Adverse Effects Of Prenatal Exposure Research Articles

The association between prenatal pyrethroids exposure and children's health - current research.

Exposure to pyrethroids, a widely used agricultural, forestry, and household insecticide, is a major public health concern due to its potential health effects on children. The aim of this review was to summarize the current knowledge of the effects of prenatal exposure to pyrethroids on the course and outcome of pregnancy, health status, and neurobehavioural development of children. A systematic and comprehensive search of the PubMed, Web of Science, and Scopus databases was conducted during January-February 2024. The review included original articles published in peerreviewed English-language journals since 2015. Based on keywords, 198 studies were identified and screened for eligibility. Ultimately, the review analyzed 25 articles including 16 that assessed the effects of prenatal exposure to pyrethroids on children's neurobehavioural development, 3 studies that assessed the effects on the course and outcome of pregnancy, and further 3 focused on respiratory disease. In addition, 1 study analyzed the development of obesity and 2 studies examined the effects on children's growth, weight and body composition in early childhood. In conclusion, there is considerable uncertainty about the adverse effects of prenatal exposure to pyrethroids on children's health. The strongest evidence has been reported for neurobehavioural development although results are also inconsistent. Further research is needed to understand the mechanisms of action and health effects of pyrethroids in susceptible populations. Int J Occup Med Environ Health. 2024;37(4):381-402.

Cognitive outcomes after fetal exposure to carbamazepine, lamotrigine, valproate or levetiracetam monotherapy: Data from the EURAP neurocognitive extension protocol

PurposePrenatal exposure to antiseizure medications (ASMs) has been associated with an increased risk of major malformations and neurodevelopmental disorders, with the latter being mainly associated with valproate (VPA). Our aim was to compare neurocognitive outcome at age 6–7 years in children exposed prenatally to lamotrigine (LTG), carbamazepine (CBZ), valproate (VPA) or levetiracetam (LEV) monotherapy. MethodsEligible mother–child pairs were identified from the observational prospective multinational EURAP cohort study. Assessor-blinded testing was conducted at age 6–7 years using WISC-III and NEPSY-II. Verbal IQ (VIQ), performance IQ (PIQ), full scale IQ (FSIQ) and performance in neuropsychological tasks were compared across ASM groups by ANOVA. Scores were adjusted for maternal IQ, paternal education, maternal epilepsy type and child sex. ResultsOf 169 children enrolled in the study, 162 (LTG n = 80, CBZ n = 37, VPA n = 27, LEV n = 18) had sufficient data from WISC-III, NEPSY-II or both, and were included in the analyses. Observed (unadjusted) PIQ and FSIQ did not differ across exposure groups, but a difference was identified for VIQ (P<0.05), with children exposed to VPA having lower scores than children exposed to LEV (P<0.05) and children from all groups combined (P<0.01). Adjusted VIQ, PIQ and FSIQ scores did not differ significantly across groups, but VPA-exposed children had borderline significantly lower adjusted VIQ scores than children from all groups combined (P=0.051). VPA-exposed children had lower scores in comprehension of instructions before and after adjustment for confounding variables than children exposed to LTG (P<0.001), LEV (P<0.01) or children from all groups combined (p < 0.001). The VPA-exposed group also had lower scores in immediate and delayed memory for faces compared to children exposed to CBZ (P<0.05 and P<0.001, respectively) and LTG (P<0.05 and P<0.02, respectively), and children from all groups combined (P<0.02 and P<0.001, respectively). LEV-exposed children had lower scores in delayed memory for names than children exposed to LTG (P<0.001), CBZ (P<0.001), VPA (P<0.05) and children from all groups combined (P<0.001). ConclusionsConsistent with previous reports, our results provide evidence for an adverse effect of prenatal exposure to valproate on verbal development. Our finding of relatively weaker performance of VPA-exposed children compared to other ASM exposures in both comprehension of instructions and face memory also suggest that children of mothers treated with VPA are at increased risk for compromised memory functions or altered processing of socially relevant information.

