Prevalence and obstetric outcome of women with red cell antibodies in pregnancy at the Leeds Teaching Hospitals NHS Trust, West Yorkshire, England

Abstract

Objective

The prevalence of red cell antibodies in pregnancy varies with ethnicity and geographical location, while the obstetric outcome depends on the available standard of care. Despite being the tertiary fetal medicine centre in West Yorkshire, the prevalence of red cell antibodies, and the outcome of pregnancies associated with these antibodies at the Leeds University Teaching Hospitals Trust remains unreported. This article aims to provide this information for the purpose of patient education and counselling.

Study design

The data of pregnant women with red cell antibodies between January 2011 and December 2016 was obtained from the Trust's database and reconciled with the Fetal Medicine Unit records using Viewpoint©. Fetal anaemia requiring in utero transfusion (IUT) was defined as a Middle Cerebral Artery Peak Systolic Velocities ≥ 1.5multiple of the median expected for gestational age. The mean gestational age at delivery, and perinatal outcomes of the pregnancies were recorded.

Result

Overall, 398 of the 96, 692 pregnant women that were screened had red cell antibodies, giving a prevalence of 1: 242 pregnancies. The Anti- E and Anti-M antibodies were the most common (114 women; 28.6%, and 112 women; 28.1% respectively), but did not cause fetal anaemia in isolation, while anti-D alloimmunization was the predominant indication for in-utero transfusion (IUT). Anti-DE and anti-Kell antibodies had the highest mean number of transfusions per pregnancy. The mean gestational age at delivery was 34 ± 2weeks. Post-transfusion fetal demise was recorded in two hydropic fetuses, both at a gestational age of 25 weeks; giving a transfusion-related mortality rate of 2.5%.

Conclusion

The prevalence of red cell antibodies at West Yorkshire is lower compared with reports from other Caucasian populations.Nevertheless, these antibodies are important causes of iatrogenic preterm delivery and fetal morbidity. The prognosis is however good with prompt diagnosis and management.

Introduction

Since the discovery of the human ABO blood group in 1901 by Nobel Laureate Karl Landsteiner, and the Rhesus blood group in 1937, in conjunction with Weiner, knowledge of the blood group antigen/antibody interaction has evolved significantly [1]. Several other red cell antigens have been described in humans in addition to the rhesus and ABO antigens, with varying significance in blood transfusion and organ transplantation services. This knowledge has also become especially important in obstetric practice, where the previously limited understanding of feto-maternal haemorrhage and maternal alloimmunization in pregnancy had led to significant morbidity and mortality among fetuses and newborns [[2], [3], [4]].

Red cell antibodies in pregnancy are common, with varying prevalence based on geographical and ethnic distribution. They may be broadly classified into three, including; 1) Antibodies that pose significant fetal and neonatal risks such as anaemia, haemolysis, hyperbilirubinaemia and its sequelae to the fetuses and neonates; 2) Antibodies that mediate blood transfusion reactions and may therefore constitute a challenge to the safe provision of blood for transfusion purposes during pregnancy and delivery, and 3) Antibodies of undetermined significance in pregnancy [4].

The most common red cell antibodies include the Rhesus group (anti-c, -C, -D, -e and -E), Kell (anti-K, Anti-Kp), Duffy (Anti-Fya and -Fyb), Kidd (Anti-Jka and -Jkb), MNS (Anti-M, -N and -S), and Lewis (Anti-Lea and -Leb) antibodies [5,6]. Rhesus alloimmunization is however reported to precipitate the most severe forms of HDFN in medical literature, especially due to maternal anti-D antibody in rhesus negative women bearing rhesus positive fetuses [4,7,8]. About 16% of the Caucasian population are reported to be rhesus D negative, with about 65,000 rhesus positive babies born to these women annually in the UK [9].

Advances in scientific knowledge and clinical care have led to a reduction in the number of women with red cell antibodies in pregnancy. Routinely, pregnant women in the UK are tested for their blood group and red cell antibodies at booking, and at a gestational age of 28 weeks if the initial screening is negative. Postpartum anti-D prophylaxis for rhesus negative women started in the UK in 1969 and antepartum administration following sensitizing events such as vaginal bleeding and amniocentesis started in 1976. Prior to these, the incidence of alloimmunization in rhesus-D negative women following the delivery of rhesus-D positive infants was in the order of 16%, reducing to about 2% following the policy of postpartum administration of anti-D immunoglobulin [2]. With improved understanding of the concept of silent feto-maternal haemorrhage and consequent alloimmunization in pregnancy, Routine Antenatal Anti-D Prophylaxis (RAADP) was recommended by the UK National Institute for Health and Clinical Excellence (NICE) in 2002 for unsensitized rhesus-D negative women, and it is estimated that the rate of alloimmunization has reduced further by ten-fold to about 0.2% [2,9,10]. This has in turn significantly reduced the perinatal mortality rate associated with haemolytic disease of the fetus and newborn [2,11].

The Leeds Teaching Hospitals Fetal Medicine Unit provides tertiary specialist care for women with high risk pregnancies, including rhesus D-negative women and women with prior or ongoing pregnancies complicated by red cell alloimmunization, using a care plan that entails routine screening in pregnancy, RAADP for rhesus negative women, immuno-prophylaxis after sensitizing events, fetal Middle Cerebral Artery (MCA) Peak Systolic Velocity (PSV) doppler monitoring of alloimmunized pregnant women for fetal anaemia, in utero fetal blood transfusion where indicated and postpartum anti-D antibody for rhesus negative women who delivered rhesus positive babies. This article seeks to review the prevalence of red cell antibodies in pregnancy at the Leeds Teaching Hospitals Trust (LTHT), and the perinatal outcomes of alloimmunized women that were managed in pregnancy at the Trust. The outcome of invasive treatments such as in utero fetal blood transfusion where undertaken, was provided for the purposes of patients’ counselling.