Neonatal jaundice: magnitude of the problem in Cairo University's neonatal intensive Care unit as a referral center

Background Neonatal jaundice is one of the most common physiologic problems requiring medical attention in newborns. It is benign in most cases; however, high levels of bilirubin are neurotoxic and can lead to serious brain damage. Objectives This study aimed at assessment of magnitude of neonatal jaundice in cases of neonatal hyperbilirubinemia admitted into neonatal intensive care unit (NICU), Cairo University Pediatric Hospital and to detect possible etiologies, management and outcome. Methods The present work is a retrospective study, included 789 neonates suffered from hyperbilirubinemia over a two-year period. Results Intensive phototherapy and exchange transfusion were used together in 6 cases. Two hundreds and twenty-two cases (28.1%) had exchange transfusion once, 44 cases had it twice, 6 cases had it 3 times and one case had it 4 times. Number of exchange transfusion significantly affects mortality among cases (P= 0.02). Conclusion Neonatal hyperbilirubinemia is an existing problem in our NICU. Intensive phototherapy is an excellent substitute for exchange transfusion. Respiratory distress and sepsis are significantly higher among dead cases. Screening for risk factors is needed to avoid critical hyperbilirubenemia.


Introduction
Jaundice is one of the most common physiologic problems requiring medical attention in the newborn. All infants, term or preterm, healthy or ill, undergo changes in bilirubin metabolism after birth. These normal transitional changes may lead to physiologic jaundice 1 . Epidemiologic studies show that about 60% of term and 80% of preterm babies develop jaundice in the first week of life 2 Neonatal jaundice can be best understood as a balance between the production and elimination of bilirubin, with a multitude of factors and conditions affecting each of these processes 3 .
Neonatal jaundice is benign in most cases; however, high levels of bilirubin are neurotoxic and can lead to serious damage to the brain 4 . Unconjugated bilirubin has a neurotoxic potential because of the ability to cross the blood-brain barrier and can cause kernicterus (chronic bilirubin encephalopathy) 5

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No clear-cut level of bilirubin above which encephalopathy is assured and below which neurologic safety is assured has been determined 6 . Although most of newborns develop some degree of jaundice, bilirubin levels high enough to put a newborn at risk of bilirubin encephalopathy and kernicterus are rare but still occur in Egypt 7 . Iskander et al in 2012 8 reported that the causes of indirect hyperbilirubinemia were ABO incompatibility (25.4%), Rh incompatibility (8.5%) with most mothers had blood group A -ve (3.6%) then O -ve and B -ve (each was 1.7%), sepsis (9.2%), dehydration (13.8%), polycythemia (4.6%), bruising (7.7%), other hemolytic disorders (5.4%), breast milk (1.5%) and undetermined (40%).
Regardless to the cause of indirect hyperbilirubinemia, the goal of therapy is to prevent neurotoxicity 9 . Phototherapy and, if unsuccessful, exchange transfusion remains the primary treatment modalities to keep maximal total serum bilirubin (TSB) below pathologic levels 4 . High-intensity phototherapy significantly reduces TSB and decreases the need for exchange transfusion 10 . When serum bilirubin is rising rapidly or approaching exchange transfusion level, intensive phototherapy must be instituted at maximal spectral power 11 . The aim of current study was to assess the magnitude of neonatal jaundice and detect possible etiologies, management and outcome.

Patients and methods
This retrospective study included all neonates suffered from neonatal hyperbilirubinemia admitted to neonatal intensive care unit (NICU) of Cairo University Pediatric Hospital (CUPH) over a two-year period from January 2010 to December 2011.
Neonates with life-threatening congenital anomalies and neonates presented with signs or symptoms suggestive of central nervous system abnormality due to other causes (e.g. hypoxic ischemic encephalopathy) were excluded from the study, because these neonates may have neurological symptoms and signs which may be mistaken with those due to kernicterus.
When an infant's serum bilirubin is rising rapidly, intensive phototherapy must be instituted at maximal spectral power [11]. American Academy of Pediatrics [6] recommends performing exchange transfusion for full-term healthy newborns at least 4 days of age if their TSB level is 25 mg/dl or more and does not decrease sufficiently with phototherapy alone. Data of each patient were recorded from their files including; a) History taking; date of birth, sex, gestational age, mode of delivery, history of maternal illness and/or drugs, previous siblings with jaundice, symptoms suggestive of kernicterus (in the form of poor suckling, lethargy, hypotonia, hypertonia, arched back and seizures), time of onset of jaundice and any associated symptoms (e.g. respiratory distress). b) Clinical examination; anthropometric parameters, neonatal reflexes, extent of jaundice, pallor and neurological examination, in addition to chest, cardiac and abdominal examination. c) Laboratory investigations; complete blood count, reticulocytic count, maternal and infant blood group (ABO and Rh typing) and blood culture for patients suspected to have sepsis. d) Therapy in the form of phototherapy and its duration with or without exchange transfusion. e) Outcome whether died or living, and the living cases whether normal or discharged with neurological sequelae.

