https://doi.org/10.15218/ejnm.2020.01 Erbil j. nurs. midwifery, Vol. 3, No. (1), May, 2020 Original Article Risk Factors Associated with Early and Late-onset of Neonatal Sepsis in Duhok City ABSTRACT INTRODUCTION Neonatal sepsis refers to bacterial, fungal, protozoan infections or any viral pathogen instantly after the delivery[1]. Neonatal inflammation indicates to the infections of newborns through the first-month of exist- ence, surrounding infections in the eyes, mouth, skin, and the umbilicus.. The mostly ways of newborn infections are during the broken skin in the umbilical cord [1,2]. Early neonatal period refers to the first seven days of newborn’s life, while the late neonatal period means the period from after seven days to 28 days of life. [2]. Maternal sepsis is the main factor leading to death of newborns with prevalence one from ten deaths. For more than 95% of maternal deaths are associated to mater- nal infections which happens in the socie- ties where incomes are low. [3]. One mil- lion newborn deaths are related with Backgrounds and objectives: Neonatal sepsis refers to bacterial, fungal, protozoan infec- tions or any viral agents or pathogens which inter to the newborns blood stream after the birth. Neonatal Sepsis is the main reason of deaths in non-developed countries. There is an overall prevalence of 54.67% in Iraq. The present study intends to explore the demo- graphic and clinical affecting factors of early and late onset of neonatal sepsis of a sample population in Duhok city. The predictors of neonatal sepsis diagnosis were determined accordingly. Methods: This cross-sectional study shows 110 neonates who were diagnosed with early or late onset of neonatal sepsis. A pediatrician diagnosed the patients through physical and clinical assessment. Results: The prevalence of early and late onset of neonatal sepsis was 52.73% and 47.7%, respectively. The Apgar scores of less than seven and more than seven were risk factors for early and late-onset of neonatal sepsis, prolonged rupture of the membranes greater than18 hours and multiple gestations are common in patients with early onset of neona- tal sepsis. Conclusions: The study showed that the early onset of neonatal sepsis or late-onset of neonatal sepsis was associated with Apgar score and prolonged rupture of the mem- branes. Keywords: Early Onset of Neonatal Sepsis; Late-Onset of Neonatal Sepsis; Risk Factors Delshad Abdallah Mohamed; Department of Nursing, College of Nursing, University of Duhok, Duhok, Iraq. )Correspondence: dilshad_msc14@yahoo.com) Salah Abdulkareem Ibrahim; Department of Pediatric, College of Medicine, University of Duhok, Duhok, Iraq. Sherzad Khudeida Suleman; Community Health and Pediatric Unit, College of Nursing, University of Duhok, Duhok, Iraq. 1 Erbil Journal of Nursing & Midwifery Received: 25/3/2019 Accepted: 17/9/2019 Published: 30/5/2020 mailto:dilshad_msc14@yahoo.com https://doi.org/10.15218/ejnm.2020.01 Erbil j. nurs. midwifery, Vol. 3, No. (1), May, 2020 Original Article maternal infection every year [4].Reduction in the neonate and child mortality is a sig- nificant world goal to achieve health for all. During the last quarter of the century, the emphasis has paid to the reduction in un- der-five childhood mortality largely through vaccination, oral rehydration ther- apy (ORS), and control of respiratory tract infections. while, this changes did not have marked influence among neonates leading to converting of infant mortality at an any age [5].In developing countries newborn infection is considered a common reason of neonatal morbidity and mortality [6]. Insufficient care and inappropriate preg- nancy treatment, including a lack of hy- giene during the obstetric and delivery, contributes to the poor care of neonates. [5-6].It’s evaluated that three million new- borns and 1.2 million children complain from sepsis globally. [7]. Neonatal sepsis in Kurdistan and Iraq A study conducted in three hospitals in Baghdad to identify the leading microor- ganism of bacteria and viruses, as well the qualification factors studied 150 weak- ened and sensitive newborns, among sen- sitive newborns, the incidence of newborn infection it was 54.67% [8]. Immature newborn, weakness, inflammation of uri- nary and reproductive system of mothers, and cesarean section delivery, leads to pre- dispose, newborns neonatal