Long-Term Maternal Use of Acetaminophen during Pregnancy Increases the Risk of ADHD in Offspring

30 May, 18

Background

Studies in past have linked acetaminophen use during pregnancy to attention-deficit/ hyperactivity disorder (ADHD) in offspring. Nevertheless, maternal use of acetaminophen is associated with impulsive personality. The possibility that acetaminophen use during pregnancy is influenced by familial factors that put the offspring at the risk of ADHD cannot be ruled out. Also, paternal use of acetaminophen might also be associated with ADHD in offspring.

Aim

To determine whether maternal use of acetaminophen during pregnancy and paternal use before pregnancy would be associated with ADHD in offspring when adjusted for familial risk for ADHD and indications of acetaminophen use

Study Participants

Participants from the Norwegian Mother and Child Cohort Study (MoBa):
- 112973 children and their parents

Method

Assessments

Assessments were conducted using self-reported questionnaires administered:
- To mother and father at 18 weeks of gestation
- To mothers later in pregnancy (week 30) and 6 months after delivery
- Information from maternal questionnaires was used when children were 6 months old, 1.5 years old and 3 years old
Information of ADHD diagnosis in children was obtained from the Norwegian Patient Registry (NPR)

Results

Of the entire study population, 2246 children were diagnosed with ADHD. It was estimated that ~4% of the children included in the study would be diagnosed with ADHD by age 13.
A total of 52707 (46.7%) women used acetaminophen during pregnancy (27% during 1^st trimester, 16% during 2^nd trimester and 3.3% during the 3^rd trimester
Prenatal maternal use of acetaminophen in 1^st, 2^nd, and 3^rd trimesters was modestly associated with a risk of ADHD in offspring when the data was adjusted for maternal use of acetaminophen before pregnancy, familial risk for ADHD, and indications of acetaminophen use (Table 1).

Table 1: HR for ADHD due to prenatal maternal use of acetaminophen

Trimester of Exposure	Hazard Ratio (HR)	95% confidence interval [CI]
1^st Trimester	1.07	0.96-1.19
2^nd Trimester	1.22	1.07-1.38
3^rd Trimester	1.27%	0.99-1.63

Prenatal use of acetaminophen for less than 7 days was negatively associated with ADHD risk. Nevertheless, use for more than 7 days was associated with an increased risk of ADHD, with the HR increasing with the increasing number of days of exposure to acetaminophen. The prenatal use of acetaminophen for 29 or more days was associated with an HR of 2.2 for ADHD in offspring.
Use of acetaminophen for fever and infections for a period of 22-28 days was strongly associated with ADHD in offspring (HR = 6.15; 95% CI 1.71–22.05).
Short-term paternal use of acetaminophen did not increase the risk of ADHD in children but similar to maternal prenatal use, paternal use for 29 days or more strongly increased the risk of ADHD (HR = 2.06; 95% CI 1.36–3.13.

Conclusions

Short-term maternal use of acetaminophen during pregnancy was negatively associated with ADHD in offspring.
Long-term maternal use of acetaminophen during pregnancy was associated with a more than two-fold increased risk of ADHD in offspring even after adjusting for various confounders including; indications of use, acetaminophen use before pregnancy and familial risk of ADHD.

Pediatrics. 2017; 140 (5): doi: 10.1542/peds.2016-3840.