Magnitude of Neonatal Jaundice and Its Associated Factor in Neonatal Intensive Care Units of Mekelle City Public Hospitals, Northern Ethiopia

Background Jaundice in the neonate is one of the most common clinical problems. Globally, every year about 1.1 million babies develop it and the vast majority reside in sub-Saharan Africa and South Asia. Study on magnitude and local factors associated with neonatal jaundice is limited in Ethiopia. So this study was aimed at assessing magnitude and predictors of neonatal jaundice among neonates admitted to neonatal intensive care unit of public hospitals in Mekelle city, Northern Ethiopia. Methods Institution based cross-sectional study was conducted from February to April 2016 in neonatal intensive care unit of Mekelle city public hospitals. Systematic random sampling technique was used to select study participants. Data was collected by interviewing mothers through structured questionnaire and reviewing neonates' medical records using checklist. Multivariable binary logistic regression analyses were employed to identify factors associated with neonatal jaundice. Results A total of 209 neonates with their mothers were included. The proportion of neonatal jaundice was found to be 37.3%. Prolonged labor [AOR = 4.39; 95% CI (1.8-10.69)], being male [AOR = 3.7; 95% CI (1.54-8.87)], maternal “O” blood group [AOR = 5.05; 95% CI (1.53-16.72)], sepsis [AOR = 2.64; 95% CI (1.15-6.05)], and blood type incompatibility [AOR = 18.21; 95% CI (6.36-52.13)] were positively associated with neonatal jaundice while night time delivery [AOR 0.42; 95% CI (0.18-0.96)] showed negative association. Conclusion The magnitude of neonatal jaundice among neonates was found to be high. Duration of labor, time of delivery, sexes of neonate, sepsis, maternal blood group, and blood type incompatibility were significantly associated with neonatal jaundice. Therefore, improving newborn care and timely intervention for neonates with ABO/Rh incompatibility are recommended.


Background
Neonatal jaundice is yellowish discoloration of the skin, sclera, and mucous membranes due to accumulation of unconjugated, nonpolar, lipid-soluble bilirubin pigment in the skin [1,2]. Jaundice in the new born is the most common clinical problem that requires close attention [3], evaluation, and treatment as it is the most common cause of neonatal readmission during neonatal period [4,5]. It is among those easily preventable and treatable clinical conditions despite the fact that letting it in advance can lead to irreversible clinical problem that ends up with neonatal mortality.
Neonatal jaundice has a significant importance in neonatal morbidity and mortality world-wide [6][7][8]. It occurs in up to 60% [9] of term and 80% [3] of preterm newborns in the first week of life. About 10% of breast-fed babies are still suffering from neonatal jaundice during the first months of their life [4]. It is also accountable for 70% neonatal morbidity and 10% mortality [6,10]. About 75% of neonatal mortality because of jaundice complication occurred in South Asia and sub-Saharan Africa [8].
In Ethiopia, neonatal mortality and morbidity are among the highest in the world, on which more than one-third of childhood death occurs within the first 28 days of age [11]. As studies revealed the incidence, etiology and risk factors of neonatal jaundice vary according to ethnicity, economic status, and geographical differences of countries [12]. But, there is limited data on the magnitude of neonatal jaundice in Ethiopia. So this study was aimed at assessing the magnitude of neonatal jaundice and its determinants in Mekelle city, Northern Ethiopia.

Study Design and
Setting. An institution based crosssectional study was conducted to assess the magnitude of neonatal jaundice and its associated factors at neonatal intensive care unit of Mekelle city public hospitals from February to April 2016. Mekelle is located 783kms north of Addis Ababa with a latitude and longitude of 13 ∘ 29 N 39 ∘ 28 E coordinates. Based on the 2007 Census conducted by the Central Statistical Agency of Ethiopia (CSA), the total population projection value of 2016 at Mekelle city is 340,858 of whom 168,261 are females [13].
Mekelle city has three public hospitals, i.e., Ayder referral hospital, Mekelle hospital, and Quiha hospital. Ayder referral hospital is one of the biggest tertiary level referral and teaching hospitals in Ethiopia which provides a broad range of medical services to both in and out patients of all age group in its catchment area [14]. Similarly, Mekelle hospital is the biggest regional hospital in Tigray region. Service of neonatal intensive care was rendered in Ayder and Mekelle hospitals but not in Quiha hospital. Therefore this study was conducted in neonatal intensive care unit (NICU) of Ayder and Mekelle hospitals.