sepsis [8-9]. In early and late onset of neonatal sepsis, Staphylococci were the predominant path- ogen in both EOS and LOS sepsis. While a large rate of this pathogen was coagulase- negative in LONS. Generally gram-positive bacteria have the most frequent level ra- ther than positive bacteria, whereas Fungi and Toxoplasma showed no significant Effect or fewer roles in neonatal sepsis among newborns in Iraqi community. To avoid increasing the percentage of deaths among neonates we should taking in account the early detection and diagnosis of the microbes as soon as possi- ble. [9-11] A study conducted in Duhok re- ported that 25.39% of the neonates diag- nosed with neonatal sepsis, including 61.9% in patients their age less than7 days [9].In another study conducted in Erbil city, 425 newborn patients were diagnosed with neonatal infections, including 53% in ages less than seven days and 47% in pa- tients between seven and 28 days. [10] The purpose of this study was to discover the demographic and clinical risk factors of early and late neonatal sepsis in a sample population in Duhok city. Also, the predic- tors of early and late-onset of neonatal sepsis diagnosis were considered in this study. This cross-sectional study targeted patients attending the out-patient clinic of a pediat- ric hospital were consecutively screened for diagnostic criteria of different types of neonatal sepsis. The patients who were recruited in a purposive way from the Neo- natal Intensive Care Unit (NICU) of Heevi Pediatric Hospital in Duhok between 1st February 2018 and 27th December 2018. The newborns who were involved in this study were the neonates diagnosed with clinical futures of newborn infections in early or late stage of neonatal infection in Duhok city. The investigators attempted to include all cases who attended the hospital between the mentioned time periods. The following patients were included in the study: Male or female, aged from birth to 28 days, diagnosed with early or late onset of neonatal sepsis, admitted to the hospi- tal. The patients whose parents did not accepted to participation were excluded from the study. Also, the patients who had other medical conditions were not includ- ed in the study. 2 Erbil Journal of Nursing & Midwifery METHODS https://doi.org/10.15218/ejnm.2020.01 Erbil j. nurs. midwifery, Vol. 3, No. (1), May, 2020 Original Article The program that which used to calculate our data were performed in SPSS (Statistical Package for Social Sciences) ver- sion 25. The ethical approval of the present investi- gation was obtained from the Scientific Research Davison of Duhok General Direc- torate of Health on 20/06/2017. The verbal consent was taken from all mothers before data collection, and the guarantee was giv- en for the confidentiality of their personal I information. Of the total 110 patients diagnosed with neonatal sepsis and included in the study, the prevalence of EONS and LONS were 52.73% and 47.7%, respectively. The re- search did not discovered an important difference in gender distribution (P= 0.345), maternal age (38.5% between 31 and 40 years in EONS and 43.1% between 21 and 30 years in LONS; P=0.387), educa- tion level of mothers (P=0.407) between mother of neonates infected by ENOS and LNOS. Moreover, the study doesn’t shows large differences in gestational age of the mother between two groups of the study (55.8% between 37 and 42 weeks in EONS and 53.4% in LONS; P=0.367), see Table 1. The multiple gestations in EONS and LONS were 59.6% and 48.3%, respectively, with no significant difference (P=0.234). Also, the study did not report the considerable difference in the mode of delivery (44.2% by cesarean section in ENOS and 55.2% in LNOS; P=0.252) and twin gestation (P=0.938), see Table 1. Baseline information was collected through self-reported by mothers and included in- formation of newborn and parents such as age, gender, education, gestational age, and mode of delivery. The discovering of newborn infection or sepsis was estab- lished by the pediatrician, and according to the following clinical criteria, temperature instability; account of heart-bit (180 bit/ minute, or 100 bit/minute; the rate of res- piration more than 60 breaths/min, desat- urations; lethargy/altered mental status; glucose intolerance (plasma glucose >10 mmol/liter); feed intolerance. [11]. Leukocytosis (WBC count >34000×109/l); leukopenia (WBC count <5000×109/l); im- mature neutrophils >10%; premature: the rate of total neutrophil >0.2; thrombocyto- penia <100000× 109/l; CRP (C - reactive protein) >10 mg/l or 2 SD (Sta. Deviation) above normal value; procalcitonin >8.1 mg/dl or 2 SD above normal value; IL-6 or IL-8 >70 g/ml. [11,13] The Apgar score is a method of newborn health assessment against infant mortality. Which is calculat- ed based on score of where 1 to 10 scores. Where high point indicate the baby’s health status is good. Appearance (skin col- or); pulse (heart rate), Grimace response (reflexes), activity (muscle tone), respira- tion are included as indicators [12]. Pre- term Premature Rupture of Membranes is defined as occurring prior to 37 week’s ges- tation when the amniotic fluid is leaking prior to exit the baby out of the mother’s vagina due to tearing of the membrane in more than 24 hours [13]. The difference between general and clinical characteristics of the patients diagnosed with early neonatal sepsis was examined through Chi-square and Fishers’ exact test. Besides, the predictors of neonatal sepsis (early and late) were examined through Univariate analysis of variance. The null hypothesis was rejected in a P-value of equal or less than 0.05. 3 Erbil Journal of Nursing & Midwifery RESULTS https://doi.org/10.15218/ejnm.2020.01 Erbil j. nurs. midwifery, Vol. 3, No. (1), May, 2020 Original Article 4 Erbil Journal of Nursing & Midwifery Table 1: General characteristics between patients in early and late onset of neonatal sepsis General characteristics (n=110) Early Onset (n=52, 47.27%) Late Onset (n=58, 52.73%) P-value (Two-sided) Gender of infant Male Female 28 (53.8) 24 (46.2) 26 (44.8) 32 (55.2) 0.345* Maternal age of mother < 20 year 21-30 years old 31-40 years old > 40 year 13 (25) 18 (34.6) 20 (38.5) 1 (1.9) 9 (15.5) 25 (43.1) 24 (41.4) 0 (0) 0.387** Educational status of mother None Primary Secondary Tertiary 15 (28.8) 14 (26.9) 12 (23.1) 11 (21.2) 12 (20.7) 13 (22.4) 22 (37.9) 11 (19) 0.407* Gestational age of mother <37 Weeks 37-42 W >42 Weeks 21 (40.4) 29 (55.8) 2 (3.8) 27 (46.6) 31 (53.4) 0 (0) 0.367** Multiple gestations Yes No 31 (59.6) 21 (40.4) 28 (48.3) 30 (51.7) 0.234* Mode of Delivery Vaginal Delivery Cesarean Section 29 (55.8) 23 (44.2) 26 (44.8) 32 (55.2) 0.252* Twin gestation Yes No 14 (26.9) 38 (73.1) 16 (27.6) 42 (72.4) 0.938* *Chi-square and **Fishers’ Exact tests were performed for statistical analyses. The numbers are in fre- quency (percentage). https://doi.org/10.15218/ejnm.2020.01 Erbil j. nurs. midwifery, Vol. 3, No. (1), May, 2020 Original Article 5 Erbil Journal of Nursing & Midwifery Table 2 showed that there is no relation- ship between ENOS and LNOS study groups in maternal fever (P=0.763), ma- ternal group B streptococcal coloniza- tion, UTI (P=0.792), prematurity rupture of membrane before the onset of labor (P=0.488), foul-smelling liquor (P=0.103), birth weight (P=0.170), resuscitation at birth (P=0.603), fetal tachycardia (P=0.365), fetal abnormalities (P=0.314), invasive procedures (P=0.899), hand washing (P=0.994) and PROM (P=0.047), see Table 2. Whereas the majority of the patients with EONS had Apgar score less than 7 (71.2%) compared to the majority with Apgar, score of more than 7 (63.8%) in LONS (P=<0.0001). Meconium-stained amniotic fluid was more prevalent in ENOS; 75.0% compared to 56.9%, respec- tively (P=0.046), see table 2. Table 2: Comparison of clinical characteristics between patients with early and late- onset of neonatal sepsis General characteristics Early-Onset (n=52) Late-Onset (n=58) P-value (Two-sided) Prolonged rupture of the membranes* (4.56)46 (6454)72 05062 Maternal Fever (..55)72 (.554)46 05244 Maternal group B Streptococcal colonization, UTI** (.254)43 (4753)44 05227 Prematurity rupture of membrane before the onset of labor. (435.)7 (..57)47 05655 Foul Smelling Liquor (5.56)46 (.0)72 05304 Apgar score (1min) than 7 (2357)42 (7555)3. (4457)73 (4455)42 <050003 Birth Weight 18 hrs. **UTI: Urinary tract infection https://doi.org/10.15218/ejnm.2020.01 Erbil j. nurs. midwifery, Vol. 3, No. (1), May, 2020 Original Article 6 Erbil Journal of Nursing & Midwifery The predictors of ENOS and LNOS were examined in univariate analysis model in Table 3. The study showed that having multiple gestations is a predictor of ENOS (P=0.013). Also, the lower Apgar score predicts ENOS, and higher Apgar score predicts LNOS. Table 3: Univariate analysis of variance of early and late neonatal sepsis Dependent Variable: Early and Late Neonatal Onset Risk Factors Mean Square F Score P-Value Effect Size Gender 05324 05220 05422 05002 Maternal Age 05333 05.04 05422 05035 Mother Education 05767 35306 054.7 05045 Gestational Age 05706 05243 05425 05077 prolonged rupture of the membranes 05.4. 