Prenatal Effects Research Articles

Impact of an mHealth intervention on parents' emotional health and on the neurodevelopment of high-risk infants.

We assess the prenatal and postnatal effect of the High-Risk Pregnancy and Baby Parenting programme, which is complemented with two mHealth (app-based) resources. The GLM Repeated Measures Model technique was used to explore differences in the emotional health of the participants and in their infants' neurodevelopment, comparing programme versus usual care groups, composed of 150 and 195 participants, respectively. The mothers presented lower levels of depression (mean difference 1.74, p = 0.04, 95% CI 0.07, 3.40) and higher levels of resilience (mean difference 4.09, p = 0.004, 95% CI 1.40, 6.78). For the fathers, positive effects on resilience were recorded (p < 0.001). A positive treatment effect was perceived in the infants' cognitive (p = 0.014), language (p < 0.001) and motor (p = 0.006) development. These findings suggest application of the programme can benefit maternal emotional health and infant neurodevelopment. M-Health technology could make this programme more accessible.

Prenatal Opioid Exposure Effect on Cleft Palate Repair Recovery.

Prenatal Opioid Exposure Effect on Cleft Palate Repair Recovery.

Maternal high BMI: Sex-dimorphic alterations in maternal and offspring stress indices

Maternal body mass index (BMI) influences pregnancy and birth outcomes along with child metabolic and neurodevelopmental health and fetal sex may be a moderating factor in these effects. Alternations in autonomic nervous system (ANS) functioning, identified in heart rate (HR) measurements, could present early markers of these prenatal programming effects in both the mother and the developing fetus. This study examines the associations between pre-pregnancy BMI and maternal and fetal ANS functioning and infant postnatal behavioral outcomes stratified by fetal sex. Pregnant women (N=176) were recruited at gestational week (GW) T1: 12–22 and categorized into Normal (BMI< 25) or High BMI (BMI > 25). Women attended laboratory sessions at T2: GW 23–28, and T3: GW 34–36 to assess maternal and fetal HR and HR variability (HRV) at baseline and after a stressor at T3. Infant behavior was assessed at 4 months using the Infant Behavior Questionnaire-Revised. Women with high BMI bearing female fetuses had higher HR and lower HRV at both gestational time points. Later in the third trimester, female fetuses of high BMI women exhibited lower HRV when challenged with a stressor. At 4 months, female infants were rated as having lower scores on the Orienting/Regulatory scale. Our findings provide evidence of female sex-specific programming of maternal pre-pregnancy BMI on maternal ANS regulation and neurodevelopment identified in-utero and continuing into early infancy.

Prenatal and postnatal source-specific PM10 effects on child cognition at 4 and 18 months in an England birth cohort

Prenatal and postnatal source-specific PM10 effects on child cognition at 4 and 18 months in an England birth cohort

The effects of illicit drug use during pregnancy and parental hostility on problem behaviors in school-aged children over and above genetic influences.

Previous work has examined the impact of prenatal illicit drug use (PDU) on children's problem behaviors. However, many PDU-related risk factors, including genetic and rearing environmental risks, can also influence offspring's problem behaviors, thus confounding PDU, genetic, and rearing environmental influences. This study aimed to (a) identify effects of PDU on school-aged children's problem behaviors, including both externalizing and internalizing behaviors at Age 7, after controlling genetic and specific rearing environmental (e.g., maternal and paternal hostility at Ages 4.5 and 6) influences and (b) examine interaction effects between PDU and maternal and paternal hostility in predicting children's problem behaviors at Age 7. We used a parent-offspring adoption design to partition genetic and prenatal effects from postnatal rearing environmental influences. Participants were 561 children adopted at birth (42% female; 56% White, 19% multiracial, 13% Black/African American, 11% Latine, and 1% other), their adoptive parents, and their birth parents. Results indicate that PDU did not show a direct impact on Age 7 problem behaviors before or after controlling genetic risks and adoptive mother's and father's hostility. However, we found significant interactions between adoptive father's hostility and PDU when predicting children's problem behaviors, such that higher paternal hostility was associated with higher externalizing and internalizing behaviors for children whose birth mothers were non-use or rare use of illicit drugs during pregnancy. The results suggest that different from non- or rare drug-exposed children, higher levels of PDU may override the effects of paternal hostility, but not maternal hostility, on problem behaviors at Age 7. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

