Taking paracetamol during pregnancy could affect fertility and the timing of menopause in daughters, according to a study published in the journal Human Reproduction Open.
Girls whose mothers had taken paracetamol during pregnancy had smaller ovaries, fewer follicles, smaller uteruses and lower levels of reproductive hormones at the age of three months, the research team reported.
The findings were consistent with results from animal studies suggesting that paracetamol taken during pregnancy can lead to reduced fertility and a shortened reproductive lifespan in female offspring, said the team led by Margit Bistrup Fischer from Rigshospitalet in Copenhagen.
The current analysis was, however, an observational study, and the data did not establish a causal link, the team also stressed.
Whether the differences would actually have consequences for fertility or the timing of menopause would need to be clarified through longer-term follow-up studies.
The foundation for later reproduction is laid in the womb: girls are born with the entire number of egg cells available to them for life. When that supply is exhausted, menopause occurs – the point of the last menstrual period, after which fertility ends permanently.
Should the guidelines be revised?
In an accompanying commentary in Human Reproduction Open, Christian De Geyter from the University Hospital Basel stressed the great significance of the findings. He said the recommendations on the use of paracetamol during pregnancy would now need to be revised.
Paracetamol is the most commonly used painkiller in pregnancy. Fischer and her colleagues analysed data from 685 women in the first trimester of pregnancy. The expectant mothers reported their paracetamol use at two-week intervals, and urine samples were also analysed. After the pregnancies ended, 302 daughters were examined at a mean age of 106 days.
Effects differed depending on the stage of pregnancy
Early use before the 17th week of pregnancy was associated with a smaller ovarian volume and a smaller uterine volume in daughters. Use from the 17th week of pregnancy onwards was associated with a lower number of follicles – the structures that contain immature egg cells. In a subgroup of girls exposed only in the early phase, levels of the hormone AMH, which is considered a marker of egg cell reserve, were also lower.
In the case of early-phase use, the authors found a roughly 40% smaller ovarian volume and a 13% smaller uterine volume in the girls.
When paracetamol was taken in the late stage of pregnancy, there were 23% fewer follicles. The analyses also pointed to a dose-response relationship, meaning a stronger effect with greater paracetamol use.
The women had taken comparatively small amounts of paracetamol, according to the researchers, and none exceeded the recommended maximum daily dose of 4,000mg.
Headaches or migraines were cited most frequently as the reason, followed by other pain, particularly musculoskeletal.
Further data confirmed the changes
The researchers also evaluated data from a separate group of 1,210 girls who were followed from infancy into adolescence.
There, a mother’s paracetamol use during pregnancy was associated with a smaller uterus in daughters during puberty and a smaller ovarian volume in adolescence. The authors see this as an indication that the observed differences could persist beyond early childhood.
“Women who took paracetamol during pregnancy should not be alarmed by our findings,” Fischer stressed. “Our study examined associations at the population level and cannot make predictions for individual women or children. Many women who took paracetamol during pregnancy had daughters whose ovarian measurements were similar to those of daughters whose mothers had not taken paracetamol.”
A link that does not exist
United States President Donald Trump had warned pregnant women at a press conference in September last year against taking paracetamol.
He suggested a link with autism in the child, however. Experts strongly disagreed.
A review study confirmed some months later that taking paracetamol during pregnancy does not increase the risk of autism, ADHD or intellectual disabilities.
Paracetamol is the most commonly used painkiller and fever-reducing medication in pregnancy, according to experts, and is recommended worldwide as the first-choice treatment for pain relief and fever reduction.
Fischer stressed that the new findings should not discourage women from taking paracetamol when medically necessary.
Rather, they should prompt conversations with the treating doctor about when medication is necessary and when alternative approaches can be considered. – dpa
