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Paracetamol use in pregnancy was not linked to autism or ADHD, while separate research found reproductive differences in girls exposed before birth.
One study analysed health records from more than 120,000 children and found no increased risk of autism following prenatal paracetamol exposure.
A separate analysis of nearly 100,000 children also found no increased risk of ADHD among those born to mothers who used the painkiller during pregnancy.
Researchers from the Hong Kong Hospital Authority examined electronic health records covering pregnancies between January 2001 and December 2023.
The autism analysis included 124,333 children, who were nine years old on average and split almost evenly between males and females. There were 3,445 autism diagnoses, representing 2.8 per cent of the group.
The ADHD analysis involved 97,285 children, who were seven years old on average and also split evenly between males and females. There were 5,168 ADHD diagnoses, representing 5.3 per cent.
Women prescribed paracetamol during pregnancy were more likely to be older and have pre-existing conditions including psychiatric disorders, as well as reasons for taking the drug such as infection, fever or chronic pain.
No association was found between prenatal paracetamol exposure and either autism or ADHD.
The findings did not differ according to the trimester in which paracetamol was taken or whether use was intermittent or daily. Advanced maternal age, defined as pregnancy in women over 35, did not alter the findings.
The researchers wrote: “Paracetamol remains a safe and essential analgesic [pain reliever] and antipyretic [fever reducer] during pregnancy, whereas alternatives, such as NSAIDs and opioids carry well-documented risks.
“Unwarranted reluctance to use paracetamol could lead to undertreatment of pain and fever, or the use of more harmful alternatives, both posing risks to the pregnancy and developing fetus.”
The authors said women should assess paracetamol use with guidance from their doctor.
A separate study involving 685 pregnant women without pre-existing conditions and 302 infant daughters found associations between prenatal paracetamol exposure and differences in reproductive organs and hormone levels.
Researchers from Copenhagen University Hospital enrolled the women during their first trimester and assessed them during the first trimester, third trimester and again when their babies were three months old.
At around three months, infants experience a temporary rise in reproductive hormones sometimes called mini-puberty.
Pregnant participants completed questionnaires every two weeks about their use of pain medicines including paracetamol. Infant girls underwent ultrasound scans of their reproductive organs and blood tests to measure hormone levels.
Researchers also examined a separate group of 1,210 girls followed from infancy to adolescence whose mothers reported paracetamol use during the third trimester.
Three-month-old girls exposed to paracetamol before birth had an average 40 per cent smaller ovarian volume, 13 per cent smaller uterine volume and 23 per cent fewer ovarian follicles.
Girls exposed during the first trimester also had lower levels of Anti-Müllerian hormone, a marker of ovarian function.
Among the older girls, those exposed before birth were more likely to have smaller uteruses at puberty and smaller ovaries during their teenage years.
Dr Margit Bistrup Fischer, lead study author and postdoctoral researcher in the Department of Growth and Reproduction at Rigshospitalet hospital in Denmark, said: “Animal studies have demonstrated that impaired formation of ovarian follicles can lead to reduced fertility and earlier reproductive aging.
“Whether the differences observed in our study have implications for fertility and age at menopause in humans remains unknown and will require long-term follow-up of the girls in our cohort.”
She cautioned that women who had used paracetamol during pregnancy “should not be alarmed by our findings”, as the study found associations rather than direct causation and outcomes for individual women and children are unclear.
“Importantly, our study does not evaluate whether [acetaminophen] causes reproductive problems, nor does it provide evidence that prenatal exposure affects future fertility or age at menopause,” she said.
“Although we observed similar associations in an independent cohort, long-term follow-up is needed to determine whether these early-life differences have any clinical significance later in life.”
