Neurodevelopmental Outcomes of Prenatal Preeclampsia Exposure.
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ABSTRACT:
SUBMITTER: Gumusoglu SB
PROVIDER: S-EPMC7170230 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundRecent studies have suggested an association between prenatal paracetamol exposure and adverse neurodevelopmental outcomes in children. However, these findings may be confounded by unmeasured factors related to maternal use of paracetamol and child outcomes.ObjectiveTo examine the association between duration and timing of prenatal paracetamol exposure on parent-reported communication skills, behaviour, and temperament in preschool-aged children, with focus on the role of unmeasured confounding.MethodsWe used data from the Norwegian Mother and Child Cohort Study. Linear and generalised linear models with inverse probability weights and robust standard errors were used to quantify the association between prenatal paracetamol exposure and continuous and categorical outcomes.ResultsOf the 32 934 children included in our study, 8374 (25.4%), 4961 (15.1%), and 1791 (5.4%) were prenatally exposed to paracetamol in one, two, and three trimesters, respectively. Children exposed to paracetamol in two trimesters scored lower on shyness compared with unexposed children (β -0.62, 95% confidence interval [CI] -1.05, -0.19). Children exposed to paracetamol in three trimesters had a moderate increased risk of internalising behaviour problems (relative risk (RR) 1.36, 95% CI 1.02, 1.80) and borderline externalising behaviour problems (RR 1.22, 95% CI 0.93, 1.60) compared with unexposed children. Children exposed to paracetamol in 2nd/3rd trimester scored lower on shyness (β -0.32, 95% CI -0.66, 0.02) compared with unexposed children. Sensitivity analyses indicated that unmeasured confounders play an important role and may potentially bias the effect estimates away from the null.ConclusionsTiming of exposure and short-term use of paracetamol during pregnancy do not seem to pose any substantial risk of the outcomes examined. Although we found an association between paracetamol use in multiple trimesters and lower shyness and greater internalising behaviour in preschool-aged children, we cannot rule out chance or unmeasured confounding as possible explanations for these findings.
| S-EPMC8285062 | biostudies-literature
Project description:BackgroundDespite the widespread use of caffeine including consumption during pregnancy, the effect of prenatal caffeine exposure on child brain development and behavior is unclear.MethodsTo address this, we used data from the Adolescent Brain and Cognitive Development Study (n = 11,875 children aged 9-11 years from 22 sites across the United States). We explored the associations between prenatal caffeine exposure and various developmental outcomes including birth outcomes, physical health, behavior problems, cognition, substance use and brain structure in children, and evaluated dose effects.ResultsAmong 9,978 children (4,745 females) who had valid data for prenatal caffeine exposure and whose mothers did not use drugs of abuse after knowing of pregnancy, 4,170 (41.79%) had no prenatal caffeine exposure, 2,292 (22.97%) had daily, 1,933 (19.37%) had weekly, and 1,583 (15.86%) had less than weekly exposures. Prenatal caffeine exposure including the widely recommended 'safe' dose was associated with greater externalizing problems, whereas greater BMI and soda consumption were only observed in children with high dose exposures (3+ per day). Notably, the effect size for association of externalizing problems with prenatal caffeine exposure was comparable with that reported for prenatal alcohol (The American Journal of Psychiatry, 177, 2020 and 1060) and prenatal cannabis (JAMA Psychiatry, 78, 2020 and 64) exposures from previous ABCD publications. Additionally, prenatal caffeine exposure was associated with brain structural changes that included greater posterior and lower frontal cortical thickness and altered parietooccipital sulcal depth.ConclusionsThe recommended 'safe' dose of caffeine during pregnancy should be carefully studied to assess whether the behavioral and brain correlates observed here are clinically relevant and determine whether it needs adjustment. Because of the high prevalence of caffeine use in the general population, studies on prenatal exposure to drugs of abuse should include prenatal caffeine use as a covariate.
