Outcomes and latency to delivery in preterm prelabour rupture of membranes at 22–28 weeks: a retrospective cohort study

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To reduce uncertainty in gestational-age–specific management and to support evidence-based counselling, large-cohort analyses are essential. In this study, we aimed to evaluate the latency to delivery and maternal and neonatal outcomes through 12 months of corrected age among pregnancies with very early PPROM (22+0–28+0 weeks gestation). Methods We conducted a single-center retrospective cohort study at SBÜ Zeynep Kamil Women’s and Children’s Diseases Training and Research Hospital between January 2018 and February 2023; the cohort included 167 pregnancies that were diagnosed with PPROM at 22+0 to 28+0 weeks. The neonatal survival analyses included 91 infants managed at our center. Pregnancies were grouped by gestational age at PPROM as 22+0 to 23+6, 24+0 to 25+6 and 26+0 to 28+0 weeks. Latency to delivery, as well as maternal and neonatal outcomes, were compared across gestational age groups. The neonatal endpoints were survival to discharge and survival without major morbidity at 12 months of corrected age. Results The mean gestational age at diagnosis was 25.0 weeks. The median latency to delivery was 6 days (IQR, 2–23) and did not differ significantly between the groups (median range 5-9 days; P = 0.896). The mean gestational age at delivery was 27.1 weeks. Maternal outcomes were similar across groups, except for placental abruption and cesarean delivery. Placental abruption and cesarean delivery were more common when PPROM occurred at 24+0–25+6 weeks (P = 0.004 and P = 0.009, respectively). Neonatal survival to discharge was 67.0% (61/91). Survival without major morbidity at 12 months of corrected age was 42.9% (39/91). Both outcomes were highest when PPROM was diagnosed at 26+0 to 28+0 weeks (P = 0.001, P = 0.001). Conclusions In PPROM at 22+0 to 28+0 weeks the median latency to delivery ranged between 5 and 9 days. An increasing gestational age at PPROM is associated with increased survival and increased survival without severe morbidity. In addition, longer latency was associated with more favourable neonatal outcomes. These data may be important for providing evidence-based counselling and management in very early PPROM. Trial registration: Not applicable. Very early PPROM latency to delivery maternal outcomes neonatal outcomes Figures Figure 1 Figure 2 Background Preterm prelabour rupture of membranes (PPROM)—rupture of the fetal membranes before labour onset and prior to 37 weeks of gestation—is a leading identifiable cause of preterm birth, accounting for approximately one-third of cases ( 1 ). PPROM complicates 2–3% of all pregnancies, and in approximately 0.4–0.7% of cases, it occurs before 28 weeks of gestation. Complications due to prematurity and early rupture of membranes are major determinants of neonatal morbidity and mortality. At these very early gestational ages, management requires an individualized balance between the potential benefits and risks of immediate delivery versus continued expectant care ( 2 , 3 ). In practice, decisions depend on the gestational age–specific risks of adverse outcomes and on the changing maternal–fetal condition, highlighting the need for clear, evidence-based counselling. The etiology of PPROM is multifactorial. Reported risk factors include a prior history of PPROM, genitourinary infections, amniocentesis, placental abruption, antepartum bleeding, cervical insufficiency, low socioeconomic status and cigarette smoking. Although each of these factors is associated with PPROM, a substantial proportion of cases occur without identifiable risks or causes ( 1 – 5 ). Periviability is commonly defined as the earliest stage of fetal maturity at which extrauterine survival may be possible, generally accepted as 22 + 0 weeks of gestation. Extremely preterm birth refers to delivery before 28 + 0 weeks. In pregnancies complicated by PPROM within this window, fetuses face the combined hazards of extreme prematurity and prolonged membrane rupture with attendant risks of severe morbidity and mortality. The timing of rupture and the length of latency to delivery are key determinants of perinatal outcomes. Among neonates, the principal contributors to mortality and severe morbidity are complications of prematurity, including respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), intraventricular haemorrhage (IVH), necrotising enterocolitis (NEC), neonatal sepsis and death (6,7). In addition, early membrane rupture is associated with increased risks of chorioamnionitis, placental abruption, cord prolapse and intrauterine fetal death. From the maternal perspective, postpartum endometritis, sepsis,the need for blood transfusion, postpartum haemorrhage, acute kidney injury, and retained placenta are important causes of morbidity ( 2 , 8 ). The optimal management of PPROM remains incompletely defined. Management varies by gestational age, the presence of complications necessitating urgent delivery (e.g. placental abruption, chorioamnionitis, cord prolapse) and maternal–fetal conditions. Gestational age at delivery is the strongest predictor of neonatal outcomes ( 9 , 10 ). In the absence of indications for emergent delivery, prolonging pregnancy through expectant management is the principal goal in very early PPROM. The ACOG recommends home care until the limits of viability for PPROM occur before 24 weeks. In cases of PPROM between 24 and 34 weeks, the goal is to prolong the latency to delivery with antibiotics and corticosteroids ( 3 , 9 , 10 ). Indeed, studies have shown that expectant management can favourably influence maternal and neonatal outcomes ( 9 , 11 , 12 ). Nevertheless, the risk of chorioamnionitis may also increase during latency to delivery; thus, careful balancing of maternal and neonatal risks is essential ( 13 ). Given its clinical importance, very early PPROM remains a multifactorial condition, and many aspects of its pathophysiology and treatment continue to be investigated. When membrane rupture occurs at the limits of viability or in the early preterm period, obstetric and neonatal teams must communicate likely neonatal outcomes to parents accurately and incorporate parental values into shared decision-making. Therefore, for early gestation PPROM, a clear definition of the balance between GA specific risks and the benefits of conservative management is critical to guide care. However, current evidence on obstetric, postpartum and long-term neonatal survival outcomes for patients with PPROM between 22 and 28 weeks remains limited. This evidence gap limits evidence-based decision-making and parental counselling. The objective of this study was to evaluate the frequency of adverse obstetric, postpartum and neonatal outcomes stratified by gestational age among pregnancies diagnosed with PPROM between 22 and 28 weeks at our center. We also analysed the latency to delivery, survival to discharge and survival without severe morbidity to a corrected age of one year. By providing gestational age–specific estimates from a large single-center cohort, this study aims to inform clinical practice and refine management protocols for very early PPROM, thereby supporting individualized decision-making in extremely preterm pregnancies. Materials and methods This study was approved by the Institutional Training Board and Clinical Research Ethics Committee of SBÜ İstanbul Zeynep Kamil Women’s and Children’s Diseases Training and Research Hospital (Decision No. 129, September 20, 2023) and conducted in accordance with the ethical standards of the Declaration of Helsinki. Because of the retrospective design, the requirement for informed consent was waived by the Ethics Committee. We conducted a single-center retrospective cohort study on singleton pregnancies that admitted to SBÜ Zeynep Kamil Women’s and Children’s Diseases Training and Research Hospital, tertiary referral perinatal center, between January 2018 and February 2023. Eligible patients were diagnosed with PPROM at 22 + 0–28 + 0 weeks gestation and subsequently delivered at our institution. Gestational age was calculated from the last menstrual period and confirmed by first-trimester crown–rump length (CRL). For pregnancies conceived via in vitro fertilization, the GA was calculated from embryo transfer dates. PPROM was diagnosed in patients with a specific history of fluid leakage plus at least one of the following on sterile speculum examinations: active amniotic fluid leakage from the cervical canal with pooling in the posterior fornix or a positive placental alpha microglobulin-1 test (AmniSure®, PAMG-1 immunoassay; Amnisure ROM test; N-Dia, New York, NY, USA). The exclusion criteria were adolescent pregnancy, multiple gestations, iatrogenic membrane rupture (amniocentesis, chorionic villus sampling or cordocentesis), termination of pregnancy, fetuses with structural or genetic anomalies and PPROM with delivery after 34 + 0 weeks. After applying these criteria, 167 pregnancies were included; 10 of these resulted in intrauterine fetal demise and 66 neonates were transferred early to external centers owing to limited NICU capacity, Follow-up and complication data were unavailable for these infants. Among the 91 infants managed at our center, 30 died before discharge, and sufficient clinical follow-up data were not available to assess the development of severe morbidity. Accordingly, analyses of neonatal complications were restricted to a complete-case cohort of 58 infants who were managed at our center, survived to discharge and were followed up through 12 months of corrected age. Obstetric and postpartum outcomes were analysed for the full maternal cohort (n = 167), whereas neonatal morbidity analyses used a complete-case approach (n = 58). All patients were managed according to a standardized protocol. In our unit, termination is offered for up to 22 + 0 weeks. From 22 + 0 weeks onward, patients with PPROM are admitted to the hospital for management. The obstetric history and demographic characteristics were obtained and baseline laboratory tests were performed. Antibiotic prophylaxis consisted of a single 1 g oral dose of azithromycin followed by intravenous ampicillin 2 g every 6 hours for 48 hours and then oral amoxicillin 500 mg every 8 hours for 5 days. For penicillin allergy, clindamycin was administered. In addition, patients with positive vaginal, cervical or urine cultures received pathogen-directed antibiotics. A single course of antenatal corticosteroids (Betamethasone; Cales®, Koçak Farma İlaç ve Kimya Sanayi A.Ş., Istanbul, Turkey) was administered to pregnancies with PPROM at 24 + 0 to 33 + 6 weeks at risk of preterm birth within 7 days. In those < 34 weeks, a rescue course corticosteroid was given once ≥ 14 days had passed since the last course and delivery was likely within 7 days. Tocolysis was generally used only in the presence of regular contractions to allow time for corticosteroid administration. For neuroprotection, patients who were expected to deliver before 32 weeks of gestation received intravenous magnesium sulfate (6 g loading dose over 30 minutes, followed by 2 g/hour maintenance) for 24 hours. Fetal growth and amniotic fluid were assessed with serial ultrasound; after 26 weeks, nonstress testing (NST) was performed. Clinical chorioamnionitis was diagnosed in the presence of maternal fever (≥ 38,0°C) without an extrauterine source plus at least two of the following: Fetal tachycardia (> 160 beats/minute) Maternal tachycardia (> 100 beats/minute) Leukocytosis in maternal blood count (> 15,000 cells/mm3) Uterine tenderness Malodorous or purulent vaginal discharge. Placental abruption was diagnosed clinically (new-onset vaginal bleeding, frequent painful contractions, bloody amniotic fluid or placental clots) and, in some cases, supported by ultrasonographic evidence of a retroplacental hematoma. Maternal sepsis was defined as maternal infection (e.g., fever, positive blood cultures) with end-organ dysfunction (e.g., hypotension, oliguria, elevated creatinine, disseminated intravascular coagulation, decreased level of consciousness, or respiratory failure). Emergency delivery was performed for chorioamnionitis, nonreassuring fetal testing, placental abruption or cord prolapse. Mode of delivery followed obstetric indications; noncephalic presentation after 24 weeks was considered an indication for cesarean delivery. All neonates were evaluated by the neonatology team for RDS, sepsis, IVH, periventricular leukomalacia (PVL), BPD, ROP, NEC and neurodevelopment. The Denver II Developmental Screening Test was administered by a pediatric neurologician for neurodevelopmental assessment. ROP surveillance was performed by the Ophthalmology Department and hearing screening and follow-up were performed by the Otorhinolaryngology Department. Infants were followed until 12 months of corrected age. Data were extracted from the hospital information system and patient charts. GA at delivery and latency to delivery (defined as the interval from membrane rupture to delivery) were recorded. Maternal demographic and obstetric characteristics and obstetric, postpartum and neonatal outcomes were recorded. Patients were categorized by GA at PPROM into three groups: 22 + 0–23 + 6, 24 + 0–25 + 6 and 26 + 0–28 + 0 weeks. For each group, we evaluated the latency to delivery and the obstetric, postpartum and neonatal outcomes up to 12 months of corrected age. The definitions of neonatal morbidities followed standard criteria (e.g. BPD according to the oxygen requirement at 36 weeks post-menstrual age; stage-based criteria for ROP; Bell staging for NEC, standardized definitions for IVH/PVL). Major morbidity was defined as the presence of any of the following: Severe bronchopulmonary dysplasia (BPD) Necrotizing enterocolitis (NEC) requiring surgery Retinopathy of prematurity (ROP) requiring