Characteristics of study participants
A total of 311 preterm neonates were studied (Table 1). Majority (75.9%) were late preterm. More than half (53.1%) were females and nearly half (50.8%) of the neonates were delivered vaginally and had birth weight ranging from 1500 – 2499 grams (55.9%). Most of them had an Apgar score ≥7 in the 1st and 5th minutes.
(see Table 1 in the Supplementary Files)
Characteristics of mothers with preterm neonates
A total of 265 mothers with preterm neonates were studied (Table 2). The overall mean age was 27.09 (SD=6.59) years. Nearly half (44.9%) were aged between 25-34 years. More than half (55.1%) lived in rural areas and had para 2-4 (55.9%) and had less than four (4) ANC visits (55.5%).
(see Table 2 in the Supplementary Files)
Mortality Risk of Preterm Neonates
A total of 311 preterm babies were followed-up to 28 days. The end point was either death within 28 days of life, censoring due to lost to follow up or alive up to 28 days of life (Figure 2). During the first day of life, 20 neonates died. At day 3 of life of each neonate, a total of 273 neonates were at risk of death. On day 7, a total of 264 were at risk. On day 14 of life, 252 were at risk and on day 28, a total at risk were 246 preterm neonates.
Neonatal complications of preterm babies
Respiratory Distress Syndrome (RDS) was the most frequent complication constituting about 26%, followed by multiple conditions (11.3%) and suspected early onset neonatal sepsis (EONS) (10.6%). Neonates with multiple conditions had either RDS and sepsis/congenital anomaly or RDS and EONS. Other conditions were infrequently observed (Figure 3).
Maternal complications of preterm mothers
The most frequent complication was urinary tract infection (UTI) 94 (35.5%) followed by Premature rupture of membrane (PROM) (20%) and Pre-eclampsia (15.9%). Other complications such as epilepsy, chorioamnitis, puerperal psychosis, post-partum hemorrhage (PPH) and hypertension were infrequently reported (Figure 4).
Frequency and mortality of preterm births
A total of 3,271 live births were assessed with their gestation age. Of these, 311 were preterm. This corresponds to frequency of preterm birth of 10%. During the follow-up, 292 preterm babies had completely known survival status. Forty-six (16%) preterm babies died within the follow up period. Most (95.7%) of deaths occurred during the hospital admission and 4.3% of deaths occurred at home post hospital discharge. Over forty-percent (43.5%) of deaths occurred within the first 24 hours of life. Three quarters (76%) of the deaths occurred within the first 7 days of life and 24% from day 7 to day 28 of life. Sixteen percent of those who had gestation age (GA) of < 32 weeks but >28 weeks died, while 95% of those with GA <28 weeks died. Only 5% of those with GA > 32 weeks died.
Neonatal Mortality Rate among preterm babies
Neonatal mortality rate of the participants has been shown in Table 3. The overall neonatal mortality rate was 6.5 deaths per 1,000 live preterm births (95% CI: 0.48-0.86). Before the event (death) had occurred, the total time contributed by all individuals was 71.3 person years.
We further calculated neonatal mortality according to neonate characteristics (Table 3). Extreme preterm babies (GA <28weeks) had the highest mortality rate of 200 deaths per 1,000 preterm live births (95% CI: 113.58 - 352.17). Mortality rate of preterm babies with birth weight of <1 Kilogram was 94 per 1,000 preterm live babies (95% CI: 52.10-169.80). Nevertheless, preterm babies with Apgar score of < 7 in the 5th minute had higher mortality rate than those with Apgar score of <7 in the 1st minute of life [87.21(95% CI: 52.58 - 144.66) versus 40.93 (95% CI: 28.61 - 58.54) per 1000 live preterm live births respectively]. Furthermore, neonatal mortality rate among preterm babies with birth asphyxia was higher compared to those with respiratory distress syndrome [37.15 (95% CI: 21.20-65.42) versus 21.68 (95% CI: 15.33-30.66) per 1,000 live preterm births] respectively.
(see Table 3 in the Supplementary Files)
Overall survival time estimate
The probability of survival rapidly decreased from day 1 to day 2, and thereafter, then it remained constant. The last event occurred on day 24 of life. Since the survival function did not fall below 50%, the median survival time could not be estimated. Instead, a restricted mean was calculated. The overall mean survival time was 24 days (Figure 5)
Survival time estimate in different groups
Preterm with GA<28 weeks had lowest survival probability compared to other gestational age groups. Most of them died within the first 24 hours with median survival time of 1 day. Preterm neonates with GA between 32-36 weeks had highest survival probability and their restricted mean survival time was 26.9 days.
Preterm with birth weight<1000grams had higher mortality compared to those who had >1,000 grams. Their median survival time was 2 days. Majority of deaths were observed on day 1 and 2 with the last death occurring on day 20. Neonates with birth weight 1,000-<1,500 grams had mean survival time of 18.2 days their survival probability decreased over time and the last neonate died on day 20. Preterm neonates with birth weight 1500 - 2,500 grams had a constant survival probability and their mean survival time was 26.1 days. However, those neonates with birth weight 2,500 grams and above had better survival probability and their mean survival time was 27.7 days. This corresponds with the survival probability for neonates with GA 32-36 weeks.
Preterm neonates with Apgar score <7 in the first minute died more on day 1 followed by day 2. Their survival probability decreased over time with median survival time of 14 days as compared to those with Apgar >7 in the first minute whose probability of survival was constant over time. Likewise, those with Apgar score <7 in the 5th minute died more on day 1 and their probability of survival decreased thereafter with time and their median survival time was 2 days. Those with Apgar score >7 in the 5th minute of life had almost a constant survival probability over time. In all the sub categories tested, the proportional hazards assumption for cox regression were seen to hold. Log rank test was significant at p<0.05 for gestation age, birth weight, and 1st and 5th minute Apgar score. This indicates difference in survival experience between categories in question (Figure 6)
Neonatal characteristics associated with neonatal mortality among preterm babies
In crude analysis, gestation age <32 weeks, 1st and 5th minute Apgar score <7, respiratory distress syndrome and birth asphyxia were significantly associated with neonatal mortality among preterm babies.
In multivariable analysis, only variables which were significant in the crude analysis were included in the final model. Gestation age<32 weeks, 1st min Apgar score<7 and respiratory distress syndrome were found to be independent predictors of neonatal mortality among preterm babies. Extreme preterm neonates had 9 times higher hazard of dying (HR: 9.21; 95% CI: 2.54-33.47) than those with gestation age 32-<37 weeks. Very preterm neonates (28-32 weeks) had 3 times higher hazards of dying (HR: 3.42; 95% CI: 1.34-8.69) compared to moderate/ late preterm ones (32- <37weeks). Preterm neonates whose 1st min Apgar score was <7 had 6 times higher hazards of dying (HR: 6.12; 95% CI: 2.76-13.58) compared with those with 1st min Apgar score of >7. Preterm neonates with RDS had 2 times higher hazards of dying (HR: 2.54; 95%CI: 1.02-6.34) than those without RDS (Table 4).
(see Table 4 in the Supplementary Files)
Maternal Factors Associated with Neonatal Mortality among Preterm babies
Adjusted analyses for maternal factors leading to mortality of preterm babies has shown only APH to be the independent predictor for mortality whereby women who experienced it had three times [3.32 (95% CI: 1.49-7.39)] more hazards to appreciate the deaths of their newborns compared to those who did not experience APH. Other factors were not statistically significant at p<0.005 as seen in Table 5 below.
(see Table 5 in the Supplementary Files)