Subtle alterations in neonatal neurodevelopment following early or late exposure to prenatal maternal immune activation in mice.
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ABSTRACT:
SUBMITTER: Guma E
PROVIDER: S-EPMC8573196 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveThe aim of the study was to examine the association of lifetime maternal depression with regulation of immune responses in the infant, measured by cytokine levels and lymphocyte proliferation (LP) in cord blood mononuclear cells collected at delivery.MethodsWe studied women recruited in early pregnancy into the Project Viva longitudinal cohort who had cord blood assayed after delivery (N = 463). Women reported about depressive symptoms in midpregnancy (Edinburgh Postnatal Depression Scale) and depression history by questionnaire. Immune responses were assayed by an index of LP, and concentrations of five cytokines (interleukin [IL]-6, IL-10, IL-13, tumor necrosis tumor necrosis factor factor α, and interferon γ) after incubation of cord blood mononuclear cells either in medium alone or stimulated with phytohemagglutinin (PHA), cockroach extract, or house dust mite extract. We examined associations of maternal depression with these sets of cytokine measures using multivariable linear or tobit regression analyses.ResultsAfter adjustment for confounders (mother's age, race/ethnicity, education, household income, season of birth, and child sex), levels of IL-10 after stimulation with cockroach or dust mite allergen were lower in cord blood from ever versus never depressed women, and a similar trend was evident in IL-10 stimulated with PHA (percentage difference: cockroach extract = -41.4, p = .027; house dust mite extract = 1-36.0, p = .071; PHA = -24.2, p = .333). No significant differences were seen in levels of other cytokines or LP.ConclusionsMaternal depression is associated with offspring immune responses at birth, which may have implications for later life atopic risk or immune function.
| S-EPMC6501810 | biostudies-literature
Project description:BACKGROUND:Birth outcome data with dolutegravir exposure during pregnancy, particularly in the first trimester, are needed. SETTING:Data were prospectively collected from the Antiretroviral Pregnancy Registry and European Pregnancy and Paediatric HIV Cohort Collaboration. METHODS:We reviewed 2 large, independent antiretroviral pregnancy registries to assess birth outcomes associated with maternal dolutegravir treatment during pregnancy. RESULTS:Of 265 pregnancies reported to the Antiretroviral Pregnancy Registry, initial exposure to dolutegravir occurred at conception or first trimester in 173 pregnancies and during the second or third trimester in 92 pregnancies. There were 246 (92.8%) live births resulting in 255 neonates (9 twins), 6 (2.3%) induced abortions, 11 (4.2%) spontaneous abortions, and 2 (0.8%) stillbirths. Birth defects occurred in 7 (2.7%) of 255 live-born neonates, 5 (3.1%) of 162 (includes 6 twins) with conception/first-trimester exposure. Of 101 pregnancies reported to the European Pregnancy and Paediatric HIV Cohort Collaboration, outcomes were available for 84 pregnancies (16 continuing to term and 1 lost to follow-up). There were 81 live births (80 with known initial dolutegravir exposure at conception or first, second, and third trimesters in 42, 21, and 17 live births, respectively), 1 stillbirth (second-trimester exposure), 1 induced abortion (first-trimester exposure), and 1 spontaneous abortion (first-trimester exposure), respectively. Birth defects occurred in 4 live births (4.9%; 95% confidence interval: 1.4 to 12.2), 3 of 42 (7.1%) with exposure at conception or first trimester. CONCLUSIONS:Our findings are reassuring regarding dolutegravir treatment of HIV infection during pregnancy but remain inconclusive because of small sample sizes.
| S-EPMC6905407 | biostudies-literature
Project description:BackgroundPrenatal alcohol exposure (PAE) is associated with postnatal iron deficiency (ID), which has been shown to exacerbate deficits in growth, cognition, and behavior seen in fetal alcohol spectrum disorders. However, the mechanisms underlying PAE-related ID remain unknown.ObjectivesWe aimed to examine biochemical measures of iron homeostasis in the mother, placenta, neonate, and 6.5-month-old infant.MethodsIn a prenatally recruited, prospective longitudinal birth cohort in South Africa, 206 gravidas (126 heavy drinkers and 80 controls) were interviewed regarding alcohol, cigarette, and drug use and diet at 3 prenatal visits. Hemoglobin, ferritin, and soluble transferrin receptor (sTfR) were assayed twice during pregnancy and urinary hepcidin:creatinine was assayed once. Infant ferritin and hemoglobin were measured at 2 weeks and 6.5 months and sTfR was measured at 6.5 months. Histopathological examinations were conducted on 125 placentas and iron transport assays (iron regulatory protein-2, transferrin receptor-1, divalent metal transporter-1, ferroportin-1, and iron concentrations) were conducted on 63.ResultsIn multivariable regression models, prenatal drinking frequency (days/week) was related to higher maternal hepcidin and to sequestration of iron into storage at the expense of erythropoiesis in mothers and neonates, as evidenced by a lower hemoglobin (g/dL)-to-log(ferritin) (ug/L) ratio [mothers: raw regression coefficient (β) = -0.21 (95% CI: -0.35 to -0.07); neonates: β = -0.15 (95% CI: -0.24 to -0.06)]. Drinking frequency was also related to decreased placental ferroportin-1:transferrin receptor-1 (β = -0.57 for logged values; 95% CI: -1.03 to -0.10), indicating iron-restricted placental iron transport. At 6.5 months, drinking frequency was associated with lower hemoglobin (β = -0.18; 95% CI: -0.33 to -0.02), and increased prevalences of ID (β = 0.09; 95% CI: 0.02-0.17) and ID anemia (IDA) (β = 0.13; 95% CI: 0.04-0.23). In causal inference analyses, the PAE-related increase in IDA was partially mediated by decreased neonatal hemoglobin:log(ferritin), and the decrease in neonatal hemoglobin:log(ferritin) was partially mediated by decreased maternal hemoglobin:log(ferritin).ConclusionsIn this study, greater PAE was associated with an unfavorable profile of maternal-fetal iron homeostasis, which may play mechanistic roles in PAE-related ID later in infancy.
