Maternal Biomarkers of Acetaminophen Use and Offspring Attention Deficit Hyperactivity Disorder

Abstract

Previous studies have suggested a positive association between self-reported maternal acetaminophen use during pregnancy and risk of attention deficit hyperactivity disorder (ADHD) in offspring. We sought to examine the prospective association between maternal plasma biomarkers of acetaminophen intake and ADHD diagnosis in the offspring. This report analyzed 1180 children enrolled at birth and followed prospectively as part of the Boston Birth Cohort, including 188 with ADHD diagnosis based on electronic medical record review. Maternal biomarkers of acetaminophen intake were measured in plasma samples obtained within 1–3 days postpartum. Odds ratios for having ADHD diagnosis or other developmental disorders were estimated using multinomial logistic regression models, adjusting for pertinent covariables. Compared to neurotypical children, we observed significant positive dose-responsive associations with ADHD diagnosis for each maternal acetaminophen biomarker. These dose–responsive associations persisted after adjusting for indication of acetaminophen use and other pertinent covariates; and were specific to ADHD, rather than other neurodevelopmental disorders. In the stratified analyses, differential point estimates of the associations were observed across some strata of covariates. However, these differences were not statistically significant. Maternal acetaminophen biomarkers were specifically associated with increased risk of ADHD diagnosis in offspring. Additional clinical and mechanistic investigations are warranted.

Association of Cesarean Delivery With Risk of Neurodevelopmental and Psychiatric Disorders in the Offspring

“…The main characteristics of the included studies are presented in Table 1, and the variables adjusted and/or matched in each study are presented in eTable 3 in the Supplement. Of the 61 included studies, 27 studies 20,23,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,83 reported on the association of cesarean delivery with a diagnosis of ASD (59 795 cases), 13 studies 19,24,42,52,55,56,57,58,59,60,61,62,63 with attention-deficit/hyperactivity disorder (ADHD) (92 718 cases), 3 studies 42,64,65 with intellectual disabilities (485 cases), 3 studies 22,66,67 with tic disorders (6181 cases), 4 studies 25,26,68,69 with eating disorders (4550 cases), 3 studies 21,70,71 with obsessive-compulsive disorder (OCD; 7295 cases), 5 studies 72,73,74,75,76 with major depression or affective psychoses (8561 cases), and 7 studies 73,77,78,79,80,81,82 with nonaffective psychoses (7195 cases). Study quality was defined as high for 18 of 22 cohorts (82%) and 20 of 40 c...…”

Association of maternal prenatal acetaminophen use with the risk of attention deficit/hyperactivity disorder in offspring: A meta-analysis

“…Eight of these were subsequently excluded: one was a commentary, three were conference abstracts, three were author responses and one was a short survey. Eight remaining publications (Avella-Garcia et al, 2016; Brandlistuen et al, 2013; Ji et al, 2018; Liew et al, 2014; Stergiakouli et al, 2016; Streissguth et al, 1987; Thompson et al, 2014; Ystrom et al, 2017) met the eligibility criteria for inclusion in this study (Figure 2).…”

“…Sample sizes ranged from 421 to 112,973. Five studies were conducted in Europe (Avella-Garcia et al, 2016; Brandlistuen et al, 2013; Liew et al, 2014; Stergiakouli et al, 2016; Ystrom et al, 2017), two in the USA (Ji et al, 2018; Streissguth et al, 1987) and one in Oceania (Thompson et al, 2014). All authors reported the diagnostic criteria of ADHD or neurodevelopment.…”

“…One study used the Attention Deficit/Hyperactivity Disorder Criteria of the Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition form list (ADHD-DSM-IV; Avella-Garcia et al, 2016). Two used the International Classification of Diseases, 10th Revision (ICD-10) as the diagnostic criteria for ADHD (Ji et al, 2018; Ystrom et al, 2017). In one study, the researchers divided the subjects into two respective groups using the SDQ and ICD-10 as the evaluation criteria (Liew et al, 2014).…”

“…However, there is little evidence of neurodevelopmental effects associated with acetaminophen. Recent studies have found a possible connection between maternal prenatal acetaminophen use and attention deficit/hyperactivity disorder (ADHD) in children (Avella-Garcia et al, 2016; Brandlistuen et al, 2013; Ji et al, 2018; Liew et al, 2014; Stergiakouli et al, 2016; Streissguth et al, 1987; Thompson et al, 2014; Ystrom et al, 2017). One study found that after exposure to acetaminophen, behavioral and cognitive deficits including autism and ADHD were observed in both human offspring and animal models of these diseases (Zucker, 2017).…”