Open Hysterotomy Research Articles

Ambulation after in-utero fetoscopic or open neural tube defect repair: predictors for ambulation at 30 months.

To compare the ambulatory status of a cohort of children who had undergone prenatal repair of an open neural tube defect (ONTD) using one of two different methods (fetoscopic or open hysterotomy) with that of a cohort who had undergone postnatal repair, and to identify the best predictors of ambulation at 30 months of age. This was a retrospective review of a cohort of children who underwent ONTD repair either prenatally (n = 110), by fetoscopic surgery (n = 73) or open hysterotomy surgery (n = 37), or postnatally (n = 51), in a single tertiary hospital between November 2011 and May 2023. The cohort comprised a consecutive sample of cases who had undergone ONTD repair in-utero following Management of Myelomeningocele Study (MOMS) trial criteria and cases who had undergone postnatal repair, meeting the same criteria, which were also followed up after birth at the same institution. Motor function assessment by ultrasound was recorded at referral, 6 weeks after prenatal repair, or after referral in postnatally repaired cases, and at the last ultrasound scan before delivery. Clinical examinations to assess motor function at birth and at 12 months were retrieved from records. Intact motor function was defined as first sacral myotome (S1) motor function. Ambulatory status data at each follow-up visit were collected. The proportion of children who were able to walk independently after 30 months of age was compared between those who had undergone fetoscopic vs open prenatal surgery and between prenatal (by either fetoscopic or open surgery) and postnatal ONTD repair. Logistic regression analyses were performed to identify predictors for independent ambulation. After 30 months, the proportion of infants who were able to walk independently was higher in prenatally vs postnatally repaired cases (51.8% vs 15.7%, P < 0.01), and there was no difference between those with fetoscopic (52.1%) vs open (51.4%) prenatal repair (P = 0.66). In the prenatally repaired group, having intact motor function at 12 months (adjusted odds ratio (aOR), 9.14 (95% CI, 2.64-31.63), P < 0.01) and at birth (aOR, 4.50 (95% CI, 1.21-16.80), P = 0.02) were significant predictors of independent walking at 30 months; an anatomical level of lesion below L2 at referral (aOR, 1.83 (95% CI, 1.30-2.58), P = 0.01) and female gender (aOR, 3.51 (95% CI, 1.43-8.61), P < 0.01) were also predictive for this outcome. Prenatally repaired cases of ONTD have a better chance of being able to walk independently at 30 months than do those who undergo postnatal repair. In patients with prenatally repaired ONTD, ambulatory status at 30 months can be predicted by observing a low lesion level at referral (below L2) and intact motor function postnatally. These results have implications for parental counseling and planning for supportive therapy in pregnancies affected by ONTD. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Prenatal surgery in fetal myelomeningocele with severe ventriculomegaly.

Prenatal myelomeningocele (MMC) repair is performed to decrease risk for treatment of hydrocephalus after birth and to preserve motor function. Some centers may not consider patients candidates for surgery if severe ventriculomegaly is present and there is no expected benefit in decreased risk for hydrocephalus treatment. This study sought to compare postnatal outcomes of fetuses with MMC and severe ventriculomegaly (>15mm) who underwent prenatal repair, with fetuses with severe ventriculomegaly who underwent postnatal repair and fetuses with ventriculomegaly (<15mm) who underwent prenatal repair. This was a retrospective study of fetuses with MMC that underwent prenatal or postnatal repair between 2012 and 2021 at a single institution. The cohort was divided based on preoperative fetal ventricular size into two groups, those with severe ventriculomegaly (≥15 mm) and those without severe ventriculomegaly (<15 mm). Fetal ventricular size was measured by MRI prior to surgery using the standardized approach and the mean of the left and right ventricle was used for analysis. Motor function of lower extremities was assessed at the time of referral by ultrasound and if flexion-extension movements of the ankle were seen, it was considered as preserved S1 motor function. Postnatal outcomes including motor function of lower extremities assessed at birth and need for diversion procedure for hydrocephalus treatment during the first year of life were collected and compared between groups. Data was presented as median and range or number and percentages as appropriate. P value >0.05 was considered statistically significant. Multivariate regression analysis was used to adjust for potential confounders. 154 patients were included in this study: 145 patients underwent fetal surgery (101 fetoscopic and 44 open hysterotomy) and 9 patients with severe ventriculomegaly underwent postnatal repair. Among the 145 patients who underwent fetal surgery, 22 presented with severe ventriculomegaly. Prenatally repaired fetuses with severe ventriculomegaly at referral were at a significantly higher need for hydrocephalus treatment by 12 months than those without severe ventriculomegaly (62% vs. 29%, p<0.01). However, motor function assessment at birth was similar between both prenatally repaired groups (OR=0.92, 95% CI [0.33-2.59], p=0.88) adjusted for the anatomical level of the lesion. The prenatally repaired group with severe ventriculomegaly had better preserved motor function levels at birth compared to the postnatal repair group with severe ventriculomegaly (L3 with 11.1% S1 motor function; p=<0.01 and p=<0.01). Prenatally repaired patients with severe ventriculomegaly had an 18.9 times chance of having an intact motor function at birth [95% CI (1.2 - 290.1)] adjusted for ethnicity, presence of clubfeet at referral, and gestational age at delivery compared to postnatal repair. There was not a significant difference in the need for hydrocephalus treatment in the first year of life between prenatal and postnatal repair of patients with severe ventriculomegaly (61.9% vs 87.5%, p=0.18). Although fetuses with MMC and severe ventriculomegaly do not seem to benefit from fetal surgery in terms of postnatal hydrocephalus treatment, they benefit from increased chance of preserved motor function at birth. Results from this study highlight the benefits of having prenatal MMC repair for cases with severe ventriculomegaly at referral to preserve motor function. This article is protected by copyright. All rights reserved.