Prenatal exposure to polybrominated diphenyl ether (PBDE) and child neurodevelopment: The role of breastfeeding duration

BackgroundPrenatal and early-life exposure to polybrominated diphenyl ethers (PBDEs) is associated with detrimental and irreversible neurodevelopmental health outcomes during childhood. Breastfeeding may be a child's largest sustained exposure to PBDE— potentially exacerbating their risk for adverse neurodevelopment outcomes. However, breastfeeding has also been associated with positive neurodevelopment. Our study investigates if breastfeeding mitigates or exacerbates the known adverse effects of prenatal exposure to PBDEs and child neurodevelopment. MethodsParticipants included 321 mother-infant dyads from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS), a longitudinal birth cohort in California. PBDE concentrations were measured in maternal serum blood samples collected during pregnancy or at delivery. Using generalized estimated equations (GEE), we estimated associations of PBDE concentrations with children's attention, executive function, and cognitive scores assessed longitudinally between 7 and 12 years of age, stratified by duration of exclusive and complementary breastfeeding. ResultsWe observed that higher maternal prenatal PBDE concentrations were associated with poorer executive function among children who were complementary breastfed for a shorter duration compared to children breastfed for a longer duration; preservative errors (β for 10-fold increase in complementary breastfeeding <7 months = −6.6; 95 % Confidence Interval (CI): −11.4, −1.8; β ≥ 7 months = −5.1; 95 % CI: −10.2, 0.1) and global executive composition (β for 10-fold increase <7 months = 4.3; 95 % CI: 0.4, 8.2; β for 10-fold increase ≥7 months = 0.6; 95 % CI: −2.8, 3.9). ConclusionsProlonged breastfeeding does not exacerbate but may mitigate some previously observed negative associations of prenatal PBDE exposure and child neurodevelopment.

Adverse Effects of Prenatal Exposure to Oxidized Black Carbon Particles on the Reproductive System of Male Mice.

Ambient black carbon (BC), a main constituent of atmospheric particulate matter (PM), is a primary particle that is mainly generated by the incomplete combustion of fossil fuel and biomass burning. BC has been identified as a potential health risk via exposure. However, the adverse effects of exposure to BC on the male reproductive system remain unclear. In the present study, we explored the effects of maternal exposure to oxidized black carbon (OBC) during pregnancy on testicular development and steroid synthesis in male offspring. Pregnant mice were exposed to OBC (467 μg/kg BW) or nanopure water (as control) by intratracheal instillation from gestation day (GD) 4 to GD 16.5 (every other day). We examined the testicular histology, daily sperm production, serum testosterone, and mRNA expression of hormone synthesis process-related factors of male offspring at postnatal day (PND) 35 and PND 84. Histological examinations exhibited abnormal seminiferous tubules with degenerative changes and low cellular adhesion in testes of OBC-exposed mice at PND 35 and PND 84. Consistent with the decrease in daily sperm production, the serum testosterone level of male offspring of OBC-exposed mice also decreased significantly. Correspondingly, mRNA expression levels of hormone-synthesis-related genes (i.e., StAR, P450scc, P450c17, and 17β-HSD) were markedly down-regulated in male offspring of PND 35 and PND 84, respectively. In brief, these results suggest that prenatal exposure has detrimental effects on mouse spermatogenesis in adult offspring.

Astaxanthin ameliorates the impairment consequence of prenatal bacterial lipopolysaccharide exposure in adult male offspring NMRI mice

