Etiologies of Neonatal Mortality in a Tertiary Care Hospital in a Resource-Limited Setting

Background: Neonatal mortality remains a major public health problem in low income countries. The survival within the first 28 days of life remains a challenge in such countries. Many strategies have been implemented to reduce deaths in children under five especially in sub-Saharan Africa. Laquintinie Douala Hospital benefits from some of these measures including a perinatal network and an emergency voucher. We aimed to describe the main causes of neonatal deaths at Laquintinie Douala Hospital. Methods: We car-ried out a cross-sectional study including files of all deceased neonates in the 95% CI 1.25 - 2.13; p = 0.0001). Conclusion: Neonatal mortality was lower than data in previous studies but remains high. This highlights the need for caregiver training and improvement of antenatal visits in our setting.


Introduction
Neonatal mortality remains a major public health problem in low-income countries. In 2016, 2.6 million children died before their 28 th day of life. Every day, almost 7000 newborns die [1]. They represent almost half of the deaths recorded in under five years children. The majority of these deaths occur in lowest-middle income countries, especially in sub-Saharan Africa and Southern Asia [1]. Neonatal mortality reflects the quality of care provided to pregnant women and newborns during the first days of life [2]. In order to achieve the fourth Millennium Goal for sustainable development, strategies have been implemented in Sub-Saharan Africa to reduce neonatal mortality [3]. Programs such as the Expanded Immunization Program, high-quality antenatal care, and integrated management of childhood illnesses as well as emergency obstetrical and neonatal care have been implemented.
Despite these strategies, the neonatal mortality rate remains high in sub-Saharan Africa. It was estimated at 35.7/1000 in Mali, 42.3/1000 in the Central African Republic and 36.6/1000 in Ivory Coast in 2016 according to UNICEF [4]. In Cameroon, the neonatal mortality rate was estimated at 28 per 1000 live births in 2015 [5]. Hospital-based studies respectively found 20.3% of deaths in 2015 at the Laquintinie Douala Hospital (LDH) and 15.7% of deaths at the Bamenda Regional Hospital in 2017 [6] [7].
Due to the burden of neonatal mortality at LDH in 2015, some cost-effective interventions were initiated to improve survival of newborns in neonatal care unit. A perinatal referral network was created for management of critically ill neonates. They also set up an emergency care voucher with recovery of deferred

Study Design and Setting
We retrospectively recorded files of newborns admitted and deceased during a 24 months' period from January 1 st , 2017 to December 31 st , 2018 in the neonatal unit of Laquintinie Douala Hospital. It is a teaching hospital located in the Littoral region, in the economic capital of Cameroon. It is a tertiary care health facility. The neonatal unit is divided into 3 areas (red area or emergency room, orange area for referred newborns and green area for newborns coming from the hospital maternity ward). It has a capacity of 38 places including 28 beds, 7 incubators and 3 neonatal resuscitation tables. It has a reception ward, an intensive care unit and a kangaroo care unit for premature babies. The medical team is

Study Population
We included records of all newborns who arrived alive and who died during hospitalization in the neonatology unit of the Laquintinie Douala Hospital.
Records of newborns were included consecutively. Records of newborns who arrived deceased and those with incomplete records were excluded ( Figure 1).

Data Collection
We collected data from neonatal unit registers and medical records. Data collection was performed with a pretested record and variables included: • The socio-demographic characteristics of the mother (age, profession, level of education) and the newborn (age, gender, birth weight, place of origin, means of transport); • Obstetrical data (parity, gestational age, number of antenatal consultations, tetanus/antianemic/antimalarial prophylaxis, serologies performed, risk factors for neonatal sepsis, place and route of delivery, apgar score);

Definition of Terms
Neonatal mortality was defined as death that occurred within the first 28 days of life. Neonatal sepsis was considered for any newborn with infectious risk factors (prolonged rupture of membranes, per partum fever, urogenital infection in the third trimester, chorioamnionitis), clinical signs of infection (fever, hypothermia, jaundice, respiratory distress, seizures, refusal to breastfeed, pallor) and biological criteria (CRP greater than 20 mg/l, with or without bacteriological or radiological evidence of infection). Respiratory distress was considered for a Silverman score greater than 2/10. Neonatal asphyxia was defined as inability to establish a cry or autonomic breathing at birth with an alteration of the Sarnat score without any other identifiable etiologies. It should be noted that there was no gas measurement to measure blood pH and base deficiency. A poor Apgar score was defined as an Apgar score less than 7 at the 5 th minute. Small for gestational age (SGA) was defined as a birth weight less than 2500 g. Prematurity was defined as a gestational age less than 37 weeks' amenorrhea.