| S-EPMC8408869 | biostudies-literature
Project description:Emerging evidence indicates that the predictability of signals early in life may influence the developing brain. This study examines links between a novel indicator of maternal mood dysregulation, mood entropy, and child neurodevelopmental outcomes. Associations between prenatal maternal mood entropy and child neurodevelopment were assessed in 2 longitudinal cohorts. Maternal mood was measured several times over pregnancy beginning as early as 15 weeks' gestation. Shannon's mood entropy was applied to distributions of mothers' responses on mood questionnaires. Child cognitive and language development were evaluated at 2 and 6-9 years of age. Higher prenatal maternal mood entropy was associated with lower cognitive development scores at 2 years of age and lower expressive language scores at 6-9 years of age. These associations persisted after adjusting for maternal pre and postnatal mood levels and for other relevant sociodemographic factors. Our findings identify maternal mood entropy as a novel predictor of child neurodevelopment. Characterizing components of maternal mood in addition to level of severity or valence may further our understanding of specific processes by which maternal mood shapes child development. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
| S-EPMC10491461 | biostudies-literature
Project description:BackgroundWe evaluated: (1) associations of prenatal manganese (Mn) levels with child neurodevelopment at 4-6 years; (2) effect modification by maternal anemia and iron deficiency; and (3) sex-specific effects.MethodsWe measured blood Mn, hemoglobin, and serum ferritin in mothers at the second trimester, third trimester, and at birth, and in cord blood from a prospective birth cohort in Mexico City (n = 571). McCarthy Scales of Children's Abilities were measured at 4-6 years. Using linear regression, we estimated associations between prenatal Mn and neurodevelopment, examined anemia and iron deficiency as effect modifiers, and analyzed associations by child sex.ResultsNo direct associations were observed between Mn, anemia, or iron deficiency and McCarthy Scales. Second trimester iron deficiency and third trimester anemia modified the effect of Mn on child neurodevelopment. For instance, second trimester Mn was positively associated child memory scores in mother's with normal ferritin (1.85 (0.02, 3.45)), but negatively associated in mother's with low ferritin (-2.41 (-5.28, 0.47), interaction P value = 0.01), a pattern observed across scales. No effect modification at birth or in cord blood was observed.ConclusionsAnemia/iron deficiency during pregnancy may modify Mn impacts on child neurodevelopment, particularly in boys.
| S-EPMC7351595 | biostudies-literature
Project description:Several studies have supported the association between maternal immune activation (MIA) caused by exposure to pathogens or inflammation during critical periods of gestation and an increased susceptibility to the development of various psychiatric and neurological disorders, including autism and other neurodevelopmental disorders (NDDs), in the offspring. In the present work, we aimed to provide extensive characterization of the short- and long-term consequences of MIA in the offspring, both at the behavioral and immunological level. To this end, we exposed Wistar rat dams to Lipopolysaccharide and tested the infant, adolescent and adult offspring across several behavioral domains relevant to human psychopathological traits. Furthermore, we also measured plasmatic inflammatory markers both at adolescence and adulthood. Our results support the hypothesis of a deleterious impact of MIA on the neurobehavioral development of the offspring: we found deficits in the communicative, social and cognitive domains, together with stereotypic-like behaviors and an altered inflammatory profile at the systemic level. Although the precise mechanisms underlying the role of neuroinflammatory states in neurodevelopment need to be clarified, this study contributes to a better understanding of the impact of MIA on the risk of developing behavioral deficits and psychiatric illness in the offspring.
