Ninety-four cases of PPROM (≥ 7 days) deliveries were included in the study period. None of the mothers underwent a prior amniocentesis. They were all admitted at onset of PPROM and were kept under observation at the maternal high-risk pregnancy ward until delivery. Demographic and clinical characteristics of the mothers and preterm infants are presented in Table 1. Briefly, the average maternal age was 28.4 ± 5.4 and the average GA at delivery was 30.8 ± 3.1weeks (range 23 - 34). Median GW at onset of PPROM was 27.1 ± 4.2 weeks (range 17 - 33) and median length of latency period in days was 16 ± 21.8 (7 - 105). Corticosteroids, magnesium and antibiotics were administrated to almost all the mothers (97.9 - 98.9%).
Table 1
Maternal and neonatal characteristics
| GW at PPROM | |
Characteristics | Total (17-33) N=94 | Group 1 (17-23) N=24 | Group 2 (24-27) N=27 | Group 3 (28-33) N=43 | p value |
Maternal characteristics | | | | | |
Maternal Age (year) | 28.4±5.4 (20-41) | 29±5 (22-41) | 28.2±5 (21-41) | 28.2±5.8 (20-41) | .401 |
Gravidity | 4.8±3.2 (1-16) | 4.8±2.8 (1-12) | 4±2.2 (1-9) | 5.1±3.8 (1-16) | .826 |
Parity | 3±2.4 (0-12) | 3±2.2 (0-8) | 2.5±1.9 (0-7) | 3±2.8 (0-12) | .493 |
Celeston (2 courses) | 93 (98.9) | 23 (95.8) | 27 (100) | 43 (100) | .229 |
Magnesium treatment | 92 (97.9) | 22 (91.7) | 27 (100) | 43 (100) | .051 |
Treatment with Antibiotics (Mercer protocol ) | 93 (98.9) | 24 (100) | 26 (96.3) | 43 (100) | .285 |
Chorioamnionitis | 18 (19.1) | 4 (16.7) | 11 (40.7) | 3 (7) | .002 |
Previous preterm delivery * | 12 (12.8) | 7 (29.2) | 0 | 5 (11.6) | .024 |
Placenta abruption | 22 (23.4) | 9 (37.5) | 7 (25.9) | 6 (14) | .086 |
GW at onset of PPROM (median, week) | 27±4.2 | 22±1.6 | 26±1.2 | 31±1.4 | < .001 |
Latency period (median, day) | 16±21.8 (7-105) | 49±28.1 (12-105) | 17±14.8 (7-61) | 12±5.7 (7-26) | < .001 |
Cesarean delivery | 45 (47.9) | 17 (70.8) | 14 (51.9) | 14 (32.6) | .01 |
Neonatal characteristics | | | | | |
GA at delivery (week) | 30.8±3.1 (23-34) | 28.5±3.3 (23-34) | 29.3±2.4 (25-34) | 33±1.3 (30-34) | < .001 |
Male gender | 60 (63.8) | 14 (58.3) | 20 (74.1) | 26 (60.5) | .416 |
Birth weight (g) | 1615.1±544.4 (488-2945) | 1270.6±472.1 (488-2120) | 1347.7±410.3 (730-2270) | 1975±428.4 (1145-2945) | < .001 |
Apgar score 1 min. | 6.8±2.5 (1-9) | 5.1±2.4 (1-9) | 6.2±2.8 (1-9) | 8.1±1.6 (2-9) | < .001 |
Apgar score 5 min. | 9.6±1.8 (3-10) | 7.6±1.4 (4-10) | 8.3±1.9 (4-10) | 9.4±1.3 (3-10) | < .001 |
Survived to Hospital discharge | 86 (91.5) | 19 (79.2) | 24 (88.9) | 43 (100) | .012 |
Data are expressed as mean/median ± standard deviation (range) or n (%). |
* 2 missing values |
GA, Gestational age; GW, Gestational week |
The cohort was further stratified per GW at onset of PPROM, as group 1 (17 - 23 weeks), group 2 (24 - 27) and group 3 (28 - 33), (Table 1). There were no significant differences in maternal comorbidities including hypothyroidism, diabetes mellitus, gestational diabetes mellitus, hypertension, epilepsy, thrombophilia, maternal fever, group B streptococcus (GBS) colonization and maternal use of selective serotonin reuptake inhibitors (SSRIs), between the groups. However, the rate of chorioamnionitis, per Chi square analysis, was significantly higher in-group 2 (p = < .001) and lower in-group 3 (p = .006) after Bonferonni correction. Furthermore, mothers in-group 3 had a significant lower rate of cesarean delivery (32.6%, p = .006) and significantly more mothers in-group 1 (29.2%) had a previous history of preterm delivery, (p = .004) than the ones in the other groups after Bonferonni correction. By Kruskal-Wallis test with post hoc comparison, the median length of latency period, in group 3, was significantly shorter than in group 2 and 1 (12 ± 5.7 vs 17 ± 14.8 and vs 49 ± 28.1, p < .001, respectively).
