Periviable premature rupture of membranes (before 24 weeks gestation): Pregnancy and neonatal outcomes

Periviable premature rupture of membranes (before 24 weeks gestation): Pregnancy and neonatal outcomes | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Periviable premature rupture of membranes (before 24 weeks gestation): Pregnancy and neonatal outcomes Audrey COSSART, Laurent STORME, Louise GHESQUIERE, Véronique HOUFFLIN-DEBARGE, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8174640/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 30 Jan, 2026 Read the published version in European Journal of Pediatrics → Version 1 posted 7 You are reading this latest preprint version Abstract Introduction : This study evaluates neonatal outcomes following periviable premature rupture of membranes (PPROM) before 24 weeks gestation, and identify factors associated with death or severe comorbidities. Methods : A retrospective analysis of pregnancies complicated by PPROM was conducted at the University Hospital of Lille from 2014 to 2019. Maternal and neonatal data until hospital discharge were collected. Results : Among 130 fetuses, 67% were live-born. The rate of medical termination of pregnancy was 8%. Seventy-five percent of those live-born were preterm. About one-third of neonates were admitted to the maternity ward without respiratory failure; 61% of neonates required neonatal intensive care unit admission for prematurity and/or immediate respiratory failure. Of the live-born infants, 90% were discharged from hospital, 74% with no severe comorbidities. Multivariate analysis identified preterm delivery (relative risk [RR] 3.51, 95% confidence interval [CI]: 1.82–6.76) and short latency from PPROM to delivery (RR 8.47, 95% CI: 1.07–66.67) as risk factors for death or severe comorbidities. Conclusion : Parent counseling should consider both current, evolving outcomes, and the unpredictable course of pregnancies complicated by PPROM. Prolonging pregnancy through close monitoring and implementation of current guidelines on neonatal management are essential to reduce adverse outcomes. neonatal outcomes periviable premature rupture of membranes prognosis Figures Figure 1 Figure 2 Figure 3 What is Known PPROM is associated with high rates of neonatal mortality and morbidity. Current literature is limited by small cohort sizes and heterogeneity in management strategies. What is new This large single-center study demonstrates that there has been an improvement PPROM-related neonatal outcomes as a result of advances in perinatal practices, compared to the historical cohort. Short latency from PPROM to delivery and earlier gestational age at delivery were identified as independent risk factors for death or severe morbidity. The study provides updated, real-world data to guide parental counseling and clinical decision-making regarding periviable PPROM. INTRODUCTION Premature rupture of membranes (PROM) is defined as the rupture of the amniotic sac and leakage of amniotic fluid before the onset of labor. PROM is considered ‘periviable’ when it occurs before the threshold for active neonatal management, generally agreed to be 23–24 weeks gestation (WG). Periviable PROM (PPROM) occurs in < 1% of pregnancies. 1 Obstetrical and neonatal outcomes after PPROM are usually considered poor, with major complications including intrauterine infection, procidentia and/or funicular compression, retroplacental hematoma, in utero fetal death, preterm birth with lung hypoplasia-associated severe respiratory failure and pulmonary hypertension, and postnatal death. PPROM management is generally expectant, aiming to prolong pregnancy and reduce risks associated with prematurity. The National College of French Gynecologists and Obstetricians recommends initial hospitalization due to the high risk of delivery within the first 48 hours, identification of intrauterine infection, antibiotic prophylaxis, antenatal corticosteroid administration from 23 WG, magnesium sulfate administration if delivery is imminent before 32 WG, weekly ultrasound monitoring of the amniotic fluid quantity, weekly monitoring of the infectious workup, delivery in a level 3 maternity hospital if rupture occurs before 26 weeks of gestation, and peripartum antibiotic prophylaxis. 2 , 3 These recommendations are based on professional guidelines, and are often extensions of those valid at later gestational ages, given the low levels of scientific evidence concerning the prevention of preterm birth defects. 1 Patients affected by PPROM may consider pregnancy termination. In France, medical termination is strictly regulated and may be performed if “continuation of the pregnancy endangers the health of the mother” or if “there is a strong probability that the unborn child will suffer from a particularly serious condition recognized as incurable at the time of diagnosis.” However, recent advancements in postnatal management make outcome assessments difficult, and challenge their predictions. Additionally, the information medical teams provide patients often varies and is generally pessimistic, despite the importance of accurate prenatal information. Thus, this study aimed at providing further information to those affected by PPROM, based on our experiences. The primary objective was to evaluate fetal outcomes after PROM before 24 WG. Secondary objectives were to identify factors associated with poor prognosis and to describe the health condition of live-born infants following PPROM. Methods This retrospective study was conducted at the University Hospital Center of Lille, France, from January 2014 to December 2019. It included all fetuses affected by PPROM before 24 0/6 WG who were monitored and delivered at the University Hospital of Lille. PPROM diagnosis was based on the presence of vaginal discharge of amniotic fluid reported by the woman and/or observed on clinical examination, and confirmed in uncertain cases by an immunochromatographic test for IGFBP-1 or PAMG-1. Gestational age was defined according to early ultrasound. We obtained the identities of the women and neonates included herein through the hospital coding system. Management was classified, following the guidelines of the National College of French Gynecologists and Obstetricians, as expectant or leading to medical termination of pregnancy. 1 We excluded fetuses unaffected by PROM in cases of multiple pregnancies, pregnancies which resulted in birth within the first 24 hours of PROM that were considered in active labor at PROM onset, and cases in which the PROM diagnosis was later invalidated (e.g., positive immunochromatographic test with clinically inconclusive results, subsequently asymptomatic patient with a normal amniotic fluid quantity). Data were collected from the electronic medical records for each woman and neonate, and from the neonate’s daily charts for those admitted to the neonatal intensive care unit (NICU). PROM was considered spontaneous if it was not preceded by an invasive procedure (cerclage, trophoblast biopsy, or amniocentesis). Amniotic fluid quantity was classified as follows: normal; moderate oligohydramnios (Chamberlain cistern 1–2 cm and/or a Phelan amniotic index 5–8 cm); severe oligohydramnios (cistern < 1 cm and/or an amniotic index < 5 cm); or anhydramnios (total absence of amniotic fluid). 4 , 5 Latency refers to the time interval between PROM and delivery. Histopathological and placenta culture data were also retrieved from laboratory reports. Neonatal management followed a standardized approach, including close monitoring of the infant's adaptation to extrauterine conditions. If admission to the NICU was necessary, pre- and post-ductal SpO2 and transcutaneous PCO2 levels were continuously monitored. A lung-protective strategy was used, with gentle ventilation techniques to minimize volo- and barotrauma, such as using the lowest effective tidal volumes, adjusting inspiratory pressures, and applying high-frequency oscillatory ventilation. Early extubation to noninvasive ventilation modes was promoted whenever possible. Permissive hypercapnia was allowed, maintaining higher levels of carbon dioxide within a safe range, to reduce the need for aggressive ventilation. Additionally, postnatal steroids were administered to prevent severe respiratory conditions and bronchopulmonary dysplasia (BPD; hydrocortisone hemisuccinate 1 mg/Kg/day for 7 days, then 0.5 mg/Kg/day for 3 days), or to facilitate weaning from mechanical ventilation (betamethasone 0.25 mg/kg for 3 days) from 3 weeks after birth. Regular and systematic echocardiographic evaluations were performed to assess pulmonary circulation. In cases of hemodynamically significant patent ductus arteriosus (DA), closure was attempted with medical treatment (ibuprofen, or paracetamol if contraindicated); if unsuccessful, surgery was considered. For pulmonary hypertension, nitric oxide (NO) treatment was rapidly initiated, along with careful management to prevent nociceptive stimuli. In cases of suprasystemic pulmonary hypertension, prostaglandin E1 (PGE1) was used to reopen the DA. Oral sildenafil was added if there was no response to inhaled NO or if prolonged administration of inhaled NO was required. Criteria for admission to kangaroo care on the maternity unit were term ≥34 0/6 WG, weight ≥1800 g, and no need for oxygen therapy. We collected data on the duration of invasive ventilation, noninvasive ventilation, and total oxygen therapy, regardless of the administration mode. Systemic corticosteroid pulmonary therapy was recorded. Diagnoses of early neonatal bacterial infection were confirmed by the presence of microorganisms in the blood culture and suspected if the C-reactive protein (CRP) concentration increased during the first 48 postnatal hours. Secondary bacterial infection was suspected if sepsis was present, CRP concentration increased, or antibiotic therapy was administered for at least 48 hours. Intubated neonates were tested for atypical microbes ( Mycoplasma hominis , Ureaplasma urealyticum ) in tracheal samples. The Bell classification was used for necrotizing enterocolitis (NEC), 6 the Papile classification for intraventricular hemorrhage, 7 and the international classification for retinopathy of prematurity (ROP). 8 Two study groups were compared: infants discharged from the hospital without severe comorbidity versus those with in utero fetal death (excluding medical termination), postnatal deaths, and discharged from the hospital with severe comorbidities. The latter was defined as the presence of at least one of the following conditions: pulmonary hypoplasia, severe BPD, pulmonary arterial hypertension requiring medical treatment at the time of discharge, severe intracranial lesions (intracranial hemorrhage grade III and IV, periventricular leukomalacia), stage II or III NEC, or ROP requiring anti-VEGF and/or laser therapy. The definition of pulmonary hypoplasia requires a formal diagnosis based on autopsy results (lung weight to total weight ratio < 0.012 for infants ≥ 28 WG and < 0.015 for infants < 28 WG); 9 we also considered that a neonate able to achieve a pCO 2 of < 60 mmHg was unlikely to have pulmonary hypoplasia. Severe BPD was defined as the combination of oxygen supplementation for at least 28 days and/or persistent oxygen dependence at 36 weeks corrected age, associated with an FiO 2 ≥30% and/or support by mechanical ventilation or positive expiratory pressure. 