depression Scale, gestational weeks 14, 24, 34) on infant striatal volumes. A robust sex-specific main effect of PRS-MDD on bilateral infant caudate volumes was observed. PRS-MDD were more positively associated with caudate volumes in boys compared to girls. No significant interaction effects of genotype PRS-MDD with the environmental risk factor "prenatal maternal depressive symptoms" (genotype-by-environment interaction) nor significant interaction effects of genotype with prenatal maternal depressive symptoms and sex (genotype-by-environment-by-sex interaction) were found for infant dorsal striatal volumes. Our study showed that a higher PRS-MDD irrespective of prenatal exposure to maternal depressive symptoms is associated with smaller bilateral caudate volumes, an indicator of greater susceptibility to major depressive disorder, in female compared to male infants. This sex-specific polygenic effect might lay the ground for the higher prevalence of depression in women compared to men.

During pregnancy, programming of the fetal central nervous system (CNS) establishes vulnerabilities for emergence of neuropsychiatric phenotypes later in life. Psychosocial influences during pregnancy, such as stressful life events or chronic stress, correlate with offspring neuropsychiatric disorders and with inflammation, respectively. Stress promotes inflammation, but the role of inflammation as a mediator between maternal psychosocial stress and offspring neuropsychiatric outcomes has not been extensively studied in humans. This review summarizes clinical evidence linking specific types of stress to maternal inflammatory load during pregnancy. We propose that inflammation is a mediator in the relationship between psychosocial stress and offspring neuropsychiatric outcomes, potentially influenced by poor maternal glucocorticoid-immune coordination. We present relevant experimental animal research supporting this hypothesis. We conclude that clinical and preclinical research support the premise that stress-induced maternal immune activation (MIA) contributes in part to prenatal programming of risk. Programming of risk is likely due to a combination of vulnerabilities, including multiple or repeated inflammatory events, timing of such events, poor maternal regulation of inflammation, genetic vulnerability, and lifestyle contributors.

Maternal nutrition is critically important for fetal development. Recent human studies demonstrate a strong connection between diet during pregnancy and offspring risk for neuropsychiatric disorders including depression, anxiety, and attention-deficit/hyperactivity disorder. Animal models have emerged as a crucial tool for understanding maternal nutrition's contribution to prenatal programming and the later development of neuropsychiatric disorders. This review highlights preclinical studies examining how maternal consumption of the three macronutrients (protein, fats, and carbohydrates) influence offspring negative-valence behaviors relevant to neuropsychiatric disorders. We highlight the translational aspects of animal models and so examine exposure periods that mirror the neurodevelopmental stages of human gestation. Because of our emphasis on programmed changes in neurobehavioral development, studies that continue diet exposure until assessment in adulthood are not discussed. The presented research provides a strong foundation of preclinical evidence of nutritional programming of neurobehavioral impairments. Alterations in risk assessment and response were observed alongside neurodevelopmental impairments related to neurogenesis, synaptogenesis, and synaptic plasticity. To date, the large majority of studies utilized rodent models, and the field could benefit from additional study of large-animal models. Additional future directions are discussed, including the need for further studies examining how sex as a biological variable affects the contribution of maternal nutrition to prenatal programming.

During pregnancy, the regulation of several neuroendocrine systems is altered to support the pregnancy and facilitate the transition to motherhood. These adaptations are organised by the mother's brain and include those that serve to optimise foetal growth, protect the foetus(es) from adverse prenatal programming by maternal stress, facilitate timely parturition and ensure the offspring are nourished and cared for after birth. Although pregnancy hormones are important in inducing and maintaining many of these adaptations, their effects are often mediated via interactions with neuropeptide systems in the brain. In particular, endogenous opioids in the maternal brain play key roles in altered regulation of the stress axis, the oxytocin system, the prolactin system and the neural circuits controlling maternal behaviour. Together, these adaptations maximise the likelihood of a successful pregnancy outcome.

At the Prenatal Programming and Toxicity (PPTox) Conference I in 2008, I presented an overview of the developmental origins of health and disease field focusing on environmental chemical exposures and disease outcomes. At that time, I noted that the field was getting off the ground with a focus on developmental exposure to a small number of endocrine disrupting chemicals (EDCs) and disease outcomes across the lifespan in animal models. In this update, I note that the DOHaD field has changed significantly over the last decade. There are new windows of susceptibility including preconception, prepuberty, a focus on the mother and not just the offspring, and a significant focus on the new field of epigenetic transgenerational inheritance. New disease focus areas have sprung up including obesity, type 2 diabetes and fatty liver disease, all with a connection to developmental exposures to EDCs. There is also a focus on the study of new EDCs, molecular mechanisms, the development of new biomarkers of exposure and disease outcomes and studies focusing on intervention and prevention studies.

