Shitran & Abed (2020): Profile of neonatal August 2020 Vol. 23 Issue 12 RISK FACTORS AND OUTCOMES OF NEONATAL JAUNDICE AT AL-RAMADI TEACHING HOSPITAL FOR MATERNITY AND CHILDHOOD

Rana F. Shitran1*,Maysam Y. Abed2

1Department of , Anbar University, Iraq

2Alramadi teaching hospital for maternity and childhood, Iraq

*Corresponding author E-mail: [email protected]

ABSTRACT

Jaundice’ is a yellow-orange discoloration of the skin and sclera because of excessive in the skin and mucous membrane. Jaundice caused by indirect neonatal hyperbilirubinemia (INH) is a common and a frequent cause of neonatal admission to health care facilities all around the world.

The main aim of this study is to determine the prevalence of neonatal jaundice and explore its risk factors in term and preterm neonates

In this cross-sectional study Newborns sampled after delivery and before discharge who developed hyperbilirubinemia and required phototherapy and/or within the first 14 days of life included in this study. Those who do not require phototherapy excluded from the study.

The investigation done according to clinical feature, and include , serum bilirubin, blood group, TSH, , reticulocyte count, ABO, Rh, G6PD and TORCH screening

The total number of study patients was 487. All of them were neonates diagnosed with neonatal jaundice. In table (1), 47% of patients were aged between 3 – 5 days; 58.7% of them developed jaundice at age between 1 – 3 days; 60.4% were males; 43.5% were delivered at Summer season; 76.8% of them were full-term; 83.6% were weighed ≥ 2500 gm; 55.2% were delivered by NVD; 37.6% were fed by breast and bottle feeding; 2.1% showed signs; 9.4% needed exchange transfusion; and two patients (0.4%) were died.

Keywords: exchange transfusion, kernicterus, neonatal hyperbilirubinemia, medical sciences

How to cite this article: Shitran RF, Abed MY (2020): Risk factors and outcome of neonatal jaundice at Al-Ramadi Teaching Hospital for maternity and childhood, Ann Trop Med & Public Health; 23(S12): SP231228. DOI: http://doi.org/10.36295/ASRO.2020.231228

INTRODUCTION

The term ‘jaundice’ used to describe the yellow-orange discoloration of the skin and sclera because of excessive bilirubin in the skin and mucous membranes(1,2). Jaundice caused by indirect neonatal

Annals of Tropical Medicine & Public Health http://doi.org/10.36295/ASRO.2020.231228

Shitran & Abed (2020): Profile of neonatal jaundice August 2020 Vol. 23 Issue 12 hyperbilirubinemia (INH) is a common and a frequent cause of neonatal admission to health care facilities all around the world(3).

Regarding poor access to care, prematurity, and Glucose-6-phosphate dehydrogenase (G6PD) deficiency are considered important causes of INH(3-5).Though phototherapy is a very efficacious tool to treat INH, it is not accessible to more than 6 million (~ 45%) of at-risk worldwide. (6)Inaccessible treatment has clinical, public health, and economic effect for both the health care and education systems (7). According to the National Hospital Statistic Report, jaundice lead to morbidity in neonates of (37.8%), & responsible for 7.4% of the neonatal mortality(8). The mechanism of neonatal jaundice is the imbalance between production and conjugation of bilirubin, resulting in an increase in bilirubin levels. (9) This imbalance mainly due to immaturity of theliver in neonate and the rapid destruction of red blood cells, which may be multifactorial(9-12). At bilirubin levels of between 85 μmol/L and 120 μmol/L, neonatal jaundice can be clinically diagnosed(13-15). Neonatal jaundice is very common and occur in 60% of term babies and up to 80% of premature babies (9,11,12,14). Neonatal jaundice is usually not hazardous and a self-limiting condition; however, very high levels of bilirubin may lead to permanent brain damage, a condition called kernicterus(16).

