Prenatal exposure to acetaminophen and risk for attention deficit hyperactivity disorder and autistic spectrum disorder

Masarwa R, Levine H, Gorelik E, Reif S, Perlman A, Matok I. Prenatal Exposure to Acetaminophen and Risk for Attention Deficit Hyperactivity Disorder and Autistic Spectrum Disorder: A Systematic Review, Meta-Analysis, and Meta-Regression Analysis of Cohort Studies. Am J Epidemiol. 2018 Apr 24. doi:10.1093/aje/kwy086. [Epub ahead of print]

Abstract

Acetaminophen is the most commonly used analgesic and antipyretic during pregnancy. Evidence of neuro-disruptive properties is accumulating. Therefore, we sought to evaluate the risk for attention deficit hyperactivity disorder (ADHD) and autistic spectrum disorder (ASD) in the offspring of women exposed to acetaminophen during pregnancy. We searched MEDLINE, EMBASE, and Cochrane up to January 2017. Data were independently extracted and assessed by two researchers. Seven eligible retrospective cohorts included 132,738 mother and child pairs and with a follow-up period of 3-11 years. Pooled risk ratio (RR) for ADHD was (RR=1.32, 95% CI 1.18,1.45, I2=61%), for ASD (RR=1.23, 95% CI1.13,1.32, I2=17%), and for hyperactivity symptoms (RR=1.23, 95% CI 1.01,1.49, I2=94%). In meta-regression analysis, the association between exposure and ADHD increased with childs' age upon follow-up and with the mean duration of exposure (β=0.0354, 95% CI 0.001,0.07), (β=0.006, 95% CI 0.009,0.01). The available data is of observational nature only. Studies differed gravely in exposure and outcome assessment. Acetaminophen use during pregnancy is associated with an increased risk for ADHD, ASD and hyperactivity symptoms. These findings are concerning, however, results should be interpreted with caution as the available evidence consists of observational studies and susceptible to several potential sources of bias.

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"Our study was the first systematic review and meta-analysis of the developmental outcomes in children whose mothers took prolonged acetaminophen during pregnancy," lead investigator Ilan Matok, PhD, of the Institute for Drug Research in the School of Pharmacy, Hebrew University, Jerusalem, Israel, told Medscape Medical News…

Recent research has suggested that acetaminophen may have harmful effects in children of mothers who used it during pregnancy, including an increased risk for neurodevelopmental disorders. 

Animal models suggest that acetaminophen might have neurodisruptive properties. Because acetaminophen crosses the human placenta barrier, the neurodisruption might be transmitted to a baby and lead to future impairments, such as ADHD and ASD.

"While the neural disruption and its potential impact on neurodevelopment is only a hypothesis and not validated right now," some previous research has pointed to a potential association between acetaminophen use and these conditions, Matok said.

Previous findings have been inconsistent, however.

"Some reports have shown an association with increased risk, while other studies didn't show this, so we wanted to investigate this discrepancy, and the best way to do so was to conduct a systematic review and meta-analysis," Matok explained.

https://www.medscape.com/viewarticle/895768