Prenatal paracetamol exposure associated with smaller ovaries in infant daughters

Danish researchers have documented a measurable difference in the reproductive anatomy of infant girls whose mothers took paracetamol during pregnancy. At three months old, these daughters had ovaries that were, on average, 40 percent smaller than those of unexposed infants. They also showed 23 percent fewer ovarian follicles—the structures that house immature eggs—along with smaller uteruses and lower levels of reproductive hormones. The findings, published in Human Reproduction Open, represent the first prospective human study to examine whether fetal exposure to the world's most commonly used pain reliever in pregnancy might affect the development of a girl's egg reserve.

The research emerged from the Copenhagen Analgesic Study, which enrolled 685 pregnant women in their first trimester between March 2020 and November 2022. Of these, 302 baby daughters were examined at three months of age. Mothers reported their paracetamol use every two weeks and provided urine samples in early pregnancy, which researchers tested for the drug's presence. Infants were sorted into three groups: those exposed before 17 weeks of gestation (92 babies), those exposed from 17 weeks onward (67 babies), and a control group with no documented exposure (143 babies). Girls exposed early in fetal development showed particularly low levels of Anti-Müllerian hormone, a marker used to assess ovarian egg reserve.

The team also examined data from a separate cohort of 1,210 girls born between 1996 onward, whose mothers had reported paracetamol use during the third trimester. This independent group, followed from infancy into adolescence, showed similar patterns: smaller uteruses at puberty and smaller ovaries during the teenage years. The consistency across two different populations strengthened the researchers' confidence in the association, though they were careful to note that association is not the same as causation.

Dr. Margit Bistrup Fischer, who led the Copenhagen study, emphasized that the mothers involved had taken relatively modest amounts of paracetamol—none exceeded the recommended daily maximum of 4,000 milligrams, and most used it for headaches or muscle pain rather than serious illness. She acknowledged the central limitation of the work: an observational study can document that two things occur together, but it cannot prove that one caused the other. Animal research has shown that paracetamol can impair the formation of ovarian follicles, potentially leading to reduced fertility and earlier reproductive aging, but whether the anatomical differences observed in these Danish infants will translate into actual reproductive consequences remains entirely unknown.

The commentary accompanying the study, written by Professor Christian De Geyter of the University Hospital of Basel, called the findings of "eminent importance" and noted that the dose-responsiveness observed in the data—meaning the effect appeared stronger with greater exposure—aligns with established toxicological principles and with prior animal research. He argued that clinical guidelines on paracetamol use in pregnancy should be reconsidered and that long-term follow-up extending into adulthood and menopause would be essential to determine whether these early differences matter for actual health outcomes.

Fischer stressed that women who took paracetamol during pregnancy should not be alarmed. The study examined population-level associations and cannot predict what will happen to any individual child. Many women who used paracetamol had daughters with normal ovarian measurements. She also emphasized that current European and UK guidelines continue to recommend paracetamol as the first-choice medication for pain and fever in pregnancy when medically necessary, partly because untreated high fever or severe pain can themselves pose risks to mother and fetus. She suggested, however, that healthcare providers and pregnant women might explore non-pharmacological alternatives—rest, hydration, physiotherapy, exercise, heat treatment—in situations where they might suffice, and that decisions about pain management should always be individualized and made in consultation with a doctor.

What remains unknown is whether the 40 percent reduction in ovarian volume and the 23 percent decrease in follicle count observed at three months will persist, worsen, or resolve as these girls grow. Whether these differences will affect their ability to conceive, the timing of their menopause, or any other aspect of reproductive health cannot be answered by this study. The researchers have called for sustained long-term follow-up of the exposed cohorts into adulthood—a process that could take decades. Until then, the findings stand as an intriguing signal from animal research now confirmed in human infants, but not yet as evidence of clinical harm.