Local host response of commercially available dural patches for fetal repair of spina bifida aperta in rabbit model.

Fetal surgery for spina bifida aperta (SBA) by open hysterotomy typically repairs anatomical native tissue in layers. Increasingly, fetoscopic repair is performed using a dural patch followed by skin closure. We studied the host response to selected commercially available patches currently being used in a fetal rabbit model for spina bifida repair. SBA was surgically induced at 23-24days of gestation (term=31days). Fetal rabbits were assigned to unrepaired (SBA group), or immediate repair with Duragen™ or Durepair™. Non-operated littermates served as normal controls. At term, spinal cords underwent immunohistochemical staining including Nissl and glial fibrillary acidic protein. We hypothesized that spinal cord coverage with a dural patch and skin closure would preserve motor neuron density within the non-inferiority limit of 201.65cells/mm2 and reduce inflammation compared to unrepaired SBA fetuses. Motor neuron density assessed by Nissl staining was conserved both by Duragen (n=6, 89.5; 95% CI -158.3 to -20.6) and Durepair (n=6, 37.0; 95% CI -132.6 to -58.5), whereas density of GFAP-positive cells to quantify inflammation was lower than in unrepaired SBA-fetuses (SBA 2366.0±669.7cells/mm2 vs. Duragen 1274.0±157.2cells/mm2 ; p=0.0002, Durepair 1069.0±270.7cells/mm2 ; p<0.0001). Covering the rabbit spinal cord with either Duragen or Durepair followed by skin closure preserves motor neuron density and reduces the inflammatory response.

Systematic classification and comparison of maternal and obstetrical complications following 2 different methods of fetal surgery for the repair of open neural tube defects

In utero repair of open neural tube defect (ONTD) using an open hysterotomy approach (hereafter referred to as "Open") has been shown to reduce the need for ventriculo-peritoneal shunting and to improve motor outcomes for affected infants. Laparotomy-assisted fetoscopic repair (hereafter referred to as "Hybrid") is an alternate approach that may confer similar neurological benefits, while reducing the incidence of hysterotomy related complications. In this study we aimed to analyze procedure related maternal and fetal complications of in-utero repair using the Clavien-Dindo classification, and to compare the outcomes of the Hybrid and Open approaches. This was a retrospective cohort study conducted in a single center between September 2011 and July 2021. All patients who met the MOMS criteria and who underwent either Hybrid or Open fetal surgery were included, Maternal complications were classified using a unique adapatation of the Clavien-Dindo scoring system allowing the development of a comprehensive complication index score specific to fetal surgery. Primary fetal outcome was defined as gestational age at delivery and summarized according to the World Health Organization definitions of preterm delivery. There were 146 fetuses with ONTD who were eligible for, and underwent, in utero repair during the study period. Of these, 102 underwent Hybrid fetoscopic repair and 44 underwent Open hysterotomy repair. Gestational age at the time of surgery was higher in the Hybrid group when compared with the Open group (25.1 vs. 24.8 weeks, p=0.004). Maternal body mass index was lower in the Hybrid compared to the Open group (25.4 vs 27.1 kg\m2, p=0.02). The duration of Hybrid fetoscopic surgery was significantly longer than for the Open repair (250 min vs 164 min, p<0.001). There was a significantly lower Clavien-Dindo grade III complication rate (4.9% vs. 43.2%, p<0.001), as well as a significantly lower overall comprehensive maternal complication index (8.7 vs. 22.6, p=0.021), in the Hybrid group vs. the Open group. Gestational age at delivery was significantly higher in the Hybrid group (38.1 weeks) compared to the Open group (35.8 weeks) p<0.001, and this finding persisted when gestational age at delivery was analyzed using the WHO definitions of preterm delivery. Utilization of our adaptation of the standardized Clavien-Dindo classification to assess the maternal complications associated with in utero ONTD repair provides a new method to objectively assess different fetal surgical approaches. It also provides a much-needed standardized tool to allow objective comparisons between methods, which can be used when counseling patients. The Hybrid ONTD repair was associated with a lower rate of maternal adverse events than the Open approach, and was associated with later gestational age at delivery and less preterm delivery.

