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Abstract

Alloimmunisation, formerly isoimmunisation, or sensitisation can occur in pregnancy when a Rhesus D (RhD)-negative woman carries an RhD-positive fetus. Incompatibility of Rh status causes development of allo anti-D antibodies in response to antigen exposure from foreign fetal red cells in fetomaternal haemorrhages (FMHs) or potential sensitising events (PSEs) i.e., iatrogenic interventions (medical or surgical treatment), silent or spontaneous transplacental haemorrhages (STHs) in pregnancy, at birth or other traumas. Anti-D antibodies are immune-mediated and can cross the placenta and attach to fetal cells causing destruction and haemolysis. Offspring of primigravida women are unaffected usually and it is later pregnancies that may suffer from haemolytic disease of the fetus/newborn (HDFN). Annually, approximately 5000 RhD-positive neonates are born to RhD-negative mothers and approximately 50 neonates develop HDFN in Ireland (HSE 2014). Absence of identification and intervention can cause disability, morbidity, and mortality for the fetus/newborn and distress for the mother. HDFN involves anaemia, bilirubinaemia, and jaundice, however hydrops fetalis in utero and kernicterus may occur, and consequently, fetal intrauterine death (IUD), miscarriage, or stillbirth can proceed (Hall and Avulakunta 2022).

As per the British Committee for Standards in Haematology (BCSH), RhD sensitisation carries a particular risk of HDFN (White et al. 2016). Administration of anti-D immunoglobulin (Ig) in postnatal prophylaxis regimens along with routine antenatal anti-D prophylaxis (RAADP) has helped in overcoming alloimmunisation and HDFN since the 1960s (Kent, Farrell and Soothill 2014). Current guidelines in Ireland for RAADP suggest administration for non-sensitised pregnant RhD-negative women at 28-30 weeks. Additional anti-D immunoprophylaxis is offered following PSEs and after birth, but 40% of healthy pregnant RhD-negative women are prenatally prescribed prophylaxis unnecessarily (HSE 2014), causing ethical issues.

Cell-free fetal deoxyribonucleic acid (cffDNA) in maternal plasma allows automated high-throughput non-invasive prenatal testing (NIPT) in fetal RHD genotyping schemes, which, with targeted routine antenatal anti-D prophylaxis (tRAADP) aim at decreasing excessive prescription and improving management of pregnant RhD-negative women carrying RhD-negative or RhD-positive fetuses (IBGRL n.d.).

Therefore, the aim is to analyse improvements in managing RhD-negative pregnancies via fetal RHD genotyping and NIPT, limiting prophylaxis to those really requiring it, all the while protecting HDFN prevalence in Ireland.

Key Objectives

  • To assess the benefits, restrictions and risks of RAADP.
  • To assess the benefits, restrictions and risks of fetal RHD genotyping, NIPT and tRAADP.
  • To discuss improvements tRAADP should bring to healthcare in Ireland.

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