Open Fetal Myelomeningocele Repair Research Articles

Effect of allograft patch closure on incidence of spinal inclusion cyst formation following open fetal myelomeningocele repair.

The aim of this study was to evaluate the incidence of spinal inclusion cyst (sIC) formation after open fetal myelomeningocele (fMMC) repair and the effect of dural patch closure. The authors conducted a retrospective review of patients who underwent open fMMC repair at their institution between March 2011 and June 2020. All patients met the criteria for intervention defined by the Management of Myelomeningocele Study (MOMS). The primary outcomes investigated were development of sIC and need for surgical intervention. Secondary outcomes included need for CSF diversion, extent of reversal of hindbrain herniation, and ambulatory status. Of 56 patients who underwent open fMMC repair, 52 had adequate spinal imaging for review. Twelve of these patients (23%) developed sIC (95% CI 0.11-0.35). Six patients experienced symptoms and required surgical detethering with sIC resection. Six additional patients had evidence of sIC on surveillance MRI but remained asymptomatic. The authors found a statistically significant relationship between the use of a dural allograft patch and sIC formation (p = 0.05). In terms of sIC development, there was no statistically significant difference between patients who underwent primary closure and those who received an allograft at the level of the fascia (p = 0.34) or skin (p = 0.26). The rate of hydrocephalus requiring CSF diversion was 52%. Interestingly, 98% of patients had improvement in extent of hindbrain herniation. Dural patch closure did not have any effect on the rate of progressive hydrocephalus (p = 0.33) or degree of reversal of hindbrain herniation (p > 0.99). This study suggested that children with prenatally repaired MMC are at higher risk for development of sIC and associated symptoms than those who undergo postnatal repair. The presentation of symptoms was also earlier in these patients than previously reported after postnatal repair. The use of a dural allograft patch appears to have a positive correlation with sIC formation. Future investigations evaluating the incidence of sIC after fetoscopic MMC repair, in which primary dural closure typically cannot be achieved and a dural patch is most often utilized, will be helpful in facilitating prenatal counseling for patients considering fetal intervention.

Open and endoscopic fetal myelomeningocele surgeries display similar in-hospital safety profiles in a large, multi-institutional database

Open intrauterine fetal myelomeningocele repair has demonstrated decreased ventriculoperitoneal shunting and improved motor outcomes despite maternal and fetal risks. Few data directly compare the safety of open vs endoscopic approaches. This study aimed to analyze in-hospital maternal and fetal outcomes of pregnant patients undergoing open vs endoscopic fetal myelomeningocele repair using a large, multi-center database. This was a review of the Pediatric Health Information System database from October 1, 2015, to December 31, 2021. All patients who underwent open or endoscopic fetal myelomeningocele repair according to the International Classification of Diseases, Tenth Revision, were identified. Demographics, gestational age, and outcomes were analyzed. Descriptive and univariate statistics were used. A total of 378 pregnant patients underwent fetal myelomeningocele repair. The approach was endoscopic in 143 cases (37.8%) and open in 235 cases (62.2%). Overall postprocedural outcomes included no maternal in-hospital mortalities or intensive care unit admissions, a median length of stay of 4 days (interquartile range, 4-5), 14 cases (3.7%) of surgical and postoperative complications, 6 cases (1.6%) of intrauterine infections, 12 cases (3.2%) of obstetrical complications (including preterm premature rupture of membranes), 3 cases (0.8%) of intrauterine fetal demise, and 16 cases (4.2%) of preterm delivery. Compared with an open approach, the endoscopic approach occurred at a later gestational age (25 weeks [interquartile range, 24-25] vs 24 weeks [interquartile range, 24-25]; P<.001) and had an increased rate of intrauterine infection (6 [4.2%] cases vs 0 [0%] case; P=.002). There was no difference between approaches in the rates of surgical complications, obstetrical complications, intrauterine fetal demise, or preterm deliveries. Compared with an open approach, endoscopic fetal myelomeningocele repair displays a comparable rate of fetal complications, including intrauterine fetal demise and preterm delivery, and a similar in-hospital maternal safety profile despite an association with increased intrauterine infection.

