Methods.
The study base comprised of singleton very preterm infants born during the defined period above at this tertiary care center. The antenatal, perinatal and postnatal data were collected through medical records review of these infants and their mothers. The hospital course and complications of both infants and mothers were studied.
We conducted both univariate and multivariate logistic regression analyses for different explanatory (independent) variables with survival as outcome. Univariate analyses were confirmed by Chi-square or Fisher’s exact test. All potential predictor variables were included in multivariate models. P < 0.05 was considered statistically significant and P = 0.05—0.10 associated with a trend only. STATA 14.0 software was used for statistical analyses.
Results.
101 very preterm infants were born during the defined study period. The mean maternal age was 28.1 ± 5.1 years and mean hemoglobin (Hb) of 11.0 ± 1.4 g/dL (n = 78) at the time of delivery; 41.6% of mothers had Hb ≤ 11 g/dL i.e. were anemic. 26 mothers had chronic hypertension, pregnancy-induced hypertension/pre-eclampsia or eclampsia and 10 mothers had pre-existing or gestational diabetes. The cause of preterm delivery was identified in 97 mothers and was preterm premature rupture of membranes (40/97, 41.2%), followed by pre-eclampsia/eclampsia 17/97 (17.5%), antepartum hemorrhage 12/97 (12.4%), fetal distress/oligohydramnios/intra-uterine growth restriction 6/97 (6.2%), preterm labor 5/97 (5.2%), cervical incompetence/cerclage 4/97 (4.1%), hepatic failure/HELLP syndrome 3/97 (3.1%), maternal cancer 3/97 (3.1%), per-vaginal bleed 2/97 (2.1%), hydrocephalus/myelomeningocele 2/97 (2.1%), septate/fibroid uterus 2/97 (2.1%) and cord prolapse 1/97 (1.0%).
The mean birth weight of these infants was 1042.1 ± 304.8 grams (range = 400—1750). 53 (52.5%) were males. 54/101 (53.5%) were born via Cesarean section and 47/101 (46.5%) had vaginal delivery. The presentation at delivery was cephalic in more than half of infants (60/95, 63.2%). 76/101 (75.3%) of infants required intubation. The median Apgar score was 5 at one minute and 7 at five minutes. Other detailed characteristics of these infants have been published elsewhere [5]. The survival incidences were 0% at 23, 16.7% at 24, 40.0% at 25, 30.0% at 26, 33.3% at 27, 68.8% at 28 and 83.9% at 29 weeks of gestation. The corresponding survival proportions were 0%, 33.3%, 55.8%, 80.6% and 100% for birth weight categories of < 400, 400—800, > 800—1200, > 1200—1600 and > 1600—2000 grams. Overall, 59/101 (58.4%) of infants survived to hospital discharge.
In univariate analyses, gestational age (per 1 week increase, OR = 2.0, 95% confidence interval (CI): 1.4—2.9); birth weight (per 100 grams increase, OR = 1.4, 1.2—1.6) and mode of delivery (Cesarean section had higher survival compared to vaginal, OR = 4.2, 1.8—9.8) were statistically significant predictors of survival (P ≤ 0.001 each) (Table 1).. Other variables that also included antenatal steroids (Reference: 0 mg; 12 mg OR = 3.2, 0.75—13.2, P = 0.12; 24 mg OR = 2.0, 0.75—5.5, P = 0.16; > 24 mg OR = 3.9, 0.95—15.7, P = 0.06) did not achieve significance. In complete case multivariate analyses after excluding n = 23 missing values for Hb at delivery, only gestational age (in per 1 week) was associated with survival with statistical significance (OR = 2.5 (95% CI: 1.1–5.5), P = 0.03. Birthweight (per 100 grams increase) and abdominal delivery were not associated—OR = 1.2 (0.88–1.6), P = 0.26 and 2.4 (0.48—12.2), P = 0.28, respectively (Table 1).. Antenatal steroid use, maternal age, year of birth, parity, history of preterm delivery, Hb at delivery, time of birth and any of maternal complications (presence of hypertension or diabetes during pregnancy) remained not associated. After removing Hb as a variable in the multivariate model and retaining all n = 101 observations, gestational age remained associated (OR = 1.9, 1.1—3.4, P = 0.03) and maternal complications was associated with a trend towards reduced odds of survival (OR = 0.30, 0.08—1.1, P = 0.07).
Sensitivity Analyses.
After removing birthweight from the multivariable model, the gestational age variable again became highly statistically significant (OR = 2.4, 1.5—3.9, P < 0.001) as in univariate analysis showing that the effect of gestational age was partially mediated through birthweight. Similarly, removing gestational age from the model also made birthweight and abdominal delivery statistically significant (OR = 1.4, 1.2—1.7, P = 0.001) and (OR = 3.6, 1.2—10.4, P = 0.02) indicating that gestational age may be a confounder.