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ObjectiveChildhood trauma exacts a lasting toll on one's own mental health and the health of one's offspring; however, limited research has examined the pathways through which this intergenerational transmission occurs. This study aimed to identify the transactions and mechanisms that link maternal early life trauma, maternal depressive symptoms, and children's internalizing symptoms.MethodA pregnancy cohort of N=1462 mothers (66% Black, 32% White, 2% Other race) reported their childhood trauma exposure and depressive symptoms during pregnancy. Maternal depressive and children's internalizing symptoms were measured repeatedly when offspring were 12, 24, 36, and 48-60months of age. A path model tested the transactional associations between maternal and child symptomatology and mediation of maternal childhood trauma on offspring symptoms via maternal depressive symptoms.ResultsMothers' childhood trauma history was related to greater prenatal and postnatal (12 and 24months) maternal depressive symptoms, which were prospectively associated with offspring internalizing problems at 36 and 48-60months. Child-directed effects on maternal depressive symptoms were not observed. The association of maternal trauma on children's internalizing at 36months was mediated by maternal depressive symptoms at 24months.LimitationsAssessments of the key study variables were provided by mothers. Childhood trauma was evaluated retrospectively.ConclusionWomen's experiences of adversity in childhood have persistent and cumulative effects on their depression during the transition to parenthood, which is associated with risk for children's internalizing. Given the two-generation influence of maternal childhood trauma exposure, attending to its impact may protect both caregivers and their children.

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.

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.

It is now well recognized that the gestational environment can have long-lasting effects not only on the life span and health span of an individual but also, through potential epigenetic changes, on future generations. This article reviews the “prenatal programming” of the neuroendocrine systems that regulate reproduction, with a specific focus on the lessons learned using ovine models. The review examines the critical roles played by steroids in normal reproductive development before considering the effects of prenatal exposure to exogenous steroid hormones including androgens and estrogens, the effects of maternal nutrition and stress during gestation, and the effects of exogenous chemicals such as alcohol and environment chemicals. In so doing, it becomes evident that, to maximize fitness, the regulation of reproduction has evolved to be responsive to many different internal and external cues and that the GnRH neurosecretory system expresses a degree of plasticity throughout life. During fetal life, however, the system is particularly sensitive to change and at this time, the GnRH neurosecretory system can be “shaped” both to achieve normal sexually differentiated function but also in ways that may adversely affect or even prevent “normal function”. The exact mechanisms through which these programmed changes are brought about remain largely uncharacterized but are likely to differ depending on the factor, the timing of exposure to that factor, and the species. It would appear, however, that some afferent systems to the GnRH neurons such as kisspeptin, may be critical in this regard as it would appear to be sensitive to a wide variety of factors that can program reproductive function. Finally, it has been noted that the prenatal programming of neuroendocrine reproductive function can be associated with epigenetic changes, which would suggest that in addition to direct effects on the exposed offspring, prenatal programming could have transgenerational effects on reproductive potential.

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.

Peripheral inflammation, both during the prenatal period and in adulthood, impairs adult neurogenesis. We hypothesized that, similar to other programming effects of prenatal treatments, only prenatal inflammation causes long-term consequences in adult neurogenesis and its neurogenic niche. To test this, pregnant Wistar rats were subcutaneously injected with lipopolysaccharide (LPS; 0.5 mg/kg) or saline solution every other day from gestational/embryonic day (GD) 14-20. In addition adult animals were injected with a single intraperitoneal saline or LPS injection (1 mg/kg) and the effects on neurogenesis were assessed 7 days later. Alternatively, to evaluate long-term consequences of adult LPS injections, LPS (1 mg/kg) was administered peripherally to adult rats four times every other day, and the effects on neurogenesis were assessed 60 days later. Prenatal and adult LPS treatments reduced adult neurogenesis and provoked specific microglial (but not astroglial) activation in the dentate gyrus (DG). However, only prenatal inflammation-mediated effects were long-lasting (at least 60 days). Moreover, these effects were specific to the DG since the Subventricular Zone (SVZ) and the Rostral Migratory Stream (RMS) were not affected. In addition, these stimuli caused differential effects on the molecular components of the neurogenic niche; only prenatal LPS treatment reduced the local levels of TGF-β1 mRNA in the DG. Finally, TGF-β1 exerted its pro-neurogenic effects via the Smad 2/3 pathway in a neural stem cell culture. Taken together, these data add evidence to the duration, regional specificity and dramatic consequences of prenatal immune programming on CNS physiology, compared with the limited response observed in the adult brain. Fil: Graciarena, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Roca, Valeria Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina Fil: Mathieu, Patricia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Depino, Amaicha Mara. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina Fil: Pitossi, Fernando Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina

Prenatal programming of the epigenome is a critical determinant in offspring outcome and stands at the interface between environment and genetics. Maternal experiences such as stress and obesity are associated with a host of neurodevelopmental and metabolic diseases, some of which have been characterized into the second and third generations. The mechanism through which determinants such as maternal diet or stress contribute to disease development likely involves a complex interaction between the maternal environment, placental changes, and epigenetic programming of the embryo. While we have begun to more fully appreciate and explore the epigenome in determination of disease risk, we know little as to the contribution embryo sex makes in epigenetic regulation. This review discusses the importance of sex differences in the transmission and inheritance of traits that are generated in the prenatal environment using models of maternal stress and diet.