P-468 Relationship between spiritual well-being and prenatal stress level of women conceiving spontaneously or with assisted reproductive techniques

Abstract Study question Is there a relationship between spiritual well-being and prenatal stress level of women who conceived with spontaneous/assisted reproductive techniques (ART)? Summary answer Women Conceiving with ART have higher prenatal stress. As the spiritual well-being of women conceiving with ART increases, the level of prenatal distress decreases. What is known already The negative effects of prenatal stress on maternal-fetal well-being are known. Spirituality provides emotional support by feeling the support of spiritual forces, affirmation in re-meaning life, strengthening the ability to cope with stress with the teachings of the belief system, and increasing hope and harmony. The stress created by fertility treatment may continue during pregnancy. It is thought that spirituality may be effective in coping with stress in pregnancies after ART. Studies in this area are limited. Study design, size, duration he comparative descriptive study was conducted with 202 pregnant women, 115 spontaneous and 87 ART pregnant women, who applied to the obstetrics outpatient clinics of a state hospital between November 2021 and June 2022. Data were collected in an average of 15-20 minutes by face-to-face interview technique. According to the statistical analysis, the effect size was calculated as 0.80 and the statistical power as 99%. Participants/materials, setting, methods Participants (a) who can speak and understand Turkish; (b) 18-49 years of age women; (c) who are 14 and above gestational weeks; (d) who haven’t risk pregnancies were included. The data of the research were collected with the “Personal Information Form”, “Spiritual Well-being Scale “ and “Tilburg Pregnancy Distress Scale”. The research data were evaluated by percentile calculations, averages, Chi-square analysis, Mann Whitney U test, Kruskal Wallis test and Bonferroni test. Main results and the role of chance The average age of women who conceived with ART is 28.91±6.06, and the average age of women who conceived spontaneously is 28.08±5.75. The Spiritual Well-being Scale (SWBS) of the pregnant groups was determined as 124.52±12.00 for the ART group and 123.92±9.02 for the spontaneous group, and there was no statistical significance in terms of spiritual well-being between the groups (p &amp;gt; 0.05). In our study prenatal distress was detected in 12.6% of pregnant women in the ART group (above 28 points) and in 9.6% of spontaneous pregnant women (above 28 points) according to the Tilburg Pregnancy Distress Scale (TPDS) cut-off score. A statistically significant and negative relationship was found between the total SWBS and TPDS (r=-0.256, p &amp;lt; 0.05) in the ART group. A statistically significant and negative relationship was found between the total SWBS and TPDS (r=-0.256, p &amp;lt; 0.05) in the ART group. Limitations, reasons for caution Since the study was conducted in a single center in a province in the west of Turkey, it is a limitation that the results of the study cannot be generalized to the whole population. Wider implications of the findings The ART group experiences higher prenatal distress than the other group. As the spiritual well-being of pregnant women in the ART group increases, the level of prenatal distress decreases. Nurses and midwives should be aware of the prenatal distress-reducing effect on spiritual well-being and provide spiritual counseling. Trial registration number not applicable

The effects of buprenorphine and morphine during pregnancy: Impact of exposure length on maternal brain, behavior, and offspring neurodevelopment

The escalating incidence of opioid-related issues among pregnant women in the United States underscores the critical necessity to understand the effects of opioid use and Medication for Opioid Use Disorders (MOUDs) during pregnancy. This research employed a translational rodent model to examine the impact of gestational exposure to buprenorphine (BUP) or morphine on maternal behaviors and offspring well-being. Female rats received BUP or morphine before conception, representing established use, with exposure continuing until postnatal day 2 or discontinued on gestational day 19 to mimic treatment cessation before birth. Maternal behaviors – including care, pup retrieval, and preference – as well as hunting behaviors and brain neurotransmitter levels were assessed. Offspring were evaluated for mortality, weight, length, milk bands, surface righting latency, withdrawal symptoms, and brain neurotransmitter levels. Our results reveal that regardless of exposure length (i.e., continued or discontinued), BUP resulted in reduced maternal care in contrast to morphine-exposed and control dams. Opioid exposure altered brain monoamine levels in the dams and offspring, and was associated with increased neonatal mortality, reduced offspring weight, and elevated withdrawal symptoms compared to controls. These findings underscore BUP's potential disruption of maternal care, contributing to increased pup mortality and altered neurodevelopmental outcomes in the offspring. This study calls for more comprehensive research into prenatal BUP exposure effects on the maternal brain and infant development with the aim to mitigate adverse outcomes in humans exposed to opioids during pregnancy.