treatment Moderate to severe neurodevelopmental impairment Sensorineural hearing loss Grade 3 to 4 intraventricular haemorrhage (IVH)/ periventricular leukomalacia (PVL) Death Continuous variables are summarized as means (SDs) or medians (IQRs), as appropriate; categorical variables are summarized as n (%). The distribution of continuous variables was assessed via Kolmogorov–Smirnov test. For categorical variables the χ² test or Fisher’s exact test was used for group comparisons. For continuous variables, two-group comparisons were performed via Student’s t test or the Mann–Whitney U test; three-group comparisons were performed via one-way ANOVA or the Kruskal–Wallis test. Correlations between continuous variables were examined with Pearson’s correlation. The possibility of preterm delivery in each gestational-age group was assessed via Kaplan–Meier analysis. P values < 0.05 were considered statistically significant. All analyses were conducted in SPSS version 17.0 (SPSS Inc., Chicago, IL, USA). No a priori sample-size calculation was performed because all eligible cases during the study period were included. Results During the study period, 36,167 births occurred at our hospital; 1,061 were complicated by PPROM (incidence, 2.93%). Among all the PPROM cases, 240 (22.6%) were diagnosed at 22 + 0–28 + 0 weeks, corresponding to an incidence of 0.66% among all births. After applying the exclusion criterias, 167 pregnancies were included in the analysis cohort (Fig. 1 ). Ten of these resulted in intrauterine fetal demise and 66 neonates were transferred early to external centers. Among the remaining infants 91 were managed at our center. Analyses of neonatal complications were restricted to a complete-case cohort of 58 infants who were managed at our center, survived to discharge and were followed up through 12 months of corrected age. The mean maternal age was 29.9 ± 6.1 years. A total of 45.5% were primiparous and 54.4% were multiparous. The mean BMI was 27.6 kg/m², within the overweight range. Among women with a prior birth, 29.3% had a previous cesarean delivery and 25.1% had a previous spontaneous vaginal delivery. Elective cerclage at 12–14 weeks was documented in 7.2% of the patients; none had a pessary. Additional baseline features, including oligohydramnios and antepartum bleeding at presentation, are shown in Table 1 . Table 1 Obstetric and demographic characteristics (n = 167) Characteristics Data Age, years,(mean ± SD) 29.9 (± 6.1) Gravidity, (mean ± SD) 2.40 (± 1.4) BMI (kg/m2), (mean ± SD) 27.6 (± 4.3) Parity Multiparous, n (%) 91(54.4) Primiparous, n (%) 76(45.5) IVF conception, n (%) 14(8.4) History of preterm labor, n (%) 27(16.2) History of PPROM, n (%) 11(6.6) First-trimester bleeding, n (%) 69(41.3) Cerclage in current pregnancy, n (%) 12(7.2) Uterine anomaly, n (%) 9(5.4) Prior uterine surgery, n (%) 9(5.4) Oligohydramnios at presentation, n (%) 67(40.1) Smoking, n (%) 15( 9 ) Table 2 summarizes the associations between gestational age at PPROM and baseline characteristics. PPROM was diagnosed at 22 + 0–23 + 6 weeks in 31.1%, 24 + 0–25 + 6 in 34.7%, and 26 + 0–28 + 0 in 34.1% of pregnancies. Maternal age, gravidity, parity, number of abortions, and BMI did not differ across GA at PPROM groups. IVF conception occurred in 8.4% overall and was more common in the 22 + 0–23 + 6 group (P = 0.009). Antepartum bleeding was present in 41.3% overall and was significantly less common in the 26 + 0–28 + 0 group (P = 0.006). Prior preterm labor (16.2%), prior PPROM (6.6%), uterine anomaly, prior uterine surgery, cerclage during current pregnancy, oligohydramnios at presentation, and cigarette smoking (9.0%) did not differ by GA at PPROM. No alcohol or illicit drug use was reported. As shown in Table 2 , the mean gestational age at delivery was 27.1 weeks, which differed across GA at PPROM groups (P < 0.001). The mean GA at PPROM was 25.0 weeks. The median latency was 6 days (IQR 2–23) and did not differ by GA at PPROM (P = 0.896). The probability of ongoing pregnancy after PPROM by GA group is depicted in the Kaplan–Meier curves (Fig. 2 ). Table 2 Obstetric and demographic characteristics of the study by GA at PPROM GA at PPROM Total (Mean GA at PPROM 25 weeks) 22 + 0–23 + 6 24 + 0–25 + 6 26 + 0–28 + 0 Characteristics n = 167 n = 52 n = 58 n = 57 P value Age, years, (mean ± SD) 29.9 (± 6.1) 31(± 6.1) 29.5(± 5.6) 29.4(± 6.4) 0.3 Parity, n (%) Primiparous, n (%) 76(45.5) 28(53.8) 24(41.4) 24(42.1) 0.2 Multiparous, n (%) 91(54.4) 24(46.2) 34(58.6) 33(57.9) Previous birth vaginal delivery*, n (%) 42(25.1) 11(45.8) 12(35.3) 19(57.6) 0.188 Previous birth cesarean section*, n (%) 49(29.3) 13(54.2) 22(64.7) 14(42.4) BMI, kg/m2, (mean ± SD) 27.6 (± 4.3) 26.9(± 4.1) 27.9(± 4.3) 28.08(± 4.3) 0.3 IVF conception, n (%) 14( 8 , 4 ) 8(13.5) 3(5.2) 3(5.3) 0.009 Smoking, n (%) 15( 9 ) 4(7.7) 6(10.3) 5(8.8) 0.9 Antenatal vaginal bleeding, n (%) 69(41.3) 27(51.9) 28(48.3) 14(24.6) 0.006 History of PPROM* 11(6.6) 4(16.6) 3(8.8) 4(12.1) 0.402 History of preterm labor* 27(16.2) 6( 25 ) 10(29.4) 11(33.3) 0.744 Latency, days, median (IQR) 6 ( 2 – 23 ) 6(2.2–26.5) 9(2-18.2) 5( 2 – 26 ) 0.896 Delivery within 48 h, n (%) 44(26.3) 13( 25 ) 16(27.5) 15(36.3) 0.954 Delivery within 7 days, n (%) 89(53.2) 29(55.7) 28(48.2) 32(56.1) 0.638 Oligohydramnios at presentation, n (%) 67(40.1) 24(46.2) 27(46.6) 26(28.1) 0.07 Gestational age at delivery, weeks, (mean ± SD) 27.1(± 0.2) 25(± 0.4) 26.9(± 0.3) 29.1(± 0.3) < 0.001 * Among women with a prior birth (where applicable). † Comparisons by GA at PPROM: Pearson‒χ2 tests for categorical variables; one-way ANOVA for normally distributed continuous variables; Kruskal–Wallis for nonnormal distributions. Maternal adverse outcomes by gestational age at PPROM are shown in Table 3. Placental abruption occurred in 18 patients (10.8%) and was more frequent in the 24 + 0–25 + 6 group than in the other groups (P = 0.04). Clinical chorioamnionitis, noncephalic presentation, cord prolapse and intrauterine fetal death did not differ across the groups. Overall, 31.1% delivered vaginally and 68.9% were delivered by cesarean. Cesarean delivery was more frequent in the 24 + 0–25 + 6 group (P = 0.009). There were no significant differences in terms of GA at PPROM for retained placenta, postpartum sepsis, postpartum bleeding or wound infection. Table 3 Maternal Outcomes by GA at PPROM GA at PPROM Total 22 + 0–23 + 6 24 + 0–25 + 6 26 + 0–28 + 0 Maternal outcome n:167 n:52 n:58 n:57 P value Obstetric outcomes Clinical chorioamnionitis, n (%) 46(27.5) 16(30.8) 15(25.9) 15(26.3) 0.8 Cord prolapse, n (%) 5( 3 ) 4(7.7) 1(1.7) 0 Noncephalic presentation, n (%) 19(11.4) 9(17.3) 5(8.6) 5(8.8) 0.3 Placental abruption, n (%) 18(10.8) 4(7.7) 11( 19 ) 3(5.3) 0.04 Intrauterine fetal demise, n (%) 10( 6 ) 6(11.5) 1(1.7) 3(5.3) 0.09 Cesarean delivery, n (%) 115(68.9) 29(55.8) 48(82.8) 38(66.7) 0.009 Postpartum outcomes Postpartum haemorrhage, n (%) 11(6.6) 6(11.5) 3(5.2) 2(3.5) 0.2 Retained placenta, n (%) 18(10.8) 9(17.3) 3(5.2) 6(10.5) 0.1 Sepsis, n (%) 7(4.2) 3(5.8) 1(1.7) 3(5.3) 0.5 Wound infection, n (%) 7(4.2) 3(5.8) 0 4(7) 0.1 *Comparisons by GA at PPROM: χ² for categorical variables; one-way ANOVA for normally distributed continuous variables; Kruskal–Wallis for non-normal distributions. The neonatal outcomes at 12 months of corrected age and survival data are presented in Table 4 . Across GA at PPROM groups, the rates of NEC, neonatal sepsis, ROP, hearing loss, IVH and RDS were similar (all P > 0.05). Among infants who were 12 months of corrected age, 36.2% had BPD, 25.9% had neurodevelopmental impairment, and 13.5% had hearing impairment. BPD was significantly greater in the 24 + 0–25 + 6 group (P = 0.003), whereas neurodevelopmental impairment and hearing loss did not differ across the groups. Overall survival to discharge was 67.0% and differed significantly across the gestational age at PPROM groups (P = 0.001), with the highest survival at 26 + 0–28 + 0 (88.6%) and the lowest survival at 22 + 0–23 + 6 (44.4%). Survival without major morbidity to 12 months of corrected age was 42.9% and likewise varied significantly by diagnosis week (P = 0.001); suvival was highest at 26 + 0–28 + 0 (60.0%) weeks and lowest at 22 + 0–23 + 6 (22.2%) weeks. Both survival and morbidity-free survival increased with advancing gestational age at PPROM. Table 4 Birth Characteristics and outcomes by GA at PPROM Neonatal birth characteristics and outcome Total GA at PPROM 22 + 0–23 + 6 24 + 0–25 + 6 26 + 0–28 + 0 n = 91* n:27 n:29 n:35 P value Birthweight, g, (mean ± SD) 1138 ± 559 880 ± 505 986 ± 447 1459 ± 536 < 0.001 Apgar 1 (n = 85), (mean ± SD) 5.4 ± 1.7 4.6 ± 1.7 5.6 ± 1.3 5.9 ± 1.8 0.007 Apgar 5 (n = 85) 7.3 ± 1.4 6.6 ± 1.6 7.4 ± 1.1 7.8 ± 1.2 0.003 Survival to discharge, n (%) 61(67) 12(44.4) 18(62.1) 31(88.6) 0.001 Survival without major morbidity at 12 months of corrected age, n (%) † 39(42.9) 6(22.2) 12(41.4) 21(60) 0.001 n = 58 ‡ n = 11 n = 17 n = 30 Intraventricular haemorrhage, n (%) 14(24.1) 3(27.3) 6(35.3) 5(16.7) 0.3 Necrotizing enterocolitis, n (%) 6(10.3) 0 2(11.8) 4(13.3) 0.5 Respiratory distress syndrome, n (%) 44(75.9) 8(72.7) 15(88.2) 21(70) 0.4 Sepsis, n (%) 32(55.2) 7(63.6) 12(70.6) 13(43.3) 0.2 Retinopathy of Prematurity, n (%) 23(39.7) 5(45.5) 10(58.8) 8(36.7) 0.2 Bronchopulmonary dysplasia, n (%) 21(36.2) 5(45.5) 11(64,7) 5(16.7) 0.003 Hearing Loss, n (%) 8(13.8) 1(9.1) 4(23.5) 3( 10 ) 0.4 Neurodevelopmental impairment, n (%) 15(25.9) 4(36.4) 4(23.5) 7(23.3) 0.7 * In-hospital neonatal cohort: excludes transfers; includes all infants managed at our center (n = 91). † Major morbidity was defined as any of: severe BPD, surgery-requiring NEC, treatment-requiring ROP, moderate–severe neurodevelopmental impairment, sensorineural hearing loss, grade 3–4 IVH/PVL or death. ‡Complete-case neonatal outcomes: analyses restricted to infants with complete follow-up to 12 months of corrected age (n = 58). § Comparisons by GA at PPROM: χ² for categorical variables; one-way ANOVA for normally distributed continuous variables; Kruskal–Wallis for nonnormal distributions. When the latency to delivery was 0.05; Table 5 ). For neonatal outcomes, the ≥ 7-day group performed better: survival to discharge was 84.1% compared with 51.1% ( P = 0.001 ) , and survival without major morbidity at 12 months of corrected age was 56.8% compared with 29.8% ( P = 0.005 ) Table 5 Outcomes by Latency to Delivery (≤ 7 vs > 7 days) Maternal outcomes (n = 167) Latency ≤ 7 gün Latency > 7gün p n = 89 n = 78 Clinical chorioamnionitis, n (%) 46 26 (29.2) 20(25.6) 0.606 Placental abruption, n (%) 18 11(12.4) 7( 9 ) 0.482 Noncephalic presentation, n (%) 19 14(15.7) 5(6.4) 0.058 Cord prolapse, n (%) 5 2(2.2) 3(3.8) 0.665 Intrauterine fetal demise, n (%) 10 8( 9 ) 2(2.6) 0.106 Retained placenta, n (%) 18 13(14.6) 5(6.4) 0.088 Wound infection, n (%) 7 3(3.4) 4(5.1) 0.706 Sepsis, n (%) 7 4(4.5) 3(3.8) 1 Postpartum haemorrhage, n (%) 11 4(4.5) 7( 9 ) 0.244 Neonatal outcome (n = 91*) n = 47 n = 44 Survival without major morbidity, n (%) † 39 14(29.8) 25(56.8) 0.005 Neonatal death, n (%) 30 23(48.9) 7(15.9) 0.001 * In-hospital neonatal cohort: excludes transfers; includes all infants managed at our center (n = 91). † Major morbidity was defined as any of: severe BPD, surgery-requiring NEC, treatment-requiring ROP, moderate–severe neurodevelopmental impairment, sensorineural hearing loss, grade 3–4 IVH/PVL or death. **Fisher exact test was used in groups with expected value < 5, and chi-square test was used in groups with expected value Discussion Across GA at PPROM groups, there were no significant differences in maternal age, BMI, gravidity/parity, prior mode of delivery, cigarette smoking, history of preterm labor, or history of PPROM. The demographic and obstetric profiles of our cohort are consistent with those of prior early–late PPROM cohorts( 14 , 15 ). Taken together, these findings suggest that gestational age at PPROM and the clinical management applied, rather than baseline maternal characteristics, are the primary determinants of outcomes in this population. In a large retrospective Danish cohort of singleton pregnancies, Lykke et al. reported that first-trimester bleeding was associated with an increased risk of PPROM and preterm birth before 34 weeks of gestation( 16 ). In our cohort, antenatal vaginal bleeding was documented in 41.3% of pregnancies and its frequency decreased with increasing GA at PPROM diagnosis (P = 0.006). Although the higher rate at earlier diagnostic windows is consistent with prior reports, causality between bleeding and the timing of rupture cannot be established in this retrospective study. We also observed that PPROM at 22 + 0–23 + 6 weeks was more common among IVF conceptions than at later diagnostic windows (P = 0.009). Given the limited sample size and potential confounding (e.g., maternal age, infertility etiology), these findings should be interpreted cautiously and confirmed in larger cohorts. In our cohort, the median latency to delivery was 6 days (IQR 2–23). For comparison, Seravalli et al. reported a median latency of 16 days for PPROM < 32 weeks and the French national EPIPAGE-2 study reported 8 days for PPROM at 22–25 weeks ( 17 , 18 ). In contrast, the review by Sim et al. described a wider range of 7–49 days( 19 ). The relatively shorter latencies in our study likely reflect our focus on very early PPROM, inpatient management from diagnosis and a higher burden of complications that prompted urgent delivery (e.g., chorioamnionitis, abruption and cord prolapse). Overall, these findings suggest that latency depends not only on the GA at diagnosis but also on other clinical findings and how the condition is managed. Several studies have reported longer latency when PPROM occurs at earlier gestational ages( 15 , 20 ). In contrast, in our cohort (mean diagnostic GA 25 weeks), latency did not differ across GA at PPROM groups within the very-early window. This pattern aligns with