Understanding the usual clinical course of periviable PROM helps physicians guide families who are making difficult decisions.
Dr. Sciscione is director of the Delaware Center for Maternal and Fetal Medicine and program director of the Christiana Care ob/gyn residency program, Newark, Delaware.
He has no conflicts of interest to report with respect to the content of this article.
Dr. Grant is a resident in the Department of Obstetrics and Gynecology at Christiana Care, Newark, Delaware.
She has no conflicts of interest to report with respect to the content of this article.
A 24-year-old G1P0 at 22 4/7 weeks’ gestation presents to labor and delivery after feeling a “pop” and experiencing a gush of fluid from her vagina. On sterile speculum exam, pooling of fluid is noted in the vaginal vault, with nitrazine and ferning tests both positive. On speculum exam the cervix appears closed and long. Transabdominal ultrasound reveals decreased amniotic fluid. You make the diagnosis of periviable rupture of the membranes. How do you counsel the patient regarding the likely clinical course, as well as potential maternal and neonatal risks and outcomes?
Premature rupture of membranes (PROM) is a condition characterized by rupture of the amniochorionic membranes prior to the onset of labor. Periviable PROM refers to instances of PROM occurring between 20 0/7 and 25 6/7 weeks’ gestation.1 Although less than 1% (approximately 0.4%)2 of pregnancies are affected by this complication, the neonatal and maternal outcomes, along with the psychological and socioeconomic impacts, can be devastating.
Understanding the usual clinical course of periviable PROM not only allows physicians to appropriately counsel families, it also provides a basis from which to guide families in making difficult decisions. The median latency period until delivery varies greatly depending upon the gestational age at which PROM occurs (Table 1).3-7 Development of intrauterine infection is the primary cause leading to delivery, with placental abruption and nonreassuring fetal testing the next-most-common indications.5,7-10 The duration of the latency period appears to be inversely related to the gestational age at which PROM occurs, with longer latency periods reported in pregnancies affected by PROM at earlier gestational ages.11 When counseling families, it is important to note that because most of the published studies are retrospective and exclude patients ineligible for expectant management (eg, pregnancies with chorioamnionitis or with a fetal demise). As a result, the latency period for pregnancies complicated by periviable PROM is likely overestimated, with maternal and neonatal morbidity likely being underreported.
Obstetric providers should carefully review the potential maternal and neonatal outcomes with the woman and any involved family members before either active or expectant management is chosen. Consultative input from maternal-fetal medicine and neonatology subspecialists, if available, helps expand understanding and facilitate a more fully informed decision by the family. If the patient is not at a Level III hospital or medical center, transfer to one with resources to care for a periviable neonate should be considered.
The fetal amniochorionic membranes are not innervated and are poorly vascularized, making physiologic wound healing, which involves local inflammation and scar formation, unlikely in the setting of spontaneous rupture.12 The rate of resealing of the amniochorionic membranes after rupture has been reported to be as high as 8%. This number, however, is likely an overestimate and more reflective of membrane resealing after an invasive event such as amniocentesis or fetoscopy rather than to spontaneous rupture.13,14 Although favorable outcomes have been reported in the literature, limited data exist describing outcomes of pregnancies that continue after membrane resealing.
There is currently no accepted definitive treatment to attempt correction of periviable PROM. In recent years, research has focused on the development of amniochorionic membrane plugs and sealants, which may patch tears in the membranes and allow for fluid reaccumulation. Various sealants have been studied, including platelets, fibrin, and gelatin.14-16 The results of some of these studies have demonstrated increased latency and improvement in neonatal survival but they are likely biased by small sample sizes and lack of comparative data.
Transabdominal amnioinfusion has similarly been reported as a potential intervention in the “treatment” of preterm PROM. A recent meta-analysis of the available data from observational studies (4 studies, N=147 total patients) and randomized controlled trials (RCTs) (3 studies, N=165 total patients) indicated a potential improvement in latency to delivery and survival when intramniotic amnioinfusion was initiated.17 Although this and other interventions may appear promising, they should still be viewed as experimental and not be performed outside of research protocols, given the limited evidence.
Rates of perinatal and neonatal morbidity and mortality are high in pregnancies complicated by periviable PROM. Antenatally, stillbirth is a significant risk from cord compression due to oligohydramnios and cord prolapse. In addition, although the live birth rate for pregnancies affected by periviable PPROM is approximately 50% (mean 47%–56%) the survival to discharge rate is only 26.3%.5,7-10
Respiratory distress syndrome, neonatal sepsis, and severe intraventricular hemorrhage are the most common contributors to neonatal mortality. These causes are not specific to periviable PROM, but rather, to delivery at the extremes of prematurity. Adverse neonatal outcomes specific to periviable PPROM most commonly result from chronic oligohydramnios, and include pulmonary hypoplasia, limb deformities (eg, clubbed feet) and other components of fetal compression syndrome. When present, the neonatal mortality rate for pregnancies complicated by pulmonary hypoplasia is very high.
