Acetaminophen, the active ingredient in Tylenol and Paracetamol among other over-the-counter pain relievers, is generally safe to use during pregnancy and is considered the go-to pain and anti-fever medication during gestation. According to the US Food and Drug Administration’s rating system, acetaminophen is safer than ibuprofen and much safer than aspirin for pregnant women.
But a number of studies in recent years have linked acetaminophen use in pregnancy to neuro-developmental disorders in children. According to a 2013 study published in the International Journal of Epidemiology, children exposed prenatally to acetaminophen, for more than 28 days, were at higher risk of behavioral problems, language delays, and poor motor development at age three. Another study, which looked at a sample size of over 64,000 children published by JAMA Pediatrics in 2014, cited an increased risk of ADHD-like behaviors in children of mothers who took acetaminophen past the first trimester.
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In a new study published this year, Israeli researchers from the Hebrew University of Jerusalem found another link between prolonged use of drugs containing acetaminophen during pregnancy, and increased risk of autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD).
The research, led by Dr. Ilan Matok at the Institute for Drug Research in the School of Pharmacy at the Hebrew University’s Faculty of Medicine, and doctoral student Reem Masarwa, found that prolonged exposure to acetaminophen during pregnancy was associated with a 30 percent increase in relative risk for ADHD (compared to those who did not take acetaminophen during pregnancy) and a 20 percent increase in relative risk for ASD. It was published in April in the American Journal of Epidemiology.
The research data covered 132,738 mother and child pairs with a follow-up period of 3-11 years, according to a university statement, which called the it “the first meta-analysis and the most comprehensive study ever conducted on the possible association between prolonged use of acetaminophen during pregnancy and risk of ASD or ADHD.”
All these studies come with a note of caution, emphasizing that they are imperfect and more research is needed.
In the abstract of their study, the Israeli researchers wrote that “results should be interpreted with caution given that the available evidence consists of observational studies and is susceptible to several potential sources of bias.”
Dr. Matok said in a statement that although a clear link was found, “the observed increase in risk was small, and the existing studies [which the meta-analysis drew from] have significant limitations.”
There is no known study that includes a randomized controlled trial. To do so, the researchers would have to instruct some pregnant women take acetaminophen and others not to, as outlined in a 2014 piece looking at the significance of these studies. Instead, the studies are observational and examine behavior, rather than cause.
This leads to another major flaw. The studies don’t take into account why expectant mothers took acetaminophen. Perhaps it was to reduce a fever, or inflammation, which have been shown to negatively affect fetal development.
“It is important to understand that pain and fever during pregnancy can have a detrimental effect on the developing fetus and that acetaminophen is still considered a safe drug for use during pregnancy,” the Israeli researchers wrote in the statement. “Therefore, if a pregnant woman has fever and/or pain, acetaminophen can be taken for a short period, and if the fever or pain continue beyond that, she should consult her physician regarding further treatment.”
“While unnecessary use of any medication should be avoided in pregnancy, we believe our findings should not alter current practice and women should not avoid use of short-term acetaminophen when clinically needed,” the researchers wrote.