A newly published consensus statement, co-signed by nearly 100 scientists, is calling for the common painkiller acetaminophen (also known as paracetamol or APAP) to be used cautiously and conservatively during pregnancy. The researchers indicate there are potential neurological and reproductive issues in children associated with excessive use of the drug during pregnancy.
The new article summarizes around 25 years of published data spanning everything from systematic reviews and large epidemiological studies to animal research investigating neurotoxicity and fetal development. The researchers present a case for APAP increasing the risk of certain reproductive and neurodevelopmental problems.
“Although some studies have shown no APAP-induced effects, an increasing body of evidence suggests that APAP has the ability to disrupt animal and human reproductive tract development, from fetal life to adulthood in both sexes,” the researchers write. “Fetal exposure in animal models has been shown experimentally to cause disorders of the male urogenital tract through reduction of androgen action. Furthermore, experimental models have consistently shown disruption of ovarian development, which results in reduced fertility at the same dose or close to the dose used by pregnant women.”
Looking at neurodevelopmental problems, the researchers identify associations between prenatal APAP exposure and behavioral problems in children, including ADHD and language delays. The article stresses these links were “generally modest,” with small effects sizes, but considering the broad use of APAP, “even a small effect size could translate into a large number of affected children.”
Alongside the 13 key authors of the article, the research has been co-signed by another 78 scientists from across the globe. The concluding recommendations call for APAP to only be used cautiously during pregnancy, “at the lowest effective dose for the shortest possible time.”
Several experts not involved with this article suggest the new recommendations could raise unnecessary anxiety. Stephen Evans, from the London School of Hygiene and Epidemiology, says it may be wise to avoid “indiscriminate use” of these drugs during pregnancy but the evidence on the topic is still incredibly inconsistent.
“Avoidance of unnecessary drugs is to be encouraged at all times, and most pregnant women are aware of this,” says Evans. “At the same time raising anxiety about their unborn child is often itself unnecessary and has obvious adverse consequences.”
Ian Musgrave, a pharmacologist from the University of Adelaide, agrees with the call for more judicious use of APAP. However, he also notes these findings should not steer pregnant individuals away from the drug altogether as there are cases where its use is important.
“… the use of any drug is a balance of benefits vs potential harms,” says Musgrave. “For example, fever is an accepted risk factor for harm to the developing child, and paracetamol is one of the few available drugs that can be used to reduce fever in pregnancy.”
The new article does indicate a probable dose-dependent relationship with potential harms from APAP. The largest effect sizes detected in the new research review came from consistent use for over two weeks. Plus, the article notes there may be greater negative effects from APAP in certain gestational windows, particularly during the earliest phases of pregnancy.
Ultimately, the consensus article calls for more research on the subject, alongside greater education to reduce unnecessary APAP use during pregnancy. Christopher Zahn, from the American College of Obstetricians and Gynecologists, says the recommendations by the authors of this article are no different from advice currently offered in clinical practice, and pregnant individuals should not be concerned about taking APAP when necessary.
“The authors are not recommending anything counter to what is already done by obstetrician-gynecologists when prescribing acetaminophen for a given clinical condition,” Zahn in a statement published by STAT News. “Physicians should not change clinical practice until definitive prospective research is done and, most importantly, patients should not be frightened away from the many benefits of acetaminophen.”
The new article was published in the journal Nature Reviews Endocrinology.