Prenatal exposure to paternal smoking and likelihood for autism spectrum disorder.
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ABSTRACT: Lay abstract
What is Already Known about This Subject: Genetics, (including de novo mutations), environmental factors (including toxic exposures), and their interactions impact autism spectrum disorder etiology. Paternal smoking is a candidate risk for autism spectrum disorder due to biological plausibility, high prevalence, and potential intervention.What This Study Adds: This original study and its replication confirms that paternal factors can substantially contribute to autism spectrum disorder risk for their offspring. It specifically indicates that paternal smoking both before and during pregnancy contributes significantly to autism spectrum disorder risk.Implications for practice, research, or policy: Smoking prevention, especially in pregnancy planning, may decrease autism spectrum disorder risk in offspring.
SUBMITTER: Kim B
PROVIDER: S-EPMC8419001 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Ambient air pollution and maternal diabetes may affect common biological pathways underlying adverse neurodevelopmental effects. However, joint effects of maternal diabetes and air pollution on autism spectrum disorder (ASD) have not been studied. OBJECTIVE:We evaluated whether prenatal and early-life air pollution exposure interacts with maternal diabetes status to affect ASD risk. METHODS:This retrospective cohort study included 246,420 singleton children born in Kaiser Permanente Southern California hospitals in 1999-2009. Children were followed from birth until age 5, during which 2471 ASD cases were diagnosed. Ozone (O3), particulate matter?<?2.5??m (PM2.5) and <10??m in aerodynamic diameter, and nitrogen dioxide measured at regulatory air monitoring stations were interpolated to estimate exposures during preconception and each pregnancy trimester, and first year of life at each child's birth address. Hazard ratios (HRs) for ASD were estimated adjusting for birth year, KPSC service areas, and relevant maternal and child characteristics. For each exposure window, interactions were tested between pollutants and a 4-category maternal diabetes variable (none, GDM???24 and <24?weeks' gestation, and pre-existing type 2 diabetes). For an exposure window with statistically significant global interaction between pollutant and diabetes (p?<?0.05), pollutant-associated HRs were estimated separately for each category of maternal diabetes. RESULTS:There were associations of ASD with preconception, first and third trimesters, and first year of life PM2.5, but not with other pollutants. There were, however, interactions of maternal diabetes with first trimester and first year of life O3. Increased ASD risk was associated with first trimester O3 among mothers with GDM?<?24?weeks' gestation [adjusted HR 1.50 per 15.7?ppb O3 (95% CI: 1.08-2.09)]. No O3 associations with ASD were observed in other categories of maternal diabetes. CONCLUSIONS:GDM onset early in pregnancy may increase children's susceptibility to prenatal O3-associated ASD risk. These novel findings merit further investigation.
| S-EPMC7250244 | biostudies-literature
Project description:ImportanceThe etiology of autism spectrum disorder (ASD) is poorly understood, but prior studies suggest associations with airborne pollutants.ObjectiveTo evaluate the association between prenatal exposures to airborne pollutants and ASD in a large population-based cohort.Design, setting, and participantsThis population-based cohort encompassed nearly all births in Metro Vancouver, British Columbia, Canada, from 2004 through 2009, with follow-up through 2014. Children were diagnosed with ASD using a standardized assessment with the Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule. Monthly mean exposures to particulate matter with a diameter less than 2.5 µm (PM2.5), nitric oxide (NO), and nitrogen dioxide (NO2) at the maternal residence during pregnancy were estimated with temporally adjusted, high-resolution land use regression models. The association between prenatal air pollution exposures and the odds of developing ASD was evaluated using logistic regression adjusted for child sex, birth month, birth year, maternal age, maternal birthplace, and neighborhood-level urbanicity and income band. Data analysis occurred from June 2016 to May 2018.ExposuresMean monthly concentrations of ambient PM2.5, NO, and NO2 at the maternal residence during pregnancy, calculated retrospectively using temporally adjusted, high-resolution land use regression models.Main outcomes and measuresAutism spectrum disorder diagnoses based on standardized assessment of the Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule. The hypothesis being tested was formulated during data collection.ResultsIn a cohort of 132 256 births, 1307 children (1.0%) were diagnosed with ASD by the age of 5 years. The final sample size for the PM2.5-adjusted model was 129 439 children, and for NO and NO2, it was 129 436 children; of these, 1276 (1.0%) were diagnosed with ASD. Adjusted odds ratios for ASD per interquartile range (IQR) were not significant for exposure to PM2.5 during pregnancy (1.04 [95% CI, 0.98-1.10] per 1.5 μg/m3 increase [IQR] in PM2.5) or NO2 (1.06 [95% CI, 0.99-1.12] per 4.8 ppb [IQR] increase in NO2) but the odds ratio was significant for NO (1.07 [95% CI, 1.01-1.13] per 10.7 ppb [IQR] increase in NO). Odds ratios for male children were 1.04 (95% CI, 0.98-1.10) for PM2.5; 1.09 (95% CI, 1.02-1.15) for NO; and 1.07 (95% CI, 1.00-1.13) for NO2. For female children, they were for 1.03 (95% CI, 0.90-1.18) for PM2.5; 0.98 (95% CI, 0.83-1.13) for NO; and 1.00 (95% CI, 0.86-1.16) for NO2.Conclusions and relevanceIn a population-based birth cohort, we detected an association between exposure to NO and ASD but no significant association with PM2.5 and NO2.
