INTRODUCTION:

Neonatal jaundice is one of the most common causes of fetus morbidity accounting for about 10%-35% of hospital admissions^1,2. It is a worldwide condition occurring in up to 80% of preterm and 60% of term neonate in first life’s week³. Neonatal jaundice may leading to encephalopathy during neonatal period and even death⁴. One of the common causes of neonatal jaundice is the ABO incompatibility⁵. Maternal-fetal ABO incompatibility occurs when the fetus has blood group A or B And his mother has blood group O. This condition arises in 15-20% of all pregnancies⁶. Hemolytic disease occurs in around 10% of ABO incompatible neonates and may be linked with clinically significant neonatal jaundice⁷.

These fetuses are founded to be at high risk for emerging severe hyperbilirubinemia when serum bilirubin level can exceed 16mg/dl⁴. While the serum bilirubin level in neonates with physiological jaundice does not usually go above 10mg/dl in term and 15 mg/dl in preterm neonate and it is became undetectable after 14 days⁸.

This study aimed to detect the prevalence and effect of maternal-fetal ABO incompatibility on neonates hyperbilirubinemia

MATERIAL AND METHODS:

Study design

The present study was across-sectional hospital based study designed to detect the prevalence and effect of ABO incompatibility on neonatal hyperbilirubinemina. This study conducted at the neonatal wards of central Child’s Hospital in Baghdad city from 1 October 2018 to 1 March 2019.

Data collection:

The data was collected from hospital case file after newborn examination and by use questionnaire method on a sample size of 75 neonates with jaundice admitted to neonatal wards of central Child’s Hospital. Ethical approval for the study was obtained by scientific committee of the hospital and written consent from each neonate caregiver was also obtained before patients enrolling in the study.

This study included neonate with hyerbilirubinemia needing phototherapy and/or exchange transfusion duo to maternal-fetal ABO incompatibility or other causes of neonatal jaundice. the diagnosis of maternal-fetal ABO blood incompatibility was made in the presence of jaundice in a neonates with blood group A or B and their mothers with blood group O.

All hospital files of neonates were reviewed, the clinical parameters and demographic data such as gender, gestational age, day of hospitalization, birth weight, serum hemoglobin and bilirubin levels on admission, blood groups, mode of treatment (phototherapy and/or exchange transfusion), and duration of phototherapy were all recorded.

Depending on 2004 American Academy of Pediatrics hyperbilirubinemia treatment guidelines, the pathologic hyperbilirubinemia was defined as any indirect (unconjugated) bilirubin level requiring phototherapy during the first life’s week⁹.

Exclusion criteria:

Exclude all cases needed emergent treatment or had history of congenital anomalies. Those whose parents did not want to participate in the study and unwilling to give their informed consent and those that were given any drugs causes decrease in bilirubin levels during first life’s week.

Investigations:

The following examinations were done.

· Diagnosis the blood group and Rh type for both mother and her baby by using the suitable antisera with slide and tube methods

· Measuring the hemoglobin level by using cyanmethemoglobin method

· Measuring serum bilirubin level on Auto analyser by Diazo method

Statistical analysis:

Data were analyzed statistically using the statistical analysis system Minitab 16.1 (2010). The study variables were compared by using the least significant difference tests, where data expressed (mean±standard deviation) and as number (%) with no significant differences at (P>0.05), significant at (*P < 0.05), Highly significant (**P < 0.01). Categorical variables were analyzed by Chi square test (χ²), Z test for two proportions, and independent T test used to compare the variables between the study groups.

RESULTS:

Table (1) showed demographic and general data for neonate with hyperbilirubinemia. Forty five (60%) patients were male and thirty patients (40%) were female with no significant difference between both gender. The mean birth weight was (2.62±1.16) kilograms. Majority of the neonates (74.7%) were of ≥37 weeks gestational age while others were ˂37weeks. More than two third (72%) of the present study neonate were >2 days of life at hospital admission while others from 1-2 days. The time of initiation of breast feeding for 88% of study neonate was ˃30 min after birth. presence of hemolysis was reported with only 5.3% of study patients. mean of serum hemoglobin and bilirubin of study patients was (17.54±2.24) and (14.55±6.41) mg/dl respectively. Highest percentage of the present study neonates had blood group O and A (41.3 and 34.7% respectively) while the lowest had blood group AB (1.3%). Statistically highly significant difference for gestational age, neonate age at admission, time of initiation of breast feeding, presence of hemolysis, and different ABO blood groups was presented among study neonates.