AIM We aimed to determine whether maternal hemoglobin levels or anemia during pregnancy are associated with the development of asthma among offspring. METHODS Data were retrieved from the birth register database of Kuopio University Hospital between 1989 and 2007 (n = 38 381). Hemoglobin levels were measured during three trimesters of pregnancy and anemia was defined according to the World Health Organization criteria. The prevalence of asthma was determined from the register of reimbursement for medication for asthma at the Finnish Social Security Institution. Cox proportional hazard regression analysis was performed to evaluate the possible associations between prenatal factors and development of asthma ever. RESULTS A total of 8198 (21.4%) women had anemia at some stage of pregnancy. Mild maternal anemia during the first trimester was associated with an increased risk of asthma among male offspring (adjusted hazard ratio, 1.46; 95% confidence interval, 1.11-1.94) compared with those with normal maternal hemoglobin levels. This finding remained significant also after applying the Bonferroni correction. CONCLUSION Male offspring with maternal anemia during the first trimester of pregnancy had significantly more asthma ever than the offspring of women with normal hemoglobin levels during pregnancy. These findings were not strong but suggest possible sex-specific effects of maternal health on prenatal programming and future risk of asthma.

Perinatal asphyxia (PA) is a burdening pathology with high short-term mortality and severe long-term consequences. Its incidence, reaching as high as 10 cases per 1000 live births in the less developed countries, prompts the need for better awareness and prevention of cases at risk, together with management by easily applicable protocols. PA acts first and foremost on the nervous tissue, but also on the heart, by hypoxia and subsequent ischemia-reperfusion injury. Myocardial development at birth is still incomplete and cannot adequately respond to this aggression. Cardiac dysfunction, including low ventricular output, bradycardia, and pulmonary hypertension, complicates the already compromised circulatory status of the newborn with PA. Multiorgan and especially cardiovascular failure seem to play a crucial role in the secondary phase of hypoxic-ischemic encephalopathy (HIE) and its high mortality rate. Hypothermia is an acceptable solution for HIE, but there is a fragile equilibrium between therapeutic gain and cardiovascular instability. A profound understanding of the underlying mechanisms of the nervous and cardiovascular systems and a close collaboration between the bench and bedside specialists in these domains is compulsory. More resources need to be directed toward the prevention of PA and the consecutive decrease of cardiovascular dysfunction. Not much can be done in case of an unexpected acute event that produces PA, where recognition and prompt delivery are the key factors for a positive clinical result. However, the situation is different for high-risk pregnancies or circumstances that make the fetus more vulnerable to asphyxia. Improving the outcome in these cases is possible through careful monitoring, identifying the high-risk pregnancies, and the implementation of novel prenatal strategies. Also, apart from adequately supporting the heart through the acute episode, there is a need for protocols for long-term cardiovascular follow-up. This will increase our recognition of any lasting myocardial damage and will enhance our perspective on the real impact of PA. The goal of this article is to review data on the cardiovascular consequences of PA, in the context of an immature cardiovascular system, discuss the potential contribution of cardiovascular impairment on short and long-term outcomes, and propose further directions of research in this field.

Allergic asthma is a chronic pulmonary disorder fundamentally linked to immune dysfunction. Since the immune system begins developing in utero, prenatal exposures can affect immune programming and increase risk for diseases such as allergic asthma. Chronic psychosocial stress during pregnancy is one such risk factor, having been associated with increased risk for atopic diseases including allergic asthma in children. To begin to define the underlying causes of the association between maternal stress and allergic airway inflammation in offspring, we developed a mouse model of chronic heightened stress hormone during pregnancy. Continuous oral administration of corticosterone (CORT) to pregnant mice throughout the second half of pregnancy resulted in an ~2-fold increase in circulating hormone in dams with no concomitant increase in fetal circulation, similar to the human condition. To determine how prolonged heightened stress hormone affected allergic immunity in offspring, we induced allergic asthma with house dust mite (HDM) and examined the airway immune response to allergen. Female mice responded to HDM more frequently and had a more robust immune cell response compared to their male counterparts, irrespective of maternal treatment. Male offspring from CORT-treated dams had a greater number of inflammatory cells in the lung in response to HDM compared to males from control dams, while maternal treatment did not affect immune cell numbers in females. Alternatively, maternal CORT caused enhanced goblet cell hyperplasia in female offspring following HDM, an effect that was not observed in male offspring. In summary, prenatal exposure to mild, prolonged heightened stress hormone had sexually dimorphic effects on allergic inflammation in airways of adult offspring.

The present review aims to offer a non-comprehensive outline of the current state-of-the-art and future perspectives on management and therapeutic tools for intrauterine growth restriction (IUGR) and associated prenatal programming in both human and animal species. Animals are used as models for the study of phenomena related to IUGR, but also for research on prenatal therapies with the main objective of designing and developing preventive and therapeutic strategies. The research is currently paying attention on maternal-focused pharmacological treatments and nutritional strategies but also on fetal-focused treatments. Fetal-focused treatments, administered either directly at the fetus or by using infusion of umbilical cord, amniotic sac or placenta, which avoids the administration of substances at high doses to the mother for allowing their availability at the fetoplacental level. The results obtained in this area of research using large animals (rabbits, pigs and ruminants) have a dual interest, for translational biomedicine and for veterinary medicine and animal production.