the findings of the French national EPIPAGE-2 study, which analysed PPROM at 22–25 weeks (mean GA 25 weeks) and likewise revealed no GA-related difference in latency( 18 ). Similarly, Seravalli et al. reported that among patients with PPROM < 32 weeks (mean diagnostic GA 26.1 weeks), latency did not vary by diagnostic GA ( 17 ). By comparison, Peaceman et al. (PPROM < 32 weeks; mean diagnostic GA, 28.1 weeks) reported a similar latency at ≤ 28 weeks but significantly shorter latency when PPROM occurred at 29–31 weeks than at ≤ 28 weeks ( 20 ). These data indicate that despite variability across studies and within very-early PPROM groups, latency to delivery changes little with gestational age at diagnosis. Larger cohorts—including those ≥ 28 weeks—are needed to confirm this. In our cohort, 26.3% had delivered within 48 hours and 53.2% within 7 days of PPROM; both proportions were similar across GA at PPROM groups (P = 0.954 and 0.638, respectively). In the EPIPAGE-2, delivery occurred in 19.4% of the patients within 48 hours and 47% of the patients within 1 week, with no difference in diagnostic GA ( 18 ). Walker et al. reported a 67% delivery rate within 1 week, whereas in the cohort by Seravalli et al. (with a similar timeframe) 15% delivered within 48 hours and 33.7% delivered within 7 days, again without GA-related differences ( 17 , 21 ). The variation across studies likely reflects management strategies (e.g., early hospitalization, standardized antibiotic/corticosteroid protocols) as well as methodological differences (gestational-age windows, intervention thresholds and inclusion/exclusion criteria). In our cohort, clinical chorioamnionitis occurred in 27.5%, cord prolapse in 3.0%, placental abruption in 10.8% and intrauterine fetal demise in 6.0%. The rates of chorioamnionitis, intrauterine fetal demise, noncephalic presentation, and cord prolapse were similar across GA at PPROM groups; only placental abruption was higher in the 24 + 0–25 + 6 group (P = 0.04). This pattern is consistent with reports focused on very-early PPROM ( 13 , 15 , 17 ). The relatively high rate of chorioamnionitis probably reflects our focus on very-early PPROM cases and continuous inpatient monitoring from the time of diagnosis, which may have increased detection. The overall cesarean delivery rate was 68.9%, with a clear peak in the 24 + 0–25 + 6 group (P = 0.009). This exceeds several published series: 53.3% in PPROM < 28 weeks (Seravalli et al.), 52.9% at 24–37 weeks (Salman et al.) and 50.8% at 23–27 weeks (Newman et al.) ( 17 , 22 , 23 ). Our higher rate is plausibly related to the greater proportion of patients with prior cesarean (29.3%), a cesarean approach for noncephalic presentation after 24 weeks, the very-early PPROM case selection and higher frequencies of urgent-delivery complications. Latency did not differ according to the presence of chorioamnionitis, abruption, intrauterine fetal demise or cord prolapse. Only noncephalic presentation was associated with shorter latency (median 4 vs 7 days for cephalic; P = 0.023). The median latency was similar with and without abruption (P = 0.253) (Additional file 1). Larger cohorts are needed to clarify how specific obstetric complications influence the latency to delivery. In our cohort, sepsis occurred in 4.2%, postpartum haemorrhage in 6.6%, uterine curettage for retained placenta in 10.8%, and wound infection in 4.2%; none differed by GA at PPROM. Among PPROM cases reported in the literature, at 18–24 weeks, Deutsch et al. reported chorioamnionitis 64.8%, sepsis 0.9%, postpartum haemorrhage 14.3%, and postpartum curettage 7.6% ( 14 ). In a 14–23-week PPROM cohort, Dotters-Katz et al. observed wound infection 1.2%, sepsis 1.2%, postpartum haemorrhage 39.0%, and postpartum curettage 2.9% ( 8 ). Differences across studies likely reflect gestational-age windows and variations in care protocols. Apgar-1, Apgar-5, birthweight and survival increased significantly with advancing GA at PPROM; however, NEC, ROP, hearing loss, IVH, RDS and neurodevelopmental impairment did not differ across diagnostic GA groups. Notably, BPD was higher in the 24 + 0–25 + 6 group (P = 0.003), a finding that may reflect a greater need for prolonged respiratory support in the periviability window. Similarly, prior reports revealed no consistent GA-related differences in neonatal complications across PPROM diagnostic strata ( 14 , 24 ). The survival gradients resulting from the GA at PPROM were clear. Survival to discharge was 67.0% overall, increasing from 44.4% at 22 + 0–23 + 6 to 62.1% at 24 + 0–25 + 6 and 88.6% at 26 + 0–28 + 0 (P = 0.001). Survival without major morbidity at 12 months of corrected age was 42.9% overall, increasing from 22.2% to 41.4% and 60.0% across the same groups (P = 0.001). These patterns align broadly with international data—for example, Manuck et al. reported survival/morbidity-free survival rates of 83.3%/24.4% at < 25 weeks and 98.0%/78.2% at ≥ 25 weeks( 15 ). EPIPAGE2 reported 68.2% survival and 51.6% morbidity-free survival at age two for 22–25 weeks ( 18 ). Compared with series from our country, survival to discharge at our center appears relatively high ( 24 , 25 ). Differences in rates likely reflect gestational-age ranges and obstetric/neonatal care protocols; nevertheless, the stepwise improvement in survival and survival without major morbidity with increasing GA is consistent. Multiple studies have linked longer latency with more favourable neonatal outcomes ( 21 , 25 , 26 ). In our cohort,a longer latency was not associated with greater rates of obstetric or postpartum complications; instead, it was associated with lower neonatal mortality and higher survival without major morbidity. These findings support the view that, when clinically safe, prolonging the intrauterine stay may be beneficial for neonatal outcomes. The strengths of this study include a relatively large cohort despite the low incidence of very-early PPROM (22 + 0–28 + 0 weeks; <1% of all births at our center during the study period) and the use of a single-center, standardized management protocol across all cases. Another strength is the stratification of outcomes by gestational age at PPROM, which enables gestational-age–specific, individualized counselling for maternal and neonatal outcomes. This study also has limitations, including its retrospective design and the absence of data for PPROM cases that opt for termination, which represents a common form of selection bias in PPROM research. In addition, some infants are transferred to outside NICUs because of capacity constraints, resulting in incomplete follow-up and long-term neonatal data were limited. These factors may affect the generalizability and the precision of some estimates. Conclusions In pregnancies with PPROM at 22 + 0–28 + 0 weeks, our data characterize how gestational age at diagnosis and latency to delivery are related to maternal and neonatal morbidity and mortality. Overall, this study provides practical, center-specific evidence to inform PPROM management and reflects advances in obstetric and neonatal care using data from our institution. Notably, the high incidences of chorioamnionitis, placental abruption and cord prolapse in this very-early PPROM group support inpatient admission with close surveillance. These findings should be corroborated in multicenter prospective studies, including studies of longer-term pediatric outcomes, to refine management strategies for very-early PPROM. Abbreviations PPROM: Preterm Premature Rupture of Membranes GA: Gestational Age BMI: Body Mass Index IVF: In Vitro Fertilization CRL: Crown Rump Length NST: Nonstress Test RDS: Respiratory Distress Syndrome BPD: Bronchopulmonary Dysplasia IVH: Intraventricular Hemorrhage PVL: Periventricular Leukomalacia NEC: Necrotising Enterocolitis ROP: Retinopathy of Prematurity NICU: Neonatal Intensive Care Unit SD: Standard Deviation IQR: Interquartile Range Declarations Ethics approval and consent to participate The study was conducted following the principles outlined in the Declaration of Helsinki, with ethical approval obtained from the Institutional Training Board and Clinical Research Ethics Committee of SBÜ İstanbul Zeynep Kamil Women’s and Children’s Diseases Training and Research Hospital (Decision No. 129, September 20, 2023). Given the study’s retrospective nature, the Ethics Committee of SBÜ İstanbul Zeynep Kamil Women’s and Children’s Diseases Training and Research Hospital granted a waiver for informed consent. Consent for publication Not applicable. Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request Competing interests The authors declare no competing interests. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Authors’ contributions İŞR and EÇ contributed to the study conception and design, resources, and data curation. İSS performed the formal statistical analysis. EÇ and GK supervised the study and validated the findings. İŞR was responsible for the investigation and methodology and drafted the original manuscript. İŞR and EÇ critically revised the manuscript for content. All the authors have read and approved the final manuscript. Acknowledgements None. Authors’ information 1.Department of Obstetrics and Gynaecology, İstanbul Medeniyet University Prof. Dr. Süleyman Yalçın City Hospital, İstanbul, Turkey 2.Department of Obstetrics and Gynaecology, SBÜ Kartal Prof.Dr. Lütfi Kırdar City Hospital, İstanbul, Turkey 3. Department of Pediatrics, Division of Neonatology, SBÜ İstanbul Zeynep Kamil Women’s and Children’s Diseases Training and Research Hospital, İstanbul, Turkey 4. Department of Obstetrics and Gynaecology, Private Clinic, İstanbul, Türkiye References Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. The Lancet. 2008 Jan;371(9606):75–84. DOI: 10.1016/S01406736(08)60074-4 Waters TP, Mercer BM. The management of preterm premature rupture of the membranes near the limit of fetal viability. Am J Obstet Gynecol. 2009 Sep;201(3):230–40. DOI: 10.1016/j.ajog.2009.06.049 Prelabor Rupture of Membranes. 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The Journal of Maternal-Fetal & Neonatal Medicine. 2016 Apr 2;29(7):1108–12. DOI: 10.3109/14767058.2015.1035643 Baser E, Aydogan Kirmizi D, Ulubas Isik D, Ozdemirci S, Onat T, Serdar Yalvac E, et al. The effects of latency period in PPROM cases managed expectantly. The Journal of Maternal-Fetal & Neonatal Medicine. 2020 Jul 2;33(13):2274–83. DOI: 10.1080/14767058.2020.1731465 Additional Declarations No competing interests reported. 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1","display":"","copyAsset":false,"role":"figure","size":73162,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart of the patient selection process (January 2018–February 2023)\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8242616/v1/68a280b465bcd09a42267341.jpg"},{"id":98437267,"identity":"ae83d1a9-9afc-47d5-86e3-dff841aa3b2d","added_by":"auto","created_at":"2025-12-17 16:57:10","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":39500,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan–Meier curves for the probability of ongoing pregnancy after PPROM by GA at diagnosis.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8242616/v1/620c16bb42c901798a0bedbc.jpg"},{"id":106809445,"identity":"1b72066c-4a6a-44e9-893d-3dc0ab292e82","added_by":"auto","created_at":"2026-04-13 16:10:57","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1115003,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8242616/v1/ec5be4e7-8484-4049-9fef-4dde0a3f3948.pdf"},{"id":98437033,"identity":"48b3eae9-9ffb-44f3-acf6-1f07d2365e5e","added_by":"auto","created_at":"2025-12-17 16:56:50","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":19777,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAdditional file\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e1. Association between latency to delivery and adverse maternal and neonatal outcomes .pdf\u003c/p\u003e","description":"","filename":"Additionalfile1.docx","url":"https://assets-eu.researchsquare.com/files/rs-8242616/v1/745cbccf3f1e22811bef63b4.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Outcomes and latency to delivery in preterm prelabour rupture of membranes at 22–28 weeks: a retrospective cohort study","fulltext":[{"header":"Background","content":"\u003cp\u003ePreterm prelabour rupture of membranes (PPROM)\u0026mdash;rupture of the fetal membranes before labour onset and prior to 37 weeks of gestation\u0026mdash;is a leading identifiable cause of preterm birth, accounting for approximately one-third of cases (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). PPROM complicates 2\u0026ndash;3% of all pregnancies, and in approximately 0.4\u0026ndash;0.7% of cases, it occurs before 28 weeks of gestation. Complications due to prematurity and early rupture of membranes are major determinants of neonatal morbidity and mortality. At these very early gestational ages, management requires an individualized balance between the potential benefits and risks of immediate delivery versus continued expectant care (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). In practice, decisions depend on the gestational age\u0026ndash;specific risks of adverse outcomes and on the changing maternal\u0026ndash;fetal condition, highlighting the need for clear, evidence-based counselling.