Long-term effects of selective fetal growth restriction (LEMON): a cohort study of neurodevelopmental outcome in growth discordant identical twins in the Netherlands

Abstract

Singletons born after fetal growth restriction (FGR) are at increased risk of poor neurodevelopmental outcomes. Studies of singletons with FGR usually compare outcomes with those without FGR, a comparison that is inherently biased by obstetrical, parental, and genetic factors. We aim to compare neurodevelopmental outcomes between the smaller and larger twin in a population of discordant identical twins who shared a single placenta (monochorionic diamniotic), naturally eliminating these confounders. This study is part of the cohort study LEMON of monochorionic diamniotic twins with selective FGR. All monochorionic diamniotic twins with selective FGR who were born in Leiden University Medical Center (Leiden, Netherlands) between March 1, 2002, and Dec 31, 2017, were eligible for inclusion. Twin pregnancies that were complicated by twin-twin transfusion syndrome, twin anaemia polycythaemia sequence, or monoamnionicity were excluded. Cognitive performance was evaluated with two standardised psychometric age-appropriate tests, producing a full-scale intelligence quotient (FSIQ). Motor functioning was assessed with a standardised neurological examination. A composite outcome of neurodevelopmental impairment (NDI) was used, subdivided into mild NDI (defined as FSIQ <85, minor neurological dysfunction or cerebral palsy grade 1, or mild visual or hearing impairment) and severe NDI (defined as FSIQ <70, severe neurological dysfunction, or severe visual or hearing impairment). Between Jan 25, 2021, and March 15, 2022, 47 twin pairs were enrolled in the study and underwent neurodevelopmental assessment. The median gestational age at birth was 33·9 weeks (IQR 31·3-36·0) for the 47 included twin pairs, with median birthweights of 1400 g (1111-1875) in the smaller twin and 2003 g (1600-2680) in the larger twin. The median age at neurodevelopmental assessment was 11 years (8-13). Median FSIQ was 94 (86-101) for the smaller twin and 100 (92-108) for the larger twin (p<0·0001). More smaller twins had mild NDI (17 [36%] of 47) than did the larger twins (five [11%] of 47; odds ratio 4·8 [95% CI 1·6-14·1]; p=0·0049). There was no difference in the proportion of children with severe NDI (two [4%] of 47 in both groups, p=1·0). As mild NDI can impede children in their daily functioning, we recommend standardised long-term follow-up, including neurodevelopmental testing, for monochorionic diamniotic twins with selective FGR to facilitate early identification of children at risk. The Dutch Heart Foundation.