Journal of Perinatology (2010) 30, 645–649 r 2010 Nature America, Inc. All rights reserved. 0743-8346/10 www.nature.com/jp ORIGINAL ARTICLE Rupture of membranes before the age of viability and birth after the age of viability: comparison of outcomes in a matched cohort study

H Soylu1, A Jefferies1, Y Diambomba1, R Windrim2 and PS Shah1 1Department of Paediatrics, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada and 2Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada

16 and 26 weeks of gestation is reported at a frequency of 1% in the Objective: To compare composite adverse outcome rate of infants United States.1,5 Despite recent advances in both obstetric and <32 weeks gestational age (GA) who were born after preterm premature neonatal care, including use of intrapartum antibiotics, antenatal rupture of membranes (PPROM) at previable gestation to those born steroids, postnatal surfactant and gentle ventilation strategies, both without PPROM. mother and infant are at high risk of adverse outcomes in Study Design: Retrospective review of prospective collected data for situations complicated by PPROM at previable gestational age 1,6,7 infants discharged between 2004 and 2007 was conducted. Cases were (GA). Maternal complications include intrauterine infection, 2,3,8,9 9 infants with >7 days of PPROM that occurred before 24 weeks. Matched oligohydramnios and placental abruption. Neonates are at cohort consisted of infants born without PPROM (matched for GA, risk of mortality and morbidities due to pulmonary hypoplasia, sex and admission date). Composite adverse outcome was assessed extreme difficulty at resuscitation, sepsis, air leaks and chronic 2,6,8,10–12 considering death or any of the following three severe morbidities disease (CLD). In a systematic review and meta- (severe neurological injury, severe retinopathy of prematurity or analyses of reports from 1980 to 1999, significant lack of good chronic lung disease). quality information of outcomes of neonates born after early PPROM was identified.6 Perinatal survival was reported to be <20% Result: The 29 cases had higher mean severity of illness score compared when PPROM occurred at both <20 and between 20 and 23 weeks with 74 matched infants. Mean duration of ROM was 45 vs 2 days gestation. On one hand, improved survival has been reported in and mean GA at the ROM was 21 vs 27 weeks, respectively. Logistic recent years by some studies12,13 whereas others have cautioned regression confirmed significantly higher risk of composite adverse against conservative management due to increasing maternal outcome rates for cases (69 vs 47%; P ¼ 0.02, adjusted odds ratio 4.0, 95% complications rates.14 CI 1.2, 13.6). Natural history suggests that approximately 75% of women Conclusion: The survival rate for infants born at <32 weeks following deliver within 1 month of PPROM and that the remaining 25% PPROM at previable age has improved significantly; however, these remain pregnant more than 1 month.8 The reported neonatal infants had a higher rate of adverse composite neonatal outcome. outcomes of such that have resulted in viable neonates Journal of Perinatology (2010) 30, 645–649; doi:10.1038/jp.2010.11; are variable.9,15 The objective of this study was to compare published online 11 March 2010 composite outcome (death or severe morbidities) of infants <32 weeks GA who were born after PPROM at previable gestation Keywords: infant; premature; morbidity; mortality; PPROM (<24 weeks GA) of at least 7 days duration with the outcome of those born without PPROM. Introduction Preterm premature rupture of the membranes (PPROM) Methods complicates 3% of pregnancies and is associated with Setting approximately one third of all preterm births.1–4 PPROM between A retrospective review of prospectively collected data was performed. Data were collected for preterm infants <32 weeks GA discharged Correspondence: Dr PS Shah, Department of Paediatrics, Mount Sinai Hospital, University of (died or survived) between July 2004 and October 2007 at our Toronto, 775A–600 University Avenue, Toronto, ON, M5G 1X5 Canada. tertiary care perinatal center in Toronto, Canada. Data related to E-mail: [email protected] Received 10 September 2009; revised 