title: Chorioamniotic membrane separation and preterm premature rupture of membranes complicating in utero myelomeningocele repair.
abstract: Since the results of the Management of Myelomeningocele Study were published, maternal-fetal surgery for the in utero treatment of spina bifida has become accepted as a standard of care alternative. Despite promise with fetal management of myelomeningocele repair, there are significant complications to consider. Chorioamniotic membrane separation and preterm premature rupture of membranes are known complications of invasive fetal procedures. Despite their relative frequency associated with fetal procedures, few data exist regarding risk factors that may be attributed to their occurrence or the natural history of pregnancies that are affected with chorionic membrane separation or preterm premature rupture of membranes related to the procedure.
  
  
  
  The objective of this study was to review chorioamniotic membrane separation and preterm premature rupture of membranes in a cohort of patients undergoing fetal management of myelomeningocele repair including identification of risk factors and outcomes.
  
  
  
  This was a retrospective review of patients undergoing fetal management of myelomeningocele repair and subsequent delivery from January 2011 through December 2013 at 1 institution. Patients were identified through the institutional fetal management of myelomeningocele repair database and chart review was performed. Perioperative factors and outcomes among patients with chorioamniotic membrane separation and preterm premature rupture of membranes were compared to those without. Risk factors associated with the development of chorioamniotic membrane separation and preterm premature rupture of membranes were determined.
  
  
  
  A total of 88 patients underwent fetal management of myelomeningocele repair and subsequently delivered during the study period. In all, 21 patients (23.9%) were diagnosed with chorioamniotic membrane separation by ultrasound and preterm premature rupture of membranes occurred in 27 (30.7%). Among the chorioamniotic membrane separation patients, 10 (47.6%) were diagnosed with global chorioamniotic membrane separation and 11 (52.4%) with local chorioamniotic membrane separation. Earlier gestational age at the time of fetal surgery was a significant risk factor for the development of chorioamniotic membrane separation (P = .01) and preterm premature rupture of membranes (P < 0.0001). Chorioamniotic membrane separation was significantly associated with preterm premature rupture of membranes (59.1% vs 21.2%, P = .008) and earlier gestational age at delivery (32.1 ± 4.2 vs 34.4 ± 3.5 weeks, P = .01). The average number of days from chorioamniotic membrane separation to preterm premature rupture of membranes was 11.0 ± 10.1 and from chorioamniotic membrane separation to delivery was 31.0 ± 22.5. The mean time interval between fetal management of myelomeningocele repair and preterm premature rupture of membranes was 47.9 days. Mean latency period from preterm premature rupture of membranes to delivery was 25 days. Gestational age at delivery was significantly lower in patients with preterm premature rupture of membranes (31.6 ± 3.4 vs 34.9 ± 3.5 weeks, P = .0001). Using logistic regression analysis, nulliparity, gestational age at fetal management of myelomeningocele repair, and membrane separation remained significant risk factors for preterm premature rupture of membranes.
  
  
  
  Chorioamniotic membrane separation after fetal management of myelomeningocele repair is a significant risk factor for subsequent development of preterm premature rupture of membranes and preterm delivery. Fetal management of myelomeningocele repair <23 weeks is associated with higher rates of preterm premature rupture of membranes and chorioamniotic membrane separation. Therefore fetal management of myelomeningocele repair should be deferred until ≥23 weeks to mitigate these complications. Nulliparity also appears to increase the risk for preterm premature rupture of membranes.
authors.affiliation: Center for Fetal Diagnosis and Treatment, Children's Hospital of Philadelphia, Philadelphia, PA.
authors.forename: Shelly
authors.initials: S
authors.lastname: Soni
authors.affiliation: Center for Fetal Diagnosis and Treatment, Children's Hospital of Philadelphia, Philadelphia, PA. Electronic address: moldenhauerj@email.chop.edu.
authors.forename: Julie S
authors.initials: JS
authors.lastname: Moldenhauer
authors.affiliation: Center for Fetal Diagnosis and Treatment, Children's Hospital of Philadelphia, Philadelphia, PA.
authors.forename: Susan S
authors.initials: SS
authors.lastname: Spinner
authors.affiliation: Center for Fetal Diagnosis and Treatment, Children's Hospital of Philadelphia, Philadelphia, PA.
authors.forename: Norma
authors.initials: N
authors.lastname: Rendon
authors.affiliation: Center for Fetal Diagnosis and Treatment, Children's Hospital of Philadelphia, Philadelphia, PA.
authors.forename: Nahla
authors.initials: N
authors.lastname: Khalek
authors.affiliation: Center for Fetal Diagnosis and Treatment, Children's Hospital of Philadelphia, Philadelphia, PA.
authors.forename: Juan
authors.initials: J
authors.lastname: Martinez-Poyer
authors.affiliation: Center for Fetal Diagnosis and Treatment, Children's Hospital of Philadelphia, Philadelphia, PA.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Johnson
authors.affiliation: Center for Fetal Diagnosis and Treatment, Children's Hospital of Philadelphia, Philadelphia, PA.
authors.forename: N Scott
authors.initials: NS
authors.lastname: Adzick
mesh_terms: D000328:Adult; D000650:Amnion / Q000000981:diagnostic imaging*; D002823:Chorion / Q000000981:diagnostic imaging*; D015331:Cohort Studies; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000209:etiology*; D005333:Fetus / Q000601:surgery*; D005865:Gestational Age; D006801:Humans; D016015:Logistic Models; D008591:Meningomyelocele / Q000601:surgery*; D010298:Parity; D011183:Postoperative Complications; D011247:Pregnancy; D011248:Pregnancy Complications; D012189:Retrospective Studies; D012307:Risk Factors
keywords: chorioamniotic membrane separation; fetal therapy; myelomeningocele; preterm premature rupture of membranes; spina bifida