Juvenile peripheral LPS exposure overrides female resilience to prenatal VPA effects on adult sociability in mice

Autism spectrum disorder (ASD) exhibits a gender bias, with boys more frequently affected than girls. Similarly, in mouse models induced by prenatal exposure to valproic acid (VPA), males typically display reduced sociability, while females are less affected. Although both males and females exhibit VPA effects on neuroinflammatory parameters, these effects are sex-specific. Notably, females exposed to VPA show increased microglia and astrocyte density during the juvenile period. We hypothesized that these distinct neuroinflammatory patterns contribute to the resilience of females to VPA. To investigate this hypothesis, we treated juvenile animals with intraperitoneal bacterial lipopolysaccharides (LPS), a treatment known to elicit brain neuroinflammation. We thus evaluated the impact of juvenile LPS-induced inflammation on adult sociability and neuroinflammation in female mice prenatally exposed to VPA. Our results demonstrate that VPA-LPS females exhibit social deficits in adulthood, overriding the resilience observed in VPA-saline littermates. Repetitive behavior and anxiety levels were not affected by either treatment. We also evaluated whether the effect on sociability was accompanied by heightened neuroinflammation in the cerebellum and hippocampus. Surprisingly, we observed reduced astrocyte and microglia density in the cerebellum of VPA-LPS animals. These findings shed light on the complex interactions between prenatal insults, juvenile inflammatory stimuli, and sex-specific vulnerability in ASD-related social deficits, providing insights into potential therapeutic interventions for ASD.

Investigating the neurobiology of maternal opioid use disorder and prenatal opioid exposure using brain organoid technology.

Over the past two decades, Opioid Use Disorder (OUD) among pregnant women has become a major global public health concern. OUD has been characterized as a problematic pattern of opioid use despite adverse physical, psychological, behavioral, and or social consequences. Due to the relapsing-remitting nature of this disorder, pregnant mothers are chronically exposed to exogenous opioids, resulting in adverse neurological and neuropsychiatric outcomes. Collateral fetal exposure to opioids also precipitates severe neurodevelopmental and neurocognitive sequelae. At present, much of what is known regarding the neurobiological consequences of OUD and prenatal opioid exposure (POE) has been derived from preclinical studies in animal models and postnatal or postmortem investigations in humans. However, species-specific differences in brain development, variations in subject age/health/background, and disparities in sample collection or storage have complicated the interpretation of findings produced by these explorations. The ethical or logistical inaccessibility of human fetal brain tissue has also limited direct examinations of prenatal drug effects. To circumvent these confounding factors, recent groups have begun employing induced pluripotent stem cell (iPSC)-derived brain organoid technology, which provides access to key aspects of cellular and molecular brain development, structure, and function in vitro. In this review, we endeavor to encapsulate the advancements in brain organoid culture that have enabled scientists to model and dissect the neural underpinnings and effects of OUD and POE. We hope not only to emphasize the utility of brain organoids for investigating these conditions, but also to highlight opportunities for further technical and conceptual progress. Although the application of brain organoids to this critical field of research is still in its nascent stages, understanding the neurobiology of OUD and POE via this modality will provide critical insights for improving maternal and fetal outcomes.

Associations of prenatal stress with 5-year-old children's executive function in a low socioeconomic status population.

