Introduction Le projet MediCA visait à créer une base nationale issue de l’appariement de deux sources complémentaires : le Système National des Données de Santé (SNDS), fournissant des données exhaustives sur la prescription et délivrance de médicaments pendant la grossesse, et quatre registres de malformations, recensant les anomalies congénitales, selon des critères standardisés définis par EUROCAT. L’objectif de cette base de données était d’évaluer le risque de malformations après exposition in utero aux médicaments. Méthodes La cohorte inclut toutes les grossesses terminées entre 2012 et 2020 chez les femmes (15-55 ans) résidant dans les zones couvertes par les registres de malformations d’Auvergne, de Bretagne, de Paris et de La Réunion. Une analyse descriptive de cette nouvelle base de données a été réalisée : caractéristiques des femmes, issues de grossesse, expositions médicamenteuses, caractéristiques des enfants. Résultats MediCA a inclut actuellement 1 043 520 grossesses. L’âge moyen maternel est de 30,7 ± 6,0 ans. Une affection de longue durée a été identifiée chez 1,2% des femmes. Dans cette cohorte, 90,5% des femmes ont reçu au moins un médicament pendant la grossesse. Le nombre moyen de principes actifs délivrés est de 9,3±8,29. Les classes les plus fréquentes sont les médicaments du système nerveux (66% des femmes), digestif et métabolique (53%), et les anti-infectieux (53%). Seules 15 % des femmes ont eu une délivrance d’acide folique trois mois avant la grossesse. Les délivrances de médicaments connus comme tératogènes et/ou fœtotoxiques majeurs concernent 6 256 soit 0,6% des femmes enceintes. Une interruption de grossesse est survenue dans 27,3% des cas. Le taux global de malformations majeures est de 3,2%, comparable aux données de la littérature. La répartition des anomalies congénitales par système est similaire entre MediCA et EUROCAT Discussion/Conclusion MediCA constitue la première base française liant des données de prescriptions et délivrances de médicaments du SNDS et les anomalies congénitales validées par les registres. MediCA offre un outil unique pour l’évaluation du risque tératogène des médicaments pendant la grossesse.

AIM:Many women take medications during pregnancy. However, the risk to the fetus from most medications is uncertain. Congenital anomalies are one of the leading causes of infant death and contribute to long-term disability. Signal detection methods can be used to systematically identify possible medication-anomaly associations that require further investigation. METHODS:Data on first trimester medication exposures in pregnancies with a congenital anomaly reported to 14 EUROmediCAT registries with a birth year of 2005-2018 were analysed. Case-malformed disproportionality analysis identified medication-anomaly signals using a disproportionality signal detection method. Identified signals were then compared to previous EUROmediCAT signal detection studies and ranked based on a proxy for the severity of impact at a population level using the number of estimated excess congenital anomaly cases within the exposed population and the average additional time in hospital over the first year of life. Generalized linear mixed models were used to assess confounding by birth year and registry within the top 20 ranked signals. RESULTS:1611 medication-outcome pairs with at least three observations were analysed, and 153 signals for 63 different medications were identified. Of the top 20 ranked signals, 10 (involving nine medications) were prioritized for further independent investigation. CONCLUSION:The signals identified here are hypothesis forming only. Independent studies that adequately account for confounding are subsequently needed to evaluate if the identified signals are causal. Further investigation of signals with low population impact, but high potential individual risk is also recommended.

Introduction The diagnosis of congenital hip dislocation is historically included in the first clinical examination of the newborn baby[1].Later,the term developmental dysplasia of the hip was defined,with congenital hip dislocation being the most severe form of developmental dysplasia of the hip[2-4].

Prenatal exposure to persistent organic pollutants (POPs) has been linked to growth and adiposity development in children. However, only few studies considered the growth dynamic and none have tracked children into adolescence. This study included 450 mother-child pairs from the PELAGIE cohort (France). Polychlorinated biphenyls (PCBs), Organochlorine pesticides (OCs), Polybrominated diphenyl ethers (PBDEs), and Perfluoroalkyl substances (PFAS) were measured in cord blood. A latent class growth model identified four types of BMI z-score (zBMI) trajectories from birth to 13 years. Associations between each POP and zBMI trajectories were assessed using multinomial regressions. POP mixture effects were explored using Quantile G-computation and grouped Weighted Quantile Sum regressions. All analyses were stratified by sex and adjusted for confounders. In girls, all PCBs were associated with higher odds of the "Low-High" trajectory (e.g., OR (95%CI) = 3.78 (1.58; 9.05) per doubling of PCB 153). The PCB mixture, HCB and β-HCH also tended to favor this trajectory, whereas dieldrin was associated with a lower odds. In boys, the "High-High" and "Low-High" trajectories were significantly associated with the POP and PFAS mixtures (with PFuDA, PFDA and PFOA as main contributors). Our study suggests sex-specific associations of prenatal exposure to POPs mixtures with growth dynamics until adolescence known as risk factors for adult cardiovascular diseases. Although these results need to be confirmed in larger studies, girls seem more vulnerable to prenatal exposure to PCBs while boys seem more vulnerable to prenatal exposure to PFAS.