Statistical Analysis
The data were recorded using EPI-INFO software version 7.2.0. We used SPSS software version 20.0 (IBM Corporation, Chicago, USA) for statistical analysis.
Continuous variables were expressed as median with the interquartile range.
Categorical variables were presented as proportions, percentages or frequencies.
We used the Chi square test to compare proportions between groups. Quantitative variables were compared using student's t test. We used a logistic regression

Ethical Considerations
This study received ethical approval from the institutional board review of the

Neonatal Mortality Rate
During the study period, 2061 newborns were admitted to the neonatal unit of LDH. Among them, 275 newborns died, for an overall neonatal hospital mortality rate of 13.3%. We excluded 5 files due to missing data. We retained 270 files ( Figure 1).

Characteristics of Deceased Newborns
In total, 77% of deceased newborns were admitted on the first day of life.

Features of Mothers of Deceased Newborns
The median age of mothers (IQR) was 28 (22.7 -31) years with a range of 17 to 43 years. The 25 -29 age group represented 34.1% of mothers, followed by the 20 -24 age group (30.4%).
Mothers working in the informal sector represented 60.4%, followed by pupils and students (26.3%). More than half of the mothers (n = 204) had made less than 4 antenatal consultations during their pregnancy ( Table 2). They had re-

Clinical Features of Deceased Newborns
Prematurity, poor Apgar score and acute fetal distress were the main reasons of admission in neonatal unit (  The newborns showed several signs of severity at the same time. Cyanosis and desaturation were found in 175 (64.8%) and 179 (66.3%) newborns, respectively.

The Delay in the Occurrence of Newborn Deaths
More than half of the newborns (n = 168; 62.2%) died at night (between 5 p.m.

Factors Associated with Neonatal Mortality
Newborns whose mothers were in the informal sector

Discussion
The aim of this study was to evaluate the impact of new strategies initiated in a tertiary care hospital in Douala to reduce neonatal mortality. It shows that the in-hospital neonatal mortality rate was 13.3%. The causes of neonatal mortality were prematurity (37.8%), neonatal infection (34.1%) and perinatal asphyxia (24.4%). Primary level of education, less than 4 antenatal visits as well as prematurity significantly increased the risk of neonatal death.

Hospital Neonatal Mortality
The neonatal mortality rate in our study was 13.3%. This result is lower than the mortality rate of 20.3% found by Kedy Koum

Causes of Neonatal Mortality
The main causes of neonatal mortality were prematurity (37.8%), neonatal sepsis (34.1%) and neonatal asphyxia (24.4%). These results are similar to those found in most studies of neonatal mortality [6]- [11].
The high proportion of deaths linked to prematurity could be justified by predominance of very preterm babies in our sample. Indeed, newborns whose gestational age is less than 32 weeks are more likely to die due to the immaturity of most vital functions. Several studies have reported a high mortality rate in this group [11] [12] [13]. They are at risk of respiratory, infectious and hemodynamic complications. In a context of scarce resources, the Kangaroo method recommended by WHO could reduce the mortality rate of premature babies [14]. Uganda reported a significant reduction in neonatal mortality after 3 training sessions in neonatal resuscitation and use of the partograph in Kampala [15]. It is therefore essential to ensure continuous training in neonatal resuscitation and the adequate equipment of birth rooms.
More than half of the deaths occurred during on-call hours (between 5 p.m. and 7 a.m.). Wang et al. in Shanghai made the same observation [16]. This situation could be explained by the absence of a sufficient number of qualified caregivers during the night, resulting in a decrease in the follow-up of newborns.
The strengthening of on-call teams seems to be necessary.

Factors Associated with Neonatal Mortality
Newborns whose mothers were in the informal sector and had a primary education had a significantly high risk of death. In an American study in California, university level was a protective factor [17]. This suggests that mothers with a low level of education have limited access to health care due to the financial means and are less aware of alarming signs.
Regarding obstetrical data, less than 4 antenatal visits and malaria during pregnancy increased the risk of neonatal death. This observation highlights the importance of high quality antenatal care for the well-being and survival of the newborn.
For newborns, cesarean section was a protective factor. This observation has also been made in California [17]. Our findings raise the question of timing and indications of cesarean section in our context assuming that this intervention should improve the prognosis of the mother and the child.
A gestational age less than 32 weeks increased the risk of death. Aguilera et al reported a high risk of death in preterm babies in Chile [18]. This is explained by the immaturity of these newborns and their high susceptibility to infections.

Limitations of the Study
The burden of neonatal mortality in sub Saharan Africa is well known. Many interventions are made to improve survival of newborns in Cameroon. The retrospective view of this study did not allow us to observe care practices at real time and identify any delays at different levels of intervention. However, we were able to identify the causes and factors associated with neonatal mortality in the neonatal department of this tertiary care hospital.

Conclusion
Our study found a reduction in neonatal mortality at Laquintinie Douala Hospital.
Prematurity, neonatal sepsis and neonatal asphyxia remain the major causes of