10 Sample characteristics are presented as numbers and percentages for categorical variables and as mean ± standard deviation or median [first quartile; third quartile] for continuous variables, based on their distribution. Group characteristics were compared using the chi-square or Fisher’s exact probability test for categorical variables and Student’s t or Wilcoxon / Mann–Whitney tests for continuous variables. Factors associated with risk of poor prognosis were investigated using univariate analysis. Risk factors were calculated with their 95% confidence intervals (CIs). All variables associated with the risk of a poor prognosis with p < 0.05 in the univariate analysis were included in the multivariate logistic regression analysis. The significance level was set at 5%. Statistical analyses were performed using IBM SPSS Statistics for Windows (version 26.0; IBM Corp., Armonk, NY). The database used herein was declared to the National Commission of Informatics and Liberties (number 731/2020). Parents’ non-opposition to the use of neonatal data for research was collected upon admission to the department of neonatology. RESULTS We included a total of 130 fetuses affected by PROM before 24 0/6 WG (Fig. 1 ). None were excluded or lost to follow-up. Table 1 summarizes the maternal and pregnancy sample characteristics. Invasive procedures before PROM were documented in 11% of pregnancies, among which there were four intrauterine fetal demises. The mean GA at PROM was 19.3 ± 3 WG. Medical pregnancy termination was decided in 10 (8%) cases and 35 (28%) fetuses died before or at birth. The earlier the average WG at PROM, the longer the average latency and, consequently, the later the delivery, as shown in Fig. 2 . A total of 85 live births occurred at an average of 31.9 ± 5 WG. The median latency period was 92 days [49–119]; in 94% of cases, latency exceeded 14 days. Intrauterine growth restriction affected 17% of cases. Deformities potentially attributable to low amniotic fluid quantity were observed in nine (7%) cases, including postural asymmetry, valgus or club feet, Potter dysmorphia, and arthrogryposis. Among the 85 live births, 65 (76%) were preterm. Immediate respiratory distress was reported in 53 (62%) cases. NICU admission occurred in n = 52 cases (61%). Table 2 provides a summary of the neonatal data. During the hospital stay, 40 (47%) neonates were intubated and received surfactant administration. The median duration of invasive ventilation was 2 days [0.5–9.2]. The median duration of noninvasive ventilation was 11 days [3–62]. The median total duration of oxygen therapy in all modes of ventilatory support was 62 days [8–94]. Ten neonates were discharged from the hospital with oxygen therapy. Pulmonary arterial hypertension was identified in 24 (28%) neonates. Among these, half had a PaCO2 level < 60 mmHg within the first postnatal hour, and 21 had PaCO2 levels < 60 mmHg within the first 12 postnatal hours. Sildenafil treatment was initiated in three neonates for prolonged pulmonary hypertension, two of whom were still receiving this treatment at discharge. These two had PaCO2 < 60 mmHg before the 6th postnatal hour. PaCO2 < 60 mmHg during the first 6 postnatal hours occurred among 79 (90%) neonates (Fig. 3 ). The median hospitalization duration was 24 days [5–86]. The rate of discharge with severe comorbidity was 25% among live-born infants. The main cause of severe comorbidity was bronchopulmonary dysplasia. During hospitalization, seven (8%) neonates died. Among these, six died while receiving palliative care for severe cerebral lesions (n = 4) or extremely preterm birth associated with major complications (digestive perforation, septic shock) (n = 2). The last infant died at 145 postnatal days from severe bronchopulmonary dysplasia and chronic pulmonary hypertension (Table 3 ). We compared the characteristics of two groups described above (those discharged without severe comorbidities versus those discharged with severe comorbidity or postnatal deaths) (Table 4 ). Univariate analysis showed that the following factors were significantly associated with poor prognosis: amniotic fluid quantity at PROM diagnosis, lowest amniotic fluid quantity during follow-up, duration of latency, term of delivery, history of cervical insufficiency, cerclage during pregnancy, GBS-positive vaginal swab, maternal infection at PROM, CRP concentration at PROM, and antenatal steroid therapy. However, only preterm delivery (relative risk [RR] 3.51, 95% CI: 1.82–6.76) and short latency period (RR 8.47, 95% CI: 1.07–66.67) were retained as significant prognostic factors on multivariate analysis. Term at PROM, amniotic fluid quantity at PROM diagnosis, and the lowest during the follow-up were not significantly associated with prognosis (Table 4 ). No antenatal factors were significant in multivariate analyses comparing the two groups (Table 5 ). DISCUSSION The outcomes of 130 fetuses affected by PROM before 24 WG, and admitted to our university hospital from 2014 to 2019, were analyzed. Two-thirds of pregnancies resulted in live births, among whom more than one-third (38%) had no respiratory failure and were admitted directly to the maternity ward. Prematurity was the main complication, affecting 75% of live births. The rate of immediate neonatal respiratory distress among live births was 61%, with 48% requiring intubation. Pulmonary arterial hypertension occurred among 28% of live births, though it improved within the initial postnatal days. Most live-born infants (68%) were discharged without severe comorbidities. Term at delivery and, consequently, short latency period were the two significant risk factors for severe comorbidities or death. These results are interesting and offer new insights into the outcomes of fetuses affected by PPROM, considering current management strategies for preterm infants. The rate of live births after PPROM (67%) was consistent with Sim’s meta-analysis findings. 11 One-third of the live-born neonates were admitted directly to the maternity ward, which is warranted for neonates weighing > 1800 g and with a gestational age > 34 weeks. To our knowledge, no previous study has reported post-delivery room infant admission. Apart from prematurity, respiratory failure is the main complication reported in the literature. The rate of immediate neonatal respiratory distress was 89% in the study by Simons et al. 12 and 56% in that by Günes et al. 13 Herein, respiratory outcomes were favorable, with most NICU-hospitalized neonates experiencing transient respiratory failure. Early infectious complications were rare herein (only one neonate with a positive blood culture and eight with significant increases in CRP concentrations but negative blood cultures). This contrasts with the studies by Günes et al. 13 and Simons et al., 12 in which suspected early sepsis occurred in 41% and 50% of live-born children, respectively, based on a clinical suspicion of infection, elevated CRP concentration, or leukocyte count. When including only live births, the survival rates at hospital discharge (90%) and without severe comorbidities (74%) were better in our study compared with others’. 11–16 Sim’s meta-analysis reported a survival rate of 59% at discharge, and the rate of discharge without severe comorbidities is < 30% in most studies. 11 The rate of severe comorbidity at discharge was particularly high (78%) in the study by Sorano et al., which may be explained by the earlier threshold for active neonatal management in Japan (as early as 22 WG). 15 In the French EPIPAGE2 study, conducted in 2011, the rate of discharge without severe comorbidities was 39% among only premature neonates born before 35 WG following PROM between 22 and 25 WG. 17 Our multivariate analysis identified preterm delivery and short latency period as risk factors for death or discharge with severe comorbidities. These are interrelated factors, as longer latency leads to later delivery. Some factors appeared to be associated with a worse prognosis in the univariate analysis: anamnios, maternal CRP concentration > 20 mg/L at PROM, cervical insufficiency, and necessity of cervical cerclage. Gestational age at PROM was not associated with a worse prognosis herein. Our results are consistent with the literature with respect to delivery term and duration of latency. 15 , 18 , 19 Studies are conflicting regarding the influence of amniotic fluid quantity on neonatal complications, though these have included rupture after 24 WG. 20–22 Wagner et al. suggested that survival without severe comorbidities depends only on delivery term. 23 Others have emphasized the importance of residual amniotic fluid quantity, which we did not find in multivariate analysis. Intrauterine fetal demise occurs more frequently in pregnancies involving low amniotic fluid quantity. 19 Morbidity has been related predominantly to respiratory distress in pregnancies involving oligohydramnios between 20 and 29 WG. 24 Neurodevelopmental outcomes were not impacted by prolonged oligohydramnios, unlike respiratory morbidity, which was significant in the first 2 postnatal years in Williams’ study of ruptures before 25 WG. 25 Kiver et al. found more pregnancy termination with rupture before 18 WG, which may be related to antenatal evidence that very early rupture is associated with negative outcome. 16 In the EPIPAGE2 cohort study, the rate of survival without severe comorbidities or neurosensory problems was better when PROM occurred at a later term when all fetuses were included in the analysis, but the rate of severe morbidity did not differ according to gestational age at PROM in the analyses of only infants alive at discharge or at 2 years. 17 Numerous studies have demonstrated improved outcomes among premature infants over time, regardless of etiology. 26 – 27 The French EPIPAGE1 and EPIPAGE2 cohort studies, respectively conducted in 1997 and 2011, followed the development of premature infants regardless of the cause of prematurity, to reveal improved outcomes over time. 28 These improvements can be attributed to advancements in medical care, notably the widespread adoption of antenatal corticosteroid therapy, refined management of the pulmonary hypertension, and innovative ventilation techniques. Additionally, our pregnancy termination rate (8%) was lower compared with other reports (ranging from 20–56%). Pulmonary hypoplasia was also uncommon. Azria’s review reported a pulmonary hypoplasia rate ranging from 2–29%, emphasizing the challenge of defining pulmonary hypoplasia, which lacks consensus and varies among authors. 1 As shown in Fig. 1 , with optimal medical management, the average PCO2 and FiO2 levels decrease by the 6th postnatal hour, demonstrating the capacity of the neonatal respiratory system to ensure correct oxygenation and decarboxylation. This highlights the functional and transient aspects of pulmonary complications. The role of the inflammatory/infectious climate associated with prolonged rupture may be important and should be explored to better understand neonatal pathology and improve its management. It is well-known that inflammatory factors can be involved in regulating fetal lung growth and development. Inflammation may stimulate certain pathways that promote accelerated lung maturation. 29 However, inflammation can also contribute to the development of transient pulmonary hypertension. Inflammatory mediators can affect vascular tone and endothelial function in the pulmonary circulation. 