Table (1): Demographic and general data for neonate

Variable	Study group		P-value^¥
Gender (neonate)	n	(%)	P-value^¥
Male	45	(60)	0.083^N.S
Female	30	(40)	0.083^N.S
Birth Wt (Kg)	2.62 ± 1.16		-----
Gestational age (weeks)	n	(%)	P-value
˂37	19	25.3	0.001^**
≥37	56	74.7	0.001^**
Neonate age at admission (days)	n	(%)	P-value
<1	0	0	0.001^**
1-2	21	28
>2	54	72
Time of initiation of breast feeding (min)	n	(%)	P-value
˂30 min	9	12	0.001^**
˃30 min	66	88	0.001^**
Presence of hemolysis	n	(%)	P-value
Yes	4	5.3	0.001^**
No	71	94.7	0.001^**
Serum laboratory result of neonate	(mean ± SD)
Serum hemoglobin level(mg/dl)	17.54± 2.24		----
Serum bilirubin level (mg/dl)	14.55± 6.41		-----
ABO blood groups (baby)	n	(%)	P-value
A	26	34.7	0.001^**
B	17	22.7
AB	1	1.3
O	31	41.3

¥: Chi square test (χ²) test for goodness of fit used N.S: No significant differences (P>0.05), * significant at 0.05 (P < 0.05), ** Highly significant (P < 0.01)

Table (2) Blood group distribution of neonates and their mothers and prevalence the ABO incompatibility

Mother's ABO blood group	Baby's ABO blood group								Total
Mother's ABO blood group	A		B		AB		O		Total
	n	%	n	%	n	%	n	%	n 0	%
A	12	16	0	0	0	0	3	4	15	20
B	1	1.3	6	8	1	1.3	1	1.3	9	12
AB	6	8	5	6.7	0	0	0	0	11	14.7
O	7	9.3	6	8	0	0	27	31	40	53.3
Total	26	34.7	17	22.7	1	1.3	31	41.3	75	100
P-Value^¥	0.001^**

¥: Chi square test (χ²) test for goodness of fit used to test more than two category proportions ** Highly significant (P < 0.01)

DISCUSSION:

Hyperbilirubinemia is a common problem occur through neonatal period due to various pathologic and physiologic conditions¹⁰.

The sociodemographic characteristics of the present study patients were similar to that reported by other studies^1,11. Male gender was predominant. Other previous studies demonstrated that higher bilirubin levels presented in males than femals^1,12,13. These outcomes suggest an increased susceptibility of male neonate to marked jaundice. In contrast, different results reported by other study¹⁴.

The mean birth weight of the present study was (2.62± 1.16). This finding was combatable with other study by (Oyapero, et al.) who found that birth weights of most neonate were between 2.5 and 2.99 kg¹. In the present study most neonate were of gestational age ≥37 weeks. Other study reported high incidence of neonatal jaundice in term neonates of 37 and 39 weeks¹. Other studies found that term neonates of low birth weight and low gestational age were more susceptible to jaundice and most be investigated for jaundice before discharge^15,16.

In the present study, the neonate age at admission for most patients was ≥ 3 days of life. This result was in agreement with (Oyapero, et al.) who reported high bilirubin level after 72 hr. of neonatal birth¹. Other study showed that mean age of hospital admission was 4.4±2.4 (0-9) days⁷. Vijaya S and Shah A reported that the mean age of neonate hospital admission was 2.92 and 2.97 days respectively^17,18. Research was observed that neonatal jaundice was a common reason for readmission of healthy newborns after early hospital discharge¹⁹.

Thus, it may be suitable to investigate all neonates for jaundice, mainly those of early gestational age before hospital discharge. Highly significant difference among the study neonates with jaundice according to time of initiation of breast feeding (P value 0.001^**) and most of the neonates(88%) were breastfed after 30 minutes. In contrast other studies reported no association between serum bilirubin level and time of initiation of breast feeding^17,20.

In the present study, the hemolytic disease was reported in only (5.3%) patients of the present study. While other studies reported higher percentage of hemolytic disease (35-38%) in neonate hospitalized with jaundice^12,21,22.

The mean initial serum hemoglobin level of this study was 17.54±2.24 and mean of serum bilirubin level was 14.55±6.41. This results was in agreement with result reported by Akgul S et al who founded that the mean serum hemoglobin level was 15.6±2.3g/dl and mean bilirubin level was 19.9±5.7mg/dl⁷. Other study by (Sabzehei MK) showed that the mean of serum bilirubin level was 17.54±4.07 mg/dL¹⁴. In contrast a study by Thakkar B et al, reported low hemoglobin level (9.0mg/dl) and high serum bilirubin level (30.0mg/dL)²³. This variation in presence of hemolysis and level of serum hemoglobin and bilirubin were due to different causes of neonatal jaundice^{7,17, 14,23}.

According to ABO blood groups, in this study high prevalence of neonatal jaundice occur in patients with blood group O (41.3%). Blood group A was more prevalent (34.7%) than blood group B (22.7%). AB blood group established only1.3%. These results were similar with other studies from different regions which reported highest prevalence of jaundice in O blood group neonate and lowest in AB blood group neonate^24,25,26,27.