| S-EPMC9291501 | biostudies-literature
Project description:Early-life lead (Pb) exposure has been linked to adverse neurodevelopmental outcomes. Recent evidence has indicated a critical role of DNA methylation (DNAm) in cognition, and Pb exposure has also been shown to alter DNAm. However, it is unknown whether DNAm is part of the mechanism of Pb neurotoxicity. This longitudinal study investigated the associations between trimester-specific (T1, T2, and T3) maternal blood Pb concentrations, gene-specific DNAm in umbilical cord blood, and infant neurodevelopmental outcomes at 12 and 24 months of age (mental development index, psychomotor development index, and behavioral rating scale of orientation/engagement and emotional regulation) among 85 mother-infant pairs from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) study. In the mediation analysis for this pilot study, P < 0.1 was considered significant. DNAm at a locus in CCSER1 (probe ID cg02901723) mediated the association between T2 Pb on 24-month orientation/engagement [indirect effect estimate 4.44, 95% confidence interval (-0.09, 10.68), P = 0.06] and emotional regulation [3.62 (-0.05, 8.69), P = 0.05]. Cg18515027 (GCNT1) DNAm mediated the association of T1 Pb [-4.94 (-10.6, -0.77), P = 0.01] and T2 Pb [-3.52 (-8.09, -0.36), P = 0.02] with 24-month EMOCI, but there was a positive indirect effect estimate between T2 Pb and 24-month psychomotor development index [1.25 (-0.11, 3.32), P = 0.09]. The indirect effect was significant for cg19703494 (TRAPPC6A) DNAm in the association between T2 Pb and 24-month mental development index [1.54 (0, 3.87), P = 0.05]. There was also an indirect effect of cg23280166 (VPS11) DNAm on T3 Pb and 24-month EMOCI [2.43 (-0.16, 6.38), P = 0.08]. These associations provide preliminary evidence for gene-specific DNAm as mediators between prenatal Pb and adverse cognitive outcomes in offspring.
| S-EPMC8206046 | biostudies-literature
Project description:The aim of this population-based study was to evaluate whether prenatal exposure to preeclampsia poses a risk for long-term ophthalmic morbidity. A population-based cohort analysis compared the risk of long-term ophthalmic morbidity among children who were prenatally exposed to preeclampsia and those who were not. The study population was composed of children who were born between the years 1991 and 2014 at a single tertiary medical center. Total ophthalmic hospitalization and time-to-event were both evaluated. A Kaplan-Meier survival curve was conducted to compare cumulative ophthalmic hospitalization incidence based on the severity of preeclampsia. Confounders were controlled using a Cox regression model. A total of 242,342 deliveries met the inclusion criteria, of which 7279 (3%) were diagnosed with mild preeclampsia and 2222 (0.92%) with severe preeclampsia or eclampsia. A significant association was found between severe preeclampsia or eclampsia and the risk of long-term vascular-associated ophthalmic morbidity in the offspring (no preeclampsia 0.3%, mild preeclampsia 0.2% and severe preeclampsia or eclampsia 0.5%, p = 0.008). This association persisted after controlling for maternal age and ethnicity (adjusted hazard ratio (HR) 1.861, 95% CI 1.051-3.295). In conclusion, within our population, prenatal exposure to severe preeclampsia or eclampsia was found to be a risk factor for long-term vascular-associated ophthalmic morbidity in the offspring.
| S-EPMC7287970 | biostudies-literature
Project description:BackgroundAntidepressant use later in pregnancy has been associated with preeclampsia and postpartum haemorrhage (PPH) in some studies.ObjectivesTo evaluate the association between patterns of prenatal antidepressant dose across gestationand risk of precclampsia and PPH.MethodsWe utilised OptumLabs® Data Warehouse (2012-2016) administrative health care claims, identifying 226 932 singleton liveborn deliveries for this retrospective cohort study. Antidepressant dispensing doses were converted to fluoxetine equivalents. Using k-means longitudinal, we identified women with similar patterns of antidepressant exposure, that is, trajectory groups, during the first 20 and 35 gestational weeks. We estimated risk ratios (RR) and 95% confidence intervals (CI) for the association between trajectory groups and preeclampisa (20-week groups) and PPH (35-week groups), adjusting for demographics, co-morbidities, and other psychotropic medications. Linear trend tests assessing increasing risk of the outcomes across groups were performed.ResultsAmong 15 041 (6.6%) pregnancies exposed to an antidepressant, the following trajectory groups were identified: A-low exposure, starting pregnancy at ~10 mg/d, with 1st trimester reduction/discontinuation, B-low sustained exposure of ~20 mg/d, C-moderate exposure (~40 mg/d) with 1st trimester reduction/discontinuation, D-moderate sustained exposure of ~40 mg/d, and E-high sustained exposure of ~75 mg/d. In the low exposure with reduction/discontinuation trajectory, risks were 8.2% for preeclampsia and 2.7% for PPH. Compared with this group, low, moderate, and high sustained trajectories were associated with preeclampsia (adjusted RR 1.17, 95% CI 1.01, 1.34; RR 1.31, 95% CI 1.12, 1.54; and RR 1.41, 95% CI 1.05, 1.90, respectively) and PPH (RR 1.32, 95% CI 1.05, 1.66; RR 1.35, 95% CI 1.03, 1.78; RR 2.51, 95% CI 1.69, 3.71, respectively); P < .01 for linear trend tests for both outcomes. There was no increased risk for either outcome for moderate exposure with reduction/discontinuation (trajectory C).ConclusionsWomen with sustained antidepressant exposure, especially at higher doses, were at increased risk for preeclampsia and PPH, but underlying depression and anxiety may contribute to the increased risk.
