Paracetamol Use During Pregnancy May Affect Reproductive Development and Future Fertility of Baby Girls, Study Finds
A new study has raised questions about the possible long-term effects of paracetamol use during pregnancy after researchers found that girls exposed to the commonly used painkiller before birth had differences in their ovaries, reproductive organs and hormone levels.
The findings have attracted attention because paracetamol, also known as acetaminophen, is one of the most widely used medicines for treating pain and fever during pregnancy. It is available over the counter in many countries and has traditionally been considered one of the preferred pain-relief options for pregnant women when used appropriately.
However, researchers behind the new study say their findings suggest that prenatal exposure to paracetamol may be associated with changes in the development of the female reproductive system.
Importantly, the study does not prove that taking paracetamol during pregnancy causes infertility in daughters.
Instead, researchers found associations between exposure to the medicine before birth and several biological markers linked to reproductive development. Whether those differences eventually translate into difficulty becoming pregnant, a shorter reproductive lifespan or earlier menopause remains unknown.
The study, published in Human Reproduction Open, examined 302 infant girls whose mothers had participated in a Danish pregnancy study. Researchers assessed whether the girls had been exposed to paracetamol during pregnancy and then examined their reproductive development during infancy. A separate group of 1,210 girls was also followed from infancy into adolescence to look for similar patterns.
The findings showed that girls exposed to paracetamol in the womb had, on average, smaller ovaries and uteruses and fewer ovarian follicles compared with girls who had not been exposed.
Researchers were particularly interested in the ovaries because they contain ovarian follicles, the structures that contain immature eggs.
A woman is born with the majority of the eggs she will have during her lifetime. The development and preservation of those follicles are therefore important parts of reproductive health.
In the Danish study, girls whose exposure began during early pregnancy, before 17 weeks, had an ovarian volume that was approximately 40% smaller on average than that of unexposed girls after adjustment for relevant factors.
Girls exposed during the middle or later stages of pregnancy had approximately 23% fewer ovarian follicles on average.
Researchers also observed lower levels of anti-Müllerian hormone, or AMH, among girls who had been exposed exclusively during early fetal development. AMH is commonly used as one indicator of ovarian reserve, although it should not be interpreted as a direct measure of an individual’s future fertility.
The findings extended beyond the ovaries.
The researchers also found smaller uterine volumes among girls exposed during early pregnancy. In the separate group followed into later childhood and adolescence, prenatal exposure was associated with smaller uteruses around puberty and smaller ovaries during adolescence.
These observations are what have prompted researchers to call for longer-term studies.
The major unanswered question is whether the differences observed in infancy and adolescence will have consequences when the girls reach adulthood.
It is possible that the differences could have little or no effect on their ability to conceive.
It is also possible that some of the observed changes could eventually be associated with reproductive problems.
At this stage, scientists simply do not know.
Study leader Margit Bistrup Fischer of Rigshospitalet in Copenhagen has stressed that women who took paracetamol during pregnancy should not be alarmed by the findings. The researchers say the study cannot determine whether the medicine itself caused the changes observed in the girls.
That distinction is particularly important because the study was observational.
In an observational study, researchers examine patterns in real-world data rather than randomly assigning participants to take a medicine or a placebo.
This means that researchers can identify associations but cannot establish with certainty that one factor caused another.
For example, women who take paracetamol during pregnancy may do so because they have pain, fever, headaches or another illness.
Those underlying conditions could themselves influence pregnancy or fetal development.
Researchers attempted to account for some of these factors, including maternal fever and other characteristics, and the associations remained. However, they acknowledged that residual confounding cannot be completely excluded.
This is one reason the researchers are calling for further studies rather than recommending that pregnant women immediately stop using paracetamol.
The study also has several strengths.
The Danish researchers did not rely entirely on mothers remembering whether they had taken the medicine.
Pregnant women in the main study reported their paracetamol use every two weeks, while researchers also analysed urine samples for evidence of paracetamol exposure.