\u003c/p\u003e \u003cp\u003eThe etiology of PPROM is multifactorial. Reported risk factors include a prior history of PPROM, genitourinary infections, amniocentesis, placental abruption, antepartum bleeding, cervical insufficiency, low socioeconomic status and cigarette smoking. Although each of these factors is associated with PPROM, a substantial proportion of cases occur without identifiable risks or causes (\u003cspan additionalcitationids=\"CR2 CR3 CR4\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePeriviability is commonly defined as the earliest stage of fetal maturity at which extrauterine survival may be possible, generally accepted as 22\u0026thinsp;+\u0026thinsp;0 weeks of gestation. Extremely preterm birth refers to delivery before 28\u0026thinsp;+\u0026thinsp;0 weeks. In pregnancies complicated by PPROM within this window, fetuses face the combined hazards of extreme prematurity and prolonged membrane rupture with attendant risks of severe morbidity and mortality. The timing of rupture and the length of latency to delivery are key determinants of perinatal outcomes. Among neonates, the principal contributors to mortality and severe morbidity are complications of prematurity, including respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), intraventricular haemorrhage (IVH), necrotising enterocolitis (NEC), neonatal sepsis and death (6,7). In addition, early membrane rupture is associated with increased risks of chorioamnionitis, placental abruption, cord prolapse and intrauterine fetal death. From the maternal perspective, postpartum endometritis, sepsis,the need for blood transfusion, postpartum haemorrhage, acute kidney injury, and retained placenta are important causes of morbidity (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe optimal management of PPROM remains incompletely defined. Management varies by gestational age, the presence of complications necessitating urgent delivery (e.g. placental abruption, chorioamnionitis, cord prolapse) and maternal\u0026ndash;fetal conditions. Gestational age at delivery is the strongest predictor of neonatal outcomes (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e10\u003c/span\u003e). In the absence of indications for emergent delivery, prolonging pregnancy through expectant management is the principal goal in very early PPROM. The ACOG recommends home care until the limits of viability for PPROM occur before 24 weeks. In cases of PPROM between 24 and 34 weeks, the goal is to prolong the latency to delivery with antibiotics and corticosteroids (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Indeed, studies have shown that expectant management can favourably influence maternal and neonatal outcomes (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Nevertheless, the risk of chorioamnionitis may also increase during latency to delivery; thus, careful balancing of maternal and neonatal risks is essential (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e13\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eGiven its clinical importance, very early PPROM remains a multifactorial condition, and many aspects of its pathophysiology and treatment continue to be investigated. When membrane rupture occurs at the limits of viability or in the early preterm period, obstetric and neonatal teams must communicate likely neonatal outcomes to parents accurately and incorporate parental values into shared decision-making. Therefore, for early gestation PPROM, a clear definition of the balance between GA specific risks and the benefits of conservative management is critical to guide care. However, current evidence on obstetric, postpartum and long-term neonatal survival outcomes for patients with PPROM between 22 and 28 weeks remains limited. This evidence gap limits evidence-based decision-making and parental counselling.\u003c/p\u003e \u003cp\u003eThe objective of this study was to evaluate the frequency of adverse obstetric, postpartum and neonatal outcomes stratified by gestational age among pregnancies diagnosed with PPROM between 22 and 28 weeks at our center. We also analysed the latency to delivery, survival to discharge and survival without severe morbidity to a corrected age of one year. By providing gestational age\u0026ndash;specific estimates from a large single-center cohort, this study aims to inform clinical practice and refine management protocols for very early PPROM, thereby supporting individualized decision-making in extremely preterm pregnancies.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cp\u003e This study was approved by the Institutional Training Board and Clinical Research Ethics Committee of SB\u0026Uuml; İstanbul Zeynep Kamil Women\u0026rsquo;s and Children\u0026rsquo;s Diseases Training and Research Hospital (Decision No. 129, September 20, 2023) and conducted in accordance with the ethical standards of the Declaration of Helsinki. Because of the retrospective design, the requirement for informed consent was waived by the Ethics Committee. We conducted a single-center retrospective cohort study on singleton pregnancies that admitted to SB\u0026Uuml; Zeynep Kamil Women\u0026rsquo;s and Children\u0026rsquo;s Diseases Training and Research Hospital, tertiary referral perinatal center, between January 2018 and February 2023. Eligible patients were diagnosed with PPROM at 22\u0026thinsp;+\u0026thinsp;0\u0026ndash;28\u0026thinsp;+\u0026thinsp;0 weeks gestation and subsequently delivered at our institution. Gestational age was calculated from the last menstrual period and confirmed by first-trimester crown\u0026ndash;rump length (CRL). For pregnancies conceived via in vitro fertilization, the GA was calculated from embryo transfer dates.\u003c/p\u003e \u003cp\u003ePPROM was diagnosed in patients with a specific history of fluid leakage plus at least one of the following on sterile speculum examinations: active amniotic fluid leakage from the cervical canal with pooling in the posterior fornix or a positive placental alpha microglobulin-1 test (AmniSure\u0026reg;, PAMG-1 immunoassay; Amnisure ROM test; N-Dia, New York, NY, USA). The exclusion criteria were adolescent pregnancy, multiple gestations, iatrogenic membrane rupture (amniocentesis, chorionic villus sampling or cordocentesis), termination of pregnancy, fetuses with structural or genetic anomalies and PPROM with delivery after 34\u0026thinsp;+\u0026thinsp;0 weeks. After applying these criteria, 167 pregnancies were included; 10 of these resulted in intrauterine fetal demise and 66 neonates were transferred early to external centers owing to limited NICU capacity, Follow-up and complication data were unavailable for these infants. Among the 91 infants managed at our center, 30 died before discharge, and sufficient clinical follow-up data were not available to assess the development of severe morbidity. Accordingly, analyses of neonatal complications were restricted to a complete-case cohort of 58 infants who were managed at our center, survived to discharge and were followed up through 12 months of corrected age. Obstetric and postpartum outcomes were analysed for the full maternal cohort (n\u0026thinsp;=\u0026thinsp;167), whereas neonatal morbidity analyses used a complete-case approach (n\u0026thinsp;=\u0026thinsp;58).\u003c/p\u003e \u003cp\u003eAll patients were managed according to a standardized protocol. In our unit, termination is offered for up to 22\u0026thinsp;+\u0026thinsp;0 weeks. From 22\u0026thinsp;+\u0026thinsp;0 weeks onward, patients with PPROM are admitted to the hospital for management. The obstetric history and demographic characteristics were obtained and baseline laboratory tests were performed. Antibiotic prophylaxis consisted of a single 1 g oral dose of azithromycin followed by intravenous ampicillin 2 g every 6 hours for 48 hours and then oral amoxicillin 500 mg every 8 hours for 5 days. For penicillin allergy, clindamycin was administered. In addition, patients with positive vaginal, cervical or urine cultures received pathogen-directed antibiotics. A single course of antenatal corticosteroids (Betamethasone; Cales\u0026reg;, Ko\u0026ccedil;ak Farma İla\u0026ccedil; ve Kimya Sanayi A.Ş., Istanbul, Turkey) was administered to pregnancies with PPROM at 24\u0026thinsp;+\u0026thinsp;0 to 33\u0026thinsp;+\u0026thinsp;6 weeks at risk of preterm birth within 7 days. In those\u0026thinsp;\u0026lt;\u0026thinsp;34 weeks, a rescue course corticosteroid was given once \u0026ge;\u0026thinsp;14 days had passed since the last course and delivery was likely within 7 days. Tocolysis was generally used only in the presence of regular contractions to allow time for corticosteroid administration. For neuroprotection, patients who were expected to deliver before 32 weeks of gestation received intravenous magnesium sulfate (6 g loading dose over 30 minutes, followed by 2 g/hour maintenance) for 24 hours.\u003c/p\u003e \u003cp\u003eFetal growth and amniotic fluid were assessed with serial ultrasound; after 26 weeks, nonstress testing (NST) was performed. Clinical chorioamnionitis was diagnosed in the presence of maternal fever (\u0026ge;\u0026thinsp;38,0\u0026deg;C) without an extrauterine source plus at least two of the following:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eFetal tachycardia (\u0026gt;\u0026thinsp;160 beats/minute)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eMaternal tachycardia (\u0026gt;\u0026thinsp;100 beats/minute)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eLeukocytosis in maternal blood count (\u0026gt;\u0026thinsp;15,000 cells/mm3)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eUterine tenderness\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eMalodorous or purulent vaginal discharge.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003ePlacental abruption was diagnosed clinically (new-onset vaginal bleeding, frequent painful contractions, bloody amniotic fluid or placental clots) and, in some cases, supported by ultrasonographic evidence of a retroplacental hematoma. Maternal sepsis was defined as maternal infection (e.g., fever, positive blood cultures) with end-organ dysfunction (e.g., hypotension, oliguria, elevated creatinine, disseminated intravascular coagulation, decreased level of consciousness, or respiratory failure). Emergency delivery was performed for chorioamnionitis, nonreassuring fetal testing, placental abruption or cord prolapse. Mode of delivery followed obstetric indications; noncephalic presentation after 24 weeks was considered an indication for cesarean delivery.\u003c/p\u003e \u003cp\u003eAll neonates were evaluated by the neonatology team for RDS, sepsis, IVH, periventricular leukomalacia (PVL), BPD, ROP, NEC and neurodevelopment. The Denver II Developmental Screening Test was administered by a pediatric neurologician for neurodevelopmental assessment. ROP surveillance was performed by the Ophthalmology Department and hearing screening and follow-up were performed by the Otorhinolaryngology Department. Infants were followed until 12 months of corrected age.\u003c/p\u003e \u003cp\u003eData were extracted from the hospital information system and patient charts. GA at delivery and latency to delivery (defined as the interval from membrane rupture to delivery) were recorded. Maternal demographic and obstetric characteristics and obstetric, postpartum and neonatal outcomes were recorded. Patients were categorized by GA at PPROM into three groups: 22\u0026thinsp;+\u0026thinsp;0\u0026ndash;23\u0026thinsp;+\u0026thinsp;6, 24\u0026thinsp;+\u0026thinsp;0\u0026ndash;25\u0026thinsp;+\u0026thinsp;6 and 26\u0026thinsp;+\u0026thinsp;0\u0026ndash;28\u0026thinsp;+\u0026thinsp;0 weeks. For each group, we evaluated the latency to delivery and the obstetric, postpartum and neonatal outcomes up to 12 months of corrected age. The definitions of neonatal morbidities followed standard criteria (e.g. BPD according to the oxygen requirement at 36 weeks post-menstrual age; stage-based criteria for ROP; Bell staging for NEC, standardized definitions for IVH/PVL). Major morbidity was defined as the presence of any of the following:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eSevere bronchopulmonary dysplasia (BPD)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eNecrotizing enterocolitis (NEC) requiring surgery\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eRetinopathy of prematurity (ROP) requiring treatment\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eModerate to severe neurodevelopmental impairment\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eSensorineural hearing loss\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eGrade 3 to 4 intraventricular haemorrhage (IVH)/ periventricular leukomalacia (PVL)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eDeath\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eContinuous variables are summarized as means (SDs) or medians (IQRs), as appropriate; categorical variables are summarized as n (%). The distribution of continuous variables was assessed via Kolmogorov\u0026ndash;Smirnov test. For categorical variables the χ\u0026sup2; test or Fisher\u0026rsquo;s exact test was used for group comparisons. For continuous variables, two-group comparisons were performed via Student\u0026rsquo;s t test or the Mann\u0026ndash;Whitney U test; three-group comparisons were performed via one-way ANOVA or the Kruskal\u0026ndash;Wallis test. Correlations between continuous variables were examined with Pearson\u0026rsquo;s correlation. The possibility of preterm delivery in each gestational-age group was assessed via Kaplan\u0026ndash;Meier analysis. P values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered statistically significant. All analyses were conducted in SPSS version 17.0 (SPSS Inc., Chicago, IL, USA). No a priori sample-size calculation was performed because all eligible cases during the study period were included.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eDuring the study period, 36,167 births occurred at our hospital; 1,061 were complicated by PPROM (incidence, 2.93%). Among all the PPROM cases, 240 (22.6%) were diagnosed at 22\u0026thinsp;+\u0026thinsp;0\u0026ndash;28\u0026thinsp;+\u0026thinsp;0 weeks, corresponding to an incidence of 0.66% among all births. After applying the exclusion criterias, 167 pregnancies were included in the analysis cohort (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Ten of these resulted in intrauterine fetal demise and 66 neonates were transferred early to external centers. Among the remaining infants 91 were managed at our center. Analyses of neonatal complications were restricted to a complete-case cohort of 58 infants who were managed at our center, survived to discharge and were followed up through 12 months of corrected age.