EXPERT REACTION: Paracetamol in pregnancy may impact future fertility

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A review of studies has found that giving mice and rats paracetamol during pregnancy may impair the future fertility of their female offspring. The finding has researchers suggesting further investigation is needed into how it might affect human fertility. The researchers looked at the results of three separate studies which all reported altered development in the reproductive systems of female offspring when the mother rodents were given paracetamol during pregnancy. The researchers say that they are not making any medical recommendations and urge pregnant women in pain to consult with their doctor.

Journal/conference: Endocrine Connections

Organisation/s: Copenhagen University Hospital

Funder: The Danish Council for Independent Research (Medical Sciences), Inserm (Institut National de la Santé et de la Recherche Médicale), University of Rennes 1, EHESP - School of Public Health, the Agence Nationale de Sécurité du Médicament et des Produits de Santé.

Media Release

From: Bioscientifica

Taking paracetamol during pregnancy may reduce fertility of daughters

Taking paracetamol during pregnancy may impair the future fertility of female offspring, according to a review published in Endocrine Connections. The article reviews three separate rodent studies that all report altered development in the reproductive systems of female offspring from mothers given paracetamol during pregnancy, which may impair their fertility in adulthood.

Paracetamol, or acetaminophen, is an over-the-counter treatment for pain relief that is commonly taken by pregnant women worldwide. Recent studies have linked paracetamol use during pregnancy with disruptions in the development of the male reproductive system but the effects on female offspring had not yet been investigated. In this article, Dr David Kristensen and colleagues from Copenhagen University Hospital, review the findings from three individual rodent studies that evaluated the effects of paracetamol taken during pregnancy on the development of the reproductive system in female offspring.

It is well known that exposure to some chemicals during pregnancy can cause developmental effects that may not manifest until much later in life. In rodents and humans, females are born with a finite number of eggs for reproduction in the future. In these reviewed studies, rodents given paracetamol during pregnancy, at doses equivalent to those that a pregnant woman may take for pain relief, produced female offspring with fewer eggs. This means that in adulthood, they have fewer eggs available for fertilisation, which may reduce their chances of successful reproduction, particularly as they get older.

Dr Kristensen comments, “Although this may not be a severe impairment to fertility, it is still of real concern since data from three different labs all independently found that paracetamol may disrupt female reproductive development in this way, which indicates further investigation is needed to establish how this affects human fertility.”

Although there are parallels between rodent and human reproductive development, these findings have yet to be firmly established in humans. However, establishing a link between paracetamol taken by mothers during pregnancy and fertility problems much later in the adult life of the child will be difficult. Dr Kristensen recommends that an inter-disciplinary approach be taken to address this, “by combining epidemiological data from human studies with more experimental research on models, such as rodents, it may be possible to firmly establish this link and determine how it happens, so that pregnant women in pain can be successfully treated, without risk to their unborn children.”

Dr Kristensen states, “As scientists, we are not in the positon to make any medical recommendations and we would urge pregnant women in pain to consult with their general practitioner, midwife or pharmacist for professional advice.”

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Expert Reaction

These comments have been collated by the Science Media Centre to provide a variety of expert perspectives on this issue. Feel free to use these quotes in your stories. Views expressed are the personal opinions of the experts named. They do not represent the views of the SMC or any other organisation unless specifically stated.

Professor Jock Findlay is a Distinguished Scientist at the Centre for Reproductive Health at the Hudson Institute of Medical Research

There is now firm evidence that exposure to different diets, toxins and the environment during and even before pregnancy can have long lasting effects on the health of offspring. The review by Arendrup et al adds another potential source of disruption of fetal reproductive development, namely commonly used analgesics such as paracetamol.

This is a comprehensive review of published literature by very reputable authors who have conducted carefully designed preliminary studies using mouse and rat models. There is now sufficient evidence to warrant further investigations as recommended in the review, but at this stage, it should not set alarm bells ringing with women who use analgesics during pregnancy in a responsible manner.

A major problem with animal models such as rodents is their relevance to humans. This underlines the need for careful studies involving both human subjects, animal models and in vitro studies as suggested by the authors of the review. While the evidence to date shows effects of analgesics on reproductive capacity in rodents, it is not at all clear if this also applies to humans. Indeed the structure of the placenta in women is vastly different to that in rodents which could influence transfer of the analgesic from mother to fetus or metabolism of the analgesic in the placenta itself.

Last updated: 05 Jan 2018 12:09pm
Declared conflicts of interest:
None declared.
Dr Luke Grzeskowiak is a pharmacist and research fellow in the Robinson Research Institute at the University of Adelaide

There are a number of differences between animals and humans. We can’t be sure whether the way animals respond to paracetamol is the same in humans. This makes it difficult to know if the same effects would be seen in humans and as it currently stands there is no evidence from human studies that paracetamol use alters female fertility.

The doses used in these small animal studies would be equivalent to women taking paracetamol at the maximum recommended dose for an entire 6 months of their pregnancy. This is not reflective of how paracetamol is commonly used in pregnancy. Most pregnant women would only take the odd dose for a short period of time. Based on this review there is no reason to change current treatment recommendations. At the end of the day, paracetamol is and remains the safest medication for treating pain and fever in pregnancy.

 Women should not be concerned about using paracetamol if needed, but as with all medications, should continue to use it at the lowest effective dose and for the shortest possible time.

Last updated: 05 Jan 2018 11:25am
Declared conflicts of interest:
None declared.

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