Open fetal myelomeningocele repair at a university hospital: surgery and pregnancy outcomes.

Myelomeningocele (MMC) is an open neural tube defect that causes great morbidity. Prenatal open repair is the standard treatment; however, there are many complications related to the procedure. This study reports preliminary findings of open in utero repair of MMC in a public tertiary hospital in Brazil and describes factors that could be associated with increased surgical morbidity. Thirty-nine patients underwent open in utero repair of MMC from October 2015 to August 2019. The Clavien-Dindo classification of surgical complications and a classification system with the preterm definitions of the World Health Organization were used, respectively, for maternal and fetal complications. A total of 28 mothers (71.8%) and 31 fetuses (79.5%) experienced at least one minor to major complication. Three mothers (7.7%) had a severe grade 4 complication. Fetal complications grades 3 to 5 occurred in 13 fetuses (33.3%). Gestational age at surgery and at birth were 24.88 ± 1.16weeks and 33.23 ± 3.68weeks, respectively. Preterm delivery occurred in 30 patients (76.9%), membrane rupture in 18 patients (46.2%) and chorioamnionitis in 13 patients (33.3%). Open fetal surgery for MMC was performed at a Brazilian public tertiary care center, resulting in three grade 4 maternal complications. Relevant fetal complications were also present. The use of a standard classification system for complications renders studies more comparable and data more useful for counseling patients. Adjustments of perioperative procedures and long-term follow-up are needed to determine the real benefit of open in utero repair of MMC at our hospital.

Postoperative Ultrasound as a Predictor of Newborn Function and Ambulation after Open Fetal Myelomeningocele Repair

Objective: Function of the lower extremities after prenatal myelomeningocele (MMC) repair is best assessed with ambulatory function at 30–36 months of age, but parents often ask about function before this milestone. Lower extremity movement can be assessed by ultrasound (US) and at the newborn exam (NE), but correlation between US, NE, and ambulation is not firmly established. Methods: This was a retrospective correlation study of fetuses that underwent open prenatal MMC repair at SSM Cardinal Glennon Fetal Care Institute, St. Louis, MO, between January 2011 and June 2017. Movement at the ankles, knees, and hips was assessed by US after open repair on postoperative days (PODs) 0–5 and at 32 weeks gestation. NE was performed by physical therapy or neurosurgery within the first month of life, and pediatric follow-up between 30 and 36 months of age was obtained to document ambulation. Results: Forty-two fetuses were included. Joint movement seen on US varied by POD: it was present on POD 1 in 7% of fetuses and 62% by POD 5. Degree of ventriculomegaly, lesion level, and lesion length did not have a significant effect on US, NE, or ambulation. Knee movement on POD 3 correlated with knee movement at NE (k = 0.58, p < 0.01), but only later knee movement correlated with ambulation (k = 0.28–0.46, p = 0.01). Hip movement at 32 weeks was the only single joint assessment that correlated with NE and ambulation (k = 0.45 and 0.46, p = 0.03 and 0.01, respectively). Conclusion: Lower extremity movement increases between POD 1 and POD 5 in fetuses after open fetal MMC repair. Knee and hip movement on US at 32 weeks correlates with ambulation at 30–36 months. These data may inform counseling, and direct therapy and spark prospective investigations.

Continuous local bupivacaine wound infusion reduces oral opioid use for acute postoperative pain control following myelomeningocele repair

