Clinical Question

Is maternal prenatal acetaminophen use associated with increased rates of attention-deficit/hyperactivity disorder (ADHD) in offspring?

Evidence-Based Answer

Pregnant patients should discuss acetaminophen use with their maternal health care professional because it is associated with an increased risk of ADHD in offspring. (Strength of Recommendation [SOR]: B, systematic review and meta-analysis of prospective cohort studies.) ADHD is most strongly related to prolonged antepartum use of acetaminophen (28 days or greater) and use during the third trimester. Fever and infections in the first trimester may also be associated with an increased risk of ADHD and may be a reason for increased acetaminophen use. (SOR: C, large prospective cohort studies with conflicting results.)

Evidence Summary

A systematic review and meta-analysis of eight prospective cohort studies (n = 244,940) evaluating a possible connection between maternal prenatal acetaminophen use and the development of ADHD in offspring found an increased risk overall (relative risk [RR] = 1.25; 95% CI, 1.17 to 1.34), with use of 28 or more days (RR = 1.63; 95% CI, 1.23 to 2.16), and with any use during the third trimester (RR = 1.26; 95% CI, 1.08 to 1.47).¹ The authors included studies from Europe (five), the United States (two), and Oceania. Six studies were rated high quality, and two were moderate quality. Seven studies used self-reported questionnaires during pregnancy, mainly during the second and third trimesters, to assess days of maternal acetaminophen use (one study used serum biomarkers; no study measured the dose or frequency). The eight studies used six standardized measures to diagnose ADHD in offspring. Study participants were followed for an average of 6.3 years (follow-up = 1.2 to 16 years).