Neonatal hyperbilirubinemia incorporates vital importance on baby morbidity and hospitalizations worldwide wherever the overwhelming majority of the affected neonates reside in sub-Saharan Africa and South Asia [29–30]. During this study prevalence of neonatal hyperbilirubinemia was 94(42.3%) which was a lower finding as reported from Malaysia (63%) [31] and South Africa (55.2%) [32]. However, it absolutely was beyond a finding from Pakistan (27.6%) [11], Benin (26.5%) [21] and Ghana (32.9%) [32]. It was also quite higher as compared to finding from Nepal [18], Indonesia (4.08%) [33], Iran (12.6%) [34], Congo Brazzaville (7.2%) [35], Uganda (22.7%) [36] and Saint Paul's millennium medical college of Ethiopia (13.3%) [27].This finding was concordant with a previous study conducted in Iran (44.8%) [37], Southeast Nigeria (35%) [38], Rwanda (44.3%) [22], and Black lion Ethiopia [39]. This disparity could be due to sampling size, study period difference, study design, study area, methodology difference, and coverage of obstetrics care, definitions of hyperbilirubinemia, and characteristics of the study participant. This study revealed that male neonates had higher odds of developing neonatal jaundice [AOR = 2.234; 95% CI (1.058–4.716)] compared to their female counterparts. The finding was corroborated by studies done in Indonesia [40], Nepal [41], and Nigeria [42]. Conversely, this result was concordant with findings in Croatia [43], Iran [34], India [44], and Egypt [45]. Furthermore, this could be due to that male newborns have comparatively low levels of ligand in which may not be able to process all the bilirubin formed from red blood cells and due to hormonal effects of transporter protein where testosterone down regulates membrane transporter protein which is involved in bilirubin metabolism.
The most affected age group by neonatal hyperbilirubinemia in this study was those neonates in early neonatal periods (1–7 days) at admission which was 50% and those > 7 days old were 6.4%. Another study conducted in Namibia 2017 [2] showed similar age group of neonates was affected to develop potential bilirubin encephalopathy were 3–6 days old after birth which accounted for 9.6%. Other studies in black lion hospitals showed that 52.5% of hyperbilirubinemia neonates were 3–6 days old at admission and those > 6 days old were 32.5% [28]. This showed that as the age of neonate increases the prevalence of neonatal hyperbilirubinemia decreases; the prevalence of neonatal hyperbilirubinemia is inversely proportional to the age of the neonate.
ABO incompatibility and hyperbilirubinemia were significantly associated in our study (AOR 3.942, CI 1.688–9.206). The number of ABO incompatibility in our study was 54 and 61.2% of them which represent 35.10% of the total hyperbilirubinemia infants who developed HB in our study. This finding was consistent with other studies conducted in Northern India [17], Nepal [18], and Ethiopia [26–28]. This finding suggests the possibility of ABO-associated hemolysis as one of the causes of NHB in our study population.
Rh isoimmunization is the most significant cause of hemolytic hyperbilirubinemia in newborn babies. In our study, 12 mother-infant pairs had Rh discordance; 10 participants developed significant hyperbilirubinemia whereas the odds of developing hyperbilirubinemia were significantly high (AOR = 7.296, CI 1.138–46.758). Intravenous immunoglobulin is being used for the treatment of jaundice in newborn infants with hemolytic anemia. This finding was higher than works of Eleje et al in Nigeria (21.3% of Rh discordant develops Neonatal hyperbilirubinemia) compared to 83.3% in our finding [42]. This disparity can be explained by the administration of anti D immunoglobulin (33 (46.5%) of these received anti-D prophylaxes) compared to (2 (16.66%) in our finding that demonstrated the relevance of antenatal screening and prevention measures.
In addition, the study discovered that neonatal hyperbilirubinemia had a significant association with sepsis. The odds of neonatal hyperbilirubinemia among neonates who had sepsis were 2. 9 times higher compared with those neonates who had no sepsis diagnosis [AOR = 2.944; 95% CI (1.164–7.447)]. Sepsis was also identified as the possible cause of neonatal jaundice in studies conducted in India [15, 40–41, 44], Ghana [46] Ethiopia [26–28]. This similarity in finding might be due to similarities in study setting i.e. intensive care unit (sepsis was a common finding in any hospital admissions and need intensive care). Sepsis could be due to poor hygienic environment, poor obstetric and nursery care, and sepsis would also possibly cause hemolysis of red blood cells and hepatic dysfunction that leads to cholestasis from septic states that leads to accumulation of serum bilirubin within the body, and conjointly arise from varied drugs used for sepsis treatment.
