ABSTRACT

Corresponding Author:
Dr. Sajith Vilambil,
Assistant Professor,
Department of Transfusion Medicine,
Government Medical College,
Thrissur-680596, Kerala.
E-mail: drsajithmenon@gmail.com

ABSTRACT

BACKGROUND

ABO incompatibility can cause neonatal jaundice and haemolytic disease of foetus and newborn (HDFN). The aim of this study is to describe the clinical profile of ABO HDFN in a tertiary care centre.

Settings and Design- This was a descriptive study conducted in neonates suffering from ABO HDFN. Setting for the research was Dept. of Transfusion Medicine and Neonatology, Division of Sree Avittom Thirunal Hospital for women and children attached to Govt. Medical College, Trivandrum.

MATERIALs and methods

Neonates who fulfilled the inclusion criteria were enrolled in this study. Demographic details, maternal history, birth details, neonatal blood group, haemoglobin, reticulocyte count, peripheral smear, bilirubin levels, mode of treatment, duration of treatment, ICU stay and followup status, etc. were recorded. Risk of jaundice, severity of disease and intensity of treatment was assessed.

Statistical Analysis- All statistical data were analysed using SPSS software version 16.

RESULTS

The mean bilirubin levels in neonates on Day 1, 2, 3, 4 and 5 were 5.16, 9.55, 11.95, 13.42 and 13.8 mg% respectively. Among 110 neonates with ABO HDFN 51 (46.4%) belonged to low risk, 22 (20%) to low intermediate risk, 19 (17.3%) to high intermediate risk and 18 (16.4%) to high risk categories. Among infants no anaemia was detected in 58 (52.7%), mild anaemia was detected in 40 (36.4%), moderate anaemia in 8 (7.3%) and severe anaemia in 4 (3.6%). Spherocytes were seen in peripheral smears of 94 (85.5%) infants, whereas it was absent in the rest 16 (14.5%) of cases. Disease was mild, moderate and severe among 101 (91.8%), 7 (6.4%) and 2 (1.8%) infants respectively; 74 (67.3%) infants required no treatment. Phototherapy alone was the modality of treatment in 21 (19.1%) infants. IVIG was given along with phototherapy in 13 (11.8%) infants; 2 (1.8%) of infants required exchange transfusion along with IVIG and phototherapy. Regarding transfusion 7 (6.4%) received packed red cells, 3 (2.7%) received platelet concentrate and 1 (0.9%) received fresh frozen plasma. Intensity of treatment was as follows- 74 (67.3%) belonged to grade-0, 21 (19.1%) belonged to grade-1, 13 (11.8%) to grade-2 and 2 (1.8%) to grade-3 category of treatment.

CONCLUSION

Majority of infants had mild hyperbilirubinaemia and no or minimal anaemia. Disease was mild in majority of infants with ABO HDFN, thereby requiring no interventions.

KEYWORDS

Haemolytic disease of foetus and newborn, hyperbilirubinaemia, antibody, ABO, phototherapy, IVIG, exchange transfusion.

BACKGROUND

ABO incompatibility is a leading cause of neonatal jaundice and haemolytic disease of foetus and newborn (HDFN) in countries with high human development index.¹ ABO HDFN had a worldwide incidence of 54.4 per 1,000 births.² Assessing the magnitude of disease by observing their clinical profile was quite an essential tool for effective planning and implementation of better management protocols. Thus, aim of this study was to describe the clinical profile of ABO HDFN in a tertiary care centre.

DISCUSSION

This was a research conducted in the Dept. of Transfusion Medicine and Neonatology division in the Dept. of Paediatrics, Govt. Medical College, Thiruvananthapuram from 2012 March to 2013 August; 110 neonates admitted in newborn nursery with ABO HDFN were included in the study.

