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).

Prenatal Exposure to Per- and Polyfluoroalkyl Substances and ASD-Related Symptoms in Early Childhood: Mediation Role of Steroids.

Previous studies regarding the associations between perfluoroalkyl and polyfluoroalkyl substances (PFAS) and autism spectrum disorder (ASD) have yielded inconsistent results, with the underlying mechanisms remaining unknown. In this study, we quantified 13 PFAS in cord serum samples from 396 neonates and followed the children at age 4 to assess ASD-related symptoms. Our findings revealed associations between certain PFAS and ASD-related symptoms, with a doubling of perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) concentrations associated with respective increases of 1.79, 1.62, and 1.45 units in language-related symptoms and PFDA exhibiting an association with higher score of sensory stimuli. Nonlinear associations were observed in the associations of 6:2 chlorinated polyfluorinated ether sulfonate (Cl-PFAES) and 8:2 Cl-PFAES with ASD-related symptoms. Employing weighted quantile sum (WQS) regression, we observed significant mixture effects of multiple PFAS on all domains of ASD-related symptoms, with PFNA emerging as the most substantial contributor. Assuming causality, we found that 39-40% of the estimated effect of long-chain PFAS (PFUnDA and PFDoDA) exposure on sensory stimuli was mediated by androstenedione. This study provides novel epidemiological data about prenatal PFAS mixture exposure and ASD-related symptoms.

Prenatal exposure to PM2.5 and its composition on child growth trajectories in the first two years: A prospective birth cohort study.

The findings on the relationship between prenatal exposure to particulate matter with aerodynamic diameter ≤2.5 µm (PM2.5) and its constituent and children's growth trajectories are inconsistent. This association's sensitive exposure time window and possible gender differences remain unclear. Our aim was to determine the association between prenatal exposure to PM2.5 and its component and children's growth trajectories by the age of two. From 2015 to 2021, 6407 mother-infant pairs were enrolled in the study. The PM2.5 include sulfate (SO42-), nitrate (NO3-), ammonium (NH4+), organic matter (OM), and black carbon (BC), from the ChinaHighAirPollutants (CHAP) datasets. Children were followed at birth, 1, 3, 6, 9, 12, 18, and 24 months. Population-based and individual-based methods were used to simulate child growth trajectories: slow growth, normal growth, and rapid growth. The distributed lags modeling was used to identify sensitive time windows for the effects of prenatal exposure to PM2.5 and its components on child growth. Sex-stratified analyses estimated sex differences. Median concentrations [interquartile ranges (IQRs)] were 57.46(17.3), 10.59(3.8), 14.26(4.4), 8.69(2.8), 13.05(3.4), and 2.53(0.7) µg/m3 for PM2.5, SO42-, NO3-, NH4+, OM, and BC, respectively. Compared with the normal growth trajectory group, exposure to PM2.5 was significantly associated with a higher risk of rapid growth trajectory in boys (ORs with 95% CI for the entire, first trimester, and second trimester of pregnancy, respectively: 1.016[1.006,1.025], 1.007[1.002,1.011], 1.007[1.002,1.011]). Exposure to PM2.5 was significantly associated with a higher risk of slow growth trajectory in girls (ORs with 95% CI for the entire, second trimester, and third trimester of pregnancy, respectively: 1.010 [1.001,1.018], 1.006 [1.001,1.011], 1.007 [1.002,1.012]). Prenatal PM2.5 and its composition exposure was positively associated with BMI peak in boys (ßs with 95% CI for PM2.5, SO42-, NO3-, NH4+, OM, BC: 0.004[0.000,0.007], 0.025[0.006,0.044], 0.012[0.002,0.023], 0.022[0.004,0.039], 0.016[0.001,0.031], 0.082[0.005,0.159]), and not statistically significant in girls. We observed a more pronounced BC effect in our cohort. Prenatal exposure to PM2.5 and its component, especially at 10-22 weeks of gestation, is associated with a higher risk of rapid growth in boys and a risk of slow growth in girls.

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

PURPOSE: Prenatal 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. METHODS: Eligible 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. RESULTS: Of 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). CONCLUSIONS: Consistent 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.