In this study, the potential effects of astaxanthin (AST) were investigated on preventing the prenatal LPS-induced injures in mothers and adult male offspring of NMRI mice.Pregnant mice were randomly divided into four groups: 1. Saline + vehicle; 2. Saline + AST: received astaxanthin (4 mg/kg for 3 days, ip) on 11–13 gestation days; 3. LPS + vehicle (LPS-treated group): injected with LPS (20 µg/kg, sc) on gestation day 11; 4. LPS + AST: administrated LPS and astaxanthin on gestation days 11 and 11–13, respectively. In each group, maternal care behaviors and TNF-α serum levels were examined until weaning of male offspring at 23 days. At 60 days old, male pups underwent analysis of body weight and length, serum gonadotropins and testosterone hormone levels, sperm quality, gonadal and brain tissues morphologies, and the expression of SOX9 and GnRH genes by real-time PCR.Serum TNF-α level increased significantly in mothers treated with LPS, while AST reduced it. In adult male offspring, serum hormone levels, sperm quality, and the number of spermatocytes and Leydig cells in the testes improved when AST was administrated. According to histological studies of the brain, neurons in the LPS-treated group were smaller and less active, whereas neurons in the LPS + AST group were larger, more numerous, and more active. LPS significantly reduced GnRH expression, while AST induction improved its expression.AST administration during pregnancy prevented the adverse effects of prenatal exposure to LPS, presumably through its genomic and non-genomic effects, in adult male offspring.

Prenatal pyrethroid exposure and lung function among school-aged children.

Previous epidemiological evidence mainly focused on the adverse effects of prenatal exposure to pyrethroid insecticides (PYRs) on respiratory health during childhood. It remains unclear whether the PYR exposures can also impact on children's lung function. To explore the potential effects of prenatal PYR exposures on lung function in a population of Chinese children. This study included 233 mother-child dyads from the Laizhou Wan Birth Cohort (LWBC), Shandong province, northern China, between September 2010 and December 2013. Three metabolites of PYRs [3-phenoxybenzoic acid (3-PBA), and cis- and trans-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (cis-DCCA and trans-DCCA)] were measured using gas chromatography-mass spectrometry (GC-MS) in maternal urine samples collected at recruitment. Lung function was assessed with spirometry in children aged 6-8 years. Multivariable linear regression and generalized linear models (GLMs) assessed the associations of prenatal PYR exposures with lung function in children. Among the PYR metabolites, 3-PBA (81.5%) were most frequently detected, followed by trans-DCCA (55.4%) and cis-DCCA (21.9%). The 3-PBA concentration was associated with a 1% decrease in FEV1/FVC in the highest quartiles of exposure compared to the lowest quartile, with a potential dose response association (p-trend=0.085). Our findings provide a suggestive effect modification by sex, with girls being more susceptible than the boys (p-trend=0.011). However, there were no associations between the trans-DCCA concentration and lung function parameters. Prenatal 3-PBA concentrations were associated with a modest decrease in FEV1/FVC among school-aged children, and the association was slightly more pronounced for the girls than for the boys.

Prenatal exposure to glucocorticoids and the prevalence of overweight or obesity in childhood.

ObjectivePrenatal exposure to excess cortisol can affect postnatal metabolic health by epigenetic mechanisms. We aimed to investigate if prenatal exposure to pharmacological glucocorticoids increases the risk of overweight/obesity in childhood.DesignA nationwide population registry-based cohort study.MethodsWe identified 383 877 children born in Denmark (2007–2012), who underwent routine anthropometric evaluation at 5–8 years of age. Prenatal exposure to glucocorticoids was divided into systemic and topical glucocorticoids, cumulative systemic dose, and use by trimester. The comparison cohort included children without exposure, born to maternal never-users. Negative control exposures were used to investigate confounding from an underlying disease or unmeasured characteristics. Such exposures included children without glucocorticoid exposure born to maternal users of non-steroidal anti-inflammatory drugs or immunotherapy during pregnancy, maternal former users of glucocorticoids, or paternal users of glucocorticoids during the pregnancy of their partner. We estimated sex-stratified adjusted prevalence ratios (aPR) of overweight/obesity at 5–8 years of age, as epigenetic modifications have shown to be sex-specific.ResultsIn the study, 21 246 (11%) boys and 27 851 (15%) girls were overweight/obese at 5–8 years of age. Overall, neither systemic nor topical glucocorticoids were associated with overweight/obesity. In boys, high-dose systemic glucocorticoids was associated with higher prevalence of overweight/obesity vs the comparison cohort (aPR: 1.41 (95% CI: 1.07–1.86), prevalence: 16% vs 11%). Negative control exposures indicated robustness to confounding.ConclusionOverweight/obesity might be an adverse effect of prenatal exposure to high-dose systemic glucocorticoids in boys. We found no association for neither prenatal exposure to lower doses of systemic nor topical glucocorticoids. These results merit clinical attention.