| S-EPMC7819597 | biostudies-literature
Project description:BACKGROUND:While use of prescription opioids and medication assisted therapy (MAT) for opioid use disorder in pregnancy, as well as the incidence of neonatal opioid withdrawal syndrome (NOWS) continue to rise, little is known about outcomes for children with NOWS beyond the newborn period. METHODS:We examined 1) prenatal MAT exposure vs. unexposed healthy controls [HC]; and 2) treatment for NOWS and NOWS severity on infant neurodevelopmental and behavioral outcomes at 5-8?months of age in 78 maternal-infant pairs from the ENRICH prospective cohort study. Data were obtained from 3 study visits: prenatal, delivery, and neurodevelopmental evaluation at 5-8?months of age. Neurodevelopmental outcomes included the Bayley Scales of Infant Development [BSID-III], caregiver questionnaires (Parenting Stress Index [PSI-SF], Infant Behavior Questionnaire [IBQ-R], Sensory Profile), and the experimental Still-Face Paradigm (SFP). RESULTS:No differences in the BSID-III, PSI-SF, or IBQ-R scores were observed between MAT and HC groups; however, MAT-exposed and HC infants differed with respect to SFP self-regulation (??=?-18.9; p?=?0.01) and Sensory Profile sensation seeking (OR?=?4.87; 95% CI: 1.55; 15.30) after adjusting for covariates. No significant differences between Treated-for-NOWS vs. not-Treated-for-NOWS were observed. Shorter timing to NOWS treatment initiation was associated with higher Total Stress (??=?-9.08; p?=?0.035), while longer hospitalization was associated with higher Parent-child dysfunctional interaction (p?=?0.018) on PSI-SF. CONCLUSIONS:Our results provide additional evidence of little-to-no effect of MAT and pharmacological treatment of NOWS on infant neurodevelopmental and behavioral outcomes at 5-8?months of age. However, prolonged hospitalization might increase family psychosocial stress and requires further examination.
| S-EPMC6348117 | biostudies-literature
Project description:ObjectiveData on the neurodevelopmental and associated behavioral effects of light to moderate in utero alcohol exposure are limited. This retrospective investigation tested for associations between reported maternal prenatal alcohol use and psychological, behavioral, and neurodevelopmental outcomes in substance-naive youths.MethodsParticipants were 9,719 youths (ages 9.0 to 10.9 years) from the Adolescent Brain Cognitive Development Study. Based on parental reports, 2,518 (25.9%) had been exposed to alcohol in utero. Generalized additive mixed models and multilevel cross-sectional and longitudinal mediation models were used to test whether prenatal alcohol exposure was associated with psychological, behavioral, and cognitive outcomes, and whether differences in brain structure and resting-state functional connectivity partially explained these associations at baseline and 1-year follow-up, after controlling for possible confounding factors.ResultsPrenatal alcohol exposure of any severity was associated with greater psychopathology, attention deficits, and impulsiveness, with some effects showing a dose-dependent response. Children with prenatal alcohol exposure, compared with those without, displayed greater cerebral and regional volume and greater regional surface area. Resting-state functional connectivity was largely unaltered in children with in utero exposure. Some of the psychological and behavioral outcomes at baseline and at the 1-year follow-up were partially explained by differences in brain structure among youths who had been exposed to alcohol in utero.ConclusionsAny alcohol use during pregnancy is associated with subtle yet significant psychological and behavioral effects in children. Women should continue to be advised to abstain from alcohol consumption from conception throughout pregnancy.
| S-EPMC7924902 | biostudies-literature
Project description:BackgroundIn a longitudinal birth cohort study of inner-city mothers and children (Columbia Center for Children's Environmental Health), we have previously reported that prenatal exposure to chlorpyrifos (CPF) was associated with neurodevelopmental problems at 3 years of age.ObjectiveThe goal of the study was to estimate the relationship between prenatal CPF exposure and neurodevelopment among cohort children at 7 years of age.MethodsIn a sample of 265 children, participants in a prospective study of air pollution, we measured prenatal CPF exposure using umbilical cord blood plasma (picograms/gram plasma) and 7-year neurodevelopment using the Wechsler Intelligence Scale for Children, 4th edition (WISC-IV). Linear regression models were used to estimate associations, with covariate selection based on two alternate approaches.ResultsOn average, for each standard deviation increase in CPF exposure (4.61 pg/g), Full-Scale intelligence quotient (IQ) declined by 1.4% and Working Memory declined by 2.8%. Final covariates included maternal educational level, maternal IQ, and quality of the home environment. We found no significant interactions between CPF and any covariates, including the other chemical exposures measured during the prenatal period (environmental tobacco smoke and polycyclic aromatic hydrocarbons).ConclusionsWe report evidence of deficits in Working Memory Index and Full-Scale IQ as a function of prenatal CPF exposure at 7 years of age. These findings are important in light of continued widespread use of CPF in agricultural settings and possible longer-term educational implications of early cognitive deficits.
