European Journal of Obstetrics & Gynecology and Reproductive Biology
Full length articlePrevalence and obstetric outcome of women with red cell antibodies in pregnancy at the Leeds Teaching Hospitals NHS Trust, West Yorkshire, England
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.
Section snippets
Materials and methods
The total number of obstetric patients screened during the six-year period between January 2011 and December 2016 was obtained from the Trust’s Blood Bank and Transfusion Services database. The subset of women with red cell antibodies was identified from the same database and reconciled with the Fetal Medicine Unit (FMU) database on women with red cell antibodies that were referred for specialist’s care using the Viewpoint© software. The indications for referral to the FMU were maternal serum
Results
In the six-year period under review, 398 out of the 96, 692 pregnant women that were screened by the blood bank and transfusion services of the Leeds Teaching Hospital Trust had circulating red cell antibodies in their sera. The prevalence of red cell antibody in pregnancy in the Trust was therefore calculated to be 1: 242 pregnant women. The median parity of the alloimmunised women was 2 (range of 1-6), and twelve of them were managed for alloimmunisation in two or more pregnancies. Two
Comments
The prevalence of red cell antibody among the pregnant women managed at LTHT between 2011 to 2016 was 1:242 pregnancies; a lower prevalence compared with the 1.80 reported among Caucasian populations from the Netherlands [4]. Although the exact reason for this disparity is uncertain, the multi-ethnic population in Leeds may be partly responsible. Among the 398 alloimmunized women, only 29 (7.3%) had fetal anaemia that was severe enough to require in utero fetal blood transfusion, indicating
Conclusion
Red cell antibody in pregnancy remains a significant cause of iatrogenic preterm delivery and fetal morbidity. While the anti-M and Anti-E antibodies were the predominant antibodies in pregnancy, the anti-D antibody remains the most significant cause of severe fetal anaemia. The use of MCA velocimetry remains reliable for monitoring fetuses at risk of anaemia in pregnancy. Intensive monitoring of alloimmunized women in pregnancy is recommended to facilitate early diagnosis, treatment and
Funding
The authors did not receive any funding for this reseach
Author’s contribution
IA, KC, JR and CS all contributed to study conception, design and data collection. All the authors reviewed the manuscript and made critical contributions to the final manuscript.
Acknowledgement
None.
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