Prenatal stress has a significant, but small, negative effect on children's executive function (EF) in middle and high socioeconomic status (SES) households. Importantly, rates and severity of prenatal stress are higher and protective factors are reduced in lower SES households, suggesting prenatal stress may be particularly detrimental for children's EF in this population. This study examined whether prenatal stress was linked to 5-year-old's EF in a predominantly low SES sample and child sex moderated this association, as males may be more vulnerable to adverse prenatal experiences. Participants were 132 mother-child dyads drawn from a prospective prenatal cohort. Mothers reported on their depression symptoms, trait anxiety, perceived stress, everyday discrimination, and sleep quality at enrollment and once each trimester, to form a composite prenatal stress measure. Children's EF was assessed at age 5 years using the parent-report Behavior Rating Inventory of Executive Function - Preschool (BRIEF-P) Global Executive Composite subscale and neuropsychological tasks completed by the children. Mixed models revealed higher prenatal stress was associated with lower BRIEF-P scores, indicating better EF, for females only. Higher prenatal stress was associated with lower performance on neuropsychological EF measures for both males and females. Results add to the limited evidence about prenatal stress effects on children's EF in low SES households.

Breeding density affects the movements of gull chicks, the size of their home ranges and their association with neighbours.

Colonies of ground-nesting species often have heterogeneous nest densities and their offspring experience different social conditions depending on the size and location of the breeding territory. For example, unintentional territory crossing by mobile chicks can trigger strong aggression from neighbouring adults, as observed in semi-precocial gulls. This would be expected to shape chicks' movement tendencies, exploratory behaviour and propensity for social contact through aversive feedback learning or pre-natal maternal effects, as mothers may pre-adapt their offspring's behaviour to the expected early life conditions. Therefore, we hypothesize that lesser black-backed gull chicks reared in denser areas of the breeding colony will move less, have smaller home ranges and have fewer social contacts with chicks from neighbouring nests. To test this, we first cross-fostered full clutches between and within high- and low-density parts of the colony, and then used ultra-wideband tags to track free-ranging chicks. In line with our predictions, we found that chicks reared in denser areas had a lower movement activity and smaller home ranges. However, these chicks still had more social contacts, although not necessarily with a higher number of unique individuals. Pre-natal breeding density had no significant effect on any of the parameters. We conclude that parental nest choice strongly affects the early social environment of their chicks, which can shape the development of their (social) phenotype, with potentially long-lasting consequences.

Pregestational fructose-induced metabolic syndrome in Wistar rats causes sexually dimorphic behavioral changes in their offspring.

Metabolic syndrome (MetS), marked by enduring metabolic inflammation, has detrimental effects on cognitive performance and brain structure, influencing behavior. This study aimed to investigate whether maternal MetS could negatively impact the neurodevelopment and metabolism of offspring. To test this hypothesis, 2 months old female Wistar rats were subjected to a 10-week regimen of tap water alone or supplemented with 20% fructose to induce MetS. Dams were mated with healthy males to generate litters: OC (offspring from control dams) and OMetS (offspring from dams with MetS). To isolate prenatal effects, all pups were breastfed by control nurse dams, maintaining a standard diet and water ad libitum until weaning. Behavioral assessments were conducted between postnatal days (PN) 22 and 95, and metabolic parameters were analyzed post-sacrifice on PN100. Results from the elevated plus maze, the open field, and the marble burying tests revealed a heightened anxiety-like phenotype in OMetS females. The novel object recognition test showed that exclusively OMetS males had long-term memory impairment. In the reciprocal social interaction test, OMetS displayed a lower number of social interactions, with a notable increase in "socially inactive" behavior observed exclusively in females. Additionally, in the three-chamber test, social preference and social novelty indexes were found to be lower solely among OMetS females. An increase in visceral fat concomitantly with hypertriglyceridemia was the relevant postmortem metabolic finding in OMetS females. In summary, maternal MetS leads to enduring damage and adverse effects on offspring neurobehavior and metabolism, with notable sexual dimorphism.

What does scientometry tell us about mercury toxicology and its biological impairments?