Background Prenatal programming describes the process in which environmental events during pregnancy shape and determine the development of the embryo with on-going implications until adulthood. One main trigger of this process is epigenetic changes, for example in DNA methylation. We also know that the genome plays an important role in the regulation of DNA-methylation and de-methylation and a variety of studies have identified meQTLs (methylation quantitative trait loci), i.e. SNPs that are significantly associated with methylation status. We evaluated whether the prenatal environment, genotype and prenatal environment or genotype x prenatal environment interaction was the best predictor of methylation levels in the child's epigenome. Methods We assessed epigenome-wide DNA-methylation levels and genome-wide SNP-genotypes from 817 Finnish cord blood samples from the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction (PREDO) cohort. Ten different prenatal environments with regard to prenatal stress (depression score, anxiety score, betamethasone intake), general maternal factors (maternal age, delivery mode, parity) as well as the mother's metabolism (pre-pregnancy BMI, maternal hypertension, gestational diabetes, oral glucose tolerance test) were investigated. Focusing on Variably Methylated Regions (VMRs) and on cis-effects (maximal distance of 1MB between SNP and CpG-site), we tested if environment, SNP-genotype, genotype and environment or genotype x environment interaction best fitted VMR methylation levels. We applied DeepSea, a machine-learning based method, on the top results to identify functionally relevant SNPs. Results 44% of all VMRs were best explained by SNP genotype alone, 32% by SNP x environment interaction and 24% by additive effects of SNP and environment. Environment alone was only once the best predictor. 8,124 (0.1%) of all investigated SNPs were predicted to be of functional significance. Functionally relevant meQTL-SNPs were located in close proximity to the specific CpG-site and enriched in promoter regions. Functionally relevant SNPs involved in genotype x environment models showed much broader peaks around the CpGs and were enriched for distal intergenic regions. Both SNP groups show different patterns with regard to enrichment for specific transcription factor binding sites. Discussion Our results suggest that either genotype, genotype and environment or genotype x environment but not environment alone predict variable methylation in newborn cord blood. Therefore, it is important to include environmental outcomes and genotypic data in epigenetic studies. Furthermore, while meQTLs were enriched in promoter regions, the broader peaks of SNPs involved in interaction models suggest long-distance effects are present in GxE interactions.

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 mother – offspring pairs from a community-based birth cohort from the Czech Republic (European Longitudinal Study of Pregnancy and Childhood; ELSPAC-CZ). MRI analyses focused on overall cortical gray matter (GM) volume and GM volume of cortical regions previously associated with major depression. Higher prenatal stress predicted more mood dysregulation, particularly higher anxiety, fatigue and anger, lower overall cortical GM volume (corrected for brain size) 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 above relationships. 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.

Prenatal stress can affect foetal neurodevelopment and result in increased risk of depression in adulthood. It promotes increased maternal hypothalamo-pituitary-adrenal gland (HPA) secretion of glucocorticoid (GC), leading to increased foetal and maternal GC receptor activity. Prenatal GC receptor activity is also increased during prenatal treatment with dexamethasone (DEX), which is commonly prescribed as a prophylactic treatment of preterm delivery associated morbid symptoms. Here, we exposed pregnant Wistar rats to 0.1 mg/kg/d DEX during the last week of pregnancy and performed cross-fostering at birth. In the adult offspring we then studied the effects of prenatal DEX exposure per se and the effects of rearing by a dam exposed to prenatal DEX. Offspring were assessed in the following paradigms testing biobehavioural processes that are altered in depression: progressive ratio schedule of reinforcement (anhedonia), Porsolt forced swim test (behavioural despair), US pre-exposure active avoidance (learned helplessness), Morris water maze (spatial memory) and HPA axis activity (altered HPA function). Responsiveness to a physical stressor in terms of HPA activity was increased in male offspring exposed prenatally to DEX. Despite this increased HPA axis reactivity, we observed no alteration of the assessed behaviours in offspring exposed prenatally to DEX. We observed impairment in spatial memory in offspring reared by DEX exposed dams, independently of prenatal treatment. This study does not support the hypothesis that prenatal DEX exposure leads to depression-like symptoms in rats, despite the observed sex-specific programming effect on HPA axis. It does however emphasise the importance of rearing environment on adult cognitive performances.