25 November 2009; accepted 10 December 2009; published all neonatal intensive care unit (NICU) admissions (including online 11 March 2010 delivery room deaths) were collected daily prospectively by either PPROM before age of viability and neonatal outcomes H Soylu et al 646 staff neonatologists or a trained data abstractor according to strict age if the birth weight was less than the third percentile for GA guidelines and definitions. according to the published data for Canadian infants.16 Clinical Risk Index for Babies (CRIB) score,17 Score of Acute Neonatal Eligibility criteria Physiology, version IIFPhysiologic Extension18 and Transport In this matched cohort study of preterm infants <32 weeks Risk Index of Physiologic Stability (TRIPS)19 are neonatal illness gestation at birth, we attempted to identify two to three comparable severity scores calculated from variables during the first day of infants for each index case. Cases were infants born with >7 days admission to the NICU. PPHN was defined as persistent labile of PPROM that occurred before 24 weeks GA. Matched cohort hypoxemia (PaO2<50 in 100% oxygen) in the absence of consisted of infants born without PPROM. The cohort was matched structural cardiovascular malformation disproportionate to the for GA (±1 week), sex and birth date (±3 months). Infants with degree of pulmonary parenchymal disease and associated with congenital anomalies other than positional malformations clinical (PaO2 difference of >15 mm Hg between pre- and post- associated with oligohydramnios, those for whom palliative care ductal values) or echocardiographic evidence of right to left was planned antenatally because of extreme prematurity or lethal shunting at atrial and/or ductal level, tricuspid regurgitation and malformations and those with antenatal diagnoses of elevated right ventricular systolic pressure. CLD was defined as chromosomal anomalies, were excluded. oxygen dependency at 36 weeks corrected GA.20 IVH was classified in four grades as suggested by Papile et al.;21 the worst findings on Ethics statement head ultrasound performed at anytime during the stay in NICU was The database and this study had approval from research ethics considered for analysis. Necrotizing enterocolitis was defined board at our institution. according to Bell’s criteria (stage 2 or higher).22 Nosocomial infection was defined by isolation of organisms from blood, urine Data collection or cerebrospinal fluid culture. Patent ductus arteriosus was The diagnosis of membrane rupture was based on history, the diagnosed clinically based on symptoms and signs. findings of amniotic fluid on sterile speculum examination, positive nitrazine and/or fern test and oligohydramnios, which was Statistical methods defined as an amniotic fluid index of less than five. Patients with Sample size was calculated expecting a case/matched cohort ratio history of PPROM were then followed up in our clinic every 2 weeks of 1:2 to 3, a of 0.05 and power of 80% as well as correlation for until they reach GA of 24 weeks and then once weekly until birth. exposure (PPROM) between cases and matched cohort of 0.1. Clinical was considered if mother had pyrexia Composite adverse outcome rate for the entire cohort was (temperature >38 1C) accompanied by uterine tenderness, approximately 40% and for an odds ratio (OR) of 4 (four times the purulent vaginal discharge, or fetal tachycardia for no other odds of mortality and severe morbidities) we needed 25 to 28 cases. reason. After the infant’s admission to NICU, data regarding daily Baseline characteristics and common outcomes between groups management and common neonatal outcomes as defined below were compared using w2-test, t-test and Mann–Whitney U-test. were collected prospectively in a database and were retrieved for Logistic regression was performed controlling for GA, sex, small for study infants. Information related to daily NICU care, as well as gestational age, receipt of antenatal steroids, mode of birth and results of head ultrasound, eye examination and clinical status was TRIPS score at birth. The SPSS, version 15 (SPSS Inc., Chicago, IL, retrieved from this database and electronic patient records. USA) was used for data analysis.

