Display options
Share it on

J Perinat Med. 2021 Apr 22;49(7):837-846. doi: 10.1515/jpm-2020-0566. Print 2021 Sep 27.

Imaging diagnosis and legal implications of brain injury in survivors following single intrauterine fetal demise from monochorionic twins - a review of the literature.

Journal of perinatal medicine

Gheorghe Cruciat, Georgiana Irina Nemeti, Roxana Popa-Stanila, Andreea Florian, Iulian Gabriel Goidescu


  1. Obstetrics and Gynecology I, Mother and Child Department, "Iuliu Ha?ieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.
  2. Department of Radiology, "Iuliu Ha?ieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.

PMID: 33882202 DOI: 10.1515/jpm-2020-0566


Brain injury of the surviving twin from monochorionic pregnancies following intrauterine fetal demise during the second and third trimesters is a rare but severe complication. Monochorionicity and gestational age at the time of stillbirth seem to be decisive factors in terms of long-term neurologic outcome prediction for the survivor. Magnetic resonance imaging (MRI), diffusion weighted imaging (DWI) in particular, seem to bring the earliest and most accurate diagnosis. Ultrasound detection of brain damage is possible in later stages of fetal brain injury. It is essential to provide early diagnosis and multidisciplinary counsel to the parents to ensure informed decision making. For couples who choose to terminate pregnancy legislation related to late abortion might lead to further distress. Our paper aims to stress the importance of MRI DWI in the evaluation of surviving twins following single intrauterine fetal demise in monochorionic pregnancies and the delicate context of the medical professionals and parents facing this clinical situation, sometimes complicated by legal constraints.

© 2021 Gheorghe Cruciat et al., published by De Gruyter, Berlin/Boston.

