Study links paracetamol during pregnancy to smaller reproductive organs in baby girls

Findings from the Copenhagen study

Researchers led by Margit Bistrup Fischer at Copenhagen University Hospital investigated the impact of prenatal paracetamol exposure on female reproductive development. The research, titled the Copenhagen Analgesic Study or Copana, recruited 685 pregnant women during their first trimester between March 2020 and November 2022. Participating mothers submitted questionnaires detailing their painkiller usage every two weeks, with maternal urine samples collected to verify the presence of the drug. Following delivery, pediatric specialists at Rigshospitalet evaluated 302 infant daughters at an average age of 106 days. Clinical examinations utilized abdominal ultrasound imaging and blood analyses to measure internal reproductive structures. The examinations revealed quantifiable anatomical differences between exposed infants and unexposed control groups.

Timing and anatomical measurements

The findings revealed distinct developmental differences tied to the gestational stage of drug exposure. Maternal intake prior to the 17th week of pregnancy was linked to a 40 percent lower ovarian volume and a 13 percent lower uterine volume in female infants. Exposure from the 17th week onward corresponded to a 23 percent decrease in ovarian follicles, the anatomical structures containing immature eggs. Girls exposed exclusively in the early gestational window also exhibited lower levels of Anti-Mullerian Hormone, a clinical biomarker for lifelong egg supply. Statistical evaluations indicated a dose-response relationship, with more extensive paracetamol use correlating with greater reductions in organ volume and follicle count.

Long-term observations and dosage

Females are born with their entire lifetime reserve of germ cells and follicles, which diminishes progressively until menopause. To assess whether the observed structural differences persist over time, researchers examined a separate longitudinal group of 1,210 girls tracked from infancy into adolescence. In that cohort, maternal paracetamol consumption was associated with smaller uterine size during puberty and smaller ovarian volume in adolescence. The mothers in the Copana group consumed modest amounts of the painkiller, and none exceeded the standard daily limit of 4,000 milligrams. Headache and migraine relief represented the most common reason for consumption, followed by musculoskeletal pain.

Clinical context and calls for review

Paracetamol has served as the standard first-line painkiller and fever medication for pregnant patients across international medical guidelines. While previous animal studies suggested the drug could act as an endocrine disruptor and shorten reproductive lifespans, prospective human evidence had not previously been documented. The study authors noted that the analysis remains observational and does not prove direct causation between the analgesic and future reproductive disorders. Further longitudinal monitoring is necessary to determine whether these organ size reductions affect future conception rates or accelerate menopause. In an accompanying commentary published in Human Reproduction Open, Christian De Geyter of University Hospital Basel stated that guidelines regarding paracetamol usage in pregnancy should be revised.