Definitions for outcomes Primary outcome was a composite adverse outcome of mortality or Results any of three severe morbiditiesFgrade 3 or 4 intraventricular During the study period, 3479 patients were admitted to our NICU, hemorrhage (IVH) or periventricular leukomalacia; severe of which 1051 patients were <32 weeks GA at birth. Twenty-nine retinopathy of prematurity (ROP) >stage 2 or CLD at 36 weeks infants with PPROM at previable age and of >7 days duration and postmenstrual age. Secondary outcomes included mortality in 74 matched infants were identified (case/matched cohort ratio of NICU, respiratory distress syndrome, air leak, persistent pulmonary 1:2.6). The infants with PPROM (cases) constituted 2.8% of the hypertension (PPHN), severe (>grade 3) IVH, CLD, necrotizing total number of infants born <32 weeks GA. Two infants had enterocolitis, patent ductus arteriosus, nosocomial infections, severe contractures noted at birth and one infant had ‘potter-like’ facial ROP, duration (days) of respiratory support, duration (days) of features. oxygen treatment, duration of intravenous support and duration of As shown in Table 1, there were no significant differences total parenteral nutrition. GA was determined by the best obstetric between the groups at birth except for severity of illness scores and estimate based on early prenatal ultrasound, obstetric examination incidence of suspected chorioamnionitis, both of which were and obstetric history. An infant was defined as small for gestational unfavorable among infants in the PPROM group, and the use of

Journal of Perinatology PPROM before age of viability and neonatal outcomes H Soylu et al 647

Table 1 Baseline characteristics Table 2 Secondary outcomes and components of primary outcomes

Characteristics Cases Controls P Outcome Cases Matched cohort P (n ¼ 29) (n ¼ 74) (n ¼ 29) (n ¼ 74)

GA (mean±s.d.) week 27±227±2 0.62 Respiratory distress syndrome, n (%) 28 (97) 62 (84) 0.08 BW (mean±s.d.) g 1048 ±379 1007±344 0.61 Air leak, n (%) 5 (17) 5 (4) 0.02* Male, n (%) 20 (69) 46 (62) 0.79 Persistent pulmonary hypertension, n (%) 6 (21) 0 (0) <0.001* IUGR, n (%) 0 (0) 4 (5) 0.20 Sepsis, n (%) 4 (14) 17 (23) 0.30 Cesarean birth, n (%) 12 (41) 42 (57) 0.12 Retinopathy of prematurity >stage 2, n (%) 5 (17) 11 (15) 0.77 Median Apgar 1 min (range) 4 (2–5) 5 (3–8) 0.19 Grade 3 or 4 IVH or PVL, n (%) 7 (24) 11 (15) 0.27 Median Apgar 5 min (range) 7 (5–9) 8 (7–9) 0.07 Chronic lung disease at 36 weeks, n (%) 10 (34) 23 (31) 0.94 CRIB score (mean±s.d.) 7±44±4 <0.01* Mortality, n (%) 7 (24) 10 (13) 0.19 TRIPS score (mean±s.d.) 31±14 20±10 <0.01* Composite adverse outcome among 13/22 (59) 25/64 (39) 0.14 Complete course of antenatal steroid, n (%) 28 (93) 48 (65) 0.015* survivors, n/N (%) Chorioamnionitis, n (%) 9 (31) 6 (8) <0.01* Duration of artificial ventilation 15±18 18±22 0.52 (mean±s.d.) days Duration of rupture of membranes (days) Duration of respiratory support 39±31 39±33 0.98 Mean+s.d. 45+30 2+1 <0.01 (mean±s.d.) days Median (range) 39 (8–103) 1 (1–7) <0.01 Duration of intravenous access 17±15 23±19 0.13 (mean±s.d.) days GA at rupture of membranes (weeks) Length of stay (mean±s.d.) days 54±43 55±41 0.86 Mean+s.d. 21±227±2 <0.01 Abbreviations: IVH, intraventricular hemorrhage; PVL, periventricular leukomalacia. Median (range) 22 (15–23) 27 (23–31) <0.01 *P<0.05. Abbreviations: BW, body weight; CRIB, Clinical Risk Index for Babies; GA, gestational age; IUGR, intrauterine growth restriction; TRIPS, Transport Risk Index of Physiologic had severe IVH/periventricular leukomalacia, three had severe ROP Stability. *P<0.05. and one developed CLD at 36 weeks. antenatal steroids, with a higher proportion of infants in the PPROM group receiving a complete course compared with the Discussion matched cohort. As expected, the duration of rupture of Counseling women who present with PPROM at previable GA is membranes (ROM) and GA at ROM were different between groups challenging. Many of these women will go into spontaneous labor, (Table 1). Results of other neonatal outcomes are reported in or will need to be delivered at a previable GA due to maternal Table 2. There was significantly increased risk of mortality or health risks. Furthermore, in