For pregnancies complicated by fetal myelomeningocele who meet the established criteria, prenatal closure is a viable management option. Prenatal closure is an open procedure, with some techniques requiring greater dissection of maternal tissue than cesarean delivery; pain control is an important postoperative goal. Given the rising rates of opioid dependence and concerns regarding the fetal and neonatal effects of opioid use, our practice has turned to nonopioid pain management techniques. This study aimed to compare postoperative opioid use and pain scores in women undergoing open fetal myelomeningocele repair with and without continuous local bupivacaine wound infusion. This was a retrospective, single-center chart review of all consecutive patients who underwent open myelomeningocele repair from March 2013 to December 2019. Women were enrolled at the time of referral and locally followed for 2 weeks postoperatively. The control group received patient-controlled epidural analgesia for 48 hours with acetaminophen and oral and intravenous opioids as needed. The treatment group received patient-controlled epidural analgesia for 24 hours with acetaminophen, oral and intravenous opioids, and continuous local bupivacaine infusion. Pain scores, medication use, and postoperative milestones and complications through discharge were abstracted from the chart and compared. Of 72 subjects, 51 were in the control group and 21 in the treatment group. Total opioid use, including intravenous doses (165 vs 52.5 mg; P=.001) and daily average oral opioid use (30 vs 10.5 mg; P=.002) were lower in the treatment group. In addition, 24% of women in the treatment group used no opioid postoperatively, compared with 4% in the control group. There was no difference in postoperative day 1 to 4 pain scores, antiemetic use, or bowel function; the treatment group was discharged significantly earlier. Postoperative opioid use was reduced in women who received continuous local wound infusion of bupivacaine for incisional pain control after prenatal myelomeningocele repair. Pain control is paramount following open myelomeningocele repair; local bupivacaine wound infusion is an important adjunct to reduce opioid use postoperatively.

Systematic classification of maternal and fetal intervention-related complications following open fetal myelomeningocele repair-results from a large prospective cohort.

To systematically categorise all maternal and fetal intervention-related complications after open fetal myelomeningocele (fMMC) repair of the first 124 cases operated at the Zurich Centre for Fetal Diagnosis and Therapy. A prospective cohort study. Single centre. Mothers and fetuses after fMMC repair. Between 2010 and 2019, we collected and entered all maternal complications following fMMC repair into the Clavien-Dindo classification. For fetal complications, a classification system based on the Medical Dictionary for Regulatory Activities terminology of Adverse Events was used including the preterm definitions of the World Health Organization. Systematic classification of maternal and fetal complications following fMMC repair. Gestational ages at surgery and birth were 25.0±0.8 and 35.4±2.0weeks, respectively. In 17% of all cases, no maternal complications occurred. Maternal intervention-related complications were observed as follows: 69% grade 1, 36% grade 2, 25% grade 3, 6% grade 4 and 0% grade 5. In 34%, no fetal complications were noted; however, 43% of the fetuses developed a grade 1, 14% a grade 2, 8% a grade 3, 2% a grade 4 and 2% a grade 5 complication. This study raises awareness of complications following open fMMC repair; 6% of mothers and 2% of fetuses experienced a severe complication (grade 4) and perinatal death rate of 2% was observed (grade 5). These data are useful for prenatal counselling, they help to improve the system of fetal surgical care, and they allow benchmarking with other centres as well as comparison with fetoscopic approaches. Systematic classification of all maternal and fetal intervention-related complications following open fMMC repair.

Outcomes after In Utero Myelomeningocele Repair Based on Delivery Location.

Maternal and pediatric delivery outcomes may vary in patients who underwent open fetal myelomeningocele repair and elected to deliver at the fetal center where their fetal intervention was performed versus at the referring physician’s hospital. A prospective cohort study of 88 patients were evaluated following in utero open fetal myelomeningocele repair at a single fetal center between the years 2011–2019. Exclusion criteria included patients that delivered within two weeks of the procedure (n = 6), or if a patient was lost to follow-up (n = 1). Of 82 patients meeting inclusion criteria, 36 (44%) patients were delivered at the fetal center that performed fetal intervention, and 46 (56%) were delivered locally. Comparative statistics found that with the exception of parity, baseline characteristics and pre-operative variables did not differ between the groups. No differences in oligohydramnios incidence, preterm rupture of membranes, gestational age at delivery or delivery indications were found. Patients who delivered with a referring physician were more likely to be multiparous (p = 0.015). With the exception of a longer neonatal intensive care unit (NICU) stay in the fetal center group (median 30.0 vs. 11.0 days, p = 0.004), there were no differences in neonatal outcomes, including wound dehiscence, cerebrospinal fluid leakage, patch management, ventricular diversion, or prematurity complications. Therefore, we conclude that it is safe to allow patients to travel home for obstetric and neonatal management after open fetal myelomeningocele repair.