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe mean maternal age was 29.9\u0026thinsp;\u0026plusmn;\u0026thinsp;6.1 years. A total of 45.5% were primiparous and 54.4% were multiparous. The mean BMI was 27.6 kg/m\u0026sup2;, within the overweight range. Among women with a prior birth, 29.3% had a previous cesarean delivery and 25.1% had a previous spontaneous vaginal delivery. Elective cerclage at 12\u0026ndash;14 weeks was documented in 7.2% of the patients; none had a pessary. Additional baseline features, including oligohydramnios and antepartum bleeding at presentation, are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eObstetric and demographic characteristics (n\u0026thinsp;=\u0026thinsp;167)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eData\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years,(mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29.9 (\u0026plusmn;\u0026thinsp;6.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGravidity, (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.40 (\u0026plusmn;\u0026thinsp;1.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m2), (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27.6 (\u0026plusmn;\u0026thinsp;4.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultiparous, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e91(54.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimiparous, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e76(45.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIVF conception, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14(8.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of preterm labor, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27(16.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of PPROM, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11(6.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFirst-trimester bleeding, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e69(41.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCerclage in current pregnancy, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12(7.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUterine anomaly, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9(5.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrior uterine surgery, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9(5.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOligohydramnios at presentation, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e67(40.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e summarizes the associations between gestational age at PPROM and baseline characteristics. PPROM was diagnosed at 22\u0026thinsp;+\u0026thinsp;0\u0026ndash;23\u0026thinsp;+\u0026thinsp;6 weeks in 31.1%, 24\u0026thinsp;+\u0026thinsp;0\u0026ndash;25\u0026thinsp;+\u0026thinsp;6 in 34.7%, and 26\u0026thinsp;+\u0026thinsp;0\u0026ndash;28\u0026thinsp;+\u0026thinsp;0 in 34.1% of pregnancies. Maternal age, gravidity, parity, number of abortions, and BMI did not differ across GA at PPROM groups. IVF conception occurred in 8.4% overall and was more common in the 22\u0026thinsp;+\u0026thinsp;0\u0026ndash;23\u0026thinsp;+\u0026thinsp;6 group (P\u0026thinsp;=\u0026thinsp;0.009). Antepartum bleeding was present in 41.3% overall and was significantly less common in the 26\u0026thinsp;+\u0026thinsp;0\u0026ndash;28\u0026thinsp;+\u0026thinsp;0 group (P\u0026thinsp;=\u0026thinsp;0.006). Prior preterm labor (16.2%), prior PPROM (6.6%), uterine anomaly, prior uterine surgery, cerclage during current pregnancy, oligohydramnios at presentation, and cigarette smoking (9.0%) did not differ by GA at PPROM. No alcohol or illicit drug use was reported. As shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, the mean gestational age at delivery was 27.1 weeks, which differed across GA at PPROM groups (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The mean GA at PPROM was 25.0 weeks. The median latency was 6 days (IQR 2\u0026ndash;23) and did not differ by GA at PPROM (P\u0026thinsp;=\u0026thinsp;0.896). The probability of ongoing pregnancy after PPROM by GA group is depicted in the Kaplan\u0026ndash;Meier curves (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eObstetric and demographic characteristics of the study by GA at PPROM\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c7\" namest=\"c3\"\u003e \u003cp\u003eGA at PPROM\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal (Mean GA at PPROM 25 weeks)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22\u0026thinsp;+\u0026thinsp;0\u0026ndash;23\u0026thinsp;+\u0026thinsp;6\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e24\u0026thinsp;+\u0026thinsp;0\u0026ndash;25\u0026thinsp;+\u0026thinsp;6\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e26\u0026thinsp;+\u0026thinsp;0\u0026ndash;28\u0026thinsp;+\u0026thinsp;0\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCharacteristics\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;167\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003eP value\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years, (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29.9 (\u0026plusmn;\u0026thinsp;6.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e31(\u0026plusmn;\u0026thinsp;6.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e29.5(\u0026plusmn;\u0026thinsp;5.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e29.4(\u0026plusmn;\u0026thinsp;6.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParity, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimiparous, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e76(45.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e28(53.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e24(41.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e24(42.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultiparous, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e91(54.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e24(46.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e34(58.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e33(57.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrevious birth vaginal delivery*, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42(25.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e11(45.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e12(35.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e19(57.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.188\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrevious birth cesarean section*, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49(29.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e13(54.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e22(64.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e14(42.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI, kg/m2, (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27.6 (\u0026plusmn;\u0026thinsp;4.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e26.9(\u0026plusmn;\u0026thinsp;4.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e27.9(\u0026plusmn;\u0026thinsp;4.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e28.08(\u0026plusmn;\u0026thinsp;4.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIVF conception, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e8(13.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e3(5.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e3(5.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e0.009\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e4(7.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e6(10.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e5(8.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntenatal vaginal bleeding, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e69(41.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e27(51.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e28(48.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e14(24.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e0.006\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of PPROM*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11(6.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e4(16.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e3(8.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e4(12.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.402\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of preterm labor*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27(16.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e6(\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e25\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e10(29.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e11(33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.744\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLatency, days, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (\u003cspan additionalcitationids=\"CR3 CR4 CR5 CR6 CR7 CR8 CR9 CR10 CR11 CR12 CR13 CR14 CR15 CR16 CR17 CR18 CR19 CR20 CR21 CR22\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e23\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e6(2.2\u0026ndash;26.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e9(2-18.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e5(\u003cspan additionalcitationids=\"CR3 CR4 CR5 CR6 CR7 CR8 CR9 CR10 CR11 CR12 CR13 CR14 CR15 CR16 CR17 CR18 CR19 CR20 CR21 CR22 CR23 CR24 CR25\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e26\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.896\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDelivery within 48 h, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44(26.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e13(\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e25\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e16(27.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e15(36.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.954\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDelivery within 7 days, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e89(53.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e29(55.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e28(48.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e32(56.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.638\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOligohydramnios at presentation, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e67(40.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e24(46.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e27(46.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e26(28.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGestational age at delivery, weeks, (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27.1(\u0026plusmn;\u0026thinsp;0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e25(\u0026plusmn;\u0026thinsp;0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e26.9(\u0026plusmn;\u0026thinsp;0.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e29.1(\u0026plusmn;\u0026thinsp;0.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"9\" nameend=\"c9\" namest=\"c1\"\u003e \u003cp\u003e* Among women with a prior birth (where applicable).\u003c/p\u003e \u003cp\u003e\u0026dagger; Comparisons by GA at PPROM:\u0026nbsp;Pearson‒χ2 tests for categorical variables;\u0026nbsp;one-way ANOVA\u0026nbsp;for normally distributed continuous variables;\u0026nbsp;Kruskal\u0026ndash;Wallis\u0026nbsp;for nonnormal distributions.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eMaternal adverse outcomes by gestational age at PPROM are shown in Table\u0026nbsp;3. Placental abruption occurred in 18 patients (10.8%) and was more frequent in the 24\u0026thinsp;+\u0026thinsp;0\u0026ndash;25\u0026thinsp;+\u0026thinsp;6 group than in the other groups (P\u0026thinsp;=\u0026thinsp;0.04). Clinical chorioamnionitis, noncephalic presentation, cord prolapse and intrauterine fetal death did not differ across the groups.\u003c/p\u003e \u003cp\u003eOverall, 31.1% delivered vaginally and 68.9% were delivered by cesarean. Cesarean delivery was more frequent in the 24\u0026thinsp;+\u0026thinsp;0\u0026ndash;25\u0026thinsp;+\u0026thinsp;6 group (P\u0026thinsp;=\u0026thinsp;0.009). There were no significant differences in terms of GA at PPROM for retained placenta, postpartum sepsis, postpartum bleeding or wound infection.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"8\" nameend=\"c8\" namest=\"c1\"\u003e \u003cp\u003eTable\u0026nbsp;3 Maternal Outcomes by GA at PPROM\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c8\" namest=\"c3\"\u003e \u003cp\u003eGA at PPROM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22\u0026thinsp;+\u0026thinsp;0\u0026ndash;23\u0026thinsp;+\u0026thinsp;6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e24\u0026thinsp;+\u0026thinsp;0\u0026ndash;25\u0026thinsp;+\u0026thinsp;6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e26\u0026thinsp;+\u0026thinsp;0\u0026ndash;28\u0026thinsp;+\u0026thinsp;0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMaternal outcome\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003en:167\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003en:52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003en:58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c9\" namest=\"c7\"\u003e \u003cp\u003en:57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eObstetric outcomes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c9\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical chorioamnionitis, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e46(27.