Are Twins Getting Enough Anti-D? New Study Reveals Differences in Antibody Persistence

Anti-D immunoglobulin remains the cornerstone of prevention for RhD alloimmunization and hemolytic disease of the fetus and newborn. However, most safety data comes from singleton pregnancies. A new study published in BMC Pregnancy and Childbirth explores whether anti-D antibodies persist as well in twin pregnancies compared to singletons—raising important questions for clinicians caring for RhD-negative mothers with multiples.

The Problem: Is Standard Anti-D Enough for Twins?

RhD-negative women who carry an RhD-positive fetus receive anti-D immunoglobulin to prevent their immune system from attacking fetal red blood cells. Standard practice is a single antenatal dose at 28 weeks. But does this “one size fits all” approach work equally well in twin pregnancies, where blood volume and fetal load are higher?

Study Design: Comparing Antibody Detectability

Researchers retrospectively reviewed 71 twin and 177 matched singleton pregnancies, all RhD-negative and given routine anti-D at 28 weeks. They checked for detectable anti-D antibodies at delivery using the indirect Coombs test—a laboratory marker for passively acquired anti-D. None of the women had developed their own anti-D (alloimmunization) prior to delivery.

Key Results: Twins Had Lower Anti-D at Delivery

Only 29.6% of twins had detectable anti-D antibodies at delivery, compared with 43.5% of singletons.

This difference was statistically significant (p=0.043), even after adjusting for age, BMI, and timing between anti-D administration and delivery.

The vast majority of both groups received only one standard dose, with no adjustment for fetal number.

What Does This Mean for Practice?

Importantly, having no detectable anti-D at delivery does not necessarily mean prophylaxis failed or that the patient is at risk for alloimmunization—this study looked only at laboratory persistence, not clinical outcomes. Still, the findings point to potential pharmacokinetic differences in twins, likely due to larger blood volume, greater placental transfer, or distribution to two fetuses. This could mean twins “use up” anti-D faster, leaving less detectable at delivery.

Human Impact: Why It Matters

For clinicians, these results serve as a reminder to remain vigilant in managing RhD-negative twin pregnancies. While current guidelines do not recommend a higher anti-D dose for twins, more research is needed to determine if practice should change. For now, the standard approach remains reasonable, but future studies should look at whether twin pregnancies might benefit from altered dosing or closer monitoring.

Conclusion

This study highlights a gap in evidence for anti-D prophylaxis in twin pregnancies and calls for prospective research. For now, clinicians should be aware of the possible difference in antibody persistence and continue to follow best practices for postpartum and targeted prophylaxis.

Key Takeaways:

Twin pregnancies are less likely to have detectable anti-D antibodies at delivery compared to singletons after standard prophylaxis.

The clinical effectiveness of anti-D in twins remains uncertain—this study looked only at lab results, not outcomes.

Standard anti-D dosing does not currently adjust for twins, but more research is needed.

Antibody persistence may be affected by higher blood volume and placental transfer in twins.

Clinicians should remain vigilant but do not need to change practice based on this study alone.

Citation:

Ünlü C, Aksoy H. Persistence of antenatal anti-D immunoglobulin G at delivery in twin versus singleton pregnancies: a retrospective cohort study. BMC Pregnancy and Childbirth. 2026; [Epub ahead of print]. doi:10.1186/s12884-026-09530-2