Mercury is a toxic pollutant that poses risks to both human and environmental health, making it a pressing public health concern. This study aimed to summarize the knowledge on mercury toxicology and the biological impairments caused by exposure to mercury in experimental studies and/or diagnosis in humans. The research was conducted on the main collection of Web of Science, employing as a methodological tool a bibliometric analysis. The selected articles were analyzed, and extracted data such as publication year, journal, author, title, number of citations, corresponding author's country, keywords, and the knowledge mapping was performed about the type of study, chemical form of mercury, exposure period, origin of exposure, tissue/fluid of exposure measurement, mercury concentration, evaluation period (age), mercury effect, model experiments, dose, exposure pathway, and time of exposure. The selected articles were published between 1965 and 2021, with Clarkson TW being the most cited author who has also published the most articles. A total of 38% of the publications were from the USA. These studies assessed the prenatal and postnatal effects of mercury, emphasizing the impact of methylmercury on neurodevelopment, including motor and cognitive evaluations, the association between mercury and autism, and an evaluation of its protective effects against mercury toxicity. In observational studies, the blood, umbilical cord, and hair were the most frequently used for measuring mercury levels. Our data analysis reveals that mercury neurotoxicology has been extensively explored, but the association among the outcomes evaluated in experimental studies has yet to be strengthened. Providing metric evidence on what is unexplored allows for new studies that may help governmental and non-governmental organizations develop guidelines and policies.

Pleiotropic effects of trisomy and pharmacologic modulation on structural, functional, molecular, and genetic systems in a Down syndrome mouse model.

Down syndrome (DS) is characterized by skeletal and brain structural malformations, cognitive impairment, altered hippocampal metabolite concentration and gene expression imbalance. These alterations were usually investigated separately, and the potential rescuing effects of green tea extracts enriched in epigallocatechin-3-gallate (GTE-EGCG) provided disparate results due to different experimental conditions. We overcame these limitations by conducting the first longitudinal controlled experiment evaluating genotype and GTE-EGCG prenatal chronic treatment effects before and after treatment discontinuation. Our findings revealed that the Ts65Dn mouse model reflected the pleiotropic nature of DS, exhibiting brachycephalic skull, ventriculomegaly, neurodevelopmental delay, hyperactivity, and impaired memory robustness with altered hippocampal metabolite concentration and gene expression. GTE-EGCG treatment modulated most systems simultaneously but did not rescue DS phenotypes. On the contrary, the treatment exacerbated trisomic phenotypes including body weight, tibia microarchitecture, neurodevelopment, adult cognition, and metabolite concentration, not supporting the therapeutic use of GTE-EGCG as a prenatal chronic treatment. Our results highlight the importance of longitudinal experiments assessing the co-modulation of multiple systems throughout development when characterizing preclinical models in complex disorders and evaluating the pleiotropic effects and general safety of pharmacological treatments.

Pleiotropic effects of trisomy and pharmacologic modulation on structural, functional, molecular, and genetic systems in a Down syndrome mouse model

Down syndrome (DS) is characterized by skeletal and brain structural malformations, cognitive impairment, altered hippocampal metabolite concentration and gene expression imbalance. These alterations were usually investigated separately, and the potential rescuing effects of green tea extracts enriched in epigallocatechin-3-gallate (GTE-EGCG) provided disparate results due to different experimental conditions. We overcame these limitations by conducting the first longitudinal controlled experiment evaluating genotype and GTE-EGCG prenatal chronic treatment effects before and after treatment discontinuation. Our findings revealed that the Ts65Dn mouse model reflected the pleiotropic nature of DS, exhibiting brachycephalic skull, ventriculomegaly, neurodevelopmental delay, hyperactivity, and impaired memory robustness with altered hippocampal metabolite concentration and gene expression. GTE-EGCG treatment modulated most systems simultaneously but did not rescue DS phenotypes. On the contrary, the treatment exacerbated trisomic phenotypes including body weight, tibia microarchitecture, neurodevelopment, adult cognition, and metabolite concentration, not supporting the therapeutic use of GTE-EGCG as a prenatal chronic treatment. Our results highlight the importance of longitudinal experiments assessing the co-modulation of multiple systems throughout development when characterizing preclinical models in complex disorders and evaluating the pleiotropic effects and general safety of pharmacological treatments.

Prenatal stress and externalizing behaviors in childhood and adolescence: A systematic review and meta-analysis.