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e16(30.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e15(25.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c9\" namest=\"c7\"\u003e \u003cp\u003e15(26.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCord prolapse, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e4(7.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e1(1.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c9\" namest=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNoncephalic presentation, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19(11.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e9(17.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e5(8.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c9\" namest=\"c7\"\u003e \u003cp\u003e5(8.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlacental abruption, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18(10.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e4(7.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e11(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e19\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c9\" namest=\"c7\"\u003e \u003cp\u003e3(5.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e0.04\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntrauterine fetal demise, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e6(11.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e1(1.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c9\" namest=\"c7\"\u003e \u003cp\u003e3(5.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.09\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCesarean delivery, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e115(68.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e29(55.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e48(82.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c9\" namest=\"c7\"\u003e \u003cp\u003e38(66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e0.009\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePostpartum outcomes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c9\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostpartum haemorrhage, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11(6.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e6(11.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e3(5.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c9\" namest=\"c7\"\u003e \u003cp\u003e2(3.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRetained placenta, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18(10.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e9(17.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e3(5.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c9\" namest=\"c7\"\u003e \u003cp\u003e6(10.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSepsis, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7(4.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e3(5.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e1(1.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c9\" namest=\"c7\"\u003e \u003cp\u003e3(5.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWound infection, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7(4.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e3(5.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c9\" namest=\"c7\"\u003e \u003cp\u003e4(7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"10\"\u003e*Comparisons by GA at PPROM:\u0026nbsp;χ\u0026sup2;\u0026nbsp;for categorical variables;\u0026nbsp;one-way ANOVA\u0026nbsp;for normally distributed continuous variables;\u0026nbsp;Kruskal\u0026ndash;Wallis\u0026nbsp;for non-normal distributions.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe neonatal outcomes at 12 months of corrected age and survival data are presented in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e4\u003c/span\u003e. Across GA at PPROM groups, the rates of NEC, neonatal sepsis, ROP, hearing loss, IVH and RDS were similar (all P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Among infants who were 12 months of corrected age, 36.2% had BPD, 25.9% had neurodevelopmental impairment, and 13.5% had hearing impairment. BPD was significantly greater in the 24\u0026thinsp;+\u0026thinsp;0\u0026ndash;25\u0026thinsp;+\u0026thinsp;6 group (P\u0026thinsp;=\u0026thinsp;0.003), whereas neurodevelopmental impairment and hearing loss did not differ across the groups.\u003c/p\u003e \u003cp\u003eOverall survival to discharge was 67.0% and differed significantly across the gestational age at PPROM groups (P\u0026thinsp;=\u0026thinsp;0.001), with the highest survival at 26\u0026thinsp;+\u0026thinsp;0\u0026ndash;28\u0026thinsp;+\u0026thinsp;0 (88.6%) and the lowest survival at 22\u0026thinsp;+\u0026thinsp;0\u0026ndash;23\u0026thinsp;+\u0026thinsp;6 (44.4%). Survival without major morbidity to 12 months of corrected age was 42.9% and likewise varied significantly by diagnosis week (P\u0026thinsp;=\u0026thinsp;0.001); suvival was highest at 26\u0026thinsp;+\u0026thinsp;0\u0026ndash;28\u0026thinsp;+\u0026thinsp;0 (60.0%) weeks and lowest at 22\u0026thinsp;+\u0026thinsp;0\u0026ndash;23\u0026thinsp;+\u0026thinsp;6 (22.2%) weeks. Both survival and morbidity-free survival increased with advancing gestational age at PPROM.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBirth Characteristics and outcomes by GA at PPROM\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeonatal birth characteristics and outcome\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e \u003cp\u003eGA at PPROM\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22\u0026thinsp;+\u0026thinsp;0\u0026ndash;23\u0026thinsp;+\u0026thinsp;6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24\u0026thinsp;+\u0026thinsp;0\u0026ndash;25\u0026thinsp;+\u0026thinsp;6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e26\u0026thinsp;+\u0026thinsp;0\u0026ndash;28\u0026thinsp;+\u0026thinsp;0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;91*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003en:27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003en:29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003en:35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003eP value\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirthweight, g, (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1138\u0026thinsp;\u0026plusmn;\u0026thinsp;559\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e880\u0026thinsp;\u0026plusmn;\u0026thinsp;505\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e986\u0026thinsp;\u0026plusmn;\u0026thinsp;447\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1459\u0026thinsp;\u0026plusmn;\u0026thinsp;536\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eApgar 1 (n\u0026thinsp;=\u0026thinsp;85), (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.007\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eApgar 5 (n\u0026thinsp;=\u0026thinsp;85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.003\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurvival to discharge, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61(67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12(44.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18(62.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e31(88.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurvival without major morbidity at 12 months of corrected age, n (%) \u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39(42.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6(22.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12(41.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21(60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;58 \u0026Dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntraventricular haemorrhage, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14(24.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(27.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6(35.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5(16.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNecrotizing enterocolitis, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6(10.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2(11.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4(13.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRespiratory distress syndrome, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44(75.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8(72.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15(88.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21(70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSepsis, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32(55.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7(63.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12(70.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13(43.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRetinopathy of Prematurity, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23(39.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(45.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10(58.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8(36.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBronchopulmonary dysplasia, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21(36.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(45.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11(64,7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5(16.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.003\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHearing Loss, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8(13.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4(23.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeurodevelopmental impairment, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15(25.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4(36.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4(23.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7(23.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e* In-hospital neonatal cohort:\u0026nbsp;excludes transfers; includes all infants managed at our center (n\u0026thinsp;=\u0026thinsp;91).\u003c/p\u003e \u003cp\u003e\u0026dagger; Major morbidity\u0026nbsp;was defined as any of: severe BPD, surgery-requiring NEC, treatment-requiring ROP, moderate\u0026ndash;severe neurodevelopmental impairment, sensorineural hearing loss, grade 3\u0026ndash;4 IVH/PVL or death.\u003c/p\u003e \u003cp\u003e\u0026Dagger;Complete-case neonatal outcomes: analyses restricted to infants with complete follow-up to 12 months of corrected age (n\u0026thinsp;=\u0026thinsp;58).\u003c/p\u003e \u003cp\u003e\u0026sect; Comparisons by GA at PPROM:\u0026nbsp;χ\u0026sup2;\u0026nbsp;for categorical variables;\u0026nbsp;one-way ANOVA\u0026nbsp;for normally distributed continuous variables;\u0026nbsp;Kruskal\u0026ndash;Wallis\u0026nbsp;for nonnormal distributions.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eWhen the latency to delivery was \u0026lt;\u0026thinsp;7 days compared with \u0026ge;\u0026thinsp;7 days, there were no significant differences in obstetric or postpartum complications (all P\u0026thinsp;\u0026gt;\u0026thinsp;0.05; Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e5\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e For neonatal outcomes, the \u0026ge;\u0026thinsp;7-day group performed better: survival to discharge was 84.1% compared with 51.1% \u003cb\u003e(\u003c/b\u003eP\u0026thinsp;=\u0026thinsp;0.001\u003cb\u003e)\u003c/b\u003e, and survival without major morbidity at 12 months of corrected age was 56.8% compared with 29.8% \u003cb\u003e(\u003c/b\u003eP\u0026thinsp;=\u0026thinsp;0.005\u003cb\u003e)\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eOutcomes by Latency to Delivery (\u0026le;\u0026thinsp;7 vs\u0026thinsp;\u0026gt;\u0026thinsp;7 days)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal outcomes (n\u0026thinsp;=\u0026thinsp;167)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLatency\u0026thinsp;\u0026le;\u0026thinsp;7 g\u0026uuml;n\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLatency\u0026thinsp;\u0026gt;\u0026thinsp;7g\u0026uuml;n\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical chorioamnionitis, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26 (29.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20(25.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.606\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlacental abruption, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11(12.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.482\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNoncephalic presentation, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14(15.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5(6.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.058\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCord prolapse, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(2.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3(3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.665\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntrauterine fetal demise, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2(2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.106\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRetained placenta, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13(14.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5(6.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.088\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWound infection, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(3.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4(5.