Keywords: DWI MRI; brain injury; legal aspects; monochorionic; surviving twin


  1. Ong, SSC, Zamora, J, Khan, KS, Kilby, MD. Prognosis for the co-twin following single-twin death: a systematic review. BJOG An Int J Obstet Gynaecol 2006;113:992–8. https://doi.org/10.1111/j.1471-0528.2006.01027.x. - PubMed
  2. Oldenburg, A, Rode, L, Bødker, B, Ersbak, V, Holmskov, A, Jørgensen, FS, et al.. Influence of chorionicity on perinatal outcome in a large cohort of Danish twin pregnancies. Ultrasound Obstet Gynecol 2012;39:69–74. https://doi.org/10.1002/uog.10057. - PubMed
  3. D’Antonio, F, Thilaganathan, B, Dias, T, Khalil, A, Bahamie, A, Bhide, A, et al.. Influence of chorionicity and gestational age at single fetal loss on risk of preterm birth in twin pregnancy: analysis of STORK multiple pregnancy cohort. Ultrasound Obstet Gynecol 2017;50:723–7. - PubMed
  4. Hillman, SC, Morris, RK, Kilby, MD. Co-twin prognosis after single fetal death: a systematic review and meta-analysis. Obstet Gynecol 2011;118:928–40. https://doi.org/10.1097/aog.0b013e31822f129d. - PubMed
  5. Schwartz, N, Keeler, SM, Fishman, S, Timor-Tritsch, IE. Neurosonography to detect brain injury in a surviving monochorionic twin after demise of its co-twin. J Clin Ultrasound 2009;37:165–7. https://doi.org/10.1002/jcu.20547. - PubMed
  6. Nielsen, BW, Scott, RC. Brain abnormalities in fetuses: in-utero MRI versus ultrasound. Lancet 2017;389:483–5. https://doi.org/10.1016/s0140-6736(16)32565-x. - PubMed
  7. Mateizel, I, Santos-Ribeiro, S, Done, E, Van Landuyt, L, Van De Velde, H, Tournaye, H, et al.. Do ARTs affect the incidence of monozygotic twinning? Hum Reprod 2016;31:2435–41. https://doi.org/10.1093/humrep/dew216. - PubMed
  8. Shipp, TD, Bromley, B, Benacerraf, B. The ultrasonographic appearance and outcome for fetuses with masses distorting the fetal face. J Ultrasound Med 1995;14:673–8. https://doi.org/10.7863/jum.1995.14.9.673. - PubMed
  9. Pharoah, POD. Neurological outcome in twins. Semin Neonatol 2002;7:223–30. https://doi.org/10.1053/siny.2002.0109. - PubMed
  10. Barigye, O, Pasquini, L, Galea, P, Chambers, H, Chappell, L, Fisk, NM. High risk of unexpected late fetal death in monochorionic twins despite intensive ultrasound surveillance: a cohort study. PLoS Med 2005;2:0521–7. https://doi.org/10.1371/journal.pmed.0020172. - PubMed
  11. Senat, M-V. Mort fœtale in utero et grossesse gémellaire. J Gynécol Obstet Biol Reprod 2009;38:S100–3. https://doi.org/10.1016/s0368-2315(09)73566-5. - PubMed
  12. Walsh, CA. Early 2nd trimester fetal demise in a monochorionic twin pregnancy: a cautionary tale. Australas J Ultrasound Med 2015;18:78–81. https://doi.org/10.1002/j.2205-0140.2015.tb00046.x. - PubMed
  13. Jarvis, D, Mooney, C, Cohen, J, Papaioannou, D, Bradburn, M, Sutton, A, et al.. A systematic review and meta-analysis to determine the contribution of mr imaging to the diagnosis of foetal brain abnormalities in utero. Eur Radiol 2017;27:2367–80. https://doi.org/10.1007/s00330-016-4563-4. - PubMed
  14. Paladini, D, Malinger, G, Pilu, G, Timor-Trisch, I, Volpe, P. The MERIDIAN trial: caution is needed. Lancet 2017;389:2103. https://doi.org/10.1016/s0140-6736(17)31337-5. - PubMed
  15. Righini, A, Salmona, S, Bianchini, E, Zirpoli, S, Moschetta, M, Kustermann, A, et al.. Prenatal magnetic resonance imaging evaluation of ischemic brain lesions in the survivors of monochorionic twin pregnancies. Report of 3 cases. J Comput Assist Tomogr 2004;28:87–92. https://doi.org/10.1097/00004728-200401000-00014. - PubMed
  16. Glenn, OA, Quiroz, EM, Berman, JI, Studholme, C, Xu, D. Diffusion-weighted imaging in fetuses with unilateral cortical malformations and callosal agenesis. Am J Neuroradiol 2010;31:1100–2. https://doi.org/10.3174/ajnr.a1863. - PubMed