Hindbrain Herniation and Banana and Lemon Sign After Open Fetal Myelomeningocele Repair - When Do These Signs Disappear and is Shunting Predictable?

The aim was to describe the sonographic follow-up of hindbrain herniation (HH), the banana and lemon sign after fetal myelomeningocele (fMMC) repair, and the time of disappearance of these signs after the intervention, and to investigate any predictive value for the necessity of shunting during the infant's first year of life. Additionally, the sonographic evolution of the transcerebellar diameter (TCD) before and after fetal intervention was assessed. The first 50 patients that underwent fMMC repair at Zurich Center for Fetal Diagnosis and Therapy (www.swissfetus.ch) were included in this study. Sonographic scans performed weekly after fMMC repair focusing on HH and banana and lemon signs were analyzed and compared between the shunted and the non-shunted group. ROC curves were generated for the time intervals of resolution of the signs in order to show their predictive accuracy for the need for shunting until 1 year of age. HH resolved in 48 fetuses (96 %) before delivery. The sonographic disappearance of HH within the first two weeks after fMMC repair was associated with a significantly lower incidence of shunt placement (OR 0.19; 95 % CI 0.4-0.9) during the first year of life (p = 0.03). All fetuses with persistent HH before delivery received a shunt. TCD growth was observed in all fetuses. The reversibility of HH within two weeks after fMMC repair is associated with an 80 % lower incidence of shunt placement during the infant's first year of life. Moreover, it allows the cerebellum to grow and to normalize its configuration.

Open Intrauterine Fetal Myelomeningocele Repair: Changes in the Surgical Procedure and Perinatal Complications during the First 8 Years of Experience at a Single Center

Introduction: Open fetal myelomeningocele (fMMC) repair is nowadays a therapeutic option in selected cases. We aimed to evaluate changes in maternal and fetal outcome after fMMC repair during the first 8 years of experience at a tertiary referral fetal medicine center in Switzerland. ­Materials and Methods: Between 2010 and 2018, fMMC repair and delivery of the neonate via planned cesarean section was performed in 67 cases. Cases were retrospectively stratified into 2 groups: a “training phase” (TP) with supervision from an external surgeon during 11 operations (2010–2014, 15 cases) followed by an “experienced phase” (EP, 2014–2018, 52 cases); each phase lasted about 4 years. Both phases were compared with regard to various maternal and fetal outcome parameters. Results: Analyses did not reveal differences between TP and EP in major outcome parameters such as gestational age at delivery, chorionic membrane separation, or the incidence of placental abruption. Although more complex surgical techniques were applied in EP (e.g., dermal closure using a rotational flap), surgery time was not different from TP. At the same time, surgical complications such as oligohydramnios (27 vs. 8%, p = 0.046) with MRI-confirmed leakage (13 vs. 4%, nonsignificant) and subchorionic hematoma (20 vs. 2%, p = 0.009) were less common in EP than TP. Conclusions: This study shows that the level of competence at our center with regard to major perinatal outcome parameters was already high in the first years of fMMC repair. However, more complex surgical techniques and significantly less minor complications were observed during the most recent years.

