Survival of neonates and predictors of their mortality in Tigray region, Northern Ethiopia: prospective cohort study

A prospective cohort study was conducted among a cohort of neonates delivered between April 2014 and July 2014 in randomly selected seven hospitals of Tigray region, which is one of the nine administrative Federal regions of Ethiopia. Tigray region has an estimated total population of 4,565,000, (2,314,000 women and 2,251,000 men). The Ethiopian health care has a decentralized four-tier system of primary, district, zonal and specialized hospitals. The primary care includes rural health posts, nested into health centers serving 25,000 populations. District hospitals form the tiers expected to serve 250,000 catchment populations. Zonal and specialized hospital serves 500,000 and 5,000,000 populations respectively. In Tigray region, one of the 11 administrative states in Ethiopia, has a total of 15 public hospitals; 6 zonal, 1 specialized hospitals, and the remaining 8 in the district and primary health care category. All hospitals provide maternal and newborn services including delivery services free of charge. Seven hospitals were randomly selected from the 15 hospitals of the region by lottery method [21]. All mothers who gave a live birth in the study hospitals came from the entire region were included in this study and followed up for a total of 28 days.

Mothers with their Neonates, who gave live birth in the study hospitals or admitted within six hours, from April -July, 2014 were included in the study. Mothers who were unable to speak and mothers with psychiatric illnesses were excluded from the study.

The sample size was 1162 neonates, which were determined by using STATA statistical package, Version 11.0. Based on the assumptions of 2.19 hazard-ratio [22] associated preceding birth of the mother, there was a variability of 0.5, probability of death 0.044 [4], 5 % marginal error and 95 % confidence interval of certainty to have a power of 80 %. It was assumed that no subjects were anticipated to withdraw from the follow-up.

Data were collected prospectively using pre-tested structured questionnaires and using a checklist for data that were collected from assessments of the neonate and mother. The questionnaire was derived from related literatures and WHO standard verbal autopsy questionnaires [23]. The questionnaire was initially developed in English and translated into local language, Tigrigna. Two midwives, with a qualification of university degree and can speak the local language from each hospital were recruited for data collection. The data collectors had been collecting information by interviewing all mothers who delivered a live birth at the selected hospitals within the first 6-h after delivery. Besides, the clinical information was extracted by assessment of the neonate and mother. Mothers and live births were followed for 28 days, using three alternatives. The data collector visited the neonate daily, while he/she was in the hospital. After the mother was discharged; the data collector met the mother every 7-days either using a phone call or by creating liaison with a health extension worker and inquired about the neonatal condition and survival. Mothers who were not at home during the scheduled visit were revisited. When death occurred, the date and cause of death was recorded and probable cause of death was assigned after agreement between midwives and physicians based on national guidelines [24] and the International classification of disease [25]. The data that were collected prospectively consisted of Time to death of neonates (Dependent variable), and the socio-demographic, economical, neonatal, and maternal and health service-related characteristics (independent variables).

The inclusion of variables was partly guided by the Mosley and Chen conceptual framework [26] previously used in similar studies with some modifications. The factors influencing NM were broadly categorized as follows:

The variables assessed in this category were: monthly reported income categorized into, low (<500 ETB), medium (500–1500 ETB) and rich (>2000ETB), and residence classified into ‘rrban’/‘rural’. Age at first marriage was measured in continuous scale yet for the sake of analysis later it was categorized into below age of 18 (teenagers), ‘18 years and above’. Similarly, educational status was first categorized in to ‘unable to read and write’,’able to read and write but no formal education’, ‘1–4 grade’, ‘5–8 grade’, ‘9–12 grade’, ‘college and above’ but later during analysis considering the few number of observations in the ‘able to read & write’ category, we merged it into (unable to read & write with able to read & write), and finally categorized into : ‘(unable to write & read or no formal education)’, ‘primary education (1–8 grade)’, ‘secondary (9–12 grade)’ and ‘tertiary (college and above grades)’.

Likewise, marital status was first categorized into married (living together), single, widowed, divorced and separated but later during analysis due to few observations, we merged the categories other than the ‘married’ category in to ‘others’. Occupation was classified based on the mothers report into ‘house wife/farmer’, ‘own business’ ‘government employee’ and ‘student’.

This category includes: Gestational age, which was measured by using last menstrual period and/or ultrasound. Gestational age was categorized into preterm (<259 days), term (259–293 days) and post term birth (> = 294 days) but during analysis due to the few observations of post term births coded with term birth. Birth weight was defined according to the WHO classification as low birth weight (<2500 gm); normal birth weight (> = 2500 and <4000 gm); and macrosomia (> = 4000 gm) [27] but later during analysis, it was coded into low birth weight and normal birth weight (> = 2500 gm) and it was measured using a standard beam balance within six hours of delivery.

Body mass index (BMI), measured by a standard height, weight measuring instrument found in the study hospitals and was categorized into underweight (BMI less than 18.5), normal (BMI 18.5–24.9), Overweight (BMI ≥25.0). Weight for gestational age was categorized according to WHO definitions into: ‘Large for gestational age’ was defined as a birth weight greater than the 90^th percentile for age, ‘Small for gestational age’ birth weights below the 10th percentile. ‘Appropriate for gestational age’ defined as birth weight between the 90–10th percentile [28]. The cut off points of weight for gestational age was derived from Alexander et al. described elsewhere [29] and adapted to our study with some modifications.

In our study, fertility (no of children) defined as the actual production of live offspring excluding stillbirths, fetal deaths and abortions. It was classified into primiparae (only the current birth), 2–4 and multiparty (> = 5). But parity was defined as the number of full term children previously borne by a woman, excluding miscarriages or abortions in early pregnancy, but in contrast to fertility it includes stillbirths. It was categorized into ‘none’ ‘one’ ‘two’ and ‘> = three’.

