The significance of the study lies partly in the sheer ubiquity of the exposure. Fungal infections are among the most frequent ailments in pregnancy, driven by hormonal and immunological changes that alter the body’s microbial balance. They are typically treated with azole antifungals, a broad family of compounds that includes both prescription drugs and, crucially, over-the-counter topical products such as creams and vaginal tablets. As Gylli Mola, a researcher and medical doctor at Rigshospitalet, points out, this is what makes the result particularly noteworthy: the treatments in question were primarily non-prescription topical preparations, which have traditionally been regarded as safe to use during pregnancy. If even these low-intensity, locally applied formulations are associated with hormonal signals in offspring, the assumption of safety may need to be re-examined with more rigorous data than currently exists.

The study rested on an unusually broad evidentiary base. The researchers analysed data from 589 Danish mother–child pairs, drawing on Denmark’s rich national registers and biobanks to compare children whose mothers had used azole antifungals during pregnancy with those who had not. Crucially, the epidemiological signal did not stand alone. The team supplemented the population data with laboratory experiments using human fetal adrenal tissue, allowing them to observe directly how azole compounds interact with the steroid-producing machinery of the gland. They also carried out studies in pregnant rats, examining both blood and adrenal tissue from the fetuses to see whether the same hormonal disruptions appeared in a controlled experimental setting. According to Monica Kam Draskau, a researcher at the DTU National Food Institute who worked on the experimental analyses, the fact that the findings in children are supported by results from both human fetal adrenal tissue and rat experiments strengthens the hypothesis that there is a genuine link with the use of azole-based antifungal medicines.

To understand why the adrenal gland matters here, it helps to consider what azoles actually do. Azole antifungals work by inhibiting enzymes in the cytochrome P450 family that fungi need to build ergosterol, an essential component of their cell membranes. The trouble is that humans rely on closely related P450 enzymes to manufacture steroid hormones, including the cortisol and other adrenal steroids that the fetus begins producing as its adrenal gland develops. A compound designed to block fungal steroid synthesis can, in principle, also interfere with human steroidogenesis, and the fetal adrenal gland is an extraordinarily active steroid-producing organ during gestation. The new findings are consistent with that mechanism: prenatal exposure to azoles appears to disrupt fetal steroidogenesis, and the disruption seems to leave traces that persist at least into early infancy.

Adrenal hormones are far from peripheral players in human physiology. They help regulate many functions in the body, including glucose metabolism, blood pressure, immune function, and growth and reproductive development. The adrenal gland also undergoes a remarkable transformation around the time of birth, known as the zona reticularis transition, when the fetal zones of the gland regress and adult-type steroid production takes over. Hormonal disturbances during this window could, in theory, ripple across multiple organ systems as a child grows. That is precisely why the Danish team is cautious but concerned: the hormone levels they measured at three months of age were still within the normal range, yet the pattern of change suggests that fetal development may have been affected in ways that standard clinical thresholds do not capture.

Professor Terje Svingen from the DTU National Food Institute, who led the work, described the persistence of the signal as striking. It is one thing, he noted, for a medicine to produce a transient hormonal blip that resolves within days; it is quite another for the use of azole-based antifungals during pregnancy to appear to affect adrenal hormone levels in children long after birth. The three-month timepoint means the differences survived the profound hormonal upheaval of delivery and the establishment of infant adrenal function. Svingen’s framing captures the careful middle ground the study occupies: the results suggest that fetal development may have been affected, but they stop well short of demonstrating harm, and the researchers are explicit that they do not know whether the differences will affect the children’s health or their ability to have children later in life.

That caution is scientifically essential. The study is observational in its human component, and it cannot directly establish that azole-based antifungal medicines cause the hormonal changes observed in children. Mothers who used antifungals may differ in other ways from those who did not, from infection severity to other medication use, and no observational design can fully exclude such confounding. Nor can the researchers conclude from this study that commonly used antifungal medicines are harmful to children. What the results do is raise a hypothesis, supported by converging lines of evidence, that now needs to be tested with dedicated studies. The authors argue that the safety of widely used antifungals during pregnancy warrants further investigation, and the triangulation of human data, human tissue experiments and animal studies gives that argument unusual weight for a finding of this kind.

The research was carried out as part of the MERLON research project and was funded by the Danish Environmental Protection Agency through the Danish Centre on Endocrine Disrupters, with additional support from the Rigshospitalet Research Council. IRSET in France was a partner in the study. That funding provenance is telling: endocrine disruption, the interference of chemicals with the body’s hormone systems, has become a major focus of European regulatory science, and medicines are increasingly scrutinised alongside industrial chemicals for their potential to perturb hormonal development. The authors declare no conflicts of interest, and the study appeared under the title ‘Prenatal antifungal exposure disrupts fetal steroidogenesis and is associated with persistent effects in 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; the measured hormone levels in the study remained within normal limits. The researchers themselves stress that they cannot conclude the medicines are harmful. The appropriate response, they suggest, is not for women to avoid needed treatment but for regulators, clinicians and researchers to generate the data needed to confirm or refute the signal. Larger cohorts, longer follow-up of exposed children, and mechanistic work clarifying which azoles, doses and exposure windows matter most would all help determine whether the hormonal differences observed at three months of age are a transient footprint or a marker of lasting developmental change.

The study also speaks to a broader lesson in pharmacology and public health: 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 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 Danish findings do not overturn clinical practice, but they add an important data point to the ongoing effort to make medication use in pregnancy evidence-based rather than assumption-based. Until that evidence matures, the study stands as a carefully hedged but consequential reminder that even the most routine treatments of pregnancy deserve continued scientific scrutiny.

Subject of Research: Effects of prenatal azole antifungal exposure on fetal steroidogenesis and infant adrenal hormone levels

Article Title: New study raises questions about antifungal treatments during pregnancy

Article References: New study raises questions about antifungal treatments during pregnancy. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: azole antifungals, pregnancy, fetal development, adrenal hormones, steroidogenesis, endocrine disruption, Communications Medicine, DTU National Food Institute, Rigshospitalet, over-the-counter medicines, child health, pharmacovigilance