Development of a Fetal Surgery Program to Improve Neonatal Outcomes

In 2017, our pediatric hospital developed a fetal surgery program offering in utero procedures to repair complex congenital anomalies. The service provides comprehensive care for the maternal-fetal dyad, in one location. Fetal surgery allows for treatment of specific fetal conditions that were once considered life threatening or only treatable after birth. Emerging evidence demonstrates that treatment of certain fetal conditions increases a baby’s chances of survival and improved health. Leadership and frontline staff collaborated with specialists and surgeons to develop guidelines and protocols in the implementation of this program. Our hospital was one of the first pediatric facilities in the United States to offer inpatient obstetric care for women who experience complex fetal diagnoses. An interprofessional response to fetal complications was well established within the center. The provision of fetal surgery options was a continuance of the center’s approach of comprehensive care for the maternal-fetal dyad. Extensive program development included the following: addition of a fetal surgeon; creation of nurse coordinator roles to provide support, education, and comprehensive follow-up care for patients; exhaustive literature reviews; development of process flow diagrams to delineate roles and responsibilities; and didactic and operative skills training for staff, including simulations, mandatory preprocedure huddles, and formalized procedure debriefing. Our team has now successfully performed more than 90 fetal surgeries, such as open fetal myelomeningocele (fMMC) repair, open fetal teratoma resection, fetoscopic laser treatment for twin-to-twin complications, and complex ex utero intrapartum treatment procedures. The center has completed 14 open fMMC repairs, with early outcomes data demonstrating a 15% postbirth shunt placement rate. These are encouraging data compared with the MOMS trial, which indicated a 40% shunt placement rate in those with prenatal repair and an 82% shunt placement rate with postnatal repair. For our center, the average gestational age at the time of repair was 25.4 weeks and the average gestational age at birth was 35.2 weeks. Program development challenges included logistics planning, resource allocation, and staff trepidation. Challenges were overcome through teamwork, research, and an unflagging focus on evidence-based, best-practice models. Inclusion of frontline nursing staff was critical to the success of this innovative program.

Risk Factors for Preterm Birth following Open Fetal Myelomeningocele Repair: Results from a Prospective Cohort

Background: Fetal myelomeningocele (fMMC) repair is a therapeutic option in selected cases. This study aimed to identify risk factors for preterm birth (PTB) following open fMMC repair. Methods: Sixty-seven women underwent fMMC repair and delivered a baby between 2010 and 2018 at our center. Demographic, surgical, and pregnancy complications, including potential risk factors for PTB such as preterm premature rupture of membranes (PPROM), chorioamniotic membrane separation (CMS), and placental abruption were evaluated. Results: Maternal body mass index, maternal age, parity, previous uterine surgery, gestational age at fetal surgery, total surgery duration, surgical subcutaneous hematoma, oligohydramnios, and amniotic fluid leakage were not identified as risk factors for PTB. CMS (p = 0.028, 92 vs. 52%) and PPROM (p = 0.001, 95 vs. 52%) were highly associated with PTB. Placental abruption was found more often in women after fMMC repair than in a general obstetrical population (12 vs. 1%) and ended in premature birth in all cases (p = 0.024, 100 vs. 60%). However, the majority of women delivered at a gestational age >35 weeks. Conclusions: In our study cohort, risk factors for PTB were PPROM, CMS, and placental abruption, whereas surgery duration did not influence outcome. We conclude that the surgery technique should aim to minimize CMS and amniotic fluid leakage.

230: Clinical factors associated with shorter latency after open fetal myelomeningocele repair

230: Clinical factors associated with shorter latency after open fetal myelomeningocele repair

Maternal Complications following Open Fetal Myelomeningocele Repair at the Zurich Center for Fetal Diagnosis and Therapy

Introduction: Despite undoubtable benefits of open fetal myelomeningocele (fMMC) repair, there are considerable maternal risks. The aim of this study was to evaluate and systematically categorize maternal complications after open fMMC repair. Methods: We analyzed data of 40 fMMC repairs performed at the Zurich Center for Fetal Diagnosis and Therapy. Maternal complications were classified according to a 5-level grading system based on a classification of surgical complications proposed by Clavien and Dindo. Results: We observed no grade 5 complication (death of a patient). Five (12.5%) women demonstrated severe grade 4 complications: 1 case of uterine rupture in a nullipara at 36 gestational weeks (GW), a third-degree atrioventricular block which needed short mechanical resuscitation, a bilateral lung embolism requiring intensive care unit (ICU) management due to low-output syndrome, and chorioamnionitis and urosepsis both requiring ICU management at 31 GW. Twenty-six (65%) women had minor (grade 1–3) complications. Conclusions: Only one grade 4 complication (uterine rupture, 2.5%) was a clear-cut direct consequence of fetal surgery. The other four grade 4 complications (10%) occurred in the context of, but cannot unequivocally be attributed to, fetal surgery, since they may occur also in other circumstances. The classification system used is a tenable step towards stringent documentation of maternal complications.

