Observational study links prenatal paracetamol exposure to altered reproductive development in daughters
· Medical Xpressby European Society of Human Reproduction and Embryology
edited by Gaby Clark, reviewed by Robert Egan
Gaby Clark
Scientific Editor
Meet our editorial team
Behind our editorial process
Robert Egan
Senior Editor
Meet our editorial team
Behind our editorial process Editors' notes
This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility:
fact-checked
trusted source
proofread
The GIST Add as preferred source
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 3 months old.
In a study published today (Wednesday) in Human Reproduction Open, the researchers said their results were consistent with findings from several previous animal studies. 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 require confirmation in further, longer-term investigations and follow-up.
A woman's reproductive function and lifespan are established during fetal life in the womb. Girls are born with all the immature egg follicles they will ever have, and these gradually deplete throughout life until menopause. Paracetamol is the most commonly used medication during pregnancy but, until now, it was unknown whether fetal 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 observed in animal studies.
To investigate this, researchers established a prospective observational study called the Copenhagen Analgesic Study (COPANA) at 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 fetal exposure to paracetamol and postnatal ovarian function.
How the study tracked exposure
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. Researchers examined 302 baby daughters when they were 3 months old.
The mothers reported paracetamol use every two weeks and provided urinary samples in the first trimester, which the researchers analyzed for paracetamol levels. The girls were classified by the timing of their initial exposure to paracetamol: during early fetal life at less than 17 weeks (92 babies) and mid- to late fetal life at 17 weeks or more (67). They were compared with 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 had reported any paracetamol use during pregnancy in the third trimester. This cohort started in 1996 and included pregnant women from three university hospitals in Copenhagen.
Dr. Margit Bistrup Fischer, a postdoctoral researcher in the Department of Growth and Reproduction at Rigshospitalet in Copenhagen, Denmark, who led the COPANA study, said, "When the babies were 3 months old, we found that those who had been exposed to paracetamol during fetal 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 fetal life had lower levels of Anti-Müllerian hormone, which is an established marker of ovarian egg reserve."
Signals seen again in adolescence
The results were supported by those from the independent confirmatory group of girls who had been followed into adolescence. In this group, fetal exposure to paracetamol was associated with smaller uteruses at puberty and smaller ovaries during adolescence.
Fischer said, "Animal studies have demonstrated that impaired formation of ovarian follicles can lead to reduced fertility and earlier reproductive aging. 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 whether 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.
Advice remains tied to clinical need
"Decisions about pain management during pregnancy should always be individualized and made in consultation with a health care 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 United Kingdom 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 fetus."
The researchers said the mothers in the study took relatively low levels of paracetamol, and none exceeded the recommended daily maximum dose of 4,000 mg. Most took it for headaches or musculoskeletal pain rather than severe illness.
"In some of these situations, nonpharmacological approaches, such as rest, hydration, physical therapy, exercise, heat treatment or other supportive measures, may be sufficient if women receive appropriate counseling," Fischer said.
In an accompanying commentary, Professor Christian De Geyter, who leads the Department of Reproductive Medicine and Gynecological Endocrinology at the University Hospital of Basel in Switzerland, writes, "The immense importance of Fischer and teams' 2026 findings cannot be stressed enough."
He continues, "Both the duration of intake and dose administered must be taken into consideration—a common principle in toxicology—but the observed dose-responsiveness of the findings points toward 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 emphasizes 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."
More information
Fetal exposure to paracetamol is associated with altered markers of ovarian development and reduced uterine volume in girls: the COPANA study, Human Reproduction Open (2026). DOI: 10.1093/hropen/hoag073
Key medical concepts
Clinical categories
Obstetrics & gynecologyPregnancyReproductive health Provided by European Society of Human Reproduction and Embryology Who's behind this story?
Gaby Clark
MA in English, copy editor since 2021 with experience in higher education and health content. Dedicated to trustworthy science news. Full profile →
Robert Egan
Bachelor's in mathematical biology, Master's in creative writing. Well-traveled with unique perspectives on science and language. Full profile →
Citation: Observational study links prenatal paracetamol exposure to altered reproductive development in daughters (2026, September 8) retrieved 9 September 2026 from https://medicalxpress.com/news/2026-09-links-prenatal-paracetamol-exposure-reproductive.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.