our local experience, a very poor severe morbidities among cases (69 vs 47%; P ¼ 0.02, unadjusted prognosis for the /neonate is often presented to the patient and OR 2.5, 95% CI 1.0, 6.1). Logistic regression analyses confirmed termination of is frequently recommended. However, PPROM at a previable age to be significantly associated with in the subset of women who experience PPROM at a previable GA composite primary outcome (adjusted OR 4.0, 95% CI 1.2, 13.6). and choose to continue their pregnancy to reach a viable GA, we Univariate subgroup analysis revealed no significant difference report a 76% survival to discharge from NICU for their preterm in composite adverse outcome between groups of infants who infants born at <32 weeks. In fact, our study may underestimate had PPROM before 20 weeks (n ¼ 12) compared with those who survival as we restricted our analysis to those infants who were had PPROM after 20 weeks (n ¼ 17) (58 vs 76%; P ¼ 0.42). born between 24 and 32 weeks GA. This cohort of preterm infants Reported causes of death among cases (n ¼ 7) were pulmonary born following very early PPROM experienced higher rates of hypoplasia in three, candida sepsis in one, bacterial sepsis in one, combined adverse outcomes including death or severe neurological severe IVH in one and extreme prematurity in one infant. injury, severe ROP or CLD than matched preterm infants. We Oligohydramnios or anhydramnios was present in 17 (63%) acknowledge that our data are from a select group of infants who cases. For all cases, a course of prophylactic antibiotics, usually survived early PPROM and not a population-based cohort of 5 days of erythromycin, was used at the time of PPROM in keeping mothers who had ruptured and were serially followed up to assess with hospital policy. There was no difference in the risk of the outcomes. composite outcome among those who had oligo- or anhydramnios Lindner et al.,12 in a retrospective matched cohort study of compared with those who did not have oligo- or anhydramnios. 19 infants, reported that PPROM before 20 weeks was associated (65 vs 70%). Among the five patients who had anhydramnios, with higher risk of mortality, CLD and air leak when compared composite outcome was present in four, two patients died, three with infants not exposed to PPROM. However, the differences were

Journal of Perinatology PPROM before age of viability and neonatal outcomes H Soylu et al 648 not statistically significantly different due to lack of power in the lung volume, ground glass appearance with or without air study. Similar to our report, initial respiratory morbidities were bronchogram and need for FiO2 >30% as our criteria for identified to be significantly worse. However, 68% of infants in their diagnosis of respiratory distress syndrome. However, some of these series survived to discharge, a smaller percentage than the 76% infants may also have component of pulmonary hypertension reported in our series. Everest et al.13 in a cohort study of 98 or prolonged transition to postnatal life. pregnancies complicated by PPROM before 24 weeks reported that The latency period between PPROM and birth is suggested as an 41% resulted in live births. Of these live-born neonates, air leak important determinant for overall outcome of the pregnancy.28 occurred in 38%, pulmonary hypoplasia was diagnosed in 25 and Winn et al.23 reported that latency was >4 weeks in the group who 70% survived to discharge. CLD was present in 43% of these had pulmonary hypoplasia whereas it was only 8 days in the group survivors. Findings from Lindner et al.,12 Everest et al.13 and our of patients who did not have pulmonary hypoplasia. Farooqi et al.7 study are in contrast with previous findings. Falk et al.10 reported reported an average latency of 70 days and in their series 60% of that all neonates born between 24 and 28 weeks GA who had patients had pulmonary hypoplasia. In our study, the latency was PPROM before 20th week GA died whereas survival was 55% if 45 days; however, only 21% of our cases showed some clinical PPROM occurred at 22 to 23 weeks GA. Shumway et al.9 reported characteristics of pulmonary hypoplasia such as PPHN and air 51% mortality if PPROM occurred between 20 and 24 