Prenatal Sonographic Head Circumference and Cerebral Ventricle Width Measurements Before and After Open Fetal Myelomeningocele Repair - Prediction of Shunting During the First Year of Life.

The aim of this study was to describe the sonographic evolution of fetal head circumference (HC) and width of the posterior horn of the lateral ventricle (Vp) after open fetal myelomeningocele (fMMC) repair and to assess whether pre- or postoperative measurements are helpful to predict the need for shunting during the first year of life. All 30 children older than one year by January 2017 who previously had fMMC repair at the Zurich Center for Fetal Diagnosis and Therapy were included. Sonographic evolution of fetal HC and Vp before and after fMMC repair was assessed and compared between the non-shunted (N = 16) and the shunted group (N = 14). ROC curves were generated for the fetal HC Z-score and Vp in order to show their predictive accuracy for the need for shunting until 1year of age. HC was not an independent factor for predicting shunting. However, the need for shunting was directly dependent on the preoperative Vp as well as the Vp before delivery. A Vp > 10 mm at evaluation for fMMC repair or > 15 mm before delivery identifies 100 % of the infants needing shunt placement at a false-positive rate of 44 % and 25 %, respectively. All fetuses with a Vp > 15 mm at first evaluation received a shunt. Fetuses demonstrating a Vp of > 15 mm before in utero MMC repair are extremely likely to develop hydrocephalus requiring a shunt during the first year of life. This compelling piece of evidence must be appropriately integrated into prenatal counseling.

Indomethacin Dosing and Constriction of the Ductus Arteriosus During Open Fetal Surgery for Myelomeningocele Repair

Introduction: The use of perioperative tocolytic agents in fetal surgery is imperative to prevent preterm labor. Indomethacin, a well-known tocolytic agent, can cause ductus arteriosus (DA) constriction. We sought to determine whether a relationship exists between preoperative indomethacin dosing and fetal DA constriction. Materials and Methods: This is an IRB-approved, single-center retrospective observational case series of 42 pregnant mothers who underwent open fetal myelomeningocele repair. Preoperatively, mothers received either 1 (QD) or 2 (BID) indomethacin doses. Maternal anesthetic drug exposures and fetal cardiac dysfunction measures were collected from surgical and anesthesia records and intraoperative fetal echocardiography. Pulsatility Index was used to calculate DA constriction severity. Comparative testing between groups was performed using t- and chi-square testing. Results: DA constriction was observed in all fetuses receiving BID indomethacin and in 71.4% of those receiving QD dosing (p = 0.0002). Severe DA constriction was observed only in the BID group (35.7%). QD indomethacin group received more intraoperative magnesium sulfate (p < 0.0001). Minimal fetal cardiac dysfunction (9.5%) and bradycardia (9.5%) were observed in all groups independent of indomethacin dosing. Conclusions: DA constriction was the most frequent and severe in the BID indomethacin group. QD indomethacin and greater magnesium sulfate dosing was associated with reduced DA constriction.

Early Administration of Magnesium Sulfate during Open Fetal Myelomeningocele Repair Reduces the Dose of Inhalational Anesthesia

Introduction: Optimal uterine relaxation is achieved through higher minimum alveolar concentration (MAC) of inhalational anesthetics, increasing risks to mother and fetus. Our objective was to determine if earlier administration of magnesium sulfate would reduce the requirement of inhalational anesthetics in fetal myelomeningocele repair. Materials and Methods: Prospective observational study of fetal myelomeningocele repair was performed from September 2011 to August 2017. Groups compared were: (1) magnesium sulfate at uterine closure; (2) magnesium sulfate at maternal skin incision. Maternal demographics, anesthetic agents, intraoperative complications, and pregnancy outcomes were reviewed. A Student t test was used for analysis. Results: There were 30 cases in group 1 and 21 cases in group 2. There was no difference in gestational age at intervention (24.92 ± 0.62 vs. 25.22 ± 0.47 weeks, p = 0.07) or at delivery (34.83 ± 2.77 vs. 33.98 ± 3.83 weeks, p = 0.38) between groups 1 and 2, respectively. The maximum MAC of sevoflurane was significantly lower in group 2 (1.84 ± 0.25 vs. 1.05 ± 0.28, p < 0.0001). There was no difference in the average dose of phenylephrine used. Discussion: Magnesium sulfate infusion initiated earlier in open fetal surgery reduces the total anesthetic exposure to the fetus.