Statistical analysis
Statistical Package for Social Science (SPSS v20) was used after transforming the data from Excel 2013 sheet. Categorical variables were presented by number and percent. They were compared using Chi-square test or Fischer's exact test when appropriate. Continuous variables were presented by mean and standard deviation or median and range. They were compared by student's t-test if parametric data and using Mann Whitney U test if non parametric data. In all tests, P value was considered significant if less than 0.05.

Results
In this study, we studied 789 neonates with hyperbilirubinemia, with demographic and medical data as shown in table (1). Table (2) shows clinical data of the patients. Figure (1) shows the blood group and Rh group of the mothers and figure (2) shows the blood group and Rh group of the neonates. Three hundred and thirty-five cases (42.5%) had ABO incompatibility, sixty-four cases (8.1%) had Rh incompatibility and twenty-seven cases (3.4%) had combined ABO and Rh incompatibility. Table  (3) shows laboratory investigations of the patients.       There were two cases used Bilisphere and died. One case used bilisphere and was discharged with poor feeding.
Average hospital stays of cases used Bilisphere (143 cases) was 3.81 days and average hospital stay of the other cases (646 cases) was 5.21 days.  combined ABO and Rh incompatibilities did not significantly affect mortality among cases with P value 0.11 and 0.39, respectively, while the number of patients who had Rh incompatibility were significantly higher among dead cases with P value 0.005. The number of days of Bilisphere use did not significantly affect the mortality among cases with P value 0.17.

Discussion
Early management with phototherapy alone or with exchange transfusion in indicated cases significantly decline the total serum bilirubin levels on follow up of cases and improve the outcome 7   . Lack of hygiene during and after delivery, poor cord care and unhygienic newborn care practices may be the major factors in acquisition of neonatal infections and sepsis in both hospital and community settings 23 . Lack of proper antenatal care by mothers and absence of being screened for infections and other risk factors may affect their babies 24 .
The outcome of our cases study showed that 20 patients African Health Sciences, Vol 23 Issue 1, March, 2023 died (2.5%) and 769 patients (97.5%) were alive; among them six (0.8%) patients were discharged with poor feeding, five (0.6%) had tone abnormality and twelve (1.5%) had seizures, controlled on anticonvulsant therapy. Henny-Harry and Trotman, 2012 14 found that there were two deaths, but these were related to extreme prematurity and only one patient was discharged with bilirubin encephalopathy. In the present study, the number of patients who had respiratory distress and number of patients who had sepsis was significantly higher among dead cases (P value < 0.001). The number of patients had ABO incompatibility and combined ABO and Rh incompatibilities did not significantly affect the outcome of the cases, while the number of patients had Rh incompatibility had a significant correlation with the outcome of cases of neonatal jaundice. The number of days of Bilisphere use did not significantly affect the mortality. This may be due to the small number of cases used Bilisphere in relation to the total number.
In the present study, two hundreds and twenty-two cases (28.1%) had exchange transfusion once (6 of them died), 44 cases (5.6%) had it twice (none of them died), six cases (0.8%) had it three times (one of them died) and one case (0.1%) had it four times (died). The number of exchange transfusion significantly affects the mortality among cases with P value 0.02. Helal et al. (2018) 25 stated that acute bilirubin encephalopathy (ABE) is still a major problem in Egypt. They reported that overall mortality was 9.9% and concluded that admission total serum bilirubin and maternal illiteracy are good predictors of bilirubin encephalopathy at admission ad discharge. 17 stated that in Egypt, several other factors predispose to severe hyperbilirubinemia and kernicterus. These include inappropriate maternal knowledge about the possible risks of severe neonatal jaundice, delay in seeking medical advice, home therapy for jaundice using neon lamps that do not provide the required wavelength, and difficulty in finding adequate medical care especially in remote areas when required. Iskander et al. (2014) 26 stated that in Egypt, severe hyperbilirubinemia and bilirubin encephalopathy are still being reported in numbers that cannot be ignored. In Egypt, screening for risk factors of severe hyperbili-rubinemia is not routinely done for newborn before discharge from the delivery hospital. The goal of screening for neonatal jaundice is to promote early identification and prompt intervention to avoid severe or critical hyperbilirubinemia that causes kernicterus 27 . Basheer et al. 28 explained lack of screening by that since health policies worldwide have changed favoring shorter hospital stays and early discharge for mothers and their newborns after delivery; kernicterus, which was thought to have almost completely disappeared, remerged and is of greater concern for neonatologists and pediatricians. The major limitation of this study was the lack of follow up of patients after discharge.

Conclusion
The present study proved that neonatal indirect hyperbilirubinemia is an existing problem in our NICU related to many etiological factors. Respiratory distress and neonatal sepsis are significantly higher among dead cases. We also concluded that intensive phototherapy is a good substitute for blood exchange. Screening for risk factors for neonatal jaundice is needed to avoid critical hyperbilirubenemia.