MATERIALS AND METHODS

A prospective study done in NCU at AL Ramadi teaching hospital for maternity and childhood. After getting permission and ethical approval, we collect the data after taking the license from parents, family members of the patient clearly informed about the objective of the study.The data collected by questionnaire prepared by the researchers. the questionnaire checked to identify any discrepancy in information quality and private coding. All the jaundiced newborns admitted to NCU of AL-Ramadi teaching hospital for maternity and childhood, from September 2018 to October 2019, enrolled in the study. Newborns who developed hyperbilirubinemia and required phototherapy and/or exchange transfusion within the first 14 days of life included in this study. Those who do not require phototherapyexcluded from the study. The investigation done according to clinical feature, all patients sent for Complete blood count, serum bilirubin, blood group. The TSH done as a neonatal screening to . Neonatal infections were diagnosed based on the presence of clinical signs of infection (fever, hypothermia, pallor, jaundice, refusal to feed, vomiting, abdominal distension, , altered consciousness, convulsions, coma) and any of the following biological criteria: leucocytosis>25,000/mm3, leucopenia <5000/mm3, platelets <100,000/mm3,C- reactive proteins >20 mg/lwith documented blood culture results revealing the causative agent(16). Coombs test and reticulocyte count were done in babies of ABO or Rh incompatibility, G6PD deficiency was screened in these babies who had rapid rise of serum bilirubin. TORCH screening was done in those who had clinically suspected congenital infection.

RESULTS

The total number of study patients was 487. All of them were neonates diagnosed with neonatal jaundice. In table (1), 47% of patients were aged between 3 – 5 days; 58.7% of them developed jaundice at age Annals of Tropical Medicine & Public Health http://doi.org/10.36295/ASRO.2020.231228

Shitran & Abed (2020): Profile of neonatal jaundice August 2020 Vol. 23 Issue 12 between 1 – 3 days; 60.4% were males; 43.5% were delivered at Summer season; 76.8% of them were full-term; 83.6% were weighed ≥ 2500 gm; 55.2% were delivered by NVD; 37.6% were fed by breast and bottle feeding; 2.1% showed kernicterus signs; 9.4% needed exchange transfusion; and two patients (0.4%) were died.

Table 1: Distribution of study patients by general and clinical characteristics Variable No. (n= 487) Percentage (%) Age (Days) < 3 37 7.6 3 - 5 229 47.0 > 5 - 10 182 37.4 > 10 39 8.0 Age of onset (Days) Within 24 hrs. 67 13.8 1 - 3 286 58.7 > 3 - 10 130 26.7 > 10 4 0.8 Gender Male 294 60.4 Female 193 39.6 Season of birth Spring (Mar, Apr, and May) 124 25.5 Summer (Jun, Jul, and Aug) 212 43.5 Autumn (Sep, Oct, and Nov) 39 8.0 Winter (Dec, Jan, and Feb) 112 23.0 Gestational age at birth (Weeks) < 32 15 3.1 32 – 36+6 98 20.1 ≥ 37 374 76.8 (kg) < 2.5 80 16.4 ≥ 2.5 407 83.6 Mode of delivery NVD 269 55.2 C/S 218 44.8 Type of feeding Breast 129 26.5 Bottle 175 35.9 Mixed 183 37.6 Presence of kernicterus signs

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Shitran & Abed (2020): Profile of neonatal jaundice August 2020 Vol. 23 Issue 12

Yes 10 2.1 No 477 97.9 Exchange transfusion need Yes 46 9.4 No 441 90.6 Outcome Discharged home 485 99.6 Death 2 0.4

Regarding risk factors of jaundice, 30.2% of cases diagnosed as physiological jaundice as shown in figure (1).

Figure 1: Risk factors of jaundice

Mean of TSB level was ranging from 4.6 – 36 mg/dl with a mean of 16.76 mg/dl and a standard deviation (SD) of ± 4.21 mg/dl. The highest proportion of study patients showed TSB level between 10 – 20 mg/dl (81.3%) as shown in figure (2).

