What is the role of intrauterine transfusion after single intrauterine death in monochorionic twin pregnancies? Evidence from a systematic review and meta-analysis

Objective: To investigate the role of intrauterine transfusion (IUT) in affecting the outcome of the surviving twin showing sign of fetal anemia after a single intrauterine fetal death (IUFD) in monochorionic (MC) twin pregnancies. Methods: PubMed, Medline and Embase databases were searched (2010-2024). The inclusion criteria were studies reporting the outcome of fetuses showing signs of fetal anemia, defined as the presence of the peak systolic velocity (PSV) of the middle cerebral artery (MCA) >1.5 MoM, after single IUFD receiving compared to those not receiving IUT. The outcomes observed were preterm birth (PTB) <34 and 28 weeks of gestation, either iatrogenic or spontaneous, co-twin intra-IUFD, co-twin neonatal death (NND), anomalies at pre- or post-natal brain imaging, abnormal neurodevelopmental outcome. Risk of bias of the included studies was assessed using the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool. The GRADE methodology was used to assess the quality of the body of retrieved evidence. Random effect meta-analyses of proportions were used to analyze the data. Results: Six studies (78 twin pregnancies complicated by single IUFD showing signs of fetal anemia) were included in the systematic review. Assessment of risk of bias of observational studies according to the ROBINS-I tool is presented. Only one study reported a non-matched comparison between anemic fetuses undergoing compared to those not undergoing IUT, so we could not calculate the summary odd ratios, and we reported the results as pooled proportions. PTB occurred in 51.25% (95% CI 35.76-66.62) of cases < 34 weeks and in 17.99% (95% CI 5.84-34.91) < 28 weeks of gestation. Co-twin IUFD and NND were reported in 8.02% (95% CI 2.30-16.78) and 15.49% (95% CI 7.89-25.05), while abnormal findings at pre-or post-natal brain imaging in 20.30% (95% CI 11.61-30.69). Abnormal neurodevelopmental outcome was reported in 5.93% (95% CI 2.50-18.30). Conclusion: There is a very low grade of evidence that IUT can affect the outcome of anemic fetuses after single IUFD in MC pregnancies. The findings how this systematic review, in view of the limitations of the included studies, highlighted the need for large multicenter studies sharing objective protocols of prenatal management and post-natal assessment of pregnancies complicated by single IUFD are needed to report whether IUT in the anemic fetus after single IUFD can prevent mortality and neuromorbidity.