weeks GA. leaks. It is probable that latency is an important determinant; Winn et al.23 reported 95% perinatal mortality for neonates with however, we cannot conclude as such from our small sample size. pulmonary hypoplasia associated with PPROM. Morales and Oligohydramnios or anhydramnios are also important variables Talley15 reported 40% survival for PPROM <25 weeks GA. Farooqi for predicting outcome.24,29 Hadi et al. reported 69% mortality for et al.7 reported 40% survival if PPROM was at <20 weeks GA. infants of 26 to 34 weeks GA if associated with oligohydramnios. In Kilbride et al.24 reported mortality of >90% if PPROM at <25 our series, we did not identify a difference in composite outcome weeks GA was associated with oligohydramnios of >14 days. Xiao rate between patients born following oligo- and anhydramnios. et al.25 reported 82% mortality for PPROM <22 weeks. Dinsmoor This may due small number of infants in each group. We also et al.1 reported 53% mortality for median GA at PPROM of 22 acknowledge that our definition of amniotic fluid index <5 for weeks and median latency of 13 days. Verma et al.26 reported 82% oligohydramnios may not be strict enough to predict pulmonary mortality following PPROM at 18 to 23 weeks GA. It is obvious that hypoplasia. there are marked differences in outcomes between studies. This is Strengths of our study include a contemporary matched cohort, probably due to heterogeneity in the base population studied, unbiased data collection for outcomes and 2 to 3 controls per case. variability in obstetrical practices, differing counseling provided to We used a composite adverse outcome of mortality and severe women and improvement in neonatal outcomes over time. morbidities. This is an important point to consider as these One of the most common problems after early and prolonged morbidities individually and in combination are associated with PPROM is pulmonary hypoplasia.6,27 Vergani et al.28 reported adverse neurodevelopmental outcome.30 We are aware that CLD ROM of as little as 5 days can interfere with lung maturation. per se would not deter any woman to terminate pregnancy; Persistent oligohydramnios, particularly when PPROM occurs however, association of CLD to higher risk of neurodevelopmental before viability, inhibits alveolar development and can lead to outcomes should be explained to mothers when counseling at lethal pulmonary hypoplasia.8 The incidence of pulmonary previable age. hypoplasia varied between studies from 1323 to 60%.7 Pulmonary Limitations of our study include lack of long-term follow-up hypoplasia is primarily a histological diagnosis. The clinical data on these infants. We can only speculate that survivors with correlates include marked delay in postnatal adaptation leading to morbidities included in adverse outcomes are at higher risk of PPHN and air leaks. In our study, 21% of the total study infants adverse neurodevelopmental outcomes. Proper long-term outcome had PPHN and 17% had air leaks. Our case infants likely had data have been a deficit in literature. Serial amnioinfusions has variable degree of alteration in their lung growth and only been suggested as one measure to improve perinatal complications long-term data from pulmonary function testing among associated with PPROM at or before mid-pregnancy.31 However, survivors can ascertain whether these infants had an element of controlled studies are needed to assess efficacy and safety of such decreased lung growth. We did not see differences in the CLD intervention. Long-term follow-up data, of both rates between cases and controls. This may be attributed, in part, to neurodevelopmental and pulmonary outcomes, are urgently the higher mortality among cases, resulting in fewer infants needed for proper counseling of mothers. surviving to develop CLD. In survivors, careful pulmonary management (for example, gentle ventilation, permissive hypercapnea) may have decreased the incidence of CLD. The Conclusion incidence of respiratory distress syndrome was higher in case group More than three quarters of infants born at <32 weeks GA after despite receipt of prenatal steroids. We used criteria of small PPROM at previable age survived in this matched cohort study.