BACKGROUND:The evidence gap relating to the risk of congenital anomalies (CA) associated with first trimester medication exposure in pregnancy is well recognized. AIMS:We describe the EUROmediCAT network and databases, and the methodological approach to pregnancy pharmacovigilance. MATERIAL AND METHODS:Multidisciplinary expertise includes CA diagnosis and epidemiology, pharmacoepidemiology, pharmacology and teratology. The EUROmediCAT central database comprises standardized data from 19 EUROCAT CA registries in 14 countries, including more than 40 000 CA cases 1995-2021 with first trimester medication exposure data recorded, and a population coverage of 14.6 million births, growing by more than 650 000 births per year. The distributed database enables federated data analysis across eight countries which can link data from CA registries to electronic healthcare data, with population coverage of up to 900 000 births per year for linkage to maternal prescriptions, of which 300 000 births per year for linkage also to data on all births. RESULTS:The databases have enabled a variety of study designs: case-malformed control studies, cohort studies, disease cohort studies, signal detection studies, prevalence and ecological studies, and medication utilization studies. DISCUSSION:A key strength is that studies of CA risk can address accurately the specificity of risk by type of CA. CONCLUSION:EUROmediCAT presents a unique data and expert resource for tackling the enormous evidence gap regarding the safety of medication during pregnancy.

BACKGROUND:Sirenomelia is a rare congenital condition most notably characterized by a single lower limb. Previous studies have suggested a prevalence of approximately 1 per 100,000 births. However, in Wales 17 cases were recorded between 1998 and 2016, suggesting a higher rate of sirenomelia in this country. OBJECTIVES:This study compared current prevalence of sirenomelia in Wales with European data. This study further reviewed detailed time, place, and person data on sirenomelia cases in Wales to investigate possible causal factors. METHOD:A retrospective cohort study from birth defect surveillance programs. Individual-level records for all welsh cases were examined for evidence of causal factors. Comparator data from other countries were obtained from EUROCAT (a European network of population-based registries for the epidemiological surveillance of congenital anomalies). RESULTS:European data from 24 national and regional registries of congenital anomalies included 97 cases of sirenomelia identified across 9.6 million births between 1998 and 2016, giving a prevalence rate of 1 per 100,000 (95% CI 0.83, 1.23). Five regions reported statistically significantly higher rates than that recorded across all registries, while one region reported a significantly lower rate. Small numbers of cases limit definitive statistical interpretation. Analysis of the Wales data did not identify common epidemiological factors between cases. CONCLUSIONS:The contemporary prevalence of sirenomelia across Europe is consistent with earlier studies at approximately 1 per 100,000 births (95% CI 0.83, 1.23). However, there is greater variation between regions than would be expected by chance. There remains no definitive evidence for causal environmental factors.

Agricultural activities generate environmental dispersion of pesticides that might be of concern for surrounding populations. While studies have suggested that the risk of congenital anomalies is higher among women living close to crops during pregnancy, few have been conducted in Europe. This study aimed to evaluate this risk in the Brittany region (France) known for its important farming activities. A case-control study was conducted between 2012-2018, based on the regional Registry of congenital anomalies in accordance with the European Surveillance of Congenital Anomalies (EUROCAT) guidelines. Controls were the two healthy births occurring after each case. Crop acreages were calculated within the 1000-m zone surrounding each maternal residence during pregnancy, for 15 groups of crops/land uses based on their common pesticide strategies. The risk of all congenital anomalies was higher among women with the greatest vegetable/flower crop acreage than among those with no such crop (OR=1.49, 95% CI: 1.07-2.07), particularly for digestive system anomalies (OR=4.5, 1.5-13.0). The presence of orchards was associated with an increased risk of congenital heart defects (OR=2.70, 1.10-6.64). An association between orchard acreage and urinary malformation was suggested, but with an unexpected U-shape. Living close to miscellaneous crop/land use plots was associated with an increased risk of digestive system anomalies, for the smallest acreages only, relative to no such crop (OR=2.97, 1.15-7.67). Living during pregnancy close to certain crops requiring the most intensive pesticide use may increase the risk of congenital anomalies, particularly those affecting the digestive and cardiovascular systems.