| S-EPMC6583438 | biostudies-literature
Project description:BackgroundEvidence from experimental and observational studies suggests that prenatal phthalate exposures may be associated with autism spectrum disorder (ASD). We examined whether prenatal phthalate exposures were associated with an increased risk of ASD.MethodsWe quantified 14 metabolites of eight phthalates in 636 multiple maternal urine samples collected during 2nd and 3rd trimesters of pregnancy from 201 mother-child pairs in MARBLES (Markers of Autism Risk in Babies - Learning Early Signs), a high-risk ASD longitudinal cohort. At 3?years old, children were clinically assessed for ASD and classified into three diagnostic categories: ASD (n?=?46), non-typical development (Non-TD, n?=?55), and typical development (TD, n?=?100). We used multinomial logistic regression to evaluate the association of phthalate metabolite concentrations with ASD and Non-TD.ResultsMost associations of phthalate biomarkers with both ASD and Non-TD were null, with the exception that monoethyl phthalate (MEP) was significantly associated with an increased risk of Non-TD (per 2.72-fold relative increase in concentration: Relative risk ratio (RRR)?=?1.38; 95% confidence interval (CI): 1.01, 1.90). When stratified by prenatal vitamin use during the first month of pregnancy, among mothers who took vitamins, ASD risk was inversely associated with mono-isobutyl phthalate (MiBP, RRR?=?0.44; 95% CI: 0.21, 0.88), mono(3-carboxypropyl) phthalate (MCPP, RRR?=?0.41; 95% CI: 0.20, 0.83) and mono-carboxyisooctyl phthalate (MCOP, RRR?=?0.49; 95% CI: 0.27, 0.88), but among mothers who did not take prenatal vitamins, Non-TD risk was positively associated with MCPP (RRR?=?5.09; 95% CI: 2.05, 12.6), MCOP (RRR?=?1.86; 95% CI: 1.01, 3.39), and mono-carboxyisononyl phthalate (MCNP, RRR?=?3.67; 95% CI: 1.80, 7.48). When stratified by sex, among boys, MEP, monobenzyl phthalate, MCPP, MCNP, and sum of di(2-ethylhexyl) phthalate metabolites (?DEHP) were positively associated with Non-TD risk, but associations with ASD were null. Among girls, associations with both ASD and Non-TD were null.ConclusionsOur study showed that phthalate exposures in mid- to late pregnancy were not associated with ASD in children from this high-risk ASD cohort. Further studies should be conducted in the general population without high-risk genes to confirm our findings.