By one-way ANOVA test with post hoc analysis, GA and BW in-group 3 were significantly higher than in group 2 and 1 (p < .001). Similarly, Apgar score at 1 and 5 min in-group 3 were significantly higher than in group 1 and 2, (p < .001 and p < .05, respectively). We found that the survival rate to discharge in neonates born to prolonged PPROM-complicated pregnancy at GW < 24 is 79.2%, compared to 88.9% in group 2 (p<0.451) and 100% in group 3(p<0.012). We further compared neonatal outcomes between group 1 and group 2, the next closest group in terms of GW at PPROM onset (Table 2). There were no significant differences between group 1 and 2 for most of the reported parameters with the exception of use of surfactant (70.8% vs 37%, respectively, p = .025, two-sided Fisher's exact test) and NO inhalation treatments (25% vs 3.7%, respectively, p = .042, two-sided Fisher's exact test). Also, mean Apgar at 5 min in group 1 was significantly lower than in group 2, (7.6 ± 1.4 vs 8.3 ± 1.9, p = .029).
Table 2
Neonatal outcomes by gestational week (GW) at PPROM
| GW at PPROM | |
| Group 1, N = 24 (17 - 23) | Group 2, N = 27 (24 - 27) | p value |
GA at delivery (week) | 28.5±3.3 (23-34) | 29.3±2.4 (25-34) | 0.366c |
Birth weight (g) | 1270.6±472.1 (488-2120) | 1347.7±410.3 (730-2270) | 0.536b |
Apgar 1 | 5.1±2.4 (1-9) | 6.2±2.8 (1-9) | 0.111c |
Apgar 5 | 7.6±1.4 (4-10) | 8.3±1.9 (4-10) | 0.029c |
SGA | 2 (8.3) | 3 (11.1) | 0.821 |
Cases of intubation | 15 (62.5) | 10 (37) | 0.095 |
NCPAP use | 16 (66.7) | 21 (77.8) | 0.531 |
Diuretics | 7 (29.2) | 4 (14.8) | 0.31 |
Surfactant treatment | 17 (70.8) | 10 (37) | 0.025a |
PPHN | 8 (33.3) | 3 (11.1) | 0.088 |
NO use | 6 (25) | 1 (3.7) | 0.042a |
BSI | 4 (16.7) | 6 (22.2) | 0.731 |
Blood products | 13 (54.2) | 11 (40.7) | 0.406 |
Steroid treatment Inhalation systemic | 4 0 | 2 1 | 0.402 |
Pneumothorax | 2 (8.3) | 3 (11.1) | 1 |
Pulmonary hemorrhage | 1 (4.2) | 1 (3.7) | 1 |
CLABSI cases | 2 (8.3) | 3 (11.1) | 1 |
Hemodynamically significant PDA Medication treated Surgery treated | 2 (8.3) 1 (4.2) | 2 (7.4) 0 | 0.794 |
Major Morbidities | | | |
BPD | 10 (41.7) | 7 (25.9) | 0.254 |
IVH grade 3-4 | 4 (16.7) | 1 (3.7) | 0.175 |
NEC | 1 (4.2) | 0 | - |
ROP | 1 (4.2) | 2 (7.4) | 1 |
Hearing loss * | 4 (23.5) | 2 (8.7) | 0.373 |
Survived to Hospital discharge | 19 (79.2) | 24 (88.9) | 0.451 |
a Fisher's Exact Test, followed by Phi Coefficient calculation, b - t-test, c – Mann-Whitney test |
* 10 missing value |
GA, Gestational age; GW, Gestational week; SGA, Small for gestational age; NCPAP, Nasal continuous positive airway pressure; BDP, Bronchopulmonary dysplasia; IVH, Intraventricular hemorrhage; PPHN, Persistent Pulmonary Hypertension of the Newborn; NO, Nitric oxide; NEC, Necrotizing enterocolitis; BSI, Blood stream infection; ROP, Retinopathy of prematurity; CLABSI, Central Line Associated Bloodstream Infections; PDA, Patent ductus arteriosus. |