Associating prenatal antibiotics exposure with attention deficit hyperactivity disorder symptoms in preschool children: The role of maternal vitamin D.

BACKGROUND: The associations between prenatal antibiotics exposure and attention-deficit/hyperactivity disorder (ADHD) in preschoolers, and the role of maternal vitamin D in these associations, remain to be explored. OBJECTIVES: To evaluate the relationships between multiple maternal urinary antibiotics levels and preschoolers' ADHD symptoms, and to identify the potential modifying effects of maternal vitamin D. METHODS: Based on a prospective birth cohort, the present study included 2033 motherchild pairs. Maternal urine and serum samples were collected during all three trimesters to measure the urinary concentrations of 43 antibiotics (including two metabolites) and the serum vitamin D levels. The ADHD symptoms of preschoolers were assessed using the Diagnostic and Statistical Manual-oriented ADHD problems scale in the Achenbach Child Behavior Checklist. Multiple informant models in the form of logistic regression were conducted to investigate the associations between prenatal antibiotics exposure and preschooler ADHD symptoms, and these associations were stratified by child sex and maternal vitamin D status. RESULTS: Compared with the lowest tertile concentrations, maternal exposure to the middle tertile concentrations of doxycycline and human antibiotics/preferred as human antibiotics (HAs/PHAs), and the highest tertile concentrations of doxycycline during the first trimester were associated with an increased risk of ADHD symptoms in children. An increased risk of ADHD symptoms was observed in girls exposed to the highest tertile levels of sulfamethazine during the second trimester. Furthermore, pregnant women with vitamin D deficiency have a greater risk of ADHD symptoms in their offspring after exposure to doxycycline in the first trimester. CONCLUSIONS: Maternal exposure to doxycycline and HAs/PHAs during the first trimester increases the risk of ADHD symptoms in preschoolers. Mid-pregnancy sulfamethazine exposure increases the risk of ADHD symptoms in girls. Maternal vitamin D deficiency during pregnancy may exacerbate the adverse effects of doxycycline exposure on ADHD symptoms.

Prenatal Exposure to Low Doses of Benzophenone-3 Elicits Disruption of Cortical Vasculature in Fetuses through Perturbations in Wnt/ß-catenin Signaling Correlating with Depression-like Behavior in Offspring Mice.

Benzophenone-3 (BP-3), commonly used in personal care products, is routinely detected in environmental and human matrices. Evidence delineates a correlation between gestational BP-3 exposure and emotional and social disorders in children and adolescents. However, sensitive target cells and the mode of action underlying the early responses to environmentally relevant level of BP-3 exposure remain unclear. In this study, 0.3 and 3mg/kg of BP-3 were administered to pregnant mice. Compared with the control group, the blood vessel development process manifested the highest susceptibility to BP-3 exposure using transcriptomic sequencing at embryonic day 14 (E14). Notably, the diminution in vascular density and tight junction proteins presence was observed in the fetal cortex at E14, concomitant with the suppressed transcriptional activity of genes essential to angiogenesis and barrier formation. Strikingly, the investigation revealed that BP-3 exposure impeded vascular sprouting in aortic ring explants and neuroendothelial migration, implicating the Wnt/ß-catenin signaling pathway. Moreover, BP-3 exposure compromised perivascular neural stem cell differentiation. Cortical vascular injury correlated with the exhibition of depression-like behavior in four-week postnatal progeny. These insights underscore the cerebrovasculature as an early sensitive target for low doses of BP-3 exposure, fostering the development of biomarkers and the establishment of the adverse outcome pathway framework for BP-3 hazard evaluation.

Cannabis and Pregnancy.

PURPOSE OF REVIEW: We review recent evidence describing the effects of prenatal exposure to cannabis in pregnant individuals. RECENT FINDINGS: In the context of changing cannabis policy, more pregnant individuals are using cannabis, despite profound risks. Recent studies show possible perinatal and longitudinal neurodevelopment risks associated with cannabis use during pregnancy and lactation. Healthcare providers are reluctant to discuss this topic with patients for a variety of reasons. With increased access to cannabis comes the possibility of increased adverse effects of cannabis upon pregnant individuals and their children. A concerted effort to educate pregnant individuals about the potential risks of cannabis might mitigate those potential effects.