Sample
Size and Sampling Procedure. The source populations were all neonates with their mothers' who were admitted to neonatal intensive care unit of those hospitals. The sample size was determined by using single population proportion formula with the assumption of 35.0% [15] prevalence of neonatal jaundice, 95% confidence level, and 5% margin of error. The sample size was calculated to be 350, but since the estimated total populations in the study area during the study period were less than 10,000 the following correction formula was used: Assumptions nf= final sample size ni= initial sample size=350 N=total estimated neonates with their mother in the study area during data collection time=416 BY adding 10 % nonresponses rate the final study participants were calculated to be 209. Study participants were selected by a systematic random sampling method. The number of neonates selected from each hospital was proportional to their case flow during the study period.

Exclusion Criteria.
Neonate whose mother critically ill or unable to give informed consent.
Neonate who was admitted to NICU more than once during data collection time but either interviewed or excluded once by this study.
Late preterm neonates

Data Collection Procedures and Quality
Control. The data were collected through interviewing of mother using structured questionnaire and review of medical records. The questionnaire was adapted from previous similar literatures [8,[15][16][17]. It had three parts; the first part was maternal sociodemographic characteristics, the second part was obstetric characteristics, and the third part embraces medical, environmental, and neonatal related factors. Data was collected by four BSc nurses who had an experience of data collection and one day training was given. The overall supervision was carried out by the principal investigators. A pretest was conducted on 10% of similar study populations at Wukro hospital, located 47 km eastern of Mekelle city, and appropriate modifications were made.

Data
Processing and Analysis. The filled questionnaires were checked for completeness and entered into EPI INFO version 3.5.3 statistical software and then exported to SPSS version 20 for further analysis. Descriptive statistics was made. Using bivariate analysis candidate variables were identified for multiple regressions at a p-value up to 0.25. Those eligible variables were entered into multiple logistic regression analysis to control the possible confounding variables and to identify independent predictors of neonatal jaundice. Finally, adjusted odds ratio (AOR) and their 95% CI were computed and variables with p-value less than 0.05 were considered as significantly associated with neonatal jaundice.
2.6. Diagnostic Criteria for Neonatal Jaundice. Gestational age is greater than or equal to 32wks.
Neonatal Jaundice. For this particular study, physician's diagnosis was used to identify neonatal jaundice. Then, since physicians did not register the type of neonatal jaundice as physiological, pathological, or kernicterus, those trained data collectors classified the type of jaundice using bilirubin level and IMNCI clinical features

Operational Definitions
Neonate. An infant from birth to 28 days of age.
Late Preterm. Newborn whose gestational age less than 32 weeks.
Neonatal Jaundice. Neonates diagnosed as jaundiced by physician.
Physiological Jaundice. Total bilirubin value along with IMNCI clinical features of physiological jaundice was used to diagnose physiological jaundice. Neonates in the presence of one more of the established IMNCI criteria (only skin on the International Journal of Pediatrics 3 face or eyes yellow and infant aged 2-13 days old) along with total bilirubin value 12mg/100ml in term babies and under 15mg/100ml in preterm babies [18,19].
Pathological Jaundice. Total bilirubin value along with IMNCI clinical features of pathological jaundice was used to diagnose pathological jaundice. Neonates in the presence of one more the established IMNCI criteria (palms and/or soles yellow or skin and eyes yellow and baby is < 24 hrs old or skin and eyes yellow and baby is ≥14 days old) along with total bilirubin more than 12mg/100ml in term and more than 15mg/100ml in preterm [18,19].
Kernicterus. It was defined on the basis of unconjugated hyperbilirubinaemia of more than 340 mol/L in the term newborn or 200 mol/L in preterm with features such as poor sucking, vomiting, drowsiness, hypertonia, paralysis of upward gaze, high pitched cry, involuntary movements, high fever, and convulsions in the established category [15].

Skilled Birth Attendant.
A midwife, physician, nurse, or other health professionals who provide basic and emergency health care service to women and newborn during pregnancy, childbirth, and postpartum period.
Neonatal Sepsis. The hematological criteria along with the established Integrated Management of Neonatal and Childhood Illness (IMNCI) clinical features of neonatal sepsis were used to diagnose neonatal sepsis in this study. Neonates in the presence of one or more of the established IMNCI clinical features [either of fever (≥37.5 ∘ C) or hypothermia (≤ 35.5 ∘ C), fast breathing (≥60 breath per minute), severe chest indrawing, not feeding well, movement only when stimulated, convulsion, and lethargic or unconscious] along with ≥ 2 of the hematological criteria, total leukocyte count (<4000 or >12000 cells/m 3 , absolute neutrophil count (<1500 cells/mm3 or >7500 cells/mm 3 ), erythrocyte sedimentation rate (ESR) (>15/1 h), and platelet count (<150 or >440 cells/m 3 ) were considered to have neonatal sepsis [20].
ABO Incompatibility. For this particular study it was defined as neonates with laboratory confirmed to have ABO incompatibility [21].