Journal of Perinatology PPROM before age of viability and neonatal outcomes H Soylu et al 649

However, these infants had a higher rate of adverse composite 14 Grisaru-Granovsky S, Eitan R, Kaplan M, Samueloff A. Expectant management of outcome of death, severe neurological injury, severe ROP or CLD midtrimester premature rupture of membranes: a plea for limits. J Perinatol 2003; 23: than a matched cohort without PPROM. This information may be 235–239. used to counsel women with previable PPROM who do not develop 15 Morales WJ, Talley T. Premature rupture of membranes at < 25 weeks: a management dilemma. Am J Obstet Gynecol 1993; 168: 503–507. spontaneous chorioamnionitis or go in to labor. However, 16 Kramer MS, Platt RW, Wen SW, Joseph KS, Allen A, Abrahamowicz M et al. A new and long-term follow-up data for surviving infants are urgently needed. improved population-based Canadian reference for birth weight for gestational age. Pediatrics 2001; 108: E35. 17 The CRIB (Clinical Risk Index for Babies) score: a tool for assessing initial neonatal Conflict of interest risk and comparing performance of neonatal intensive care units. The International Neonatal Network. Lancet 1993; 342: 193–198. The authors declare no conflict of interest. 18 Richardson DK, Corcoran JD, Escobar GJ, Lee SK. SNAP-II and SNAPPE-II: simplified newborn illness severity and mortality risk scores. J Pediatr 2001; 138: 92–100. 19 Lee SK, Zupancic JA, Pendray M, Thiessen P, Schmidt B, Whyte R et al. Transport Risk References Index of Physiologic Stability: a practical system for assessing infant transport care. J Pediatr 2001; 139: 220–226. 1 Dinsmoor MJ, Bachman R, Haney EI, Goldstein M, Mackendrick W. Outcomes after 20 Shennan AT, Dunn MS, Ohlsson A, Lennox K, Hoskins EM. Abnormal pulmonary expectant management of extremely preterm premature rupture of the membranes. outcomes in premature infants: prediction from oxygen requirement in the neonatal Am J Obstet Gynecol 2004; 190: 183–187. period. Pediatrics 1988; 82: 527–532. 2 Kilpatrick SJ, Patil R, Connell J, Nichols J, Studee L. Risk factors for previable 21 Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal premature rupture of membranes or advanced cervical dilation: a case control study. and intraventricular hemorrhage: a study of infants with birth weights less than Am J Obstet Gynecol 2006; 194: 1168–1174. 1500 gm. J Pediatr 1978; 92: 529–534. 3 Mercer BM. Preterm premature rupture of the membranes: current approaches 22 Bell MJ, Ternberg JL, Feigin RD, Keating JP, Marshall R, Barton L et al. Neonatal to evaluation and management. Obstet Gynecol Clin North Am 2005; 32: necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg 411–428. 1978; 187:1–7. 4 Newton ER. Preterm labor, preterm premature rupture of membranes, and 23 Winn HN, Chen M, Amon E, Leet TL, Shumway JB, Mostello D. Neonatal pulmonary chorioamnionitis. Clin Perinatol 2005; 32: 571–600. hypoplasia and perinatal mortality in patients with midtrimester rupture of amniotic 5 Yang LC, Taylor DR, Kaufman HH, Hume R, Calhoun B. Maternal and fetal outcomes membranesFa critical analysis. Am J Obstet Gynecol 2000; 182: 1638–1644. of spontaneous preterm premature rupture of membranes. J Am Osteopath Assoc 2004; 24 Kilbride HW, Yeast J, Thibeault DW. Defining