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Submitted: May 12, 2021 | Approved: June 15, 2021 | Published: June 16, 2021

How to cite this article: Nyenga AM, Mukuku O, Mutombo AK, Mpoy CW, Luboya ON, et al. Predictors of mortality in neonatal sepsis in a resource-limited setting. J Adv Pediatr Child Health. 2021; 4: 057-061.

DOI: 10.29328/journal.japch.1001034

Copyright: © 2021 Nyenga AM, et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Keywords: Neonatal sepsis; Risk factors; Mortality; Lubumbashi

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Predictors of mortality in neonatal sepsis in a resource-limited setting

Adonis Muganza Nyenga1, Olivier Mukuku2, André Kabamba Mutombo3, Charles Wembonyama Mpoy4, Oscar Numbi Luboya1,2 and Stanis Okitotsho Wembonyama1*

1Department of Pediatrics, Faculty of Medicine, University of Lubumbashi, Lubumbashi, Democratic Republic of Congo
2Institut Supérieur des Techniques Médicales, Lubumbashi, Democratic Republic of Congo
3Department of Pediatrics, Faculty of Medicine, University of Mbuyi-Mayi, Mbuji-Mayi, Democratic Republic of Congo
4Department of Obstetrics and Gynecology, Faculty of Medicine, University of Lubumbashi, Lubumbashi, Democratic Republic of Congo

*Address for Correspondence: Dr. Stanis Okitotsho Wembonyama, Professor, Department of Pediatrics, Faculty of Medicine, University of Lubumbashi, Lubumbashi, Democratic Republic of Congo, Email: wembostanis@outlook.fr

Introduction: Sepsis remains a major cause of death in neonatal period. Although significant advances in diagnosis, therapeutic and prevention strategies have been noted, sepsis remains a common concern in clinical practice especially in low-resource countries. The aim of this study was to determine the predictors of mortality in neonatal sepsis in Lubumbashi city (Democratic Republic of Congo).

Methods: The records of newborns with sepsis managed in Neonatal Intensive Care Units in two University Hospitals between November 2019 and October 2020 were studied. Binary and multiple logistic regressions have been used to observe the association between independent variables and dependent variable.

Results: A total of 162 cases of neonatal sepsis were reviewed. The mortality rate of neonatal sepsis was 21% of babies admitted. Very low birth weight (< 1500 grams) and primiparity were significantly associated with mortality in neonatal sepsis (AOR = 12.66; 95% CI 2.40 to 66.86; p = 0.003 and AOR = 3.35; 95% Cl 1.31 to 8.59; p = 0.012, respectively).

Conclusion: The mortality rate of neonatal sepsis was 21%. Very low birth weight and primiparity were significantly associated with mortality in neonatal sepsis.

Neonatal sepsis (NS) is a systemic infection that occurs in newborns under 28 days of life. It is a condition of bacterial, viral or fungal origin which is accompanied by a range of clinical manifestations [1,2]. The newborns exposed to these pathogens during the perinatal period are sensitive to invasive infections because of their relatively weakened immune system [3]. The incidence of NS varies from 1 to 170 per 1,000 live births [4.5]. In Lubumbashi (in the Democratic Republic of the Congo [DRC]), it was 31.39% [6].

NS remains a major cause of death in this population, although significant advances in diagnosis, therapeutic and prevention strategies [2]. In 2019, the World Health Organization (WHO) estimated that 2.4 (2.3 - 2.7) million newborns died within 28 days of birth [7]. The main causes of these neonatal deaths were infections (35%), premature births (28%), intrapartum complications (24%) and asphyxia (23%). In developing countries, each year, sepsis is the most common cause of neonatal mortality and is probably responsible for 30 to 50% of the total neonatal deaths [8.9]. Nyenga, et al. [10], in a recent study conducted in Lubumbashi (in the DRC), reported that sepsis was responsible for 21% neonatal deaths.

The purpose of our study was to identify the factors associated with NS mortality in Lubumbashi, DRC.

We conducted an analytical cross-sectional study in Neonatal Intensive Care Units in two University Hospitals in Lubumbashi (University Clinics and Sendwe Hospital) in the Haut-Katanga Province in the November 2019 to October 2020. We included all the newborn admitted NS in neonatal intensive care units of these tertiary care hospitals. The recruitment of the subjects was exhaustive and consecutive to the oral consent of their mother. The sample size was 162.

NS is a clinical syndrome with or without a bacteremia occurring during the first month of life. In this study, sepsis has been diagnosed on the basis of clinical symptoms by applying the criteria of the WHO [11,12]. This clinical diagnosis was supplemented by the iterative dosage of the C-reactive protein at a significant threshold ≥ 20 mg/L from the 24th hour after suspicion of the infection.

NS was classified in early onset sepsis (EONS) if it occurred at the beginning of 72 hours of life and late onset sepsis (LONS) if it occurred after 72 hours of life. The results have been defined as the condition of the patient at the exit and grouped by living and deceased. The variables studied were related to: maternal sociodemographic characteristics (age, parity, marital status, level of education, occupation) and neonatal characteristics (gestational age, birth weight, sex, delivery routes, admission mode, type of sepsis, concept of medical assistance and presence of antecedent of infectious risk).