Economic analysis of prenatal fetoscopic vs open-hysterotomy repair of open neural tube defect.

Fetal repair of an open neural tube defect (ONTD) by open hysterotomy has been shown to reduce the need for ventriculoperitoneal shunting and improve motor outcomes for infants, but increases the risk of Cesarean section and prematurity. Fetoscopic repair is an alternative approach that may confer similar neurological benefits but allows for vaginal delivery and reduces the incidence of hysterotomy-related complications. We sought to compare the costs of care from fetal surgery until neonatal discharge, as well as the clinical outcomes, associated with each surgical approach. This was a retrospective cohort study of patients who underwent prenatal ONTD repair, using either the open-hysterotomy or the fetoscopic approach, at a single institution between 2012 and 2018. Clinical outcomes were collected by chart review. A cost-consequence analysis was conducted from the hospital perspective, and included all inpatient and ambulatory hospital and physician costs incurred for the care of mothers and their infants, from the time of maternal admission for fetal ONTD repair up to postnatal maternal and infant discharge. Costs were estimated using cost-to-charge ratios for hospital billing and the Medicare physician fee schedule for physician billing. Seventy-eight patients were included in the analysis, of whom 47 underwent fetoscopic repair and 31 underwent open-hysterotomy repair. In the fetoscopic-repair group, compared with the open-repair group, fewer women underwent Cesarean section (53% vs 100%; P < 0.001) and the median gestational age at birth was significantly higher (38.1 weeks (interquartile range (IQR), 35.2-39.1 weeks) vs 35.7 weeks (IQR, 33.9-37.0 weeks); P < 0.001). No case of uterine dehiscence was observed in the fetoscopic-repair group, compared with an incidence of 16% in the open-repair group. After adjusting for baseline characteristics, there was no significant difference in the total cost of care between the fetoscopic-repair and the open-repair groups (median, $76 978 (IQR, $60 312-$115 386) vs $65 103 (IQR, $57 758-$108 103); P = 0.458). Fetoscopic repair of ONTD, when compared with the open-hysterotomy approach, reduces the incidence of Cesarean section and preterm delivery with no significant difference in total costs of care from surgery to infant discharge. This novel approach may represent a cost-effective alternative to improve maternal and neonatal outcomes for this high-risk population. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Longitudinal evaluation of motor function in patients who underwent prenatal or postnatal neural tube defect repair.