Early programming is the adaptation process by which nutrition and environmental factors alter development pathways during prenatal growth, inducing changes in postnatal metabolism and diseases. The aim of this narrative review, is evaluating the current knowledge in the scientific literature on the e ects of nutrition, environmental factors, physical activity and sleep on development pathways. If in utero adaptations were incorrect, this would cause a mismatch between prenatal programming and adulthood. Adequate caloric intake, protein, mineral, vitamin, and long-chain fatty acids, have been noted for their relevance in the o spring brain functions and behavior. Fetus undernutrition/malnutrition causes a delay in growth and have detrimental e ects on the development and subsequent functioning of the organs. Pregnancy is a particularly vulnerable period for the development of food preferences and for modifications in the emotional response. Maternal obesity increases the risk of developing perinatal complications and delivery by cesarean section and has long-term implications in the development of metabolic diseases. Physical exercise during pregnancy contributes to overall improved health post-partum. It is also interesting to highlight the relevance of sleep problems during pregnancy, which influence adequate growth and fetal development. Taking into account these considerations, we conclude that nutrition and metabolic factors during early life play a key role of health promotion and public health nutrition programs worldwide to improve the health of the o spring and the health costs of hospitalization., University of Granada

The fetal origin of adult disease hypothesis postulates that a stressful in utero environment can have deleterious consequences on fetal programming, potentially leading to chronic disease in later life. Factors known to impact fetal programming include the timing, intensity, duration and nature of the external stressor during pregnancy. As such, dynamic modulation of fetal programming is heavily involved in shaping health throughout the life course, possibly by influencing metabolic parameters including insulin action, hypothalamic-pituitary-adrenal activity and immune function. The ability of prenatal insults to program adult disease is likely to occur as a result of reduced functional capacity in key organs-a "thrifty" phenotype-where more resources are re-allocated to preserve critical organs such as the brain. Notably, it has been postulated that the manifestation of neuropsychiatric disorders in individuals priorly exposed to prenatal stress may arise from the interaction between hereditary factors and the intrauterine environment, which together precipitate disease onset by disrupting the trajectory of normal brain development. In this review we discuss the evidence linking prenatal programming to neuropsychiatric disorders, mainly schizophrenia, via a "Thrifty psychiatric phenotype" concept. We start by outlining the conception of the thrifty psychiatric phenotype. Next, we discuss the convergence of potential mechanistic pathways through which prenatal insults may trigger epigenetic changes that contribute to the increased morbidity and early mortality observed in neuropsychiatric disorders. Finally, we touch on the public health importance of fetal programming for these disorders. We conclude by providing a brief outlook on the future of this evolving field of research.

We have previously demonstrated that dexamethasone administered to pregnant rats during specific times during gestation results in a reduction in glomerular number and hypertension in offspring at 2 and 6 months of age. In this study, we examined the effect of prenatal dexamethasone administered daily on days 15 and 16 of gestation in male and female offspring after 1 year of age on glomerular filtration rate. The prenatal dexamethasone male group had a higher systolic blood pressure than the vehicle male group. Females had lower systolic blood pressures than the males and prenatal dexamethasone did not affect blood pressure in female offspring. Prenatal dexamethasone resulted in a reduction in glomerular filtration rate in male but not in female rats. When corrected for body weight, the control male rats had a lower glomerular filtration rate than the control female rats. Males had greater protein excretion than females and prenatal dexamethasone increased the protein excretion only in male rats. Glomerulosclerosis was also greater in male rats than females but was not affected by prenatal dexamethasone. In summary, male rats appear to have evidence of a decline in glomerular filtration rate after 1 year of age and prenatal dexamethasone programs an accelerated decline in glomerular filtration rate in male but not in female offspring.

