Background
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.
Objective
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.
Study Design
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.
Results
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.
Conclusion
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.
Introduction
Myelomeningocele (MMC) is the most common nonlethal congenital defect of the central nervous system. It is characterized by protrusion of the meninges and spinal cord that results in permanent neurologic damage. The estimated frequency of MMC is 3.4 per 10,000 live births. This number is an underestimation as approximately one third of these pregnancies are aborted. There is significant lifelong morbidity associated with MMC that includes bladder and bowel incontinence, lower extremity paralysis, difficulty in ambulation, and hydrocephalus that might require ventricular shunting. It is one of the few nonlethal fetal anomalies for which prenatal surgery is currently offered. Evidence from the Management of MMC Study (MOMS) revealed decreased need for shunting, reversal of hindbrain herniation, and improved motor function in the prenatal surgery group compared to the postnatal surgery group.
Despite promise with fetal MMC (fMMC) repair, there are significant complications to consider. These include chorioamniotic membrane separation (CMS), preterm premature rupture of membranes (PPROM), and preterm labor that lead to preterm delivery, oligohydramnios, pulmonary edema, placental abruption, uterine scar concerns, and maternal transfusion at the time of delivery. In the MOMS trial, CMS and PPROM complicated 26% and 46% of cases, respectively, which remain significant issues with open fetal surgery. The objective of this study was to identify risk factors associated with CMS and PPROM after fMMC repair, as well as describe the clinical course of CMS and PPROM in this scenario.
Materials and Methods
This was a retrospective cohort study of patients undergoing fMMC repair and subsequent delivery from January 2011 through December 2013 at 1 institution. Patients were identified through the institutional fMMC database and chart review was performed. The study was approved by the institutional review board.
Patient inclusion and exclusion criteria were similar to those used in the MOMS trial. The MOMS trial was a randomized trial comparing prenatal repair of fMMC to standard postnatal repair. Pregnancies considered candidates for in utero repair were singletons, maternal body mass index ≤35, maternal age >18 years, gestational age 19 0/7 to 25 6/7 weeks, lesion level T1-S1 with hindbrain herniation and no associated anomalies, normal karyotype, and no maternal obstetrical contraindications or medical contraindications. Exclusion criteria included severe kyphosis, increased risk of preterm birth, abnormal placentation, previous hysterotomy in the active uterine segment, and body mass index >35. Perioperative evaluation and operative technique were also similar to those used in the MOMS trial. The hysterotomy technique included placing 2 full-thickness sutures of 0 polydioxanone suture under ultrasound guidance followed by making a small incision through the myometrium and the membranes using electrocautery. A uterine stapling device (Covidien Auto Suture, Norwalk, CT) was passed into the uterine cavity to create a transverse hysterotomy approximately 6-8 cm in length. Postoperative care included strict bed rest for the first week postoperatively followed by slowly increasing activity over the first postoperative month. Women were seen weekly for prenatal care and ultrasound was performed to monitor for evidence of CMS, oligohydramnios, and general fetal status. A departure from the MOMS trial protocol allowed for women who opted to return to their referring center for ongoing prenatal care and delivery. This occurred at approximately 3-4 weeks after the fetal surgery provided that the patient and fetus were stable.
Membrane separation was identified on serial ultrasound evaluations. The diagnosis of CMS was made solely by ultrasound findings and was not associated with overt leakage of fluid. Membrane separation was classified depending on the extent of detachment. Membrane separation confined to a small area of the uterine wall that could be visualized in 1 plane of transducer imaging was defined as local membrane separation. Membrane separation extending beyond 1 imaging plane that could be traced the entire length of the uterine wall was defined as global separation. Patients with local membrane separation were treated as outpatients with weekly follow-up and were counseled regarding symptoms to monitor including leaking of fluid, vaginal bleeding, contractions, abdominal pain, and changes in fetal movement patterns. Patients with global separation were treated as inpatients, including fetal surveillance 2-3 times daily. The decision to proceed with delivery was based on various factors such as gestational age, PPROM, preterm labor, fetal status, and evidence of chorioamnionitis. Perioperative factors and outcomes among patients with CMS were compared to those without CMS.
Patients admitted with a presumed diagnosis of PPROM were included in the PPROM group. PPROM was clinically diagnosed with associated leakage of fluid from the vagina. Those admitted with ruptured membranes after fMMC repair received standard care for PPROM. Those ≥34 weeks were immediately delivered. Women <34 weeks received antenatal steroids, latency antibiotics, and neuroprotective magnesium sulfate as indicated by gestational age. Delivery was then carried out at 34 weeks unless evidence of preterm labor, vaginal bleeding or concern for abruption, chorioamnionitis, or nonreassuring fetal monitoring developed prior to that gestational age. PPROM was based on clinical symptoms, including overt vaginal leakage of fluid, pooling of amniotic fluid in the vaginal vault, nitrazine and/or ferning positive on exam, or persistent oligohydramnios.
Student t test was used for continuous variables and the χ 2 test or the Fischer exact test for categorical variables. A P value ≤ .05 was considered significant. Multiple logistic regression was used when appropriate. Statistical analyses were performed using software (STATA, Version 10.1; StataCorp, College Station, TX).
Materials and Methods
This was a retrospective cohort study of patients undergoing fMMC repair and subsequent delivery from January 2011 through December 2013 at 1 institution. Patients were identified through the institutional fMMC database and chart review was performed. The study was approved by the institutional review board.