To compare the evolution of motor function from mid-gestation to 12 months of age between prenatally and postnatally repaired cases of open neural tube defect (ONTD). This was a retrospective cohort study of all fetuses that underwent prenatal (fetoscopic or open hysterotomy) or postnatal ONTD repair at a single institution between November 2011 and December 2018. The anatomical level of the lesion was defined as the upper bony spinal defect at initial magnetic resonance imaging assessment. Prenatal motor function of the lower extremities was evaluated by ultrasound according to the metameric level of the neurological lesion, based on the methodology of Carreras et al. Fetal motor function was assessed at referral, at 6 weeks after surgery in prenatally repaired cases or 6 weeks after referral in postnatally repaired cases (6-week follow-up) and at the last scan before delivery. In addition, motor function was assessed by a detailed neurological examination at birth and 12 months of age. First sacral (S1) neurological level of the lesion was considered as intact motor function. For statistical comparisons, we attributed numerical scores to each neurological level and motor function was expressed as median (range) neurological level. Motor function (as numerical score) and the proportion of cases with intact motor function and with motor function two or more levels better than expected based on the anatomical level of the lesion were compared between the prenatal- and postnatal-repair groups. Fetal motor function was compared to the anatomical level of the lesion at referral and a better motor function was defined when it was two or more levels better than the anatomical level of the lesion. To assess the evolution of motor function, we compared motor function at referral with that at each follow-up assessment using paired t-tests. We included 127 patients with ONTD, of whom 93 underwent prenatal (51 fetoscopic and 42 open hysterotomy) and 34 postnatal repair. At the time of referral, cases in the prenatal- and postnatal-repair groups presented with a similar anatomical level of lesion (L3 (T9-S1) vs L3 (T7-S1); P = 0.52), similar motor function (S1 (L1-S1) vs S1 (L1-S1); P = 0.52) and a similar proportion of cases with intact motor function (81% vs 79%; P = 0.88) and with motor function two or more levels better than expected based on the anatomical level of the lesion (62% vs 74%; P = 0.24). When compared with prenatally repaired cases, postnatally repaired cases showed worse motor function at birth (S1 (L1-S1) vs L4 (L1-S1); P < 0.01) and at 12 months of age (S1 (L1-S1) vs L4 (L1-S1); P < 0.01). In the prenatal-repair group, motor function remained stable from the time of referral to 12 months of age (P = 0.26). Furthermore, the proportion of patients with intact motor function at referral (81% (75/93)) was similar to that at the 6-week follow-up (74% (64/87)), at the last scan before birth (74% (42/57)), at birth (68% (63/93)) and at 12 months of age (67% (39/58)) in the prenatal-repair group. In the postnatal-repair group, worse motor function, starting from the third trimester to 12 months of age, was observed. The proportion of patients with intact motor function at referral (79% (27/34)) was similar to that at 6-week follow-up (80% (12/15); P = 0.92), but was lower at the last assessment before birth (25% (2/8); P < 0.01), at birth (24% (8/34); P < 0.01) and at 12 months of age (28% (7/25); P < 0.01). Similar findings were noted when assessing the evolution of the proportion of cases with motor function two or more levels better than expected based on the anatomical level of the lesion in each group. Infants with ONTD that underwent postnatal repair had worse motor function at birth and at 12 months of age than at mid-gestation and when compared with infants that underwent prenatal ONTD repair. Prenatal motor function assessment by ultrasound is an adequate tool to identify those infants who should have a good clinical motor function after delivery. Information obtained by fetal motor function assessment can have an important role for patient counseling and case selection for surgery. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Role of Imaging in Obstetric Interventions: Criteria, Considerations, and Complications.

US has an established role in the prenatal detection of congenital and developmental disorders. Many pregnant women undergo US at 18-20 weeks of gestation for assessment of fetal anatomy and detection of structural anomalies. With advances in fetoscopy and minimally invasive procedures, in utero fetal interventions can be offered to address some of the detected structural and physiologic fetal abnormalities. Most interventions are reserved for conditions that, if left untreated, often cause in utero death or a substantially compromised neonatal outcome. US is crucial for preprocedural evaluation and planning, real-time procedural guidance, and monitoring and assessment of postprocedural complications. Percutaneous needle-based interventions include in utero transfusion, thoracentesis and placement of a thoracoamniotic shunt, vesicocentesis and placement of a vesicoamniotic shunt, and aortic valvuloplasty. Fetoscopic interventions include myelomeningocele repair and tracheal balloon occlusion for congenital diaphragmatic hernia. In rare cases, open hysterotomy may be required for repair of a myelomeningocele or resection of a sacrococcygeal teratoma. Monochorionic twin pregnancies involve specific complications such as twin-twin transfusion syndrome, which is treated with fetoscopic laser ablation of vascular connections, and twin reversed arterial perfusion sequence, which is treated with radiofrequency ablation. Finally, when extended placental support is necessary at delivery for repair of congenital high airway obstruction or resection of lung masses, ex utero intrapartum treatment can be planned. Radiologists should be aware of the congenital anomalies that are amenable to in utero interventions and, when necessary, consider referral to centers where such treatments are offered. Online supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article. ©RSNA, 2021.

