Ultrasound capabilities in diagnosis and control of invasive interventions in the treatment of severe fetal anemia as a complication of 5-th stage twing-to-twing transfusion syndrome

Twin-to-twin transfusion syndrome (TTTS) Stage V is a severe complication of monochorionic multiple pregnancy associated with a high risk of severe anemia in the surviving co-twing, cerebral hemorrhage or ischemic stroke and fast intrauterine fetal death of this co-twin.

A 27-year-old pregnant patient D., admitted with the diagnosis: second pregnancy, 21 weeks 1 day, TTTS Stage V (intrauterine death of the hydropic donor twin), underwent ultrasound evaluation of the surviving fetus, which demonstrated signs of severe anemia (peak systolic velocity in the middle cerebral artery [MCA-PSV] 1.77 MoM), hydrops, and absent end-diastolic flow in the umbilical artery). The first step was amnioreduction of 2500 ml, followed by fetal transfusion of 20 ml.. Fetal hemoglobin levels were  normalized (45–134 g/L, 0.39–1.17 MoM), and hemodynamics  was stabilized. Despite this, the fetus developed persistent anuria for 48 hours, and hemorrhagic central nervous system injury was diagnosed. The pregnancy was terminated for medical reasons. All abnormalities were confirmed morphologically, and karyotypic discordance between the twins was identified.

The clinical case demonstrates that Doppler assessment of fetal MCA-PSV allows reliable detection of anemia in TTTS, highlights the significant compensatory capacity of the fetal cardiovascular system that may permit successful treatment of severe anemia even under critical hemodynamic conditions, and emphasizes the importance of comprehensive morphological and genetic evaluation following an adverse pregnancy outcome to ensure correct interpretation of obstetric management decisions. 

1. Kostyukov K.V., Gladkova K.A., Sakalo V.A. et al. Fetal Medicine: Literature Review and the Experience of V.I. Kulakov National Medical Scientific Centre of Obstetrics, Gynaecology and Perinatal Medicine. Doctor.Ru. 2019; 11(166): 35–43. https://doi.org/10.31550/1727-2378-2019-166-11-35-43 (In Russian)

2. Mikhailov A.V., Romanovsky A.N., Kashtanova T.A. et al. Twin anemia polycythemia sequence – modern approaches to diagnosis and antenatal correction. Gynecology, Obstetrics and Perinatology. 2021; 20 (2): 134–140. https://doi.org/10.20953/1726-1678-2021-2-134-140 (In Russian)

3. Mikhailov A.V., Romanovsky A.N., Volchenkova V.E. et al. Acute twin-to-twin transfusion in monochorionic multiple pregnancy. Obstetrics and Gynecology. 2023; 2: 5–11 https://dx.doi.org/10.18565/aig.2022.259 (In Russian)

4. Mikhailov A.V., Romanovsky A.N., Volchenkova V.E. et al. Development of acute feto-fetal transfusion in delivery of monochorionic diamniotic twins. Gynecology, Obstetrics and Perinatology. 2024; 23 (1): 39–46. https://dx.doi.org/10.20953/1726-1678-2024-1-39-46 (In Russian)

5. Kuznetsov A.A., Romanovsky A.N., Shlykova A.V. et al. Single fetal demise in multiple pregnancy. Translational Medicine. 2019; 6 (5): 31–38. (In Russian)

6. Shlykova A.V., Romanovsky A.N., Kuznetsov A.A. et al. The management of monochorionic pregnancy with twin reversed arterial perfusion. Translational Medicine. 2019; 6 (5): 45–54. (In Russian)

7. Odibo A.O. Single intrauterine fetal death in twin pregnancies is associated with increased risk of preterm birth and abnormal antenatal brain imaging in the surviving co-twin. BJOG. 2019; 126 (5): 579. https://doi.org/10.1111/1471-0528.15599

8. Lanna M.M., Consonni D., Faiola S. et al. Incidence of Cerebral Injury in Monochorionic Twin Survivors after Spontaneous Single Demise: Long-Term Outcome of a Large Cohort. Fetal Diagn. Ther. 2020; 47 (1): 66–73. https://doi.org/10.1159/000500774

9. Shinar S., Harris K., Van Mieghem T. et al. Early imaging predictors of fetal cerebral ischemic injury in monochorionic twin pregnancy complicated by spontaneous single intrauterine death. Ultrasound Obstet. Gynecol. 2022; 59 (4): 497–505. https://doi.org/10.1002/uog.24844

