1. Exposure to acetaminophen prenatally was linked with an increased risk of receiving a diagnosis of Hyperkinetic Disorder (HKD), being prescribed ADHD medications, or exhibiting ADHD-like behaviors.
2. Increased frequency of acetaminophen use during pregnancy, particularly in the second and third trimester, increased the aforementioned risk.
Evidence Rating Level: 2 (Good)
Study Rundown: Acetaminophen is used by over 50% of pregnant women in the United States and Denmark. Recent animal and human studies suggest that this drug may interfere with certain endocrine functions, especially during early development. The results of the study suggested that there was an increased risk of HKD/ADHD in the offspring whose mothers who used acetaminophen during pregnancy. This risk was increased as acetaminophen was used with increasing frequency and later in pregnancy.
The major strengths of this study include the large population that was studied, which makes the result more generalizable. Also, the presence of a national registry and access to the prescriptions ensured that those who met the endpoints were accurately recorded. There are, however, several weaknesses in the study. The investigators included participants who were on combination medications with the acetaminophen, so those could potentially be responsible for the noted differences. Also, they asked the parents to answer questions about their own childhood developmental issues, and those who self-reported problems during childhood were more likely to provide a higher score for their own children. Lastly, more than one-quarter of the women did not accurately remember the timeline of their acetaminophen use.
In-Depth [prospective cohort]: This study consisted of 64,322 women from the nationwide Danish National Birth Cohort from 1996-2002. Phone interviews were conducted at various times during pregnancy to determine the frequency and timeline of acetaminophen use. The endpoints examined were hospital diagnosis of HKD, prescription of ADHD medications, and ADHD-like behaviors as determined by the parents’ answers to the Strengths and Difficulties Questionnaire. The women were surveyed three times, twice during their pregnancy and once more six months after delivery.
The three endpoints for the study were in-hospital diagnosis of HKD, prescriptions for ADHD medications, and presence of ADHD-like behavior by age 7 (determined by the parents’ response to Strengths and Difficulties Questionnaire).During this study period, more than half of the women reported acetaminophen use during pregnancy. The study found that children whose mothers used acetaminophen during pregnancy were more likely to have a hospital diagnosis of HKD (HR 1.37; 95% CI, 1.19-1.59), more likely to be prescribed medications for ADHD (HR 1.29, 95% CI, 1.15-1.44), and more likely to have ADHD-like behavior by age 7 (RR 1.13; 95% CI, 1.01-1.27).
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