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Twin anemia polycythemia sequence and the risk of iron deficiency in donors and iron overload in recipients

Journal of Perinatology (2025)Cite this article

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Twin anemia polycythemia sequence (TAPS) is a rare condition that occurs in 3–5% of monochorionic twins, caused by inter-twin blood transfusion through tiny placental anastomoses, resulting in anemia in the donor and polycythemia in the recipient twin [1]. The optimal antenatal management remains unclear and includes intrauterine transfusions and fetoscopic laser surgery of the anastomoses. Donor twins have a four-fold increased risk of neurodevelopmental impairment (NDI) compared to recipients, with a 44% risk of motor and/or cognitive delay and a 15% risk of bilateral deafness [1]. The cause of this discrepancy between donors and recipient is unknown but is possibly associated with chronic fetal anemia, fetal growth restriction, and hypoalbuminemia. Since the introduction of ferritin level measurements in TAPS in our institution, significant disparities in iron status between donor and recipient twins have been observed, with donors often affected by iron deficiency (ID). However, data on the iron status and clinical relevance in twins with spontaneous TAPS remain limited. Therefore, we evaluated iron status at birth in donor and recipient twins with spontaneous TAPS.

The institutional review board stated that this retrospective study did not apply to the Medical Research Involving Human Subjects Act and informed consent was deemed unnecessary (reference number 25-3006). This retrospective cohort study included all monochorionic twin pregnancies delivered at our institution between December 2022 and March 2025 that met the established antenatal and postnatal criteria for spontaneous TAPS, with complete neonatal iron status data available at birth. We evaluated ferritin levels at birth in twins with spontaneous TAPS born at our institution. Since December 2022, ferritin measurements within 48 h after birth have been part of our routine clinical assessment in TAPS survivors, along with hemoglobin levels, reticulocyte counts and albumin levels. TAPS was diagnosed based established criteria [1]. ID was defined as ferritin levels <76 µg/L and hyperferritinemia as >400 µg/L [2,3,4]. Clinical data included gestational age at birth, birthweight, intrauterine transfusion (IUT), automated auditory brainstem response (AABR) results, and cerebral ultrasound findings. Cord clamping times were recorded at delivery. We excluded spontaneous TAPS cases treated with fetoscopic laser surgery. Ferritin levels between donors and recipients were compared using the Mann–Whitney U test.

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Fig. 1: Ferritin levels in donors and recipients by twin pair.

Data availability

Data available on request from the authors.

References

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Acknowledgements

We acknowledge the Neonatal and Fetal Therapy Research Group at Leiden University Medical Center for their valuable contribution.

Funding

Funding was received from the European Society for Paediatric Research (ESPR), Leids Universitair Fonds (LUF) and, Gratama Stichting (2023-10/W233029-2 GSL), StrongBabies (SB-JO-2023-15), Honors College Leids Universitair Medisch Centrum (240426), Janivo Stichting, Gisela Thier Fonds, Raynor Foundation, and Vaillant Stichting.

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Authors and Affiliations

  1. Willem-Alexander Children’s Hospital, Department of Pediatrics, Division of Neonatology, Leiden University Medical Center, Leiden, the Netherlands

    Mathies Rondagh, Sylke J. Steggerda, Jeanine M. M. van Klink, Linda S. de Vries, Sophie G. Groene & Enrico Lopriore

  2. Department of Gynecology, Division of Fetal Therapy, Leiden University Medical Center, Leiden, The Netherlands

    Margot J. A. van de Sande, Lisanne S. A. Tollenaar & Femke Slaghekke

Authors
  1. Mathies Rondagh
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  2. Margot J. A. van de Sande
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  3. Lisanne S. A. Tollenaar
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  4. Sylke J. Steggerda
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  5. Jeanine M. M. van Klink
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  6. Linda S. de Vries
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  7. Femke Slaghekke
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  8. Sophie G. Groene
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  9. Enrico Lopriore
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Contributions

Mathies Rondagh and Dr Enrico Lopriore conceptualized and designed the study, drafted the initial manuscript, critically reviewed and revised the manuscript, and conducted the statistical analysis. Margot van de Sande, Dr. Lisanne Tollenaar, Dr. Sylke Steggerda, Dr. Jeanine van Klink, Dr. Linda de Vries, Dr. Femke Slaghekke, Dr. Sophie Groene, and Dr. Enrico Lopriore contributed to the acquisition, analysis, and interpretation of the data, and critically reviewed and revised the manuscript. Mathies Rondagh, Dr. Sophie Groene, Dr. Sylke Steggerda, and Dr. Enrico Lopriore obtained funding for the study. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

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Correspondence to Mathies Rondagh.

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The authors declare no competing interests.

Ethical approval

The non-WMO Committee stated that this retrospective study did not apply to the Medical Research Involving Human Subjects Act and informed consent was deemed unnecessary (reference number 25-3006).

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Rondagh, M., van de Sande, M.J.A., Tollenaar, L.S.A. et al. Twin anemia polycythemia sequence and the risk of iron deficiency in donors and iron overload in recipients. J Perinatol (2025). https://doi.org/10.1038/s41372-025-02386-y

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