Few studies have evaluated the impact of prenatal exposure to persistent organic pollutants (POPs) on menstruation characteristics. Therefore, the aim of our study was to investigate the associations between cord blood concentrations of POPs and menstruation characteristics including menarche status, menstrual regularity, pain and duration in girls at age 12. We used data from the French PELAGIE mother-child cohort follow-up at 12 years old which included a questionnaire on menstruation characteristics. POP concentrations of 14 organochlorine pesticides (OCPs), 17 polychlorinated biphenyls (PCBs), 5 polybrominated diphenyl ethers (PBDEs), and 9 per-polyfluoroalkyl substances (PFAS) were measured on cord blood sampled at birth. We used multivariate logistic regression and Poisson regression to study the relation between prenatal POPs and menarche status, regularity of menstruations, menstruation duration, and severe pain in the lower abdomen or cramps (N = 296). The effect of mixtures of POPs on these outcomes were assessed using quantile g-computation. The majority of POPs were associated with a non-statistically significant increased risk of menarche at 12 years old, especially for the PCB mixture (OR = 1.29, 95 % CI [0.99; 1.68]). We also observed a statistically significant association between the second tercile of dieldrin (OR = 2.91, 95 % CI [1.13; 7.82]) and PFNA (OR = 3.13, 95 % CI [1.01; 10.43]) and severe pain in the lower abdomen or cramps, and a statistically significant association between the second tercile of hexachlorobenzene and menstruation duration (% change = 25.6 %, 95 % CI [1.2; 56.6]). For others POPs and other menstrual characteristics we did not observe any associations. Further longitudinal studies are needed to confirm these results, possibly through combined analyses of several mother-child cohorts to increase study power.

PurposeAntiretroviral drugs are recommended during pregnancy to achieve HIV viral suppression and reduce mother-to-child transmission. Congenital anomaly signals were reported after fetal exposure to antiretroviral drugs in several studies warranting further investigation. We aimed to evaluate the risk of congenital anomalies after fetal exposure to antiretroviral drugs using the European congenital anomaly registry data.MethodsA case/non-case study was performed, using the EUROmediCAT central database. All the congenital anomalies, exposed to any antiretroviral drugs, were included from 1995 to 2019. We explored each signal identified from the literature for associations between congenital anomalies and specific antiretroviral exposures. We compared antiretroviral exposure between the signal anomalies (cases) and all other malformed registrations (controls). Reporting odds ratio (ROR) and their 95% confidence intervals were estimated and adjusted for registry and maternal age.ResultsBetween 1995 and 2019, 173 cases of congenital anomalies were observed after any exposure to antiretroviral drugs. The signal previously identified in the literature between congenital heart defects and exposure to zidovudine was confirmed in the main analysis (aROR 3.66 [1.63-8.23]). Other signals identified in the literature were not confirmed, although two cases of hypospadias and two cases of limb defects were reported after zidovudine and atazanavir exposure, respectively. The signal detection analysis did not reveal any new signal after applying the Bonferroni correction.ConclusionsOur study does not reveal new signals but confirms the previously identified signal between congenital heart defects and fetal exposure to zidovudine. The physio-pathological hypothesis induced by zidovudine exposure should be explored in future studies.