  17. Deveer, R, Engin-Ustun, Y, Mert, I, Sarikaya, E, Bozkurt, S, Deveer, M, et al.. Twin pregnancies with single fetal death: analysis of 38 cases. Fetal Pediatr Pathol 2013;32:71–5. https://doi.org/10.3109/15513815.2012.671446. - PubMed
  18. Cleary-Goldman, J, D’Alton, M. Management of single fetal demise in a multiple gestation. Obstet Gynecol Surv 2004;59:285–98. https://doi.org/10.1097/01.ogx.0000120165.52159.04. - PubMed
  19. Hoffmann, C, Weisz, B, Yinon, Y, Hogen, L, Gindes, L, Shrim, A, et al.. Diffusion MRI findings in monochorionic twin pregnancies after intrauterine fetal death. Am J Neuroradiol 2013;34:212–6. https://doi.org/10.3174/ajnr.a3279. - PubMed
  20. Okamura, K, Murotsuki, J, Tanigawara, S, Uehara, S, Yajima, A. Funipuncture for evaluation of hematologic and coagulation indices in the surviving twin following co-twin’s death. Obstet Gynecol 1994;83:975–8. https://doi.org/10.1097/00006250-199406000-00016. - PubMed
  21. Nicolini, U, Poblete, A. Editorial Single intrauterine death in monochorionic twin pregnancies. Ultrasound Obstet Gynecol 1999;14:297–301. https://doi.org/10.1046/j.1469-0705.1999.14050297.x. - PubMed
  22. Conte, G, Righini, A, Griffiths, PD, Rustico, M, Lanna, M, Mackie, FL, et al.. Brain-injured survivors of monochorionic twin pregnancies complicated by single intrauterine death: MR findings in a multicenter study. Radiology 2018;288:582–90. https://doi.org/10.1148/radiol.2018171267. - PubMed
  23. Sato, H, Murata, H, Sato, K, Kawaharamura, K, Hamanishi, S, Hirose, M. Encephalomalacia in surviving twin after single fetal death diagnosed at 18 weeks of gestation in monochorionic twin pregnancy. Am J Case Rep 2013;14:341-4. https://doi.org/10.12659/AJCR.889478. - PubMed
  24. O’Donoghue, K, Rutherford, MA, Engineer, N, Wimalasundera, RC, Cowan, FM, Fisk, NM. Transfusional fetal complications after single intrauterine death in monochorionic multiple pregnancy are reduced but not prevented by vascular occlusion. BJOG An Int J Obstet Gynaecol 2009;116:804–12. - PubMed
  25. Van Klink, JMM, Van Steenis, A, Steggerda, SJ, Genova, L, Sueters, M, Oepkes, D, et al.. Single fetal demise in monochorionic pregnancies: incidence and patterns of cerebral injury. Ultrasound Obstet Gynecol 2015;45:294–300. https://doi.org/10.1002/uog.14722. - PubMed
  26. Govaert, P, Ramenghi, L, Taal, R, De Vries, L, Deveber, G. Diagnosis of perinatal stroke I: definitions, differential diagnosis and registration. Acta Paediatr 2009;98:1556–67. https://doi.org/10.1111/j.1651-2227.2009.01461.x. - PubMed
  27. Fusi, L, Gordon, H. Twin pregnancy complicated by single intrauterine death. Problems and outcome with conservative management. BJOG An Int J Obstet Gynaecol 1990;97:511–6. https://doi.org/10.1111/j.1471-0528.1990.tb02521.x. - PubMed
  28. Yoshida, K, Matayoshi, K. A study on prognosis of surviving cotwin. Acta Genet Med Gemellol (Roma) 1990;39:383–8. https://doi.org/10.1017/s0001566000005316. - PubMed
  29. Mackie, FL, Morris, RK, Kilby, MD. Fetal brain injury in survivors of twin pregnancies complicated by demise of one twin: a review. Twin Res Hum Genet 2016;19:262–7. https://doi.org/10.1017/thg.2016.39. - PubMed
  30. Griffiths, PD, Sharrack, S, Chan, KL, Bamfo, J, Williams, F, Kilby, MD. Fetal brain injury in survivors of twin pregnancies complicated by demise of one twin as assessed by in utero MR imaging. Prenat Diagn 2015;35:583–91. https://doi.org/10.1002/pd.4577. - PubMed
  31. Simonazzi, G, Segata, M, Ghi, T, Sandri, F, Ancora, G, Bernardi, B, et al.. Accurate neurosonographic prediction of brain injury in the surviving fetus after the death of a monochorionic cotwin. Ultrasound Obstet Gynecol 2006;27:517–21. https://doi.org/10.1002/uog.2701. - PubMed