| S-EPMC6280477 | biostudies-literature
Project description:ImportancePrenatal exposure to certain medications has been hypothesized to influence the risk of autism spectrum disorders (ASD). However, the underlying effects on the neurotransmitter systems have not been comprehensively assessed.ObjectiveTo investigate the association of early-life interference with different neurotransmitter systems by prenatal medication exposure on the risk of ASD in offspring.Design, setting, and participantsThis case-control study included children born from January 1, 1997, through December 31, 2007, and followed up for ASD until January 26, 2015, within a single Israeli health maintenance organization. Using publicly available data, 55 groups of medications affecting neurotransmitter systems and prescribed to pregnant women in this sample were identified. Children prenatally exposed to medications were compared with nonexposed children. Data were analyzed from March 1, 2017, through June 20, 2018.Main outcome and measuresHazard ratios (HRs) and 95% CIs of ASD risk associated with exposure to medication groups using Cox proportional hazards regression, adjusted for the relevant confounders (eg, birth year, maternal age, maternal history of psychiatric and neurologic disorders, or maternal number of all medical diagnoses 1 year before pregnancy).ResultsThe analytic sample consisted of 96 249 individuals (1405 cases; 94 844 controls; mean [SD] age at the end of follow-up, 11.6 [3.1] years; 48.8% female), including 1405 with ASD and 94 844 controls. Of 34 groups of medications, 5 showed nominally statistically significant association with ASD in fully adjusted models. Evidence of confounding effects of the number of maternal diagnoses on the association between offspring exposure to medication and ASD was found. Adjusting for this factor, lower estimates of ASD risk among children exposed to cannabinoid receptor agonists (HR, 0.72; 95% CI, 0.55-0.95; P = .02), muscarinic receptor 2 agonists (HR, 0.49; 95% CI, 0.24-0.98; P = .04), opioid receptor κ and ε agonists (HR, 0.67; 95% CI, 0.45-0.99; P = .045), or α2C-adrenergic receptor agonists (HR, 0.43; 95% CI, 0.19-0.96; P = .04) were observed. Exposure to antagonists of neuronal nicotinic acetylcholine receptor α was associated with higher estimates of ASD risk (HR, 12.94; 95% CI, 1.35-124.25; P = .03).Conclusions and relevanceMost of the medications affecting neurotransmitter systems in this sample had no association with the estimates of ASD risk. Replication and/or validation using experimental techniques are required.
| S-EPMC6421849 | biostudies-literature
Project description:Sexual differentiation is a major developmental process. Sex differences resulting from sexual differentiation have attracted the attention of researchers. Unraveling what contributes to and underlies sex differences will provide valuable insights into the development of neurodevelopmental disorders that exhibit sex biases. Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects an individual's social interaction and communication abilities, and its male preponderance has been consistently reported in clinical studies. The etiology of male preponderance remains unclear, but progress has been made in studying prenatal sex hormone exposure. The present review examined studies that focused on the association between prenatal testosterone exposure and ASD development, as well as sex-specific behaviors in individuals with ASD. This review also included studies on maternal immune activation-induced developmental abnormalities that also showed striking sex differences in offspring and discussed its possible interacting roles in ASD so as to present a potential approach for future studies on sex biases in ASD.
| S-EPMC9916422 | biostudies-literature
Project description:BackgroundStudies have shown that air pollution exposures during pregnancy are associated with an increased risk of autism spectrum disorder (ASD) in children, and the risk appears to be greater for boys. However, studies assessing gestational windows of susceptibility have been mostly limited by trimesters.ObjectiveWe identified sensitive windows of exposure to regional air pollution and risk of ASD and examined sex differences in a large birth cohort.MethodsThis population-based retrospective cohort study included 294,937 mother-child pairs with singleton deliveries in Kaiser Permanente Southern California (KPSC) hospitals from 2001 to 2014. Children were followed using electronic medical records until clinical ASD diagnosis, non-KPSC membership, death, or 31 December 2019, whichever came first. Weekly mean fine particulate matter [PM with an aerodynamic diameter of ≤2.5μm (PM2.5)], nitrogen dioxide (NO2), and ozone (O3) pregnancy exposures were estimated using spatiotemporal prediction models. Cox proportional hazard models with distributed lags were used to estimate weekly pollutant exposure associations with ASD risk for the entire cohort, and separately for boys and for girls. Models were adjusted for child sex (for full cohort), maternal race/ethnicity, maternal age at delivery, parity, maternal education, maternal comorbidities, medical center, census tract median household income, birth year, and season.ResultsThere were 5,694 ASD diagnoses (4,636 boys, 1,058 girls). Sensitive PM2.5 exposure windows associated with ASD were found early in pregnancy, statistically significant throughout the first two trimesters [1-27 wk of gestation, cumulative hazard ratio (HR)=1.14 [95% confidence interval (CI): 1.06, 1.23] per interquartile range (IQR) (7.4-μg/m3) increase]. O3 exposure during 34-37 wk of gestation was associated with increased risk [HR=1.06 (95% CI: 1.01, 1.11) per IQR (17.4 ppb) increase] but with reduced risk during 20-28 wk of gestation [HR=0.93 (95% CI: 0.89, 0.98)]. No associations were observed with NO2. Sex-stratified early gestational PM2.5 associations were stronger among boys [boys HR=1.16 (95% CI: 1.08, 1.26); girls HR=1.06 (95% CI: 0.89, 1.26)]. O3 associations in later gestation were observed only in boys [boys HR=1.10 (95% CI: 1.04, 1.16); girls HR=0.94 (95% CI: 0.84, 1.05)].ConclusionsExposures to PM2.5 in the first two gestational trimesters were associated with increased ASD risk in children, with stronger associations observed for boys. The role of O3 exposure on ASD risk merits further investigation. https://doi.org/10.1289/EHP9509.
