Highlights
1. Fetal reduction from triplets to twins was associated with a significantly lower risk of neurodevelopmental disorders in surviving children.
2. The cumulative incidence of neurodevelopmental disorders by age 15 was 4.2% in the reduced group vs. 10.7% in the non-reduced group.
3. The adjusted hazard ratio for neurodevelopmental disorders following fetal reduction was 0.33, indicating a substantial protective effect.
Background
Triplet pregnancies are known to carry high risks of prematurity and subsequent neurodevelopmental disorders due to complications such as low birth weight and neonatal intensive care admissions. While fetal reduction from triplets to twins has been shown to improve short-term obstetric outcomes, its long-term impact on neurodevelopmental health remained uncertain. This study aimed to fill that gap by comparing neurodevelopmental outcomes in children from reduced versus non-reduced triplet pregnancies.
Study Design
The study was a nationwide, population-based cohort analysis utilizing the Danish Fetal Medicine Database, linked to national health registries and prenatal records. It included all trichorionic triamniotic (TCTA) triplet pregnancies diagnosed during the first-trimester scan (11-14 weeks’ gestation) with estimated due dates between 2008 and 2018. Liveborn children were followed until an outcome of interest, death, emigration, or the end of the study period in 2022. The primary outcome was a composite of neurodevelopmental disorders, including epilepsy, cerebral palsy, and intellectual disability.
Key Findings
Among 313 eligible pregnancies, 70% underwent fetal reduction to twins, while 28% did not. A total of 625 liveborn children were included, with 64% from reduced pregnancies. Over a median follow-up of 9.3 years, neurodevelopmental disorders were diagnosed in 34 children. The cumulative incidence at 15 years was 6.6% overall, but stratified analysis revealed a striking difference: 4.2% in the reduced group versus 10.7% in the non-reduced group. Adjusted analyses confirmed a significantly lower hazard of neurodevelopmental disorders following fetal reduction (HR 0.33, 95% CI 0.15-0.71). For individual disorders like epilepsy, the protective effect was directionally similar but less precise due to smaller numbers.
Expert Commentary
This study provides robust evidence supporting fetal reduction as a strategy to mitigate long-term neurodevelopmental risks in triplet pregnancies. The findings align with previous research linking multifetal pregnancy reduction to improved perinatal outcomes. However, limitations include potential residual confounding and the observational nature of the study. Further research is needed to explore mechanisms, such as whether the benefit stems from reduced prematurity or other factors.
Conclusion
Fetal reduction from triplets to twins is associated with a substantially lower risk of severe neurodevelopmental disorders in surviving children. These findings should inform counseling for families with triplet pregnancies and highlight the importance of long-term follow-up in multifetal gestations.