Scientists suggests that pregnant women only take paracetamol/acetaminophen if it is medically necessary

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A group of 13 scientists from the U.S., the U.K., Scotland, Israel, Europe, Canada, Brazil and Australia has penned a consensus statement regarding the use of paracetamol/acetaminophen (APAP) by pregnant women.

In their paper, published in the journal Nature Reviews Endocrinology, the group suggests that pregnant women only take paracetamol/acetaminophen if it is medically necessary.

Nature has also published an Editorial in the same journal issue, outlining the consensus statement and noting that its authors are not calling for a ban on the drug being used, instead they are suggesting that it be taken more cautiously by pregnant women because of a possible risk of birth defects.

In their paper, the authors note that research over the past several years has shown that it is possible under some circumstances for APAP to alter fetal development which in some cases can lead to problems with neurological, urological and reproductive disorders in the baby – they looked at 29 studies and found evidence of birth defects in 26 of them.

They call for more research to be conducted to better understand possible problems with the drug being used by pregnant women.

They also acknowledge – as do several experts in a reaction piece published on the Science Media Centre, site – that APAP is the only drug currently available for pain management for pregnant women. And they point out that medical use of APAP is generally warranted when the mother experiences problems that can negatively impact her baby – such as having a fever.

But they also note that use of APAP by pregnant women appears to have crept up into general use as it has gained a reputation as being safe to use as an all-purpose analgesic.

Notably, both the expert group and the authors of the new paper point out that the recommendation does not differ from that already in use by most OB/GYNs – and similar wording generally appears on bottles of products based on APAP, such as Tylenol.

The authors of the consensus statement further suggest that their intent in publishing such an article is to bring renewed and more focused attention to the possibility of APAP use leading to certain birth defects and the conditions under which they might arise.

They note that current research has shown, for example, that the possibility of harm seems to increase as the duration of APAP use goes up. Thus, they suggest pregnant women consider using the drug for short term pain management, rather than as a long-term solution.

Associations between prenatal APAP exposure, reproductive and neurobehavioural development suggested from observational human studies.

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Human observational studies suggest prenatal N-acetyl-p-aminophenol (APAP) exposure might be associated with both reproductive and neurobehavioural abnormalities in both sexes. APAP exposure during pregnancy might increase risk of male urogenital and reproductive tract abnormalities, as studies have found an elevated risk of undescended testicles (cryptorchidism) and reduced distance between the anus and the base of the penis, a measure known as the anogenital distance (AGD). Both reduced AGD and cryptorchidism are indicators of disturbed masculinization and risk factors for reproductive disorders in later life. Prenatal APAP exposure has also been associated with earlier female pubertal development. Additionally, epidemiological studies consistently suggest prenatal APAP exposure might increase the risk of adverse neurodevelopmental and behavioural outcomes, such as attention deficit hyperactivity disorder (ADHD), autism spectrum disorder, language delay (in girls) and decreased intelligence quotient. Collectively, the studies suggest that the timing and duration of maternal APAP use are critical factors.

Paracetamol (acetaminophen) is the most widely used international analgesic and antipyretic and it is recommended as a first-line therapy in the treatment of mild-to-moderate pain by the World Health Organization (WHO) [1]. Furthermore, paracetamol is one of the most commonly used medications during pregnancy [2,3], being classified as a low-risk for gestation [4,5].

However, recent investigations have suggested that paracetamol exposure during pregnancy may affect several child health outcomes including alterations to the endocrine system and hormonal regulation [2]. The mechanisms underlying these findings may be related to the potential antiandrogenic effect of paracetamol [6,7,8].

Experimental trials in rodents have demonstrated that intra-uterine exposure to paracetamol reduces plasma testosterone levels through a reduction of its secretion by Leydig cells in fetal testicles [8,9,10]. Nonetheless, as the European Medicines Agency indicated in 2019, epidemiological studies in children whose mothers consumed paracetamol during pregnancy showed unclear results [11].

Moreover, international and national health organizations have stated that the use of paracetamol in therapeutic doses and for the shortest possible time does not produce adverse effects on pregnant women, the fetus or newborns [11,12].

Anogenital distance (AGD) is a biomarker of the intra-uterine hormonal environment. It has been demonstrated that AGD depends largely on androgen levels to which the fetus was exposed during prenatal life [13,14,15]. Particularly, this relationship is of great interest during the first trimester of pregnancy, known as the masculinization programming window (MPW) [16,17]. In this period, a sufficient exposure to androgens is necessary to ensure the subsequent adequate development and differentiation of the male reproductive tract and function [18].

Recent studies in large birth cohorts have found an association between maternal paracetamol consumption during pregnancy and a shorter AGD in their male offspring [18,19]. In this line, the relationship between AGD and maternal paracetamol consumption might be due to the potential antiandrogenic action of paracetamol.

This action could disrupt the masculinization process, resulting in a shorter AGD in male children [6,9,10]. Moreover, as Sharpe (2020) indicated recently, maternal lifestyle and diet during pregnancy including the use of painkillers may be more important than other environmental chemical exposures in the origin of several reproductive pathologies in humans.

Overall, the current knowledge of the potential effect of paracetamol on prenatal male reproductive system development is still scarce and inconclusive. Therefore, it is relevant to explore and evaluate these potential associations in other birth cohorts.

Thus, our objective was to assess whether maternal paracetamol use during pregnancy was associated with AGD measures in their male offspring in the Spanish birth cohort ‘Nutrition in Early Life and Asthma’ (NELA).

reference link : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8296170/


More information: Ann Z. Bauer et al, Paracetamol use during pregnancy—a call for precautionary action, Nature Reviews Endocrinology (2021). DOI: 10.1038/s41574-021-00553-7

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