490: Tocolytic options for open fetal repair of myelomeningocele: Systematic review

To describe current evidence on selection, regimen, efficacy and risks of perioperative tocolytic medications at the time of fetal repair of myelomeningocele. A search of MEDLINE, EMBASE, and SCOPUS databases was conducted from inception to March 2017. Studies that described their tocolytic protocol, gestational age at delivery, prenatal and postnatal outcomes were included. Studies that do not specify fetal myelomeningocele or do not adequately report outcomes were excluded. Neither sample size nor language was a basis for exclusion. Selection was done by 2 independent reviewers. Out of 570 studies retrieved on initial search, 462 were excluded for irrelevance. Of the 61 remaining titles, 17 were animal studies, 17 were reviews, 12 were not limited to fetal myelomeningocele, 3 studied the fetoscopic approach, 4 did not report neonatal outcomes, and 1 article was retracted. Eventually, seven articles were included. Four studies were conducted in the US; 1 study used preoperative indomethacin while the 4 studies used loading and maintenance doses of magnesium sulfate intra- and postoperatively along with postoperative indomethacin. Three of these studies used postoperative terbutaline. Three studies were done outside the US; 2 used preoperative indomethacin and one used diclofenac and Nifedipine. Magnesium sulfate was given intraoperatively. Postoperatively, magnesium sulfate was used in 2 studies and nifedipine was reported in 2 studies in different dosages. Among studies conducted in the US, average latency was 7.3 weeks (range 5.8-10.3 weeks). For studies conducted outside the US, the average latency was 13.7 weeks (range was 12 to 15.4 weeks). However, comparing a single to multiple agents, latency was comparable. Complications related to tocolysis are limited; incidence of pulmonary edema was 3.8% (2.2-5.5%) and is not altered by a single versus multiple medications. Preoperative indomethacin, intra- and postoperative course of magnesium sulfate seem to be the most commonly used and effective tocolytic options in women with open fetal myelomeningocele repair. The risk of pulmonary edema is generally small. There is no evidence that the use of multiple drugs would prolong latency compared to magnesium sulfate alone. However, further studies are needed to optimize the duration of postoperative treatment.

Tocolysis for in utero Surgery: Atosiban Performs Distinctly Better than Magnesium Sulfate

Introduction: To compare tocolysis with magnesium sulfate versus atosiban regarding the occurrence of short-term preterm labor and maternal side effects during and after open fetal myelomeningocele (MMC) repair. Material and Methods: A prospective nonrandomized cohort study was performed including 30 fetal MMC cases. The first 15 cases (group 1) received magnesium sulfate according to the MOMS protocol. In the following 15 cases (group 2), magnesium sulfate was substituted by atosiban. Chorioamniotic membrane separation (CMS), premature prelabor rupture of the fetal membranes (PPROM), preterm delivery <3 weeks after fetal MMC repair, and maternal complications due to the tocolytic medication were the major endpoints. Results: In both groups, one CMS but no PPROM was diagnosed <3 weeks after fetal MMC repair. One patient of group 2 delivered <3 weeks after fetal MMC repair because of an intraoperative placental abruption at 25 weeks. All women of group 1 showed an electrolyte imbalance during magnesium sulfate administration. One woman of group 1 developed several episodes of a third-degree atrioventricular block within the first 3 days after fetal surgery. Lethargy was found in all women during magnesium sulfate therapy. No maternal side effects were found under atosiban. Discussion: The use of atosiban resulted in an almost identical short-term uterine outcome without any serious maternal complications as seen when magnesium sulfate was given. Thus, the authors suggest using atosiban instead of magnesium sulfate in the context of open fetal surgery.