Introduction While a number of studies have examined the effects of prenatal exposure to per- and polyfluoroalkyl substances (PFAS) on childhood obesity, the results reported have been inconsistent and few studies have integrated biological markers. The aim of this study was to investigate the associations between prenatal exposure to PFAS and cardiometabolic health parameters at age 12, taking pubertal stage into consideration. Method This study included 394 mother-child pairs enrolled in the PELAGIE mother-child cohort (France). Nine PFAS were measured in umbilical cord blood, and the children attended a clinical examination at age 12. Anthropometry, blood metabolic markers, and blood pressure were measured and used to build an internal cardiometabolic score. Linear regression and Quantile G-computation models were used to evaluate individual and mixture PFAS effects, adjusting for confounders and stratifying by sex and pubertal stage. Results No statistically significant association was observed between prenatal exposure to PFAS and cardiometabolic score at age 12. In post-menarche girls, perfluorohexane sulfonate (PFHxS) and perfluorodecanoic acid (PFDA) were statistically significantly associated with a decrease in a number of adiposity parameters (e.g., Body mass index z-score: beta [95%CI] = -0.37 [-0.67; -0.07]), as well as a decrease in low-density lipoproteins (LDL) and leptin levels. Similar results were observed with PFAS mixture, with statistically significantly decreased tricipital skinfolds (beta [95%CI] = -1.30 [(-2.54;-0.06)]). Isolated associations, including higher systolic blood pressure, changes in cholesterol levels, and lower adiponectin levels were observed in specific subgroups. Conclusion There is no clear evidence of an association between prenatal exposure to PFAS and the cardiometabolic health at earlier stage of pubertal development. However, inverse associations between PFAS and anthropometric measures have been observed in post-menarche girls. While the literature on this topic is scarce in pre-adolescents, these results suggest the importance of considering sex and pubertal stage in these associations.

INTRODUCTION:Breastfeeding has been shown to be associated with improved child cognitive performance, but the causality of this association is still debated because it tends to disappear when accounting for maternal cognitive performance and socioeconomic status. We aimed to explore the relationship between breastfeeding and the cognitive performance of children in the French general population. METHODS:From the PELAGIE woman-child cohort, which included pregnant women between 2002 and 2006 in Brittany (France), 286 children were evaluated using the Wechsler Intelligence Scale for Children (WISC-IV) and the Developmental Neuropsychological Assessment (NEPSY) scales at age 6. Associations between breastfeeding and cognitive performance were assessed using multivariable linear regression models adjusted for maternal verbal cognitive performance and education level, familial stimulation and environment (Home Observation for Measurement of the Environment scale), and Rey's Social Deprivation Index (contextual indicator). In addition, we performed structural equation modeling (SEM) to investigate the complex interrelation between these variables. RESULTS:Children who were breastfed for at least 4 months had significantly higher scores on the WISC Verbal Comprehension Index (WISC-VCI) than those who were never breastfed or who were breastfed less than 15 days (βadjusted, 4.95 points; 95% CI, 0.54-9.37). Among the 193 children who were breastfed, the duration of breastfeeding, in particular during the first 4 months, was increasingly associated with the WISC-VCI score. We also observed statistically significant associations between breastfeeding itself or the duration of breastfeeding and better performance on several NEPSY subtests, including visual attention, design copying, arrows, and narrative memory. SEM analysis confirmed these associations. No statistical association was observed between breastfeeding and the WISC Working Memory Index or other NEPSY subtests. DISCUSSION:These data support current national and World Health Organization global 2025 targets of promoting breastfeeding for at least 4 to 6 months.

BACKGROUND:Emerging evidence suggests that prenatal and prepubertal exposure to organochlorine compounds (OCs) and perfluoroalkyl substances (PFASs) is associated with children's reproductive health. This study examines the potential impact of these exposures on pubertal development in 12-year-old children. METHODS:Based on the French PELAGIE mother-child cohort, concentrations of OCs and PFASs were measured in cord blood (from 2003 to 2006) and in blood at age 12 (from 2016 to 2018). Medical staff assessed pubertal development (Tanner stages) at age 12, and girls self-reported age at menarche annually (ages 9-16). Associations between exposures and delayed or earlier pubertal development were analyzed using multinomial logistic and Cox regression models, adjusting for confounders, and using quantile g-computation for compound mixtures. RESULTS:Among 502 children (250 girls, 252 boys; median age: 12.8 years), prenatal PFUdA exposure in girls was associated with delayed breast development [OR (95 %CI): 2.05 (1.03,4.06)]. In boys, prenatal PFHxS exposure was associated with reduced risk of earlier gonadal development [0.47 (0.26,0.83)], and β-HCH with reduced risks of both delayed [0.66 (0.43,0.99)] and earlier [0.69 (0.48,0.97)] pubic hair development. Prepubertal exposure in girls to HCB, PCBs, and PFASs was associated with increased risk of delayed breast development [e.g. , PFOA:2.53 (1.04,6.12)] and later age at menarche [e.g., ΣPCBs: HR 0.77 (0.61,0.97)]. In boys, prepubertal p,p'-DDE was associated with increased risk of earlier puberty [gonadal development: 1.77 (1.09,2.88); pubic hair growth: 1.56 (1.01,2.44)], while PCB-118 was associated with delayed development. Prepubertal PFASs were associated with reduced risk of earlier puberty [e.g., PFHxS-gonadal stages: 0.39 (0.20,0.75)]. In mixture analyses, no associations were observed with regards to prenatal exposure, but prepubertal exposure was associated with delayed pubertal development in girls. CONCLUSION:Prenatal and prepubertal exposure to OCs and PFASs may alter pubertal development at age 12 in girls and boys, underscoring the need for further research.