Suboptimal conditions during prenatal ontogeny can impair development of several physiological systems and result in cardiometabolic diseases in adulthood. The kidney has been identified as one of the most sensitive organs for developmental programming, but underlying mechanisms are not fully understood. Therefore, in our study we explored the consequences of prenatally increased angiotensin II (Ang II) on the structural development of the kidney and its damage by infiltrated immune cells under normal diet and after an increased salt intake, as a second insult representing a lifestyle factor in humans. Female rats were implanted with osmotic mini-pumps continuously releasing Ang II of dose 2 µg/kg/h during last two weeks of pregnancy, whereas control females were sham operated. Immunohistological and ultrastructural evaluations of the kidneys and their infiltration with immune cells were performed in mature male progeny kept either on a standard or increased salt (2% NaCl) diet. Glomerular volume decreased and the cortical tubulointerstitial injury increased in the offspring prenatally exposed to Ang II with no additional effect of increased salt. Ultrastructural examination demonstrated degenerative changes in proximal tubules, mainly fewer and shorter microvilli in the brush border, enlarged mitochondria, and an increased number of lysosomes in the epithelial cells in the progeny prenatally exposed to Ang II. Moreover, the treatment resulted in increased infiltration of T-cells and macrophages in the renal cortex compared to controls. These changes paralleled with reduced numbers of cytotoxic T-cells in circulation and higher oxidative burst of neutrophils in the progeny of Ang II-treated mothers compared to controls. Altogether, results suggest that prenatally increased Ang II promoted infiltration of immune cells in the kidney and subsequent oxidative stress, which induced a damage of renal glomerular and tubular system entailing negative consequences on the cardiovascular system.Impact statementSuboptimal prenatal conditions can contribute to development of cardiovascular diseases and an altered renin-angiotensin-aldosterone system (RAAS) can be involved in the process. In our study, increased angiotensin II in pregnant female rats resulted in renal cortical interstitial damage, and renal ultrastructural changes in the glomeruli, the brush border of proximal tubules and mitochondria in mature male offspring. The treatment promoted infiltration of T cells and macrophages in the kidneys and primed an oxidative burst of circulating neutrophils, indicating a pro-inflammatory state in the progeny of angiotensin II-treated mothers. Deregulated RAAS of mothers is involved in developmental programming of hypertension in adult male offspring via damaging kidney morphology and function. These findings suggest that preventing the activation of RAAS and oxidative stress during perinatal development might protect against hypertension development in adult male progeny.

Developmental exposure to stress hormones, i.e. glucocorticoids, is central to the process of prenatal programming of later-life health. Glucocorticoid overexposure, through stress or exogenous glucocorticoids, results in a reduced birthweight, as well as affective and neuropsychiatric outcomes in adults, combined with altered hypothalamus-pituitary-adrenal (HPA) axis activity. As such, glucocorticoids are tightly regulated during development through the presence of the metabolizing enzyme 11β-hydroxysteroid dehydrogenase type 2 (HSD2). HSD2 is highly expressed in 2 hubs during development, i.e. the placenta and the fetus itself, protecting the fetus from inappropriate glucocorticoid exposure early in gestation. Through manipulation of HSD2 expression in the mouse placenta and fetal tissues, we are able to determine the relative contribution of glucocorticoid exposure in each compartment. Feto-placental HSD2 deletion resulted in a reduced birthweight and the development of anxiety- and depression-like behaviours in adult mice. The placenta itself is altered by glucocorticoid overexposure, which causes reduced placental weight and vascular arborisation. Furthermore, altered flow and resistance in the umbilical vessels and modification of fetal heart function and development are observed. However, brain-specific HSD2 removal (HSD2BKO) also generated adult phenotypes of depressive-like behaviour and memory deficits, demonstrating the importance of fetal brain HSD2 expression in development. In this review we will discuss potential mechanisms underpinning early-life programming of adult neuropsychiatric disorders and the novel therapeutic potential of statins.

OBJECTIVE Complications of prematurity may be related to dysregulation of the hypothalamic-pituitary-adrenal axis in preterm infants. Increased intrauterine exposure to cortisol may be responsible for adverse prenatal programming and subsequent dysfunction of the infant's hypothalamic-pituitary-adrenal axis. The aim of the study was to describe maternal social variables and their association with infant cortisol levels and complications of prematurity. METHODS Preterm infants

Prenatal insults, such as maternal dietary protein deprivation and uteroplacental insufficiency, lead to small for gestational age (SGA) neonates. Epidemiological studies from many different parts of the world have shown that SGA neonates are at increased risk for hypertension and early death from cardiovascular disease as adults. Animal models, including prenatal administration of dexamethasone, uterine artery ligation and maternal dietary protein restriction, result in SGA neonates with fewer nephrons than controls. These models are discussed in this educational review, which provides evidence that prenatal insults lead to altered sodium transport in multiple nephron segments. The factors that could result in increased sodium transport are discussed, focusing on new information that there is increased renal sympathetic nerve activity that may be responsible for augmented renal tubular sodium transport. Renal denervation abrogates the hypertension in programmed rats but has no effect on control rats. Other potential factors that could cause hypertension in programmed rats, such as the renin-angiotensin system, are also discussed.