10. Duyos I., Ordás P., Herrero B. et al. Single fetal demise in monochorionic twins: How to predict cerebral injury in the survivor co-twin? Acta Obstet. Gynecol. Scand. 2023; 102 (8): 1125–1134. https://doi.org/10.1111/aogs.14604

11. Mackie F.L., Morris R.K., Kilby M.D. Fetal Brain Injury in Survivors of Twin Pregnancies Complicated by Demise of One Twin: A Review. Twin Res. Hum. Genet. 2016; 19 (3): 262–7. https://doi.org/10.1017/thg.2016.39

12. Morris R.K., Mackie F., Garces A.T. et al. The incidence, maternal, fetal and neonatal consequences of single intrauterine fetal death in monochorionic twins: A prospective observational UKOSS study. PLoS One. 2020; 15 (9): e0239477. https://doi.org/ 10.1371/journal.pone.0239477

13. Conte G., Righini A., Griffiths P.D. et al. Brain-injured Survivors of Monochorionic Twin Pregnancies Complicated by Single Intrauterine Death: MR Findings in a Multicenter Study. Radiology. 2018; 288 (2): 582–590. https://doi.org/ 10.1148/radiol.2018171267

14. Moore C.M., McAdams A.J., Sutherland J. Intrauterine disseminated intravascular coagulation: a syndrome of multiple pregnancy with a dead twin fetus. J. Pediatr. 1969; 74 (4): 523–528. https://doi.org/10.1016/s0022-3476(69)80034-x

15. Morokuma S., Tsukimori K., Anami A. et al. Brain injury of the survivor diagnosed at 18 weeks of gestation after intrauterine demise of the co-twin: a case report. Fetal Diagn. Ther. 2008; 23 (2): 146–8. https://doi.org/ 10.1159/000111596

16. Khan L.H., Manzar S.. Ischaemic limb lesion in monochorionic twin infant. Arch. Dis. Child. Fetal Neonatal Ed. 2018; 103 (6): F546. https://doi.org/10.1136/archdischild-2017-314118

17. Nekrasova E.S. Prenatal diagnosis of multiple pregnancy. Moscow: Vidar-M, 2019. 220 p. (In Russian)

18. Bajoria R., Wee L.Y., Anwar S., Ward S. Outcome of twin pregnancies complicated by single intrauterine death in relation to vascular anatomy of the monochorionic placenta. Hum. Reprod. 1999; 14 (8): 2124–2130. https://doi.org/10.1093/humrep/14.8.2124.

19. Iwagaki S., Takahashi Y., Chiaki R. et al. Case of resuscitation from cardiac failure by intrauterine transfusion after single fetal death in monochorionic twin pregnancy. J. Obstet. Gynaecol. Res. 2019; 45 (10): 2105–2110. https://doi.org/ 10.1111/jog.14082

20. Meller C., Kleppe S., Aiello H., Otaño L. Monochorionic twin pregnancy from the perspective of the theory of complexity. Arch. Argent. Pediatr. 2024; 122 (4): e202310097. https://doi.org/10.5546/aap.2023-10097.eng

21. Hillman S.C., Morris R.K., Kilby M.D. Co-twin prognosis after single fetal death: a systematic review and meta-analysis. Obstet. Gynecol. 2011; 118 (4): 28–40. https://doi.org/10.1097/AOG.0b013e31822f129d

22. Mackie F.L., Rigby A., Morris R.K., Kilby M.D. Prognosis of the co-twin following spontaneous single intrauterine fetal death in twin pregnancies: a systematic review and meta-analysis. BJOG. 2019; 126 (5): 569–578. https://doi.org/ 10.1111/1471-0528.15530

23. Kanda M., Noguchi S., Yamamoto R. et al. Perinatal outcomes of intrauterine transfusion for the surviving twin in monochorionic twin gestation involving a single fetal demise. J. Obstet. Gynaecol. Res. 2020; 46 (8): 1319–1325. https://doi.org/ 10.1111/jog.14338

24. Mari G., Norton M.E., Stone J. et al. Society for Maternal-Fetal Medicine (SMFM) Clinical Guideline #8: the fetus at risk for anemia--diagnosis and management. Am. J. Obstet. Gynecol. 2015; 212 (6): 697–710. https://doi.org/ 10.1016/j.ajog.2015.01.059

25. Maisonneuve E., Ben M'Barek I., Leblanc T. et al. Managing the Unusual Causes of Fetal Anemia. Fetal Diagn. Ther. 2020; 47 (2): 156–164. https://doi.org/ 10.1159/000501554

