Paracetamol is one of the most commonly used medicines during pregnancy, often taken for headaches, fever, or muscle pain. But a new study has raised questions about whether exposure to the drug before birth could influence the reproductive development of baby girls.
Researchers in Denmark found that three-month-old girls whose mothers had taken paracetamol during pregnancy had, on average, smaller ovaries and uterus, fewer ovarian follicles and, in some cases, lower levels of a hormone associated with ovarian reserve.
The findings, published on Wednesday in Human Reproduction Open, do not establish that paracetamol causes reproductive problems. The researchers stressed that their study was observational and that the significance of the differences for fertility or the age at menopause remains unknown.
That distinction is important because paracetamol continues to be recommended as a first-choice medicine for pain and fever during pregnancy when clinically required in Europe and the UK.
The study was part of the Copenhagen Analgesic Study (COPANA), a prospective observational study conducted at Copenhagen University Hospital–Rigshospitalet between March 2020 and November 2022.
Of 3,425 healthy pregnant women invited to participate, 685 enrolled during the first trimester. Researchers subsequently examined 302 of their daughters at three months of age.
The mothers reported their paracetamol use every two weeks and also provided urine samples during the first trimester, which were analyzed for paracetamol levels.
The girls were divided according to whether exposure had occurred early in fetal development, before 17 weeks of pregnancy, or later. The study team compared exposed girls with unexposed peers in the drug exposure analysis.
The differences were notable. According to the researchers, exposed girls had an average 40% smaller ovarian volume, 13% smaller uterine volume, and 23% fewer ovarian follicles at three months.
Girls exposed during early fetal life also had lower levels of anti-Müllerian hormone (AMH), a hormone widely used as a marker of ovarian reserve.
The findings have attracted attention because a woman’s reproductive potential begins taking shape before birth.
Baby girls are born with the ovarian follicles that contain the immature eggs they will have during their lifetime. The number of these follicles gradually declines with age.
Any factor that alters ovarian follicle formation in fetal life could have later implications. The exact nature of these implications remains uncertain. We do not know whether the differences seen in this study translate into reduced fertility. Observed differences may accelerate reproductive aging or lead to menopause earlier, yet evidence is lacking.
That will require long-term follow-up of the girls in our cohort. Dr Margit Bistrup Fischer is the study’s lead researcher and a postdoctoral researcher at Rigshospitalet.
A separate group of 1,210 girls in the Copenhagen Mother-Child Cohort supported the study’s results. Prenatal paracetamol exposure correlated with smaller uterus around puberty and smaller ovaries during adolescence.
This extra finding supports pursuing further research. It still does not prove the drug caused the changes.
Fischer advised pregnant women who had taken paracetamol during pregnancy to remain calm. The study looked at associations at the population level and cannot predict outcomes for an individual mother or child.
Many women who used the drug during pregnancy had daughters with ovarian measurements. These measurements were similar to those of girls whose mothers did not take it.
In the study, paracetamol use was typically low. None of the women reached the 4,000 mg daily limit. Most reported using it for headaches or musculoskeletal pain rather than serious illness.
Thus, the findings raise a research question. They do not provide a reason for women to stop medically indicated treatment on their own.
An additional consideration complicates the issue. When pain or high fever remains untreated in pregnancy, it can endanger both mother and fetus.
Fischer stated that patients should tailor pain-management decisions and discuss them with a healthcare professional.
Non-drug measures can be sufficient for milder problems. These include rest, hydration, physiotherapy, exercise, heat treatment, or other supportive approaches, depending on the condition.
The message is not to replace paracetamol with another medicine. The message aims to ensure people use medication only when genuinely needed and at an appropriate dose.
The Danish findings are likely to generate debate because their possible implications extend far beyond infancy.
The researchers advocate longer-term studies to determine whether the smaller ovarian and uterine measurements observed in infancy and adolescence have any clinical consequences.
That may ultimately be the most important question: whether researchers detect a difference in early life or whether it will change a woman’s reproductive health decades later.
Until such evidence emerges, experts caution against turning an observational finding into a blanket warning. For pregnant women, the priority remains a careful balance between treating conditions that require medication and avoiding unnecessary drug exposure—decisions best made with appropriate medical advice.