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.706\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSepsis, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4(4.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3(3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostpartum haemorrhage, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4(4.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.244\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeonatal outcome (n\u0026thinsp;=\u0026thinsp;91*)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurvival without major morbidity, n (%) \u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14(29.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25(56.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.005\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeonatal death, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23(48.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7(15.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e* In-hospital neonatal cohort:\u0026nbsp;excludes transfers; includes all infants managed at our center (n\u0026thinsp;=\u0026thinsp;91).\u003c/p\u003e \u003cp\u003e\u0026dagger; Major morbidity\u0026nbsp;was defined as any of: severe BPD, surgery-requiring NEC, treatment-requiring ROP, moderate\u0026ndash;severe neurodevelopmental impairment, sensorineural hearing loss, grade 3\u0026ndash;4 IVH/PVL or death.\u003c/p\u003e \u003cp\u003e**Fisher exact test was used in groups with expected value\u0026thinsp;\u0026lt;\u0026thinsp;5, and chi-square test was used in groups with expected value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAcross GA at PPROM groups, there were no significant differences in maternal age, BMI, gravidity/parity, prior mode of delivery, cigarette smoking, history of preterm labor, or history of PPROM. The demographic and obstetric profiles of our cohort are consistent with those of prior early\u0026ndash;late PPROM cohorts(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Taken together, these findings suggest that gestational age at PPROM and the clinical management applied, rather than baseline maternal characteristics, are the primary determinants of outcomes in this population.\u003c/p\u003e \u003cp\u003eIn a large retrospective Danish cohort of singleton pregnancies, Lykke et al. reported that first-trimester bleeding was associated with an increased risk of PPROM and preterm birth before 34 weeks of gestation(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e16\u003c/span\u003e). In our cohort, antenatal vaginal bleeding was documented in 41.3% of pregnancies and its frequency decreased with increasing GA at PPROM diagnosis (P\u0026thinsp;=\u0026thinsp;0.006). Although the higher rate at earlier diagnostic windows is consistent with prior reports, causality between bleeding and the timing of rupture cannot be established in this retrospective study. We also observed that PPROM at 22\u0026thinsp;+\u0026thinsp;0\u0026ndash;23\u0026thinsp;+\u0026thinsp;6 weeks was more common among IVF conceptions than at later diagnostic windows (P\u0026thinsp;=\u0026thinsp;0.009). Given the limited sample size and potential confounding (e.g., maternal age, infertility etiology), these findings should be interpreted cautiously and confirmed in larger cohorts.\u003c/p\u003e \u003cp\u003eIn our cohort, the median latency to delivery was 6 days (IQR 2\u0026ndash;23). For comparison, Seravalli et al. reported a median latency of 16 days for PPROM\u0026thinsp;\u0026lt;\u0026thinsp;32 weeks and the French national EPIPAGE-2 study reported 8 days for PPROM at 22\u0026ndash;25 weeks (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e18\u003c/span\u003e). In contrast, the review by Sim et al. described a wider range of 7\u0026ndash;49 days(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e19\u003c/span\u003e). The relatively shorter latencies in our study likely reflect our focus on very early PPROM, inpatient management from diagnosis and a higher burden of complications that prompted urgent delivery (e.g., chorioamnionitis, abruption and cord prolapse). Overall, these findings suggest that latency depends not only on the GA at diagnosis but also on other clinical findings and how the condition is managed.\u003c/p\u003e \u003cp\u003eSeveral studies have reported longer latency when PPROM occurs at earlier gestational ages(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e20\u003c/span\u003e). In contrast, in our cohort (mean diagnostic GA 25 weeks), latency did not differ across GA at PPROM groups within the very-early window. This pattern aligns with the findings of the French national EPIPAGE-2 study, which analysed PPROM at 22\u0026ndash;25 weeks (mean GA 25 weeks) and likewise revealed no GA-related difference in latency(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Similarly, Seravalli et al. reported that among patients with PPROM\u0026thinsp;\u0026lt;\u0026thinsp;32 weeks (mean diagnostic GA 26.1 weeks), latency did not vary by diagnostic GA (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e17\u003c/span\u003e). By comparison, Peaceman et al. (PPROM\u0026thinsp;\u0026lt;\u0026thinsp;32 weeks; mean diagnostic GA, 28.1 weeks) reported a similar latency at \u0026le;\u0026thinsp;28 weeks but significantly shorter latency when PPROM occurred at 29\u0026ndash;31 weeks than at \u0026le;\u0026thinsp;28 weeks (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e20\u003c/span\u003e). These data indicate that despite variability across studies and within very-early PPROM groups, latency to delivery changes little with gestational age at diagnosis. Larger cohorts\u0026mdash;including those\u0026thinsp;\u0026ge;\u0026thinsp;28 weeks\u0026mdash;are needed to confirm this.\u003c/p\u003e \u003cp\u003eIn our cohort, 26.3% had delivered within 48 hours and 53.2% within 7 days of PPROM; both proportions were similar across GA at PPROM groups (P\u0026thinsp;=\u0026thinsp;0.954 and 0.638, respectively). In the EPIPAGE-2, delivery occurred in 19.4% of the patients within 48 hours and 47% of the patients within 1 week, with no difference in diagnostic GA (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Walker et al. reported a 67% delivery rate within 1 week, whereas in the cohort by Seravalli et al. (with a similar timeframe) 15% delivered within 48 hours and 33.7% delivered within 7 days, again without GA-related differences (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e21\u003c/span\u003e). The variation across studies likely reflects management strategies (e.g., early hospitalization, standardized antibiotic/corticosteroid protocols) as well as methodological differences (gestational-age windows, intervention thresholds and inclusion/exclusion criteria).\u003c/p\u003e \u003cp\u003eIn our cohort, clinical chorioamnionitis occurred in 27.5%, cord prolapse in 3.0%, placental abruption in 10.8% and intrauterine fetal demise in 6.0%. The rates of chorioamnionitis, intrauterine fetal demise, noncephalic presentation, and cord prolapse were similar across GA at PPROM groups; only placental abruption was higher in the 24\u0026thinsp;+\u0026thinsp;0\u0026ndash;25\u0026thinsp;+\u0026thinsp;6 group (P\u0026thinsp;=\u0026thinsp;0.04). This pattern is consistent with reports focused on very-early PPROM (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e17\u003c/span\u003e). The relatively high rate of chorioamnionitis probably reflects our focus on very-early PPROM cases and continuous inpatient monitoring from the time of diagnosis, which may have increased detection.\u003c/p\u003e \u003cp\u003eThe overall cesarean delivery rate was 68.9%, with a clear peak in the 24\u0026thinsp;+\u0026thinsp;0\u0026ndash;25\u0026thinsp;+\u0026thinsp;6 group (P\u0026thinsp;=\u0026thinsp;0.009). This exceeds several published series: 53.3% in PPROM\u0026thinsp;\u0026lt;\u0026thinsp;28 weeks (Seravalli et al.), 52.9% at 24\u0026ndash;37 weeks (Salman et al.) and 50.8% at 23\u0026ndash;27 weeks (Newman et al.) (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Our higher rate is plausibly related to the greater proportion of patients with prior cesarean (29.3%), a cesarean approach for noncephalic presentation after 24 weeks, the very-early PPROM case selection and higher frequencies of urgent-delivery complications.\u003c/p\u003e \u003cp\u003eLatency did not differ according to the presence of chorioamnionitis, abruption, intrauterine fetal demise or cord prolapse. Only noncephalic presentation was associated with shorter latency (median 4 vs 7 days for cephalic; P\u0026thinsp;=\u0026thinsp;0.023). The median latency was similar with and without abruption (P\u0026thinsp;=\u0026thinsp;0.253) (Additional file 1). Larger cohorts are needed to clarify how specific obstetric complications influence the latency to delivery.\u003c/p\u003e \u003cp\u003eIn our cohort, sepsis occurred in 4.2%, postpartum haemorrhage in 6.6%, uterine curettage for retained placenta in 10.8%, and wound infection in 4.2%; none differed by GA at PPROM. Among PPROM cases reported in the literature, at 18\u0026ndash;24 weeks, Deutsch et al. reported chorioamnionitis 64.8%, sepsis 0.9%, postpartum haemorrhage 14.3%, and postpartum curettage 7.6% (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e14\u003c/span\u003e). In a 14\u0026ndash;23-week PPROM cohort, Dotters-Katz et al. observed wound infection 1.2%, sepsis 1.2%, postpartum haemorrhage 39.0%, and postpartum curettage 2.9% (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Differences across studies likely reflect gestational-age windows and variations in care protocols.\u003c/p\u003e \u003cp\u003eApgar-1, Apgar-5, birthweight and survival increased significantly with advancing GA at PPROM; however, NEC, ROP, hearing loss, IVH, RDS and neurodevelopmental impairment did not differ across diagnostic GA groups. Notably, BPD was higher in the 24\u0026thinsp;+\u0026thinsp;0\u0026ndash;25\u0026thinsp;+\u0026thinsp;6 group (P\u0026thinsp;=\u0026thinsp;0.003), a finding that may reflect a greater need for prolonged respiratory support in the periviability window. Similarly, prior reports revealed no consistent GA-related differences in neonatal complications across PPROM diagnostic strata (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e24\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe survival gradients resulting from the GA at PPROM were clear. Survival to discharge was 67.0% overall, increasing from 44.4% at 22\u0026thinsp;+\u0026thinsp;0\u0026ndash;23\u0026thinsp;+\u0026thinsp;6 to 62.1% at 24\u0026thinsp;+\u0026thinsp;0\u0026ndash;25\u0026thinsp;+\u0026thinsp;6 and 88.6% at 26\u0026thinsp;+\u0026thinsp;0\u0026ndash;28\u0026thinsp;+\u0026thinsp;0 (P\u0026thinsp;=\u0026thinsp;0.001). Survival without major morbidity at 12 months of corrected age was 42.9% overall, increasing from 22.2% to 41.4% and 60.0% across the same groups (P\u0026thinsp;=\u0026thinsp;0.001). These patterns align broadly with international data\u0026mdash;for example, Manuck et al. reported survival/morbidity-free survival rates of 83.3%/24.4% at \u0026lt;\u0026thinsp;25 weeks and 98.0%/78.2% at \u0026ge;\u0026thinsp;25 weeks(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e15\u003c/span\u003e). EPIPAGE2 reported 68.2% survival and 51.6% morbidity-free survival at age two for 22\u0026ndash;25 weeks (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Compared with series from our country, survival to discharge at our center appears relatively high (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e25\u003c/span\u003e). Differences in rates likely reflect gestational-age ranges and obstetric/neonatal care protocols; nevertheless, the stepwise improvement in survival and survival without major morbidity with increasing GA is consistent.\u003c/p\u003e \u003cp\u003eMultiple studies have linked longer latency with more favourable neonatal outcomes (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e26\u003c/span\u003e). In our cohort,a longer latency was not associated with greater rates of obstetric or postpartum complications; instead, it was associated with lower neonatal mortality and higher survival without major morbidity. These findings support the view that, when clinically safe, prolonging the intrauterine stay may be beneficial for neonatal outcomes.\u003c/p\u003e \u003cp\u003eThe strengths of this study include a relatively large cohort despite the low incidence of very-early PPROM (22\u0026thinsp;+\u0026thinsp;0\u0026ndash;28\u0026thinsp;+\u0026thinsp;0 weeks; \u0026lt;1% of all births at our center during the study period) and the use of a single-center, standardized management protocol across all cases. Another strength is the stratification of outcomes by gestational age at PPROM, which enables gestational-age\u0026ndash;specific, individualized counselling for maternal and neonatal outcomes.\u003c/p\u003e \u003cp\u003eThis study also has limitations, including its retrospective design and the absence of data for PPROM cases that opt for termination, which represents a common form of selection bias in PPROM research. In addition, some infants are transferred to outside NICUs because of capacity constraints, resulting in incomplete follow-up and long-term neonatal data were limited. These factors may affect the generalizability and the precision of some estimates.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn pregnancies with PPROM at 22\u0026thinsp;+\u0026thinsp;0\u0026ndash;28\u0026thinsp;+\u0026thinsp;0 weeks, our data characterize how gestational age at diagnosis and latency to delivery are related to maternal and neonatal morbidity and mortality. Overall, this study provides practical, center-specific evidence to inform PPROM management and reflects advances in obstetric and neonatal care using data from our institution. Notably, the high incidences of chorioamnionitis, placental abruption and cord prolapse in this very-early PPROM group support inpatient admission with close surveillance. These findings should be corroborated in multicenter prospective studies, including studies of longer-term pediatric outcomes, to refine management strategies for very-early PPROM.