Neonatal mortality and risk factors in the University Hospital of the Mother and Child Lagoon in Cotonou, Benin, 2015-2016

Introduction: The neonatal period is one of the most vulnerable periods for a child’s survival because of the various attacks and infections, majority of which are avoidable mainly through preventive measures. We assessed neonatal hospital mortality and associated factors in a specialized hospital neonatal center. Methods: We conducted a retrospective descriptive study and then a case-control study from January 1, 2015 to December 31, 2016 at the Mother and child University Hospital in Cotonou, Benin. We considered all children hospitalized for any condition in the neonatal unit from January 1, 2015 to December 31, 2016 to conduct the descriptive study. From this population, we selected cases and controls for the case-control study. A case was defined as any newborn hospitalized for any condition in the University Hospital of the Mother and Child Lagoon (CHU MEL) neonatal unit, and who died before the 28th day of life and control was defined as any newborn hospitalized for any affection in the neonatal unit of CHU MEL and discharged alive during the period from January 1, 2015 to December 31, 2016. Socio-demographic, clinical and hospital-related data were recorded. We calculated the proportion and ratio. We conducted univariate, stratified, and logistic regression analysis and calculated odds ratio (ORs), adjusted odds ratios (aOR) and 95% confidence interval to identify risk factors associated with neonatal mortality. Results: We included 2,235 infants in the descriptive study and 828 for the case-control study. The sex ratio Male to female (HF) was 1.2. Mortality was 19% CI (17.08% -20.35%). The main diseases were neonatal jaundice at 33%, neonatal infections (NNI) (30%), prematurity (25%), perinatal asphyxia and other respiratory distress (19%).The risk factors for neonatal death were neonatal infections (aOR = 1.76 95% CI [1.09-2.85], p = 0.020), vaginal delivery (aOR = 1.68 95% CI [1.04-2.71] p = 0.031), preterm birth (aOR = 2.51 95% CI [1.28-3.60], p = 0.003), perinatal asphyxia (aOR = 2.78 95% CI [1.62-4.79] p = 0.0012), low birth weight (aOR = 9.35 95% CI [5.19-16.83] p <0.01), other health center origin (aOR = 1.80 95% CI [1.10-2.94] p = 0.018), resuscitation (aOR = 2.15 95% CI [1.34-3.45] p = 0.001) and malformation (aOR = 28.86 95% CI [7.92-105.15] p < 0.01). Conclusion: Neonatal mortality is high at CHU MEL. In the neonatal period, 80% of deaths occurred. Improvement in the follow-up of newborns, especially those exposed to its factors, will reduce this mortality. The health workers should consider these factors in care management of newborns.


Introduction
A neonatal death is death of any baby showing signs of life at 20 weeks gestation or beyond or weighing at least 400g if gestation is unknown, that occurs up until midnight of the 27th day of life ( neonatal period) [1].A neonatal death is defined as a death during the first 28 days of life (0-27 days) [2] .Globally approximately one million babies died on the first day of life in 2015, and neonatal deaths accounted for 45% of total under five mortality in the same year). In sub-Saharan Africa newborn deaths accounted for approximately one-third of deaths among children under 5 years [3] The first 28 days of life -the neonatal period -is the most vulnerable time for a child´s survival. Children face the highest risk of dying in their first month of life at an average global rate of 18 deaths per 1,000 live births in 2017. Regionally, neonatal mortality was highest in sub-Saharan Africa and South Asia, with each estimated at 27 deaths per 1,000 live births in 2017. A child born in sub-Saharan Africa or in South Asia is nine times more likely to die in the first month than a child born in a high-income country. Across countries, the risk of dying in the first month of life was about 50 times higher in the highest mortality country than in the lowest mortality country [4].
Despite progress made in improving maternal and child health, approximately 4 million neonatal deaths still occur annually; 75% of which happen in the first week with the highest risk of death being on the first day of life. High levels of neonatal deaths occur in countries in East and South-Central Asia, however the highest neonatal mortality rates are generally recorded in sub-Saharan Africa [5].
Globally, the main direct causes of neonatal death are estimated to be preterm birth (28%), severe infections (26%), and asphyxia (23%). Low birth weight is an important indirect cause of death. Maternal complications during labor increase the risk of neonatal death, and poverty has been strongly associated with an increased risk of neonatal mortality [5]. Approximately 450 newborn babies die every hour, mainly from preventable causes; it is therefore imperative to understand the causes in order to put in place effective preventive and control measures [5].
In 2015, the global neonatal mortality was 19.2 ‰ with regional disparities; [6] 28% in sub-Saharan Africa, 26.6% in the Mediterranean region , 24.3% in South-East Asia,7.7% in the Americas, 6.7%in the Western Pacific and 6% in Europe [6]. In Benin, neonatal mortality dropped from 40 deaths per 1,000 live births in 1990 to 28 deaths per 1,000 live births in 2012. However, neonatal mortality increased to 31.8 deaths per 1,000 live births in 2015 [6]. The hospital neonatal mortality rate is much higher than the global one [7][8][9][10].
One of the targets of the three goals of the Sustainable Development Goals is the reduction of neonatal mortality to less than 12 per 1000 [11]. If for most cases the causes are known, it is important to analyze in different contexts, the risk factors associated with these deaths. Several factors have been associated with neonatal mortality in different studies in Africa [12][13][14][15][16][17]. In Benin, studies conducted at the Parakou Regional Hospital Center in 2013 only focused on perinatal and early neonatal period [18], and were more relevant to perinatal and early neonatal mortality. We conducted a study to determine the factors associated with neonatal mortality at the University Hospital of the Mother and Child Lagoon in Cotonou in Benin.

