Girls whose mothers took paracetamol (acetaminophen) during pregnancy had smaller ovaries at three months old, on average, than those whose mothers didn’t take the drug, according to a study of about 300 infant girls in Denmark. Infant boys whose mothers took paracetamol had smaller testes on average too, the study found. That doesn’t prove paracetamol caused the reduction in the average size of ovaries and testes, though – this association could be a result of the conditions that led to the women taking paracetamol during pregnancy, or even due to chance alone.
Nor is it clear whether having smaller ovaries or testes as an infant affects fertility in adulthood. However, the findings are in line with separate studies done in rats and mice, in isolated human ovaries and in human embryonic cells. Upheavals to the oral microbiome in pregnancy may be behind tooth loss “We still recommend that pregnant women should use paracetamol with high fever or strong pain,” says Margit Bistrup Fischer at Copenhagen University Hospital–Rigshospitalet.
Not doing so can be risky, she says. But most of the women in the study used paracetamol for headaches or musculoskeletal pain, rather than fevers, and could have managed their pain or discomfort in other ways, such as via rest, heat treatment or physiotherapy, says Fischer. Maybe it shouldn’t be the first thing that we grab when we have discomfort.” The issue is that there are almost no safe drug-based alternatives to paracetamol for pregnant women.
Most other painkillers aren’t recommended because they can cause congenital conditions. Fischer’s team recruited 685 pregnant women during their first trimester, who were asked about their use of medicines every two weeks. They had an fetal ultrasound during their third trimester, and 302 daughters were examined around three months after birth.
Those exposed to paracetamol as a fetus had, on average, 40 per cent smaller ovaries by volume, 13 per cent smaller uteruses by volume and 23 per cent fewer ovarian follicles – the sacs that nurture immature eggs – compared with those who weren’t exposed. Higher doses were associated with a bigger effect, says Fischer, but no women took more than the recommended daily maximum of 4000 milligrams. A study of more than 10 million siblings suggests that firstborns are more likely to be autistic and have allergies, while conditions like migraine and shingles tend to affect their younger sibling The researchers also analysed data from another study on 1210 girls born in Copenhagen between 1997 and 2002, and found a link between fetal exposure to paracetamol and smaller ovaries during adolescence.
In animal studies, such effects led to reduced fertility and earlier reproductive ageing, but it isn’t clear whether this applies to people. That will require long-term follow-up, which is hard to do. The team also examined the boys who were born to the 685 women.
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