Simple Summary Overweight and obesity can cause many diseases, and several studies indicate a close relationship between the obesity of parents and the health of their offspring. Our aim was to investigate whether there is a programming influence of parental obesity on the skeletal system in weaned female and male offspring rats. In undertaking this, analysis of bone material was carried out using isolated tibia, and densitometry (DXA), peripheral (pQCT) and micro (µCT) computed tomography were performed. Mechanical tests and blood serum biochemistry were also carried out. Our work showed a significant programming influence of parental obesity on neonatal skeletal development. The tibiae isolated from offspring originating from obese parents were characterized by more intense mineralization and higher fracture resistance. However, numerous studies demonstrate the destructive effect of obesity on the skeletal system. Our research and the available literature suggest the existence of a “fat threshold”, the exceeding of which changes of the osteotropic effect of adipose tissue to become unfavorable. Therefore, there is a need for further research to determine the time-dependent metabolic relationship between adipose tissue and bone in both animals and humans. Abstract Our study aimed to verify the hypothesis of the existence of a programming effect of parental obesity on the growth, development and mineralization of the skeletal system in female and male rat offspring on the day of weaning. The study began with the induction of obesity in female and male rats of the parental generation, using a high-energy diet (group F). Females and males of the control group received the standard diet (group S). After 90 days of dietary-induced obesity, the diet in group F was changed into the standard. Rats from groups F and S were mated to obtain offspring which stayed with their mothers until 21 days of age. Tibia was tested using dual-energy X-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT), micro-computed tomography (µCT) and mechanical strength using the three-point bending test. Biochemical analysis of blood serum bone metabolism markers was performed. DXA analysis showed higher tibia bone mineral content (BMC) and area. pQCT measurements of cortical and trabecular tissue documented the increase of the volumetric bone mineral density and BMC of both bone compartments in offspring from the F group, while µCT of the trabecular tissue showed an increase in trabecular thickness and a decrease of its separation. Parental obesity, hence, exerts a programming influence on the development of the skeletal system of the offspring on the day of the weaning, which was reflected in the intensification of mineralization and increased bone strength.

Depression is a common condition affecting up to 20% of all pregnant women, and is associated with subsequent developmental and behavioral problems in children, such as conduct disorder and ADHD. One proposed mechanism underlying these associations is modification of the fetal hypothalamic pituitary adrenal (HPA)-axis and the autonomic nervous system (ANS), resulting in altered responses to stress. This review examined the evidence regarding altered HPA-axis and ANS reactivity in children prenatally exposed to high maternal depressive symptoms. A systematic search was conducted in the electronic databases MEDLINE, EMBASE and PsycINFO, for studies published till 25 July 2017. A total of 13 studies comprising 2271 mother-infant dyads were included. None of the studies were suitable for meta-analysis. Risk of bias assessment showed low risk for four studies. Only three studies described an independent association between exposure to high maternal prenatal depressive symptoms and altered stress reactivity in children. There is limited evidence of an independent association between prenatal exposure to maternal depression and altered HPA or ANS reactivity in children.

Recent findings highlight that there are prenatal risks for affective disorders that are mediated by glucocorticoid mechanisms, and may be specific to females. There is also evidence of sex differences in prenatal programming mechanisms and developmental psychopathology, whereby effects are in opposite directions in males and females. As birth weight is a risk for affective disorders, we sought to investigate whether maternal prenatal cortisol may have sex-specific effects on fetal growth. Participants were 241 mothers selected from the Wirral Child Health and Development Study (WCHADS) cohort (n=1233) using a psychosocial risk stratifier, so that responses could be weighted back to the general population. Mothers provided saliva samples, which were assayed for cortisol, at home over 2 days at 32 weeks gestation (on waking, 30-min post-waking and during the evening). Measures of infant birth weight (corrected for gestational age) were taken from hospital records. General population estimates of associations between variables were obtained using inverse probability weights. Maternal log of the area under the curve cortisol predicted infant birth weight in a sex-dependent manner (interaction termP=0.029). There was a positive and statistically significant association between prenatal cortisol in males, and a negative association in females that was not statistically significant. A sex interaction in the same direction was evident when using the waking (P=0.015), and 30-min post-waking (P=0.013) cortisol, but not the evening measure. There was no interaction between prenatal cortisol and sex to predict gestational age. Our findings add to an emerging literature that suggests that there may be sex-specific mechanisms that underpin fetal programming.

The concept of the developmental origins of health and disease via prenatal programming has informed many etiologic models of health and development. Extensive experimental research in non-human animal models has revealed the impact of in utero exposure to stress on fetal development and neurodevelopment later in life. Stress exposure, however, is unlikely to occur de novo following conception, and pregnancy health is not independent of the health of the system prior to conception. For these reasons, the preconception period is emerging as an important new focus for research on adverse birth outcomes and offspring neurodevelopment. In this review, we summarize the existing evidence for the role of preconception stress exposure on pregnancy health and offspring neurodevelopment across species and discuss the implications of this model for addressing health disparities in obstetrics and offspring outcomes.

Synthetic glucocorticoids are frequently used antenatally in order to reduce morbidity and mortality in babies born preterm and have been used in the management of fetuses known to be at risk of congenital adrenal hyperplasia. Although such treatment has short term advantages, evidence suggests that it can affect health in later life. Several studies have reported negative consequences of prenatal exposure to the synthetic glucocorticoid dexamethasone on offspring behavior in humans and in animal models, in association with changes in brain structure, hypothalamic–pituitary–adrenal axis function, neurotransmitter pathways, gene transcription and epigenetic regulation. These studies also highlight the importance of timing and tissue/organ-specific and sex-specific effects of prenatal glucocorticoid exposure. Here we review the evidence from human and animal studies that links prenatal synthetic glucocorticoid exposure with an increased risk for neurodevelopmental disorders.