Mothers of infants with ABO HDFN were mainly primipara (64.6%). ABO incompatible infants of first pregnancy were at risk of significant haemolysis, because ABO antibodies were naturally occurring. Harvey Klein and David Anstee described that in about 50% of cases of ABO HDFN, first ABO incompatible infant was affected.They added that a severe ABO haemolytic disease in first born infant could be followed by a similar severe disease in subsequent infants.⁶ Our research yielded similar results.

Mode of delivery was mainly vaginal (68.2%) among mothers of infants with ABO HDFN; 48.2% of infants were males. An analysis by Chan Shu et al had narrated that there was no significant difference in the sex distribution of affected infants in ABO HDFN.⁷ Slight female preponderance in ABO HDFN in the present study might be a reflection of population statistics in Kerala, the female-male ratio being 1084:1000.⁸

AAP chart was used to stratify the risk related to bilirubin levels. Among 110 neonates with ABO HDFN 51 (46.4%) belonged to low risk, 22 (20%) to low intermediate risk, 19 (17.3%) to high intermediate risk and 18 (16.4%) to high risk categories. Gilja BK and Shah VP observed that in ABO incompatible infants, minor degrees of red cell destruction frequently raised neonatal bilirubin levels and slightly dropped haemoglobin concentration.⁹ Halbrecht found out that one in 70 - 180 ABO incompatible infants developed jaundice within 24 hours of birth.¹⁰ In a study by Valentine, one in 70 - 180 ABO incompatible infants developed jaundice within 24 hours of birth.¹¹ Sherer et al observed that in ethnic groups expressing strong, numerous and branched A or B antigen sites, high bilirubin levels, severe anaemia, nucleated red cells and even hydrops fetalis was witnessed.¹² Schellong G had opined that premature infants were protected from ABO HDFN due to fewer A and B sites on erythrocytes.¹³ In a research carried out by David and Levine, cord blood bilirubin was not diagnostic of haemolytic disease but was moderately predictive of peak bilirubin levels in ABO HDFN.¹⁴ Whyte J and Graham observed that the cord blood bilirubin was not diagnostic of haemolytic disease, but it correctly predicted on peak bilirubin levels.¹⁵

In our study, among 110 infants with ABO HDFN, 66.4% had low (risk) bilirubin levels and 33.6% had high (risk) bilirubin levels. History of neonatal jaundice in siblings and severity of disease in ABO HDFN were significantly associated with a higher risk of high bilirubin levels. As found out in our research, Gilja et al and Sherer et al postulated that severe disease was likely to be followed by a similar severe disease in subsequent siblings of the same blood group.^9,12 In our study, during followup after two weeks one infant with ABO HDFN was readmitted for treatment of hyperbilirubinaemia.

In present research among infants with ABO HDFN, majority had no anaemia. Quite accordingly, Shah and Gilja observed that minor degrees of red cell destruction resulted only in slight lowering of haemoglobin concentration in infants with ABO HDFN.⁹ In this research mild anaemia was detected in 40 (36.4%), moderate anaemia in 8 (7.3%) and severe anaemia in 4 (3.6%). Mollison and Cutbush observed that in moderately severe ABO haemolytic disease, the cord blood haemoglobin concentration was below normal limits. But it was short lived and anaemia was unusual after first two weeks of life.¹⁶ Murray postulated that severe anaemia was observed in ethnic groups expressing strong, numerous and branched A and B antigen sites substantiates our above mentioned finding.¹⁷ As with Cutbush and Mollison, who noticed that anaemia was unusual after first 2 weeks in moderately severe ABO haemolytic disease, was similar in our study too.¹⁶ Dufour D R, Monoghan W P opined that sex, race, gravidity, birth weight, blood type, etc. of the infant had no significant relationship to clinical outcome.²

In this study, haemoglobin levels displayed a significant negative correlation with intensity of treatment and severity of disease. Close negative correlation between the haemoglobin concentration in cord blood and the infant’s chance of survival was demonstrated by Mollison and Cutbush.¹⁸