Associations of paranormal and superstitious beliefs with digit ratio (2D:4D) and absolute finger length (putatively indexing prenatal and pubertal-adolescent androgen levels, respectively), fluctuating asymmetry (FA; indexing developmental instability), and body measures at birth (indexing non-optimal fetal growth) were examined in a sample of 1118 adults. Higher (feminised) 2D:4D correlated with stronger beliefs in men, even when controlled for age, education, adult height and weight, and birth length and weight. Shorter (feminised) finger length correlated with more superstition among women, but not when controlled for the same covariates. Finger FA was unrelated to beliefs in both sexes. Shorter birth length (in men and women) and lighter adult weight (in women) were associated with stronger beliefs. Effects of 2D:4D on men’s beliefs were weak (1–3% attributable variance), but commensurable with those of known non-biological belief correlates (age: 1%; education: 2%). This evidence may be informative for narrowing down possible developmental pathways of paranormal and superstitious beliefs. Propensities contributing to sex and individual differences in these beliefs probably arise in utero, may partly be due to prenatal testosterone and other prenatal programming effects, but less likely due to pubertal-adolescent androgen action or developmental instability.

Prenatal stress is an important risk factor in schizophrenia, and the aetiological factors mediating this relationship are central to the neurodevelopmental hypothesis of schizophrenia. The glucocorticoid receptor (GR) agonist dexamethasone (DEX) is commonly prescribed for prenatal conditions, and results in GR activation, which is part of the stress response. To investigate animal evidence for whether prenatal DEX leads to development of schizophrenia-like phenotypes, Wistar rats were prenatally exposed to DEX (0.1 mg/kg/day) between the gestational days 15 and 21, and tested in two paradigms known to be disrupted in schizophrenia patients: prepulse inhibition (PPI) and latent inhibition (LI). A cross-fostering design was used to allow dissociation of any direct prenatal effects on offspring from effects dependent on DEX exposure of the rearing dam. Pup birth weight was reduced by prenatal DEX treatment. DEX-treated dams demonstrated increased pup-directed behaviour. There were additive effects of prenatal DEX treatment and DEX treatment of rearing dam in terms of reduced body weight in adulthood. In one of two replications, PPI was increased by prenatal DEX in males only and specific to the highest prepulse intensity. There was no evidence that LI was disrupted by prenatal DEX treatment. This study does not provide support for the hypothesis that prenatal DEX exposure leads to schizophrenia-like deficits in PPI or LI, suggesting that GR prenatal programming is not a mechanism of direct relevance to the neurodevelopmental hypothesis of schizophrenia.

OBJECTIVE To explore cultural idea systems related to maternal diet and diabetes with 2 generations of women in an Aboriginal community. METHODS Semi-structured and unstructured interviews with a theoretical sample of 14 mothers and 14 grandmothers were audiorecorded, transcribed fully and analyzed thematically. RESULTS Diabetes was discussed in 20 of 35 interviews, with a focus on causation theories and ways to prevent diabetes. Both groups linked sugar and processed foods with diabetes. More grandmothers talked about decreasing activity patterns and increasing maternal size, while more mothers emphasized the role of stress in diabetes during pregnancy. Both groups discussed prevention measures, such as an increased consumption of wild meat and fresh foods. CONCLUSIONS Both generations expressed concern about diabetes and recommended preventative actions. Indications of cross-generational learning suggest community resources may be helpful in prenatal programming for Aboriginal women.

This paper reviews three designs that compare co-twins in tests of prenatal programming. The first design uses co-twin comparisons to attempt within-family replications of between-family associations, reported in non-twins, between reduced fetal growth and risk for later disease or behavior disorder. These replication efforts are mixed, perhaps due to small samples of weight-discordant twins, perhaps confounded by differences in the meaning of fetal growth in twins. The second design compares monozygotic co-twins from pairs differing in their placentation, with some evidence, again constrained by sample limitations that twins sharing a single placenta are more alike in dimensions of cognitive ability and personality. A third design employs a dermatoglyphic index of bilateral asymmetry as a marker of reduced buffering from environmental noise, with positive results from MZ twins that await necessary replication in longitudinal data from non-twins. Twin comparisons, especially the comparisons of monozygotic co-twins, offer an informative and incisive approach for research on prenatal programming in humans.