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cstrong\u003ePPROM:\u003c/strong\u003e Preterm Premature Rupture of Membranes\u003cbr\u003e\u003cstrong\u003eGA:\u003c/strong\u003e Gestational Age\u003cbr\u003e\u003cstrong\u003eBMI:\u003c/strong\u003e Body Mass Index\u003cbr\u003e\u003cstrong\u003eIVF:\u003c/strong\u003e In Vitro Fertilization\u003cbr\u003e\u003cstrong\u003eCRL:\u003c/strong\u003e Crown Rump Length\u003cbr\u003e\u003cstrong\u003eNST:\u003c/strong\u003e Nonstress Test\u003cbr\u003e\u003cstrong\u003eRDS:\u003c/strong\u003e Respiratory Distress Syndrome\u003cbr\u003e\u003cstrong\u003eBPD:\u003c/strong\u003e Bronchopulmonary Dysplasia\u003cbr\u003e\u003cstrong\u003eIVH:\u003c/strong\u003e Intraventricular Hemorrhage\u003cbr\u003e\u003cstrong\u003ePVL:\u003c/strong\u003e Periventricular Leukomalacia\u003cbr\u003e\u003cstrong\u003eNEC:\u003c/strong\u003e Necrotising Enterocolitis\u003cbr\u003e\u003cstrong\u003eROP:\u003c/strong\u003e Retinopathy of Prematurity\u003cbr\u003e\u003cstrong\u003eNICU:\u003c/strong\u003e Neonatal Intensive Care Unit\u003cbr\u003e\u003cstrong\u003eSD:\u003c/strong\u003e Standard Deviation\u003cbr\u003e\u003cstrong\u003eIQR:\u003c/strong\u003e Interquartile Range\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was conducted following the principles outlined in the Declaration of Helsinki, with ethical approval obtained from the Institutional Training Board and Clinical Research Ethics Committee of SBÜ İstanbul Zeynep Kamil Women’s and Children’s Diseases Training and Research Hospital (Decision No. 129, September 20, 2023).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGiven the study’s retrospective nature, the Ethics Committee of SBÜ İstanbul Zeynep Kamil Women’s and Children’s Diseases Training and Research Hospital granted a waiver for informed consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors’ contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eİŞR and EÇ contributed to the study conception and design, resources, and data curation. İSS performed the formal statistical analysis. EÇ and GK supervised the study and validated the findings. İŞR was responsible for the investigation and methodology and drafted the original manuscript. İŞR and EÇ critically revised the manuscript for content. All the authors have read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors’ information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e1.Department of Obstetrics and Gynaecology, İstanbul Medeniyet University Prof. Dr. Süleyman Yalçın City Hospital, İstanbul, Turkey\u003c/p\u003e\n\u003cp\u003e2.Department of Obstetrics and Gynaecology, SBÜ Kartal Prof.Dr. Lütfi Kırdar City Hospital, İstanbul, Turkey\u003c/p\u003e\n\u003cp\u003e3. Department of Pediatrics, Division of Neonatology, SBÜ İstanbul Zeynep Kamil Women’s and Children’s Diseases Training and Research Hospital, İstanbul, Turkey\u003c/p\u003e\n\u003cp\u003e4. Department of Obstetrics and Gynaecology, Private Clinic, İstanbul, Türkiye\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eGoldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. The Lancet. 2008 Jan;371(9606):75\u0026ndash;84. DOI: 10.1016/S01406736(08)60074-4 \u003c/li\u003e\n\u003cli\u003eWaters TP, Mercer BM. The management of preterm premature rupture of the membranes near the limit of fetal viability. Am J Obstet Gynecol. 2009 Sep;201(3):230\u0026ndash;40. DOI: 10.1016/j.ajog.2009.06.049 \u003c/li\u003e\n\u003cli\u003ePrelabor Rupture of Membranes. Obstetrics \u0026amp; Gynecology. 2020 Mar;135(3):e80\u0026ndash;97. DOI: 10.1097/AOG.0000000000003700 \u003c/li\u003e\n\u003cli\u003eMercer BM, Goldenberg RL, Moawad AH, Meis PJ, Iams JD, Das AF, et al. The Preterm Prediction Study: Effect of gestational age and cause of preterm birth on subsequent obstetric outcome. Am J Obstet Gynecol. 1999 Nov;181(5):1216\u0026ndash;21. DOI: 10.1016/s0002-9378(99)70111-0 \u003c/li\u003e\n\u003cli\u003eMercer BM, Goldenberg RL, Meis PJ, Moawad AH, Shellhaas C, Das A, et al. The Preterm Prediction Study: Prediction of preterm premature rupture of membranes through clinical findings and ancillary testing. Am J Obstet Gynecol. 2000 Sep;183(3):738\u0026ndash;45. DOI: 10.1067/mob.2000.106766 \u003c/li\u003e\n\u003cli\u003eStoll BJ, Hansen NI, Bell EF, Shankaran S, Laptook AR, Walsh MC, et al. Neonatal Outcomes of Extremely Preterm Infants From the NICHD Neonatal ResearchNetwork. Pediatrics. 2010 Sep 1;126(3):443\u0026ndash;56. DOI: 10.1542/peds.2009-2959 \u003c/li\u003e\n\u003cli\u003eAncel PY, Goffinet F, Kuhn P, Langer B, Matis J, Hernandorena X, et al. Survival and Morbidity of Preterm Children Born at 22 Through 34 Weeks\u0026rsquo; Gestation in France in 2011. JAMA Pediatr. 2015 Mar 1;169(3):230.DOI: 10.1001/jamapediatrics.2014.3351 \u003c/li\u003e\n\u003cli\u003eDotters-Katz SK, Panzer A, Grace MR, Smid MC, Keku JA, Vladutiu CJ, et al. Maternal Morbidity After Previable Prelabor Rupture of Membranes. Obstetrics \u0026amp; Gynecology. 2017 Jan;129(1):101\u0026ndash;6. DOI: 10.1097/AOG.0000000000001803 \u003c/li\u003e\n\u003cli\u003eCLARK EAS, VARNER M. Impact of Preterm PROM and its Complications on Long-term Infant Outcomes. Clin Obstet Gynecol. 2011 Jun;54(2):358\u0026ndash;69.DOI: 10.1097/GRF.0b013e318217ee18 \u003c/li\u003e\n\u003cli\u003eManuck TA, Eller AG, Esplin MS, Stoddard GJ, Varner MW, Silver RM. Outcomes of Expectantly Managed Preterm Premature Rupture of Membranes Occurring Before 24 Weeks of Gestation. Obstetrics \u0026amp; Gynecology. 2009 Jul;114(1):29\u0026ndash;37. DOI: 10.1097/AOG.0b013e3181ab6fd3 \u003c/li\u003e\n\u003cli\u003eMorris JM, Roberts CL, Bowen JR, Patterson JA, Bond DM, Algert CS, et al. Immediate delivery compared with expectant management after preterm pre-labour rupture of the membranes close to term (PPROMT trial): a randomised controlled trial.The Lancet. 2016 Jan;387(10017):444\u0026ndash;52. DOI: 10.1016/S0140-6736(15)00724-2 \u003c/li\u003e\n\u003cli\u003eBond DM, Middleton P, Levett KM, van der Ham DP, Crowther CA, Buchanan SL, et al. Planned early birth versus expectant management for women with preterm prelabour rupture of membranes prior to 37 weeks\u0026rsquo; gestation for improving pregnancy outcome. Cochrane Database of Systematic Reviews. 2017 Mar 3;2017(3). DOI: 10.1002/14651858.CD004735.pub4 \u003c/li\u003e\n\u003cli\u003eKibel M, Asztalos E, Barrett J, Dunn MS, Tward C, Pittini A, et al. Outcomes of Pregnancies Complicated by Preterm Premature Rupture of Membranes Between 20 and 24 Weeks of Gestation. Obstetrics \u0026amp; Gynecology. 2016 Aug;128(2):313\u0026ndash;20. DOI: 10.1097/AOG.0000000000001530 \u003c/li\u003e\n\u003cli\u003eDeutsch A, Deutsch E, Totten C, Downes K, Haubner L, Belogolovkin V. Maternal and neonatal outcomes based on the gestational age of midtrimester preterm premature rupture of membranes. The Journal of Maternal-Fetal \u0026amp; Neonatal Medicine. 2010 Dec 17;23(12):1429\u0026ndash;34.DOI: 10.3109/14767051003678069 \u003c/li\u003e\n\u003cli\u003eManuck TA, Varner MW. Neonatal and early childhood outcomes following early vs later preterm premature rupture of membranes. Am J Obstet Gynecol. 2014 Sep;211(3):308.e1-308.e6. DOI: 10.1016/j.ajog.2014.05.030 \u003c/li\u003e\n\u003cli\u003eLykke JA, Dideriksen KL, Lidegaard \u0026Oslash;, Langhoff-Roos J. First-Trimester Vaginal Bleeding and Complications Later in Pregnancy. Obstetrics \u0026amp; Gynecology.2010;115(5):935\u0026ndash;44. DOI: 10.1097/AOG.0b013e3181da8d38 \u003c/li\u003e\n\u003cli\u003eSeravalli V, Colucci C, Di Cencio C, Morucchio A, Barsanti F, Di Tommaso M. Latency to delivery and incidence of adverse obstetric and perinatal outcomes in preterm premature rupture of membranes before 32 weeks. Arch Gynecol Obstet. 2025 Feb 10;311(6):1569\u0026ndash;77. DOI: 10.1007/s00404-025-07970-3 \u003c/li\u003e\n\u003cli\u003eLorthe E, Torchin H, Delorme P, Ancel PY, Marchand-Martin L, FoixL\u0026rsquo;H\u0026eacute;lias L, et al. Preterm premature rupture of membranes at 22\u0026ndash;25 weeks\u0026rsquo; gestation: perinatal and 2-year outcomes within a national population-based study (EPIPAGE-2). Am J Obstet Gynecol. 2018 Sep;219(3): 298.e1-298.e14.DOI: 10.1016/j.ajog.2018.05.029 \u003c/li\u003e\n\u003cli\u003eSim WH, Ng H, Sheehan P. Maternal and neonatal outcomes following expectant management of preterm prelabor rupture of membranes before viability. The Journal of Maternal-Fetal \u0026amp; Neonatal Medicine. 2020 Feb 16;33(4):533\u0026ndash;41.DOI: 10.1080/14767058.2018.1495706 \u003c/li\u003e\n\u003cli\u003ePeaceman A, Lai Y, Rouse D, Spong C, Mercer B, Varner M, et al. Length of Latency with Preterm Premature Rupture of Membranes before 32 Weeks\u0026rsquo; Gestation. Am J Perinatol. 2014 May 12;32(01):057\u0026ndash;62. DOI: 10.1055/s-0034-1373846 \u003c/li\u003e\n\u003cli\u003eWalker MW, Picklesimer AH, Clark RH, Spitzer AR, Garite TJ. Impact of duration of rupture of membranes on outcomes of premature infants. Journal of Perinatology. 2014 Sep 24;34(9):669\u0026ndash;72. DOI: 10.1038/jp.2014.73 \u003c/li\u003e\n\u003cli\u003eSalman L, Aviram A, Holzman R, Hay-Azogui H, Ashwal E, Hadar E, et al. Predictors for cesarean delivery in preterm premature rupture of membranes. The Journal of Maternal-Fetal \u0026amp; Neonatal Medicine. 2020 Nov 16;33(22):3761\u0026ndash;6.DOI: 10.1080/14767058.2019.1585422 \u003c/li\u003e\n\u003cli\u003eNewman DE, Paamoni-Keren O, Press F, Wiznitzer A, Mazor M, Sheiner E. Neonatal outcome in preterm deliveries between 23 and 27 weeks\u0026rsquo; gestation with and without preterm premature rupture of membranes. Arch Gynecol Obstet. 2009 Jul 25;280(1):7\u0026ndash;11. DOI: 10.1007/s00404-008-0836-8 \u003c/li\u003e\n\u003cli\u003eHerzlich J, Mangel L, Halperin A, Lubin D, Marom R. Neonatal outcomes in women with preterm premature rupture of membranes at periviable gestational age. Sci Rep. 2022 Jul 14;12(1):11999. DOI: 10.1038/s41598-022-16265-5 \u003c/li\u003e\n\u003cli\u003eEsteves JS, de S\u0026aacute; RAM, de Carvalho PRN, Coca Velarde LG. Neonatal outcome in women with preterm premature rupture of membranes (PPROM) between 18 and 26 weeks. The Journal of Maternal-Fetal \u0026amp; Neonatal Medicine. 2016 Apr 2;29(7):1108\u0026ndash;12. DOI: 10.3109/14767058.2015.1035643 \u003c/li\u003e\n\u003cli\u003eBaser E, Aydogan Kirmizi D, Ulubas Isik D, Ozdemirci S, Onat T, Serdar Yalvac E, et al. The effects of latency period in PPROM cases managed expectantly. The Journal of Maternal-Fetal \u0026amp; Neonatal Medicine. 2020 Jul 2;33(13):2274\u0026ndash;83. DOI: 10.1080/14767058.2020.1731465 \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Very early PPROM, latency to delivery, maternal outcomes, neonatal outcomes","lastPublishedDoi":"10.21203/rs.3.rs-8242616/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8242616/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePreterm prelabour rupture of membranes (PPROM) is a major obstetric complication associated with adverse obstetric and neonatal outcomes. To reduce uncertainty in gestational-age–specific management and to support evidence-based counselling, large-cohort analyses are essential. \u0026nbsp;In this study, we aimed to evaluate the latency to delivery and maternal and neonatal outcomes through 12 months of \u0026nbsp;corrected age among pregnancies with very early PPROM (22+0–28+0 weeks gestation).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe conducted a single-center retrospective cohort study at SBÜ Zeynep Kamil Women’s and Children’s Diseases Training and Research Hospital between January 2018 and February 2023; the cohort included 167 pregnancies that were diagnosed with PPROM at 22+0 to 28+0 weeks. \u0026nbsp;The neonatal survival analyses included 91 infants managed at our center. Pregnancies were grouped by gestational age at PPROM as 22+0 to 23+6, 24+0 to 25+6 and 26+0 to 28+0 weeks. Latency to delivery, as well as maternal and neonatal outcomes, were compared across gestational age groups. The neonatal endpoints were survival to discharge and survival without major morbidity at 12 months of corrected age.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe mean gestational age at diagnosis was 25.0 weeks. The median latency to delivery was 6 days (IQR, 2–23) and did not differ significantly between the groups (median range 5-9 days; P = 0.896). The mean gestational age at delivery was 27.1 weeks. Maternal outcomes were similar across groups, except for placental abruption and cesarean delivery. Placental abruption and cesarean delivery were more common when PPROM occurred at 24+0–25+6 weeks (P = 0.004 and P = 0.009, respectively). Neonatal survival to discharge was 67.0% (61/91). Survival without major morbidity at 12 months of corrected age was 42.9% (39/91). Both outcomes were highest when PPROM was diagnosed at 26+0 to 28+0 weeks (P = 0.001, P = 0.001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn PPROM at 22+0 to 28+0 weeks the median latency to delivery ranged between 5 and 9 days. An increasing gestational age at PPROM is associated with increased survival and increased survival without severe morbidity. In addition, longer latency was associated with more favourable neonatal outcomes. These data may be important for providing evidence-based counselling and management in very early PPROM.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial registration:\u003c/strong\u003e Not applicable.\u003c/p\u003e","manuscriptTitle":"Outcomes and latency to delivery in preterm prelabour rupture of membranes at 22–28 weeks: a retrospective cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-16 15:02:37","doi":"10.21203/rs.3.rs-8242616/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision 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