Acetaminophen use during pregnancy is associated with neurobehavioral problems in 3-year-old offspring

Recent findings suggest that acetaminophen use during pregnancy may contribute to neurobehavioral problems in offspring. The study, published in the journal PLOS One, found that children exposed to acetaminophen in utero exhibited higher sleep and attention problems at age 3.

Acetaminophen, the active ingredient in Tylenol, is a drug used for pain relief and fever reduction. In the United States, this medication is considered safe to take during pregnancy and is commonly used by pregnant women. But in the past few years, scientists have expressed concern that acetaminophen can lead to neurobehavioral issues in offspring.

Study author Kristin K. Sznajder and her team conducted a study to investigate the link between maternal acetaminophen use and child development. In contrast to most previous studies on the topic, the researchers examined child behavior problems in preschool-aged children. They also explored the possible confounding effects of prenatal stress.

“Recently there is emerging evidence that acetaminophen is associated with child behavioral problems. We were interested on whether we would see similar trends in our data after controlling for perinatal factors not controlled for in previous studies and at 36 months of age,” explained Sznajder, an assistant professor of public health sciences at Penn State College of Medicine.

Sznajder and her colleagues analyzed data from a longitudinal cohort study called the First Baby Study. The study sample consisted of pregnant women from Pennsylvania who were between the ages of 18 and 35. During their first trimester of pregnancy, the women completed telephone interviews and responded to questions about their health history, health habits, depression symptoms, stress during pregnancy, and sociodemographics. They also indicated any medications they were taking since becoming pregnant. At 36 months postpartum, about 81% of the women (2,423) participated in a follow-up interview which included the Child Behavior Checklist (CBCL).

The researchers found that about 42% of the women reported using acetaminophen during pregnancy. The most common reason for taking acetaminophen was to treat headaches or migraines. The researchers also found that maternal acetaminophen use was associated with three of the seven outcomes on the CBCL. Mothers who took acetaminophen during pregnancy had children who were more withdrawn, had more sleep problems, and had more attention problems. When controlling for multiple confounding variables (including prenatal stress), the effects for sleep and attention problems remained significant.

Notably, the link between maternal acetaminophen use and offspring attention problems has been previously documented. However, this study was the first to find that maternal acetaminophen use can predict offspring’s sleep problems at preschool age. The authors note that sleep and attention issues are both signs of self-regulation difficulties.

“Acetaminophen use is associated with attention and sleep problems at 36 months of age even after we took into account other variables such as factors surrounding delivery and maternal stress,” Sznajder told PsyPost. “We did not expect to find this association after taking into account confounding factors. So, the association was surprising, but is in line with other studies that have found an association between acetaminophen use during pregnancy and child behavior.”

The researchers say that exposure to acetaminophen may be impacting the regulation of sleep and attention through prenatal neurology. The drug has indeed been linked to reduced brain connectivity of the amygdala, which is a brain region involved in self-regulation.

Of all the factors assessed, psychosocial stress during pregnancy was the most strongly associated with Child Behavior Checklist scores and was linked to all seven CBCL outcomes. Alcohol consumption during pregnancy and being diagnosed with depression or anxiety prior to pregnancy were also associated with some CBCL outcomes. Of note, women with either medium or high prenatal stress were more likely to report acetaminophen use compared to women with low prenatal stress.

Some strengths of the study include the longitudinal data and large sample size. However, the researchers note that the study sample was not representative of the U.S. population. Furthermore, the dosage and frequency of acetaminophen use were unknown, as were the specific weeks during pregnancy when acetaminophen was taken. The study authors say that future research could assess these variables through daily diaries. Future studies will also be needed to elucidate the mechanism through which acetaminophen use is associated with child development.

“Future studies need to consider the frequency, dose, and duration of prenatal acetaminophen use and whether there is a dose response relationship between acetaminophen use and child behavior,” Sznajder said.

The study, “Maternal use of acetaminophen during pregnancy and neurobehavioral problems in offspring at 3 years: A prospective cohort study”, was authored by Kristin K. Sznajder, Douglas M. Teti, and Kristen H. Kjerulff.

© PsyPost