Prenatal Antifungal Use Linked to Altered Infant Hormone Levels

A new study links maternal use of common antifungal medicines during pregnancy to altered adrenal hormone levels in children at three months of age. The research, involving 589 Danish mother-child pairs, found that prenatal exposure to azole-based antifungals was associated with persistent changes in infant hormone profiles.

While all measured hormone levels remained within the normal clinical range, the findings raise questions about potential long-term effects. The antifungal treatments examined were primarily over-the-counter topical preparations, such as creams and vaginal tablets. Researchers cannot yet say whether the observed differences have consequences for future health or fertility.

How the research was conducted across human and animal models

The investigation combined human mother-child data, fetal adrenal tissue experiments, and rat studies to examine the impact of antifungal exposure on steroidogenesis. Scientists from the Technical University of Denmark’s National Food Institute and Copenhagen University Hospital led the work.

The study used data from Denmark’s national registers and biobanks. Laboratory experiments used human fetal adrenal tissue, and separate studies examined blood and adrenal tissue from rat fetuses. The research was carried out as part of the MERLON project.

Azole antifungals work by inhibiting enzymes in the cytochrome P450 family. Humans rely on closely related P450 enzymes to manufacture steroid hormones, including cortisol. The fetal adrenal gland is an extraordinarily active steroid-producing organ during gestation. The three-month timepoint in infants means the differences survived the hormonal upheaval of birth and the establishment of infant adrenal function. The human component of the study is observational and cannot establish causation.

What the findings mean for maternal and child health

Adrenal hormones help regulate glucose metabolism, blood pressure, immune function, growth, and reproductive development. The researchers do not yet know whether the hormonal differences will affect children's health or future fertility. They stress that the study cannot establish that azole-based antifungals cause the hormonal changes, nor can it conclude that commonly used antifungal medicines are harmful to children.

For pregnant women, the immediate practical message is one of reassurance rather than alarm. Untreated fungal infections carry their own risks, and no current evidence indicates that a course of azole treatment harms a child. Pregnancy is a period of exquisite hormonal sensitivity, and the fetal adrenal gland is one of the most hormonally active tissues in the body. The study adds an important data point to making medication use in pregnancy evidence-based rather than assumption-based.

Researchers call for more data to clarify long-term risks

The researchers believe the safety of widely used antifungals during pregnancy warrants further investigation. They argue that medicines assumed to be safe because they are old, familiar, and available without prescription are not automatically free of subtle developmental effects. Topical preparations deliver lower systemic doses than oral drugs, but the fetal system is highly sensitive.

The appropriate response, according to the study authors, is for regulators, clinicians, and researchers to generate data to confirm or refute the signal. Larger cohorts, longer follow-up, and mechanistic work are needed to determine if hormonal differences are transient or lasting. Funding for the study came from the Danish Environmental Protection Agency through the Danish Centre on Endocrine Disrupters, with additional support from the Rigshospitalet Research Council and partnership with IRSET in France.

The study shows the need for more data through larger cohorts, longer follow-up, and mechanistic studies to confirm or refute the potential developmental effects of prenatal antifungal exposure.