Chlordecone is a persistent organochlorine insecticide that was widely used to control banana root borer in the French West Indies until 1993. Animal studies have reported an impact of chlordecone exposure on female fertility, but no data are available for humans. Here, we investigated the association between chlordecone exposure in women and time to pregnancy (TTP). We included 668 pregnant women from the Timoun mother-child cohort study performed in Guadeloupe between 2004 and 2007. TTP was measured with a questionnaire at the inclusion visit. Chlordecone concentrations in maternal blood samples were determined at the time of delivery. A discrete-time Cox model was used to estimate fecundability odds ratios (fOR) and their 95

BACKGROUND:Surveillance of congenital anomaly prevalence over time can identify new teratogens. Anomalies with a genetic cause are excluded from the monitoring. OBJECTIVES:We examined temporal changes in the proportion of genetic diagnoses among cases with a congenital anomaly. METHODS:Data was used from twenty EUROCAT congenital anomaly registries over the birth years 2013 and 2022. All pregnancy outcomes were included. Multilevel binomial regression models were fitted to estimate the annual change in the proportion of genetic diagnoses of all anomalies by registry. Results were additionally reported, excluding cases with trisomy 13, 18, or 21. RESULTS:Overall, 20% of the 100,099 cases in the study had a genetic diagnosis, and this proportion increased annually by 1.4% (95% CI, 0.8%-1.9%); an absolute increase of approximately 3% from 2013 to 2022. After excluding the trisomies, the overall proportion was 10% with an annual increase of 1.2% (95% CI 0.4%-2.0%). There was considerable variation in the proportion of genetic cases per registry. An increasing proportion of genetic diagnoses was found for five congenital anomaly groups, after excluding the trisomies. We hypothesise that the increase in genetic diagnoses is due to increased access to clinical genetic services, more extensive genetic testing, and the identification of new genes as causes of congenital anomalies. CONCLUSIONS:The modest increase in genetic diagnoses among cases with a congenital anomaly is not expected to have a large impact on the surveillance of the non-genetic anomalies in the EUROCAT network. EUROCAT will continue to monitor the proportion of genetic diagnoses every five years.

BACKGROUND:There is a growing concern about the potential role of environmental exposure in congenital male anomalies. OBJECTIVE:We aimed to assess the association between the domestic use of products containing solvents or pesticides during pregnancy and the risk of hypospadias in the offspring. METHODS:We included newborns from the PENEW case-control study, which took place in Brittany, France, from October 2012 to December 2018. Newborns affected with hypospadias (n = 100) were matched with one to four controls (n = 283) according to the biological sex assigned at birth, center of birth, year, and season of birth. We assessed self-reported domestic exposure to solvents (cosmetics, house cleaning, and home renovation products) and pesticides (used indoors and outdoors) through a maternal questionnaire at birth. We performed multivariable conditional logistic regression, adjusting for potential confounders. RESULTS:The self-reported use of indoor pesticides during pregnancy was associated with an increased risk of hypospadias in offspring (adjusted odds ratio [aOR] = 2.68, 95% CI = 1.5, 4.81), especially those against wood insects (aOR = 13.19, 95% CI = 1.11, 59.57), rodents (aOR = 4.61, 95% CI = 1.03, 20.7), and flying and crawling insects (aOR = 2.77, 95% CI = 1.46, 5.28). Other studies have shown that domestic exposure was not statistically significantly associated with a risk of hypospadias. CONCLUSION:The use of indoor pesticides during pregnancy may be associated with a higher risk of hypospadias in offspring, especially those against flying and crawling insects. Further studies might be needed to identify specific molecules to target and confirm our results on a larger sample.