Two-port, exteriorized uterus, fetoscopic meningomyelocele closure has fewer adverse neonatal outcomes than open hysterotomy closure

In utero closure of meningomyelocele using an open hysterotomy approach is associated with preterm delivery and adverse neonatal outcomes. This study compared the neonatal outcomes in inutero meningomyelocele closure using a 2-port, exteriorized uterus, fetoscopic approach vs the conventional open hysterotomy approach. This retrospective cohort study included all consecutive patients who underwent in utero meningomyelocele closure using open hysterotomy (n=44) or a 2-port, exteriorized uterus, fetoscopic approach (n=46) at a single institution between 2012 and 2020. The 2-port, exteriorized uterus, fetoscopic closure was composed of the following 3 layers: a bovine collagen patch, a myofascial layer, and a skin. The frequency of respiratory distress syndrome and a composite of other adverse neonatal outcomes, including retinopathy of prematurity, periventricular leukomalacia, and perinatal death, were compared between the study groups. Regression analyses were performed to determine any association between the fetoscopic closure and adverse neonatal outcomes, adjusted for several confounders, including gestational age of <37 weeks at delivery. The fetoscopic closure was associated with a lower rate of respiratory distress syndrome than the open hysterotomy closure (11.5% [5 of 45] vs 29.5% [13 of 44]; P=.037). The proportion of neonates with a composite of other adverse neonatal outcomes in the fetoscopic group was half of that observed patients in the open hysterotomy group; however, this difference did not reach statistical significance (4.3% [2 of 46] vs 9.1% [4 of 44]; P=.429). Here, regression analysis has demonstrated that fetoscopic meningomyelocele closure was associated with a lower risk of respiratory distress syndrome (adjusted odds ratio, 0.23; 95% confidence interval, 0.06-0.84; P=.026) than open hysterotomy closure. In utero meningomyelocele closure using a 2-port, exteriorized uterus, fetoscopic approach was associated with a lower risk of respiratory distress syndrome than the conventional open hysterotomy meningomyelocele closure.

81 A three-layer fetoscopic spina bifida closure has fewer neonatal complications than open in-utero closure

Spina bifida is one of the most common congenital anomalies of the central nervous system. This study compares neonatal outcomes between in-utero closure of spina bifida using a three-layer fetoscopic approach and the conventional open hysterotomy approach. This retrospective cohort study included all consecutive patients who underwent in-utero spina bifida closure using either open hysterotomy (n=43) or a three-layer fetoscopic approach (n=41) at a single institution, between 2012 and 2020. The three-layer fetoscopic closure comprised a bovine collagen patch, a myofascial layer and a skin layer. The frequency of a composite of adverse neonatal outcomes including low 5-minute Apgar scores (≤3), respiratory distress syndrome, retinopathy of prematurity, necrotizing enterocolitis and neonatal death were compared between the study groups. Regression analyses were performed to determine the association of a three-layer fetoscopic spina bifida closure and the composite of adverse neonatal outcomes adjusted for maternal BMI, gestational age (GA) at surgery, chorioamniotic membrane separation, delivery mode, preterm prelabor rupture of membranes and GA at delivery at <37 weeks. The three-layer fetoscopic spina bifida closure was associated with a lower rate of the composite of adverse neonatal outcomes than the open hysterotomy spina bifida closure (14.6% vs. 37.2%; p=0.025). The median gestational age at delivery and birthweight in the three-layer fetoscopic approach group were significantly higher than in the open hysterotomy approach group; whereas maternal BMI was significantly higher in the latter group (see Table 1). Regression analysis demonstrated that the three-layer fetoscopic spina bifida closure is associated with a lower risk for the composite of adverse neonatal outcomes adjusted for confounding variables (adjusted odds ratio: 0.15; 95% CI: 0.04-0.57; p=0.006). In-utero spina bifida closure using a three-layer fetoscopic approach is associated with fewer adverse neonatal outcomes than the conventional open hysterotomy spina bifida closure.

Prenatal predictors of motor function in children with open spina bifida: a retrospective cohort study.

