Impact Of Prenatal Exposure Research Articles

Cohort Study of Maternal Gestational Weight Gain, Gestational Diabetes, and Childhood Asthma.

Data on the association of maternal gestational weight gain (GWG) and gestational diabetes mellitus (GDM) with childhood asthma are limited and inconsistent. We aimed to investigate these associations in a U.S. pre-birth cohort. Analyses included 16,351 mother-child pairs enrolled in the Massachusetts General Hospital Maternal-Child Cohort (1998-2010). Data were obtained by linking electronic health records for prenatal visits/delivery to determine BMI, GWG, and GDM (National Diabetes Data Group criteria) and to determine asthma incidence and allergies (atopic dermatitis or allergic rhinitis) for children. The associations of prenatal exposures with asthma were evaluated using logistic regression adjusted for maternal characteristics. A total of 2306 children (14%) developed asthma by age 5 years. Overall, no association was found between GWG and asthma. GDM was positively associated with offspring asthma (OR 1.46, 95% CI 1.14-1.88). Associations between GDM and asthma were observed only among mothers with early pregnancy BMI between 20 and 24.9 kg/m2 (OR 2.31, CI 1.46-3.65, p-interaction 0.02). We report novel findings on the impact of prenatal exposures on asthma, including increased risk among mothers with GDM, particularly those with a normal BMI. These findings support the strengthening of interventions targeted toward a healthier pregnancy, which may also be helpful for childhood asthma prevention.

Associations Between Prenatal Exposure to Serotonergic Medications and Biobehavioral Stress Regulation: Protocol for a Systematic Review and Meta-analysis.

BackgroundUp to 20% of mothers experience antenatal depression and approximately 30% of these women are treated with serotonergic psychotropic pharmacological therapy during pregnancy. Serotonergic antidepressants readily cross the placenta and the fetal blood-brain barrier, altering central synaptic serotonin signaling and potentially altering serotonin levels in the developing fetal brain.ObjectiveThe aim of this study is to assess the impact of prenatal exposure to serotonergic antidepressants, accounting for maternal mood disturbances, on markers of stress regulation during childhood.MethodsWe will follow PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and will search MEDLINE, Embase, CINAHL, PsycINFO, and ClinicalTrials.gov for full-length studies that assessed physiological (eg, cortisol level, heart rate variability, salivary amylase, pupillary size, C-reactive protein) indices of stress regulation in children of pregnant people who were treated with a serotonergic antidepressant at any point during pregnancy. We will assess the quality of observational studies using the Newcastle-Ottawa Scale and the quality of experimental studies using the Cochrane risk-of-bias tool. When possible, we will conduct a random-effects meta-analysis. If meta-analysis is not possible, we will conduct a narrative review. If a sufficient number of studies are found, we will perform subgroup analysis and assess outcomes measured by drug class, dose, trimester of exposure, and child’s age and gender.ResultsWe registered our review protocol with PROSPERO (International Prospective Register of Systematic Reviews; CRD42021275750), completed the literature search, and initiated title and abstract review in August 2021. We expect to finalize this review by April 2022.ConclusionsFindings should identify the impact of prenatal antidepressant effects on stress regulation and distinguish it from the impact of prenatal exposure to maternal mood disturbances. This review should inform decisions about serotonergic antidepressant use during pregnancy.Trial RegistrationPROSPERO CRD42021275750; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=275750International Registered Report Identifier (IRRID)PRR1-10.2196/33363