Few studies have specifically evaluated the long-term morbidity associated with expectant management of periviable PROM. This is likely a result of the small population of neonates surviving this condition. In a secondary analysis of a multicenter RCT conducted by the Maternal-Fetal Medicine Units Network and Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Manuck et al. reported that neonates born following pregnancies complicated by PROM at <25 weeks gestational age suffered severe early childhood morbidity (defined as mild or severe cerebral palsy, Bayley MDI/PDI scores >2 SD below mean, or death) in 51.5% of cases.9
One tool that can also be of assistance in counseling regarding neonatal prognosis, although not specifically designed for PROM, is the use of the NICHD Neonatal Research Network (NRN) Extremely Preterm Birth Outcome Data estimator (www.nichd.nih.gov/about/org/der/branches/ppb/programs/epbo/pages/epbo_case.aspx?start=10:43:23). Based on 5 patient characteristics (gestational age, fetal plurality, birth weight, fetal gender, and exposure to antenatal corticosteroids), this tool provides estimates for overall survival and intact survival.18
Although the focus of many studies has been on neonatal outcomes, it is important to consider that expectant management of periviable PROM pregnancies can also pose a significant risk to the mother. Intrauterine infection is the most common complication affecting periviable PPROM; chorioamnionitis has been reported to occur in 31.6% to 54% of these pregnancies, placing the pregnant women at significant risk of sepsis.5,7-10 In addition, delivery by cesarean (34%), venous thromboembolism (4%), and in very rare instances, maternal death, have also been described in the literature.5,7-10
Retrospective studies have identified risk factors for periviable PROM that include intrauterine infection, history of cervical insufficiency, cerclage, antepartum bleeding, multifetal gestation, history of prior pregnancy affected by PROM or preterm labor, smoking, and both amniocentesis and fetoscopy.5,7-10
The risks and outcomes associated with periviable PROM following invasive procedures, such as genetic amniocentesis and fetoscopy, are quite different than those seen with spontaneous PROM. The incidence of PROM following midtrimester genetic amniocentesis has been reported as 1% to 2%.19,20 Pregnancies complicated by PROM after midtrimester genetic amniocentesis, however, have much better perinatal outcomes than pregnancies complicated by spontaneous PROM at comparable gestational ages. In a retrospective study by Borgida et al., pregnancies complicated by PROM following genetic amniocentesis achieved both longer latencies from the time of membrane rupture to delivery (124 days compared to 28 days) and higher gestational ages at delivery (34 weeks compared to 21.6 weeks), when compared to pregnancies with spontaneous periviable PROM.19 In addition, the perinatal survival rate was 91% after periviable PROM following genetic amniocentesis versus 9% when the PROM was spontaneous. Rates of periviable PROM following fetal surgical procedures varies greatly based on the type and indication for surgery, but is in the range of 20% to 30%. The type of surgery, indication, and size of ports used in fetoscopy directly influence both the gestational age at PROM and neonatal outcomes.19,20
Patients are most often presented with three management options following periviable PROM: pregnancy termination, indicated delivery, or expectant management. Pregnancy termination in the setting of PROM prior to viability should be discussed as an option given the neonatal prognosis and maternal risks. This management is selected in approximately one of three pregnancies in which PROM occurred prior to viability.5,7-10 For patients who elect to continue the pregnancy, the potential need for medically indicated delivery regardless of gestational age must still be assessed and discussed. Expectant management is therefore reserved for those without indications for delivery (and would exclude patients with chorioamnionitis, placental abruption, active hemorrhage, or labor).
The primary goals of expectant management are to prolong latency and improve neonatal outcomes while limiting maternal risk. Multiple antenatal interventions that have been shown to improve outcomes for pregnancies >24 weeks (antenatal corticosteroids, antibiotics, and magnesium sulfate for neuroprotection) have unknown effectiveness for those <24 wks since most clinical trials testing these interventions have not included pregnancies <24 wks.19,21-26
In February 2014, a joint workshop held by the NICHD, the Society for Maternal-Fetal Medicine, American Academy of Pediatrics, and American College of Obstetricians and Gynecologists addressed management of periviable pregnancies.1 At this workshop, general guidance for management was categorized based on GA <22 weeks 0 days, 22 weeks to 22 weeks 6 days, and ≥23 weeks 0 days (Table 2).
Patients with prior periviable PROM are at increased risk of recurrent premature PROM and preterm birth, but most women who present with periviable PROM have no prior history. A detailed evaluation focusing on the potentially modifiable causes of periviable PROM is of particular importance (eg, smoking or cervical insufficiency). A discussion regarding the potential benefits and risks of progestogens supplementation (17 OHPC 250 mg IM weekly starting at 16 weeks) and sonographic cervical length screening for future pregnancies is appropriate.22
Table 3 lists clinical recommendations for periviable PROM and the strength of evidence for those recommendations.
1. Raju TN, Mercer BM, Burchfield DJ, Joseph GF Jr. Periviable birth: executive summary of a joint workshop by Eunice Kennedy Shriver National Institute of Child Health and Human Development, Society for Maternal-Fetal Medicine, American Academy of Pediatrics, and American College of Obstetricians and Gynecologists. Am J Obstet Gynecol. 2014; 210(5):406–417.