Study Design
First, we conducted a retrospective descriptive study and then a case-control study from January 1, 2015 to December 31, 2016.

Study site and Study Population
We conducted this study at the Mother and Child University Hospital in Cotonou (CHU MEL). Cotonou, is the administrative capital city of Benin, located in the southern part of the country. The population of Cotonou is cosmopolitan and was estimated to be 752833 in 2016. Cotonou has two national referral hospitals, four private hospitals, and 318 public and private health centers. CHU MEL is a hospital with various services focused on the health of the mother and the child. It has a gynecologyobstetrics department; a pediatrics department that hosts the neonatology unit; a laboratory service, a pediatric surgery unit, radiology, social affairs, and pharmacy services.
The neonatal unit is manned by three pediatricians, 20 nurses, 11 caregivers, and three support/maintenance workers. The neonatal unit admits newborns referred from the gynecologyobstetrics unit of the hospital as well as newborns referred from other health centers. The neonatal unit has a breastfeeding room to allow mothers of children to breastfeed children at the facility.
The study population consisted of newborns from 0 to 27 days old admitted at the neonatal unit of CHU MEL from January 1, 2015 to December 31, 2016.

Data Collection
We defined a case and a control for a case-control study. We defined a case as any neonate hospitalized for any condition in the CHU MEL neonatal unit and who died before the 28th day of life during the period January 1, 2015 to December 31, 2016. A control was defined as any newborn hospitalized for any condition in the neonatal unit of CHU MEL and discharged alive during the period January 1, 2015 to December 31, 2016. Inclusion criteria: We included all neonates whose files were available and complete.

Exclusion criteria:
We excluded all children who went through the neonatal unit for a systematic examination only.
Sampling ( Figure 1) : For the descriptive study, we conducted exhaustive sampling of all children´s files that were completely filled. For the case control study, we calculated the sample size for the casecontrol study with the Statcalc utility of the Epi info software using 95% confidence interval, 80% power, unmatched 1 case for 1 control, and 30% of exposed controls to prematurity and an OR of 1.55, we considered the lowest value of OR that would make our study of public health interest. The minimum estimated sample size was 764.

Selection of cases:
We conducted an exhaustive census of all the cases of neonatal deaths that occurred from January 1, 2015 to December 31, 2016. All the 414 deaths that had occurred at the neonatal unit were included in the study.

Sampling of controls:
We generated a list of controls and selected 414 controls from the list of files corresponding to the definition of controls. For each cases, we selected every newborns that had been admitted on the same day and was discharged as alive. If there were more than one controls we randomly selected among the identified controls.

Data collection tools:
We used a data extraction form to capture data from hospital records (i.e. registers and patient files).

