Long-Term Effects of Fetal Growth Restriction on Cardiovascular Structure and Function: A Cohort Study in Growth-Discordant Identical Twins.

Abstract

To investigate the effect of fetal growth restriction (FGR) on cardiovascular structure and function in childhood in a growth-discordant identical twin model, thereby adjusting naturally for genetic, obstetric, and environmental confounding factors. This study is part of the LEMON cohort study of growth-discordant identical twins born at the Leiden University Medical Center, The Netherlands. Echocardiography was prospectively performed in 42 twin pairs aged between 5 and 17 years. Growth discordance was defined as a birth weight discordance ≥20%. Outcome measures were compared between the smaller and larger twin and included structural measures (left ventricular [LV] dimensions and carotid intima-media thickness) as well as functional measures (LV systolic and diastolic function using Doppler and LV strain imaging, and aortic pulsed wave velocity). Median gestational age at birth was 34.1 weeks (IQR 31.6-36.0) with median birth weights of 1471 g (IQR 1114-1876) and 2025 g (IQR 1623-2705) for the smaller and larger twin, respectively. Median age at echocardiography was 11 years (IQR 9-14). Smaller twins presented with significantly lower LV global longitudinal strain (-19.6% vs -20.7%), and higher mitral peak E and A velocities, and mitral E/e' ratio compared with larger co-twins. No within-pair differences were found regarding structural cardiovascular parameters, carotid intima-media thickness and aortic pulsed wave velocity. In a growth-discordant identical twin model, FGR is associated with subclinical changes in myocardial structure and systolic and diastolic LV function in the smaller growth-restricted twin compared with the larger appropriately-grown co-twin. This finding indicates that adverse cardiovascular remodeling after FGR persists into childhood, potentially influencing long-term risk of cardiovascular disease. International Clinical Trial Registry Platform ID NL9833 (https://trialsearch.who.int/).