Dataset Information

Association of Cord Plasma Biomarkers of In Utero Acetaminophen Exposure With Risk of Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder in Childhood.

ABSTRACT: Importance:Prior 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. Objective:To 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 Participants:This 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. Exposures:Three 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 Measures:Physician-diagnosed ADHD, ASD, and other DDs as documented in the child's medical records. Results:Of 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 Relevance:Cord 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.

SUBMITTER: Ji Y

PROVIDER: S-EPMC6822099 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Association of Cord Plasma Biomarkers of In Utero Acetaminophen Exposure With Risk of Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder in Childhood.

Ji Yuelong Y Azuine Romuladus E RE Zhang Yan Y Hou Wenpin W Hong Xiumei X Wang Guoying G Riley Anne A Pearson Colleen C Zuckerman Barry B Wang Xiaobin X

JAMA psychiatry 20200201 2

<h4>Importance</h4>Prior 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.<h4>Objective</h4>To examine the prospective associations between cord plasma acetaminophen metabolites and physician-diagnosed ADHD, ASD, both ADHD and ASD, and developmental disabilities (DDs) in childhood.<h4>Des ...[more]

PMID: 31664451

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Project description:Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorders (ASD) are two of the most represented neurodevelopmental conditions in childhood. The diagnostic shift introduced by the DSM-5, allowing a combined diagnosis of ADHD and ASD, poses different clinical challenges related to diagnostic overshadowing, accuracy of clinical judgment and potential delay in an ASD diagnosis in children presenting with ADHD. Here we tried to disentangle the clinical phenotype and specificity of the two co-occurring conditions in relation to autism traits and empathy, by comparing children with ASD with and without comorbid ADHD with children presenting ADHD only and children with typical development. The child versions of the Autism Quotient (C-AQ) and Empathy Quotient (C-EQ) were administered to a total sample of 198 male children between 6 and 14 years old with age appropriate language skills and normal intelligence. Univariate analysis demonstrated no significant differences in the C-AQ total and subscale scores as well as the C-EQ between children with ASD and children with ASD + ADHD, while children with ADHD alone presented an intermediate phenotype between ASD and TD. Furthermore, a receiver operating characteristic (ROC) analysis was applied to discriminate among the different phenotypes. We found that the C-AQ and C-EQ were accurate at distinguishing with satisfactory reliability between: (a) ASD vs. non- ASD (N-ASD) groups comprising both ADHD and TD children (Area Under the Curve AUC 88% for C-AQ and 81% for C-EQ); (b) ASD and TD (AUC 92% for C-AQ and 95% for C-EQ); (c) ASD and ADHD (AUC 80% for C-AQ and 68% for C-EQ). Our data confirm the reliability of the C-AQ and C-EQ as behavioral markers to differentiate ASD (regardless of comorbid ADHD) from an ADHD condition and TD. Interestingly, in our sample an ADHD condition does not increase the severity of the clinical phenotype in terms of autism traits distribution and empathy, suggesting that the psychological measures detected by the two quantitative instruments are independent of ADHD traits. This evidence will contribute to the translational efforts in developing better tailored treatments and preventive strategies.

