Prenatal risk factors of neurodevelopmental impairment after fetoscopic laser photocoagulation for twin-twin transfusion syndrome: a systematic review and meta-analysis

OBJECTIVE Monochorionic pregnancies complicated by twin-twin transfusion syndrome (TTTS) and treated with fetoscopic laser photocoagulation (FLP) can be associated with neurodevelopmental impairment (NDI). This meta-analysis aimed to identify the prevalence and risk factors of NDI among TTTS survivors after FLP. METHODS We searched PubMed, Embase, Scopus and Web of Science, from the inception of the database until 13th February 2021. Data regarding the severity of TTTS at the time of diagnosis (by Quintero staging), FLP procedure related complications and perinatal outcomes were compared between the survivors with and without NDI (defined as performance on a cognitive or developmental assessment tool > 2 SD below than the mean or a defined neurological disability). The random-effect model was used to pool the mean differences or odds ratios (OR) and the corresponding 95% confidence intervals (CIs). Heterogeneity was assessed using the I2 value. RESULTS Nine studies with a total of 1499 TTTS survivors were included. The overall incidence of NDI was 14.0% (95% CI, 9.0-18.0%). Occurrence of NDI in TTTS survivors was associated with higher gestational age (GA) at FLP (weeks) (mean difference 0.94, 95% CI 0.50, 1.38, P <0.001; I2 0%), lower GA at delivery (weeks) (mean difference -1.44, 95% CI -2.28, -0.61, P <0.001; I2 49%) and lower birth weight (grams) (mean difference -343.26, 95% CI -470.59, -215.92, P <0.001; I2 27%). Using different GA cut-off values, preterm birth < 32 weeks was associated with risk of NDI later in childhood (OR 2.25, 95% CI 1.02, 4.94, P 0.04; I2 35%). No statistical difference was found between NDI vs non-NDI survivors in terms of Quintero staging, being recipient or donor status, development of post-laser TAPS, recurrence of TTTS, rates of small for gestational age (SGA) and co-twin fetal demise. CONCLUSION TTTS survivors with advanced GA at the time of FLP, lower GA at delivery and lower birth weight are at the higher risk of developing NDI. No significant association was found between Quintero staging and risk of NDI. Together, our findings may be helpful for parental counseling and highlighting the need for future studies to better understand the risk factors of NDI among TTTS survivors. This article is protected by copyright. All rights reserved.