30 Limited studies have investigated the prenatal and postnatal dimensions of PPROM. Our sample is similar to others’ regarding the gestational age at PROM (mean 19.3 WG herein, compared with 16.9–23.7 WG in the studies included in Sim’s meta-analysis), the median latency duration (63.5 [16.5–108] days herein, longer than the 7–49-day median reported in Sim’s meta-analysis), and the term of delivery (average 28.8 WG for all pregnancies and 31.7 WG for live births herein, versus 22–29.5 WG in Sim’s meta-analysis including all pregnancies, though some studies did not account for in utero deaths). The 24 WG threshold was chosen because it is the standard for active neonatal management in French centers. While there is a tendency to lower this threshold, doing so requires distinguishing between 22–23 WG and 24 WG, given the resuscitation difficulties in this population. We included the earliest ruptures (before 15 WG) and pregnancies with intrauterine fetal demise or medical termination to avoid overestimating the survival rate, which represents a bias in other studies. Our sample size was relatively large given the rarity of the problem studied. The description of neonatal health status through hospital discharge was exhaustive. Our study was monocentric, at a tertiary-level university perinatal center, which helped avoid biases related to different practices. This type of study is subject to the competitive risk between mortality and morbidity, limited to survivors. Long-term outcomes studies, particularly regarding neurological and respiratory outcomes, are essential. CONCLUSION While PPROM presents a significant risk of prematurity, the potential outcomes remain unpredictable, ranging from poor long-term prognosis, such as bronchopulmonary dysplasia, to normal development. Parental counseling should be individualized, considering the evolving outcomes and the uncertain trajectory of pregnancies complicated by PPROM. This counseling must be tailored to each specific case. Moreover, extending pregnancy through vigilant monitoring and adherence to current neonatal management guidelines is crucial, as it can reduce the risk of adverse outcomes and enhance the likelihood of a healthier outcome for both mother and infant. Declarations Ethics approval and consent to participate This retrospective cohort study involving human participants was in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The national commission of information and liberty (CNIL) approved this study (number 731/2020). Parents’ non-opposition to the use of neonatal data for research was collected upon admission to the department of neonatology. Authors' contributions AC, KLD and MRB contributed to formal analysis and manuscript writing, review, and editing. LS contributed to formal analysis and manuscript review. LG and VHD substantively revised the manuscript. All authors read and approved the final manuscript. Consent for publication Not applicable Availability of data and material The dataset generated and/or analyzed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare no competing interests. Funding This work received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. 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Biomolecules 12:484 Tables Table 1 Maternal and pregnancy characteristics Maternal and pregnancy data, n (%) Maternal age (years), mean ± SD BMI ≥30 kg/m² Primigravida Primiparity Spontaneous pregnancy Twin pregnancy Active smoking Gestational diabetes; requiring insulin therapy Vaginal swab Streptococcus B-positive Antenatal steroids Urinary or vaginal germ at PROM CRP level > 20 mg/L at PROM Leucocytes count > 15 G/L at PROM WG at PROM < 16 0/6 WG at PROM 16 0/6 to 20 6/6 WG at PROM 21 0/6 to 24 0/6 WG at PROM, mean ± SD Normal amniotic fluid quantity at PROM Moderate oligohydramnios at PROM Severe oligohydramnios at PROM Anhydramnios at PROM Moderate oligohydramnios during monitoring Severe oligohydramnios during monitoring Anhydramnios during monitoring Total = 130 30.3 ± 5.7 10 (8%) 27 (21%) 14 (11%) 116 (89%) 17 (13%) 20 (15%) 9 (7%); 7 (5%) 20 (15%) 80 (62%) 8 (6%) 27 (21%) 16 (12%) 26 (20%) 54 (42%) 50 (38%) 19.3 ± 3 73 (57%) 20 (16%) 11 (9%) 23 (18%) 16 (14%) 8 (7%) 42 (36%) Table 2 Peripartum and neonatal characteristics Peripartum and neonatal data, n (%) Delivery term (WG) for the total sample, mean ± SD Delivery term (WG) for live births, mean ± SD Delivery term (WG) for intrauterine fetal demise, mean ± SD Latency duration (day) for live births, mean ± SD Intrauterine fetal demise Medical pregnancy termination Live births Spontaneous labor onset General anesthesia Low or absent amniotic fluid Meconium-stained amniotic fluid; hemorrhagic fluid Tocolysis Magnesium sulfate Prolapse; cord encirclement Retroplacental hematoma Male sex Musculoskeletal deformity Intrauterine growth restriction Vaginal delivery Cephalic presentation Delayed cord clamping Term at birth ≥ 37 0/6 WG Term at birth from 36 6/6 to 35 0/6 WG Term at birth from 34 6/6 to 32 0/6 WG Term at birth from 31 6/6 to 27 0/6 WG Term at birth from 26 6/6 to 22 0/6 WG Birth weight (g), median [IQ] Apgar score < 7 at 1-min Apgar score at 5-min Apgar score at 10-min Respiratory distress syndrome Intubation in the delivery room Admission to NICU Admission directly to maternity ward (including Kangaroo unit) Total = 130 28.5 ± 7 31.9 ± 5 21.3 ± 4 88 [49–118] 35 (27%) 10 (8%) 85 (65%) 67 (52%) 14 (11%) 33 (25%) 3 (2%); 9 (7%) 16 (12%) 25 (19%) 9 (7%); 1 (1%) 13 (10%) 63 (54%) 9 (7%) 19 (17%) Total live births = 85 57 (67%) 62 (73%) 61 (71%) 22 (26%) 15 (17%) 7 (8%) 24 (28%) 19 (22%) 1886 [945–2730] 31 (36%) 19 (22%) 6 (7%) 53 (62%) 40 (47%) 52 (61%) 33 (39%) Table 3 Infant characteristics during hospitalization Infant data during hospital stay, n (%) Spontaneous breathing room air Intubation during hospital stay Surfactant administration Pneumothorax Pulmonary hemorrhage Duration of invasive ventilation (days), median [IQ] Duration of noninvasive ventilation (days), median [IQ] Duration of oxygen therapy (days), median [IQ] Discharge with oxygen therapy Postnatal steroids Hypotension in the first 24 hours Fluid resuscitation in the first 24 hours Vasoactive drugs Pulmonary hypertension Inhaled NO Oral sildenafil PGE1 Medical closure of DA (ibuprofen or paracetamol) Surgical closure of the DA Early antibiotic therapy Confirmed early onset sepsis Significant CRP elevation within the first 48 hours Atypical organisms in tracheal sample Late onset sepsis Necrotizing enterocolitis Isolated digestive perforation Intracranial lesion at day 7 Intracranial lesion at term Retinopathy stage 1 Retinopathy stage 2 Retinopathy stage 3 Anti-VEGF treatment Laser therapy Deafness Length of hospital stay (days), median [IQ] Death during hospitalization Severe comorbidity at discharge including: - Severe bronchopulmonary dysplasia - Treated pulmonary hypertension - Severe necrotizing enterocolitis - Severe retinopathy - Severe intracranial lesion at cranial ultrasound Total = 85 36 (42%) 41 (48%) 41 (48%) 3 (4%) 2 (2%) 2 [0.5–9.2] 11 [3–62] 62 [8–94] 10 (12%) 34 (40%) 13 (15%) 7 (8%) 11 (13%) 24 (28%) 22 (26%) 3 (4%) 1 (1%) 12 (14%) 4 (5%) 50 (59%) 1 (1%) 8 (9%) 6 (7%) 21 (25%) 0 (0%) 3 (4%) 1 (1%) 1 (1%) 1 (1%) 4 (5%) 5 (6%) 4 (5%) 2 (2%) 1 (1%) 24 [5–86] 8 (9%) 21 (25%) 14 (16%) 2 (2%) 0 (0%) 4 (5%) 1 (1%) Table 4 Factors associated with death or severe morbidities in univariate and multivariate analyses Death or severe morbidities Univariate analysis P Multivariate analysis RR; 95% CI Yes (n = 56) No (n = 64) Gestational age at PROM, median [IQ] 14 days 15 [5–49.2] 4 15 9 28 106 [64–127] 1 0 0 63 0.000 8.47; 1.07 – 66.67 Amniotic fluid quantity at PROM Normal Moderate oligohydramnios Severe oligohydramnios Anhydramnios 25 9 7 15 49 8 2 5 0.002 0.76; 0.04–13.69 Monitoring of amniotic fluid quantity Normal Moderate oligohydramnios Severe oligohydramnios Anhydramnios 15 5 3 33 39 11 5 9 0.000 0.37; 0.01–7.62 History of cervical insufficiency 7 1 0.025 0.12; 0.01–0.98 Cervical cerclage 7 1 0.025 0.12; 0.01–0.98 Vaginal swab streptococcus B-positive 8 12 0.001 0.04; 0.01–0.21 Infection at PROM No infection Suspected infection Confirmed infection 27 14 11 44 10 8 0.009 0.11; 0.00–5.42 CRP at PROM 20 mg/L 17 15 17 29 19 7 0.023 0.66; 0.08–0.54 Leucocytes at PROM 15 G/L 22 16 8 33 15 5 0.295 0.80; 0.00–10.7 Antenatal corticotherapy 24 53 0.000 0.04; 0.00–0.08 Term at delivery, median [IQ] 33 0/6 WG 23 [20–26] 36 3 11 6 0 35 [30–37] 0 3 6 13 42 0.000 3.51; 1.82 – 6.76 Table 5 Factors associated with death or severe comorbidities at PROM Death or severe morbidities Multivariate analysis RR; 95% CI Yes (n = 56) No (n = 64) Gestational age at PROM, median [IQ] < 16 0/6 WG 16 0/6 to 20 6/6 WG 21 0/6 to 24 0/6 WG 19 [17–21] 11 27 18 21 [17–22] 12 21 31 0.94; 0.14–6.29 Amniotic fluid quantity at PROM Normal Moderate oligohydramnios Severe oligohydramnios Anhydramnios 25 9 7 15 49 8 2 5 0. 0.01–29.08 Monitoring of amniotic fluid quantity Normal Moderate oligohydramnios Severe oligohydramnios Anhydramnios 15 5 3 33 39 11 5 9 0.06; 0.00–0.59 Infection at PROM No infection Suspected infection Confirmed infection 27 14 11 44 10 8 0. 0.14–2.62 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 30 Jan, 2026 Read the published version in European Journal of Pediatrics → Version 1 posted Editorial decision: Revision requested 30 Dec, 2025 Reviews received at journal 27 Dec, 2025 Reviewers agreed at journal 06 Dec, 2025 Reviewers invited by journal 05 Dec, 2025 Editor assigned by journal 02 Dec, 2025 Submission checks completed at journal 02 Dec, 2025 First submitted to journal 21 Nov, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8174640","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":556300018,"identity":"7d796e82-2811-4b16-a585-8c43e76c65c2","order_by":0,"name":"Audrey COSSART","email":"","orcid":"","institution":"Lille University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Audrey","middleName":"","lastName":"COSSART","suffix":""},{"id":556300019,"identity":"a730cbf7-3519-4039-a177-6cce17f942e6","order_by":1,"name":"Laurent STORME","email":"","orcid":"","institution":"Lille University 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1","display":"","copyAsset":false,"role":"figure","size":301652,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart\u003c/p\u003e","description":"","filename":"Picture1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8174640/v1/f4211b3842db42073412057f.jpg"},{"id":97899785,"identity":"40aa529c-3a94-49f8-803f-e8d3e99c9ed5","added_by":"auto","created_at":"2025-12-10 15:44:53","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":182726,"visible":true,"origin":"","legend":"\u003cp\u003eLatency period following term rupture of membranes\u003c/p\u003e","description":"","filename":"Picture2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8174640/v1/5d616629a0bf96719275d76c.jpg"},{"id":97874048,"identity":"10af1e49-975e-4381-b0f8-3b04a8846a62","added_by":"auto","created_at":"2025-12-10 10:50:23","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":175883,"visible":true,"origin":"","legend":"\u003cp\u003eChanges in FiO2, pCO2, and lactate levels during NICU admission.\u003c/p\u003e","description":"","filename":"Picture3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8174640/v1/e7e1900f0240acb95f28a4d2.jpg"},{"id":101691056,"identity":"c68b3c5f-2c51-4ede-a724-4db77bff4f79","added_by":"auto","created_at":"2026-02-02 16:11:52","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1674903,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8174640/v1/4e6eaf09-14ef-41e9-acf3-23add3e841e9.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Periviable premature rupture of membranes (before 24 weeks gestation): Pregnancy and neonatal outcomes","fulltext":[{"header":"What is Known","content":"\u003cul\u003e\n \u003cli\u003ePPROM is associated with high rates of neonatal mortality and morbidity.\u003c/li\u003e\n \u003cli\u003eCurrent literature is limited by small cohort sizes and heterogeneity in management strategies.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eWhat is new\u003c/strong\u003e\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eThis large single-center study demonstrates that there has been an improvement PPROM-related neonatal outcomes as a result of advances in perinatal practices, compared to the historical cohort.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eShort latency from PPROM to delivery and earlier gestational age at delivery were identified as independent risk factors for death or severe morbidity.\u003c/li\u003e\n \u003cli\u003eThe study provides updated, real-world data to guide parental counseling and clinical decision-making regarding periviable PPROM.\u003csup\u003e\u003cbr\u003e\u0026nbsp;\u003c/sup\u003e\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"INTRODUCTION","content":"\u003cp\u003ePremature rupture of membranes (PROM) is defined as the rupture of the amniotic sac and leakage of amniotic fluid before the onset of labor. PROM is considered \u0026lsquo;periviable\u0026rsquo; when it occurs before the threshold for active neonatal management, generally agreed to be 23\u0026ndash;24 weeks gestation (WG). Periviable PROM (PPROM) occurs in \u0026lt;\u0026thinsp;1% of pregnancies.