  32. Robinson, A, Teoh, M, Edwards, A, Fahey, M, Goergen, S. Fetal brain injury in complicated monochorionic pregnancies: diagnostic yield of prenatal MRI following surveillance ultrasound and influence on prognostic counselling. Prenat Diagn 2017;37:611–27. https://doi.org/10.1002/pd.5059. - PubMed
  33. Larroche, JC, Droullé, P, Delezoide, AL, Narcy, F, Nessmann, C. Brain damage in monozygous twins. Biol Neonate 1990;57:261–78. https://doi.org/10.1159/000243201. - PubMed
  34. Langer, B, Boudier, E, Gasser, B, Christmann, D, Messer, J, Schlaeder, G. Antenatal diagnosis of brain damage in the survivor after the second trimester death of a monochorionic monoamniotic co-twin. Fetal Diagn Ther 1997;12:286–91. https://doi.org/10.1159/000264487. - PubMed
  35. Khalil, A, Rodgers, M, Baschat, A, Bhide, A, Gratacos, E, Hecher, K, et al.. ISUOG Practice Guidelines: role of ultrasound in twin pregnancy. Ultrasound Obstet Gynecol 2016;47:247–63. https://doi.org/10.1002/uog.15821. - PubMed
  36. Paladini, D, Quarantelli, M, Sglavo, G, Pastore, G, Cavallaro, A, D’Armiento, MR, et al.. Accuracy of neurosonography and MRI in clinical management of fetuses referred with central nervous system abnormalities. Ultrasound Obstet Gynecol 2014;44:188–96. https://doi.org/10.1002/uog.13243. - PubMed
  37. Pistorius, LR, Hellmann, PM, Visser, GHA, Malinger, G, Prayer, D. Fetal neuroimaging: ultrasound, MRI, or both?. Obstet Gynecol Surv 2008;63:733–45. https://doi.org/10.1097/ogx.0b013e318186d3ea. - PubMed
  38. Goidescu, IG, Nemeti, G, Caracostea, G, Eniu, DT, Chiorean, A, Pintican, R, et al.. The role of imaging techniques in the diagnosis, staging and choice of therapeutic conduct in pregnancy associated breast cancer. Med Ultrason 2019;21:336–43. https://doi.org/10.11152/mu-1958. - PubMed
  39. Muller, TB, Haraldseth, O, Jones, RA, Sebastiani, G, Godtliebsen, F, Lindboe, CF, et al.. Combined perfusion and diffusion-weighted magnetic resonance imaging in a rat model of reversible middle cerebral artery occlusion. Stroke 1995;26:451–8. https://doi.org/10.1161/01.str.26.3.451. - PubMed
  40. Cannie, M, De Keyzer, F, Meersschaert, J, Jani, J, Lewi, L, Deprest, J, et al.. A diffusion-weighted template for gestational age-related apparent diffusion coefficient values in the developing fetal brain. Ultrasound Obstet Gynecol 2007;30:318–24. https://doi.org/10.1002/uog.4078. - PubMed
  41. Schneider, MM, Berman, JI, Baumer, FM, Glass, HC, Jeng, S, Jeremy, RJ, et al.. Normative apparent diffusion coefficient values in the developing fetal brain. Am J Neuroradiol 2009;30:1799–803. https://doi.org/10.3174/ajnr.a1661. - PubMed
  42. Cartry, C, Viallon, V, Hornoy, P, Adamsbaum, C. Diffusion du cerveau fœtal normal: Limites et espoirs. J Radiol 2010;91:561–6. https://doi.org/10.1016/s0221-0363(10)70088-3. - PubMed
  43. Boyer, AC, Gonçalves, LF, Lee, W, Shetty, A, Holman, A, Yeo, L, et al.. Magnetic resonance diffusion-weighted imaging: reproducibility of regional apparent diffusion coefficients for the normal fetal brain. Ultrasound Obstet Gynecol 2013;41:190–7. https://doi.org/10.1002/uog.11219. - PubMed
  44. Sartor, A, Arthurs, O, Alberti, C, Belarbi, N, Tilea, B, Boizeau, P, et al.. Apparent diffusion coefficient measurements of the fetal brain during the third trimester of pregnancy: how reliable are they in clinical practice? Prenat Diagn 2014;34:357–66. https://doi.org/10.1002/pd.4309. - PubMed
  45. Righini, A, Kustermann, A, Parazzini, C, Fogliani, R, Ceriani, F, Triulzi, F. Diffusion-weighted magnetic resonance imaging of acute hypoxic-ischemic cerebral lesions in the survivor of a monochorionic twin pregnancy: case report. Ultrasound Obstet Gynecol 2007;29:453–6. https://doi.org/10.1002/uog.3967. - PubMed