Increasing Temporal Sensitivity of Omics Association Studies with Epigenome-Wide Distributed Lag Models.

Current methods for identifying temporal windows of effect for time-varying exposures in omics settings can control false discovery rates at the biomarker-level but cannot efficiently screen for timing-specific effects in high dimensions. Current approaches leverage separate models for site screening and identification of susceptible time windows, which miss associations that vary over time. We introduce the epigenome-wide distributed lag model (EWDLM), a novel approach that combines traditional false discovery rate methods with the distributed lag model (DLM) to screen for timing-specific effects in high dimensional settings. This is accomplished by marginalizing DLM effect estimates over time and correcting for multiple comparisons. In a simulation investigating timing-specific effects of ambient air pollution during pregnancy on DNA methylation across the epigenome at age 12 years, EWDLM achieved an increased sensitivity for associations limited to specific periods of time compared to traditional two-stage approaches. In a real-world EWDLM analysis, 353 CpG sites at which DNAm measured at age 12 was significantly associated with PM2.5 exposure during pregnancy were identified. EWDLM is a novel method that provides an efficient and sensitive way to screen epigenomic datasets for associations with exposures localized to specific time periods.

Prenatal exposure to PFAS and the association with neurobehavioral and social development during childhood.

Exposure to per- and polyfluoroalkyl substances (PFAS) is ubiquitous and may be associated with neurodevelopmental toxicity. However, epidemiological studies report mixed results on the risks of gestational PFAS exposure for children's neurobehavioral impairment. We aimed to examine the associations between prenatal PFAS exposure and children's neurobehavioral and social problems. We measured plasma concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), and perfluorohexane sulphonate (PFHxS) in first-trimester blood from 757 women from the Canadian Maternal-Infant Research on Environmental Chemicals (MIREC) study. Children were assessed at 3-4 years with the Behavior Assessment System for Children-2 (BASC-2) and the Social Responsiveness Scale-2 (SRS-2) (n = 756 and 496, respectively). We used multivariable linear regression to examine associations between individual and summed log2-transformed PFAS and scores on these assessments. Effect modification by sex was evaluated through interaction terms and stratified analyses. In the sample combining both sexes, a doubling of maternal PFOA was significantly associated with lower T-scores on the following SRS-2 scales: Social Motivation, DSM-Social Communication, and SRS Total score (B ranging from -1.08 to -0.78), suggesting lesser impairments with higher exposure. In sex-stratified analysis, PFOA was related to significantly lower T-scores in boys for these BASC-2 scales: Behavioral Symptoms Index, Externalizing Problems, Aggression, and Hyperactivity (B ranging from -1.32 to -1.03). In girls, however, PFAS were significantly associated more problem behaviors, but most associations were small and the CIs included the null, with the exception of PFOA being significantly associated with higher T-scores for the BASC-2Anxiety scale (B = 1.84, 95% CI: 0.36, 3.32). In conclusion, we did not observe strong associations between prenatal exposure to the PFAS evaluated and children's neurobehavioral and social development in this population with low exposure levels. The results show mixed findings, depending on children's sex, neurodevelopmental outcome, and specific PFAS.

Prenatal and early life exposure to fine particulate matter and telomere length in early childhood.