Study variables:
The dependent variable was either dead or alive. The independent variables were newborn related factors including gestational age at birth, birth weight, and final diagnosis recorded at discharge. We also abstracted variable on maternal factors including age, occupation; parity, conditions during pregnancy, mode of delivery, place of delivery, and type of pregnancy.

Data management
We entered and cleaned the data in Excel, and imported in Epi Info 7.1.1.14 for analysis. We performed bivariate and multivariate analysis using logistic regression and calculated odds ratio (ORs), adjusted odds ratios (aOR) and 95% confidence interval to identify risk factors. We carried out stratified analysis to control for confounding and assess for effect modification. All the factors whose p ≤ 0.20 in bivariate analysis were included in the logistic regression model.

Statistical analysis
Used Epi info 7.1.1.we calculated proportions and ratios for characteristics of newborns and causes of death and mortality rate. We compared proportions using the Pearson chi square test. We conducted bivariate and multivariate analysis using logistic regression to obtain associated factors. For stratified analysis, we performed crude analysis by calculating crude OR for each factor with confidence interval and p-value; we stratified the data by potential confounders and effect modifiers including age group and place of delivery , multiple pregnancy, resuscitation performed at birth, birth weight, delivery mode, diagnosed of infection, malformation and asphyxia.
We calculated stratum-specific OR; age groups <7 days and ≤7days of age were considered. We evaluated for effect modification by comparing stratum-specific OR. Where effect modification was present, we reported stratum-specific OR. Where effect modification was absent, we assessed and controlled for confounding by comparing the stratum-specific OR with the crude OR. If the crude OR value did not fall within the range of the smallest and the largest stratum-specific OR, confounding was present; we then calculated the weighted average of stratum-specific OR (Mantel-Haenszel summary OR) and compared the adjusted OR with the crude OR to see if they were "appreciably different".
For multivariate analysis, we introduced a logistic regression model and included the variables whose p values were less than or equal to 0.20 to look for confounding factors. We used Odds ratios (OR) and their 95% confidence interval (95% CI) to estimate the strength of the association. The threshold meaning was at 5% and the adequacy of the final model was tested by the Hosmer and Lemeshow test.

Ethical considerations
We obtained approval from the Ministry of Health. We ensured anonymity by not extracting identification details such as names from files at the Neonatology Unit of CHU MEL hospital. Confidentiality was assured and maintained throughout the study.

Characteristics of newborns hospitalized in CHU MEL neonatal unit, Cotonou Benin from January 2015 to December 2016
We recorded 2235 files of neonates who had been hospitalized for any condition from January  Table 3).

Stratified analysis
Factors associated with neonatal mortality were stratified by age to assess for possible confounding and effect modification. Age appeared to be an effect modifier of resuscitation. Newborns who were less than 7 days old and had been resuscitated were 4.51 times more likely to die compared to newborns who were more than 7 days old and had been resuscitated. This effect was also found in newborns of preterm birth and those who had been diagnosed with asphyxia. Age less than 7 days old appeared to be factor of very low birth weight (  Table 5 ).