The neonates who did not survive in group 1 had a lower GW at PPROM (20 ± 2.3 vs 22 ± 1.2, p = .036) and were more susceptible to infection (40% of CLABSI cases, p = .036) than those who survived (Table 3). In group 2, the neonates who did not survive had a significantly lower Apgar score at 5 min than those who did survive (6 ± 2 vs 8.6 ± 1.7, respectively, p = .036), suffered from more PPHTN and pneumothorax (66.7% vs 4.2%, respectively, p = .025), and had a higher rate of CLABSI infection (66.7% vs 4.2%, respectively, p = .025) (Table 3).
Table 3
Neonatal characteristics by survival outcome
| Group 1 (17-23 weeks) | | Group 2 (24 – 27 weeks) | |
| Survived to discharged N=19 | Exitus N=5 | p value | Survived to discharged N=24 | Exitus N=3 | p value |
Maternal characteristics | | | | | |
GW at PPROM (median, week) | 22±1.2 (19-23) | 21±2.3 (17-22) | .036 | 26±1.2 (24-27) | 24±1.2 (24-26) | .139 |
Latency period (median, day) | 50±27.9 (12-105) | 40±31.9 (16-85) | 1 | 17±15.6 (7-61) | 24±5.6 (17-28) | .635 |
Neonatal outcomes | | | | | | |
GA at delivery (week) | 29±3.3 (24-34) | 26.8±2.8 (23-30) | .235 | 29.4±2.5 (25-34) | 28±1.7 (27-30) | .437 |
Gender (male) | 10 (52.6) | 4 (80) | .358 | 17 (70.8) | 3 (100) | .545 |
Birth weight (g) | 1330.6±473.9 (520-2120) | 1042.6±434.5 (488-1560) | .265 | 1393.2±412 (730-2270) | 983±107.2 (880-1094) | .101 |
Apgar 1 | 5.4±2.5 (1-9) | 4±2.1 (1-7) | .235 | 6.5±2.7 (1-9) | 4±2.6 (2-7) | .139 |
Apgar 5 | 7.5±1.5 (4-10) | 7.8±0.8 (7-9) | .731 | 8.6±1.7 (4-10) | 6±2 (4-8) | .036 |
SGA | 1 (5.3) | 1 (20) | .380 | 2 (8.3) | 1 (33.3) | .308 |
Cases of intubation | 10 (52.6) | 5 (100) | .118 | 7 (29.2) | 3 (100) | .041 |
NCPAP use | 16 (84.2) | 0 | .001 | 20 (83.3) | 1 (33.3) | .115 |
Surfactant treatment | 12 (63.2) | 5 (100) | .272 | 8 (33.3) | 2 (66.7) | .535 |
PPHTN | 5 (26.3) | 3 (60) | .289 | 1 (4.2) | 2 (66.7) | .025 |
NO | 4 (21.1) | 2 (40) | .568 | 0 | 1 (33.3) | .111 |
Blood products | 9 (47.4) | 4 (80) | .327 | 10 (41.7) | 1 (33.3) | 1 |
Steroid treatment | 4 (21.1) | 0 | 1 | 2 (8.3) | 1 (33.3) | .308 |
Pneumothorax | 1 (5.3) | 1 (20) | .380 | 1 (4.2) | 2 (66.7) | .025 |
BSI | 2 (10.5) | 2 (0.4) | .179 | 4 (16.7) | 2 (66.7) | .115 |
CLABSI | 0 | 2 (40) | .036 | 1 (4.2) | 2 (66.7) | .025 |
Hemodynamically significant PDA | 3 (15.8) | 0 | 1 | 2 (8.3) | 0 | 1 |
Major Morbidities | | | | | | |
BPD | 10 (52.6) | 0 | 0.053 | 6 (25) | 1 (33.3) | 1 |
IVH grade 3-4 | 2 (10.5) | 2 (20) | 0.179 | 0 | 1 (33.3) | 0.111 |
NEC | 1 (5.3) | 0 | 1 | 0 | 0 | 1 |