BACKGROUND: Telomere length is a biomarker of molecular aging that may be impacted by air pollution exposure starting in utero. We aimed to examine the association between prenatal and early life exposure to fine particulate matter (PM2.5) and leukocyte telomere length (LTL) in children and explore sex differences. METHODS: Analyses included 384 mother-child pairs enrolled in the Programming Research in Obesity, Growth, and Environmental Stressors (PROGRESS) birth cohort in Mexico City. Exposure to PM2.5 was estimated at the residential level using a satellite based spatio-temporally resolved prediction model. Average relative LTL was measured in DNA isolated from blood collected at age 4-6 years using quantitative real-time polymerase chain reaction. Linear regression models were used to examine the association between average PM2.5 across pregnancy, individual trimesters, first postnatal year, and LTL. Models were adjusted for maternal age and education at enrollment, prenatal environmental tobacco smoke exposure, child sex, age, and body mass index z-score at LTL measurement. Effect modification by sex was investigated with interaction terms and stratification. RESULTS: In trimester specific models, we found an association between 2nd trimester PM2.5 and elongated LTL (ß: 4.34, 95%CI [0.42, 8.42], per 5 µg/m3 increase). There was suggestive effect modification by sex on average 2nd trimester PM2.5 with stronger associations seen in females compared to males (ß: 7.12, [95%CI: 0.98, 13.6] and ß: 1.43 [95%CI: -3.46, 6.57]) per 5 µg/m3 increase respectively. CONCLUSION: Second trimester PM2.5 levels were associated with changes in LTL in early childhood. Understanding temporal and sex differences in PM2.5 exposure may provide insights into telomere dynamics over early life.

Prenatal black carbon exposure and DNA methylation in umbilical cord blood.

BACKGROUND/OBJECTIVES: Prenatal exposure to ambient air pollution is associated with adverse cardiometabolic outcomes in childhood. We previously observed that prenatal black carbon (BC) was inversely associated with adiponectin, a hormone secreted by adipocytes, in early childhood. Changes to DNA methylation have been proposed as a potential mediator linking in utero exposures to lasting health impacts. METHODS: Among 532 mother-child pairs enrolled in the Colorado-based Healthy Start study, we performed an epigenome-wide association study of the relationship between prenatal exposure to a component of air pollution, BC, and DNA methylation in cord blood. Average pregnancy ambient BC was estimated at the mother's residence using a spatiotemporal prediction model. DNA methylation was measured using the Illumina 450K array. We used multiple linear regression to estimate associations between prenatal ambient BC and 429,246 cysteine-phosphate-guanine sites (CpGs), adjusting for potential confounders. We identified differentially methylated regions (DMRs) using DMRff and ENmix-combp. In a subset of participants (n = 243), we investigated DNA methylation as a potential mediator of the association between prenatal ambient BC and lower adiponectin in childhood. RESULTS: We identified 44 CpGs associated with average prenatal ambient BC after correcting for multiple testing. Several genes annotated to the top CpGs had reported functions in the immune system. There were 24 DMRs identified by both DMRff and ENmix-combp. One CpG (cg01123250), located on chromosome 2 and annotated to the UNC80 gene, was found to mediate approximately 20% of the effect of prenatal BC on childhood adiponectin, though the confidence interval was wide (95% CI: 3, 84). CONCLUSIONS: Prenatal BC was associated with DNA methylation in cord blood at several sites and regions in the genome. DNA methylation may partially mediate associations between prenatal BC and childhood cardiometabolic outcomes.

Mercury exposure in ringed seals (Pusa hispida saimensis) in Lake Saimaa, Finland, and the placenta as a possible non-invasive biomonitoring tool.

The Saimaa ringed seal (Pusa hispida saimensis) is a subspecies of ringed seal, landlocked in Lake Saimaa, Finland. The small population of less than 500 seals is facing many human-induced threats, including chemical contaminants. Mercury, in particular, has previously been suggested to be one of the chemicals affecting the viability of this endangered population. We analysed mercury concentrations from placentas and lanugo pup tissues (blubber, brain, kidney, liver, and muscle) to determine current prenatal exposure levels. These pups were found dead in or near birth lairs and were less than 3 months old. Additionally, we used threshold values available in the literature to estimate the potential mercury toxicity to the Saimaa ringed seal. We also determined selenium concentrations for its potential to alleviate the adverse effects of mercury. We further supplemented our study with brain samples collected from various seal age classes. These seals were found dead by either natural causes or by being caught in gillnets. The analysed chemicals were present in all tissues. For lanugo pups, mercury concentrations were the highest in the kidney and liver, whereas the highest selenium to mercury molar ratio was observed in placentas. The toxicity evaluation suggested that, in severe cases, mercury may cause adverse effects in lanugo and older pups. In these cases, the selenium concentrations were low and selenium to mercury ratio was below 1:1 threshold ratio and thus unlikely to provide adequate protection from the adverse effects of mercury. Furthermore, adverse effects are more likely to occur in adult seals, as mercury bioaccumulates, leading to higher concentrations in older individuals. Placental mercury concentrations correlated to those in the livers and muscle tissues of lanugo pups. This, together with the fact that placentas can be collected non-invasively and in good condition, provides a potential novel method for biomonitoring mercury exposure in Saimaa ringed seals.