limits of survival: lethal pulmonary 104: 537–542. hypoplasia after midtrimester premature rupture of membranes. Am J Obstet Gynecol 6 Dewan H, Morris JM. A systematic review of pregnancy outcome following preterm 1996; 175: 675–681. premature rupture of membranes at a previable gestational age. Aust N Z J Obstet 25 Xiao ZH, Andre P, Lacaze-Masmonteil T, Audibert F, Zupan V, Dehan M. Gynaecol 2001; 41: 389–394. Outcome of premature infants delivered after prolonged premature rupture of 7 Farooqi A, Holmgren PA, Engberg S, Serenius F. Survival and 2-year outcome with membranes before 25 weeks of gestation. Eur J Obstet Gynecol Reprod Biol 2000; expectant management of second-trimester rupture of membranes. Obstet Gynecol 90: 67–71. 1998; 92: 895–901. 26 Verma U, Goharkhay N, Beydoun S. Conservative management of preterm premature 8 Mercer BM. Preterm premature rupture of the membranes: diagnosis and rupture of membranes between 18 and 23 weeks of gestationFmaternal and neonatal management. Clin Perinatol 2004; 31: 765–782, vi. outcome. Eur J Obstet Gynecol Reprod Biol 2006; 128: 119–124. 9 Shumway JB, Al Malt A, Amon E, Cohlan B, Amini S, Abboud M et al. 27 McIntosh N. Dry lung syndrome after oligohydramnios. Arch Dis Child 1988; 63: Impact of oligohydramnios on maternal and perinatal outcomes of spontaneous 190–193. premature rupture of the membranes at 18–28 weeks. J Matern Fetal Med 1999; 28 Vergani P, Locatelli A, Verderio M, Assi F. Premature rupture of the membranes at 8: 20–23. <26 weeks’ gestation: role of amnioinfusion in the management of oligohydramnios. 10 Falk SJ, Campbell LJ, Lee-Parritz A, Cohen AP, Ecker J, Wilkins-Haug L et al. Expectant Acta Biomed 2004; 75(Suppl 1): 62–66. management in spontaneous preterm premature rupture of membranes between 14 29 Hadi HA, Hodson CA, Strickland D. Premature rupture of the membranes between 20 and 24 weeks’ gestation. J Perinatol 2004; 24: 611–616. and 25 weeks’ gestation: role of amniotic fluid volume in perinatal outcome. Am J 11 Furman B, Shoham-Vardi I, Bashiri A, Erez O, Mazor M. Clinical significance and Obstet Gynecol 1994; 170: 1139–1144. outcome of preterm prelabor rupture of membranes: population-based study. Eur J 30 Schmidt B, Asztalos EV, Roberts RS, Robertson CM, Sauve RS, Whitfield MF. Impact of Obstet Gynecol Reprod Biol 2000; 92: 209–216. bronchopulmonary dysplasia, brain injury, and severe retinopathy on the outcome 12 Lindner W, Pohlandt F, Grab D, Flock F. Acute respiratory failure and short-term of extremely low-birth-weight infants at 18 months: results from the trial of outcome after premature rupture of the membranes and oligohydramnios before indomethacin prophylaxis in preterms. JAMA 2003; 289: 1124–1129. 20 weeks of gestation. J Pediatr 2002; 140: 177–182. 31 Locatelli A, Ghidini A, Verderio M, Andreani M, Strobelt N, Pezzullo J et al. Predictors of 13 Everest NJ, Jacobs SE, Davis PG, Begg L, Rogerson S. Outcomes following prolonged perinatal survival in a cohort of pregnancies with severe oligohydramnios due to preterm premature rupture of the membranes. Arch Dis Child Fetal Neonatal Ed 2008; premature rupture of membranes at <26 weeks managed with serial amnioinfusions. 93: F207–F211. Eur J Obstet Gynecol Reprod Biol 2006; 128: 97–102.

Journal of Perinatology