Adverse effects of prenatal exposure to residential dust on post-natal brain development

BackgroundPrevious studies have shown an association between prenatal exposure to particulate matter (PM) and adverse brain development. However, it is unclear whether gestational exposure to community-sampled residential PM has an impact on the developing brain. ObjectivesWe aimed to test whether in utero exposure to PM from residential roof spaces (ceiling voids) alters critical foetal neurodevelopmental processes. MethodsPregnant C57BL/6 mice were intranasally exposed to 100 μg of roof space particles (~5 mg kg−1) in 50 μl of saline, or saline alone under light methoxyflurane anaesthesia, throughout mid-to-late gestation. At 2 weeks post-natal age, pups were sacrificed and assessed for body and brain growth. The brain tissue was collected and examined for a range of neurodevelopmental markers for synaptogenesis, synaptic plasticity, gliogenic events and myelination by immunohistochemistry. ResultsGestational exposure to roof space PM reduced post-natal body and brain weights. There was no significant effect of roof space PM exposure on synaptogenesis, synaptic plasticity or astrocyte density. However, PM exposure caused increased myelin load in the white matter and elevated microglial density which was dependent on the PM sample. These effects were found to be consistent between male and female mice. ConclusionsOur data suggest that exposure to residential roof space PM during pregnancy impairs somatic growth and causes neuropathological changes in the developing brain.

Adverse effects of fetal exposure of electronic-cigarettes and high-fat diet on male neonatal hearts

Epidemiological studies have shown an increased risk of cardiovascular diseases in children born to mothers who smoked during pregnancy. The cardiovascular risk in the offspring associated with in utero nicotine exposure is further exaggerated by maternal obesity. The consumption of electronic cigarettes (e-cigarettes) is alarmingly increasing among adolescents and young adults without the knowledge of their harmful health effects. There has also been a substantial increase in e-cigarette use by women of reproductive age. This study investigates the detrimental effects of gestational exposure of e-cigarette and a high-fat diet (HFD) on neonatal hearts. Time-mated pregnant mice were fed a HFD and exposed to saline or e-cigarette aerosol with 2.4% nicotine from embryonic day 4 (E4) to E20. We demonstrated that in utero exposure of e-cigarettes and HFD from E4 to E20 triggers cardiomyocyte (CM) apoptosis in the offspring at postnatal day1 (PND1), PND3, and PND14. Induction of CM apoptosis following gestational exposure of e-cigarettes and HFD was associated with inactivation of AMP-activated protein kinase (AMPK), increased cardiac oxidative stress coupled with perturbation of cardiac BAX/BCL-2 ratio and activation of caspase 3 at PND 14. Electron microscopy further revealed that left ventricles of pups at PND14 after e-cigarette exposure exhibited apoptotic nuclei, convoluted nuclear membranes, myofibrillar derangement, and enlarged mitochondria occasionally showing signs of crystolysis, indicative of cardiomyopathy and cardiac dysfunction. Our results show profound adverse effects of prenatal exposure of e-cigarette plus HFD in neonatal hearts that may lead to long-term adverse cardiac consequences in the adult.

