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Postnatal Acetaminophen and Potential Risk of Autism Spectrum Disorder among Males.

ABSTRACT: Some evidence from the literature suggests that postnatal acetaminophen exposure may be associated with increased risk of autism spectrum disorder (ASD). Using a data set obtained from a previous study that was derived from an Internet-based survey among parents on 1515 children from the US, an adjusted odds ratio (aOR) and gender-specific aORs for doses of postnatal acetaminophen provided before age two were calculated against the outcome of ASD. Separately, parental uncertainty on the number of doses of acetaminophen provided was analyzed. A population attributable fraction (PAF) associated with postnatal acetaminophen exposure before age two for ASD among males was also estimated. Postnatal acetaminophen exposure, measured in doses before age two, was found to be associated with ASD among male children (aOR 1.023, CI 1.005-1.043, p = 0.020*), and parental uncertainty on the number of doses of acetaminophen provided before age two was also found to be associated with ASD. Using this data set, the PAF associated with postnatal acetaminophen was estimated to be about 40% of the risk of ASD among male children in the US. These results suggest the possibility that postnatal acetaminophen may be a significant contributor to the risk of ASD among males in the US.

SUBMITTER: Bittker SS

PROVIDER: S-EPMC7017213 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Postnatal Acetaminophen and Potential Risk of Autism Spectrum Disorder among Males.

Bittker Seth S SS Bell Kathleen R KR

Behavioral sciences (Basel, Switzerland) 20200101 1

Some evidence from the literature suggests that postnatal acetaminophen exposure may be associated with increased risk of autism spectrum disorder (ASD). Using a data set obtained from a previous study that was derived from an Internet-based survey among parents on 1515 children from the US, an adjusted odds ratio (aOR) and gender-specific aORs for doses of postnatal acetaminophen provided before age two were calculated against the outcome of ASD. Separately, parental uncertainty on the number o ...[more]

PMID: 31906400

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Project description:BackgroundEarly identification and treatment of individuals with autism spectrum disorder (ASD) improves outcomes, but specific evidence needed to individualize treatment recommendations is lacking. Biomarkers that could be routinely measured within the clinical setting could potentially transform clinical care for patients with ASD. This demonstration project employed collection of biomarker data during regular autism specialty clinical visits and explored the relationship of biomarkers with clinical ASD symptoms.MethodsEighty-three children with ASD, aged 5-10 years, completed a multi-site feasibility study integrating the collection of biochemical (blood serotonin, urine melatonin sulfate excretion) and clinical (head circumference, dysmorphology exam, digit ratio, cognitive and behavioral function) biomarkers during routine ASD clinic visits. Parents completed a demographic survey and the Aberrant Behavior Checklist-Community. Cognitive function was determined by record review. Data analysis utilized Wilcoxon two-sample tests and Spearman correlations.ResultsParticipants were 82% male, 63% White, 19% Hispanic, with a broad range of functioning. Group means indicated hyperserotonemia. In a single regression analysis adjusting for race and median household income, higher income was associated with higher levels of blood serotonin and urine melatonin sulfate excretion levels (p = 0.004 and p = 0.04, respectively). Melatonin correlated negatively with age (p = 0.048) and reported neurologic problems (p = 0.02). Dysmorphic status correlated with higher reported stereotyped behavior (p = 0.02) and inappropriate speech (p = 0.04).ConclusionThis demonstration project employed collection of multiple biomarkers, allowed for examination of associations between biochemical and clinical measures, and identified several findings that suggest direction for future studies. This clinical research model has promise for integrative biomarker research in individuals with complex, heterogeneous neurodevelopmental disorders such as ASD.

Project description:ImportancePrior studies have raised concern about maternal acetaminophen use during pregnancy and increased risk of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in their children; however, most studies have relied on maternal self-report.ObjectiveTo examine the prospective associations between cord plasma acetaminophen metabolites and physician-diagnosed ADHD, ASD, both ADHD and ASD, and developmental disabilities (DDs) in childhood.Design, setting, and participantsThis prospective cohort study analyzed 996 mother-infant dyads, a subset of the Boston Birth Cohort, who were enrolled at birth and followed up prospectively at the Boston Medical Center from October 1, 1998, to June 30, 2018.ExposuresThree cord acetaminophen metabolites (unchanged acetaminophen, acetaminophen glucuronide, and 3-[N-acetyl-l-cystein-S-yl]-acetaminophen) were measured in archived cord plasma samples collected at birth.Main outcomes and measuresPhysician-diagnosed ADHD, ASD, and other DDs as documented in the child's medical records.ResultsOf 996 participants (mean [SD] age, 9.8 [3.9] years; 548 [55.0%] male), the final sample included 257 children (25.8%) with ADHD only, 66 (6.6%) with ASD only, 42 (4.2%) with both ADHD and ASD, 304 (30.5%) with other DDs, and 327 (32.8%) who were neurotypical. Unchanged acetaminophen levels were detectable in all cord plasma samples. Compared with being in the first tertile, being in the second and third tertiles of cord acetaminophen burden was associated with higher odds of ADHD diagnosis (odds ratio [OR] for second tertile, 2.26; 95% CI, 1.40-3.69; OR for third tertile, 2.86; 95% CI, 1.77-4.67) and ASD diagnosis (OR for second tertile, 2.14; 95% CI, 0.93-5.13; OR for third tertile, 3.62; 95% CI, 1.62-8.60). Sensitivity analyses and subgroup analyses found consistent associations between acetaminophen buden and ADHD and acetaminophen burden and ASD across strata of potential confounders, including maternal indication, substance use, preterm birth, and child age and sex, for which point estimates for the ORs vary from 2.3 to 3.5 for ADHD and 1.6 to 4.1 for ASD.Conclusions and relevanceCord biomarkers of fetal exposure to acetaminophen were associated with significantly increased risk of childhood ADHD and ASD in a dose-response fashion. Our findings support previous studies regarding the association between prenatal and perinatal acetaminophen exposure and childhood neurodevelopmental risk and warrant additional investigations.

Dataset Information

Postnatal Acetaminophen and Potential Risk of Autism Spectrum Disorder among Males.

Publications

Postnatal Acetaminophen and Potential Risk of Autism Spectrum Disorder among Males.

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