Objective: 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.
Study design: 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).
Results: 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.
Conclusions: 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.
Trial registration: International Clinical Trial Registry Platform ID NL9833 (https://trialsearch.who.int/).
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