| S-EPMC9968168 | biostudies-literature
Project description:Fetal alcohol spectrum disorder (FASD) is a common developmental behavioral disorder caused by maternal drinking during pregnancy. Children born with FASD often face additional stress, particularly maternal separation that adds yet additional deficits. The mechanism associated with this phenomenon is not known. Using a mouse model, prenatal ethanol exposure and maternal separation stress have resulted in behavioral deficits and the combination of treatments results in more than additive effects. In addition, behavioral alterations are associated with changes in hippocampal gene expression that persist into adulthood. What initiates and maintains these changes remains to be established and forms the focus of this research. Specifically, MeDIP-Seq was used to assess how changes in promoter DNA methylation are affected by the combination of prenatal ethanol exposure and maternal separation stress with the potential to affect gene expression. The novel results show different sets of genes implicated by promoter DNA methylation affected by both treatments independently, and a relatively unique set of genes affected by the combination of treatments. Prenatal ethanol exposure leads to altered promoter DNA methylation at genes important for brain function and transcriptional regulation. Maternal separation stress leads to changes at genes important for histone methylation and immune response, and the combination of two treatments results in DNA methylation changes at genes important for neuronal migration and immune response. Our dual results on gene expression and DNA methylation from the same samples have allowed comparison of the two observations. There is minimal reciprocal overlap between changes in promoter DNA methylation and gene expression, although overlapping genes tend to be critical for brain development and function. These results suggest that epigenetic mechanisms beyond promoter DNA methylation must be involved in lasting gene expression alterations leading to behavioral deficits implicated in FASD.
2019-09-26 | GSE137984 | GEO
Project description:Epigenetic changes such as DNA cytosine methylation modulate gene function across brain and are implicated in the pathophysiology of neurodevelopmental disorders including schizophrenia and autism. Epigenetic changes can be caused by environmental exposures such as inflammation, and may at least partly explain why prenatal exposure to inflammation increase risk of neurodevelopmental disorders. We used an MIA mouse model to investigate the postnatal epigenetic changes associated with exposure to the viral analogue PolyI:C. The effect of dietary supplement with omega-3 polyunsaturated fatty acids (PUFA) on exposed mice was also examined. Methylation was estimated genome-wide across gene regulatory regions. Widespread epigenetic changes were observed following exposure to inflammation during prenatal life. The differentially methylated gene set was enriched for genes involved in nervous system development and function. Omega-3 intervention modified the epigenetic profile, including a number of genes which were affected by MIA. These experiments indicate that environmental and genetic risk factors modulate similar biological pathways that are associated with neurodevelopmental disorders.
2019-08-15 | GSE102942 | GEO
Project description:BackgroundDepression and/or anxiety during pregnancy have been associated with impaired fetal growth and neurodevelopment. Because placental imprinted genes play a central role in fetal development and respond to environmental stressors, we hypothesized that imprinted gene expression would be affected by prenatal depression and anxiety.MethodsPlacental gene expression was compared between mothers with prenatal depression and/or anxiety/obsessive compulsive disorder/panic and control mothers without psychiatric history (n=458) in the Rhode Island Child Health Study.ResultsTwenty-nine genes were identified as being significantly differentially expressed between placentae from infants of mothers with both depression and anxiety (n=54), with depression (n=89), or who took perinatal psychiatric medications (n=29) and control mother/infant pairs, with most genes having decreased expression in the stressed group. Among placentae from infants of mothers with depression, we found no differences in expression by medication use, indicating that our results are related to the stressor rather than the treatments. We did not find any relationship between the stress-associated gene expression and neonatal neurodevelopment, as measured using the Neonatal Intensive Care Unit Network Neurobehavioral Scale.ConclusionsThis variation in expression may be part of an adaptive mechanism by which the placenta buffers the infant from the effects of maternal stress.
| S-EPMC5959758 | biostudies-literature
Project description:Environmental phenols and parabens are commonly used in personal care products and other consumer products and human exposure to these chemicals is widespread. Although human and animal studies suggest an association between exposure to phenols and parabens and thyroid hormone levels, few studies have investigated the association of in utero exposure to these chemicals and thyroid hormones in pregnant women and their neonates. We measured four environmental phenols (triclosan, benzophenone-3, and 2,4- and 2,5-dichlorophenol), and three parabens (methyl-, propyl-, and butyl paraben) in urine collected from mothers at two time points during pregnancy as part of the CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas) study. We measured free thyroxine (T4), total T4, and thyroid-stimulating hormone (TSH) in serum of the pregnant women (N = 454) and TSH in their neonates (N = 365). We examined potential confounding by a large number of additional chemical exposures and used Bayesian Model Averaging (BMA) to select the most influential chemicals to include in regression models. We observed negative associations of prenatal urinary concentrations of propyl paraben and maternal TSH (β for two-fold increase = -3.26%, 95% CI: -5.55, -0.90) and negative associations of 2,4-dichlorophenol and maternal free T4 (β for two-fold increase = -0.05, 95% CI: -0.08, -0.02), after controlling for other chemical exposures. We observed negative associations of triclosan with maternal total T4 after controlling for demographic variables, but this association became non-significant after controlling for other chemicals (β for two-fold increase = -0.05, 95% CI: -0.11, 0.00). We found evidence that environmental phenols and parabens are associated with lower TSH and free T4 in pregnant women after controlling for related chemical exposures.
| S-EPMC6470297 | biostudies-literature