We defined gravidity as the number of pregnancies (completed or incomplete) experienced by a woman in contrast to fertility and gravidity it includes all pregnancies. We categorized it into ‘no pregnancy’, ‘one pregnancy’, ‘two pregnancy’ and ‘> = three pregnancy’.

Antenatal follow up was assessed by categorizing in to ‘Yes’, if the mother ever had at least one antenatal follow up, ‘No’ if the mother never had antenatal follow up.

Diagnosed medical disease was assessed using, ‘Yes’ if the mother had a medically known/diagnosed disease such as HIV/AIDS, Hypertension, Diabetes mellitus, epilepsy and ‘others’. ‘No’, if the mother did not have medically diagnosed disease.

History abortion defined as mother history of abortion either induced, spontaneous or self initiated abortion before the current birth. It was categorized into ‘Yes’/‘No’.

Induced abortion was defined as an abortion induced medically by a health professional, but self induced abortion was defined as abortion initiated by the women without medical and legal indication. Spontaneous abortion was defined as an abortion, which is neither medically induced nor self initiated, but the fetus spontaneously aborted itself. Similarly, history of still birth was categorized into ‘Yes’ and ‘No’.

Place of birth (inborn or out born) was defined ‘Inborn’ if the neonate was delivered inside the study hospitals, ‘out born’ if the neonate was delivered in either health facility or home outside the study hospital. We categorized into ‘Yes’ if inborn or ‘No’ if out born.

Place of death was defined as the place where the neonate died after included in the study, which was categorized into ‘hospital’ if the neonate died inside the hospital where he/she delivered, ‘Home’ if he/she died after discharged from the given hospital, ‘other health facility’ if the neonate died in other health facility other than the given hospital.

Birth type was initially categorized into ‘single’, ‘twin’, ‘triple and above’. Yet for the purpose of analysis twin and triple birth were merged into ‘Multiple births’. Mothers who gave twin and triple birth were counted separately for each birth for the sake of analysis.

Distance was recorded in continuous scale, but later categorized in to <5 km far from the nearest health facility, 5–10 km and > =10 km far from the nearest health facility.

Mode of delivery is classified into ‘spontaneous vaginal delivery’, ‘operative (instrumental) vaginal delivery’ and ‘cesarean section’. Instrumental delivery was defined as the application of either forceps or a vacuum device to assist the mother in effecting vaginal delivery of a fetus.

The variables considered in this category were: Hypothermia in which it was classified according to WHO recommendations into ‘Yes’ if body temperature below the normal range (36.5 °C–37.5 °C), ‘No’ if it is within the normal range and above [30].

Temperature control for the hypothermic neonates categorized into: ‘Yes’ if the hypothermic neonate temperature returns to normal after appropriate interventions was undertaken and ‘No’ if the hypothermic neonate temperature is not returned to normal range after the intervention. We did not consider this variable in the Cox-regression model due to large missing values.

Exclusive breast feeding (EBF) (Yes/No): was defined as feeding with only breast milk and nothing else, with the exception of vitamin supplements and prescribed medicines.

Maternal complication categorized into ‘yes’ or ‘No’, which is considered present if the mother had an obstetric hemorrhage, puerperal sepsis and pyrexia, prolonged labor, eclampsia and preeclampsia, mal-presentation and mal-position, premature rupture of membrane (PROM), cord prolapse, obstructed labor, cephalopelvic disproportion (CPD), emergency cesarean section, and retained placenta.

Neonatal complication is considered presented if the neonate had asphyxia, prematurity, infection, hypothermia, jaundice and other rare complications during birth.

Early neonatal mortality rate (ENM) was defined as the probability of dying before 7 completed days of life. Late neonatal mortality rate (LNM) as the probability of dying between 7 completed days and before 28 completed days; and overall NM was defined as death of a newborn within 28 days of his/her birth. NMR was defined as the number of deaths of neonates per 1000 live births. NM was categorized into ‘Yes’ if the neonate died ‘No’ if the neonate censored.

Censored births were the neonates who were alive at the end of follow up, withdrawal and lost-to-follow-up. Time-to-death was defined as death of a neonate at specific time (day) within the 28 days follow-up time.

The outcome of the follow up was categorized into ‘death’ if he/she died during follow up, ‘lost to follow up’ if the mother phone was not working, moves to another area from the original place of residence and not met by health extension worker. ‘Withdrawal’ if the mother refuses the follow up due to inconvenience and ‘alive’ if the neonate survival is assured by the data collector at the last follow- up time.

Death of neonate was the event of interest and the coding were “1” for death and “0” for censored. Time-to-death was calculated by subtracting the date of death from birth.

Data was entered, cleaned, recoded and analyzed using STATA version-11.1. For description, frequencies, percentages, and rates, Kaplan Meier curves were used to estimate survival time. Log-rank test was used to look statistical differences among/between the categories of variables. To identify potential predictors of NM, Cox-proportional hazard regression model was fitted by successive stepwise backward elimination. Statistical significance was declared at p-value <0.05. Confounding and effect modification was checked by looking at regression coefficient change if greater than or equal to 15 % and multi-collinearity was checked using variance inflation factor and value of <10 was used as a cutoff point, indicating no colinearity.

Proportional hazard assumption was tested by using covariate specific Proportional hazard assumption test. Residuals were checked using goodness-of-fit test by Cox Snell residuals.

Ethical clearance was obtained from Mekelle University, College of Health Sciences Ethical review board. Permission letters were also sought from Tigray Regional Health Bureau. Written Informed consent from the mother was obtained after clear explanation of the purpose of the study. Confidentiality and anonymity was maintained.