Original Article International Journal of Pediatrics, Vol.1, Serial No.1, Dec 2013 Hyperbilirubinemia and Neonatal Infection Gholamali Maamouri1, Fatemah Khatami1, Ashraf Mohammadzadeh1, Reza saeidi1, Ahmad shah Farhat1, Mohammad Ali Kiani1,*Hassan Boskabadi1 1Neonatal Research Center , Mashhad University of Medical Science (MUMS), Mashhad, Iran. Abstract Introduction: Hyperbilirubinemia is a relatively common disorder among infants in Iran. Bacterial infection and jaundice may be associated with higher morbidity. Previous studies have reported that jaundice may be one of the signs of infection. The aim of this study was to determine the incidence rate, presentation time, severity of jaundice, signs and complications of infection within neonatal hyperbilirubinemia. Materials and Methods: This cross sectional study was conducted between 2003 and 2011, at Ghaem Hospital, Mashhad- Iran. We prospectively evaluated 1763 jaundiced newborns. We finally found 434 neonates who were categorized into two groups.131 neonates as case group (Blood or/and Urine culture positive or sign of pneumonia) and 303 neonates with idiopathic jaundice as control group. Demographic data including prenatal, intrapartum, postnatal events and risk factors were collected by questionnaire. Biochemical markers including bilirubin level, urine and blood cultures were determined at the request of the clinicians. Results: Jaundice presentation time, age on admission, serum bilirubin value and hospitalization period were reported significantly higher among case group in comparison with control group (p<0.0001). Urinary tract infection (UTI), sepsis and pneumonia were detected in 102 (8%), 22 (1.7%) and 7 (0.03%) cases, respectively. Conclusion: We concluded that bacterial infection was a significant cause of unexplained Hyperbilirubinemia among jaundice newborns (10%). Therefore, we advise performing screening test for UTI as part of the evaluation in asymptomatic jaundice infants presenting after five days of life and sepsis workup should be request in symptomatic infant especially in the first week of life. Keywords: Neonate, Urinary tract infection, Sepsis, Hyperbilirubinemia, Pneumonia *Corresponding Author: Associated Professor of Pediatrics, Neonatologist, Mashhad University of Medical Science (MUMS), Ahmadabad Street, Mashhad,Iran. E-mail: [email protected] Received: Oct 20, 2013; Accepted: Oct 25, 2013 5 Neonatal Infection and Hyperbilirubinemia Introduction University of Medical Science approved this Hyperbilirubinemia is a common and in study and all parents signed the informed most cases benign problem in first mouth of consent.1763 neonates with the chief life which is often physiologic and complaint of jaundice were admitted to our intervention is not usually necessary. neonatal ward during this study period, but Jaundice appears during the first week of life only 1269 infants were evaluated for in approximately 60% of term and 80% of infection. 827 cases were excluded from the preterm infants. Jaundice may develop study because of jaundice due to definite or serious complications like kernicterus and probable reason. Neonates with hemolysis lifelong disability (1,2). (ABO and Rh isoimmunization), hypothyro- Providing practitioners with new insights for idism, G6PD Deficiency, congenital heart predisposing factors, exacerbating or disease and etc were excluded from the study. etiologic factors for jaundice could help them We finally found 434 neonates who were to the better management (3). One of these categorized into two groups.131 neonates as factors is infection which is a serious clinical case group which had the criteria for infection problem among newborns (5,6). The (Blood or/and Urine culture positive or sign incidence rate of hyperbilirubinemia due to of pneumonia in Chest-X-Ray) and 303 infection is unknown (7,8). It is well known neonates with idiopathic jaundice as control that clinical manifestations of neonatal group (Figure. 1). Clinical jaundice was infection pretends as a wide spectrum, determined as yellowish color of the skin, ranging from nonspecific signs and mucous membranes or sclera. Information symptoms to severe illness as well as poor were collected and recorded by neonatal feeding, fever, vomiting, renal failure and fellowship and neonatologist. respiratory distress (9,10). Hyperbili- Maternal data like history of pregnancy and rubinemia may be the only manifestation of delivery, age, blood group, disease, type of infection, especially UTI within neonatal delivery and duration of hospitalization after period (10-12). delivery were all recorded. Neonate’s data Bacterial infection has been well- like time of jaundice onset and discharge documented as a cause of neonatal jaundice from hospital, signs and symptoms on in previous studies (6) but the prevalence admission, duration of hospitalization and rate, jaundice presentation time and the treatment plan were recorded and complete differences between the jaundice associated physical examination was done. with infection and other types of jaundice Complete blood count (CBC) with was