This provided researchers with both reported medication use and biological measurements of exposure.
The study involved women recruited during the first trimester and followed their children after birth. The researchers then compared girls exposed at different stages of pregnancy with girls whose mothers reported no exposure.
The researchers also found indications of a dose-response relationship.
Higher reported maternal paracetamol exposure and higher urinary paracetamol concentrations were associated with lower ovarian and uterine volumes.
Such patterns can strengthen the case for further investigation, although they still do not prove that paracetamol was responsible for the differences.
The study is particularly significant because previous evidence has largely come from animal research.
Animal studies have suggested that exposure to paracetamol during fetal development may interfere with the formation of ovarian follicles and could potentially affect reproductive function later in life.
The new Danish research is among the first human studies specifically designed to examine whether prenatal exposure is associated with markers of ovarian development in girls.
The researchers say the human findings broadly resemble observations from animal studies.
That consistency has increased interest in the results.
But researchers and medical experts are also urging caution.
A biological difference observed in an infant does not automatically translate into a disease or reproductive problem decades later.
The reproductive system changes substantially during childhood, puberty and adulthood.
A girl with a smaller ovarian volume as an infant could still experience normal puberty, normal ovulation and normal fertility later in life.
The study itself acknowledges that long-term clinical implications remain uncertain and that the girls need to be followed for much longer.
Researchers say future studies should ideally continue following exposed children through adulthood and potentially into menopause.
Only long-term follow-up could help determine whether the differences observed early in life are associated with outcomes such as time to pregnancy, fertility treatment, ovarian reserve, age at menopause or other reproductive health measures.
This is why the headline that paracetamol “may affect fertility” needs to be understood carefully.
The research found changes in markers related to reproductive development.
It did not follow the girls long enough to determine whether they eventually became infertile.
There is currently no evidence from this study showing that a woman who takes paracetamol during pregnancy will have a daughter who cannot have children.
The distinction is important for pregnant women who may read alarming headlines and become frightened.
Paracetamol remains widely recommended for treating pain and fever during pregnancy when medically necessary and used according to appropriate guidance.
Reuters reported that current guidelines continue to recommend paracetamol or acetaminophen for pain and fever during pregnancy, noting that untreated severe pain or high fever can themselves present risks to a pregnant woman and fetus.
This creates an important medical balance.
Pregnancy does not mean that women should simply endure severe pain or high fever because they are worried about medicines.
Pain and fever can sometimes require treatment.
The appropriate approach is to consider why the medicine is being taken, how much is being taken and for how long.
Pregnant women should therefore discuss regular or prolonged medicine use with their healthcare providers instead of making medication decisions based solely on social media posts or headlines.
Another important point is that the study involved relatively low levels of exposure.
According to Reuters, none of the women in the main study exceeded the recommended maximum daily dose of 4,000 milligrams, and most used the medicine for headaches or musculoskeletal pain.
This makes the findings particularly interesting to researchers because the observed differences were found even without the participants taking unusually high amounts.
At the same time, the study was not designed to determine whether there is a specific “safe” amount of paracetamol during pregnancy that carries no reproductive-development risk.
It also could not establish whether the timing, frequency or duration of use was responsible for the observed differences.
The researchers noted that their analysis could not fully determine how different patterns of use might influence the outcomes.
For the wider public, the study is another reminder that medicines that are considered generally safe can still require careful consideration during pregnancy.
Pregnancy is a period of rapid development in which the fetus is exposed to substances that cross the placenta.
Paracetamol can cross the placenta, which is one reason researchers have been interested in understanding whether exposure during fetal development could have effects that only become apparent much later in life.
The female reproductive system is established to a significant extent before birth.
That means events during fetal development can potentially influence reproductive biology decades later.
However, establishing such a connection in humans is extremely difficult.
Scientists need to separate the effect of a medicine from numerous other factors that influence reproductive development.