Data were analyzed using the Stata software (version 15.0). Variables have been categorized and summarized in percentages. A bivariate analysis was performed followed by a multivariate analysis to reduce the effect of confounding factors. Adjusted odds ratios (AOR) with Confidence intervals of 95% (95% CI) were used to measure the degree of association between the variables. A p - value of 0.05 was considered statistically significant.

Ethical authorization was obtained from the Medical Ethics Committee of the University of Lubumbashi (Approval No. UNILU/CEM/038/2019). The privacy of the respondent and the confidentiality of the information has been ensured throughout the study procedure.

We found that most cases of NS occurred in male newborns (51.85%), those born at term (68.52%), those born with low weight (52.46%), and those born spontaneously by vaginal route (71.6%).

Of the 162 newborns with NS, most cases (93.21%) were EONS. Most patients (82.72%) had at least one infectious risk factor; the main maternal risk factors identified were genito-urinary tract infections (42.59%), premature membrane rupture (32.10%), meconium-stained amniotic fluid (25.31%) and prolonged labor (20.37%).

The mortality rate was 21%. In a bivariate analysis, NS-related mortality was significantly correlated with: primiparity (OR = 2.56 [1.17-5.59]; p = 0.016), admission mode (OR = 2.50 [1.16-5.41]; p = 0.017), gestational age < 37 weeks (OR = 3.80 [1.73-8.34]; p = 0.0005), birth weight < 1500 grams (OR = 12.59 [4.27-37.10]; p < 0.0001), and non-medical assistance at birth (OR = 2.49 [1.08-5.74]; p = 0.029) (Tables 1 and 2). Further analysis by multivariate logistic regression showed that primiparity (adjusted OR = 3.35 [1.31-8.59]; p = 0.012) and birth weight < 1500 grams (adjusted OR = 12.66 [2.40-66.86]; p = 0.003) were significantly associated with NS-related mortality (Table 3).

Table 1: Unadjusted association between neonatal sepsis related mortality and socio-demographic characteristics of mothers.
Variable Neonatal sepsis Crude OR [95% CI] p - value
Total
(N = 162)
Non survivor
(n = 34)
Survivor
(n = 128)
Maternal age              
< 20 years 28 9 32.14% 19 67.86% 1.67 [0.67-4.18] 0.272
20-34 years 104 23 22.12% 81 77.88% Reference  
≥35 years 30 2 6.67% 28 93.33% 0.25 [0.03-1.14] 0.065
Parity              
Primiparous 49 16 32.65% 33 67.35% 2.56 [1.17-5.59] 0.016
Multiparous 113 18 15.93% 95 84.07% Reference  
Marital status              
Single 15 5 33.33% 10 66.67% 2.03 [0.64-6.41] 0.218
Married 147 29 19.73% 118 80.27% Reference  
Education level              
Primary 20 5 25.00% 15 75.00% 1.51 [0.45-5.05] 0.497
Secondary 81 18 22.22% 63 77.78% 1.30 [0.56-3.00] 0.539
Higher/University 61 11 18.03% 50 81.97% Reference  
Profession              
Student 3 2 66.67% 1 33.33% 14.67 [0.61-526.05] 0.056
Functionary 21 4 19.05% 17 80.95% 2.01 [0.30-15.48] 0.434
Liberal 29 3 10.34% 26 89.66% Reference  
Housewife 109 25 22.94% 84 77.06% 2.56 [0.69-14.33] 0.194
N: Number; OR: Odds Ratio; 95% CI: Confidence Interval at 95%.
Table 2: Unadjusted association between neonatal sepsis related mortality and neonatal characteristics.
Variable Neonatal sepsis Crude OR [95% CI] p - value
Total
(N = 162)
Non survivor
(n = 34)
Survivor
(n = 128)
Type of sepsis              
EONS 151 32 21.19% 119 78.81% 1.21 [0.23-12.04] 1.000
LONS 11 2 18.18% 9 81.82% Reference  
Transfer from another hospital              
Yes 62 19 30.65% 43 69.35% 2.50 [1.16-5.41] 0.017
No 100 15 15.00% 85 85.00% Reference  
Gestational age              
< 37 weeks 51 19 37.25% 32 62.75% 3.80 [1.73-8.34] 0.0005
≥ 37 weeks 111 15 13.51% 96 86.49% Reference  
Sex              
Female 78 19 24.36% 59 75.64% Reference  
Male 84 15 17.86% 69 82.14% 1.48 [0.69-3.17] 0.310
Birth weight              
< 1500 grams 24 15 62.50% 9 37.50% 12.59 [4.27-37.10] <0.00001
1500-2499 grams 61 10 16.39% 51 83.61% 1.48 [0.56-3.91] 0.426
≥ 2500 grams 77 9 11.69% 68 88.31% Reference  
Delivery mode              
Obstructed vaginal delivery 4 1 25.00% 3 75.00% 0.96 [0.10-9.54] 1.000
Caesarean section 42 3 7.14% 39 92.86% 0.22 [0.06-0.77] 0.013
Eutocical delivery 116 30 25.86% 86 74.14% Reference  
Medical assistance at birth              
No 35 12 34.29% 23 65.71% 2.49 [1.08-5.74] 0.029
Yes 127 22 17.32% 105 82.68% Reference  
Infectious risk              
Yes 134 29 21.64% 105 78.36% 1.27 [0.44-3.63] 0.655
No 28 5 17.86% 23 82.14% Reference  
N: Number; OR: Odds Ratio; 95% CI: Confidence Interval at 95%; EONS: Early Onset Sepsis; LONS: Late Onset Sepsis.
Table 3: Multiple logistic regression of risk factors for neonatal sepsis related mortality in newborns in Lubumbashi.
Variable Adjusted OR St. Error t-value p - value [95% Confidence Interval]
Medical assistance at birth            
Yes 2.09 1.13 1.36 0.174 0.72 6.04
No Ref.          
Delivery mode            
Obstructed vaginal delivery 2.36 3.02 0.67 0.503 0.19 29.05
Cesarean section 0.57 0.41 -0.78 0.434 0.14 2.30
Eutocical delivery Ref.          
Gestationnel age            
< 37 weeks 0.99 0.66 -0.01 0.992 0.27 3.62
≥ 37 weeks Ref.          
Birth weight            
< 1500 grams 12.66 10.75 2.99 0.003 2.40 66.86
1500-2499 grams 1.82 1.14 0.96 0.339 0.53 6.19
≥ 2500 grams Ref.          
Parity            
Primiparous 3.35 1.61 2.52 0.012 1.31 8.59
Multiparous Ref.          
Transfer from another hospital            
Yes 2.31 1.19 1.62 0.106 0.84 6.35
No Ref.          

