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

Objective: Monochorionic twins with twin–twin transfusion syndrome (TTTS) treated with fetoscopic laser photocoagulation (FLP) are at increased risk of neurodevelopmental impairment (NDI). This meta-analysis aimed to identify the prevalence of and perinatal risk factors for NDI in TTTS survivors treated with FLP. Methods: We performed a search in PubMed, EMBASE, Scopus and Web of Science, from inception to 13 February 2021, for studies evaluating perinatal risk factors for NDI in children diagnosed prenatally with TTTS managed by FLP. Data on severity of TTTS at the time of diagnosis, defined according to the Quintero staging system, FLP-related complications and perinatal outcomes were compared between children with a history of TTTS treated with FLP with and those without NDI, which was defined as performance on a cognitive or developmental assessment tool ≥ 2 SD below the mean or a defined motor or sensory disability. A random-effects model was used to pool the mean differences or odds ratios (OR) with the corresponding 95% CIs. Heterogeneity was assessed using the I² statistic. 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%). The occurrence of NDI in TTTS survivors was associated with later gestational age (GA) at FLP (mean difference, 0.94 weeks (95% CI, 0.50–1.38 weeks); P < 0.0001, I² = 0%), earlier GA at delivery (mean difference, –1.44 weeks (95% CI, –2.28 to –0.61 weeks); P = 0.0007, I² = 49%) and lower birth weight (mean difference, –343.26 g (95% CI, –470.59 to –215.92 g); P < 0.00001, I² = 27%). Evaluation of different GA cut-offs showed that preterm birth before 32 weeks was associated with higher risk for NDI later in childhood (OR, 2.25 (95% CI, 1.02–4.94); P = 0.04, I² = 35%). No statistically significant difference was found between cases with and those without NDI with respect to Quintero stage of TTTS, recipient or donor status, development of postlaser twin anemia–polycythemia sequence, recurrence of TTTS and incidence of small- for-gestational age or cotwin fetal demise. Conclusions: TTTS survivors with later GA at the time of FLP, earlier GA at delivery and lower birth weight are at higher risk of developing NDI. No significant association was found between Quintero stage of TTTS and risk of NDI. Our findings may be helpful for parental counseling and highlight the need for future studies to understand better the risk factors for NDI in TTTS survivors.