Background: Maternal stress during pregnancy can have deleterious consequences, increasing risk for prematurity and low birth weight, as well as postnatal effects on emotional regulation and neuromotor development. It is less clear, however, whether moderate and brief gestational disturbances have similar effects. Objective: To determine the impact of a delimited period of moderate maternal stress on infant growth, emotional reactivity, and neurobehavioral maturity in a nonhuman primate model. Methods: Eighty-three infant rhesus monkeys were generated from disturbed pregnancies, either early or late gestation, and compared with 51 undisturbed infants. Maternal stress was induced with an acoustical startle protocol for 25% of gestation. Infant weights, anthropometrics, and neurobehavioral data were obtained. Analyses focused on differential effects of prenatal stress on male and female infants. Results: The disturbance manipulation elevated cortisol levels acutely in the gravid females and they gained less weight by term. Nevertheless, female infants from the early stress condition were significantly larger at birth. This differential growth trajectory was then sustained through 6 months of age. Infants from stress conditions were more emotionally reactive and evinced immature neuromotor reflexes, especially when gestated by late stress mothers. Conclusions: Even moderate maternal disturbance impacted infant temperament and neuromotor development in this nonhuman primate model. Effects on fetal and infant growth differed from typical reports of growth inhibition, both in other animal species and human studies. The findings convey the importance of considering the duration and severity of prenatal insults, and the potential for fetal plasticity and recovery, permitting compensatory growth responses.

Prenatal programming results in an increase in blood pressure in adult offspring. We have shown that compared to control adult offspring whose mothers were fed a 20% protein diet, programmed adults whose mothers were fed a 6% protein diet during the last half of pregnancy have an increase in renal sympathetic nerve activity and urinary angiotensinogen/creatinine levels. We hypothesized that the increase in urinary angiotensinogen was mediated by renal sympathetic nerve activity in programmed rats. In this study performed in 3 month old rats, renal denervation resulted in normalization of blood pressure in the 6% programmed group (150 ± 3 Hg in 6% sham vs. 121 ± 4 Hg in 6% denervated, P

Background: Prenatal maternal depression has been associated with multiple problems in offspring involving affect, cognition, and neuroendocrine functioning. This suggests that prenatal depression influences neurodevelopment. However, the underlying neurodevelopmental mechanism remains unclear. We prospectively assessed whether maternal depressive symptoms during pregnancy and at the child's age 3 years are related to white matter microstructure in 690 children. The association of paternal depressive symptoms with childhood white matter microstructure was assessed to evaluate genetic or familial confounding. Methods: Parental depressive symptoms were measured using the Brief Symptom Inventory. In children aged 6-9 years, we used diffusion tensor imaging to assess white matter microstructure characteristics including fractional anisotropy (FA) and mean diffusivity (MD). Results: Exposure to maternal depressive symptoms during pregnancy was associated with higher MD in the uncinate fasciculus and to lower FA and higher MD in the cingulum bundle. No associations of maternal depressive symptoms at the child's age of 3 years with white matter characteristics were observed. Paternal depressive symptoms also showed a trend toward significance for a lower FA in the cingulum bundle. Conclusions: Prenatal maternal depressive symptoms were associated with higher MD in the uncinate fasciculus and the cingulum bundle. These structures are part of the limbic system, which is involved in motivation, emotion, learning, and memory. As paternal depressive symptoms were also related to lower FA in the cingulum, the observed effect may partly reflect a genetic predisposition and shared environmental family factors and to a lesser extent a specific intrauterine effect.

This study aimed to determine whether prenatal stress, measured by the number of stressful life events during the first 20 weeks of pregnancy, might relate to mood dysregulation and altered brain structure in young adulthood. Participants included 93 young adults from a community-based birth cohort from the Czech Republic. Information on prenatal stress exposure was collected from their mothers in 1990-1992. Magnetic resonance imaging (MRI) and mood-related data were collected from the young adults in 2015. MRI analyses focused on overall gray matter (GM) volume and GM volume of cortical regions previously associated with major depression. Higher prenatal stress predicted more mood dysregulation, lower overall GM volume, and lower GM volume in mid-dorsolateral frontal cortex, anterior cingulate cortex, and precuneus in young adulthood. We observed no prenatal stress by sex interactions for any of the relations. We conclude that prenatal stress is an important risk factor that relates to worse mood states and altered brain structure in young adulthood irrespective of sex. Our results point to the importance and long-lasting effects of prenatal programming and suggest that offspring of mothers who went through substantial stress during pregnancy might benefit from early intervention that would reduce the odds of mental illness in later life.