Sociodemographic Characteristic of Mothers.
In this study a total of 209 neonates with their mother were included making 100% response rate. The median (±IQ range) age of mothers was 27±7 years ranging from 18 to 50 years, and age range of more than three-fourths of the mothers was between 20 and 35 years. About 142 (67.9%) mothers were living in urban areas. About 189 (90.4%) and 191 (91.4%) mothers were Tegaru in ethnicity and orthodox in religion, respectively. Of the total interviewed mothers, 90 (43.1%) were housewives by occupation.
Regarding educational status, unable to read and write (n=45), able to read and write (n=14), primary education (n=42), secondary education (n=49), and college and above (n=59) were documented among study participants.

Neonate Characteristics.
One hundred twenty-five (59.8%) neonates were male in sex and the median (±IQ range) of age at the time of admission was 1±3 days ranging from 1 to 26 days of whom 90% (188) of neonates age lies within a week. As well, about 103 (49.3%) neonates were delivered at term with birth weight of 2.5 kg and above. In this study, APGAR score of 7-10 was recorded by 149 (71.3%) neonates. Regarding the feeding status, 191 (91.3%) neonates fed breast milk of whom 184 (88%) were EBF. In this study the blood group of neonates was assessed, blood groups A" "B", "AB", "O", and unknown were recorded by 43,36, 22, 58, and 50 respondents, respectively [ Table 2].
With regard to mode of delivery, spontaneous vaginal delivery accounted for 150 (71.8%) whereas instrumental and cesarean section 14 (6.7%) and 45 (21.5%) mothers, respectively. The duration of labor ranges from 4 to 72 hours of which normal duration of labor was recorded by 146 (69.9%) participants. Oxytocin was used as induction of labor by 97 (46.6%) mothers.

Environmental and Medical Factors.
One hundred and thirty-one (62.7%) and 67 (32.1%) neonates were delivered at hospital and health center, respectively. Home delivery was accounted by 11(5.3%) mothers. Regarding birth attendant, 198 (94.7%) deliveries were attended by a skilled birth attendant, 10 (4.8%) by a traditional birth attendant, and 1 (0.5%) no attendant at all. About 113 (54.1%) neonates were delivered at day time.

Proportion of Neonatal
Jaundice. The proportion of neonatal jaundice among neonates admitted to the neonatal intensive care unit of Mekelle city public hospitals was found to be 37.3% (78). Among these 46 (22%) cases were pathological jaundice and the rest 32 (15%) were found to be physiological jaundice. All jaundiced neonates took phototherapy as a mode of treatment, but no exchange blood transfusion.  Table 3].

Factors Associated with Neonatal Jaundice.
Multivariable binary logistic regression analysis was done by taking variables showing significant association on bivariate analysis at p-value of ≤0.25 to control (adjust) the possible confounding. Prolonged duration of labor, time of delivery, mothers blood group, sex of neonate, sepsis, and blood incompatibility had a significant association with neonatal jaundice at p-value <0.05 in multivariate analysis.
The finding of this study showed that the odds of having neonatal jaundice among neonates who were delivered with long duration of labor were almost 4.4 times higher compared with those who were delivered with a normal duration of labor [AOR = 4.39; 95% CI (1.8-10.69)]. As well, neonates who were born during night time were 58% less likely to have odds of neonatal jaundice compared with those neonates who were born during day time [AOR = 0.42; 95% CI (0.18-0.96)], The odd of neonatal jaundice among male neonates was 3.7 times higher compared with those female neonates [AOR = 3.7; 95% CI (1.54-8.87)]. Similarly, the odds of developing neonatal jaundice among neonates whose mother had "O" blood group were five times higher compared with those neonates whose mother had "A" blood group [AOR = 5.05; 95% CI (1.53-16.72)].
In this study sepsis and blood type incompatibility had significant association with the dependent variable. The odds of neonatal jaundice among neonates who had sepsis was 2.6 times higher compared with those neonates who had no sepsis diagnosis [AOR = 2.64; 95% CI (1.15-6.05)]. In the same way, neonates with blood type incompatibility had higher odds of neonatal jaundice compared with those neonates without blood type incompatibility [AOR = 18.21; 95% CI (6.36-52.13)] (Table 4).