Project description:BackgroundChildren with autism spectrum disorder (ASD) often have co-occurring symptoms of attention-deficit/hyperactivity disorder (ADHD) and/or anxiety. It is unclear whether these disorders arise from shared or distinct developmental pathways. We explored this question by testing the specificity of early-life (infant and toddler) predictors of mid-childhood ADHD and anxiety symptoms compared to ASD symptoms.MethodsInfants (n = 104) at high and low familial risk for ASD took part in research assessments at 7, 14, 24 and 38 months, and 7 years of age. Symptoms of ASD, ADHD and anxiety were measured by parent report at age 7. Activity levels and inhibitory control, also measured by parent report, in infancy and toddlerhood were used as early-life predictors of ADHD symptoms. Fearfulness and shyness measured in infancy and toddlerhood were used as early-life predictors of anxiety symptoms. Correlations and path analysis models tested associations between early-life predictors and mid-childhood ADHD and anxiety symptoms compared to mid-childhood ASD symptoms, and the influence of controlling for ASD symptoms on those associations.ResultsIncreased activity levels and poor inhibitory control were correlated with ADHD symptoms and not ASD or anxiety; these associations were unchanged in path models controlling for risk-group and ASD symptoms. Increased fearfulness and shyness were correlated with anxiety symptoms, but also ASD symptoms. When controlling for risk-group in path analysis, the association between shyness and anxiety became nonsignificant, and when further controlling for ASD symptoms the association between fearfulness and anxiety became marginal.ConclusionsThe specificity of early-life predictors to ADHD symptoms suggests early developmental pathways to ADHD might be distinct from ASD. The overlap in early-life predictors of anxiety and ASD suggests that these disorders are difficult to differentiate early in life, which could reflect the presence of common developmental pathways or convergence in early behavioural manifestations of these disorders.

Project description:ImportanceClinical overlap between autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) is increasingly appreciated, but the underlying brain mechanisms remain unknown to date.ObjectiveTo examine associations between white matter organization and 2 commonly co-occurring neurodevelopmental conditions, ASD and ADHD, through both categorical and dimensional approaches.Design, setting, and participantsThis investigation was a cross-sectional diffusion tensor imaging (DTI) study at an outpatient academic clinical and research center, the Department of Child and Adolescent Psychiatry at New York University Langone Medical Center. Participants were children with ASD, children with ADHD, or typically developing children. Data collection was ongoing from December 2008 to October 2015.Main outcomes and measuresThe primary measure was voxelwise fractional anisotropy (FA) analyzed via tract-based spatial statistics. Additional voxelwise DTI metrics included radial diffusivity (RD), mean diffusivity (MD), axial diffusivity (AD), and mode of anisotropy (MA).ResultsThis cross-sectional DTI study analyzed data from 174 children (age range, 6.0-12.9 years), selected from a larger sample after quality assurance to be group matched on age and sex. After quality control, the study analyzed data from 69 children with ASD (mean [SD] age, 8.9 [1.7] years; 62 male), 55 children with ADHD (mean [SD] age, 9.5 [1.5] years; 41 male), and 50 typically developing children (mean [SD] age, 9.4 [1.5] years; 38 male). Categorical analyses revealed a significant influence of ASD diagnosis on several DTI metrics (FA, MD, RD, and AD), primarily in the corpus callosum. For example, FA analyses identified a cluster of 4179 voxels (TFCE FEW corrected P < .05) in posterior portions of the corpus callosum. Dimensional analyses revealed associations between ASD severity and FA, RD, and MD in more extended portions of the corpus callosum and beyond (eg, corona radiata and inferior longitudinal fasciculus) across all individuals, regardless of diagnosis. For example, FA analyses revealed clusters overall encompassing 12121 voxels (TFCE FWE corrected P < .05) with a significant association with parent ratings in the social responsiveness scale. Similar results were evident using an independent measure of ASD traits (ie, children communication checklist, second edition). Total severity of ADHD-traits was not significantly related to DTI metrics but inattention scores were related to AD in corpus callosum in a cluster sized 716 voxels. All these findings were robust to algorithmic correction of motion artifacts with the DTIPrep software.Conclusions and relevanceDimensional analyses provided a more complete picture of associations between ASD traits and inattention and indexes of white matter organization, particularly in the corpus callosum. This transdiagnostic approach can reveal dimensional relationships linking white matter structure to neurodevelopmental symptoms.

Dataset Information

Association of Cord Plasma Biomarkers of In Utero Acetaminophen Exposure With Risk of Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder in Childhood.

Publications

Association of Cord Plasma Biomarkers of In Utero Acetaminophen Exposure With Risk of Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder in Childhood.

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