Summary The Human Genome Project, completed ten years ago, widely opened the door for the field of Epigenetics as a new venue to study the causes of human disease and to search for predictive biomarkers and therapeutic targets for a wide range of disorders. The field of behavioral and psychiatric epigenetics is still very young, but increasing evidence suggests that epigenetic mechanisms contribute to the development of neuropsychiatric disorders. The prenatal period is particularly vulnerable to epigenetic disruption, and it seems likely that adverse in utero environments can induce epigenetic dysregulation and predispose an individual to mental disease later in life. Emerging evidence from animal studies has shown that maternal exposure to drugs, stress, and toxicants can alter epigenetic gene programming in the brain and contribute to neurodevelopmental and behavioral deficits in the offspring. The evidence from human studies is more limited but is in agreement with animal data. Several human studies have shown that prenatal risk factors, such as maternal food deprivation and stressful life events, are associated with persistent epigenetic changes in genes that are linked to neurodevelopmental disorders and psychopathology. Although these studies support the hypothesis that epigenetic mechanisms may be involved in prenatal programming of psychopathology, a collaborative effort of basic, clinical and epidemiological research is needed to advance this field. Nevertheless, this field holds great promise to facilitate our understanding of environmental contribution to human mental disease and to reveal new predictive biomarkers as well as preventive and therapeutic approaches for various neuropsychiatric disorders.

Emerging evidence suggests that prenatal exposures may affect long-term health outcomes. In utero exposure to smoking is associated with an increased risk of overweight and obesity in children and adolescents. However, few studies have examined how prenatal exposure to parental smoking influences the risk of obesity during adulthood and whether these associations are independent of childhood and adolescent adiposity. The aim of the current study was to investigate whether prenatal exposure to parental smoking influences body size during adulthood and whether any association may be mediated by childhood and adolescent body size. We investigated the association between parental smoking during pregnancy and the risk of being overweight and obese during adulthood and at age 18 and adiposity during childhood among 35 370 participants in the Nurses’ Health Study II. Data on smoking during pregnancy and socioeconomic variables were provided by the mothers, and anthropometric data and adult risk factors were reported by participants. After adjustment for socioeconomic and behavioral variables, maternal smoking during pregnancy was associated with adiposity at ages 5–10, 18 and during adulthood. For age 18 overweight, the odd ratios, ORs (95% confidence intervals, CIs) for 1–14, 15–24 and 25+cigarettes per day were 1.13 (1.18–1.50), 1.40 (1.20–1.64) and 1.15 (0.79–1.69), and for obesity were 1.41 (1.14–1.75), 1.69 (1.31–2.18) and 2.36 (1.44–3.86). The corresponding ORs (95% CIs) for obesity during adulthood were 1.26 (1.16–1.37), 1.46 (1.30–1.63) and 1.43 (1.10–1.86). Risk of adiposity was not increased among daughters whose mothers stopped smoking during the first trimester (OR (95% CI) for overweight (1.03 (95% CI 0.90–1.17)) and for obesity (1.12 (95% CI 0.97–1.30)). Women whose fathers smoked during pregnancy were also at an increased risk of being overweight and obese during adulthood with covariate-adjusted ORs (95% CIs) for obesity of 1.19 (1.11–1.29) for 1–14 cigarettes per day, 1.27 (1.18–1.37) for 15–24 cigarettes per day and 1.40 (1.27–1.54) for 25+ cigarettes per day compared with fathers who did not smoke (Ptrend

The observation of poor nutrition in childhood and the development of disease in later life date from far back in Medicine. Ando so does the use of somatic growth, as a surrogate measure of nutrition. However, both the definition and meaning of adequate growth, particularly during intrauterine life, remain controversial.

Small-for-gestational-age infants are known to develop hypertension in adulthood. This prenatal programming of hypertension (PPH) can result from several insults including maternal dietary protein deprivation, uteroplacental insufficiency, and prenatal administration of glucocorticoids. The mechanisms underlying the development of hypertension remain unclear although the sympathetic nervous system has been indirectly implicated. This study was designed to directly measure renal sympathetic nerve activity both at rest and during physical stress in an animal model of PPH. The adult male offspring of rats fed either a 6% (PPH) or 20% protein diet (control) were investigated. Conscious systolic blood pressure measured by tail cuff was significantly higher in PPH compared with control (140 ± 3 versus 128 ± 3 mm Hg; P P P P

Early – intrauterine – environmental factors are linked to the development of cardiovascular disease in later life. Traditionally, these factors are considered to be maternal factors such as maternal under and overnutrition, exposure to toxins, lack of micronutrients, and stress during pregnancy. However, in the recent years, it became obvious that also paternal environmental factors before conception and during sperm development determine the health of the offspring in later life. We will first describe clinical observational studies providing evidence for paternal programming of adulthood diseases in progeny. Next, we describe key animal studies proving this relationship, followed by a detailed analysis of our current understanding of the underlying molecular mechanisms of paternal programming. Alterations of noncoding sperm micro-RNAs, histone acetylation, and targeted as well as global DNA methylation seem to be in particular involved in paternal programming of offspring's diseases in later life.