An Evaluation of In Utero Polycyclic Aromatic Hydrocarbon Exposure on the Neonatal Meconium Microbiome.

INTRODUCTION: In utero exposure to environmental polycyclic aromatic hydrocarbon (PAH) is associated with neurodevelopmental impairments[1-8], prematurity[9-12] and low birthweight[9,13-15]. The gut microbiome serves as an intermediary between self and external environment; therefore, exploring the impact of PAH on microbiota may elucidate their role in disease. Here, we evaluated the effect of in utero PAH exposure on meconium microbiome. METHODS: We evaluated 49 mother-child dyads within Fair Start Birth Cohort with full term delivery and adequate meconium sampling. Prenatal PAH was measured using personal active samplers worn for 48 hours during third trimester. Post-processing, 35 samples with adequate biomass were evaluated for association between tertile of PAH exposure (high (H) vs low/medium (L/M)) and microbiome diversity. RESULTS: No significant differences were observed in alpha diversity metrics, Chao1 and Shannon index, between exposure groups for total PAH. However, alpha diversity metrics were negatively associated with log benzo[a]anthracene (BaA) and log chrysene (Chry) with high exposure, but positively associated with log benzo[a]pyrene (BaP) with low/medium exposure. After adjustment for birthweight and sex, alpha diversity metrics were negatively associated with log BaA, BaP, Chry, Indeno[1,2,3-cd]pyrene (IcdP) and total PAH with high exposure. Conversely, with low/medium exposure, alpha diversity metrics positively correlated with log BaP and benzo[b]fluoranthane (BbF). No significant difference in beta diversity was observed across groups using UniFrac, weighted UniFrac, or Bray-Curtis methods. Differential expression analysis showed differentially abundant taxa between exposure groups. CONCLUSION: Bacterial taxa were detectable in 35/49 (71%) meconium samples. Altered alpha diversity metrics and differentially abundant taxa between groups suggest in utero PAH exposure may impede early colonization. Sample size is limited, but these findings provide supporting evidence for wider scale research. Research on long-term impact of prenatal PAH exposure on childhood health outcomes is ongoing. Differential effects of specific PAHs need further evaluation.

Prenatal exposure to dibutyl phthalate contributes to erectile dysfunction in offspring male rats by activating the RhoA/ROCK signalling pathway.

Prenatal exposure to dibutyl phthalate (DBP) has been reported to cause erectile dysfunction (ED) in adult offspring rats. However, its underlying mechanisms are not fully understood. Previously, we found that DBP activates the RhoA/ROCK pathway in the male reproductive system. This study investigated how prenatal exposure to DBP activates the RhoA/ROCK signalling pathway, leading to ED in male rat offspring. Pregnant rats were stratified into DBP-exposed and NC groups, with the exposed group receiving 750 milligrams per kilogram per day (mg/kg/day) of DBP through gavage from days 14-18 of gestation. DBP exposure activated the RhoA/ROCK pathway in the penile corpus cavernosum (CC) of descendants, causing smooth muscle cell contraction, fibrosis, and apoptosis, all of which contribute to ED. In vitro experiments confirmed that DBP induces apoptosis and RhoA/ROCK pathway activation in CC smooth muscle cells. Treatment of DBP-exposed offspring with the ROCK inhibitor Y-27632 for 8 weeks significantly improved smooth muscle cell condition, erectile function, and reduced fibrosis. Thus, prenatal DBP exposure induces ED in offspring through RhoA/ROCK pathway activation, and the ROCK inhibitor Y-27632 shows potential as an effective treatment for DBP-induced ED.