Birth asphyxia was also an important determinant of Neonatal hyperbilirubinemia [AOR = 4.131; 95% CI (1.367–12.481)]. Different studies conducted in Kerala India [40], Southern Nigeria [47], and Northern Ethiopia [48] supported that neonatal jaundice is influenced by birth asphyxia. This similarity in finding was because perinatal asphyxia remains a common problem in the neonatal nursery and is a significant coincidence with neonatal hyperbilirubinemia in neonatal intensive care and it was also an insult to the newborn due to lack of oxygen, lack of perfusion to various organs which ends up in multi-organ system dysfunction due to hypoxic damage principally on brain, lung, liver and intraventricular hemorrhage that affect bilirubin conjugation ability of the liver that leads to jaundice [49]. Also, perinatal asphyxia with the hypoxic-ischemic neurological disorder will disrupt the blood-brain barrier, thereby permitting free entry of the unconjugated bilirubin to the neurons leading to a neurological disorder. Besides, kidney damage perinatal asphyxia also causes less excretion of the conjugated bilirubin, thereby inflicting conjugated hyperbilirubinemia and jaundice.
In this study induction of labor with oxytocin had a significant effect on the development of hyperbilirubinemia in neonates [AOR = 3.734; 95% CI (1.653–8.433)]. Our study was consistent with the studies of Shagun Gupta et al [20], Abdul-Aziz et al [45] Garosi E et al [50]. However, the finding was discordant with the study of Kavehmanesh, et al [34] and studies conducted in Poland [51]. Since Oxytocin causes osmotic swelling of erythrocytes leading to decreased deformability and hence more rapid destruction with resultant hyperbilirubinemia in the neonate. Neonatal hyperbilirubinemia had a significant association with the feeding mode of neonates particularly with exclusive breastfeeding [AOR = 3.794; 95% CI (1.441–9.990)]. The association was described in studies conducted by Xavier R et al [52], Maisels etal[53], Yang Fe[54] Garg S[41].Safaa Abu Mostafa et al [55]. This is due to decreased caloric intake/starvation, inhibition of hepatic excretion of bilirubin and an increase in intestinal absorption of bilirubin (enterohepatic circulation) [56], UDGT genetic variation in breast milk [57], and a component of breast milk [58] are suggested mechanisms for the hyperbilirubinemia associated with breast-feeding.
Inadequate enteral feeding favors increased entero-hepatic circulation and delays defecations of meconium and in our study participants 47.8% of had prolonged initiation of breastfeeding after birth. Consequently, participants who had prolonged initiation of breastfeeding after birth were more likely to develop HB and have delayed patterns of defecations[39] Similarly, the odds of developing neonatal hyperbilirubinemia among neonates who had prolonged type defecations of meconium were 6.8 times higher compared with normal one [AOR = 6.800; 95% CI (1.908–24.237)]. It was similar to the finding of Seyedi R et al [59]. However, it was inconsistent with the study conducted in Turkey [60] and Brazil [61]. The disparity could be due to characteristics' of studies subjects i.e. thirty- four percent (34%) of our study neonates were preterm in gestation and prematurity is associated with prolonged Passage of meconium when compared to term infants[62]. This is because one gram of wet meconium contains an equal amount of milligram of bilirubin, delayed passage of meconium and decreased frequency of meconium passage may increase enterohepatic circulation and contribute to the development of jaundice in neonates.
Thirty- four percent of our study neonates were preterm in gestation which was consistent with available studies [44]. Neonates born preterm had higher chances of developing hyperbilirubinemia than neonates born at term [AOR = 3.504; 95% CI (1.436–8.549)]. Prematurity was also identified as the possible cause of neonatal hyperbilirubinemia in studies conducted in India [43], Iran [63], Ghana [46], and Ethiopia [28]. This more common in preterm infants was due to the relative immaturity of the red blood cells, hepatic cells, and gastrointestinal tract than in neonates born at term.
Hematological abnormality is one of the commonest problems encountered in the neonatal intensive care unit (NICU). Of this thrombocytopenia and leukocytosis is prevalent, associated with, and commonly follow hyperbilirubinemia due to bacterial infections [64]. Neonatal hyperbilirubinemia had significant association with both thrombocytopenia [AOR = 2.924; 95% CI (1.279–6.681)] and leukocytosis [AOR = 7.070; 95% CI (2.538–19.694)] in our studies respectively. Most of the available works of literature associate thrombocytopenia as complications of phototherapy in hyperbilirubinemia neonates[65]; however thrombocytopenia due to hereditary thrombotic thrombocytopenic purpura (TTP) caused by ADAMTS13 mutations is a rare but serious condition, often presenting during the newborn period with microangiopathic hemolytic anemia could be a risk factor for neonatal hyperbilirubinemia[66].
Study Limitation
The study design has some limitations in particular the generalizability of findings will be limited to infants admitted to NICU. Since the present study evaluated only the hospitalized newborns and the status of outpatient infants is not known. The studies also could not do blood film and G6PD assay to comment and confirm infection and hemolysis.