Open neural tube defect occurs in 1 in 3,000 live births and is associated with significant motor and sensory dysfunction of the lower extremities, bowel, bladder, and reproductive organs.1,2 The Management of Myelomeningocele Study demonstrated that prenatal repair of an open neural tube defect reduces the need for postnatal shunting by 12 months and improves motor outcomes at 30 months.1 After the Management of Myelomeningocele Study, hysterotomy-based prenatal open neural tube defect repair has become more common. However, the hysterotomy-based approach is associated with increased risk of preterm delivery, placental abruption, and uterine thinning or dehiscence compared with postnatal repair.1 In addition, the hysterotomy location (usually uterine upper segment) mandates cesarean delivery,1 and future pregnancies after hysterotomy have been shown to be at risk for miscarriage, placenta previa, placenta accreta, placental abruption, uterine rupture, stillbirth, and need for hysterectomy.3
Minimally invasive techniques for prenatal neural tube defect repair use two distinct approaches—percutaneous4–6 and laparotomy with uterine exteriorization7—which use partial amnioreduction and CO2 insufflation to improve access and visualization. Early results from the exteriorized-uterus fetoscopic approach7 used at Texas Children's Fetal Center have demonstrated comparable neonatal neurologic advantage as well as nonneurologic benefits, including the possibility of vaginal delivery.7
As fetoscopic neural tube defect repair becomes more widespread, there is a need to disseminate information about strategies for managing labor and vaginal delivery. The objective of this study is to report the labor, delivery, and neonatal outcomes in a cohort of women who delivered neonates after fetoscopic neural tube defect repair.
MATERIALS AND METHODS
We conducted a retrospective cohort study of all patients with both completed fetoscopic neural tube defect repair and delivery at our institution from April 2014 to January 2018 (ClinicalTrials.gov NCT02230072). Oversight of our fetoscopic repair protocol is provided by the U.S. Food and Drug Administration (#G140201), the Baylor College of Medicine institutional review board (34680), the Baylor College of Medicine Fetal Therapy Board, and a data safety monitoring board.
All patients met the Management of Myelomeningocele Study eligibility criteria1 (singleton, maternal age 18 years old or older, maternal body mass index (calculated as weight (kg)/[height (m)]2) less than 35, neural tube defect upper boundary between T1 and S1, hindbrain herniation, gestational age between 19 0/7 and 25 6/7 weeks, normal karyotype, no anomalies unrelated to spina bifida, no severe kyphosis, no risk factors for preterm birth [eg, short cervix or previous preterm birth], no pre-existing placental abruption, and no contraindication to surgery including previous hysterotomy in the active uterine segment). We excluded from the cohort those cases that were intraoperatively converted from fetoscopic to open repair (n=4), that were abandoned (n=2), and that delivered at an outside institution (n=1). We included patients with both iterative and standardized fetoscopic approaches,7 which involve low transverse laparotomy, uterine exteriorization, and placement of ports in the uterine wall. In the iterative approach (n=11), we used either two ports (n=6) or three ports (n=5) with a combination of 5-French, 7-French, 12-French, and 16-French ports. In the standardized approach (n=23), all patients had two 12-French ports in the uterine wall. After port placement, minimally invasive neural tube defect repair was then performed by a pediatric neurosurgeon, closing skin and dura in a single layer. Details of our fetoscopic procedure have been previously described7 (Appendix 1, available online at http://links.lww.com/AOG/B85). Management of labor and vaginal or cesarean delivery was standardized, and induction and augmentation of labor used a low-dose oxytocin protocol in accordance with American College of Obstetricians and Gynecologists guidelines.8 All patients receiving oxytocin had epidural analgesia.