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Shitran & Abed (2020): Profile of neonatal jaundice August 2020 Vol. 23 Issue 12

Figure 2: TSB level among study patients

Association between the need for exchange transfusion and certain characteristics is shown in table (2). We noticed that the need to exchange transfusion is increased significantly with earlier onset of jaundice (22.4% of babies who showed jaundice within 24 hrs. of age needed exchange transfusion; P= 0.001). About 25% of patients who diagnosed with G6PD as a risk factor for jaundice needed exchange transfusion with a significant association (P= 0.001) between need to exchange transfusion and risk factors of jaundice. No statistically significant associations (P ≥ 0.05) betweenneed to exchange transfusion and all other characteristics

Table 2: Association between need for exchange transfusion and certain characteristics Exchange transfusion Total (%) Variable Yes (%) No (%) P - Value n= 487 n= 46 n= 441 Gender Male 26 (8.8) 268 (91.2) 294 (60.4) 0.341 Female 20 (10.4) 173 (89.6) 193 (39.6) Age of onset (Day) Within 24 hrs. 15 (22.4) 52 (77.6) 67 (13.8) 1 - 3 23 (8.0) 263 (92.0) 286 (58.7) 0.001 > 3 - 10 8 (6.2) 122 (93.8) 130 (26.7) > 10 0 (0) 4 (100.0) 4 (0.8) Gestational age Preterm 8 (7.1) 105 (92.9) 113 (23.2) 0.216 Term 38 (10.2) 336 (89.8) 374 (76.8)

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Risk factors of jaundice Physiological 2 (1.4) 145 (98.6) 147 (30.2) ABOincompatibility 15 (12.6) 104 (87.4) 119 (24.4) 5 (9.1) 50 (90.9) 55 (11.3) G6PD 13 (25.5) 38 (74.5) 51 (10.5) 0.001 Rh incompatibility 6 (12.0) 44 (88.0) 50 (10.3) Prematurity alone 2 (5.4) 35 (94.6) 37 (7.6) Others 3 (10.7) 25 (89.3) 28 (5.7) Birth weight (kg) < 2.5 9 (11.3) 71 (88.8) 80 (16.4) 0.335 ≥ 2.5 37 (9.1) 370 (90.9) 407 (83.6)

DISCUSSION

In our study population male (60.4%) were predominant with male to female ratio 1.54:1 this agree with Boskabadi et al. showed that bilirubin level was higher among male newborns, compared to the female (17). The explanation is unknown. in our study the first week of life, most newborns developed hyperbilirubinemia and jaundice symptoms. This physiological phenomenon is the result of impairment in bilirubin excretion mechanisms, these are similar to what is stated in Deng G, et al. (18).

In the present study, elevated bilirubin levels were noticed in four seasons; however, there is recognizable rise in summer. This agrees with the study of Gonazales, who found an obvious increase in bilirubin levels in summer. Main cause of increase in bilirubin level is summer heat with subsequently higher dehydration rate (19).

This is contrary to Dolas et al. who found, the rise of serum bilirubin in winters is higher, can possibly due to less sunshine duration and due to the fact that children born in the winter period are more exposed to other contributing agents, such as infections leading to inflammation of the -biliary system and obstructive jaundice, thus increasing direct bilirubin (20).

In this study, we noticed that babies born naturally are more likely to develop neonatal hyperbilirubinemia than babies born by caesarean section, this is due to andoxytocin induction are considered as risk factors for hyperbilirubinemia, this agree with Chang et al., Cheo and Karen (21, 22).

Our study showed the breast feeding constitute about (26.5%), bottle feeding (35.9%) and mixed feeding (37.6%), these results are contrary to previous researches who found that breast-fed infants lose more weight than bottle-fed infants and that there is an association between BW loss and hyperbilirubinemia, so the breast feeding more exposed to hyperbilirubinemia according to other studies; this explained by most of mixed fed babies have breast feeding initially and their caregivers introduce formula lately (23- 25).

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Also, Regardless of type of feeding, the time also has an effect on jaundice; Newborns who are fed in the first 3 h of birth usually pass meconium in the next 4 hours. As 1 g of meconium contains 1 mg of bilirubin, delayed meconium excretion increases the intestinal-hepatic flow, thereby increasing neonatal jaundice (26).