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e Obstetrical and neonatal outcomes after PPROM are usually considered poor, with major complications including intrauterine infection, procidentia and/or funicular compression, retroplacental hematoma, in utero fetal death, preterm birth with lung hypoplasia-associated severe respiratory failure and pulmonary hypertension, and postnatal death.\u003c/p\u003e\u003cp\u003ePPROM management is generally expectant, aiming to prolong pregnancy and reduce risks associated with prematurity. The National College of French Gynecologists and Obstetricians recommends initial hospitalization due to the high risk of delivery within the first 48 hours, identification of intrauterine infection, antibiotic prophylaxis, antenatal corticosteroid administration from 23 WG, magnesium sulfate administration if delivery is imminent before 32 WG, weekly ultrasound monitoring of the amniotic fluid quantity, weekly monitoring of the infectious workup, delivery in a level 3 maternity hospital if rupture occurs before 26 weeks of gestation, and peripartum antibiotic prophylaxis.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e These recommendations are based on professional guidelines, and are often extensions of those valid at later gestational ages, given the low levels of scientific evidence concerning the prevention of preterm birth defects.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003ePatients affected by PPROM may consider pregnancy termination. In France, medical termination is strictly regulated and may be performed if \u0026ldquo;continuation of the pregnancy endangers the health of the mother\u0026rdquo; or if \u0026ldquo;there is a strong probability that the unborn child will suffer from a particularly serious condition recognized as incurable at the time of diagnosis.\u0026rdquo;\u003c/p\u003e\u003cp\u003eHowever, recent advancements in postnatal management make outcome assessments difficult, and challenge their predictions. Additionally, the information medical teams provide patients often varies and is generally pessimistic, despite the importance of accurate prenatal information. Thus, this study aimed at providing further information to those affected by PPROM, based on our experiences. The primary objective was to evaluate fetal outcomes after PROM before 24 WG. Secondary objectives were to identify factors associated with poor prognosis and to describe the health condition of live-born infants following PPROM.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis retrospective study was conducted at the University Hospital Center of Lille, France, from January 2014 to December 2019. It included all fetuses affected by PPROM before 24\u003csup\u003e0/6\u003c/sup\u003e WG who were monitored and delivered at the University Hospital of Lille. PPROM diagnosis was based on the presence of vaginal discharge of amniotic fluid reported by the woman and/or observed on clinical examination, and confirmed in uncertain cases by an immunochromatographic test for IGFBP-1 or PAMG-1.\u003c/p\u003e\u003cp\u003eGestational age was defined according to early ultrasound. We obtained the identities of the women and neonates included herein through the hospital coding system. Management was classified, following the guidelines of the National College of French Gynecologists and Obstetricians, as expectant or leading to medical termination of pregnancy.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eWe excluded fetuses unaffected by PROM in cases of multiple pregnancies, pregnancies which resulted in birth within the first 24 hours of PROM that were considered in active labor at PROM onset, and cases in which the PROM diagnosis was later invalidated (e.g., positive immunochromatographic test with clinically inconclusive results, subsequently asymptomatic patient with a normal amniotic fluid quantity). Data were collected from the electronic medical records for each woman and neonate, and from the neonate\u0026rsquo;s daily charts for those admitted to the neonatal intensive care unit (NICU).\u003c/p\u003e\u003cp\u003ePROM was considered spontaneous if it was not preceded by an invasive procedure (cerclage, trophoblast biopsy, or amniocentesis). Amniotic fluid quantity was classified as follows: normal; moderate oligohydramnios (Chamberlain cistern 1\u0026ndash;2 cm and/or a Phelan amniotic index 5\u0026ndash;8 cm); severe oligohydramnios (cistern\u0026thinsp;\u0026lt;\u0026thinsp;1 cm and/or an amniotic index\u0026thinsp;\u0026lt;\u0026thinsp;5 cm); or anhydramnios (total absence of amniotic fluid).\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e Latency refers to the time interval between PROM and delivery. Histopathological and placenta culture data were also retrieved from laboratory reports.\u003c/p\u003e\u003cp\u003eNeonatal management followed a standardized approach, including close monitoring of the infant's adaptation to extrauterine conditions. If admission to the NICU was necessary, pre- and post-ductal SpO2 and transcutaneous PCO2 levels were continuously monitored. A lung-protective strategy was used, with gentle ventilation techniques to minimize volo- and barotrauma, such as using the lowest effective tidal volumes, adjusting inspiratory pressures, and applying high-frequency oscillatory ventilation. Early extubation to noninvasive ventilation modes was promoted whenever possible. Permissive hypercapnia was allowed, maintaining higher levels of carbon dioxide within a safe range, to reduce the need for aggressive ventilation. Additionally, postnatal steroids were administered to prevent severe respiratory conditions and bronchopulmonary dysplasia (BPD; hydrocortisone hemisuccinate 1 mg/Kg/day for 7 days, then 0.5 mg/Kg/day for 3 days), or to facilitate weaning from mechanical ventilation (betamethasone 0.25 mg/kg for 3 days) from 3 weeks after birth. Regular and systematic echocardiographic evaluations were performed to assess pulmonary circulation. In cases of hemodynamically significant patent ductus arteriosus (DA), closure was attempted with medical treatment (ibuprofen, or paracetamol if contraindicated); if unsuccessful, surgery was considered. For pulmonary hypertension, nitric oxide (NO) treatment was rapidly initiated, along with careful management to prevent nociceptive stimuli. In cases of suprasystemic pulmonary hypertension, prostaglandin E1 (PGE1) was used to reopen the DA. Oral sildenafil was added if there was no response to inhaled NO or if prolonged administration of inhaled NO was required.\u003c/p\u003e\u003cp\u003eCriteria for admission to kangaroo care on the maternity unit were term \u0026ge;34\u003csup\u003e0/6\u003c/sup\u003e WG, weight \u0026ge;1800 g, and no need for oxygen therapy. We collected data on the duration of invasive ventilation, noninvasive ventilation, and total oxygen therapy, regardless of the administration mode. Systemic corticosteroid pulmonary therapy was recorded. Diagnoses of early neonatal bacterial infection were confirmed by the presence of microorganisms in the blood culture and suspected if the C-reactive protein (CRP) concentration increased during the first 48 postnatal hours. Secondary bacterial infection was suspected if sepsis was present, CRP concentration increased, or antibiotic therapy was administered for at least 48 hours. Intubated neonates were tested for atypical microbes (\u003cem\u003eMycoplasma hominis\u003c/em\u003e, \u003cem\u003eUreaplasma urealyticum\u003c/em\u003e) in tracheal samples. The Bell classification was used for necrotizing enterocolitis (NEC),\u003csup\u003e6\u003c/sup\u003e the Papile classification for intraventricular hemorrhage,\u003csup\u003e7\u003c/sup\u003e and the international classification for retinopathy of prematurity (ROP).\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eTwo study groups were compared: infants discharged from the hospital without severe comorbidity versus those with in utero fetal death (excluding medical termination), postnatal deaths, and discharged from the hospital with severe comorbidities. The latter was defined as the presence of at least one of the following conditions: pulmonary hypoplasia, severe BPD, pulmonary arterial hypertension requiring medical treatment at the time of discharge, severe intracranial lesions (intracranial hemorrhage grade III and IV, periventricular leukomalacia), stage II or III NEC, or ROP requiring anti-VEGF and/or laser therapy. The definition of pulmonary hypoplasia requires a formal diagnosis based on autopsy results (lung weight to total weight ratio\u0026thinsp;\u0026lt;\u0026thinsp;0.012 for infants\u0026thinsp;\u0026ge;\u0026thinsp;28 WG and \u0026lt;\u0026thinsp;0.015 for infants\u0026thinsp;\u0026lt;\u0026thinsp;28 WG);\u003csup\u003e9\u003c/sup\u003e we also considered that a neonate able to achieve a pCO\u003csub\u003e2\u003c/sub\u003e of \u0026lt;\u0026thinsp;60 mmHg was unlikely to have pulmonary hypoplasia. Severe BPD was defined as the combination of oxygen supplementation for at least 28 days and/or persistent oxygen dependence at 36 weeks corrected age, associated with an FiO\u003csub\u003e2\u003c/sub\u003e \u0026ge;30% and/or support by mechanical ventilation or positive expiratory pressure.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eSample characteristics are presented as numbers and percentages for categorical variables and as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or median [first quartile; third quartile] for continuous variables, based on their distribution. Group characteristics were compared using the chi-square or Fisher\u0026rsquo;s exact probability test for categorical variables and Student\u0026rsquo;s t or Wilcoxon / Mann\u0026ndash;Whitney tests for continuous variables. Factors associated with risk of poor prognosis were investigated using univariate analysis. Risk factors were calculated with their 95% confidence intervals (CIs). All variables associated with the risk of a poor prognosis with p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 in the univariate analysis were included in the multivariate logistic regression analysis. The significance level was set at 5%. Statistical analyses were performed using IBM SPSS Statistics for Windows (version 26.0; IBM Corp., Armonk, NY).\u003c/p\u003e\u003cp\u003eThe database used herein was declared to the National Commission of Informatics and Liberties (number 731/2020). Parents\u0026rsquo; non-opposition to the use of neonatal data for research was collected upon admission to the department of neonatology.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eWe included a total of 130 fetuses affected by PROM before 24\u003csup\u003e0/6\u003c/sup\u003e WG (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). None were excluded or lost to follow-up. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e summarizes the maternal and pregnancy sample characteristics.\u003c/p\u003e\u003cp\u003eInvasive procedures before PROM were documented in 11% of pregnancies, among which there were four intrauterine fetal demises. The mean GA at PROM was 19.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3 WG. Medical pregnancy termination was decided in 10 (8%) cases and 35 (28%) fetuses died before or at birth. The earlier the average WG at PROM, the longer the average latency and, consequently, the later the delivery, as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\u003cp\u003eA total of 85 live births occurred at an average of 31.9\u0026thinsp;\u0026plusmn;\u0026thinsp;5 WG. The median latency period was 92 days [49\u0026ndash;119]; in 94% of cases, latency exceeded 14 days.\u003c/p\u003e\u003cp\u003eIntrauterine growth restriction affected 17% of cases. Deformities potentially attributable to low amniotic fluid quantity were observed in nine (7%) cases, including postural asymmetry, valgus or club feet, Potter dysmorphia, and arthrogryposis. Among the 85 live births, 65 (76%) were preterm. Immediate respiratory distress was reported in 53 (62%) cases. NICU admission occurred in n\u0026thinsp;=\u0026thinsp;52 cases (61%). Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e provides a summary of the neonatal data.