The Seychelles Child Development Study of methyl mercury from fish consumption: analysis of subscales from the Child Behaviour Checklist at age 107 months in the main cohort

Methyl mercury (MeHg) is neurotoxic and all fish contain at least trace amounts. Consequently, prenatal or fetal exposure occurs when pregnant women consume fish and children are exposed postnatally when they breastfeed or consume fish. However, the level of exposure at which toxicity occurs is presently unknown. Since behavioural endpoints can be sensitive indicators of toxic exposure, we administered the Child Behaviour Checklist (CBCL) to measure behaviour as part of a prospective, longitudinal, double blind study (n=779) of prenatal MeHg exposure, the Seychelles Child Development Study (SCDS). The CBCL Total T score was a primary endpoint at 66 and 107 month evaluations of the cohort and showed no association with prenatal or postnatal MeHg exposure. This paper reports the results of a secondary analysis of the CBCL subscales to see if specific aspects of behaviour might show associations. The SCDS main cohort was enrolled in 1989-90 and evaluated on five occasions through 107 months of age. The child's primary caregiver completed the CBCL at the 107 month evaluation. Prenatal exposure was determined by measuring total mercury (THg) in maternal hair growing during pregnancy and recent postnatal exposure by analysing the child's hair taken at the 107 month evaluation. Analysis included linear and nonlinear multiple regression models. For prenatal MeHg exposure, the Social Problems subscale was significantly associated and the Somatic Complaints subscale was marginally associated. Both were beneficial associations. For postnatal exposure the Thought Problems subscale was associated in an adverse direction. This secondary analysis identified a small number of subtle beneficial and adverse associations with prenatal and postnatal MeHg exposure for specific CBCL subscales. These analyses provide no evidence for an adverse effect of prenatal exposure. The adverse postnatal association is difficult to interpret because we measured only recent (about one month) exposure and no adjustment was made for the multiplicity of endpoints.

Environmental pollutants affecting children's growth and development: Collective results from the MOCEH study, a multi-centric prospective birth cohort in Korea

BackgroundThe Mothers and Children's Environmental Health study (MOCEH) is a multi-centric prospective birth cohort study investigating effects of various environmental pollutants like heavy metals, endocrine disruptors, air pollutants, nutrition and lifestyle on birth outcomes, growth and development, health and disease of children. In this study, we report all the outcomes from the MOCEH study describing the different environmental pollutants affecting children’s health and disease. MethodsIn MOCEH study, 1,751 pregnant women in their first trimester were recruited at 3 centers from 2006 to 2010 in South Korea. The children were followed from birth up to 6 years. Information on health outcomes of children including birth parameters, demographic characteristics, medical and child-rearing history, and nutritional status, were repeatedly obtained through the follow-ups by questionnaires administration, clinical evaluation, and biological specimen collection and measurements. Prenatal and postnatal measurement in biospecimen, i.e., lead, mercury, cadmium, manganese, 1-hydroxypyrene, 2-naphthol, malonadialdehyde, hippuric acid, bisphenol A and phthalate metabolites, and measurement in air samples, i.e., particulate matter, nitrogen dioxide, and total volatile organic compounds were performed. ResultsThe results show the adverse effect of prenatal exposure to heavy metals like mercury, lead and cadmium on children’s physical, cognitive and neurobehavioral development. Exposure to endocrine disruptors, air pollution, second hand smoke, and mother’s lifestyle during pregnancy affects children’s growth and development. We also identified specific window periods of exposure of pollutants significantly related to children’s health outcomes. ConclusionThe collective results from MOCEH study provide strong scientific evidence that exposures to prenatal and postnatal environmental pollutants have a negative effect on growth and development of children, which will be useful in implementing effective national policy to improve children’s environmental health.

Ambient air pollution and the risk of stillbirth: a population-based prospective birth cohort study in the coastal area of China.