Risk Factors Associated with Preterm Delivery After Open Fetal Myelomeningocele Repair [30N

INTRODUCTION: Although open fetal myelomeningocele (MMC) repair increases the risk of preterm delivery (PTD), specific risk factors for this outcome have not been identified. The objective of this study is to determine whether gestational age at the time of open fetal MMC repair is a risk factor for PTD. METHODS: A retrospective cohort of 51 consecutive open fetal MMC repairs between 2011-2016 was analyzed by gestational age at time of surgery. Primary outcome was delivery &lt;37w0d. Secondary outcomes were PPROM, delivery &lt; 34w0d, latency from MMC repair to delivery and neonatal outcomes. RESULTS: Groups were similar in demographic and intraoperative factors. On univariate analysis, delivery &lt;37w0d was more frequent with earlier MMC repair (94% &lt; 24w0d, 69% 24w0d-24w6d and 57% &gt;25w0d, p=0.031), whereas delivery &lt; 34w0d was not (41% &lt; 24w0d, 23% 24w0d-24w6d and 19% &gt;25w0d, p=0.317). Survival-curve pairwise comparisons demonstrated a difference between the &lt; 24w0d and &gt; 25w0d groups (p=0.027). PPROM was more frequent with earlier MMC repair (71% &lt; 24w0d, 31% 24w0d-24w6d and 30% &gt;25w0d, p=0.041). Mean latency from MMC repair to delivery was similar among groups (73 days for &lt; 24w0d, 73 days for 24w0d-24w6d and 67 days for &gt;25w0d, p=0.727), as were neonatal outcomes. On multivariate analysis, earlier gestational age at MMC repair was associated with delivery before 34 weeks (p=0.039; RR 2.13; 95% CI 1.04-4.36) and 37 weeks (p=0.016; RR 3.47; 95% CI 1.26-9.59). CONCLUSION: Earlier gestational age at open fetal MMC repair was associated with preterm delivery before 37 and 34 weeks and PPROM.

PPROM Following Open Fetal Myelomeningocele Repair [2Q

INTRODUCTION: The objective is to characterize the risk of PPROM following open fetal MMC repair. METHODS: This retrospective cohort of 51 patients who underwent open fetal MMC repair was analyzed in two groups based on PPROM. Primary outcome was occurrence of PPROM. Secondary outcomes included latency from repair to delivery and gestational age at delivery. Intraoperative factors, obstetric complications and delivery outcomes were also evaluated. RESULTS: Demographics were similar between groups. PPROM occurred in 22 patients (43%) at a mean gestational age of 31w1d. Mean latency from surgery to PPROM was 50 days. Patients with PPROM had a lower gestational age at repair (24.7 + 0.7 weeks without PPROM; 23.9 + 1.2 weeks with PPROM; p &lt; 0.007), latency from MMC repair to delivery (78.3 + 17.3 days without PPROM; 61.4 + 25.8 days with PPROM; p = 0.008) and gestational age at delivery (35.9 + 2.6 weeks without PPROM; 32.7 + 3.4 weeks with PPROM; p &lt; 0.005). Patients with PPROM had lower infant birth weights (2614 g without PPROM; 1990 g with PPROM; p=0.001) and one-minute Apgars (7.2 without PPROM; 5.5 with PPROM; p=0.016) but similar five-minute Apgars. In multivariate analysis, greater gestational age at repair was protective against PPROM (RR 0.286; 95% CI 0.095-0.861; p=0.026), as was multiparity (RR 0.122; 95% CI 1.064-62.792; p = 0.043). CONCLUSION: PPROM occurred frequently among patients undergoing open fetal MMC repair and was associated with preterm delivery, earlier gestational age at repair and lower one-minute Apgar but not the occurrence of preterm labor, abruption or chorioamnionitis.