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

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 had greater problems with sleep and attention at age 3.

Acetaminophen, the active ingredient in Tylenol, is a medicine used to relieve pain and reduce fever. In the United States, this drug is considered safe to take during pregnancy and is commonly used by pregnant women. But in recent years, scientists have expressed concern that acetaminophen may cause neurobehavioral problems in offspring.

Study author Kristin K. Sznajder and her team conducted a study to investigate the link between maternal acetaminophen use and child development. Unlike most previous studies on the subject, the researchers looked at behavior problems in preschoolers. They also explored the possible confounding effects of prenatal stress.

“Recently, there is new evidence that acetaminophen is associated with behavioral problems in children. We wanted to know if we would see similar trends in our data after controlling for perinatal factors not controlled in previous studies and at 36 months of age,” explained Sznajder, assistant professor of public health sciences at Penn State College of Medicine.

Sznajder and his colleagues analyzed data from a longitudinal cohort study called the First Baby Study. The study sample consisted of pregnant Pennsylvania women between the ages of 18 and 35. During their first trimester of pregnancy, the women answered telephone interviews and questions about their medical history, health habits, symptoms of depression, stress during pregnancy, and sociodemographics. They also listed all the medications they had been taking since becoming pregnant. At 36 months postpartum, approximately 81% of women (2423) participated in a follow-up interview that included the Child Behavior Checklist (CBCL).

Researchers found that about 42% of 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 CBCL outcomes. Mothers who took acetaminophen during pregnancy had more withdrawn children, had more sleep problems, and had more attention problems. When controlling for several confounding variables (including prenatal stress), the effects on sleep and attention problems remained significant.

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

“Acetaminophen use is associated with problems with attention and sleep at 36 months, even after controlling for other variables such as factors surrounding childbirth and maternal stress,” Sznajder told PsyPost. “We did not expect to find this association after accounting for confounders. Thus, the association was surprising, but is consistent with other studies that have found an association between acetaminophen use during pregnancy and child behavior.

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

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

Some strengths of the study include the longitudinal data and the large sample size. However, the researchers note that the study sample was not representative of the US population. Additionally, the dosage and frequency of acetaminophen use were unknown, as were the specific weeks of pregnancy when the 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 by which acetaminophen use is associated with child development.

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

The study, “Maternal Acetaminophen Use 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.

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