| S-EPMC8765363 | biostudies-literature
Project description:BackgroundMaternal folic acid (FA) protects against developmental toxicity from certain environmental chemicals.ObjectiveWe examined combined exposures to maternal FA and pesticides in relation to autism spectrum disorder (ASD).MethodsParticipants were California children born from 2000-2007 who were enrolled in the Childhood Autism Risks from Genetics and the Environment (CHARGE) case-control study at age 2-5 y, were clinically confirmed to have ASD (n=296) or typical development (n=220), and had information on maternal supplemental FA and pesticide exposures. Maternal supplemental FA and household pesticide product use were retrospectively collected in telephone interviews from 2003-2011. High vs. low daily FA intake was dichotomized at 800μg (median). Mothers' addresses were linked to a statewide database of commercial applications to estimate agricultural pesticide exposure.ResultsHigh FA intake (≥800μg) during the first pregnancy month and no known pesticide exposure was the reference group for all analyses. Compared with this group, ASD was increased in association with <800μg FA and any indoor pesticide exposure {adjusted odds ratio [OR]=2.5 [95% confidence interval (CI): 1.3, 4.7]} compared with low FA [OR=1.2 (95% CI: 0.7, 2.2)] or indoor pesticides [OR=1.7 (95% CI: 1.1, 2.8)] alone. ORs for the combination of low FA and regular pregnancy exposure (≥6 mo) to pet pesticides or to outdoor sprays and foggers were 3.9 (95% CI: 1.4, 11.5) and 4.1 (95% CI: 1.7, 10.1), respectively. ORs for low maternal FA and agricultural pesticide exposure 3 mo before or after conception were 2.2 (95% CI: 0.7, 6.5) for chlorpyrifos, 2.3 (95% CI: 0.98, 5.3) for organophosphates, 2.1 (95% CI: 0.9, 4.8) for pyrethroids, and 1.5 (95% CI: 0.5, 4.8) for carbamates. Except for carbamates, these ORs were approximately two times greater than those for either exposure alone or for the expected ORs for combined exposures under multiplicative or additive models.ConclusionsIn this study population, associations between pesticide exposures and ASD were attenuated among those with high versus low FA intake during the first month of pregnancy. Confirmatory and mechanistic studies are needed. https://doi.org/10.1289/EHP604.
| S-EPMC5915192 | biostudies-literature
Project description:ImportanceThe prevalence of autism spectrum disorder (ASD) has been increasing rapidly, with current estimates of 1 in 68 children affected. Simultaneously, use of prenatal ultrasonography has increased substantially, with limited investigation into its safety and effects on brain development. Animal studies have demonstrated that prenatal ultrasonography can adversely affect neuronal migration.ObjectiveTo quantify prenatal ultrasound exposure by the frequency, timing, duration, and strength of ultrasonographic scans in children with later ASD, developmental delay, and typical development.Design, setting, and participantsThis case-control study included 107 patients with ASD, 104 control individuals with developmental delay, and 209 controls with typical development. Participants were identified from medical records based on prenatal care and delivery at Boston Medical Center, a diverse, academic, safety-net medical center, from July 1, 2006, through December 31, 2014, with a gestational age at birth of at least 37 weeks. Data were analyzed from May 1, 2015, through November 30, 2017.ExposuresUltrasonographic exposure was quantified by the number and timing of scans, duration of exposure, mean strength (depth, frame rate, mechanical index, and thermal index), and time of Doppler and 3- and 4-dimensional imaging.Main outcomes and measuresAmong participants with ASD and controls with developmental delay and typical development, ultrasound exposure was quantified and compared per trimester and for the entire pregnancy, with adjustment for infant sex, gestational age at birth, and maternal age.ResultsA total of 420 participants were included in the study (328 boys [78.1%] and 92 girls [21.9%]; mean age as of January 1, 2016, 6.6 years; 95% CI, 6.5-6.8 years). The ASD group received a mean of 5.9 scans (95% CI, 5.2-6.6), which was not significantly different from the 6.1 scans (95% CI, 5.4-6.8) in the developmental delay group or the 6.3 scans (95% CI, 5.8-6.8) in the typical development group. Compared with the typical development group, the ASD group had