Accumulating evidence has shown that prenatal ambient air pollution exposure is associated with elevated stillbirth risk; however, the results are inconsistent. This population-based prospective cohort study aimed to explore the association between prenatal air pollution exposure and stillbirth rate in the coastal area in China. Data of air pollution and birth outcomes between January 1, 2015, and December 31, 2017, were collected. Among the 59,868 eligible births, there were 587 stillbirths and 59,281 live births. Although the air quality in this study was relatively better than most of the major cities in China, a positive association was still found between prenatal air pollution exposure and stillbirth rate. Every 10μg/m3 increase of fine particulate matters (PM2.5) in each trimester, as well as in the entire pregnancy, was associated with increased stillbirth rate (RR = 1.14, 1.11, 1.15, and 1.14 for the first, second, third trimester, and entire pregnancy, respectively). In addition, every 10μg/m3 increase of PM10 in the first trimester (RR = 1.09, 95% CI: 1.04-1.14), and 10μg/m3 increase of O3 in the first (RR = 1.05, 95% CI: 1.01-1.09) and third (RR = 1.04, 95% CI: 1.00-1.08) trimesters was also associated with increased stillbirth rate. The effects of PM2.5 on stillbirth rate were found to be robust in the two-pollutant models. The findings of this study especially underscored the adverse effects of prenatal exposure of high levels of PM2.5 on stillbirth. More studies are needed to verify our findings and further investigate the underlying mechanisms.

Associations between urinary total arsenic levels, fetal development, and neonatal birth outcomes: A cohort study in Taiwan

BackgroundArsenic exposure is a global health concern. Several studies have focused on chronic arsenic exposure in adults; however, limited data are available regarding the potential adverse effects of prenatal exposure on fetuses and neonates. ObjectivesTo assess which time point maternal arsenic exposure may influence the fetus during pregnancy and birth outcomes. MethodsIn this study, total arsenic concentrations were analyzed in urine samples collected from 130 women with singleton pregnancies (22–45years old) in Taiwan from March to December of 2010. All fetal biometric measurements in each trimester period and birth outcomes at delivery were obtained. We applied a generalized estimating equation model and multivariate regression models to evaluate the associations between maternal urinary total arsenic (UtAs) exposure during pregnancy, fetal biometric measurements, and neonatal birth outcomes. ResultsWe observed statistically significant correlations between maternal UtAs levels and the fetal biparietal diameter over all three trimesters (β=−1.046mm, p<0.05). Multiple regression analyses showed a negative association between maternal UtAs levels and chest circumference in the first trimester (β=−0.721cm, p<0.05), and second-trimester UtAs exposure was associated with decreases in birth weight (β=−173.26g, p<0.01), head circumference (β=−0.611cm, p<0.05), and chest circumference (β=−0.654cm, p<0.05). Dose-response relationships were also observed for maternal UtAs exposure and birth outcomes. ConclusionsWe identified a negative relationship between maternal UtAs levels during pregnancy, fetal development, and neonatal birth outcomes. These findings should be confirmed in future studies with large sample sizes.

Georgia State Obstetrician Counseling Practices Regarding Prenatal Environmental Toxin Exposures [3B

INTRODUCTION: Recent studies have underscored the adverse effects of prenatal exposure to bisphenol-A (BPA), pesticides, mercury, and lead. The purpose of this pilot study was to assess the counseling practices and level of comfort discussing prenatal environmental exposures among obstetricians in the state of Georgia. METHODS: We surveyed 100 practicing obstetricians, including Georgia private practice physicians in addition to residents and faculty from the largest residency training program in the state. RESULTS: The majority (72%) of physicians agreed that assessing environmental exposures during prenatal care is important in preventing adverse pregnancy outcomes. While 97.9% felt confident discussing cigarette smoking, few felt confident discussing the impact of other toxin exposures on pregnancy as follows: BPA (48.4%), pesticides (46.2%), mercury (42.1%), and lead (36.8%). Furthermore, less than 1 in 4 obstetricians reported routinely discussing each of these exposures as part of prenatal care: BPA (3.2%), pesticides (16.1%), mercury (22.6%), and lead (8.6%). There was no significant difference in either counseling practices or comfort discussing these topics when stratified by age, years in practice, and percentage of practice dedicated to obstetrics. CONCLUSION: Prenatal exposure to environmental toxins can have a significant impact on reproductive and developmental health, yet many obstetricians are not confident discussing the effect of environmental exposures on health outcomes with their patients. Currently most Georgia obstetricians are only evaluating a fraction of the environmental exposures recommended by the American College of Obstetricians and Gynecologists experts. There is a profound opportunity for improvement in counseling patients and educating reproductive health providers on this topic.

