In a large study following 64,322 children in Denmark, acetaminophen (Tylenol) use was determined during pregnancy and 6 months after child birth. More than 50% of women reported taking the medication during pregnancy. Children whose mothers took acetaminophen drugs during pregnancy were 37% more likely to have a hyperkinetic diagnosis - and 29% more likely to have an ADHD diagnosis at age 7, compared to children not exposed to the drugs. Further supporting the conclusion, a dose-response effect was noted as increasing use of the medication increased the likelihood of neurological problems.
ABSTRACT
Importance Acetaminophen (paracetamol) is the most commonly used medication for pain and fever during pregnancy in many countries. Research data suggest that acetaminophen is a hormone disruptor, and abnormal hormonal exposures in pregnancy may influence fetal brain development.
Objective
To evaluate whether prenatal exposure to acetaminophen increases the risk for developing attention-deficit/hyperactivity disorder (ADHD)–like behavioral problems or hyperkinetic disorders (HKDs) in children.
Design, Setting, and Participants
We studied 64 322 live-born children and mothers enrolled in the Danish National Birth Cohort during 1996-2002.
Exposures
Acetaminophen use during pregnancy was assessed prospectively via 3 computer-assisted telephone interviews during pregnancy and 6 months after child birth.
Main Outcomes and Measures
To ascertain outcome information we used (1) parental reports of behavioral problems in children 7 years of age using the Strengths and Difficulties Questionnaire; (2) retrieved HKD diagnoses from the Danish National Hospital Registry or the Danish Psychiatric Central Registry prior to 2011; and (3) identified ADHD prescriptions (mainly Ritalin) for children from the Danish Prescription Registry. We estimated hazard ratios for receiving an HKD diagnosis or using ADHD medications and risk ratios for behavioral problems in children after prenatal exposure to acetaminophen.
Results
More than half of all mothers reported acetaminophen use while pregnant. Children whose mothers used acetaminophen during pregnancy were at higher risk for receiving a hospital diagnosis of HKD (hazard ratio = 1.37; 95% CI, 1.19-1.59), use of ADHD medications (hazard ratio = 1.29; 95% CI, 1.15-1.44), or having ADHD-like behaviors at age 7 years (risk ratio = 1.13; 95% CI, 1.01-1.27). Stronger associations were observed with use in more than 1 trimester during pregnancy, and exposure response trends were found with increasing frequency of acetaminophen use during gestation for all outcomes (ie, HKD diagnosis, ADHD medication use, and ADHD-like behaviors; P trend < .001). Results did not appear to be confounded by maternal inflammation, infection during pregnancy, the mother’s mental health problems, or other potential confounders we evaluated.
Conclusions and Relevance
Maternal acetaminophen use during pregnancy is associated with a higher risk for HKDs and ADHD-like behaviors in children. Because the exposure and outcome are frequent, these results are of public health relevance but further investigations are needed.
FINAL CONCLUSIONS
Using prospective data from a well-designed large cohort of pregnant women with a long duration of follow-up and registry-based outcome assessment, we found that prenatal exposures to acetaminophen may increase the risk in children of receiving a hospital diagnosis of HKD or ADHD medication and of exhibiting ADHD-like behaviors, with higher use frequency increasing risk in an exposure-response manner. Because the exposure is frequent, these associations might explain some of the increasing incidence in HKD/ADHD but further studies are needed.