75662 05377 05075 Maternal Fever 05705 052.7 05447 05033 Urinary tract infections 050.7 05744 05475 05004 Multiple Gestation 35637 456.. 05034 05023 Premature rupture of membrane* 05002 05040 05544 05000 Mode of delivery 05035 05053 05222 05003 Foul Smelling Liquor 05454 35265 05320 05070 Inadequate hand Washing 05006 05070 05552 05000 Apgar Score 45754 3.500. 05000 053.7 Birth weight 05043 05363 05202 05007 Resuscitation at Birth 05063 05355 05444 05007 Meconium-stained amniotic fluid 05706 05240 05445 05033 Twin Gestation 05023 05636 05.77 0500. Fetal Tachycardia 05046 05723 05.23 05004 Fetal Abnormalities 0504. 05724 05.55 05006 Invasive Procedures 05342 05227 05457 05002 *PRM: Prematurity rupture of membrane before the onset of labor. https://doi.org/10.15218/ejnm.2020.01 Erbil j. nurs. midwifery, Vol. 3, No. (1), May, 2020 Original Article 7 Erbil Journal of Nursing & Midwifery In the present study the general and clini- cal risk factors of neonatal sepsis in a sam- ple population of neonates were deter- mined. In the study, gender of neonate was not determined to be a predictor of neonatal sepsis. There are contradictory reports about the dangerous of gender for neonatal sepsis [14]. Sexual dimorphism from the human immune response is quite clear; female babies produce the more active of cellular immune reaction so that they are more resistant to the infection. [15]. The differences with the present study could be due to the sample size or study design. Mother’s maternal age and level of education was not significantly associated with neonatal sepsis [16, 17], possibly due to the lack of mother infor- mation and experience about newborn care. Prolong rapture of membrane (≥18 hours) was shown to not be associated with neonatal sepsis; Other researches in other communities shows the same re- sults to the results of our study[18, 19]. One of the most common reason of up- grade of pathogens to rise from vagina and cervical canal in to the amniotic fluid and fetal sac are easy and late tearing of the membrane as asphyxia which leading to sepsis [19, 20]. In the present study, intrapartum fever was not shown a signifi- cant influence in the newborn infection and sepsis. The newborns were delivered from mothers with high body temperature during delivery have six times higher odds of developing sepsis compared to new- borns that delivered from mothers their body temperature were normal during the labor. [19, 21]. Intra partum fever is an indicator of maternal infections that are frequently transmitted to the baby inside the uterus or through the delivery canal when the newborn pass through this ca- nal, which always leading to early-onset sepsis [22, 19]. The study determined that those infants with Apgar score less than seven usually are affected by EONS and the infants with Apgar score greater than seven affect by LNOS (P<0.0001). The previous study have shown that Apgar score less than seven in the first minute have a risk of 14.05 times (95% CI 5.487-35.987) to the EONS occurrence. A study considered that the EONS happens in newborns with Apgar score less than seven in the early minutes rises 11.1 times with a sig- nificant ratio P-value 0.001 [14]. Also there were a same results and it was very closed to the previous study which shows a high significant rate in neonates with Apgar less than seven with p value 0.002 [23, 24]. Generally there were a relationship between the Apgar score in the moment of first life span of the new- born and the Hydrogen Potential (pH) cord blood and during delivery depres- sion, but there was no relationship with the consequences, while the Apgar score refers to the changes which happen in the infant’s health condition and the per- formance of resuscitation applied. [25]. Several factors can cause perinatal hy- poxia-ischemia, while in the consistent consequences which performed from the previous study, explained that low