26. Zulfa F., Tjahyadi D., Sasotya R.M.S. et al. Conservative Management of a Monochorionic Twin Pregnancy with an Intrauterine Fetal Death at 20-21 Weeks and Successful Term Delivery of the Second Twin. Am. J. Case Rep. 2024; 25: e942321. https://doi.org/10.12659/AJCR.942321

27. Hadlock F.P., Harrist R.B., Martinez-Poyer J. In utero analysis of fetal growth: a sonographic weight standard. Radiology. 1991; 181 (1): 129–133. https://doi.org/10.1148/radiology.181.1.1887021

28. Deka D., Dadhwal V., Sharma A.K. et al. Perinatal survival and procedure-related complications after intrauterine transfusion for red cell alloimmunization. Arch. Gynecol. Obstet. 2016; 293 (5): 967–973. https://doi.org/10.1007/s00404-015-3915-7

29. Nicolaides K.H., Soothill P.W., Clewell W.H. et al. Fetal haemoglobin measurement in the assessment of red cell isoimmunization. Lancet. 1988; 1 (8594): 1073–1075. https://doi.org/10.1016/s0140-6736(88)91896-x

30. Makogon A.V., Volkova V.M., Andryushina I.V. Reference values of fetal middle cerebral artery peak systolic velocity (12–40 weeks of gestation). Ultrasound and Functional Diagnostics. 2021; 3: 90–103. https://doi.org/10.24835/1607-0771-2021-3-90-103 (In Russian)

31. Srisupundit K., Luewan S., Tongsong T. Prenatal Diagnosis of Fetal Heart Failure. Diagnostics (Basel). 2023; 13 (4): 779–808. https://doi.org/10.3390/diagnostics13040779

32. Gasymova Sh.R., Donnikov A.E. Somatic tissue chromosome 16 mosaicism and its relationship to fetal growth retardation. Obstetrics and Gynecology. 2022; 7: 28–33 https://dx.doi.org/10.18565/aig.2022.7.28-33 (In Russian)

33. Yoshida A., Kaji T., Sogawa E. et al. Monochorionic Dizygotic Twins Conceived Spontaneously Showed Chimerism in Karyotype and Blood Group Type. Twin Res. Hum. Genet. 2021; 24 (3): 184–186. https://doi.org/ 10.3390/diagnostics13040779

34. Peters H.E., König T.E., Verhoeven M.O. et al. Unusual Twinning Resulting in Chimerism: A Systematic Review on Monochorionic Dizygotic Twins. Twin Res. Hum. Genet. 2017; 20 (2): 161–168. https://doi.org/10.1017/thg.2017.4

35. Chmait R.H., Floyd R., Benirschke K. Duplicity. Am. J. Obstet. Gynecol. 2011; 205: 87.e1–2. https://doi.org/10.1016/j.ajog.2011.02.063

36. Barkov I.Yu., Shubina Je., Kim L.V. et al. Placental mosaicism in pregnancies at high risk for trisomy 16 according to genome-wide DNA-based noninvasive prenatal screening for aneuploidies. Obstetrics and Gynecology. 2022; 7: 131–136. https://doi.org/10.18565/aig.2022.7.131-136 (In Russian)

37. Waldvogel S.M., Posey J.E., Goodell M.A. Human embryonic genetic mosaicism and its effects on development and disease. Nat. Rev. Genet. 2024; 25 (10): 698–714. https://doi.org/10.1038/s41576-024-00715-z

38. Sparks T.N., Thao K., Norton M.E. Mosaic trisomy 16: what are the obstetric and long-term childhood outcomes? Genet. Med. 2017; 19 (10): 1164–1170. https://doi.org/ 10.1038/gim.2017.23

39. Chen C.P., Lan F.H., Chern S.R. et al. Prenatal diagnosis of mosaic trisomy 16 by amniocentesis in a pregnancy associated with abnormal first-trimester screening result (low PAPP-A and low PlGF), intrauterine growth restriction and a favorable outcome. Taiwan J. Obstet. Gynecol. 2021; 60 (6): 1107–1111. https://doi.org/10.1016/j.tjog.2021.09.026

40. Faieta M., Falcone R., Duca S. et al. Test performance and clinical utility of expanded non-invasive prenatal test: Experience on 71,883 unselected routine cases from one single center. Prenat. Diagn. 2024; 44 (8): 936–945. https://doi.org/10.1002/pd.6580

41. Eiben B., Glaubitz R., Winkler T., Teubert A., Borth H. Clinical Experience with Noninvasive Prenatal Testing in Twin Pregnancy Samples at a Single Center in Germany. J. Lab. Physicians. 2023; 15 (4): 590–595. https://doi.org/10.1055/s-0043-1770066