In current the study, physiological (30.2%) was the most common cause of neonatal hyperbilirubinemia, due to breakdown of red blood cell and immaturity of newborn's liver which cannot effectively metabolize the bilirubin, this is similar to ChoudhuryHabiburRasul, et al. (27) whereas ABO incompatibility and prematurity were report as commonest causes of hyperbilirubinemia by Guaran et al. from Australia and by Dawodu et al. from United Arab Emirates (UAE). The prematurity was the most common cause of hyperbilirubinemia in Bangladesh reported by el-Beshbishi et al. Neonates' liver is premature and their digestive system cannot void the bilirubin. This causes unconjugated hyperbilirubinemia in preterm neonates, this may be due unfitting sucking posture and inadequate feeding (28- 30)

In our study ABO incompatibility was the second most common cause of neonatal jaundice (24.4%), antibodies that can attack the newborn's blood and causes the , ABO is the most common cause of hemolytic disease in newborn baby, we found it by positive coomb's test, this agree withStevenson DK et al., and MacDonald MG, et al. (31, 32).

Sepsis was involved in 55 (11.3%) cases, most cases of sepsis we found it in the outborn NCU not in the inborn NCU, the mechanism of jaundice in maybe associated to liver involvement by infection or hemolysis, although this mechanism is not well known. Conjugated hyperbilirubinemia can be related to cholestasis secondary to bacterial infection. The mechanism in which infection causes cholestasis is not known, but possible mechanisms involve microcirculatory changes in the liver, direct effects from bacterial products, and/or from endotoxin induced mediatorsthis is due to cytokine release with sepsis, so the bodies therefore cannot process bilirubin normally, leading buildup of bilirubin. Whereas one of the similar studies published by Roelofsen H. et al. there is a relationship between sepsis and neonatal hyperbilirubinemia (33, 34).

In this study, G6PD assay was done for newborns whose bilirubin level was rapidly rising and they constitute about 10.5% of total number. This differs from Akhter N, et.al. who found that 7.7% had G6PD deficiency among infants with neonatal jaundice, may be explained by genetic factor (35).

In this study about 13 cases of G6PD deficiency patients required exchange transfusion while 38 cases required phototherapy with conservative treatment, this agree with SayesYousef who found majority of the G6PD deficient patients required just phototherapy (35).

In current study About 46 (9.4%) patient required exchange transfusion this result differs from Arrif K. et al. who found that only (3.3%) patients required exchange transfusion, this explained by majority of patient in our study presented lately with higher levels of TSB and inefficient phototherapyequipment's (36).

In our study most cases needed exchange transfusion was ABO, this is similar to.RajeshBansal, et al. The frequency of RH negative blood group in our study is 12%, it is 5% in India as against 15% in European. The incidence of RH HDN as the most common cause of neonatal jaundice is decreasing because of prophylactic antenatal immunization with anti D globulin mother (37).

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According to our study,ninety nine percent of the study population was discharged home following treatment, while the death rate for neonatal jaundice was 2(0.4%) cases related to sepsis and prematurity. This is similar to the causes of death which Owa et al found in Ile Ife Nigeria, in which septicemia was associated with high TSB level and the highest fatality. Neonates who suffering from sepsis are likely to develop high TSB from increased hemolysis and defective conjugation of bilirubin. the cause of increase TSB of Premature babies are that liver function is inefficient resulting in defective conjugation of bilirubin and increased hemolysis from reduced red cell life span (38, 39, 40).

CONCLUSION The hospital prevalence of neonatal jaundice in this study is quite high. In our study physiological and, ABO incompatibility were found to be most frequent causes of neonatal jaundice. Hemolytic causes like rhesus, ABO incompatibility and glucose-6-phosphate dehydrogenase (G6PD) deficiency were found significant. The babies who died developed septicemia. Adequate treatment of sepsis will significantly reduce mortality in these babies. A well-designed population-based study needed to confirm the risk factors related to newborn jaundice, which in turn help prevention of neonatal mortality and morbidity in Iraq.

ETHICAL CLEARANCE

The Research Ethical Committee at scientific research by ethical approval of both environmental and health and higher education and scientific research ministries in Iraq

CONFLICT OF INTEREST

The authors declare that they have no conflict of interest.

FUNDING: Self-funding

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