Prenatal exposure to bisphenol AF causes toxicities in liver, spleen, and kidney tissues of SD rats.

As a replacement for bisphenol A (BPA), bisphenol AF (BPAF) showed stronger maternal transfer and higher fetal accumulation than BPA. Therefore, concerns should be raised about the health risks of maternal exposure to BPAF during gestation on the offspring. In this study, SD rats were exposed to BPAF (0, 50, and 100 mg/kg/day) during gestation to investigate the bioaccumulation and adverse effects in liver, spleen, and kidney tissues of the offspring at weaning period. Bioaccumulation of BPAF in these tissues with concentrations ranging from 1.56 ng/mg (in spleen of males) to 55.44 ng/mg (in liver of females) led to adverse effects at different biological levels, including increased relative weights of spleen and kidneys, histopathological damage in liver, spleen, and kidney, organ functional damage in liver, spleen, and kidney, upregulated expression of genes related to lipid metabolism (in liver), oxidative stress response (in kidney), immunity and inflammatory (in spleen). Furthermore, dysregulated metabolomics was identified in spleen, with 217 differential metabolites screened and 9 KEGG pathways significantly enriched. This study provides a comprehensive insight into the systemic toxicities of prenatal exposure to BPAF in SD rats. Given the broad applications and widespread occurrence of BPAF, its safety should be re-considered.

Identifying Patients at Risk for Alcohol-Exposed Pregnancies: The Importance of Addressing Multiple Risk Factors.

BACKGROUND: The increasing prevalence of fetal alcohol spectrum disorders is a critical public health issue. Two behaviors, consuming alcohol and using less effective pregnancy prevention, may result in alcohol-exposed pregnancies (AEPs) in individuals who can become pregnant. In the context of alcohol screening and brief intervention (SBI) services, cutoff scores on widely used alcohol risk assessments (eg, Alcohol Use Disorders Identification Test, U.S. version [USAUDIT]) may fail to identify individuals whose relatively low alcohol consumption may still put them at risk for an AEP due to their pregnancy prevention method. METHODS: To identify this gap in alcohol SBI service delivery, we examined data from 2 reproductive healthcare systems implementing alcohol SBI, to explore the prevalence of individuals who met both of the following risk conditions: reported any alcohol use on the USAUDIT and a pregnancy prevention method less than 88% effective. Electronic health records for individuals aged 18 to 49 presenting for preventive care in 2021 were analyzed. RESULTS: Of 11 567 screened, 7638 reported some alcohol use, but screened at a lower-risk level and were not flagged to receive an alcohol-focused brief intervention (BI). Of these, 1477 were using a method of pregnancy prevention that was less than 88% effective. In addition, 118 of the 1676 who screened positive on the USAUDIT were using less effective contraception and did not receive a BI. In summary, the number of individuals at risk of an AEP who did not receive an alcohol BI was 1595 (13.8%) of the total patients screened for at-risk alcohol use. CONCLUSIONS: There is a need for system modifications to assess multiple behaviors simultaneously and alert providers when a combination of behaviors increases a specific health risk, such as an AEP. Tailored alcohol BIs that include the risks/benefits of various pregnancy prevention methods to reduce AEPs provide opportunities to enhance the reach of standard alcohol SBI services.

Associations of prenatal exposure to individual and mixed organophosphate esters with ADHD symptom trajectories in preschool children: The modifying effects of maternal Vitamin D.