The INMA-INfancia y Medio Ambiente-(Environment and Childhood) project: More than 10 years contributing to environmental and neuropsychological research.

In 2003 the INMA-INfancia y Medio Ambiente (Environment and Childhood) project, a Spanish national network of birth cohorts including more than 3500 participants, was set up with the aim to assess the health impacts of pre- and postnatal environmental exposures on children. The project has published more than 60 papers on maternal and environmental factors related to neuropsychological development in children, one of the main research interests within the project. With the present review, we evaluate the evidence provided by the INMA project on this topic and discuss how the data can contribute to cover the challenges that children's environmental health research will face in the coming years. The INMA project has contributed to provide increasing evidence of the association between prenatal exposure to persistent organic pollutants (POPs) and child neuropsychological development, but it has also shown, using innovative methodologies, that postnatal exposure to these compounds does not play a role in this association. The project has also contributed to show the detrimental influence of certain air pollutants on child neuropsychological development, as well as how a balanced maternal fish intake can protect from the potential adverse effects of prenatal exposure to mercury. Also, the project has contributed to the understanding of impacts of nutritional factors including supplement intake and vitamin D levels during pregnancy and the role of breastfeeding on the neuropsychological benefits. INMA findings underscore the importance of continued research on the delineation of the sensitive windows of exposure both during pregnancy and postnatally and on the combined effects of environmental exposures, denoted the exposome. In terms of health policy, INMA findings have important implications for the development of public health policies to advance the health and development of children.

Prenatal airborne polycyclic aromatic hydrocarbon exposure, LINE1 methylation and child development in a Chinese cohort

BackgroundPolycyclic aromatic hydrocarbons (PAH) are carcinogenic, neurotoxic environmental pollutants generated during incomplete combustion of fossil fuel and other organic material. PAH exposure has been associated with adverse fetal development and epigenetic alterations in cord blood. Several molecular epidemiology studies have established PAH-DNA adducts as biomarkers of PAH exposure. ObjectivesWe investigated the relationship between LINE1 DNA methylation and PAH-DNA adduct levels in cord blood, and with neurodevelopmental outcomes. MethodsIn Tongliang County, China, the current study enrolled two population-based cohorts of nonsmoking pregnant women before (2002) and after (2005) the closure of a local coal-fired power plant in May 2004. We analyzed cord blood samples collected from mothers in the two cohorts (n=110 from 2002 cohort and n=107 from 2005 cohort) for PAH-DNA adducts and genomic LINE1 DNA methylation. Neurodevelopmental data on children were collected using the Gesell Developmental Scales (GDS) at age 2 and using the Wechsler Intelligence Scale for Children (WISC) at age 5. ResultsA significant inverse relationship was observed between PAH-DNA adducts and LINE1 DNA methylation (β=−0.010, p<0.038). A significant, positive association between LINE1 methylation and scores on WISC full scale and verbal (β=85.31, p<0.005; β=94.36, p<0.003) but not on the GDS. Mediation analysis did not find LINE1 to be a direct mediator between PAH-DNA adducts and IQ score. ConclusionLINE1 methylation in cord blood DNA was a positive predictor of IQ at age 5 and was decreased at higher levels of prenatal PAH exposure measured by PAH-DNA adducts in cord blood. However, the adverse effects of prenatal exposure to PAH on IQ scores did not appear to be directly mediated by altered LINE1 methylation.

The exposure of pregnant women and their offspring to Phtalates – Preliminary results from the “Environment, Mother, and Child” study in Jerusalem

Introduction:There is a growing concern regarding possible adverse effects of prenatal exposure to phthalates. Such exposure was suggested to be associated with genital development, and impaired ne...

Induced adverse effects of prenatal exposure to silver nanoparticles on neurobehavioral development of offspring of mice.