unknown yet. differential, serum fractionated bilirubin level The aim of this study was to determine the (direct and indirect), Coombs test, reticulocyte incidence rate, symptoms, and age at count, blood group of the baby and mother, presentation, predisposing factors, characteri- thyroid function tests, glucose-6 phosphate stics, the severity of jaundice associated with dehydrogenase (G6PD) level, urinalysis and infection and complications and the etiology urine culture were performed for evaluation of infection among neonates with hyperbiliru- of etiology and severity of jaundice. Blood binemia in the first month- of life. culture, urine culture, blood sugar, urea, creatinin, Na, K and calcium were Materials and Methods determined at the request of the clinicians. This study has been accomplished on 1763 Urine sample obtained by suprapubic neonates with jaundice aged 1-29 days who aspiration and its result was considered were admitted to Ghaem Hospital, Mashhad- positive if any colony forming unit of a single Iran, between February 2003 and October pathogen was isolated. Urine samples were 2011.The ethic committee of Mashhad examined for leukocyturia and bactriuria in 6 Maamouri Gh A, et al the clinical laboratory by microscopy. cystourethrogram (VCUG) were requested Leukocyturia was defined as >5 leukocytes in cases of positive results for UTI. per HPF. Statistical analysis was carried out using Treatment period, the result of blood and SPSS 13.5 statistical package, for comparing urine cultures were recorded and proper groups. Descriptive data were reported as follow-up was performed after discharging mean ± standard deviation, and were from the newborn nursery. During follow- analyzed by Fisher exact test, the X2 test and up, renal ultrasonography and voiding Student t test. Fig 1: Selection, enrollment, and diagnosis of the study subjects. Results Mashhad from February 2003 to October A total of 1763 jaundiced neonates were 2011 for evaluation of jaundice and were referred to the newborn nursery and enrolled for recruitment. Among them, emergency department of Ghaem Hospital, finally 131 neonates that had the criteria for 7 Neonatal Infection and Hyperbilirubinemia infection and 303 jaundiced neonates with control group. Eighty-seven percent of an unknown etiology were placed as case neonates were born at term (37–42 weeks′ and control groups, respectively (Figure 1). gestational ages) and forty-five percent of The mean age was reported 12.6±7.5 days the case group was born via Caesarean in the case group and 8.7±6.0 days in the section delivery (Table 1). Table 1: Demographic characteristics of thecase and control groups. Control group Case group Characteristics P value N=358 N=132 Age on admission (day) 8.7±6.0 12.6±7.5 0.000 Birth weight (g) 3000±610 3200±480 0.033 Weight on admission (g) 2940±680 3160±650 0.003 Gestational age (term/ preterm) 238/44 118/13 0.061 maternal age (year) 26.1±5.2 26.0±5.0 0.183 Mode of delivery (CS/NVD) 215/126 38/36 0.052 Jaundice presentation time (day) 2.5± 1.7 3.7± 1.9 0.000 No statistically significant differences were hospitalization period, serum indirect and found for sex, gestational age, delivery direct bilirubin values had significant type, birth weight and maternal age between differences between two groups (P<0.05), two groups (P>0.05). Age and weight on (Table 1,2). admission, jaundice presentation time, Table 2: Comparison of clinical and laboratory findings in the subgroups study. UTI group Sepsis group Pneumonia Characteristics P value (N=102) (N=22) group(N=7) Age on admission (day) 13.9±7.3 6.6±3.6 9.0±5.2 0.000 Jaundice presentation time (day) 4.0± 1.9 3.0± 1.5 7.1± 2.1 0.000 Serum indirect bilirubin value (gr/dl) 16.8±4.9 23.8±6.0 16.4±6.3 0.000 Serum direct bilirubin value (gr/dl) 0.9±0.53 2.2±1.0 1.2±1.1 0.01 Hematocrit (%) 45±5.7 43.6±7.8 44.4±1.3 0.041 Hospitalization period (day) 5.6±1.9 12±2.6 10.1±2 0.000 Neonatal infection was found in 81 cases with bacteriuria and 71 cases with approximately 10% of jaundiced newborns. leukocyturia were detected in the case group. The most common infection associated Moreover 50 neonates had both bacteriuria with neonatal jaundice was UTI (77.9%), and leukocyturia. Although, not statistically Sepsis (16.8%) and pneumonia (5.3%), in significant, infection was more common in order. The most common pathogen isolated male neonates comparison with females from UTI was Klebsiella pneumonia (48 (P>0.9). In the current study we did not find infant), followed by Escherichia coli 2 (38), UTI among jaundiced neonates aged 5 days proteus (6), Staphylococcus epidermidis (5), and younger. UTI was detected among 24 Staphylococcus aurous (3) and Acinetobacter neonates who presented with jaundice (2). The most common pathogen isolated between 5–7 days of age. Patients who were from sepsis was Staphylococcus aurous, jaundice after 7 days of age had a higher followed by Staphylococcus epidermidis, incidence of UTIs (78 cases) which means proteus, entrobacter, Klebsiella pneumoniae that it is necessary to screen jaundice and Escherichia coli (Figure 2).