  46. Baldoli, C, Righini, A, Parazzini, C, Scotti, G, Triulzi, F. Demonstration of acute ischemic lesions in the fetal brain by diffusion magnetic resonance imaging. Ann Neurol 2002;52:243–6. https://doi.org/10.1002/ana.10255. - PubMed
  47. Mackie, FL, Rigby, A, Morris, RK, Kilby, MD. Prognosis of the co-twin following spontaneous single intrauterine fetal death in twin pregnancies: a systematic review and meta-analysis. BJOG An Int J Obstet Gynaecol 2019;126:569–78. - PubMed
  48. Kocaoglu, M, Kline-Fath, BM, Calvo-Garcia, MA, Zhang, B, Nagaraj, UD. Magnetic resonance imaging of the fetal brain in monochorionic diamniotic twin gestation: correlation of cerebral injury with ultrasound staging and survival outcomes. Pediatr Radiol 2020;50:1131–8. https://doi.org/10.1007/s00247-020-04661-w. - PubMed
  49. Scher, AI, Petterson, B, Blair, E, Ellenberg, JH, Grether, JK, Haan, E, et al.. The risk of mortality or cerebral palsy in twins: a collaborative population-based study. Pediatr Res 2002;52:671–81. https://doi.org/10.1203/00006450-200211000-00011. - PubMed
  50. Van Der Toorn, A, Syková, E, Dijkhuizen, RM, Voříšek, I, Vargová, L, Škobisová, E, et al.. Dynamic changes in water ADC, energy metabolism, extracellular space volume, and tortuosity in neonatal rat brain during global ischemia. Magn Reson Med 1996;36:52–60. https://doi.org/10.1002/mrm.1910360110. - PubMed
  51. Shrot, S, Hoffmann, C, Katorza, E. Reversible parenchymal ischemic injury on fetal brain MRI following fetoscopic laser coagulation—implication on parental counseling. Radiol Case Rep 2020;15:1369–72. https://doi.org/10.1016/j.radcr.2020.06.006. - PubMed
  52. Jelin, AC, Norton, ME, Bartha, AI, Fick, AL, Glenn, OA. Intracranial magnetic resonance imaging findings in the surviving fetus after spontaneous monochorionic cotwin demise. Am J Obstet Gynecol 2008;199:398.e1–e5. https://doi.org/10.1016/j.ajog.2008.06.062. - PubMed
  53. Aertsen, M, Van Tieghem De Ten Berghe, C, Deneckere, S, Couck, I, De Catte, L, Lewi, L. The prevalence of brain lesions after in utero surgery for twin-to-twin transfusion syndrome on third-trimester MRI: a retrospective cohort study. Eur Radiol 2020. https://doi.org/10.1007/s00330-020-07452-x. - PubMed
  54. Weisstanner, C, Gruber, GM, Brugger, PC, Mitter, C, Diogo, MC, Kasprian, G, et al.. Fetal MRI at 3T-ready for routine use? Br J Radiol 2017;90:20160362. https://doi.org/10.1259/bjr.20160362. - PubMed
  55. Priego, G, Barrowman, NJ, Hurteau-Miller, J, Miller, E. Does 3T fetal MRI improve image resolution of normal brain structures between 20 and 24 weeks’ gestational age? Am J Neuroradiol 2017;38:1636–42. https://doi.org/10.3174/ajnr.a5251. - PubMed
  56. Petterson, B, Nelson, KB, Watson, L, Stanley, F. Twins, triplets, and cerebral palsy in births in Western Australia in the 1980s. Br Med J 1993;307:1239–43. https://doi.org/10.1136/bmj.307.6914.1239. - PubMed
  57. Bonellie, S, Currie, D, Chalmers, J. Comparison of risk factors for cerebral palsy in twins and singletons. Dev Med Child Neurol 2005;47:587–91. https://doi.org/10.1017/s0012162205001167. - PubMed
  58. Luu, TM, Vohr, B. Twinning on the brain: the effect on neurodevelopmental outcomes. Am J Med Genet Part C Semin Med Genet 2009;151C:142–7. https://doi.org/10.1002/ajmg.c.30208. - PubMed
  59. Jatzko, B, Rittenschober-Böhm, J, Mailath-Pokorny, M, Worda, C, Prayer, D, Kasprian, G, et al.. Cerebral lesions at fetal magnetic resonance imaging and neurologic outcome after single fetal death in monochorionic twins. Twin Res Hum Genet 2015;18:606–12. https://doi.org/10.1017/thg.2015.49. - PubMed
  60. Lanna, MM, Consonni, D, Faiola, S, Izzo, G, Scelsa, B, Cetin, I, 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;47:66–73. https://doi.org/10.1159/000500774. - PubMed

Publication Types