\u003c/p\u003e\u003cp\u003eDuring the hospital stay, 40 (47%) neonates were intubated and received surfactant administration. The median duration of invasive ventilation was 2 days [0.5\u0026ndash;9.2]. The median duration of noninvasive ventilation was 11 days [3\u0026ndash;62]. The median total duration of oxygen therapy in all modes of ventilatory support was 62 days [8\u0026ndash;94]. Ten neonates were discharged from the hospital with oxygen therapy.\u003c/p\u003e\u003cp\u003ePulmonary arterial hypertension was identified in 24 (28%) neonates. Among these, half had a PaCO2 level\u0026thinsp;\u0026lt;\u0026thinsp;60 mmHg within the first postnatal hour, and 21 had PaCO2 levels\u0026thinsp;\u0026lt;\u0026thinsp;60 mmHg within the first 12 postnatal hours. Sildenafil treatment was initiated in three neonates for prolonged pulmonary hypertension, two of whom were still receiving this treatment at discharge. These two had PaCO2\u0026thinsp;\u0026lt;\u0026thinsp;60 mmHg before the 6th postnatal hour. PaCO2\u0026thinsp;\u0026lt;\u0026thinsp;60 mmHg during the first 6 postnatal hours occurred among 79 (90%) neonates (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe median hospitalization duration was 24 days [5\u0026ndash;86]. The rate of discharge with severe comorbidity was 25% among live-born infants. The main cause of severe comorbidity was bronchopulmonary dysplasia.\u003c/p\u003e\u003cp\u003eDuring hospitalization, seven (8%) neonates died. Among these, six died while receiving palliative care for severe cerebral lesions (n\u0026thinsp;=\u0026thinsp;4) or extremely preterm birth associated with major complications (digestive perforation, septic shock) (n\u0026thinsp;=\u0026thinsp;2). The last infant died at 145 postnatal days from severe bronchopulmonary dysplasia and chronic pulmonary hypertension (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eWe compared the characteristics of two groups described above (those discharged without severe comorbidities versus those discharged with severe comorbidity or postnatal deaths) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Univariate analysis showed that the following factors were significantly associated with poor prognosis: amniotic fluid quantity at PROM diagnosis, lowest amniotic fluid quantity during follow-up, duration of latency, term of delivery, history of cervical insufficiency, cerclage during pregnancy, GBS-positive vaginal swab, maternal infection at PROM, CRP concentration at PROM, and antenatal steroid therapy. However, only preterm delivery (relative risk [RR] 3.51, 95% CI: 1.82\u0026ndash;6.76) and short latency period (RR 8.47, 95% CI: 1.07\u0026ndash;66.67) were retained as significant prognostic factors on multivariate analysis. Term at PROM, amniotic fluid quantity at PROM diagnosis, and the lowest during the follow-up were not significantly associated with prognosis (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). No antenatal factors were significant in multivariate analyses comparing the two groups (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThe outcomes of 130 fetuses affected by PROM before 24 WG, and admitted to our university hospital from 2014 to 2019, were analyzed. Two-thirds of pregnancies resulted in live births, among whom more than one-third (38%) had no respiratory failure and were admitted directly to the maternity ward. Prematurity was the main complication, affecting 75% of live births. The rate of immediate neonatal respiratory distress among live births was 61%, with 48% requiring intubation. Pulmonary arterial hypertension occurred among 28% of live births, though it improved within the initial postnatal days. Most live-born infants (68%) were discharged without severe comorbidities. Term at delivery and, consequently, short latency period were the two significant risk factors for severe comorbidities or death.\u003c/p\u003e\u003cp\u003eThese results are interesting and offer new insights into the outcomes of fetuses affected by PPROM, considering current management strategies for preterm infants. The rate of live births after PPROM (67%) was consistent with Sim\u0026rsquo;s meta-analysis findings.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e One-third of the live-born neonates were admitted directly to the maternity ward, which is warranted for neonates weighing\u0026thinsp;\u0026gt;\u0026thinsp;1800 g and with a gestational age\u0026thinsp;\u0026gt;\u0026thinsp;34 weeks. To our knowledge, no previous study has reported post-delivery room infant admission. Apart from prematurity, respiratory failure is the main complication reported in the literature. The rate of immediate neonatal respiratory distress was 89% in the study by Simons et al.\u003csup\u003e12\u003c/sup\u003e and 56% in that by G\u0026uuml;nes et al.\u003csup\u003e13\u003c/sup\u003e Herein, respiratory outcomes were favorable, with most NICU-hospitalized neonates experiencing transient respiratory failure. Early infectious complications were rare herein (only one neonate with a positive blood culture and eight with significant increases in CRP concentrations but negative blood cultures). This contrasts with the studies by G\u0026uuml;nes et al.\u003csup\u003e13\u003c/sup\u003e and Simons et al.,\u003csup\u003e12\u003c/sup\u003e in which suspected early sepsis occurred in 41% and 50% of live-born children, respectively, based on a clinical suspicion of infection, elevated CRP concentration, or leukocyte count. When including only live births, the survival rates at hospital discharge (90%) and without severe comorbidities (74%) were better in our study compared with others\u0026rsquo;.\u003csup\u003e11\u0026ndash;16\u003c/sup\u003e Sim\u0026rsquo;s meta-analysis reported a survival rate of 59% at discharge, and the rate of discharge without severe comorbidities is \u0026lt;\u0026thinsp;30% in most studies.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e The rate of severe comorbidity at discharge was particularly high (78%) in the study by Sorano et al., which may be explained by the earlier threshold for active neonatal management in Japan (as early as 22 WG).\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e In the French EPIPAGE2 study, conducted in 2011, the rate of discharge without severe comorbidities was 39% among only premature neonates born before 35 WG following PROM between 22 and 25 WG.\u003csup\u003e17\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eOur multivariate analysis identified preterm delivery and short latency period as risk factors for death or discharge with severe comorbidities. These are interrelated factors, as longer latency leads to later delivery. Some factors appeared to be associated with a worse prognosis in the univariate analysis: anamnios, maternal CRP concentration\u0026thinsp;\u0026gt;\u0026thinsp;20 mg/L at PROM, cervical insufficiency, and necessity of cervical cerclage. Gestational age at PROM was not associated with a worse prognosis herein. Our results are consistent with the literature with respect to delivery term and duration of latency.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e,\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e,\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e Studies are conflicting regarding the influence of amniotic fluid quantity on neonatal complications, though these have included rupture after 24 WG.\u003csup\u003e20\u0026ndash;22\u003c/sup\u003e Wagner et al. suggested that survival without severe comorbidities depends only on delivery term.\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e Others have emphasized the importance of residual amniotic fluid quantity, which we did not find in multivariate analysis. Intrauterine fetal demise occurs more frequently in pregnancies involving low amniotic fluid quantity.\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e Morbidity has been related predominantly to respiratory distress in pregnancies involving oligohydramnios between 20 and 29 WG.\u003csup\u003e24\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eNeurodevelopmental outcomes were not impacted by prolonged oligohydramnios, unlike respiratory morbidity, which was significant in the first 2 postnatal years in Williams\u0026rsquo; study of ruptures before 25 WG.\u003csup\u003e25\u003c/sup\u003e Kiver et al. found more pregnancy termination with rupture before 18 WG, which may be related to antenatal evidence that very early rupture is associated with negative outcome.\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e In the EPIPAGE2 cohort study, the rate of survival without severe comorbidities or neurosensory problems was better when PROM occurred at a later term when all fetuses were included in the analysis, but the rate of severe morbidity did not differ according to gestational age at PROM in the analyses of only infants alive at discharge or at 2 years.\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eNumerous studies have demonstrated improved outcomes among premature infants over time, regardless of etiology.\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e The French EPIPAGE1 and EPIPAGE2 cohort studies, respectively conducted in 1997 and 2011, followed the development of premature infants regardless of the cause of prematurity, to reveal improved outcomes over time.\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e These improvements can be attributed to advancements in medical care, notably the widespread adoption of antenatal corticosteroid therapy, refined management of the pulmonary hypertension, and innovative ventilation techniques. Additionally, our pregnancy termination rate (8%) was lower compared with other reports (ranging from 20\u0026ndash;56%).\u003c/p\u003e\u003cp\u003ePulmonary hypoplasia was also uncommon. Azria\u0026rsquo;s review reported a pulmonary hypoplasia rate ranging from 2\u0026ndash;29%, emphasizing the challenge of defining pulmonary hypoplasia, which lacks consensus and varies among authors.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e As shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, with optimal medical management, the average PCO2 and FiO2 levels decrease by the 6th postnatal hour, demonstrating the capacity of the neonatal respiratory system to ensure correct oxygenation and decarboxylation. This highlights the functional and transient aspects of pulmonary complications. The role of the inflammatory/infectious climate associated with prolonged rupture may be important and should be explored to better understand neonatal pathology and improve its management. It is well-known that inflammatory factors can be involved in regulating fetal lung growth and development. Inflammation may stimulate certain pathways that promote accelerated lung maturation.\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e However, inflammation can also contribute to the development of transient pulmonary hypertension. Inflammatory mediators can affect vascular tone and endothelial function in the pulmonary circulation.\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eLimited studies have investigated the prenatal and postnatal dimensions of PPROM. Our sample is similar to others\u0026rsquo; regarding the gestational age at PROM (mean 19.3 WG herein, compared with 16.9\u0026ndash;23.7 WG in the studies included in Sim\u0026rsquo;s meta-analysis), the median latency duration (63.5 [16.5\u0026ndash;108] days herein, longer than the 7\u0026ndash;49-day median reported in Sim\u0026rsquo;s meta-analysis), and the term of delivery (average 28.8 WG for all pregnancies and 31.7 WG for live births herein, versus 22\u0026ndash;29.5 WG in Sim\u0026rsquo;s meta-analysis including all pregnancies, though some studies did not account for in utero deaths).