The primary outcomes of interest included frequency of vaginal delivery and frequency of term delivery. Secondary outcomes of interest included obstetric and neonatal outcomes after oxytocin use and rate of intralabor cesarean delivery for obstetric or fetal indications. Complications of interest included preterm prelabor rupture of membranes (PROM), chorioamnionitis, placental abruption, postdelivery transfusion, uterine dehiscence or rupture, neonatal Apgar score less than 7 at 5 minutes, and neonatal umbilical artery acidosis (pH less than 7.15). We reviewed the electronic medical records of eligible patients to extract data regarding maternal, surgical, obstetric, and neonatal characteristics as well as data regarding management of labor. The following definitions were used in data extraction. A patient experienced labor if adequate contractions to produce cervical change had been documented. Prelabor rupture of membranes was defined as leakage of fluid before onset of labor confirmed by positive testing with one or more of the following: Nitrazine paper, microscopic ferning, or overt vaginal pooling of fluid. Diagnosis of placental abruption was based on clinical signs and symptoms as well as confirmatory placental histology. Diagnosis of chorioamnionitis was based on clinical and laboratory assessment.9,10 Neonatal biometrics were converted to percentiles using nomogram calculators available from INTERGROWTH-21st.11
For analysis, patients were grouped by mode of delivery and oxytocin use. Descriptive statistics were generated using proportions to describe frequency and using median and range to describe central tendency, because the sample size was limited. For statistical comparisons, Wilcoxon rank-sum and Fisher exact test were used. Confidence intervals for point estimates were generated using the Clopper-Pearson exact method for proportions. Data analysis was performed using STATA 14.2 for Mac.
Thirty-four patients underwent fetoscopic neural tube defect repair; subsequently, 17 (50%, 95% CI 32–68%) delivered vaginally and 17 delivered by cesarean. Excluding the eight nonurgent, prelabor cesarean deliveries, 26 patients experienced labor (76%, 95% CI 59–89%) (Fig. 1). Median gestational age was 38 1/7 weeks at vaginal delivery (range 26 0/7–40 2/7 weeks of gestation) and 37 1/7 weeks at cesarean delivery (range 25 5/7–40 5/7 weeks of gestation, P=.38). Of all deliveries, 62% (95% CI 44–78%) occurred at or after 37 weeks of gestation.
There were no significant differences in maternal characteristics between women undergoing vaginal or cesarean delivery (Table 1). Both groups had neural tube defect repair surgery at comparable gestational ages in the second trimester, and there were no differences between those who underwent a standardized or an iterative approach (although sample sizes were underpowered to detect a difference). The cesarean delivery group had a higher proportion of anterior placentas and a longer duration of neural tube defect repair surgery (median difference 40 minutes). The vaginal delivery group had a lower volume of estimated blood loss at delivery and their neonates had a shorter length of stay in the neonatal intensive care unit. History of PROM, gestational age at delivery, Apgar score, neonatal biometrics, and maternal complications did not differ between neonates who were delivered vaginally or by cesarean (Table 1).
Three women delivered by nonurgent, prelabor cesarean delivery: one with severe intrauterine growth restriction and breech presentation at 37 1/7 weeks of gestation and two at 39 weeks of gestation—one as a result of a history of a prior cesarean delivery and one with significant macrocephaly secondary to hydrocephalus.
Five women delivered by urgent, prelabor cesarean delivery. Of these, four were admitted for preterm PROM and cesarean delivery was deemed necessary as a result of nonreassuring fetal heart tracing. One fetus decompensated intraoperatively during fetoscopic neural tube defect repair, without recovery to resuscitative measures, and a transverse lower uterine segment cesarean delivery was performed at 25 5/7 weeks of gestation.
Twenty-six patients underwent labor (Fig. 1; Appendix 2 [Appendix 2 is available online at http://links.lww.com/AOG/B85]), 17 of whom delivered vaginally (65%, 95% CI 44–83%) and nine of whom underwent urgent intrapartum cesarean delivery (35%, 95% CI 17–56%), for nonreassuring fetal heart tracings (n=6), breech presentation (n=2), and failed induction (n=1). Oxytocin practices are detailed in Appendix 3, available online at http://links.lww.com/AOG/B85. Eleven cases (42%, 95% CI 23–63%) received low-dose oxytocin8 (six induced, five augmented); we started at 1–2 milliunits per minute and increased by 1–2 milliunits per minute every 30–60 minutes until a maximum of 20–36 milliunits per minute. Oxytocin was administered for a median of 13.9 hours (range 5.3–36.0 hours) with no difference between induced and augmented patients (22.9 [5.6–36.0] hours vs 5.6 [5.3–24.0] hours, P=.08). In all patients with oxytocin exposure, 5-minute Apgar scores were reassuring (greater than 7) and no neonates demonstrated acidosis. Of 34 deliveries, the following obstetric outcomes occurred (Tables 1 and 2). Three underwent operative vaginal delivery (one vacuum for nonreassuring fetal heart tracings and two Kielland's rotational forceps). One was a successful vaginal delivery after cesarean. There were three placental abruptions (9%, 95% CI 2–24%) and one suspected case of chorioamnionitis after preterm PROM, not confirmed on histology (3%, 95% CI 0–15%). In all 17 cesarean deliveries, inspection of the uterus showed no evidence of uterine dehiscence and all port sites were well healed and of normal myometrial thickness (Fig. 2); no vaginal deliveries were concerning for uterine rupture at any time. No mothers required a transfusion during or after delivery.
