A small study suggests taking paracetamol in the first 4 months of pregnancy could be linked to smaller ovaries and wombs in three-month-old babies.
Baby girls exposed to paracetamol later in pregnancy tended to have fewer follicles (where immature eggs are stored) in their ovaries, the study found.
The authors say the study can’t prove paracetamol causes the differences, or whether they have any long-term effects.
The SMC asked NZ experts to comment.
Professor Beverley (Bev) Lawton, Director of the Centre for Women’s Health Research – Te Tātai Hauora o Hine, Faculty of Health, Victoria University of Wellington, comments:
“Unfortunately it’s very hard to make overall statements from these cohort studies. The evidence is not strong that paracetamol has a lasting affect on the baby. The worry is the reason for taking the paracetamol – fever can be causing the harm and we know fever is not good for the baby.
“The advice is to only take medications in pregnancy if you need to. Not treating the fever is potentially harmful for the pregnancy – ask a doctor or midwife for advice.”
Conflict of interest statement: “None to declare.”
Associate Professor Gergely Toldi, Liggins Insitute, University of Auckland and consultant neonatologist, Starship Children’s Health, comments:
“This thorough, well-designed study, conducted in Denmark, reinforces the importance of minimising paracetamol intake during pregnancy, particularly before 17 weeks of gestation, suggesting that paracetamol might have previously less appreciated negative effects on the developing reproductive organs of female fetuses. Whether this also translates to a reproductive disadvantage or reduced fertility in exposed infants is yet to be determined in future studies. However, the findings will likely prompt a more cautious use of paracetamol during pregnancy than before.
“This further limits potential pain medication options during pregnancy, shifting the emphasis to non-pharmaceutical pain management, such as massage, warm or cool compresses, healthy diet and adequate hydration. Please consult your doctor or midwife for the best medication options available to you should your symptoms not improve with these measures.”
Conflict of interest statement: “None.”
Professor Andrew Shelling, Department of Obstetrics, Gynaecology and Reproductive Sciences, The University of Auckland, comments:
“There are previous animal studies that provide some support for the associations reported in this epidemiological study. The research appears to have been conducted rigorously by an experienced group with expertise in this field and has been published in a reputable, peer-reviewed journal.
“However, this single study should not be regarded as definitive evidence of an association. Rather, it highlights the need for further research to investigate these findings and determine whether they can be replicated in other populations and settings.
“The study also underscores the value of longitudinal human research, which can provide a depth of information that is difficult to achieve through retrospective studies. The biological changes observed appear to be meaningful and may have implications for female reproductive health later in life.
“At the same time, it is important to consider these findings in a broader context. Although fertility rates have declined over recent decades, the average age of menopause has not changed substantially, and paracetamol has been widely used for many decades.
“As a result, this publication is likely to generate considerable public concern and anxiety. It will therefore be important to emphasise that this is an early study and that much more research is needed. In particular, our understanding of the mechanisms by which paracetamol might influence reproductive biology and function remains limited.”
Conflict of interest statement: “There is no conflict of interest, I’m an academic with interest in the area, and nearly 30 years of research into understanding of ovarian function and the age of menopause.”
Dr Lakshmi Ravikanti, President of the New Zealand Gynaecology Society, comments:
“The study reports associations between prenatal paracetamol exposure and a number of surrogate markers of ovarian and uterine development in infancy. Some of the reported differences reach statistical significance, but the absolute effect sizes are very small, the outcomes are indirect measures rather than clinical endpoints, and the study remains observational, leaving considerable scope for residual confounding.
“One example is the reported reduction in uterine volume of 0.16 cm³ in exposed infant girls. While statistically significant, this is an extremely small anatomical difference in an organ that is already challenging to visualize and measure accurately in infancy using ultrasound. Even if the finding is entirely real, it is difficult to see how a difference of this magnitude could be confidently linked to any future reproductive impairment. The distinction between statistical significance and clinical significance is important here.
“Most importantly, there is currently no evidence that paracetamol exposure in pregnancy impairs the future fertility of female offspring. The study did not assess fertility, fecundity, time to pregnancy, IVF outcomes, age at menopause, or any other clinically meaningful reproductive endpoint. Instead, it identifies associations with infant and adolescent anatomical and hormonal measurements whose long-term significance remains uncertain.
“While the authors reference supporting animal data, translating subtle differences in ovarian volume, follicle counts or uterine dimensions in infancy into predictions about adult reproductive capability is a substantial leap. At present, that link remains hypothetical.
“I think there is a real risk that studies such as this generate unnecessary anxiety among pregnant women. Paracetamol remains one of the most widely used medications in pregnancy, and many women reading headlines about this work may conclude that taking paracetamol could compromise their daughter’s fertility. That is simply not a conclusion supported by the available evidence.
“For me, this is an interesting hypothesis-generating study that warrants further investigation and long-term follow-up. It is not a practice-changing paper, nor does it provide evidence that occasional or clinically indicated paracetamol use during pregnancy causes infertility in female offspring.”
Conflict of interest statement: Dr Ravikanti is a fertility consultant and shareholder at Fertility Associates.