Exercise precaution while using paracetamol during pregnancy: Consensus statement

USA: A Consensus Statement was issued to focus research activities and give evidence-based medical recommendations for pregnant women who take Paracetamol (N-acetyl-p-aminophenol (APAP). The study's findings suggest that pregnant women should take APAP with caution and for the least amount of time feasible. Long-term or high-dose usage should be confined to indications prescribed by a doctor. Pregnant women often use APAP since regulatory authorities, such as the FDA and EMA, have long deemed it safe to use during pregnancy when taken as recommended.

Ann Z. Bauer and colleagues review the epidemiological research and animal studies that have studied neurological, urogenital, and reproductive effects linked with maternal and perinatal use of APAP in this article. The findings of this study were published in Nature Reviews Endocrinology on 23rd September 2021.

The work of a worldwide panel of specialists, including physicians, epidemiologists, and fundamental scientists, resulted in this Consensus Statement. The 13 writers produced the declaration independently of individual groups and universities. The reference lists of the publications that were discovered were then searched for more relevant articles. Only studies that looked at APAP as an independent exposure were included. An executive writing group created the initial text after debate and deliberation among the writers, which was sent to all authors for critical evaluation. In addition to the 13 writers, 78 signees endorsed the final declaration, which takes into account diverse foreign viewpoints, prescription patterns, and clinical concerns.

APAP has been shown to penetrate the placenta and the blood-brain barrier49,50. Changes in APAP metabolism occur during pregnancy, which may render pregnant women and their foetuses more sensitive to harmful consequences. Increasing clinical data shows that APAP's activity in suppressing prostaglandin signalling in the third trimester can result in ductus arteriosus constriction, which can result in fetal loss or life-threatening cardiac failure in the new-born. Taken together, APAP possesses several of the important criteria for identifying an endocrine-disrupting chemical's danger.

Five of these studies' findings imply that prenatal APAP exposure is linked to male urogenital and reproductive system abnormalities, including an increased chance of male undescended testicles (cryptorchidism) and a shorter anogenital distance (AGD). Furthermore, exposure to APAP for more than two weeks raised the chance of cryptorchidism. Although not directly connected to evidence of APAP's effects in utero, studies have found that adult males who took APAP had a longer time to conception, lower testosterone levels, and sperm abnormalities such as DNA fragmentation.

A large number of studies have been conducted, with 26 of these studies identifying positive associations between APAP exposure during pregnancy and a variety of clinically assessed and parent-reported neurodevelopmental outcomes, primarily attention deficit hyperactivity disorder (ADHD) and related behavioral abnormalities, but also autism spectrum disorder (ASD), language delays, decreased IQ, cerebrum malformations, and cerebrovascular disease.

In conclusion, considering the high frequency of APAP usage among pregnant women, and its documented effects on the system, the public health consequences of reducing use might be significant.

Reference:

Bauer, A. Z., Swan, S. H., Kriebel, D., Liew, Z., Taylor, H. S., Bornehag, C.-G., Andrade, A. M., Olsen, J., Jensen, R. H., Mitchell, R. T., Skakkebaek, N. E., Jégou, B., & Kristensen, D. M. (2021). Paracetamol use during pregnancy — a call for precautionary action. Nature Reviews Endocrinology. https://doi.org/10.1038/s41574-021-00553-7