Long-term spatial tracking of cells affected by environmental insults

BackgroundHarsh environments surrounding fetuses and children can induce cellular damage in the developing brain, increasing the risk of intellectual disability and other neurodevelopmental disorders such as schizophrenia. However, the mechanisms by which early damage leads to disease manifestation in later life remain largely unknown. Previously, we demonstrated that the activation of heat shock (HS) signaling can be utilized as a unique reporter to label the cells that undergo specific molecular/cellular changes upon exposure to environmental insults throughout the body. Since the activation of HS signaling is an acute and transient event, this approach was not intended for long-term tracing of affected cells after the activation has diminished. In the present study, we generated new reporter transgenic mouse lines as a novel tool to achieve systemic and long-term tracking of affected cells and their progeny.MethodsThe reporter transgenic mouse system was designed so that the activation of HS signaling through HS response element (HSE) drives flippase (FLPo)-flippase recognition target (FRT) recombination-mediated permanent expression of the red fluorescent protein (RFP), tdTomato. With a priority on consistent and efficient assessment of the reporter system, we focused on intraperitoneal (i.p.) injection models of high-dose, short prenatal exposure to alcohol (ethanol) and sodium arsenite (ethanol at 4.0 g/kg/day and sodium arsenite at 5.0 mg/kg/day, at embryonic day (E) 12 and 13). Long-term reporter expression was examined in the brain of reporter mice that were prenatally exposed to these insults. Electrophysiological properties were compared between RFP+ and RFP− cortical neurons in animals prenatally exposed to arsenite.ResultsWe detected RFP+ neurons and glia in the brains of postnatal mice that had been prenatally exposed to alcohol or sodium arsenite. In animals prenatally exposed to sodium arsenite, we also detected reduced excitability in RFP+ cortical neurons.ConclusionThe reporter transgenic mice allowed us to trace the cells that once responded to prenatal environmental stress and the progeny derived from these cells long after the exposure in postnatal animals. Tracing of these cells indicates that the impact of prenatal exposure on neural progenitor cells can lead to functional abnormalities in their progeny cells in the postnatal brain. Further studies using more clinically relevant exposure models are warranted to explore this mechanism.

190-OR: Impact of Prenatal Exposure to Maternal Obesity and Child Physical Activity Levels on Neurocognition

Prenatal exposure to maternal obesity is linked to neurocognitive deficits in offspring. In contrast, engaging in physical activity (PA) is beneficial for cognition and brain development. We aimed to determine if greater PA is associated with higher intelligence quotient (IQ) scores and greater brain white matter integrity in children born to mothers with a range of pre-pregnancy BMI. Ninety-nine children (59 girls) ages 7-13 years completed the study. Maternal pre-pregnancy BMI was obtained from electronic medical records. Wechsler Abbreviated Scale of Intelligence was used to measure IQ. Diffusion tensor imaging was used to measure mean global fractional anisotropy (FA), a marker of white matter integrity. Time spent in moderate-to-vigorous PA (MVPA) and vigorous PA (VPA) was assessed using 3-day PA recalls. Linear regressions were used to assess whether maternal pre-pregnancy BMI or child MVPA and VPA were associated with child IQ scores and global FA. Maternal pre-pregnancy BMI ranged from 19.0-54.0 kg/m2 (43% obese). Mean±SD child IQ was 106.4±14.0, MVPA was 132.8±95.4 min/day, and VPA was 19.0±27.1 min/day. Maternal pre-pregnancy BMI was negatively associated with child IQ scores (β=-0.31; p=0.10); this marginal association remained after adjusting for child age, sex, puberty, BMI z-score, and socioeconomic status (β=-0.42; p=0.095). MVPA was not associated with child IQ (β=2.63; p=0.16). However, children who spent more time in VPA had higher IQ scores before (β=7.05; p=0.003) and after adjusting for the same co-variates (β=5.65; p=0.024) and further adjusting for maternal pre-pregnancy BMI (β=5.01; p=0.049). Children who spent more time in VPA also had greater mean global FA (unadjusted: β=0.01; p=0.017; adjusted: β=0.01; p=0.005). These findings suggest that engaging in VPA is beneficial for cognition and white matter microstructure in children, independent of maternal pre-pregnancy BMI. Disclosure J. Alves: None. B.C. Angelo: None. S.H. Luo: None. T. Chow: None. A.G. Yunker: None. A. Xiang: None. K.A. Page: None. J. Zink: None. B.R. Belcher: None. K. Clark: None. Funding American Diabetes Association (1-14-ACE-36 to K.A.P.); National Institute of Diabetes and Digestive and Kidney Diseases (R01DK116858); National Institute of Mental Health (F31MH115640)

Impact of prenatal exposure to diethylstilbestrol (DES) on psychological outcome: a national survey of DES daughters and unexposed controls.

