How Dupilumab's Molecular Structure Influences Placental Transfer
Dupixent, the brand name for dupilumab, is a type of medication known as a biologic. Unlike small-molecule drugs that can often cross the placenta easily by passive diffusion, dupilumab is a much larger molecule—a fully human monoclonal antibody of the immunoglobulin G (IgG)4 subclass. Because of its large size (approximately 147 kilodaltons), it does not cross the placenta through simple diffusion in the same way smaller drugs do. Instead, IgG antibodies are actively and specifically transported across the placenta via a specialized receptor, the neonatal Fc receptor (FcRn). This process is part of the normal transfer of maternal immunity to the fetus.
The Timing and Extent of Fetal Exposure
For large-molecule antibodies like Dupixent, the amount of drug that crosses the placenta is not uniform throughout pregnancy. The transfer is minimal during the first trimester, when the fetus is undergoing critical organogenesis. However, the efficiency of the FcRn-mediated transport mechanism increases significantly during the second and third trimesters, meaning fetal exposure to Dupixent is highest during the later stages of pregnancy. The thickness of the placental barrier also changes over gestation, becoming thinner later in pregnancy, which further increases its permeability.
Current Clinical Safety Data and Pregnancy Registry
Because of the potential for fetal exposure, the safety of Dupixent during pregnancy is a critical topic. Due to ethical limitations, large-scale, controlled trials on pregnant women are not available. However, data from other sources provide valuable insight:
- Case Reports and Series: Multiple case reports and small case series of pregnant women exposed to dupilumab, often for atopic dermatitis, have been published. These generally report favorable maternal and fetal outcomes with no major adverse events.
- Systematic Reviews and Meta-analyses: Recent reviews analyzing published data on pregnant women exposed to dupilumab have found reassuring evidence. One meta-analysis found no significant increase in the risk of miscarriage or congenital malformations compared to the general population, though it noted the inconclusive nature of the results due to the limited number of large studies.
- Pregnancy Exposure Registry: A registry is available to monitor pregnancy outcomes in women exposed to Dupixent. Healthcare providers are encouraged to enroll patients, and pregnant women can also register themselves. This helps gather more data on pregnancy outcomes over time.
- Retrospective Studies: A large propensity-matched retrospective cohort study presented in 2024 found no increased risk of adverse pregnancy outcomes with dupilumab use and even suggested a reduced risk of preterm labor, though further research is needed.
The Importance of Controlling the Underlying Disease
While there is potential for fetal exposure, it is crucial to recognize that uncontrolled, severe inflammatory conditions can pose a significant risk to both the mother and the fetus. For example, poorly controlled asthma during pregnancy is associated with risks such as preeclampsia, prematurity, and low birth weight. For many patients, Dupixent provides the best control over their disease. The decision to continue Dupixent during pregnancy must therefore weigh the potential risk of fetal exposure against the documented risks of an uncontrolled disease flare.
Navigating the Discussion with Your Healthcare Provider
Making a decision about continuing Dupixent during pregnancy requires a careful and individualized assessment with your medical team. This conversation should involve both your specialist (e.g., dermatologist, allergist) and your obstetrician.
Comparison of Placental Drug Transfer: Dupixent vs. Small-Molecule Drug
| Feature | Dupixent (dupilumab) | Typical Small-Molecule Drug |
|---|---|---|
| Molecular Weight | High (~147 kDa) | Low (<500 Da) |
| Transfer Mechanism | Active transport via FcRn receptor | Passive diffusion |
| Transfer Timing | Primarily during 2nd and 3rd trimesters | Throughout all trimesters, if transferred |
| Likelihood of Transfer | Expected to cross the placenta | Readily crosses the placenta |
| Potential for Ion Trapping | Negligible (large, non-ionizable protein) | Possible for certain weakly basic drugs in acidic fetal circulation |
| Current Safety Evidence | Generally reassuring, based on limited data | Variable depending on the specific drug |
Conclusion
Based on current knowledge, Dupixent (dupilumab) is an immunoglobulin G (IgG) antibody that is expected to cross the placental barrier, with the highest concentration of fetal exposure occurring in the later stages of pregnancy. The available data from case reports and observational studies have been generally reassuring, suggesting no increased risk of major birth defects or adverse fetal outcomes. However, large-scale prospective studies are still limited, and the full long-term effects of exposure are not yet fully understood. The decision to continue Dupixent during pregnancy should be a shared and informed one between the patient and their healthcare providers, carefully weighing the documented risks of an untreated, severe underlying condition against the potential for fetal exposure. Enrollment in the Dupixent pregnancy exposure registry can contribute valuable data for future research.