| S-EPMC3237355 | biostudies-literature
Project description:BackgroundExposure to chemical mixtures is recognized as the real-life scenario in all populations, needing new statistical methods that can assess their complex effects.ObjectivesWe aimed to assess the joint effect of in utero exposure to arsenic, manganese, and lead on children's neurodevelopment.MethodsWe employed a novel statistical approach, Bayesian kernel machine regression (BKMR), to study the joint effect of coexposure to arsenic, manganese, and lead on neurodevelopment using an adapted Bayley Scale of Infant and Toddler Development™. Third Edition, in 825 mother-child pairs recruited into a prospective birth cohort from two clinics in the Pabna and Sirajdikhan districts of Bangladesh. Metals were measured in cord blood using inductively coupled plasma-mass spectrometry.ResultsAnalyses were stratified by clinic due to differences in exposure profiles. In the Pabna district, which displayed high manganese levels [interquartile range (IQR): 4.8, 18 ?g/dl], we found a statistically significant negative effect of the mixture of arsenic, lead, and manganese on cognitive score when cord blood metals concentrations were all above the 60th percentile (As?0.7 ?g/dl, Mn?6.6 ?g/dl, Pb?4.2 ?g/dl) compared to the median (As=0.5 ?g/dl, Mn=5.8 ?g/dl, Pb=3.1 ?g/dl). Evidence of a nonlinear effect of manganese was found. A change in log manganese from the 25th to the 75th percentile when arsenic and manganese were at the median was associated with a decrease in cognitive score of ?0.3 (?0.5, ?0.1) standard deviations. Our study suggests that arsenic might be a potentiator of manganese toxicity.ConclusionsEmploying a novel statistical method for the study of the health effects of chemical mixtures, we found evidence of neurotoxicity of the mixture, as well as potential synergism between arsenic and manganese. https://doi.org/10.1289/EHP614.
| S-EPMC5744746 | biostudies-literature
Project description:BACKGROUND:Evidence suggests that cytokine imbalances may be at the root of deficits that occur in numerous neurodevelopmental disorders, including schizophrenia and autism spectrum disorder. Notably, while clinical studies have demonstrated maternal cytokine imbalances with alcohol consumption during pregnancy-and data from animal models have identified immune disturbances in alcohol-exposed offspring-to date, immune alterations in alcohol-exposed children have not been explored. Thus, here we hypothesized that perturbations in the immune environment as a result of prenatal alcohol exposure will program the developing immune system, and result in immune dysfunction into childhood. Due to the important role of cytokines in brain development/function, we further hypothesized that child immune profiles might be associated with their neurodevelopmental status. METHODS:As part of a longitudinal study in Ukraine, children of mothers reporting low/no alcohol consumption or moderate-to-heavy alcohol consumption during pregnancy were enrolled in the study and received neurodevelopmental assessments. Group stratification was based on maternal alcohol consumption and child neurodevelopmental status resulting in the following groups: A/TD, alcohol-consuming mother, typically developing child; A/ND, alcohol-consuming mother, neurodevelopmental delay in the child; C/TD, control mother (low/no alcohol consumption), typically development child; and C/ND, control mother, neurodevelopmental delay in the child. Forty cytokines/chemokines were measured in plasma and data were analyzed using regression and constrained principle component analysis. RESULTS:Analyses revealed differential cytokine network activity associated with both prenatal alcohol exposure and neurodevelopmental status. Specifically, alcohol-exposed children showed activation of a cytokine network including eotaxin-3, eotaxin, and bFGF, irrespective of neurodevelopmental status. However, another cytokine network was differentially activated based on neurodevelopmental outcome: A/TD showed activation of MIP-1?, MDC, and MCP-4, and inhibition of CRP and PlGF, with opposing pattern of activation/inhibition detected in the A/ND group. By contrast, in the absence of alcohol-exposure, activation of a network including IL-2, TNF-?, IL-10, and IL-15 was associated with neurodevelopmental delay. CONCLUSIONS:Taken together, this comprehensive assessment of immune markers allowed for the identification of unique immune milieus that are associated with alcohol exposure as well as both alcohol-related and alcohol-independent neurodevelopmental delay. These findings are a critical step towards establishing unique immune biomarkers for alcohol-related and alcohol-independent neurodevelopmental delay.
| S-EPMC6988366 | biostudies-literature