Danish researchers conducted a study to determine the possible consequences of paracetamol use during pregnancy, not only for the mother and fetus but also for the future reproductive health of daughters. The study monitored women from early pregnancy, recorded the number of tablets taken, and measured paracetamol levels in urine. After the girls were born, their reproductive systems were assessed during the so-called mini-puberty period.

Context of Paracetamol Use During Pregnancy

Paracetamol is often prescribed to pregnant women to reduce pain and fever, as other painkillers may pose risks to fetal development. Typically, the minimum effective dose and short-term use are recommended, since finding a safe alternative is not always possible.

Experimental Data and Previous Studies

Earlier experiments on rodents showed that prenatal exposure to paracetamol can reduce the follicle reserve in offspring, decrease their number by up to 40% from baseline, lower fertility, and accelerate reproductive aging in females. Laboratory studies also examined the drug’s effects on fragments of human fetal ovaries at early developmental stages. It was found that paracetamol reduces the number of certain embryonic cells and disrupts the production of steroid hormones, including progesterone and estradiol.

Main Study Procedure and Results

From March 2020 to November 2022, 685 pregnant women were observed starting from the first trimester. Every two weeks, participants reported their use of painkillers and provided urine samples to determine paracetamol concentration. In the third trimester, fetal ultrasounds were performed. After birth, 302 girls underwent follow-up examinations at three months to assess reproductive indicators.

In the first months of life, newborn girls experience temporary activation of the hypothalamic-pituitary-gonadal axis, allowing early assessment of reproductive system development. Among girls whose mothers took paracetamol up to the 17th week of pregnancy, the average ovarian volume was about 41% smaller, and uterine volume was 13% smaller. In children whose mothers started taking the drug after the 17th week, there was a 23% reduction in the number of antral follicles in the ovaries, while ovarian and uterine volumes did not differ significantly from the control group. The median total dose of paracetamol among women who took it was two grams for the entire pregnancy.

Verification of Results in an Independent Sample

To confirm the findings, data from the Copenhagen Mother-Child Cohort were used, which tracked 1,210 girls from infancy to adolescence. Among girls exposed to paracetamol or nonsteroidal anti-inflammatory drugs in utero, uterine volume during puberty was about 4.11 cubic centimeters smaller, and ovarian volume in adolescence was 2.76 cubic centimeters smaller.

Limitations and the Need for Further Research

The data obtained cannot be unequivocally interpreted as proof of harm from paracetamol. Women took the medication for medical reasons, most often due to headaches or muscle pain, not high fever. The observed differences could be due not only to the drugs but also to health conditions that led mothers to take painkillers, as well as other individual factors such as diet, lifestyle, and genetics. Researchers accounted for these factors in statistical analysis, but could not completely rule out their influence.

It is also unknown how reduced ovarian and uterine volumes in infancy affect future fertility, as organ size at this age does not predict reproductive capacity decades later. Further studies and long-term monitoring of children until reproductive age are needed to draw definitive conclusions.

The scientific study was published in the journal Human Reproduction Open.