The established results of ABO incompatibility vary among different studies^{1,14,28,29,30}. For this study, the calculated percentage of woman carrying blood group O and give birth to a child who was A or B phenotype was17.3%. Result of the present study was in consistent with results of previous studies in this regard, a study in Czech republic founded the ABO incompatibility frequency was 14%³⁰. Where as in Venezuela, it was reported to be 16%⁽²⁸⁾. Other study in Puerto Rico done on two different hospitals, the frequency of ABO incompatibility in Puerto Rico hospital was 28.3%, while in North Carolina hospital the frequency was 18.4%³¹. Other studies reported more lower percentage of neonatal ABO incompatibility prevalence^29,30. Different factors that have been related to neonatal jaundice were analyzed by this study, which might be (at least to best knowledge) the first attempt to evaluate and compared these factors between the ABO compatible and incompatibility neonates. In the present study high similarity was founded for mean of serum bilirubin and hemoglobin levels between both ABO compatible and incompatible neonate with no significant difference. In cases of ABO incompatibility, different studies showed wide range of serum bilirubin levels^7,17,18,32. Akgul S et al reported wide range of initial serum bilirubin from 7.1 to 41.3mg/dl (mean 19.9±5.7) and initial hemoglobin from 8.2-20.8g/dl (mean 15.6±2.3)⁷. Shah A, reported serum bilirubin level from 15-19-9 mg/dl¹⁸. Other study founded that serum bilirubin levels will elevated day by day and reach dangerous levels after birth for neonates suffering from hemolytic disease due to ABO incompatibility¹².

While a study for ABO compatible neonate showed that serum bilirubin level reach maximum rise for up (30 mg/dL) and lowest hemoglobin (9mg/dl)²³. Other studies founded that the ABO hemolytic disease was associated with Racial difference and the higher jaundice level that associated with ABO incompatibility founded in Asian and African patients^33,34,35.

Phototherapy and exchange transfusion were the main therapeutic intervention for neonatal hyperbilirubinemia in hospital. Several studies showed different treatment thresholds for phototherapy and exchange transfusion. The minimum treatment threshold of serum bilirubin level for significant hyperbilirubinemia across different studies was 10–12 mg/d. for term neonates. In general, phototherapy was applied at approximately TSB ≥12 mg/dL (204 µmol/L)³⁶.

In the present study, phototherapy needed for more than 24 hrs. for most ABO compatible and incompatible patients to decrease level of serum bilirubin with no significant difference in duration of phototherapy between both groups.

Exchange transfusion was used when total serum bilirubin level reached ≥20mg/dL (340µmol/L) for healthy term infants, and sometimes in very ill term infants the exchange transfusion used if total serum bilirubin <20mg/dL (340µmol/L) with or without features of kernicterus³⁶.

In the present study, only (9.68%) ABO compatible neonates were received blood transfusions while ABO incompatible neonates did not need blood transfusion and there was no significant difference between ABO compatible and incompatible neonates for blood transfusion. This result was in agreement with (Firouzi M et al) who founded that only 0.4% of infants with ABO incompatible were received blood transfusions ¹². While other study by Lucas GN founded that the rate of exchange transfusion was 40%³³.

Different study founded that most cases of neonatal hyperbilirubinemia due to ABO incompatibility were mild, these studies showed that about 9%-21.3% of neonate with significant hyperbilirubinemia required phototherapy and 4% of neonate with severe hyperbilirubinemia required exchange transfusion^37,38,39.

Gilja et al., in1988, founded no need to treat neonatal hemolytic disease related to blood incompatibility and less common need to blood transfusions for severe hemolysis cases⁴⁰.

However blood group should be evaluated as soon as possible for all neonates born to O positive mother to detect the high risk neonates developing hyperbilirubinemia and or hemolytic disease due to ABO incompatibility.

The data of present study was limited to only small size population and restricted for only one city. Inability to detected and compared the different causes of neonatal hyperbilirubinemia was another limitation of this study.

CONCLUSION:

This study revealed that the prevalence of neonatal ABO incompatibility was (17.33%). There was no significant difference in mean of serum bilirubin and hemoglobin levels between the ABO compatible and incompatible neonates. This study concluded no need of exchange transfusion for ABO incompatible neonates and majority of both ABO compatible and incompatible neonates needed the duration of phototherapy for ≥24 hours and there was no significant difference in duration of phototherapy between both ABO compatible and incompatible neonates

ACKNOWLEDGMENT:

The authors would like to thank Mustansiriyah University (www.uomustansiriyah.edu.iq), Baghdad - Iraq for its support in the present work and special thanks to central Child’s Hospital for their help in providing the practical platform of this study.

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Received on 11.06.2019 Modified on 05.07.2019

Research J. Pharm. and Tech. 2020; 13(1): 141-146.

DOI: 10.5958/0974-360X.2020.00028.1

Variable	ABO compatible neonates (group 1)	ABO incompatible neonates (group 2)	P-Value^¥
Variable	(no=62)	(no=13)	P-Value^¥
Serum bilirubin level (mg/dl)	13.94 ± 5.21	15.15 ±3.29	0.295 ^NS
Serum hemoglobin level	17.69 ± 2.18	16.87 ± 2.49	0.289 ^NS
Type of treatment	n (%)	n (%)	P-Value ©
Exchange Transfusion	6 (9.68)	0	0.014*
duration of phototherapy(hours)	n (%)	n (%)	P-Value €
˂ 24	13 (21%)	4 (30.7%)	0.478
≥24	49 (79%)	9 (69.3%)	0.478