Apgar score in the first minute may be due to the infants infection factors which happens from the perinatal period, usu- ally a number of weeks, immediately be- fore and after birth [24, 25].Birth weight, resuscitation at birth, meconium-stained amniotic fluid, twin gestation, fetal tachy- cardia, fetal abnormalities, poor feeding were not found to be predisposing fac- tors of newborn infection or sepsis in this study in disagreement with some studies in the literature review [26]. This study shows that adequate hand washing be- fore and after clinical procedures is not DISCUSSION https://doi.org/10.15218/ejnm.2020.01 Erbil j. nurs. midwifery, Vol. 3, No. (1), May, 2020 Original Article 8 Erbil Journal of Nursing & Midwifery a significant predictor of late onset of neo- natal sepsis. More than quarter of neona- tal mortality is related to sepsis or infec- tions. Caregivers, mothers and nurses hy- giene and hand washing with soap and detergents usually decrease neonatal sep- sis and infections. A study examined the effect of plenty handwashing advancing the hand washing style and behavior of mothers. In Nepal there was a significant difference between mothers who wash their hands several times rather than mothers who did not wash their hands or has washing their hand few times, and the first group were at 44% lower risk of neo- natal infection and death rather than the second group [27]. In a study conducted between two groups of mothers, which shows that good handwashing with deter- gents and antiseptic agents were signifi- cantly increased before and after breastfeeding, feces contact among case mothers than among controls. [28] there- fore, the hygiene of mothers and hand washing with detergents before and after fecal attaches were less frequent rather than the spread of this style marked among mothers of small children in devel- oping communities, which confirms the large barriers to hand washing progressed by mothers of newborns [28].Lastly, the study showed that invasive clonal proce- dure is not a predictor for neonatal sepsis types. In another study shows that the lumbar puncture (LP) meningitis can be the main indicator of neonatal sepsis in approximately 3% sample size; subse- quently cerebrospinal fluid aspiration analysis ought to be considered in the ma- jority of newborns with late-onset of neo- natal sepsis prior using of antibiotics. [20]. When septicemia or blood infection, are shows in the positive blood culture and clinical picture, this refers to presence of EONS, LP, so LP should be delayed in that cases [29] There are several blood investigations other than culture used to detect sepsis. I: T ratio, micro ESR (Erythrocyte Sedimentation Rate) [30]. STRENGTH AND LIMITATION The strong point of the present investiga- tion must be searched in the study design as the mostly of the previous studies fo- cused on cross-sectional design rather than a comparative design. The study was performed in one clinical setting, preclud- ing us from generalizing the findings to other settings across the country. There was evidence in the analyzing sta- tistics which obvious that Apgar score is only a predictable factor of early and late onset of newborn sepsis. The majority of the subjects who were infected by ENOS had long term tearing down of the mem- branes longer than 18 hours, and their mothers had multiple gestations. The authors of the study would like to present their deepest thanks to the clini- cal staff of Pediatric Heevi Hospital. This study was not supported financially. The authors announced that there were no conflicts of interest. The corresponding author claims that all authors of the present study had suffi- cient contribution to study design, review, concept, assessment, diagnosis, and anal- ysis. CONCLUSION ACKNOWLEDGMENTS FUNDING CONFLICTS OF INTEREST AUTHORSHIP https://doi.org/10.15218/ejnm.2020.01 Erbil j. nurs. midwifery, Vol. 3, No. (1), May, 2020 Original Article 9 Erbil Journal of Nursing & Midwifery [1] Rosdahl CB, Kowalski MT. Textbook of basic nursing: Lippincott Williams & Wilkins; 2008. [2] Thacker N. Improving status of neonatal health in India. Indian acad pediatrics mau- lana azad medical college, dept pediatrics, new delhi, 110 002, india; 2007. [4] Say L, Chou D, Gemmill A, Tunçalp Ö, Moller A-B, Daniels J, et al. 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