These include genetics, maternal health, nutrition, infections, environmental exposures, smoking, alcohol use, body weight, socioeconomic circumstances and other medications.
This is why a single study should not be interpreted as the final word on paracetamol and pregnancy.
The new research is better understood as an important signal that deserves further investigation.
The findings could also encourage researchers to look more closely at how common medicines affect fetal development beyond the immediate outcomes normally considered after birth.
Most medication safety research during pregnancy focuses on obvious outcomes such as birth defects, miscarriage, premature birth or low birth weight.
But some effects may not become visible until many years later.
Reproductive development is one such area.
A baby may appear completely healthy at birth while subtle changes in organ development could potentially influence health later in life.
That possibility makes long-term follow-up particularly important.
The Danish researchers are therefore calling for additional studies that follow girls exposed to paracetamol during pregnancy for many years.
Such research could eventually answer questions that the current study cannot.
Do exposed girls have the same fertility rates as unexposed girls?
Do they enter puberty at the same age?
Do they have similar ovarian reserve levels in adulthood?
Is there any difference in the age at which menopause occurs?
Do they have different rates of fertility treatment?
These questions remain unanswered.
Until those answers are available, it would be premature to tell pregnant women that paracetamol will damage the future fertility of their daughters.
It would be equally premature to dismiss the study completely.
The findings are scientifically significant because they identify measurable differences in reproductive development and are broadly consistent with previous animal research.
The appropriate response is therefore continued research and careful medical guidance rather than panic.
For women who have already taken paracetamol during pregnancy, the researchers’ message is particularly important.
There is no reason from this study alone to assume that their daughters will experience fertility problems.
Many women in the study who used paracetamol had daughters whose ovarian measurements were similar to those of girls whose mothers did not use the medicine.
That individual variation is another reason why population-level findings should not be converted into predictions about a particular child.
A statistical association does not determine an individual’s future.
The findings also do not mean that every pregnant woman should stop taking paracetamol without medical advice.
Stopping an appropriate treatment can sometimes create a different health risk.
For example, a serious fever may require treatment, and leaving significant pain untreated may also have consequences.
The safest approach is for pregnant women to seek professional advice about the cause of their symptoms and the most appropriate treatment.
The study’s publication is nevertheless likely to trigger renewed discussion among doctors, researchers and regulators about how commonly used medicines should be assessed during pregnancy.
If future studies confirm the findings, medical guidelines could eventually change.
But that would require evidence from larger populations and, most importantly, long-term follow-up demonstrating whether the early reproductive differences have meaningful consequences.
For now, the Danish study provides a new piece of evidence in a complicated scientific debate.
It suggests that fetal exposure to paracetamol may be associated with measurable differences in the development of girls’ reproductive systems.
It does not establish that the medicine causes infertility.
It does not show that exposed girls will struggle to have children.
And it does not overturn current medical guidance on the appropriate treatment of pain and fever during pregnancy.
Instead, it raises a question that scientists will need years to answer.
Could a medicine taken by a mother during pregnancy have subtle effects on her daughter’s reproductive health decades later?
The new findings suggest that the question deserves serious investigation.
As researchers continue to follow the girls and study larger groups, the medical community will have a better opportunity to determine whether the observed differences are temporary developmental variations or signs of a long-term reproductive effect.
Until then, pregnant women should avoid unnecessary self-medication, follow recommended doses and speak with qualified healthcare professionals when they need treatment.
The most important message from the study is therefore not that pregnant women should be afraid of paracetamol.
It is that pregnancy medication decisions should be made carefully, based on the balance between the benefits of treating a mother’s illness and the potential risks of exposing the developing fetus.
The new research adds an important question to that conversation, but it does not yet provide a definitive answer.
For now, the possibility that prenatal paracetamol exposure could influence the future reproductive development of baby girls remains a subject for further scientific investigation rather than an established medical fact.