To explore whether prenatal exposure to diethylstilbestrol (DES) is associated with increased risk of poor psychological outcome independently of the occurrence of major somatic complications related to DES exposure. Data on health outcome were collected in women prenatally exposed to DES (n=2566) and unexposed women (n=2967) recruited in a French national survey. Women prenatally exposed to DES were 1.7 times more likely to have consulted a mental health specialist compared to unexposed women (adjusted odds ratio=1.69, 95% confidence interval 1.47-1.96), independently of demographic characteristics, poor gynecological or obstetrical outcome, or history of cancer. Frequency of consultation with a mental health specialist in persons with a history of gynecological complications or cancer was comparable in women prenatally exposed to DES and unexposed women. Findings regarding psychological outcome obtained in the high-risk group of women prenatally exposed to DES may contribute to improving identification of psychological needs of all women presenting with gynecological abnormalities.

Application of targeted maximum likelihood estimation technique to assess the impact of prenatal exposure to nitrogen dioxide and ozone on stillbirth in a California cohort study

Application of targeted maximum likelihood estimation technique to assess the impact of prenatal exposure to nitrogen dioxide and ozone on stillbirth in a California cohort study

Влияние пренатальной экспозиции бенз(а)пирена, стирола и формальдегида на массу тела при рождении в зависимости от полиморфизомов генов системы детоксикации

Влияние пренатальной экспозиции бенз(а)пирена, стирола и формальдегида на массу тела при рождении в зависимости от полиморфизомов генов системы детоксикации

Prenatal antiepileptic exposure associates with neonatal DNA methylation differences

Antiepileptic drugs (AEDs) are used to treat a variety of neuropsychiatric illnesses commonly encountered in women during their reproductive years, including epilepsy and bipolar disorder. Despite their widespread use, the impact of prenatal exposure on fetal development remains obscure. To evaluate whether AEDs taken by pregnant mothers influence DNA methylation patterns in their neonates, DNA was extracted from the umbilical cord blood of 201 neonates whose mothers were treated for neuropsychiatric illness during pregnancy and interrogated across 27,578 CpG sites using the Illumina HumanMethylation27 BeadChip. The association of each methylation value with the cumulative duration of prenatal AED exposure was examined using a linear mixed model. The average methylation level across all CpG sites was calculated for each subject, and this global methylation measure was evaluated similarly. Neonates with a longer duration of AED exposure in pregnancy showed a decrease in average global methylation (p = 0.0045). Further, DNA methylation of CpG sites in 14 genes significantly decreased with the duration of prenatal AED exposure even after adjusting for multiple comparisons (FDR < 0.05). For a small subset (n = 19) of these neonates, a second tissue, placenta, was available in addition to cord blood. Methylation of 3 of these 14 CpG sites was also significantly decreased in placental tissue. These novel data suggest decreased DNA methylation in neonates of mothers who took AEDs during pregnancy. The long-term stability and potential impact of these changes warrant further attention, and caution may be warranted before prescribing AEDs to pregnant women.

Prenatal Characteristics of Infants with a Neuronal Migration Disorder: A National-Based Study

The development of the central nervous system is complex and includes dorsal and ventral induction, neuronal proliferation, and neuronal migration, organization, and myelination. Migration occurs in humans in early fetal life. Pathogenesis of malformations of the central nervous system includes both genetic and environmental factors. Few epidemiological studies have addressed the impact of prenatal exposures. All infants born alive and included in the Swedish Medical Birth Register 1980–1999 were included in the study. By linkage to the Patient Register, 820 children with a diagnosis related to a neuronal migration abnormality were identified. Through copies of referrals for computer tomography or magnetic resonance imaging of the brain, the diagnosis was confirmed in 17 children. Median age of the mothers was 29 years. At the start of pregnancy, four out of 17 women smoked. Almost half of the women had a body mass index that is low or in the lower range of average. All infants were born at term with normal birth weights. Thirteen infants had one or more concomitant diseases or malformations. Two infants were born with rubella syndrome. The impact of low maternal body mass index and congenital infections on neuronal migration disorders in infants should be addressed in future studies.