2. Waters TP, Mercer BM. The management of preterm premature rupture of the membranes near the limit of fetal viability. Am J Obstet Gynecol. 2009; 201(3):230–240.
3. Xiao ZH, Andre P, Lacaze-Masmonteil T, Audibert F, Zupan V, Dehan M. Outcome of premature infants delivered after prolonged premature rupture of membranes before 25 weeks of gestation. Eur J Obstet Gynecol Reprod Biol. 2000;90(1):67–71.
4. Grisaru-Granovsky S, Eitan R, Kaplan M, Samueloff A. Expectant management of midtrimester premature rupture of membranes: a plea for limits. J Perinatol. 2003; 23(3):235–239.
5. Falk SJ, Campbell LJ, Lee-Parritz A, Cohen AP, Ecker J, Wilkins-Haug L, Lieberman E. Expectant management in spontaneous preterm premature rupture of membranes between 14 and 24 weeks’ gestation. J Perinatol. 2004;24(10):611–616.
6. Dinsmoor MJ, Bachman R, Haney El, Goldstein M, Mackendrick W. Outcomes after expectant management of extremely preterm premature rupture of membranes. Am J Obstet Gynecol. 2004;190(1):183–187.
7. Muris C, Girard B, Creveuil C, Durin L, Herlicoviez M, Dreyfus M. Management of premature rupture of membranes before 25 weeks. Eur J Obstet Genecol Reprod Biol. 2007;131(2):163–168.
8. Gonzales-Mesa E, Herrera JA, Urgal A, Lazarraga C, Benitez MJ, Gomez C. Temporal trends of latency period and perinatal survival after very early preterm premature rupture of fetal membranes. Arch Gynecol Obstet. 2012;286(2): 347-52.
9. Manuck TA, Eller AG, Esplin MS, Stoddard GJ, Varner MW, Silver RM. Outcomes of expectantly managed preterm premature rupture of membranes occurring before 24 weeks of gestation. Obstet Gynecol. 2009;114(1):29–37.
10. Al Riyami N, Al-Ruheili I, Al-Shezaw F, Al-Khabori M. Extreme preterm premature rupture of membranes: risk factors and feto maternal outcomes. Oman Med J. 2013;28(2):108–111.
11. Melamed N, Hadar E, Ben-Haroush A, Kaplan B,Yogev Y. Factors affecting the duration of the latency period in preterm premature rupture of membranes. Matern Fetal and Neonatal Med. 2009;22(11):1051–1056.
12. Jain VD, Sciscione A. Considerations in membrane resealing after preterm PROM. Clin Obstet Gynecol. 2011;54(2):351–357.
13. French JI, McGregor JA. The pathobiology of premature rupture of membranes. Semin Perinatol.1996;20(5): 344–368.
14. Sciscione AC, Manley JS, Pollock M, et al. Intracervical fibrin sealants: a potential treatment for early preterm premature rupture of the membranes. Am J Obstet Gynecol. 2001;184(3):368–373.
15. O’Brien JM, Barton JR, Milligan DA. An aggressive interventional protocol for early midtrimester premature rupture of the membranes using gelatin sponge for cervical plugging. Am J Obstet Gynecol. 2002;187(5):1143–1146.
16. Reddy UM, Shah SS, Nemiroff RL, et al. In vitro sealing of punctured fetal membranes: potential treatment for midtrimester premature rupture of membranes. Am J Obstet Gynecol. 2001;185(5):1090–1093.
17. Porat S, Amsalem H, Shah PS, Murphy KE. Transabdominal amnioinfusion for preterm premature rupture of membranes: a systematic review and metaanalysis of randomized and observational studies. Am J Obstet Gynecol. 2012;207(5): 393.e1–11.
18. Tyson JE, Parikh NA, Langer J, Green C, Higgins RD; National Institute of Child Health and Human Development Neonatal Research Network. Intensive care for extreme prematurity-moving beyond gestational age. N Engl J Med. 2008;358(16):1672–1681.
19. Borgida AF, Mills AA, Feldman DM, Rodis JF, Egan JF. Outcome of pregnancies complicated by rupture of membranes after genetic amniocentesis. Am J Obstet Gynecol. 2000;183(4):937–939.
20 . Beck V, Lewi P, Gucciardo L, Devlieger R. Preterm prelabor rupture of membranes and fetal survival after minimally invasive fetal surgery: a systematic review of the literature. Fetal Diagn Ther. 2012;31(1):1–9.
21. Carlo WA, McDonald SA, Fanaroff AA, et al. Eunice Kennedy Shriver National Institute of Child Health and Neonatal Research Network. Association of antenatal corticosteroids with mortality and neurodevelopmental outcomes among infants born at 22 to 25 weeks’ gestation. JAMA. 2011;306(21):2348–2358.
22. Society for Maternal-Fetal Medicine Publications Committee, with assistance of Vincenzo Berghella. Progesterone and preterm birth prevention: translating clinical trials data into clinical practice. Am J Obstet Gynecol. 2012;206(5):376–386.