Accumulating evidence suggests that psychological distress during pregnancy is linked to offspring risk for externalizing outcomes (e.g., reactive/aggressive behaviors, hyperactivity, and impulsivity). Effect sizes across studies have varied widely, however, due to differences in study design and methodology, including control for the confounding continuation of distress in the postnatal period. Clarifying these inconsistencies is necessary to guide the precision of prevention efforts and inform public health policies. A meta-analysis was conducted with 55 longitudinal studies to investigate the association between prenatal psychological distress (anxiety, depression, and perceived stress) and offspring externalizing behaviors. Results revealed a significant but small effect (r = .160) of prenatal distress on externalizing behaviors. The magnitude of the prenatal effect size remained largely unchanged after adjusting for postnatal distress (r = .159), implicating a unique effect of psychological distress during the prenatal period in the etiology of externalizing behaviors. Moderation tests showed that prenatal effects did not vary based on type and timing of psychological distress during pregnancy. Greater instability of distress from prenatal to postnatal periods predicted larger effects. Prenatal effects were comparable across most externalizing outcomes, consistent with the common comorbidity of externalizing spectrum disorders, although effects appeared smaller for nonaggressive rule-breaking (vs. aggressive) behaviors. Significant associations persisted across all developmental periods, appearing slightly larger in early childhood. We discuss these results in the context of developmental and psychobiological theories of externalizing behavior, offer preliminary clinical and public health implications, and highlight directions for future research including the need for longitudinal studies with more racially and socioeconomically diverse families. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Maternal Diet Associates with Offspring Bone Mineralization, Fracture Risk and Enamel Defects in Childhood and Influences the Prenatal Effect of High-Dose Vitamin D Supplementation.

We previously demonstrated a beneficial effect of high-dose vitamin D in pregnancy on offspring bone and dental health. Here, we investigated the effect of maternal dietary patterns during pregnancy on the risk of bone fractures, bone mineralization and enamel defects until age 6 years in the offspring. Further, the influence of diet on the effect of high-dose vitamin D was analyzed in the COPSAC2010 mother-child cohort including 623 mother-child pairs. A weighted network analysis on FFQs revealed three specific maternal dietary patterns that associated (Bonferroni p < 0.05) with both offspring bone and dental health. The effect of prenatal high-dose (2800 IU/day) vs. standard-dose (400 IU/day) vitamin D on offspring bone mineral content (adjusted mean difference (aMD): 33.29 g, 95% CI: 14.48-52.09, p < 0.001), bone mineral density (aMD: 0.02 g/cm2 (0.01-0.04), p < 0.001), fracture risk (adjusted incidence rate ratio: 0.36 (0.16-0.84), p = 0.02), and enamel defects in primary (adjusted odds ratio (aOR): 0.13 (0.03-0.58), p < 0.01) and permanent molars (aOR: 0.25; (0.10-0.63), p < 0.01) was most pronounced when mothers had lower intake of fruit, vegetables, meat, eggs, sweets, whole grain, offal and fish. This study suggests that prenatal dietary patterns influence offspring bone and dental development, and should be considered in order to obtain the full benefits of vitamin D to enhance personalized supplementation strategy.

Behavioral and Molecular Characterization of Prenatal Stress Effects on the C57BL/6J Genetic Background for the Study of Autism Spectrum Disorder.

Stress-inducing events during pregnancy are associated with aberrant neurodevelopment resulting in adverse psychiatric outcomes, including autism spectrum disorder (ASD). While numerous preclinical models for the study of ASD are frequently generated using C57BL/6J mice, few studies have investigated the effects of prenatal stress on this genetic background. In the current manuscript, we stressed C57BL/6 dams during gestation and examined numerous behavioral and molecular endophenotypes in the adult male and female offspring to characterize the resultant phenotype as compared with offspring born from nonstressed (NS) dams. Adult mice born from prenatal restraint stressed (PRS) dams demonstrated reduced sociability and reciprocal social interaction along with increased marble burying behaviors relative to mice born from nonstressed control dams. Differential expression of genes related to excitatory and inhibitory neurotransmission was evaluated in the medial prefrontal cortex, amygdala, hippocampus, nucleus accumbens and caudate putamen via qRT-PCR. The male PRS mouse behavioral phenotype coincided with aberrant expression of glutamate and GABA marker genes (e.g., Grin1, Grin2b, Gls, Gat1, Reln) in neural substrates of social behavior. Rescue of the male PRS sociability deficit by a known antipsychotic with epigenetic properties (i.e., clozapine (5 mg/kg) + 18 hr washout) indicated possible epigenetic regulation of genes that govern sociability. Clozapine treatment increased the expression levels of genes involved in DNA methylation, histone methylation, and histone acetylation in the nucleus accumbens. Identification of etiology-specific mechanisms underlying clinically relevant behavioral phenotypes may ultimately provide novel therapeutic interventions for the treatment of psychiatric disorders including ASD.

