Taking Tylenol or generic acetaminophen during pregnancy may be associated with changes in female reproductive organ development, researchers said, while stressing that their findings do not establish a causal link or suggest future fertility problems.
Whether the differences observed in the Danish study of infants have implications for fertility later in life and age at menopause will require long-term follow-up, study leader Margit Bistrup Fischer of Rigshospitalet in Copenhagen said in a statement.
Women who during pregnancy used the medicine, typically sold generically as paracetamol in Europe, should not be alarmed by the findings, Fischer said. The generic version of Tylenol sold in the U.S. is acetaminophen.
Kenvue, which owns the Tylenol brand name product, in an emailed statement advised pregnant or breastfeeding women to check with a health professional before using acetaminophen, which the company says is the most studied and safest pain reliever during pregnancy.
It noted that the study has methodology limitations and does not support a causal relationship between the drug and postnatal reproductive development. Kenvue shares were off more than 3%.
Fischer's team studied 302 3-month-old girls whose mothers' use of some version of the drug had been tracked during pregnancy. Participants did not report which manufacturer's product they used.
Ninety-two of the infants were first exposed to the pain medicine in utero before 17 weeks of pregnancy, 67 were first exposed after 17 weeks, and 143 were born to mothers who had not used the drug.
Exposure to paracetamol or branded versions sold in Denmark was assessed based on questionnaires and urine samples provided by the women at regular intervals. The mothers took relatively low amounts, and none exceeded the recommended daily maximum dose of 4,000 milligrams. Most took it for headaches or musculoskeletal pain.
On average, infants exposed in utero had smaller ovaries, fewer ovarian follicles, which are the structures that contain immature eggs, smaller uteruses and lower levels of reproductive hormones, researchers reported on Wednesday in Human Reproduction Open.
A woman’s reproductive function and window are established while she’s still in the womb, the researchers explained, and girls are born with all the eggs they will ever have.
Animal studies have suggested that fetal exposure to the medicine, the most commonly used drug in pregnancy, might affect ovarian egg reserve and later reproductive function, but no one has reported similar findings in humans until now.
U.S. President Donald Trump has linked the use of Tylenol during pregnancy to autism, a claim that has been widely dismissed by the medical community and major health organizations as lacking scientific backing.
The 3-month-old girls in the study who were exposed to the drug in utero had, on average, a 40% smaller ovarian volume, a 13% smaller uterine volume and 23% fewer ovarian follicles, the researchers found.
Babies exposed early in pregnancy - before 17 weeks - also had a lower average level of Anti-Müllerian hormone, an indicator of the amount and quality of eggs in the ovaries.
The researchers also looked at a separate group of 1,210 girls who were followed from infancy to adolescence and whose mothers had reported paracetamol use during pregnancy. In this group, fetal exposure was associated with smaller uteruses at puberty and smaller ovaries during adolescence.
The study cannot predict outcomes for any individual woman or child, Fischer said, noting that many women who used the drug during pregnancy had daughters whose ovarian measurements were similar to those of daughters born to women who did not use the medicine.
Current guidelines continue to recommend paracetamol or acetaminophen as safe for treating pain and fever during pregnancy. Untreated high fever or severe pain can themselves pose risks to the mother and the fetus, Fischer said.
In an accompanying commentary, Dr. Christian De Geyter, a reproductive medicine specialist at the University Hospital of Basel, Switzerland, said the researchers’ findings fit well with data from research in animals.
Follow-up of girls exposed to the widely used pain and fever reducer in utero should extend into menopause, he said, adding that recommendations on its use during pregnancy should be reconsidered.