Reticulocyte count was increased in 80% of infants in present study. Crawfard et al witnessed that a slight increase in reticulocytes was a common feature in ABO HDFN and in an analysis by Levine et al, reticulocyte count exceeded 15% in 54.5% of neonates.^19,20 In present research, spherocytosis was seen in 85.5% of infants with ABO HDFN. Grumbach summarised that in ABO HDFN microspherocytes were frequently prominent in blood films.²¹

Treatment options of HDFN included phototherapy, IVIG and exchange transfusions with supplementary top-up transfusions. In present study majority of infants with ABO HDFN (67.3%) required no interventions, while a few required phototherapy alone (19.1%). Our results were similar to the observations of Bel et al, who described that 26% DAT positive infants with hyperbilirubinaemia needed phototherapy.²² Osborn et al opined that phototherapy usually prevented further rise in serum bilirubin levels.²³ Murray et al and Osborn et al explained that even dangerous levels of bilirubin concentration in full-term infants with ABO HDFN could be controlled by modern phototherapy alone.¹⁷ They observed that high dose of IVIG and exchange transfusion might be required in certain ethnic groups who express strong A and B sites.¹⁷

Vreman HJ too opined that moderate hyperbilirubinaemia and even dangerous levels of bilirubin concentration in full-term infants with ABO HDFN could be controlled by modern phototherapy alone.²⁴ But M D Eugene Kaplan clearly opined that in severely affected infants a trial period of phototherapy was justified, but would not exclude consideration of an exchange transfusion.²⁵ Severe ABO HDFN which required exchange transfusion was relatively rare in few analyses; none among 1500 neonates in one study, 3 out of 14,000 consecutive births in another study, 3 out of 8000 births in a third study and 6 out of 5704 infants in fourth one.^26,27,28 Falterman C G and Richardson J has observed that transfusion of adult A or B red cells with more antigenic sites might undergo rapid destruction which could result in severe jaundice, kernicterus, haemoglobinuria and even death.²⁹

In a Saudi Arabian research, the value of phototherapy along with IVIG was compared with phototherapy alone in reducing the requirement for exchange transfusion in ABO HDFN. They found out that without any side effects IVIG reduced exchange transfusion rate to one-fourth as compared to control group.³⁰ An alternative successful regime for exchange transfusion was suggested by Lakatos et al which included oral D-penicillamine, phototherapy, intravenous fluids and recombinant human erythropoietin.³¹ In a trial by Romano et al, bilirubin levels became normal in 10 out of 13 infants within 5 - 6 days of treatment with A or B trisaccharides as compared to the control group who never received trisaccharides.³²

The research was a cross-sectional descriptive study. So the assessment of risk and correlation between variables was done with a limited data. Long term analytical studies with greater number of samples are needed for assessing correlation or risk in ABO HDFN.

CONCLUSION

1. Majority of infants had mild hyperbilirubinaemia and no or minimal anaemia.
2. Disease was mild in majority of infants with ABO HDFN, thereby requiring no interventions.
3. There is significant association between neonatal jaundice in siblings and high bilirubin levels in next infants, moderate and severe disease and high bilirubin levels, high bilirubin levels and anaemia and anaemia and ICU stay.
4. Cord blood haemoglobin is negatively correlated with intensity of treatment and severity of disease.

ACKNOWLEDGEMENT

We acknowledge Dr. Anupa Lucas, Dr. Rajany Jose and Dr. Reshmi Ramachandran, Assistant Professors in Dept. of Community Medicine, Govt. Medical College, Thrissur, for their unwavering support and perpetual inspiration in this research. We offer our sincerest obligation to Dr. Lalitha Kailas, Professor and HOD in Dept. of Paediatrics, Gokulam Medical College, Trivandrum, and Dr. Shobha Kumar, Professor in Dept. of Paediatrics, Govt. Medical College Trivandrum, for their scholarly guidance in the course of this work.