Obesity is a significant and increasing public health concern in the United States and worldwide. Clinical and epidemiological evidence clearly shows that genetic and environmental factors contribute to the increased susceptibility of humans to obesity and its associated comorbidities; the interplay of these factors is explained by the concept of epigenetics. The impact of maternal obesity goes beyond the newborn period; fetal programming during the critical window of pregnancy, can have long term detrimental effects on the offspring as well as future generations. Emerging evidence is uncovering a link between the clinical and molecular findings in the offspring with epigenetic changes in the setting of maternal obesity. Research targeted towards reducing the transgenerational propagation and developmental programming of obesity is vital in reducing the increasing rates of disease.

Background Identifying the prenatal origins of mental conditions is of increasing interest, yet most studies have focused on high-risk populations and cannot disentangle prenatal and postnatal programming effects. Thus, we examined whether profiles of neurobehaviour indicative of future risk could be identified in healthy 1–3-day-old infants, and examined associations with perinatal risk factors. Methods Participants included 627 healthy mothers and term infants from a population-based US cohort. Neurobehaviour was assessed within 24–72 h after delivery with the NICU Network Neurobehavioural Scales (NNNS). A model-based clustering algorithm was used to derive neurobehavioural profiles from NNNS scores. Maternal health histories, pregnancy conditions and behaviours, labour/delivery factors, and infant attributes were examined in relation to the neurobehavioural profiles. Results Seven discrete neurobehavioural profiles were identified, including one average functioning profile, and two inversely patterned below and above average profiles. Higher pregnancy weight gain (OR 1.44, 95% CI 1.10, 1.88) and birthweight percentiles (OR 1.46, 95% CI 1.10, 1.95) were associated with greater odds of below average newborn neurobehaviour. Above average neurobehaviour was associated with experiencing longer gestations (OR 1.29, 95% CI 1.02, 1.64) and higher 5-min APGAR scores (OR 2.43, 95% CI 1.07, 5.52). Maternal pregnancy alcohol use (OR 0.54, 95% CI 0.33, 0.89), and fetal distress (OR 0.10, 95% CI 0.01, 0.72) were associated with lower likelihood of having average neurobehaviour. Conclusion Distinct profiles of neurobehaviour can be derived in a healthy population of newborns, with different sets of perinatal factors predicting different patterns of neurobehaviour. These findings suggest a potential in utero origin for mental health risk.

Emerging evidence suggests environmental chemical exposures during critical windows of development may contribute to the escalating prevalence of obesity. We tested the hypothesis that prenatal air pollution exposure would predispose the offspring to weight gain in adulthood. Pregnant mice were exposed to filtered air (FA) or diesel exhaust (DE) on embryonic days (E) 9-17. Prenatal DE induced a significant fetal brain cytokine response at E18 (46-390% over FA). As adults, offspring were fed either a low-fat diet (LFD) or high-fat diet (HFD) for 6 wk. Adult DE male offspring weighed 12% more and were 35% less active than FA male offspring at baseline, whereas there were no differences in females. Following HFD, DE males gained weight at the same rate as FA males, whereas DE females gained 340% more weight than FA females. DE-HFD males had 450% higher endpoint insulin levels than FA-HFD males, and all males on HFD showed decreased activity and increased anxiety, whereas females showed no differences. Finally, both DE males and females fed HFD showed increased microglial activation (30-66%) within several brain regions. Thus, prenatal air pollution exposure can "program" offspring for increased susceptibility to diet-induced weight gain and neuroinflammation in adulthood in a sex-specific manner.

Background/Aims: Dietary protein deprivation during pregnancy causes hypertension in offspring when they become adults. This study examined if postnatal rearing had an effect on blood pressure and glomerular number in male rats whose mothers were fed either a control diet or a low protein diet. Methods: Neonates were cross fostered at 1 day of age to a different mother. After birth, all nursing and weaned rats were fed a control diet. Blood pressure and glomerular number were measured in adult offspring. Results: Control rats cross fostered to another control mother had a lower blood pressure than low protein rats cross fostered to another low protein mother (133 ± 4 vs. 151 ± 4 mm Hg, p < 0.05) and a greater number of glomeruli (28,388 ± 989 vs. 25,045 ± 851, p < 0.05). Fostering pups from the 20% group to mothers that were fed a 6% diet during pregnancy did not cause hypertension or a reduction in the number of glomeruli. However, fostering the 6% group on to mothers that were fed a 20% protein diet during pregnancy resulted in normalization of the blood pressure and number of glomeruli. Conclusion: The hypertension and reduced glomerular number resulting from prenatal dietary protein deprivation can be normalized by improving the postnatal environment.