\u003c/p\u003e\u003cp\u003eThe 24 WG threshold was chosen because it is the standard for active neonatal management in French centers. While there is a tendency to lower this threshold, doing so requires distinguishing between 22\u0026ndash;23 WG and 24 WG, given the resuscitation difficulties in this population. We included the earliest ruptures (before 15 WG) and pregnancies with intrauterine fetal demise or medical termination to avoid overestimating the survival rate, which represents a bias in other studies. Our sample size was relatively large given the rarity of the problem studied. The description of neonatal health status through hospital discharge was exhaustive. Our study was monocentric, at a tertiary-level university perinatal center, which helped avoid biases related to different practices. This type of study is subject to the competitive risk between mortality and morbidity, limited to survivors. Long-term outcomes studies, particularly regarding neurological and respiratory outcomes, are essential.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eWhile PPROM presents a significant risk of prematurity, the potential outcomes remain unpredictable, ranging from poor long-term prognosis, such as bronchopulmonary dysplasia, to normal development. Parental counseling should be individualized, considering the evolving outcomes and the uncertain trajectory of pregnancies complicated by PPROM. This counseling must be tailored to each specific case. Moreover, extending pregnancy through vigilant monitoring and adherence to current neonatal management guidelines is crucial, as it can reduce the risk of adverse outcomes and enhance the likelihood of a healthier outcome for both mother and infant.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective cohort study involving human participants was in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The national commission of information and liberty (CNIL) approved this study (number\u0026nbsp;731/2020). Parents’ non-opposition to the use of neonatal data for research was collected upon admission to the department of neonatology.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAC, KLD and MRB contributed to formal analysis and manuscript writing, review, and editing. LS contributed to formal analysis and manuscript review. LG and VHD substantively revised the manuscript. All authors read and approved the final manuscript.\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 material\u003cbr\u003e\u003c/strong\u003eThe dataset generated and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003cbr\u003e\u003c/strong\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003cbr\u003e\u003c/strong\u003eThis work received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAzria E (2018) Antenatal management in case of preterm premature rupture of membranes before fetal viability: CNGOF Preterm Premature Rupture of Membranes Guidelines. Gynecol Obstet Fertil Senol 46:1076\u0026ndash;1088\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKayem G, Sentilhes L, Senat MV, Schmitz T (2018) Preterm Premature Rupture of Membranes: CNGOF Guidelines for Clinical Practice - Introduction. Gynecol Obstet Fertil Senol 46:994\u0026ndash;995\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSchmitz T et al (2019) Preterm premature rupture of the membranes: Guidelines for clinical practice from the French College of Gynaecologists and Obstetricians (CNGOF). Eur J Obstet Gynecol Reprod Biol 236:1\u0026ndash;6\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChamberlain PF, Manning FA, Morrison I, Harman CR, Lange IR (1984) Ultrasound evaluation of amniotic fluid I. The relationship of marginal and decreased amniotic fluid volumes to perinatal outcome. Am J Obstet Gynecol 150:245\u0026ndash;249\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePhelan JP, Smith CV, Broussard P, Small M (1987) Amniotic fluid volume assessment with the four-quadrant technique at 36\u0026ndash;42 weeks\u0026rsquo; gestation. J Reprod Med 32:540\u0026ndash;542\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBell MJ et al (1978) Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg 187:1\u0026ndash;7\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePapile LA, Burstein J, Burstein R, Koffler H (1978) Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr 92:529\u0026ndash;534\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eInternational Committee for the Classification of Retinopathy of Prematurity (2005) The International Classification of Retinopathy of Prematurity revisited. Arch Ophthalmol 123:991\u0026ndash;999\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDe Paepe ME, Friedman RM, Gundogan F, Pinar H (2005) Postmortem lung weight/body weight standards for term and preterm infants. Pediatr Pulmonol 40:445\u0026ndash;448\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEhrenkranz RA et al (2005) Validation of the National Institutes of Health consensus definition of bronchopulmonary dysplasia. Pediatrics 116:1353\u0026ndash;1360\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSim WH, Araujo J\u0026uacute;nior E, Da Silva Costa F, Sheehan PM (2017) Maternal and neonatal outcomes following expectant management of preterm prelabour rupture of membranes before viability. J Perinat Med 45:29\u0026ndash;44\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSimons NE et al (2021) Maternal, perinatal and childhood outcomes of the PPROMEXIL-III cohort: Pregnancies complicated by previable prelabor rupture of membranes. Eur J Obstet Gynecol Reprod Biol 265:44\u0026ndash;53\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eG\u0026uuml;nes A et al (2022) Predicting previable preterm premature rupture of membranes (pPPROM) before 24 weeks: maternal and fetal/neonatal risk factors for survival. J Obstet Gynaecol 42:597\u0026ndash;606\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKibel M et al (2016) Outcomes of pregnancies complicated by preterm premature rupture of membranes between 20 and 24 Weeks of Gestation. Obstet Gynecol 128:313\u0026ndash;320\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSorano S, Fukuoka M, Kawakami K, Momohara Y (2020) Prognosis of preterm premature rupture of membranes between 20 and 24 weeks of gestation: A retrospective cohort study. Eur J Obstet Gynecol Reprod Biol X 5:100102\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKiver V, Boos V, Thomas A, Henrich W, Weichert A (2018) Perinatal outcomes after previable preterm premature rupture of membranes before 24 weeks of gestation. J Perinat Med 46:555\u0026ndash;565\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLorthe E et al (2018) 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). \u003cem\u003eAm. J. Obstet. Gynecol\u003c/em\u003e. 219, 298.e1-298.e14\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBrumbaugh JE et al (2014) Neonatal survival after prolonged preterm premature rupture of membranes before 24 weeks of gestation. Obstet Gynecol 124:992\u0026ndash;998\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePylypjuk C, Majeau L (2021) Perinatal outcomes and influence of amniotic fluid volume following previable, preterm prelabor rupture of membranes (pPPROM): A historical cohort study. Int J Womens Health 13:627\u0026ndash;637\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAshwal E et al (2014) The association between isolated oligohydramnios at term and pregnancy outcome. Arch Gynecol Obstet 290:875\u0026ndash;881\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eVoxman EG, Tran S (2022) Wing \u0026amp; D.A. Low amniotic fluid index as a predictor of adverse perinatal outcome. J Perinatol 22:282\u0026ndash;285\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKansara VM, Kadakar KD, Chikani AS, Pateliya PA (2022) The association between isolated oligohydramnios at term and pregnancy outcome and perinatal outcome in case of isolated oligohydramnosis: a retrospective analysis. Int J Reprod Contracept Obstet Gynecol 11:136\u0026ndash;140\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWagner P et al (2016) Outcome of pregnancies with spontaneous PPROM before 24\u0026thinsp;+\u0026thinsp;0 weeks\u0026rsquo; gestation. Eur J Obstet Gynecol Reprod Biol 203:121\u0026ndash;126\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWeiner E et al (2019) Amniotic fluid volume at presentation with early preterm prelabor rupture of membranes and association with severe neonatal respiratory morbidity. Ultrasound Obstet Gynecol 54:767\u0026ndash;773\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWilliams O, Michel B, Hutchings G, Debauche C, Hubinont C (2012) Two-year neonatal outcome following PPROM prior to 25 weeks with a prolonged period of oligohydramnios. Early Hum Dev 88:657\u0026ndash;661\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSheng L et al (2024) Quality improvement in the golden hour for premature infants: a scoping review. BMC Pediatr 24:88\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJohnson S, Marlow N (2017) Early and long-term outcome of infants born extremely preterm. Arch Dis Child 102:97\u0026ndash;102\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAncel PY et al (2015) Survival and morbidity of preterm children born at 22 through 34 weeks\u0026rsquo; gestation in France in 2011: results of the EPIPAGE-2 cohort study. JAMA Pediatr 169:230\u0026ndash;238\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJobe AH, Ikegami M (2001) Antenatal infection/inflammation and postnatal lung maturation and injury. Respir Res 2:27\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSantos-Gomes J, Le Ribeuz H, Br\u0026aacute;s-Silva C, Antigny F, Ad\u0026atilde;o R (2022) Role of ion channel remodeling in endothelial dysfunction induced by pulmonary arterial hypertension. Biomolecules 12:484\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\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\u003eMaternal and pregnancy characteristics\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\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMaternal and pregnancy data, n (%)\u003c/b\u003e\u003c/p\u003e\u003cp\u003eMaternal age (years), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003cp\u003eBMI \u0026ge;30 kg/m\u0026sup2;\u003c/p\u003e\u003cp\u003ePrimigravida\u003c/p\u003e\u003cp\u003ePrimiparity\u003c/p\u003e\u003cp\u003eSpontaneous pregnancy\u003c/p\u003e\u003cp\u003eTwin pregnancy\u003c/p\u003e\u003cp\u003eActive smoking\u003c/p\u003e\u003cp\u003eGestational diabetes; requiring insulin therapy\u003c/p\u003e\u003cp\u003eVaginal swab Streptococcus B-positive\u003c/p\u003e\u003cp\u003eAntenatal steroids\u003c/p\u003e\u003cp\u003eUrinary or vaginal germ at PROM\u003c/p\u003e\u003cp\u003eCRP level\u0026thinsp;\u0026gt;\u0026thinsp;20 mg/L at PROM\u003c/p\u003e\u003cp\u003eLeucocytes count\u0026thinsp;\u0026gt;\u0026thinsp;15 G/L at PROM\u003c/p\u003e\u003cp\u003eWG at PROM\u0026thinsp;\u0026lt;\u0026thinsp;16\u003csup\u003e0/6\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eWG at PROM 16\u003csup\u003e0/6\u003c/sup\u003e to 20\u003csup\u003e6/6\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eWG at PROM 21\u003csup\u003e0/6\u003c/sup\u003e to 24\u003csup\u003e0/6\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eWG at PROM, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003cp\u003eNormal amniotic fluid quantity at PROM\u003c/p\u003e\u003cp\u003eModerate oligohydramnios at PROM\u003c/p\u003e\u003cp\u003eSevere oligohydramnios at PROM\u003c/p\u003e\u003cp\u003eAnhydramnios at PROM\u003c/p\u003e\u003cp\u003eModerate oligohydramnios during monitoring\u003c/p\u003e\u003cp\u003eSevere oligohydramnios during monitoring\u003c/p\u003e\u003cp\u003eAnhydramnios during monitoring\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eTotal\u0026thinsp;=\u0026thinsp;130\u003c/b\u003e\u003c/p\u003e\u003cp\u003e30.3\u0026thinsp;\u0026plusmn;\u0026thinsp;5.7\u003c/p\u003e\u003cp\u003e10 (8%)\u003c/p\u003e\u003cp\u003e27 (21%)\u003c/p\u003e\u003cp\u003e14 (11%)\u003c/p\u003e\u003cp\u003e116 (89%)\u003c/p\u003e\u003cp\u003e17 (13%)\u003c/p\u003e\u003cp\u003e20 (15%)\u003c/p\u003e\u003cp\u003e9 (7%); 7 (5%)\u003c/p\u003e\u003cp\u003e20 (15%)\u003c/p\u003e\u003cp\u003e80 (62%)\u003c/p\u003e\u003cp\u003e8 (6%)\u003c/p\u003e\u003cp\u003e27 (21%)\u003c/p\u003e\u003cp\u003e16 (12%)\u003c/p\u003e\u003cp\u003e26 (20%)\u003c/p\u003e\u003cp\u003e54 (42%)\u003c/p\u003e\u003cp\u003e50 (38%)\u003c/p\u003e\u003cp\u003e19.