Discussion
Neonatal jaundice has a significant importance on neonatal morbidity and a little bit on neonatal mortality worldwide. The vast majority of the affected neonates reside in sub-Saharan Africa and South Asia [15,22]. Limited data were available on magnitude and local factors associated with neonatal jaundice in Ethiopia. This study was aimed at assessing proportion and predictors of neonatal jaundice among neonates admitted to neonatal intensive care unit of public hospitals in Mekelle city, Northern Ethiopia.
This study had shown that prolonged duration of labor had significant effect on development of neonatal jaundice. The odd of jaundice was about four times higher among neonates who were born with long duration of labor compared with those neonates born in normal labor. This finding was in line with findings in Nepal [16]. This might be attributed to bruising and swelling of scalp of newborns due to the excessive pressure applied by birth attendants as a solution for prolonged labor in turn increases risk of jaundice by increasing bilirubin level in the blood [28].
Timing of delivery was significantly associated with neonatal jaundice with an increased risk observed among neonates born during day time. Neonates who were born during night time were 58% less likely to develop neonatal jaundice compared to those who were born during day time. This could be explained by the fact that room temperature is high during day time compared with night time. Considering the relative high room temperature during day time there might be improper immediate new born care especially on keeping the newborn warm that leads to hypothermia which is a known risk factor of neonatal jaundice by increasing unconjugated serum bilirubin level [29].
This study revealed that male neonates had higher odds of developing neonatal jaundice compared to their female counterparts. The finding was supported by studies done in Nepal [16] and Nigeria [25]. Conversely, this result was inconsistent with findings in Croatia [23], Iran [5], and Egypt [24]. This finding could explain that male newborns have relatively immature liver which may not be able to process all the bilirubin formed from red blood cells [30,31].
It was also found that the odds of developing neonatal jaundice among neonates whose mother had "O" blood group were almost five times higher compared with those neonates whose mother had "A" blood group. Study done in Iran showed that mothers of "O" blood group had no significant effect on development of neonatal jaundice [5].
Moreover, the study revealed that neonatal jaundice had significant association with sepsis. The odds of developing neonatal jaundice among neonates who had sepsis were about two times higher compared with those neonates who had no sepsis diagnosis. Sepsis was also identified as the possible causes of neonatal jaundice in studies conducted in India [22,32,33], Iran [34,35], and Nigeria [15,26]. This might be due to the fact that sepsis might cause hemolysis of red blood 6 International Journal of Pediatrics  cells and hepatic dysfunction that leads to accumulation of serum bilirubin in the body [36,37]. Another contributing factor of neonatal jaundice was blood incompatibility. In this study 27 (93.1%) neonates with ABO incompatibility developed neonatal jaundice and it represents that 34.62% of the total jaundiced neonates had ABO incompatibility. Similarly, this disorder was reported as a leading cause of neonatal jaundice in the studies conducted in Canada [38], India [22,33], Iran [35], Egypt [24], and Benin [17].
The limitation of the study was using small sample size; study participants with unknown ABO blood group were numbered as lacking ABO/Rh incompatibility; and G6PD was not assessed.

Conclusion
Neonatal jaundice is one of the common causes of neonatal morbidity in neonatal intensive care unit (NICU). The magnitude of neonatal jaundice among neonates admitted to 8 International Journal of Pediatrics neonatal intensive care unit of Mekelle city public hospitals was high. Being male, day time delivery, prolonged duration of labor, maternal "O" blood group, sepsis, and blood type incompatibility were the independent predictors of neonatal jaundice. It is recommended to have blood test during pregnancy with early intervention for those who had risks of fetomaternal blood group incompatibility.

AOR:
Adjusted odds ratio ANC: Antenatal care APGAR score: Appearance pulse grimace activity respirationscore COR: Crude odds ratio EDHS: Ethiopian Demographic and Health Survey PNC: Postnatal care NICU: Neonatal intensive care unit.

Data Availability
Data supporting this finding can be found upon request.

Ethical Approval
Ethical clearance was obtained from institutional review board of Mekelle University. Official letter of permission was written to the respective hospitals. The interview was conducted in a private environment convenient for the participants.

Consent
After giving clear and deep explanation about the aim of the study, all mothers that were involved in the study were asked for their willingness and informed written consent was obtained from each respondent. Persons who were unwilling to response were exempted from the study.