Twenty-one neonates (62%, 95% CI 44–78%) were delivered at term, and 13 were delivered at less than 37 weeks of gestation. One neonate (3%, 95% CI 0–15%) exhibited umbilical artery acidosis after emergent prelabor cesarean delivery for fetal bradycardia (pH 6.99, base excess unavailable). There were two neonates with 5-minute Apgar scores less than 7 but no evidence of acidosis; both were delivered by urgent cesarean for category III fetal heart tracings (25 5/7 weeks and 31 3/7 weeks of gestation). Most neonates (94%, 95% CI 80–99%) had normal 5-minute Apgar scores.
These data regarding the outcomes of a trial of labor and vaginal delivery after fetoscopic neural tube defect repair are reassuring and suggest that vaginal delivery may reduce the risk of maternal morbidity from cesarean delivery while achieving similar neonatal outcomes. Of 34 women with completed fetoscopic repairs, 50% (95% CI 32–68%) had vaginal delivery and 35% underwent intralabor cesarean delivery (95% CI 17–57%). Using low-dose oxytocin for induction and augmentation, consistent with American College of Obstetricians and Gynecologists’ guidelines,8 we had one failed induction and no cases of uterine dehiscence or rupture. Compared with published studies reporting outcomes after open1 and minimally invasive neural tube defect repair,4–6 our cohort is the only study with vaginal delivery; we also demonstrate a higher rate of term delivery (62%, 95% CI 44–78%), lower rate of preterm PROM, and similar rates of chorioamnionitis, placental abruption, transfusion, and uterine dehiscence or rupture (Table 2). Overall, 94% (95% CI 80–99%) of our cohort had normal 5-minute Apgar scores and only one case had transient neonatal acidosis.
Vaginal delivery is contraindicated after hysterotomy-based neural tube defect repair for fear of uterine rupture, and most fetuses that have undergone hysterotomy-based neural tube defect repair are delivered preterm (34–36 weeks of gestation). In the Management of Myelomeningocele Study trial, 36% of hysterotomy-based prenatal neural tube defect repair cases had uterine thinning or dehiscence at the time of cesarean delivery.1 Additionally, Wilson et al12 demonstrated that 18% of women undergoing open fetal surgery in the index pregnancy had uterine dehiscence or rupture at the time of repeat cesarean delivery in a subsequent pregnancy. In our study, no patients with fetoscopic neural tube defect repair were noted to have uterine rupture or dehiscence. In addition, no cases with total percutaneous neural tube defect repair in other studies had uterine dehiscence or rupture (Pedreira et al: 0/10 cases; Kohl 2014 and Degenhardt et al: 0/51 cases).4–6 Combining all cases with cesarean delivery after minimally invasive neural tube defect repair (all cases from Pedreira and Kohl plus 17 cases from this cohort), there are 78 patients with inspection of the uterine surface at delivery who did not have any dehiscence or rupture; additionally, our 17 patients who delivered vaginally did not have any signs concerning for uterine rupture. Together, this suggests that labor and vaginal delivery according to standard obstetric principles is a reasonable option after minimally invasive neural tube defect repair.
Limitations of our study include the retrospective nature and modest sample size. Thus, this study has limited power to detect differences resulting from small sample sizes, and we cannot state conclusively that vaginal delivery after fetoscopic neural tube defect repair is safe.
In conclusion, these data regarding a trial of labor, low-dose oxytocin, and vaginal delivery after previous fetoscopic neural tube defect repair are reassuring. Notably, fetoscopic repair appears to allow for delivery at a more advanced gestational age than open repair. Perinatal outcomes of fetoscopic neural tube defect repair cases are excellent, independent of the mode of delivery.
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