Neurodevelopmental disorders following fetal reduction of triplet pregnancies: a nationwide cohort study.

Abstract

Triplet pregnancies carry high risks of prematurity and subsequent neurodevelopmental disorders. Fetal reduction from triplets to twins improves short-term obstetric outcomes, but long-term neurodevelopmental outcomes among surviving children remain uncertain. To compare the long-term risk of neurodevelopmental disorders among liveborn children from trichorionic triamniotic triplet pregnancies managed with fetal reduction from 3 to 2 fetuses vs no reduction. We conducted a nationwide, population-based cohort study using the Danish Fetal Medicine Database, linked to national health registries and local prenatal records. We included all trichorionic triamniotic triplet pregnancies diagnosed at the routine first-trimester scan (11-14 weeks' gestation) with estimated due dates from January 1, 2008, through December 31, 2018. Liveborn children were then followed from birth until an outcome of interest, death, emigration, or the end of the study period (December 31, 2022). The outcomes of interest were neurodevelopmental disorders, defined by diagnoses of epilepsy, cerebral palsy, or intellectual disability, combined into a primary composite outcome of any of these disorders. Cumulative incidence through age 15 years was estimated in each group, with death as a competing risk. Moreover, cause-specific hazard ratios (HRs) were estimated using multivariable Cox regression with robust variance to account for clustering within pregnancies, adjusted for maternal age, educational level, and assisted reproduction. Among 313 eligible trichorionic triamniotic pregnancies, 219 (70%) underwent 3-2 fetal reduction at a median gestational age of 11+6 weeks (IQR 11+5-12+1), and 87 (28%) did not. Overall, 625 liveborn children were included (399 (64%) from reduced pregnancies and 226 (36%) from nonreduced pregnancies). Over a median follow-up of 9.3 years (IQR 6.5-12.5), 34 children were diagnosed with at least one neurodevelopmental disorder (cumulative incidence at 15 years, 6.6% (95% CI 4.4%% to 9.5%)). Neurodevelopmental disorders were diagnosed in 13 children after reduction and in 21 without. Thus, the cumulative incidence of neurodevelopmental disorders by age 15 was 4.2% (95% CI 2.1-7.5) after 3-2 fetal reduction and 10.7% (95% CI 6.5%% to 16.2%) with no reduction (Gray test, P<0.001). Furthermore, fetal reduction was associated with a lower hazard of neurodevelopmental disorders (adjusted HR, 0.33 (95% CI 0.15-0.71)). For individual disorders, estimates were directionally similar but imprecise due to small numbers; for epilepsy, the adjusted HR was 0.37 (0.14-0.98) following fetal reduction. Among all pregnancies with at least one surviving child, the absolute risk of minimum one child being diagnosed with a neurodevelopmental disorder was 5.9% (12/202) following fetal reduction; however, 19,8% (17/86) without. Among liveborn children from trichorionic triamniotic triplet pregnancies, fetal reduction from 3 to 2 fetuses was associated with a substantially lower long-term risk of severe neurodevelopmental disorders compared with no reduction.