The neonatal mortality rate is a reliable criterion for assessing the overall progress of perinatal care in a community. Knowledge of local or regional health problems is a prerequisite for an effective health care delivery system [13]. The mortality rate of NS varies between hospitals and between countries. This study reports a mortality rate of 21%. Comparable rates have been found in other studies conducted in India (16%) [14], Nigeria (19.3%) [15], South Africa (20.8%) [16] and Indonesia (28.3%) [17]. While high rates were reported in Nigeria (32.2%) [18], India (38.24%) [19], Mexico (43.9%) [20], and Iraq (44.2%) [13]. These differences in mortality rates between studies are attributable to many factors such as socio-economic factors, geographical factors, equipment levels and the effectiveness of each hospital’s prophylactic and therapeutic approach [13]. NS may have subtle, diverse and non-specific symptoms and signs, often leading to delayed diagnosis and treatment leading to high morbidity and mortality [21].

We found that primiparity was a risk factor for neonatal death in the case of sepsis. Munan, et al. [22] reported that perinatal death was higher in primipares than in multipares and noted that the need for neonatal intensive care was significantly recorded in primiparous newborns. According to these authors, this would be due to high rates of intrapartal complications (prolonged or obstructed labour, dystocies, caesarean sections, fetal distress, poor Apgar scores) in primipares [22]. The same finding was reported by Kaur and Kaur, [23]. Although these authors did not take an interest in NS, it is logical that this finding is also applicable in the case of NS. This combination of primiparity-related morbid events could compromise the life-threatening prognosis of the newborn with sepsis. Primiparous newborn is therefore considered to be at risk and gestation as the postnatal period should be given special care [24]. Trotman, et al. [25] found an association between early childhood and death in neonates with sepsis. Similarly, young age may be considered a characteristic of primiparous mothers in our contexts where the prevalence of teenage motherhood is high [26]. In our series, we found a high death rate among mothers under 20 years of age (32.1%) although this association with maternal age was not statistically significant. Lack of experience with lower-risk behavior during pregnancy would also be an important factor.

This study showed that low birth weight (< 1500 grams) was a risk factor for death in neonates with sepsis. A similar finding has been reported in many previous studies in different countries [13,14,19,20]. Infectious disease morbidity and mortality are known to be high in low-birth-weight infants [27]. This is explained either by an inherent immune deficiency or because these newborns require prolonged hospitalization that increases the risk of nosocomial infection. Infection is therefore added to all the complications that already darken the life-threatening prognosis of low-birth-weight infants. Transplacental maternal antibodies are mainly involved in humoral and cellular immunity, so premature neonates are less likely to receive as many immunoglobulins as neonates born at term [25]. Indeed, although prematurity in general is not a statistically related factor to NS-related mortality in our series, we nonetheless noted a high mortality rate in premature neonates (37.3%).

The results of this study should be interpreted with certain limitations. First, because of the cross-sectional nature of the study. Secondary to the fact that the study is conducted with newborns admitted to urban reference hospitals, the results may not be generalizable to the general population.

This study identified primiparity and very low birth weight as independent risk factors for mortality in NS. Strategies to reduce morbidity and mortality in newborns with sepsis should include measures that will reduce the incidence of low birth weight or even premature birth. Primiparity will need to be given particular attention in programs to monitor mother-to-child infections and to manage the risk of sepsis-related complications.

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