The rhesus incompatible pregnancy and its consequences for affected fetuses and neonates

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Abstract

Rhesus incompatibility in pregnancy may result in haemolytic disease of the fetus and newborn (HDFN). This review discusses the fetal, neonatal and long-term consequences of HDFN and its management. Untreated, the fetal and neonatal prognosis of HDFN is poor. Provision of intravascular intrauterine transfusion (IUT) in a dedicated referral centre significantly reduces perinatal loss. Early-onset, severe fetal anaemia carries a greater risk of adverse fetal and neonatal outcomes and is less amenable to treatment with IUT. Interventions to prevent and treat severe, early onset disease have been investigated, however evidence from randomised controlled trials is required. Neonatal consequences of Rhesus haemolytic disease include early and late postnatal anaemia, and hyperbilirubinaemia leading to bilirubin-induced neurological dysfunction. Neurodevelopmental impairment and adult cardiovascular disease are long-term complications that have been reported in association with severe fetal anaemia. Strategies to prevent fetal hydrops, and further research into the long-term impacts of fetal anaemia may improve health outcomes for adult survivors of HDFN.

Introduction

Rhesus incompatibility in pregnancy is the discordance between maternal and fetal red cell antigens belonging to the Rhesus blood group system (most commonly D, E, e, C & c). Maternal alloimmunisation to antigens on fetal erythrocytes can result in the significant and potentially fatal consequence of haemolytic disease of the fetus and newborn (HDFN). A significant reduction in the prevalence of maternal alloimmunisation to the D antigen has resulted where widespread use of anti-D immune globulin prophylaxis has been implemented for Rhesus-D negative pregnant women. Despite this, Rhesus incompatibility in pregnancy continues to contribute to perinatal morbidity and mortality worldwide. With the availability of modern surveillance techniques and expert therapeutic interventions, consequences of the disease and its treatment are minimised, and the overall outcomes for the fetus and neonate are favourable [1].

Section snippets

Pathogenesis and natural history of HDFN

The pathophysiology underlying HDFN stems from discordance between maternal and fetal red cell antigens. Fetal red cells with paternally inherited surface antigens may enter the maternal circulation during pregnancy or at the time of delivery. Some episodes of fetal-maternal haemorrhage occur in sufficient volumes to cause a maternal immune response to the foreign antigens on fetal erythrocytes. This is well recognised where a Rhesus-D negative woman forms antibodies to a paternally inherited D

Fetal and postnatal outcomes associated with HDFN and its management

Whilst the natural history of severe Rhesus alloimmunisation confers a poor outlook for the fetus and neonate, the trajectory of the disease has been significantly altered by modern management. Significant reduction in the prevalence of Rhesus-D alloimmunisation has occurred as a result of anti-D prophylaxis. Widespread screening for maternal alloantibodies during pregnancy allows for surveillance of at-risk pregnancies and earlier detection of fetal anaemia. Advances in non-invasive

Conclusion

Left untreated, haemolytic disease of the fetus and newborn is associated with significant morbidity and risk of death. With access to current, expert surveillance and interventions for Rhesus incompatible pregnancies, favourable outcomes for the fetus and neonate can be expected. Ongoing investigation of the long-term consequences for fetuses and neonates affected by Rhesus incompatibility will provide further opportunities to optimise the health of adult survivors of HDFN.

Source of funding

No specific grants from funding agencies in the public, commercial, or not-for-profit sectors were received.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

CRediT authorship contribution statement

Caroline Tyndall: Writing - original draft. Rocco Cuzzilla: Writing - review & editing. Stefan C. Kane: Supervision, Writing - review & editing.

Acknowledgements

None.

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