Impact of Prenatal Exposure to Piperonyl Butoxide and Permethrin on 36-Month Neurodevelopment

Impact of Prenatal Exposure to Piperonyl Butoxide and Permethrin on 36-Month Neurodevelopment

Antidepressant Use During Pregnancy: A Critical Systematic Review of the Literature

Over the past 15 years, the number of studies investigating the potential teratogenic effects of antidepressants has drastically increased. Prescribing antidepressants during pregnancy is becoming a challenge for health care providers because of conflicting data on their teratogenic potential. A critical systematic review of studies describing the relationship between antidepressant use during pregnancy and its impact on congenital malformations, prematurity, low birth weight (LBW), and child development was undertaken to summarize the current evidence-based findings. Most antidepressants do not pose a major teratogenic risk, although the data supporting this conclusion vary from one type to another. While SSRIs and tricyclics have been examined in a considerable number of studies, only scarce data is available on new antidepressants. The use of paroxetine during organogenesis has been linked to an increase in the risk of cardiovascular malformations. The impact of prenatal exposure to antidepressants on prematurity and LBW remains controversial, and most studies evaluating these outcomes are limited by their small sample size and lack of adequate reference group. Finally, information on the long-term effects of gestational antidepressant use on child development is only starting to emerge, and existing information is too limited to determine the risk.

The Lifelong Neurological Impact of Prenatal Exposures

The Lifelong Neurological Impact of Prenatal Exposures

Effect of prenatal exposure to fine particles and postnatal indoor air quality on the occurrence of respiratory symptoms in the first two years of life

The purpose of this study was to assess an impact of prenatal exposure to fine particles (PM2.5) on the risk of developing respiratory symptoms in early childhood. The study was carried out in a cohort of 465 newborns in Krakow (Poland) who have been followed over the first two years of life. The children exposed to medium level of PM2.5 (>35.3?53.4 µg/m³) had 13% more wheezing days (IRR = 1.13; 95% CI: 1.03?1.23), and those exposed to higher PM2.5 (>53.4 µg/m³) had on average 62% more wheezing days (IRR = 1.62; 95% CI: 1.42?1.86) compared with the low exposure group (≤35.3 µg/m³). The presence of moulds in the household (IRR = 1.13; 95% CI: 1.03?1.24), parity (IRR = 1.18; 95% CI: 1.10?1.28), and maternal atopy (IRR = 1.45; 95% CI: 1.28?1.63) were also significantly associated with the number of wheezing days. Children only exposed to higher PM2.5 (>53.4 µg/m³) had significantly more days with difficult breathing (IRR = 1.54; 95% CI: 1.34?1.78). Since that prenatal exposure to fine particles increases burden of respiratory symptoms among infants and young children the current PM2.5 health air quality guidelines may be too high to protect the sensitive subgroups of population.

Impact of Prenatal Exposure to Anticonvulsants Appears Small

Impact of Prenatal Exposure to Anticonvulsants Appears Small

Evaluation of prenatal aldrin intoxication in rats

The aim of the present study was to evaluate the impact of prenatal exposure to low doses of aldrin on physical and behavioral developments of rats (1-21 days old). To detect the possible persistent adversities produced by this exposure, the animals were also tested when adults (90 days old). Plasma determinations of both aldrin and its metabolite dieldrin and histopathological evaluations of brain slices were also performed in adult animals. Pregnant female rats were subcutaneously (s.c.) treated with aldrin (1.0 mg/kg) or with its vehicle (0.9% NaCl solution plus Tween-80) from day 1 of pregnancy until delivery. Results show that prenatal aldrin administration was able to decrease the median effective time (TE50) for incisor teeth eruption and to increase the TE50 for testes descent; other parameters indicative of physical development were not modified. Aldrin and dieldrin were not found in plasma of the adult rats; no differences were observed between control and experimental rats in the cellular and structural organization of the cerebral cortex neurones. Prenatal aldrin administration produced no impairment of adult animal's behavior in an avoidance learning test; nevertheless, the locomotor frequency of the experimental rats was higher than that of controls at 21 and 90 days old. When adults, these experimental rats had their performance in a hole-board apparatus (total number and duration of head-dips) also higher than that of the control ones. It was concluded that prenatal aldrin exposure induced not only developmental changes in the rat pups but also persistent behavioral alterations in adulthood, when the pesticide was not present in these animals.