Patient inclusion and exclusion criteria were similar to those used in the MOMS trial. The MOMS trial was a randomized trial comparing prenatal repair of fMMC to standard postnatal repair. Pregnancies considered candidates for in utero repair were singletons, maternal body mass index ≤35, maternal age >18 years, gestational age 19 0/7 to 25 6/7 weeks, lesion level T1-S1 with hindbrain herniation and no associated anomalies, normal karyotype, and no maternal obstetrical contraindications or medical contraindications. Exclusion criteria included severe kyphosis, increased risk of preterm birth, abnormal placentation, previous hysterotomy in the active uterine segment, and body mass index >35. Perioperative evaluation and operative technique were also similar to those used in the MOMS trial. The hysterotomy technique included placing 2 full-thickness sutures of 0 polydioxanone suture under ultrasound guidance followed by making a small incision through the myometrium and the membranes using electrocautery. A uterine stapling device (Covidien Auto Suture, Norwalk, CT) was passed into the uterine cavity to create a transverse hysterotomy approximately 6-8 cm in length. Postoperative care included strict bed rest for the first week postoperatively followed by slowly increasing activity over the first postoperative month. Women were seen weekly for prenatal care and ultrasound was performed to monitor for evidence of CMS, oligohydramnios, and general fetal status. A departure from the MOMS trial protocol allowed for women who opted to return to their referring center for ongoing prenatal care and delivery. This occurred at approximately 3-4 weeks after the fetal surgery provided that the patient and fetus were stable.
Membrane separation was identified on serial ultrasound evaluations. The diagnosis of CMS was made solely by ultrasound findings and was not associated with overt leakage of fluid. Membrane separation was classified depending on the extent of detachment. Membrane separation confined to a small area of the uterine wall that could be visualized in 1 plane of transducer imaging was defined as local membrane separation. Membrane separation extending beyond 1 imaging plane that could be traced the entire length of the uterine wall was defined as global separation. Patients with local membrane separation were treated as outpatients with weekly follow-up and were counseled regarding symptoms to monitor including leaking of fluid, vaginal bleeding, contractions, abdominal pain, and changes in fetal movement patterns. Patients with global separation were treated as inpatients, including fetal surveillance 2-3 times daily. The decision to proceed with delivery was based on various factors such as gestational age, PPROM, preterm labor, fetal status, and evidence of chorioamnionitis. Perioperative factors and outcomes among patients with CMS were compared to those without CMS.
Patients admitted with a presumed diagnosis of PPROM were included in the PPROM group. PPROM was clinically diagnosed with associated leakage of fluid from the vagina. Those admitted with ruptured membranes after fMMC repair received standard care for PPROM. Those ≥34 weeks were immediately delivered. Women <34 weeks received antenatal steroids, latency antibiotics, and neuroprotective magnesium sulfate as indicated by gestational age. Delivery was then carried out at 34 weeks unless evidence of preterm labor, vaginal bleeding or concern for abruption, chorioamnionitis, or nonreassuring fetal monitoring developed prior to that gestational age. PPROM was based on clinical symptoms, including overt vaginal leakage of fluid, pooling of amniotic fluid in the vaginal vault, nitrazine and/or ferning positive on exam, or persistent oligohydramnios.
Student t test was used for continuous variables and the χ 2 test or the Fischer exact test for categorical variables. A P value ≤ .05 was considered significant. Multiple logistic regression was used when appropriate. Statistical analyses were performed using software (STATA, Version 10.1; StataCorp, College Station, TX).
Results
A total of 88 patients underwent fMMC repair and subsequent delivery during the study period. In all, 21 patients (23.9%) were diagnosed with CMS by ultrasound and PPROM occurred in 27 patients (30.7%). Among the CMS patients, 10 (47.6%) were diagnosed with global CMS and 11 (52.4%) with local CMS. Six patients initially diagnosed with local CMS had progression to global CMS. Table 1 describes the maternal and preoperative variables in the CMS and non-CMS groups. Membrane separation was higher in patients undergoing fMMC repair at a lower gestational age (22.5 vs 23.4 weeks, P = .01). None of the other preoperative variables were statistically significantly different between the 2 groups, although placental location approached significance. Pregnancy outcomes between CMS and no CMS are presented in Table 2 . The CMS group had a significantly higher rate of PPROM ( P = .008) and a lower gestational age at delivery (32.1 vs 34.4 weeks in CMS vs non-CMS groups, respectively).
| Chorioamniotic membrane separation, N = 21 | No membrane separation, N = 67 | P value | ||
|---|---|---|---|---|
| Age, y, mean ± SD | 30.7 ± 3.6 | 29.2 ± 4.8 | .2 | |
| Parity [nulliparous], N (%) | 5 (23.8) | 28 (41.8) | .13 | |
| BMI, kg/m 2 , mean ± SD | 28.0 ± 4.4 | 26.1 ± 4.2 | .07 | |
| Intraoperative version done, N (%) | 5 (22.7) | 30 (45.4) | .44 | |
| Placental location, N (%) | Anterior placenta | 6 (28.6) | 36 (53.7) | |
| Posterior placenta | 15 (68.2) | 31 (47.0) | .05 | |
| Gestational age at fMMC repair, wk, mean ± SD | 22.5 ± 1.6 | 23.4 ± 1.3 | .01 | |
| Total operative time, min, mean ± SD | 77.9 ± 13.3 | 79.5 ± 11.6 | .6 | |
| Hysterotomy time, min, mean ± SD | 38.4 ± 7.8 | 36.9 ± 10.2 | .6 | |
| LOS, post-fMMC repair, d, mean ± SD | 4.2 ± 0.6 | 4.2 ± 1.0 | .65 | |
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