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

Acetaminophen is a widely used medication for fever and pain management during pregnancy. However, recent studies have found a possible connection between maternal prenatal acetaminophen use and attention deficit/hyperactivity disorder in children.

We aimed to explore the association between maternal acetaminophen use during pregnancy and the risk of attention deficit/hyperactivity disorder in offspring.

PubMed, Embase, Web of Science and Cochrane Library were searched from their initial publications through November 2018 for studies.

We included all studies that examined the association between maternal acetaminophen use during pregnancy and the risk of attention deficit/hyperactivity disorder in offspring if the authors reported odds ratios, risk ratios, hazard ratios, regression coefficient, standard error and 95% confidence intervals.

Two reviewers independently extracted data on the definition of exposure and outcome, exposed, non-exposed and total number of participants in the sample population, adjusted potential confounders and outcome parameters. Study quality was also assessed.

Eight cohort studies with a total of 244,940 participants were included. Maternal exposure to acetaminophen during pregnancy increased the risk of attention deficit/hyperactivity disorder in offspring with a pooled adjusted risk ratio of 1.25 (95% confidence interval = [1.17, 1.34]). Children exposed prenatally to acetaminophen in the third trimester seemed to have the greatest risk of developing attention deficit/hyperactivity disorder (risk ratio: 1.26; 95% confidence interval = [1.08, 1.47]). In addition, a longer duration of maternal acetaminophen use during pregnancy was correlated with a higher risk ratio. Children whose mothers used acetaminophen for 28 or more days during gestation had a higher risk of developing attention deficit/hyperactivity disorder (risk ratio: 1.63; 95% confidence interval = [1.23, 2.16]).

There is an association between maternal acetaminophen use during pregnancy and the risk of attention deficit/hyperactivity disorder in offspring. The timing and duration of acetaminophen use during pregnancy may have a major effect on the risk of attention deficit/hyperactivity disorder.