Poverty and neighborhood opportunity effects on neonate DNAm developmental age.

Children from families with low socioeconomic status (SES), as determined by income, experience several negative outcomes, such as higher rates of newborn mortality and behavioral issues. Moreover, associations between DNA methylation and low income or poverty status are evident beginning at birth, suggesting prenatal influences on offspring development. Recent evidence suggests neighborhood opportunities may protect against some of the health consequences of living in low income households. The goal of this study was to assess whether neighborhood opportunities moderate associations between household income (HI) and neonate developmental maturity as measured with DNA methylation. Umbilical cord blood DNA methylation data was available in 198 mother-neonate pairs from the larger CANDLE cohort. Gestational age acceleration was calculated using an epigenetic clock designed for neonates. Prenatal HI and neighborhood opportunities measured with the Childhood Opportunity Index (COI) were regressed on gestational age acceleration controlling for sex, race, and cellular composition. Higher HI was associated with higher gestational age acceleration (B = .145, t = 4.969, p = 1.56x10-6, 95% CI [.087, .202]). Contrary to expectation, an interaction emerged showing higher neighborhood educational opportunity was associated with lower gestational age acceleration at birth for neonates with mothers living in moderate to high HI (B = -.048, t = -2.08, p = .03, 95% CI [-.092, -.002]). Female neonates showed higher gestational age acceleration at birth compared to males. However, within males, being born into neighborhoods with higher social and economic opportunity was associated with higher gestational age acceleration. Prenatal HI and neighborhood qualities may affect gestational age acceleration at birth. Therefore, policy makers should consider neighborhood qualities as one opportunity to mitigate prenatal developmental effects of HI.

Long-term consequences of acute toxic prenatal hypoxia induced by sodium nitrite in rat experiments

Introduction. Gestational hypoxia plays an important role in fetal development, as it causes the development of oxidative stress and delayed psychomotor development. The aim of the study was to evaluate the prenatal effect of sodium nitrite on indices characterizing orienting and exploratory activity, mental activity and the degree of hypoxia in rat offspring. Materials and methods. Acute hypoxia was modeled by administration of sodium nitrite at a dose of 30 mg/kg intramuscularly to five pregnant rats during 16–19 days of gestation. Five females constituted a control group. In 50 born rats, orientation and exploration activity, cognitive functions, intensity of lipid peroxidation and glycolysis were studied. Results. The offspring of females that underwent acute hypoxia significantly lagged behind in the positive dynamics of body weight gain compared to control individuals. Thirty-day-old rats showed a pronounced disorder of the structure of behavioral pattern, learning process and long-term memory, increased content of diene conjugates, malonic dialdehyde and the level of lactate dehydrogenase activity in blood. Discussion. It was found that offspring whose mothers suffered acute hypoxia of toxic genesis developed pronounced behavioral disorders of psychomotor agitation and cognitive dysfunction characterized by decreased learning ability and impaired long-term memory. The content of primary and secondary products of lipid peroxidation and lactate dehydrogenase was increased in rats. The development of cellular oxidative stress under conditions of intrauterine hypoxia leads to oxygen deficiency in the fetus and a switch from tissue respiration to glycolysis, which underlies CNS damage. Conclusion. It was shown that sodium nitrite administration during the period from the 16th to the 19th day of gestation caused hyperactivity, depressed emotional status, and decreased orienting and exploratory activity and the ability to learn and retain a memory trace in rat offspring. Increased levels of diene conjugates and malonic dialdehyde, lactate dehydrogenase activity were observed in rats.