Researchers in Denmark have found that girls whose mothers took paracetamol during pregnancy had smaller ovaries, fewer ovarian follicles (the structures that contain immature eggs), smaller uteruses and lower levels of reproductive hormones at three months old.
In a study published today (Wednesday) in Human Reproduction Open [1], one of the world's leading reproductive medicine journals, the researchers said their results were consistent with findings from several previous studies in animals. However, they noted that, as this was an observational study, the findings do not establish a direct cause-and-effect relationship. They said women should not be alarmed by their findings, which required confirmation in further, longer-term investigations and follow-up.
A woman's reproductive function and lifespan is established during her foetal life in the womb. Girls are born with all the immature egg follicles they will ever have and these gradually deplete throughout life until the menopause. Paracetamol is the most commonly-used medication in pregnancy but, until now, it was unknown whether foetal exposure to the drug might affect the development of the ovarian egg reserve and later reproductive function in girls and women in the same way that had been observed in animal studies.
To investigate this, researchers established a prospective observational study called the Copenhagen Analgesic Study (COPANA) at the Copenhagen University Hospital–Rigshospitalet that ran from March 2020 to November 2022. As far as they are aware, this is the first prospective study to evaluate the associations between foetal exposure to paracetamol and postnatal ovarian function.
A total of 3,425 healthy pregnant women were invited to participate and, of these, 685 women were enrolled during the first trimester of pregnancy and 302 baby daughters were examined when they were three months old.
The mothers reported paracetamol use every two weeks and provided urinary samples in the first trimester, which the researchers analysed for paracetamol levels. The girls were classified by the timing of their initial exposure to paracetamol: during early foetal life at less than 17 weeks (92 babies) and mid-late foetal life at 17 weeks or more (67). They were compared to a control group of babies who had not been exposed to paracetamol (143).
The researchers also looked at a separate group of 1,210 girls from the Copenhagen Mother-Child Cohort, who were followed from infancy to adolescence and whose mothers, during the third trimester, had reported any paracetamol use during pregnancy. This cohort started in 1996 and included pregnant women from three university hospitals in Copenhagen.
Dr Margit Bistrup Fischer, a post-doctoral researcher in the Department of Growth and Reproduction at the Rigshospitalet, Copenhagen, Denmark, who led the COPANA study, said: "When the babies were three months old, we found that those who had been exposed to paracetamol during foetal life had, on average, a 40% smaller ovarian volume, a 13% smaller uterine volume and 23% fewer ovarian follicles. The girls who had been exposed to paracetamol in early foetal life had lower levels of Anti-Müllerian hormone, which is an established marker of ovarian egg reserve."
The results were supported by those from the independent confirmatory group of girls who had been followed into adolescence. In this group, foetal exposure to paracetamol was associated with smaller uteruses at puberty and smaller ovaries during adolescence.
Dr Fischer said: "Animal studies have demonstrated that impaired formation of ovarian follicles can lead to reduced fertility and earlier reproductive ageing. Whether the differences observed in our study have implications for fertility and age at menopause in humans remains unknown and will require long-term follow-up of the girls in our cohort.
"Women who have used paracetamol during pregnancy should not be alarmed by our findings. Our study examined associations at the population level and cannot predict outcomes for any individual woman or child. Many women who used paracetamol during pregnancy had daughters whose ovarian measurements were similar to those of daughters born to women who did not use paracetamol.
"Importantly, our study does not evaluate if paracetamol causes reproductive problems, nor does it provide evidence that prenatal exposure affects future fertility or age at menopause. Although we observed similar associations in an independent cohort, long-term follow-up is needed to determine whether these early-life differences have any clinical significance later in life.
"Decisions about pain management during pregnancy should always be individualised and made in consultation with a healthcare professional. Therefore, our findings should not discourage women from using paracetamol when it is medically indicated but rather encourage informed discussions about when medication is necessary and when alternative approaches may be considered. Current guidelines in Europe and the UK continue to recommend paracetamol as the first-choice medication for treating pain and fever during pregnancy when clinically needed. Untreated conditions such as high fever or severe pain can themselves pose risks to both the mother and the developing foetus."
The researchers say that the mothers in the study took relatively low levels of paracetamol and none exceeded the recommended daily maximum dose of 4,000mg. Most took it for headaches or musculoskeletal pain rather than severe illness.
"In some of these situations, non-pharmacological approaches, such as rest, hydration, physiotherapy, exercise, heat treatment, or other supportive measures, may be sufficient if women receive appropriate counselling," said Dr Fischer.
In an accompanying commentary [2], Professor Christian De Geyter, who leads the department of Reproductive Medicine and Gynecological Endocrinology at the University Hospital of Basel, Switzerland, writes: "The eminent importance of Fischer et al's (2026) findings cannot be stressed enough!"
He continues: "Both the duration of intake and applied dosage must be taken into consideration, this being a common principle in toxicology, but the observed dose-responsiveness of the findings points towards a distinctive effect and fits well with the already published animal research data. Recommendations on the use of paracetamol during pregnancy must now be revised."
He emphasises the importance of follow-up that should extend into adulthood and up to menopause. He concludes: "The attention this study is likely to generate among both professionals and the general public will hopefully encourage sustained long-term follow-up of the exposed individuals."
