Long-term cardiovascular outcome following fetal anaemia and intrauterine transfusion: A cohort study

Objective: To compare long-term cardiovascular outcomes in survivors of fetal anaemia and intrauterine transfusion with those of non-anaemic siblings. Design: Retrospective cohort study. Setting: Auckland, New Zealand. Participants: Adults who received intrauterine transfusion for anaemia due to rhesus disease (exposed) and their unexposed sibling(s). Exposure: Fetal anaemia requiring intrauterine transfusion. Main outcome measures: Anthropometry, blood pressure, lipids, heart rate variability and cardiac MRI, including myocardial perfusion. Results: Exposed participants (n=95) were younger than unexposed (n=92, mean±SD 33.7±9.3 vs 40.1 ±10.9 years) and born at earlier gestation (34.3±1.7 vs 39.5±2.1 weeks). Exposed participants had smaller left ventricular volumes (end-diastolic volume/body surface area, difference between adjusted means -6.1, 95% CI -9.7 to -2.4 mL/m²), increased relative left ventricular wall thickness (difference between adjusted means 0.007, 95% CI 0.001 to 0.012 mm.m²/mL) and decreased myocardial perfusion at rest (ratio of geometric means 0.86, 95% CI 0.80 to 0.94). Exposed participants also had increased low frequency-to-high frequency ratio on assessment of heart rate variability (ratio of geometric means 1.53, 95% CI 1.04 to 2.25) and reduced high-density lipoprotein concentration (difference between adjusted means -0.12, 95% CI -0.24 to 0.00 mmol/L). Conclusions: This study provides the first evidence in humans that cardiovascular development is altered following exposure to fetal anaemia and intrauterine transfusion, with persistence of these changes into adulthood potentially indicating increased risk of cardiovascular disease. These findings are relevant to the long-term health of intrauterine transfusion recipients, and may potentially also have implications for adults born preterm who were exposed to anaemia at a similar postconceptual age.