Steadily increased use of silver nanoparticles (Ag-NPs), has increased the amount of its exposure to humans and animals. Current scarce knowledge about the influences of prenatal exposure to Ag-NPs on postnatal outcomes, motivated us to investigate whether being exposed to it during pregnancy has any effects on neurobehavioral development of the adult offspring. Thirty virgin female NMRI mice were mated and treated subcutaneously once every three days from gestation day 3 until delivery, by 0, 0.2 and 2 mg/kg of bodyweight (BW) of Ag-NPs. Behavioral functions of adult offspring including spatial memory, passive avoidance learning, stress, anxiety-like behaviors and locomotor activities were assessed by commonly used neurobehavioral paradigms and the results were compared according to treatment and sex. Prenatal exposure to Ag-NPs significantly impaired their cognitive behavior in the Morris water maze. Although no evidence was observed indicating more anxiety-like behaviors in the treated offspring in the elevated plus maze, the number of defecations and leanings in the open field assay and number of passages in the light-dark box were greater in groups prenatally treated by Ag-NPs. Most of the impairments were more apparent in the offspring which had been prenatally exposed to high doses of Ag-NPs, particularly female ones. The present study indicated that the exposure of pregnant animals to Ag-NPs may lead to various neurobehavioral disorders in their offspring. Thus, more attention should be paid to avoid exposure to Ag-NPs, especially from pregnant females.

Evaluation of neuroprotection by melatonin against adverse effects of prenatal exposure to a nonsteroidal anti-inflammatory drug during peripheral nerve development

The potential ability of melatonin to protect against impairment of the fetal peripheral nerve system due to maternal consumption of diclofenac sodium (DS) was investigated. Eighty-four pregnant rats were divided into seven groups: control (CONT), saline administered (PS), DS administered (DS), DS with low-dose melatonin administered (DS+MLT10), DS with high-dose melatonin administered (DS+MLT50), low-dose melatonin administered (MLT10), and high-dose melatonin administered (MLT50). After the pregnancy, six male newborn rats from each group were sacrificed at 4 and 20 weeks of age. Their right sciatic nerves were harvested, and nerve fibers were evaluated using stereological techniques. Mean numbers of myelinated axons, axon cross-section areas and the mean thickness of the myelin sheet were estimated. Four-week-old prenatally DS-exposed rats had significantly fewer axons, a smaller myelinated axonal area, and a thinner myelin sheath compared to CONT group (p<0.05). Although melatonin at both doses significantly increased axon numbers, only a high dose of melatonin increased the diameter of those axons (p<0.05). At 20-weeks of age, myelinated axon number in the DS group was not only significantly lower than all other groups (p<0.05) but also the cross-sectional area of these axons was smaller than all other groups (p<0.05). There were no differences between the groups regarding the mean thickness of the myelin sheet. The current study indicates that prenatal exposure to DS decreases the number and the diameter of sciatic nerve axons and that melatonin prophylaxis can prevent these effects.

Prenatal Exposure to a Polychlorinated Biphenyl (PCB) Congener Influences Fixation Duration on Biological Motion at 4-Months-Old: A Preliminary Study

Adverse effects of prenatal exposure to polychlorinated biphenyl (PCB) congeners on postnatal brain development have been reported in a number of previous studies. However, few studies have examined the effects of prenatal PCB exposure on early social development. The present study sought to increase understanding of the neurotoxicity of PCBs by examining the relationship between PCB congener concentrations in umbilical cord blood and fixation patterns when observing upright and inverted biological motion (BM) at four-months after birth. The development of the ability to recognize BM stimuli is considered a hallmark of socio-cognitive development. The results revealed a link between dioxin-like PCB #118 concentration and fixation pattern. Specifically, four-month-olds with a low-level of prenatal exposure to PCB #118 exhibited a preference for the upright BM over inverted BM, whereas those with a relatively high-level of exposure did not. This finding supports the proposal that prenatal PCB exposure impairs the development of social functioning, and indicates the importance of congener-specific analysis in the risk analysis of the adverse effects of PCB exposure on the brain development.