Discussion
We found that the neonatal mortality rate was high in the hospital. The hospital based mortality founded in our study was 18.7% which was higher compared to neonatal mortality at the national level estimated at 3.18% in 2015 [6]. This could be explained by the fact that in this study only newborns with a condition were considered for the total population. In addition, not all neonates had been admitted to the neonatal unit. Our hospital based mortality are close to those found by other authors, including FLA Kouéta (15,3%) [12,20]. The mortality in our study was also lower than that found by Imoudou (25,9%) at the Azare hospital in Nigeria [9]. These differences can be explained by the ways in which these studies were conducted and the places of study. Kedy Koum[20] worked in a resource-limited hospital where only newborns weighing 1500g or over were admitted and the birth term was greater than 32 weeks whereas in our study we included newborns with very low birth weight and premature babies. The difference in results could also be due to the fact that Harir Noria [12] considered the denominator as the number who were born in the hospital, which is different from our study where we considered only children who had been hospitalized for a condition similar to the cases but were discharged alive. Imoudou [9] worked in an area where the majority of deliveries were done at home before the newborns were transferred to hospital; in our study, little newborn came from home.
We also found that the most common conditions in our study were neonatal jaundice ( Neonatal deaths occurred in the early neonatal period in high proportion. This proportion is close to that of Yenan at the University Hospital of Bouaké, Bezzaoucha at Blida University Hospital in Algeria [19,22].Others studies had higher proportions: Azoumah at Kara University Hospital, Harir Noria at the hospital Sidi Bel Abbes in Algeria [12,23] . This is explained by the fact that the early neonatal period is one of the delicate periods of the child's life and that if the care at this period is done according to the standards (asepsis), and without a rigorous follow-up to detect early the problems of the newborn, he may die.
We also found factors such as prematurity, very low birth weight, vaginal delivery, having a congenital malformation, perinatal asphyxia and neonatal infection were significantly associated with neonatal death.
Prematurity is one of the causes of neonatal deaths often found in the literature. In our study, prematurity was significantly associated with neonatal death. Koum [17], Harir Noria in a study at Gynecology-Obstetrics Hospital Sidi Bel Abbes, Algeria also used low weight and found that it was related to death (OR: 4.5 CI 1.6-10.5) [12]. The very low birth weights in our environment cause serious problems for the health worker staff from their medical care. Also the lack of equipment does not allow adequate and effective treatment. Their care being delicate, it will be necessary that our hospitals are well equipped to ensure a good follow-up.
The vaginal delivery may be normal, obstructed, forceps or episiotomy and it is significantly associated with death. Kisito at El Fateh Suka hospital in Ouagadougou found this as a risk factor (OR = 6.57, CI 1.33-32.29) [19,8] . During vaginal delivery, several complications can occur and be a source of morbidity in the newborn. Moreover, without proper surveillance, early detection of complications for decision-making without delay leads to newborn childbirth with morbidities that can lead to death. The presence of malformation is associated with death in our study. Fla described it as a major condition leading to death, but did not have a significant association [7]. Malformed newborns often have multiple malformations, making their management difficult, hence the majority of deaths observed. The asphyxia is one of the top three causes of death worldwide. It is related to death in our study. Michel K.N. at the Kolwezi Hospital (DRC) (OR 7.86, IC2.02-30.64) [10] also found it. Neonatal infections were with prematurity and asphyxia, the three leading causes of death in 2015 globally. Associated with death in our study, and although most studies have described it as one of the leading causes of death, they have not been able to demonstrate a significant association. Neonatal infections have several causes that can be of antenatal, perinatal or post-natal origin. The diagnosis of certainty is made by laboratory examinations, the costs of which are borne by the parents, sometimes resulting in a clinical diagnosis. In some cases, the treatment must be precise, which is still not the case.

Limitations
In this study, some of the case and control patient files had some missing data. However, the missing data was very low at about 5% and would minimally change the overall findings.

Conclusion
Neonatal mortality is high at CHU MEL. In the neonatal period, 80% of deaths occurred. The most common conditions found in deaths are, prematurity followed by birth asphyxia and other respiratory distress and neonatal infection. Several factors are related to this mortality. Improvement in the followup of newborns, especially those exposed to these factors, will reduce this mortality. The health workers should consider these factors in care management of newborns.
What is known about this topic  Neonatal mortality remains high  Conditions leading to death in newborns are infections, prematurity and perinatal asphyxia 7 |Page number not for citation purposes What this study adds  Malformations and low delivery are also factors related to neonatal mortality  Mortality will be reduced at the Hospital by taking account the factors detected by health workers in care management of newborns

Competing interests
The authors declare that they have no competing interests.

Consent to publish
Consent to publish was sought from all the authors and was obtained.

Funding
This study was not funded by any organization.

Availability of data and materials
The dataset for this study can be availed upon request. The dataset is an Excel dataset.
Authors' contributions MAH, BS, SA, MS, YAGH developed the protocol, collected the data. MAH, BS, YAGH, LO, BS, SA, MS analyzed the data and interpreted the data and wrote the manuscripts. MAH, BS, SA, YAGH reviewed several drafts and made a substantial contribution to the writing of the manuscripts. All authors read and approved the final manuscript.

Acknowledgments
The authors would like to thank the following institutions:  West African Field Epidemiology Training Program  African Field Epidemiology Network  West African Health Organization (WAHO)  CDC-Atlanta  Health workers in neonatal unit in CHU MEL  Ministry of Health, Benin