Reacción a "Researchers are investigating the link between paracetamol use during pregnancy and possible abnormalities in the reproductive development of baby girls"

This study has several notable weaknesses.

Even at face value, the statistical evidence that paracetamol usage is linked to fetal outcomes is weak. The headline result - that paracetamol usage is linked to reduced ovarian volume - only just achieves the minimal conventional threshold to be declared as a scientific finding. As part of this analysis, the authors considered 11 other outcomes - only one other outcome achieved the same threshold. The scientists appear to have tested a lot of different hypotheses, and focus their presentation on the small number of findings that show associations - this is selective reporting. The associations are all based on small sample sizes, and so there is a considerable risk that these are chance findings. There is also a substantial amount of missing data - only two-thirds of girls in this study had measurements of ovarian volume.

Mothers who took paracetamol during pregnancy are likely to differ substantially from those that did not – this is known as confounding. Confounding makes it difficult to know whether differences between outcomes are attributable to paracetamol itself or to other characteristics of the mothers or their pregnancies.

Even if these differences are statistically robust and even if they are attributable to paracetamol, this study cannot establish paracetamol as a cause. It may be that these findings are driven by infection or fever - women take paracetamol due to mild sickness, and this sickness is the cause of differences in early-life ovarian volume. It may be that impaired fetal development and its causes are what lead to increased paracetamol usage, not that increased paracetamol usage leads to impaired fetal development.

Finally, it is not clear whether the relatively small differences in ovarian volume, follicle number, and hormone levels observed in infancy have any meaningful clinical consequences. It is also not clear whether they are sustained into adulthood, or whether they have any effect on fertility or reproductive lifespan.

Paracetamol has been taken for over 100 years, and so the burden of proof that it is harmful should be high. It is one of the only pain-relieving medications that can be taken during pregnancy. Even if there are negative consequences of taking paracetamol during pregnancy (which this study only provides weak evidence to support), there are also likely future negative consequences attributable to taking away one of the only remaining available and widely-tolerated medications from pregnant women.

This is a small study which performed many different analyses, the majority of which did not show associations with paracetamol usage. If you perform many analyses, you will observe some associations solely due to chance alone. But even if we accept the associations as meaningful, they fall short of showing that paracetamol has a harmful effect: paracetamol usage may be an indicator of impaired fetal development, rather than its cause.