BACKGROUND:Congenital ocular anomalies (COA) are among the most common causes of visual impairment in children in high-income countries. The aim of the study is to describe the prevalence of the various COA recorded in European population-based registries of CA (EUROCAT) participating in the EUROmediCAT consortium. METHODS:Data from 19 EUROmediCAT registries and one healthcare database (EFEMERIS) were included in this descriptive epidemiological study. Cases of COA included live births, FD from 20 weeks gestational age (GA), and termination of pregnancy for fetal anomaly. RESULTS:The prevalence of total COA was 3.47/10,000 births (95% CI [3.61-3.82]), ranging from 1.41 to 13.46/10,000 depending on the registry. Among COA cases, congenital lens anomalies were the most frequent anomalies (31%), of which over half were single ocular anomalies (presenting with only one ocular anomaly). An/microphthalmia was the second most frequent COA (24%) of which three-quarters were multiply malformed (associated to extraocular major anomalies). Among single COA cases, 58 were prenatally diagnosed (4%), of which, 58% were diagnosed in the second trimester. Known genetic causes of COA explained 2.5%-25% of COA depending on their class. CONCLUSIONS:This is the first European study describing COA. The detailed prevalence data offered in this study could improve screening and early diagnosis of different classes of COA. As COA are rare, epidemiological surveillance of large populations and accurate clinical descriptions are essential.

Background: Hypospadias is a male genital tract defect for which an increase in prevalence has been documented over the last few decades. A role for environmental risk factors is suspected, including prenatal exposure to pesticides. Objectives: To study the risk of hypospadias in association with multiple pesticide measurements in meconium samples. Methods: The Brittany Registry of Congenital Anomalies (France) conducted a case–control study between 2012 and 2018. Cases were hypospadias, ascertained by a pediatrician and a pediatric surgeon, excluding genetic conditions, following European Surveillance of Congenital Anomalies guidelines (N = 69). Controls (N = 135) were two male infants without congenital anomaly born after each case in the same maternity unit. Mothers in the maternity units completed a self-administered questionnaire, we collected medical data from hospital records, and medical staff collected meconium samples. We performed chemical analysis of 38 pesticides (parent compound and/or metabolite) by UHPLC/MS/MS following strict quality assurance/quality control criteria and blind to case–control status. We carried out logistic regression accounting for frequency-matching variables and major risk factors. Results: Among the 38 pesticides measured, 16 (42%) were never detected in the meconium samples, 18 (47%) were in <5% of samples, and 4 (11%) in ≥5% of the samples. We observed an association between the detection of fenitrothion in meconium and the risk of hypospadias (OR = 2.6 [1.0–6.3] with n cases = 13, n controls = 21), but not the other pesticides. Conclusions: Our small study provides a robust assessment of fetal exposure. Fenitrothion’s established antiandrogenic activities provide biologic plausibility for our observations. Further studies are needed to confirm this hypothesis.

BACKGROUND:Organic solvents are used in formulating an extensive range of products for professional use. Animal and human studies suggest that in utero solvent exposure may affect neurodevelopment. Our objective was to assess the association between occupational exposure to solvents during pregnancy and child behavior aged 2-12 years. METHODS:The French mother-child cohort PELAGIE (2002-2006) included 3,421 women recruited in early pregnancy. Occupational exposure to solvents was self-reported. For 459 children, parents used a questionnaire derived from the Child Behavior Checklist and the Preschool Social Behavior Questionnaire to assess their child's behavior, at age 2, and the Strengths and Difficulties Questionnaire at ages 6 and 12. A cross-lagged structural equation modeling approach was used to assess direct and indirect associations between exposure and child behavior. RESULTS:At age 2, an increased externalizing behavior score was suggested with prenatal exposure to solvents (mean change in standardized score (95%CI): 0.28 (-0.01, 0.57) for occasional exposure and 0.23 (-0.05, 0.51) for regular exposure). At ages 6 and 12, distinct sex-specific patterns were observed: among boys, no association with externalizing behavior was observed, while among girls, an association was seen for both occasional and regular exposure (total effect at age 12: 0.45 (0.06,0.83) and 0.40 (0.03, 0.76), respectively). For both sexes, occasional exposure may be associated with internalizing behavior at ages 6 and 12 (total effect at age 6: 0.37 (0.06, 0.68) and at age 12: 0.27 (-0.08, 0.62)). CONCLUSIONS:Occupational exposure to solvents during pregnancy may impact child behavior through either direct or cumulative effects during childhood; these associations may persist until early adolescence, especially among girls.