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Long-term cardiovascular outcome following fetal anaemia and intrauterine transfusion: a cohort study
  1. Alexandra H Wallace1,2,
  2. Stuart R Dalziel1,3,
  3. Brett R Cowan4,
  4. Alistair A Young4,
  5. Kent L Thornburg5,
  6. Jane E Harding1
  1. 1Liggins Institute, University of Auckland, Auckland, New Zealand
  2. 2Department of Paediatrics, Waikato Hospital, Hamilton, New Zealand
  3. 3Children's Emergency Department, Starship Children's Hospital, Auckland, New Zealand
  4. 4Department of Anatomy with Radiology, Centre for Advanced MRI and Auckland MRI Research Group, University of Auckland, Auckland, New Zealand
  5. 5Heart Research Center, Oregon Health and Sciences University, Portland, USA
  1. Correspondence to Professor Jane E Harding, Liggins Institute, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand; j.harding{at}auckland.ac.nz

Abstract

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.

  • blood transfusion, intrauterine
  • Fetal Medicine
  • Neonatology
  • Imaging

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Footnotes

  • Contributors All authors contributed to the study design and reviewed the draft manuscript. In addition, AHW and SRD contributed to the literature search, study design, data collection, analysis and interpretation; BRC and AAY contributed to the design of the MRI protocol and analysis of MRI data; KLT contributed to data interpretation and JEH contributed to data analysis and interpretation, approved the final manuscript as submitted and had overall responsibility for the study.

  • Funding Health Research Council of New Zealand (grant number: 09/095A) and the New Zealand Lottery Grant Board (grant numbers: 265071, 362747).

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval New Zealand Multi-Region Ethics Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Unpublished data relating to the perinatal characteristics of the study cohort, and the socioeconomic, demographic and self-reported health status of study participants are available to authors JH, SD and AW. No other unpublished data are available.

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