Binge eating (BE) is a common aberrant form of eating behavior, characterized by overconsumption of food in a brief period of time. Recurrent episodes of BE constitute the BE disorder, which mostly affects females and is associated with early-life adversities. Here, we show that corticotropin releasing factor (CRF)-induced prenatal stress (PNS) in late gestation predisposes female offspring to BE-like behavior that coincides with hypomethylation of hypothalamic miR-1a and downstream dysregulation of the melanocortin system through Pax7/Pax3. Moreover, exposing the offspring to a methyl-balanced diet during adolescence prevents the dysregulation and predisposition from being triggered. We demonstrate that gestational programming, per se, will not lead to BE-like behavior, but pre-existing alterations due to prenatal programming are revealed only when challenged during adolescence. We provide experimental evidence for long-term epigenetic abnormalities stemming from PNS in predisposing female offspring to BE disorder as well as a potential non-invasive prevention strategy.

Prenatal programming of adult hypertension in the rat.BackgroundEpidemiological studies have suggested that low birthweight is a risk factor for the development of essential hypertension in adulthood, but the mechanism is unknown.MethodsA rat model of intrauterine growth retardation was employed. Pregnant Sprague-Dawley rats were kept on 6% protein or on control isocaloric 20% protein diet from gestational day 12 until term. Systolic blood pressures of the offspring were monitored by the tail cuff method. Apoptosis was determined by the TUNEL method, cell proliferation by anti-Ki67 antibody, and the total number of glomeruli by the maceration method. Results are mean ± SD.ResultsThe kidney and body sizes of the offspring from the low-protein pregnancies (LP) were proportionately decreased at birth. Full catch-up growth occurred during the first two weeks of life. The kidneys were normal by standard histology but exhibited increased apoptosis without increased cell proliferation at eight weeks of age. The total number of glomeruli per kidney was decreased by 28% in males (P < 0.001) and by 29% in females (P < 0.01). By eight weeks of age, both male and female LP had systolic blood pressures that were 20 to 25 mm Hg higher than those of control animals (P < 0.001), and their 18-month survival was significantly decreased (44 vs. 93%, P < 0.01). During the prehypertensive stage, at four weeks of age, PRA in LP was low (1.7 ± 1.4 vs. 19.7 ± 5.5 ng/mL/hour in males, P < 0.0001; 4.9 ± 2.2 vs. 14.9 ± 7.2 ng/mL/hour in females, P < 0.0005), and aldosterone was high (93 ± 15 vs. 54 ± 27 pg/mL in males, P < 0.005; 93 ± 20 vs. 48 ± 20 pg/mL in females, P < 0.0001). Smaller but significant differences persisted at eight weeks of age.ConclusionsAdult blood pressure profile is susceptible to prenatal programming by maternal low-protein diet in the rat. The mechanism may involve an altered renin-aldosterone axis and a deficit in total nephron number.

The steroid milieu of differentiating mammals influences aspects of growth and development. Changes to the steroid milieu of a differentiating mammal results in physiological changes to that animal. These changes can be permanent and identified as phenomena measured in later life. During prenatal development, steroids programme the timing of critical events such as birth, puberty and death. They also influence body shape and composition, growth rates, physiology, placental morphology, behaviour and sexual differentiation. Prenatal steroids programme livestock and their manipulation can result in enhanced growth characters in domestic livestock.

subcutaneous cellular tissue and fascia is necessary for the diagnosis. In the initial stages the inflammatory infiltrate is composed of plasma cells and abundant eosinophils, which are more scarce or nonexistent in advanced lesions. Isolated fibrosis of miocitos can exist as well as areas of mild myositis. The presence of rimeed vacuoles (Pic. 1) raises the differential diagnosis with inclusion body myositis, but in this entity, the facial and interstitial affectation is not so striking in the aspect of fibrosis reparative.

Background Maternal stress in early life has been associated with the development of asthma in children, although it is unclear whether there are any critical periods of exposure. The association of asthma with prenatal exposure to maternal stress has not been reported. Objective We tested whether prenatal and postnatal anxiety and/or depression in pregnant women predicted the risk of their offspring developing asthma in childhood. Methods The Avon Longitudinal Study of Parents and Children is a population-based birth cohort recruited during pregnancy. Data were available on maternal anxiety scores and asthma at age 7½ years in 5810 children. Anxiety was assessed at 18 and 32 weeks of gestation by using the validated Crown-Crisp Experiential Index. Asthma was defined at age 7½ years as doctor-diagnosed asthma with current symptoms or treatment in the previous 12 months. Multivariable logistic regression was used to determine the association of prenatal anxiety with asthma (odds ratio; 95% CI). Results Independent of postnatal anxiety and adjusted for a number of likely confounders, there was a higher likelihood of asthma at age 7½ years (odds ratio, 1.64; 95% CI, 1.25-2.17) in children of mothers in the highest compared with lowest quartile of anxiety scores at 32 weeks of gestation, with evidence for a dose-response ( P value for trend Conclusions Maternal anxiety symptoms as an indicator of stress during fetal life may program the development of asthma during childhood.