shorter duration of ultrasound exposure during the first (290.4 seconds [95% CI, 212.8-368.0 seconds] vs 406.4 seconds [95% CI, 349.5-463.3 seconds]) and second (1687.6 seconds [95% CI, 1493.8-1881.4 seconds] vs 2011.0 seconds [95% CI, 1868.9-2153.1 seconds]) trimesters but no difference in the number of scans. The ASD group had greater mean depth of ultrasonographic penetration than the developmental delay group in the first trimester (12.5 cm [95% CI, 12.0-13.0 cm] vs 11.6 cm [95% CI, 11.1-12.1 cm]). The ASD group had greater mean depth than the typical development group during the first (12.5 cm [95% CI, 12.0-13.0 cm] vs 11.6 cm [95% CI, 11.3-12.0 cm]) and the second (12.9 cm [95% CI, 12.6-13.3 cm] vs 12.5 cm [95% CI, 12.2-12.7 cm]) trimesters.Conclusions and relevanceThis study found significantly greater mean depth of ultrasonographic penetration in the ASD group compared with the developmental delay group in the first trimester and compared with the typical development group in the first and second trimesters. Further research is needed to determine whether other variables of ultrasound exposure also have adverse effects on the developing fetus.
| S-EPMC5875374 | biostudies-literature
Project description:We examined associations between maternal smoking and autism spectrum disorder (ASD) in children in a statewide population-based cohort and sibling-comparison design using California birth records (n = 2,015,104) with information on maternal smoking, demographic factors, and pregnancy (2007-2010). ASD cases (n = 11,722) were identified through California Department of Developmental Services records with diagnoses based on the Diagnostic and Statistical Manual of Mental Disorders-IV-TR. We estimated odds ratios for ASD with and without intellectual disability in the full cohort using logistic regression and in a sibling comparison using conditional logistic regression. In the full cohort, the adjusted odds ratio for ASD and maternal smoking 3 months before/during pregnancy compared with nonsmoking was 1.15 (95% confidence interval (CI): 1.04, 1.26), and it was similar in cases with (odds ratio = 1.12, 95% CI: 0.84, 1.49) and without intellectual disability (odds ratio = 1.15, 95% CI: 1.04, 1.27). Heavy prenatal smoking (≥20 cigarettes/day in any trimester) was related to an odds ratio of 1.55 (95% CI: 1.21, 1.98). In the sibling comparison, the odds ratio for heavy smoking was similarly elevated but the confidence interval was wide. Our findings are consistent with an increased risk for ASD in offspring of mothers who smoked ≥20 cigarettes/day during pregnancy; associations with lighter smoking were weaker.
| S-EPMC8096427 | biostudies-literature
Project description:BackgroundExposure to endocrine disruptors is unavoidable. Many such compounds are suspected to impact neurologic development of children, but most studies conducted have considered effects of individual chemicals in isolation. Because exposures co-occur, it is important to consider their health impacts in a single regression framework.MethodsWe applied Bayesian statistical tools (including shared mean and mixture priors for 25 unique chemicals) to study independent associations of endocrine disruptor biomarkers with autism spectrum disorder (ASD) (n = 491) and intellectual disability (n = 155), compared with 373 general population controls, in the Early Markers for Autism study. We measured biomarkers in maternal serum collected and stored from midpregnancy and considered them individually or as a class (i.e., summed polychlorinated biphenyls). We adjusted all models for original matching factors (child sex and month and year of birth), maternal age, maternal race/ethnicity, parity, and maternal education at the time samples were collected. We estimated the change in the odds of ASD or intellectual disability per 1 SD increase in the z-score of measured biomarker concentration for each chemical.ResultsOdds of ASD and intellectual disability did not change with increasing concentration for any specific endocrine disruptor. The effect estimates for each chemical were centered on or near an odds ratio of 1.00 in both models where we applied a shared mean or a mixture prior.ConclusionOur mixtures analyses do not suggest an independent relationship with ASD or intellectual disability with any of the 25 chemicals examined together in this mixtures analysis.
| S-EPMC6456403 | biostudies-literature