April 16, 2018

expert reaction to study looking at effects of paracetamol and ibuprofen on tissue samples of human foetal testes and ovaries, and in mice

A study, published in Environmental Health Perspectives, investigates the side-effects of taking painkillers during pregnancy, specifically examining whether it affects the fertility of future generations.

Dr Patrick O’Brien, Consultant Obstetrician and spokesperson for the Royal College of Obstetricians and Gynaecologists (RCOG), said:

“This is an interesting study which suggests taking paracetamol and ibuprofen during pregnancy might affect the fertility of the unborn child by reducing the number of cells that give rise to sperm and eggs.

“It is important to note that this study was carried out on human fetal testes and ovaries and animal models, so definitive conclusions cannot be drawn.  It is also not possible to translate the findings into a recommendation on what would be a safe or unsafe amount of paracetamol or ibuprofen to take while pregnant.

“More research is needed into the long term effects of paracetamol and ibuprofen use in pregnancy on the fertility of the unborn child.

“Women should not be alarmed by the results of this study.  Paracetamol is widely accepted as a safe painkiller for pregnant women to take, and can be very beneficial when a pregnant woman is suffering with a migraine, for example.  We recommend that women follow current guidance and take the lowest effective dose of paracetamol for the shortest possible time.  If this doesn’t treat the pain, they should to speak to their GP, midwife, or obstetrician. Pregnant women are generally advised to avoid taking ibuprofen as it is associated with an increased risk of complications.”

Prof Ieuan Hughes, member of the Society for Endocrinology, and Emeritus Professor of Paediatric Endocrinology, University of Cambridge, said:

“This paper is a magnum opus of methodology from a well recognised research group exploring the effect and mechanism of analgesic exposure during pregnancy on the fetal gonads of offspring.  Clearly, this cannot be studied directly in humans but the Edinburgh group has utilised a number techniques with in vitro, ex vivo (using human fetal testis implants in rodents) and direct animal studies to assess the effects of acetaminophen (paracetamol) and ibuprofen.

“The doses used reflected those commonly used by adults.  The results showed that such exposure reduced the number of germ producing cells in both the fetal testis and ovary.  The observation affecting the developing ovary is particularly important as the finite number of eggs a female has for reproduction is set well before birth.  The mechanism appears to be via the action of prostaglandins which, the study shows, can be blocked by prostaglandin-inhibitors.  Another remarkable observation in this study was that these effects may be passed on to the next generation via epigenetic effects.

“So what does the latest study in this field mean for women who are pregnant and need to take an analgesic for some reason?  As with previous studies in this area, the authors emphasise that paracetamol is probably still safe in pregnancy but to use the smallest dose for the shortest time, as a precautionary principle.  However, there has now been a steady drip-feed of epidemiological and experimental studies reporting that analgesics taken during pregnancy may have adverse effects on the reproductive system of the offspring.  Is it not time for investigators in this field of endocrine disruption to get together to formulate a large scale prospective study of the potential health risks of women taking analgesics while pregnant?”

Dr Channa Jayasena, Society for Endocrinology and Senior Clinical Lecturer in Reproductive Endocrinology at Imperial College London, said:

“Paracetamol and ibuprofen are commonly used during pregnancy.  However, over the last year, a growing number of reports have suggested that we might need to take a closer look at their safety in unborn babies.  This latest study raises the possibility that paracetamol and ibuprofen may reduce the growth of the ‘germ cells’ which later become eggs or sperm in unborn babies.  It is important to recognise that the study only looks at tissue in the lab, which limits its relevance in humans.  However, when its results are considered in the context of similar recent studies, they become more interesting.  While it is still premature to stop taking these important drugs, there is a growing case to investigate their safety for pregnant women.”

Dr Sarah Branch, Deputy Director of the MHRA’s Vigilance and Risk Management of Medicines Division, said:

“Women should avoid taking medicines during pregnancy unless absolutely necessary and should speak to their doctor, midwife or pharmacist before doing so.  Paracetamol is generally considered to be a safe treatment for pain relief during pregnancy but should be taken at the lowest possible dose for the shortest time.  Ibuprofen is not recommended for use during pregnancy.

“The safety of all medicines is carefully monitored.  These findings will be carefully evaluated, as with any study, to determine whether they have any implications for the safe use of paracetamol or ibuprofen.”

* ‘Effects of exposure to acetaminophen and ibuprofen on fetal germ cell development in both sexes in rodent and human using multiple experimental systems’ by Pablo Hurtado-Gonzalez et al. published in Environmental Health Perspectives on Monday 16 April 2018.

Declared interests

Prof Ieuan Hughes: “I declare no conflict of interest.”

Dr Channa Jayasena: “No conflicts.”

Dr Sarah Branch: “No conflicts of interest to declare.”

None others received.