ROP | 1 (5.3) | 0 | 1 | 2 (8.3) | 0 | 1 |
Hearing impairment* | 4 (21.1) | - | NA | 2 (8.3) | - | NA |
Data are expressed as mean ± standard deviation, median ± standard deviation or n (%). |
* 7 missing values in group 1 and 4 missing values in group 2 |
GA, Gestational age; GW, Gestational week; SGA, Small for gestational age; NCPAP, Nasal continuous positive airway pressure; BDP, Bronchopulmonary dysplasia; IVH, Intraventricular hemorrhage; PPHN, Persistent Pulmonary Hypertension of the Newborn; NO, Nitric oxide; NEC, Necrotizing enterocolitis; BSI, Blood stream infection; ROP, Retinopathy of prematurity; CLABSI, Central Line Associated Bloodstream Infections; PDA, Patent ductus arteriosus; NA. not assessed. |
Spearman's correlation was computed to assess the relationship between the following variables, GW at PPROM, GA, Apgar score at 1 and 5 min, latency period length and BW within groups 1 and 2. There were strong positive correlations between latency period and BW (rs = .662, n = 51, p < .001), latency period and GA (rs = .704, n = 51, p < .001) and between GA and BW (rs = .812, n = 51, p < .001). Additionally, there were moderate positive correlations between GA and Apgar score 1 min (rs= .458, n = 51, p = .001), BW and Apgar score 5 min (rs = .465, n = 51, p = .001) and between Apgar score 1 min and 5 min (rs = .52, n = 51, p < .001). Finally, the latency period length was inversely related to GW at PPROM onset (rs = -.457, n = 51, p = .001) (Figure 1). In binary logistic regression analysis, none of these variables (GA, GW, BW, Apgar score 1 and 5 min, and latency period length) remained significant in predicting survival to discharge within groups 1 and 2.
Per two-sided Fisher exact test, the rate of neonates affected by major morbidities, including ROP, IVH grade 3-4, NEC stage 2-3, BPD and hearing impairment, were similar between groups 1 and 2 (Table 2). Among the 19 surviving neonates in group 1, 63.2% (12) were affected by one, two or three major morbidities (37%, 21% and 5.3% respectively) (Table 3) and none of the discharged neonates were affected by more than three major morbidities. In group 2, 33.3% (8) of the surviving neonates were affected by one or two major morbidities (25% and 8.3%, respectively) (Table 3). None of the neonates in group 2 were affected by three or more major morbidities.
However, it worth noting that the prevalence of illness with irreversible damages (ROP, IVH 3-4 and hearing impairment) among the surviving neonates was only 31.6% (affected by one or two illnesses) in group 1 and only half of it, 16.7%, (affected by one illness) in group 2. None of the neonates in none of the groups were affected by all three major morbidities.