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3\u003c/p\u003e\u003cp\u003e73 (57%)\u003c/p\u003e\u003cp\u003e20 (16%)\u003c/p\u003e\u003cp\u003e11 (9%)\u003c/p\u003e\u003cp\u003e23 (18%)\u003c/p\u003e\u003cp\u003e16 (14%)\u003c/p\u003e\u003cp\u003e8 (7%)\u003c/p\u003e\u003cp\u003e42 (36%)\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\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\u003ePeripartum and neonatal characteristics\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\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePeripartum and neonatal data, n (%)\u003c/b\u003e\u003c/p\u003e\u003cp\u003eDelivery term (WG) for the total sample, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003cp\u003eDelivery term (WG) for live births, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003cp\u003eDelivery term (WG) for intrauterine fetal demise, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003cp\u003eLatency duration (day) for live births, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003cp\u003eIntrauterine fetal demise\u003c/p\u003e\u003cp\u003eMedical pregnancy termination\u003c/p\u003e\u003cp\u003eLive births\u003c/p\u003e\u003cp\u003eSpontaneous labor onset\u003c/p\u003e\u003cp\u003eGeneral anesthesia\u003c/p\u003e\u003cp\u003eLow or absent amniotic fluid\u003c/p\u003e\u003cp\u003eMeconium-stained amniotic fluid; hemorrhagic fluid\u003c/p\u003e\u003cp\u003eTocolysis\u003c/p\u003e\u003cp\u003eMagnesium sulfate\u003c/p\u003e\u003cp\u003eProlapse; cord encirclement\u003c/p\u003e\u003cp\u003eRetroplacental hematoma\u003c/p\u003e\u003cp\u003eMale sex\u003c/p\u003e\u003cp\u003eMusculoskeletal deformity\u003c/p\u003e\u003cp\u003eIntrauterine growth restriction\u003c/p\u003e\u003cp\u003eVaginal delivery\u003c/p\u003e\u003cp\u003eCephalic presentation\u003c/p\u003e\u003cp\u003eDelayed cord clamping\u003c/p\u003e\u003cp\u003eTerm at birth\u0026thinsp;\u0026ge;\u0026thinsp;37\u003csup\u003e0/6\u003c/sup\u003e WG\u003c/p\u003e\u003cp\u003eTerm at birth from 36\u003csup\u003e6/6\u003c/sup\u003e to 35\u003csup\u003e0/6\u003c/sup\u003e WG\u003c/p\u003e\u003cp\u003eTerm at birth from 34\u003csup\u003e6/6\u003c/sup\u003e to 32\u003csup\u003e0/6\u003c/sup\u003e WG\u003c/p\u003e\u003cp\u003eTerm at birth from 31\u003csup\u003e6/6\u003c/sup\u003e to 27\u003csup\u003e0/6\u003c/sup\u003e WG\u003c/p\u003e\u003cp\u003eTerm at birth from 26\u003csup\u003e6/6\u003c/sup\u003e to 22\u003csup\u003e0/6\u003c/sup\u003e WG\u003c/p\u003e\u003cp\u003eBirth weight (g), median [IQ]\u003c/p\u003e\u003cp\u003eApgar score\u0026thinsp;\u0026lt;\u0026thinsp;7 at 1-min\u003c/p\u003e\u003cp\u003eApgar score at 5-min\u003c/p\u003e\u003cp\u003eApgar score at 10-min\u003c/p\u003e\u003cp\u003eRespiratory distress syndrome\u003c/p\u003e\u003cp\u003eIntubation in the delivery room\u003c/p\u003e\u003cp\u003eAdmission to NICU\u003c/p\u003e\u003cp\u003eAdmission directly to maternity ward (including Kangaroo unit)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eTotal\u0026thinsp;=\u0026thinsp;130\u003c/b\u003e\u003c/p\u003e\u003cp\u003e28.5\u0026thinsp;\u0026plusmn;\u0026thinsp;7\u003c/p\u003e\u003cp\u003e31.9\u0026thinsp;\u0026plusmn;\u0026thinsp;5\u003c/p\u003e\u003cp\u003e21.3\u0026thinsp;\u0026plusmn;\u0026thinsp;4\u003c/p\u003e\u003cp\u003e88 [49\u0026ndash;118]\u003c/p\u003e\u003cp\u003e35 (27%)\u003c/p\u003e\u003cp\u003e10 (8%)\u003c/p\u003e\u003cp\u003e85 (65%)\u003c/p\u003e\u003cp\u003e67 (52%)\u003c/p\u003e\u003cp\u003e14 (11%)\u003c/p\u003e\u003cp\u003e33 (25%)\u003c/p\u003e\u003cp\u003e3 (2%); 9 (7%)\u003c/p\u003e\u003cp\u003e16 (12%)\u003c/p\u003e\u003cp\u003e25 (19%)\u003c/p\u003e\u003cp\u003e9 (7%); 1 (1%)\u003c/p\u003e\u003cp\u003e13 (10%)\u003c/p\u003e\u003cp\u003e63 (54%)\u003c/p\u003e\u003cp\u003e9 (7%)\u003c/p\u003e\u003cp\u003e19 (17%)\u003c/p\u003e\u003cp\u003e\u003cb\u003eTotal live births\u0026thinsp;=\u0026thinsp;85\u003c/b\u003e\u003c/p\u003e\u003cp\u003e57 (67%)\u003c/p\u003e\u003cp\u003e62 (73%)\u003c/p\u003e\u003cp\u003e61 (71%)\u003c/p\u003e\u003cp\u003e22 (26%)\u003c/p\u003e\u003cp\u003e15 (17%)\u003c/p\u003e\u003cp\u003e7 (8%)\u003c/p\u003e\u003cp\u003e24 (28%)\u003c/p\u003e\u003cp\u003e19 (22%)\u003c/p\u003e\u003cp\u003e1886 [945\u0026ndash;2730]\u003c/p\u003e\u003cp\u003e31 (36%)\u003c/p\u003e\u003cp\u003e19 (22%)\u003c/p\u003e\u003cp\u003e6 (7%)\u003c/p\u003e\u003cp\u003e53 (62%)\u003c/p\u003e\u003cp\u003e40 (47%)\u003c/p\u003e\u003cp\u003e52 (61%)\u003c/p\u003e\u003cp\u003e33 (39%)\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\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eInfant characteristics during hospitalization\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\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eInfant data during hospital stay, n (%)\u003c/b\u003e\u003c/p\u003e\u003cp\u003eSpontaneous breathing room air\u003c/p\u003e\u003cp\u003eIntubation during hospital stay\u003c/p\u003e\u003cp\u003eSurfactant administration\u003c/p\u003e\u003cp\u003ePneumothorax\u003c/p\u003e\u003cp\u003ePulmonary hemorrhage\u003c/p\u003e\u003cp\u003eDuration of invasive ventilation (days), median [IQ]\u003c/p\u003e\u003cp\u003eDuration of noninvasive ventilation (days), median [IQ]\u003c/p\u003e\u003cp\u003eDuration of oxygen therapy (days), median [IQ]\u003c/p\u003e\u003cp\u003eDischarge with oxygen therapy\u003c/p\u003e\u003cp\u003ePostnatal steroids\u003c/p\u003e\u003cp\u003eHypotension in the first 24 hours\u003c/p\u003e\u003cp\u003eFluid resuscitation in the first 24 hours\u003c/p\u003e\u003cp\u003eVasoactive drugs\u003c/p\u003e\u003cp\u003ePulmonary hypertension\u003c/p\u003e\u003cp\u003eInhaled NO\u003c/p\u003e\u003cp\u003eOral sildenafil\u003c/p\u003e\u003cp\u003ePGE1\u003c/p\u003e\u003cp\u003eMedical\u0026nbsp;closure of DA (ibuprofen or paracetamol)\u003c/p\u003e\u003cp\u003eSurgical closure of the DA\u003c/p\u003e\u003cp\u003eEarly antibiotic therapy\u003c/p\u003e\u003cp\u003eConfirmed early onset sepsis\u003c/p\u003e\u003cp\u003eSignificant CRP elevation within the first 48 hours\u003c/p\u003e\u003cp\u003eAtypical organisms in tracheal sample\u003c/p\u003e\u003cp\u003eLate onset sepsis\u003c/p\u003e\u003cp\u003eNecrotizing enterocolitis\u003c/p\u003e\u003cp\u003eIsolated digestive perforation\u003c/p\u003e\u003cp\u003eIntracranial lesion at day 7\u003c/p\u003e\u003cp\u003eIntracranial lesion at term\u003c/p\u003e\u003cp\u003eRetinopathy stage 1\u003c/p\u003e\u003cp\u003eRetinopathy stage 2\u003c/p\u003e\u003cp\u003eRetinopathy stage 3\u003c/p\u003e\u003cp\u003eAnti-VEGF\u0026nbsp;treatment\u003c/p\u003e\u003cp\u003eLaser therapy\u003c/p\u003e\u003cp\u003eDeafness\u003c/p\u003e\u003cp\u003eLength of hospital stay (days), median [IQ]\u003c/p\u003e\u003cp\u003eDeath during hospitalization\u003c/p\u003e\u003cp\u003eSevere comorbidity at discharge including:\u003c/p\u003e\u003cp\u003e- Severe bronchopulmonary dysplasia\u003c/p\u003e\u003cp\u003e- Treated pulmonary hypertension\u003c/p\u003e\u003cp\u003e- Severe necrotizing enterocolitis\u003c/p\u003e\u003cp\u003e- Severe retinopathy\u003c/p\u003e\u003cp\u003e- Severe intracranial lesion at cranial ultrasound\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eTotal\u0026thinsp;=\u0026thinsp;85\u003c/b\u003e\u003c/p\u003e\u003cp\u003e36 (42%)\u003c/p\u003e\u003cp\u003e41 (48%)\u003c/p\u003e\u003cp\u003e41 (48%)\u003c/p\u003e\u003cp\u003e3 (4%)\u003c/p\u003e\u003cp\u003e2 (2%)\u003c/p\u003e\u003cp\u003e2 [0.5\u0026ndash;9.2]\u003c/p\u003e\u003cp\u003e11 [3\u0026ndash;62]\u003c/p\u003e\u003cp\u003e62 [8\u0026ndash;94]\u003c/p\u003e\u003cp\u003e10 (12%)\u003c/p\u003e\u003cp\u003e34 (40%)\u003c/p\u003e\u003cp\u003e13 (15%)\u003c/p\u003e\u003cp\u003e7 (8%)\u003c/p\u003e\u003cp\u003e11 (13%)\u003c/p\u003e\u003cp\u003e24 (28%)\u003c/p\u003e\u003cp\u003e22 (26%)\u003c/p\u003e\u003cp\u003e3 (4%)\u003c/p\u003e\u003cp\u003e1 (1%)\u003c/p\u003e\u003cp\u003e12 (14%)\u003c/p\u003e\u003cp\u003e4 (5%)\u003c/p\u003e\u003cp\u003e50 (59%)\u003c/p\u003e\u003cp\u003e1 (1%)\u003c/p\u003e\u003cp\u003e8 (9%)\u003c/p\u003e\u003cp\u003e6 (7%)\u003c/p\u003e\u003cp\u003e21 (25%)\u003c/p\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003cp\u003e3 (4%)\u003c/p\u003e\u003cp\u003e1 (1%)\u003c/p\u003e\u003cp\u003e1 (1%)\u003c/p\u003e\u003cp\u003e1 (1%)\u003c/p\u003e\u003cp\u003e4 (5%)\u003c/p\u003e\u003cp\u003e5 (6%)\u003c/p\u003e\u003cp\u003e4 (5%)\u003c/p\u003e\u003cp\u003e2 (2%)\u003c/p\u003e\u003cp\u003e1 (1%)\u003c/p\u003e\u003cp\u003e24 [5\u0026ndash;86]\u003c/p\u003e\u003cp\u003e8 (9%)\u003c/p\u003e\u003cp\u003e21 (25%)\u003c/p\u003e\u003cp\u003e14 (16%)\u003c/p\u003e\u003cp\u003e2 (2%)\u003c/p\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003cp\u003e4 (5%)\u003c/p\u003e\u003cp\u003e1 (1%)\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\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 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eFactors associated with death or severe morbidities in univariate and multivariate analyses\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=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\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\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eDeath or severe morbidities\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eUnivariate analysis\u003c/p\u003e\u003cp\u003eP\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eMultivariate analysis\u003c/p\u003e\u003cp\u003eRR; 95% CI\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eYes\u003c/b\u003e (n\u0026thinsp;=\u0026thinsp;56)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003eNo\u003c/b\u003e (n\u0026thinsp;=\u0026thinsp;64)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGestational age at PROM, median [IQ]\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u0026lt;\u0026thinsp;16\u003csup\u003e0/6\u003c/sup\u003e WG\u003c/p\u003e\u003cp\u003e16\u003csup\u003e0/6\u003c/sup\u003e to 20\u003csup\u003e6/6\u003c/sup\u003e WG\u003c/p\u003e\u003cp\u003e21\u003csup\u003e0/6\u003c/sup\u003e to 24\u003csup\u003e0/6\u003c/sup\u003e WG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19 [17\u0026ndash;21]\u003c/p\u003e\u003cp\u003e11\u003c/p\u003e\u003cp\u003e27\u003c/p\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21 [17\u0026ndash;22]\u003c/p\u003e\u003cp\u003e12\u003c/p\u003e\u003cp\u003e21\u003c/p\u003e\u003cp\u003e31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.155\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.58; 0.02\u0026ndash;1.16\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLatency, median [IQ]\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u0026le;\u0026thinsp;2 days\u003c/p\u003e\u003cp\u003e3 to 7 days\u003c/p\u003e\u003cp\u003e8 to 14 days\u003c/p\u003e\u003cp\u003e\u0026gt;\u0026thinsp;14 days\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15 [5\u0026ndash;49.2]\u003c/p\u003e\u003cp\u003e4\u003c/p\u003e\u003cp\u003e15\u003c/p\u003e\u003cp\u003e9\u003c/p\u003e\u003cp\u003e28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e106 [64\u0026ndash;127]\u003c/p\u003e\u003cp\u003e1\u003c/p\u003e\u003cp\u003e0\u003c/p\u003e\u003cp\u003e0\u003c/p\u003e\u003cp\u003e63\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.000\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e8.47; 1.07\u003c/b\u003e\u0026ndash;\u003cb\u003e66.67\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAmniotic fluid quantity at PROM\u003c/b\u003e\u003c/p\u003e\u003cp\u003eNormal\u003c/p\u003e\u003cp\u003eModerate oligohydramnios\u003c/p\u003e\u003cp\u003eSevere oligohydramnios\u003c/p\u003e\u003cp\u003eAnhydramnios\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e25\u003c/p\u003e\u003cp\u003e9\u003c/p\u003e\u003cp\u003e7\u003c/p\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e49\u003c/p\u003e\u003cp\u003e8\u003c/p\u003e\u003cp\u003e2\u003c/p\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.002\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.76; 0.04\u0026ndash;13.69\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMonitoring of amniotic fluid quantity\u003c/b\u003e\u003c/p\u003e\u003cp\u003eNormal\u003c/p\u003e\u003cp\u003eModerate