BACKGROUND: Organophosphate esters (OPEs) are a class of environmental chemicals with endocrine-disrupting properties. Epidemiologic studies have demonstrated that prenatal OPEs exposure is associated with neurodevelopmental disorders in offspring. However, studies assessing the effects of prenatal OPEs exposure on the dynamic changes in attention deficit hyperactivity disorder (ADHD) symptoms in preschoolers are scarce. Since vitamin D has been demonstrated to have a "neuroprotective" effect, the modifying effects of maternal vitamin D were estimated. METHODS: The present study included 2410 pregnant women from the Ma'anshan Birth Cohort. The levels of OPEs in the mothers' urine were examined in the three trimesters. The Chinese version of the Conners Abbreviated Symptom Questionnaire was used to examine preschoolers' ADHD symptoms at 3, 5, and 6 years of age. ADHD symptom trajectories were fitted via group-based trajectory modeling. We used multinomial logistic regression, Bayesian kernel machine regression, quantile-based g-computation, and generalized linear models to assess individual and mixed relationships between OPEs during pregnancy and preschoolers' ADHD symptoms and trajectories. RESULTS: Preschoolers' ADHD symptom scores were fitted to 3 trajectories, including the low-score, moderate-score, and high-score groups. First-trimester dibutyl phosphate (DBP), second-trimester bis(2-butoxyethyl) phosphate (BBOEP), and third-trimester diphenyl phosphate (DPHP) were associated with an increased risk in the high-score group (p < 0.05). BBOEP in the third trimester was associated with decreased risk in the moderate-score group (OR = 0.89, 95% CI: 0.79, 1.00). For mothers with 25(OH)D deficiency, a positive relationship was observed between OPEs during pregnancy and symptom trajectories. Our results did not reveal any mixed effects of OPEs on ADHD symptom trajectories. CONCLUSION: Prenatal exposure to OPEs had heterogeneous associations with ADHD symptom trajectories in preschoolers. Additionally, the effect of individual OPEs on symptom trajectories was intensified by vitamin D deficiency.

Prenatal heavy metal exposure and pediatric asthma, allergic rhinitis, atopic dermatitis: a systematic review and meta-analysis.

OBJECTIVE: We review the prevalence of allergic diseases in children across prenatal exposures to heavy metals. METHODS: This systematic review and meta-analysis is registered in the PROSPERO database (CRD42023478471). A comprehensive search of PubMed, Web of Science, Medline and Cochrane library was conducted from the database inception until 31 October 2023. The Newcastle-Ottawa Quality Assessment Scale (NOS) was used to assess the quality of included studies. We used a random-effects model to summarize the effects from the studies. RESULTS: A total of 16 studies were included, 120,065 mother-child pairs enrolled. The NOS scores indicated that the quality of the literature included in the study was of a high standard. CONCLUSION: The final results indicate that prenatal exposure to Pb increased the incidence of wheeze and Eczema in infants, and exposure to Ni and CD increased the incidence of AD in infants.

Prenatal cigarette smoke exposure sensitizes acetaminophen-induced liver injury by modulating miR-34a-5p in male offspring mice.

Introduction: Cigarette smoke (CS) exacerbates the severity of diseases not only in lungs, but also in systemic organs having no direct contact with smoke. In addition, smoking during pregnancy can have severe health consequences for both the mother and the fetus. Therefore, our aim was to evaluate effects of prenatal exposure to CS on acetaminophen (APAP)-induced acute liver injury (ALI) in offspring. Methods: Female C57BL/6 mice on day 6 of gestation were exposed to mainstream CS (MSCS) at 0, 150, 300, or 600 µg/L for 2 h a day, 5 days a week for 2 weeks using a nose-only exposure system. At four weeks old, male offspring mice were injected intraperitoneally with a single dose of APAP at 300 mg/kg body weight to induce ALI. Results: Maternal MSCS exposure significantly amplified pathological effects associated with ALI as evidenced by elevated serum alanine aminotransferase levels, increased hepatocellular apoptosis, higher oxidative stress, and increased inflammation. Interestingly, maternal MSCS exposure reduced microRNA (miR)-34a-5p expression in livers of offspring. Moreover, treatment with a miR-34a-5p mimic significantly mitigated the severity of APAP-induced hepatotoxicity. Overexpression of miR-34a-5p completely abrogated adverse effects of maternal MSCS exposure in offspring with ALI. Mechanistically, miR-34a-5p significantly decreased expression levels of hepatocyte nuclear factor 4 alpha, leading to down-regulated expression of cytochrome P450 (CYP)1A2 and CYP3A11. Discussion: Prenatal exposure to MSCS can alter the expression of miRNAs, even in the absence of additional MSCS exposure, potentially increasing susceptibility to APAP exposure in male offspring mice.