Liggins Institute


Fetal anaemia and the adult heart: long-term effects of intrauterine anaemia.


In New Zealand coronary heart disease is a leading cause of death. It is well recognised that genetics and adult lifestyle are key risk factors. However, recently the importance of early life events has also been recognised: the so-called developmental origins of adult disease.

Fetal anaemia is known to induce a number of adaptations in the fetus in order to preserve myocardial and systemic oxygen supply, and hence end-organ oxygen consumption. In sheep, brief fetal anaemia for only a week results in marked changes to coronary conductance, flow and architecture in adult animals. The long-term significance of these changes in coronary conductance for the life of the animal is currently unknown. It is also not known if these changes occur in humans who suffer fetal anaemia.

In man, the most common cause of fetal anaemia is Rhesus disease, which forms a clinical spectrum from mild haemolytic anaemia to severe hydrops fetalis and fetal death. In 1963 Sir William Liley performed the first in utero transfusion for fetal anaemia due to Rhesus Disease at National Women’s Hospital, Auckland.

The pioneering process developed by Liley remains the international standard treatment for severe fetal anaemia and significantly decreases mortality and morbidity. Small follow-up studies of babies who received in utero transfusion have found no major effect on their development into teenage years. However, there have been no follow-up studies of later cardiovascular function.

As the first recipients of this treatment anywhere in the world, and hence the oldest survivors, were treated in Auckland, a unique opportunity exists to investigate the long-term effects of fetal anaemia and its treatment. We have previous experience in tracing and studying adults many years after their prenatal treatment at National Women’s Hospital.



The study aims to determine the long-term health outcomes of adults who suffered fetal anaemia and were treated with in utero transfusion. Specifically, we wish to measure cardiac function, myocardial blood flow, heart rate variability, cardiovascular risk factors, renal and liver function in adult survivors of severe Rhesus disease.


Design and study subjects

We are conducting a matched cohort study, with the affected cohort composed of adults who suffered fetal anaemia due to Rhesus disease and were treated with in utero transfusion at National Women’s Hospital between 1963 and 1990. The unaffected cohort is composed of siblings of affected participants; hence they are well matched for both genes and environment. Affected and unaffected participants undertake the same study protocol.


Main outcome measures

  • Cardiac MRI is used to assess cardiac function, including assessment at rest and under conditions of stress, induced by adenosine infusion, to assess myocardial blood flow at maximal vasodilatation.
  • Heart rate variability
  • Other health outcomes including cardiovascular risk factors (body size, blood pressure, serum lipids, glucose tolerance), kidney and liver function.

This study will provide the first direct evidence of the effects of fetal anaemia on adult cardiac structure and function in man. It will also provide the first data regarding the effects of severe Rhesus disease and its treatment on adult health. The findings will have potential relevance to the management and long term health implications of this and other causes of anaemia in babies, including twin-twin transfusion syndrome and anaemia of prematurity. The results will contribute to the development of evidence-based management of these problems.