oligohydramnios\u003c/p\u003e\u003cp\u003eSevere oligohydramnios\u003c/p\u003e\u003cp\u003eAnhydramnios\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15\u003c/p\u003e\u003cp\u003e5\u003c/p\u003e\u003cp\u003e3\u003c/p\u003e\u003cp\u003e33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e39\u003c/p\u003e\u003cp\u003e11\u003c/p\u003e\u003cp\u003e5\u003c/p\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.000\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.37; 0.01\u0026ndash;7.62\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHistory of cervical insufficiency\u003c/b\u003e\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\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.025\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.12; 0.01\u0026ndash;0.98\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCervical cerclage\u003c/b\u003e\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\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.025\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.12; 0.01\u0026ndash;0.98\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eVaginal swab streptococcus B-positive\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.04; 0.01\u0026ndash;0.21\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eInfection at PROM\u003c/b\u003e\u003c/p\u003e\u003cp\u003eNo infection\u003c/p\u003e\u003cp\u003eSuspected infection\u003c/p\u003e\u003cp\u003eConfirmed infection\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e27\u003c/p\u003e\u003cp\u003e14\u003c/p\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e44\u003c/p\u003e\u003cp\u003e10\u003c/p\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.009\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.11; 0.00\u0026ndash;5.42\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCRP at PROM\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u0026lt;\u0026thinsp;5 mg/L\u003c/p\u003e\u003cp\u003eBetween 5 and 20 mg/L\u003c/p\u003e\u003cp\u003e\u0026gt;\u0026thinsp;20 mg/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17\u003c/p\u003e\u003cp\u003e15\u003c/p\u003e\u003cp\u003e17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e29\u003c/p\u003e\u003cp\u003e19\u003c/p\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.023\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.66; 0.08\u0026ndash;0.54\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLeucocytes at PROM\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u0026lt;\u0026thinsp;10 G/L\u003c/p\u003e\u003cp\u003eBetween 10 and 15 G/L\u003c/p\u003e\u003cp\u003e\u0026gt;\u0026thinsp;15 G/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e22\u003c/p\u003e\u003cp\u003e16\u003c/p\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e33\u003c/p\u003e\u003cp\u003e15\u003c/p\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.295\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.80; 0.00\u0026ndash;10.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAntenatal corticotherapy\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e53\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.000\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.04; 0.00\u0026ndash;0.08\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTerm at delivery, median [IQ]\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u0026lt;\u0026thinsp;24\u003csup\u003e0/6\u003c/sup\u003e WG\u003c/p\u003e\u003cp\u003e24\u003csup\u003e0/6\u003c/sup\u003e to 25\u003csup\u003e6/6\u003c/sup\u003e WG\u003c/p\u003e\u003cp\u003e26\u003csup\u003e0/6\u003c/sup\u003e to 28\u003csup\u003e6/6\u003c/sup\u003e WG\u003c/p\u003e\u003cp\u003e29\u003csup\u003e0/6\u003c/sup\u003e to 32\u003csup\u003e6/6\u003c/sup\u003e WG\u003c/p\u003e\u003cp\u003e\u0026gt;\u0026thinsp;33\u003csup\u003e0/6\u003c/sup\u003e WG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e23 [20\u0026ndash;26]\u003c/p\u003e\u003cp\u003e36\u003c/p\u003e\u003cp\u003e3\u003c/p\u003e\u003cp\u003e11\u003c/p\u003e\u003cp\u003e6\u003c/p\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e35 [30\u0026ndash;37]\u003c/p\u003e\u003cp\u003e0\u003c/p\u003e\u003cp\u003e3\u003c/p\u003e\u003cp\u003e6\u003c/p\u003e\u003cp\u003e13\u003c/p\u003e\u003cp\u003e42\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.000\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e3.51; 1.82\u003c/b\u003e\u0026ndash;\u003cb\u003e6.76\u003c/b\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\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eFactors associated with death or severe comorbidities at PROM\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=\"char\" char=\".\" 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\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eDeath or severe morbidities\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eMultivariate analysis\u003c/p\u003e\u003cp\u003eRR; 95% CI\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"1\" nameend=\"c5\" namest=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eYes\u003c/b\u003e (n\u0026thinsp;=\u0026thinsp;56)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003eNo\u003c/b\u003e (n\u0026thinsp;=\u0026thinsp;64)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"1\" nameend=\"c5\" namest=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGestational age at PROM, median [IQ]\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u0026lt;\u0026thinsp;16\u003csup\u003e0/6\u003c/sup\u003e WG\u003c/p\u003e\u003cp\u003e16\u003csup\u003e0/6\u003c/sup\u003e to 20\u003csup\u003e6/6\u003c/sup\u003e WG\u003c/p\u003e\u003cp\u003e21\u003csup\u003e0/6\u003c/sup\u003e to 24\u003csup\u003e0/6\u003c/sup\u003e WG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19 [17\u0026ndash;21]\u003c/p\u003e\u003cp\u003e11\u003c/p\u003e\u003cp\u003e27\u003c/p\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21 [17\u0026ndash;22]\u003c/p\u003e\u003cp\u003e12\u003c/p\u003e\u003cp\u003e21\u003c/p\u003e\u003cp\u003e31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.94; 0.14\u0026ndash;6.29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c5\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAmniotic fluid quantity at PROM\u003c/b\u003e\u003c/p\u003e\u003cp\u003eNormal\u003c/p\u003e\u003cp\u003eModerate oligohydramnios\u003c/p\u003e\u003cp\u003eSevere oligohydramnios\u003c/p\u003e\u003cp\u003eAnhydramnios\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e25\u003c/p\u003e\u003cp\u003e9\u003c/p\u003e\u003cp\u003e7\u003c/p\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e49\u003c/p\u003e\u003cp\u003e8\u003c/p\u003e\u003cp\u003e2\u003c/p\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0. 0.01\u0026ndash;29.08\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c5\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMonitoring of amniotic fluid quantity\u003c/b\u003e\u003c/p\u003e\u003cp\u003eNormal\u003c/p\u003e\u003cp\u003eModerate oligohydramnios\u003c/p\u003e\u003cp\u003eSevere oligohydramnios\u003c/p\u003e\u003cp\u003eAnhydramnios\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15\u003c/p\u003e\u003cp\u003e5\u003c/p\u003e\u003cp\u003e3\u003c/p\u003e\u003cp\u003e33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e39\u003c/p\u003e\u003cp\u003e11\u003c/p\u003e\u003cp\u003e5\u003c/p\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.06; 0.00\u0026ndash;0.59\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c5\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eInfection at PROM\u003c/b\u003e\u003c/p\u003e\u003cp\u003eNo infection\u003c/p\u003e\u003cp\u003eSuspected infection\u003c/p\u003e\u003cp\u003eConfirmed infection\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e27\u003c/p\u003e\u003cp\u003e14\u003c/p\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e44\u003c/p\u003e\u003cp\u003e10\u003c/p\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0. 0.14\u0026ndash;2.62\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\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":"european-journal-of-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejpe","sideBox":"Learn more about [European Journal of Pediatrics](https://www.springer.com/journal/431)","snPcode":"431","submissionUrl":"https://submission.nature.com/new-submission/431/3","title":"European Journal of Pediatrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"neonatal outcomes, periviable premature rupture of membranes, prognosis","lastPublishedDoi":"10.21203/rs.3.rs-8174640/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8174640/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction\u003c/strong\u003e: This study evaluates neonatal outcomes following periviable premature rupture of membranes (PPROM) before 24 weeks gestation, and identify factors associated with death or severe comorbidities.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: A retrospective analysis of pregnancies complicated by PPROM was conducted at the University Hospital of Lille from 2014 to 2019. Maternal and neonatal data until hospital discharge were collected.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: Among 130 fetuses, 67% were live-born. The rate of medical termination of pregnancy was 8%. Seventy-five percent of those live-born were preterm. About one-third of neonates were admitted to the maternity ward without respiratory failure; 61% of neonates required neonatal intensive care unit admission for prematurity and/or immediate respiratory failure. Of the live-born infants, 90% were discharged from hospital, 74% with no severe comorbidities. Multivariate analysis identified preterm delivery (relative risk [RR] 3.51, 95% confidence interval [CI]: 1.82–6.76) and short latency from PPROM to delivery (RR 8.47, 95% CI: 1.07–66.67) as risk factors for death or severe comorbidities.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: Parent counseling should consider both current, evolving outcomes, and the unpredictable course of pregnancies complicated by PPROM. Prolonging pregnancy through close monitoring and implementation of current guidelines on neonatal management are essential to reduce adverse outcomes.\u003c/p\u003e","manuscriptTitle":"Periviable premature rupture of membranes (before 24 weeks gestation): Pregnancy and neonatal outcomes","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-10 10:50:12","doi":"10.21203/rs.3.rs-8174640/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-12-30T14:44:14+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-27T18:50:36+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"30117098474621650953394647465095133472","date":"2025-12-06T17:45:51+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-12-05T11:17:03+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-12-02T23:46:18+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-12-02T23:36:38+00:00","index":"","fulltext":""},{"type":"submitted","content":"European Journal of Pediatrics","date":"2025-11-21T14:34:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejpe","sideBox":"Learn more about [European Journal of Pediatrics](https://www.springer.com/journal/431)","snPcode":"431","submissionUrl":"https://submission.nature.com/new-submission/431/3","title":"European Journal of Pediatrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"6409e531-6980-405a-b297-708f3abb0a82","owner":[],"postedDate":"December 10th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-02-02T16:07:21+00:00","versionOfRecord":{"articleIdentity":"rs-8174640","link":"https://doi.org/10.1007/s00431-026-06773-1","journal":{"identity":"european-journal-of-pediatrics","isVorOnly":false,"title":"European Journal of Pediatrics"},"publishedOn":"2026-01-30 15:59:19","publishedOnDateReadable":"January 30th, 2026"},"versionCreatedAt":"2025-12-10 10:50:12","video":"","vorDoi":"10.1007/s00431-026-06773-1","vorDoiUrl":"https://doi.org/10.1007/s00431-026-06773-1","workflowStages":[]},"version":"v1","identity":"rs-8174640","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8174640","identity":"rs-8174640","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}