Incidence and outcome of prenatal brain abnormality in twin-to-twin transfusion syndrome: systematic review and meta-analysis.

Objectives: To evaluate the incidence of antenatally diagnosed brain injury in twin pregnancy complicated by twin-to-twin transfusion syndrome (TTTS) and to quantify the perinatal mortality, morbidity and long-term neurodevelopmental outcome of these fetuses.

Methods: MEDLINE, EMBASE, ClinicalTrials.gov and The Cochrane Library databases were searched. Inclusion criteria were studies reporting on brain abnormality diagnosed antenatally in twin pregnancies complicated by TTTS. The primary outcome was the incidence of prenatal brain abnormality. The secondary outcomes were intrauterine demise (IUD), neonatal death, termination of pregnancy (TOP) and long-term morbidity. Outcomes were explored in the population of fetuses with antenatal diagnosis of brain abnormality. Subgroup analysis according to the type of treatment, gestational age, Quintero stage at diagnosis and/or treatment, and cotwin death was planned. Meta-analysis of proportions was used to combine data and pooled proportions and their 95% CI were reported.

Results: Thirteen studies including 1573 cases of TTTS and 88 fetuses with an antenatal diagnosis of brain abnormality were included in the systematic review. The meta-analysis included only studies reporting on brain abnormality in twin pregnancy complicated by TTTS cases and treated with laser surgery. Overall, brain injury occurred in 2.2% (52/2410) of fetuses (eight studies). Brain abnormality was reported in 1.03% and 0.82% of recipients and donors, respectively. The most common type of abnormality was ischemic lesions (30.4% (95% CI, 19.1-43.0%)), followed by destructive lesions (23.9% (95% CI, 13.7-35.9%)), ventriculomegaly (19.9% (95% CI, 10.6-31.3%)) and hemorrhagic lesions (15.3% (95% CI, 7.1-25.8%)). Spontaneous IUD occurred in 13.4% (95% CI, 5.1-24.8%) of fetuses, while TOP was chosen by parents in 53.5% (95% CI, 38.9-67.8%) cases. Neonatal death was reported by only three studies, with an incidence of 15.4% (95% CI, 2.8-35.4%). Finally, only two studies reported on composite morbidity, with an overall rate of the outcome of 20.4% (95% CI, 2.5-49.4%) and rates of 29.7% and 20.4% in the recipient and donor fetuses, respectively. Due to the small numbers, only composite morbidity was analyzed and no information on neonatal intensive care unit admission, respiratory distress syndrome or other long-term outcomes, such as neurodevelopmental delay and cerebral palsy, could be retrieved reliably.

Conclusions: The overall incidence of antenatally diagnosed fetal brain abnormality in twin pregnancy complicated by TTTS treated with laser surgery is around 2% and is mainly ischemic in nature (30.4%). TOP was chosen by parents in more than half of cases (53.5%). No information could be retrieved on morbidity outcomes, highlighting the urgent need for long-term follow-up studies of these children. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.