To identify predictors for intact motor function (MF) at birth and at 12months of life in babies with prenatally versus postnatally repaired open spina bifida (OSB). Retrospective cohort study. Texas Children's Hospital, 2011-2018. Patients who underwent either prenatal or postnatal OSB repair. Prenatal MF of the lower extremities was evaluated by ultrasound following a metameric distribution at the time of diagnosis (US1), 6weeks postoperatively (or 6weeks after initial evaluation in postnatally repaired cases) (US2) and at the last ultrasound before delivery (US3). At birth and at 12months, MF was assessed clinically. Intact MF (S1) was defined as the observation of plantar flexion of the ankle. Results from logistic regression analysis are expressed as odds ratios (95% confidence intervals, P values). A total of 127 patients were included: 93 with prenatal repair (51 fetoscopic; 42 open hysterotomy repair) and 34 with postnatal repair. In the prenatal repair group, predictors for intact MF at birth and at 12months included: absence of clubfeet (OR11.3, 95%CI 3.2-39.1, P<0.01; OR10.8 95%CI 2.4-47.6, P<0.01); intact MF at US1 (OR19.7, 95%CI 5.0-76.9, P<0.01; OR8.7, 95%CI 2.0-38.7, P<0.01); intact MF at US2 (OR22, 95%CI 6.5-74.2, P<0.01; OR13.5, 95%3.0-61.4, P<0.01); intact MF at US3 (OR13.7, 95%CI 3.4-55.9, P<0.01; OR12.6, 95%CI 2.5-64.3, P<0.01); and having a flat lesion (OR11.2, 95%CI 2.4-51.1, P<0.01; OR4.1, 95%CI 1.1-16.5, P=0.04). In the postnatal repair group, the only predictor of intact MF at 12months was having intact MF at birth (OR15.2, 95%CI 2.0-113.3, P=0.03). The detection of intact MF inutero from mid-gestation to delivery predicts intact MF at birth and at 12months in babies who undergo prenatal OSB repair. Detection of intact motor function inutero predicts intact motor function at birth and at 1year in fetuses who undergo prenatal OSB repair.

Foetal therapies and their influence on preterm birth.

Foetal therapy aims to improve perinatal survival or to prevent severe long-term handicap. Foetal medicine opens a new territory by treating the foetus as a patient. The mother has nothing to gain in terms of health benefits, yet she is inherently also undergoing treatment. In utero foetal interventions can be divided into ultrasound-guided minimally invasive procedures, fetoscopic procedures and open hysterotomy procedures, which carry an inherent risk of ruptured membranes and preterm birth. In this review, we summarise the conditions that may benefit from foetal therapy and review the current therapies on offer, each with their associated risk of ruptured membrane and preterm birth. We also look into some risk limiting and preventative strategies to mitigate these complications.

Maternal and obstetric complications in fetal surgery for prenatal myelomeningocele repair: a systematic review.

Comparing prenatal and postnatal surgical repair techniques for myelomeningocele (MMC), in utero fetal surgery has increasingly gained acceptance and is considered by many specialized centers the first choice of treatment. Despite its benefits, as demonstrated in the Management of Myelomeningocele Study (MOMS), including reduced need for CSF shunting in neonates and improved motor outcomes at 30 months, there is still an ongoing debate on fetal and maternal risks associated with the procedure. Prenatal open hysterotomy, fetoscopic MMC repair techniques, and subsequent delivery by cesarean section are associated with maternal complications. The aim of this systematic review is to assess the available literature on maternal and obstetric complication rates and perinatal maternal outcomes related to fetal MMC repair. The authors identified references for inclusion in this review by searching PubMed and MEDLINE, with restrictions to English language, case series, case reports, clinical trials, controlled clinical trials, meta-analyses, randomized controlled trials, reviews, and systematic reviews. The rate of maternal and obstetric complications was analyzed based on studies focusing on this issue and presenting clear results on the matter. Of 1264 articles screened, 36 were included in this systemic review, whereof 11 were eligible for data analysis and comparison. The average overall rate of maternal and obstetric complications corresponds to 78.6%. The majority of the described events are obstetric complications, varying from chorioamniotic membrane separation in 65.6% of cases, oligohydramnios in 13.0% of cases, placental abruption in 5.0% of cases, spontaneous or preterm premature membrane rupture in 42.0% of cases, and early preterm delivery in 11.3% of cases due to uterine dehiscence, occurring in 0.9% of cases. The most common medical complications are development of pulmonary edema occurring in 2.8%, gestational diabetes in 3.7%, gestational hypertension/preeclampsia in 3.7%, and need for blood transfusions in 3.2% of cases. Limitations of the review arise from the lack of data in the current literature, with maternal and obstetric complications being underreported. Although the efforts of further advancement of intrauterine prenatal MMC repair aim to increase neonatal outcomes, maternal health hazard will continue to be an issue of crucial importance and further studies are required.

Prenatal and postnatal MRI findings in open spinal dysraphism following intrauterine repair via open versus fetoscopic surgical techniques.

The purpose of the study is to examine MRI findings of the brain and spine on prenatal and postnatal MRI following intrauterine repair of open spinal dysraphism (OSD) by open hysterotomy and fetoscopic approaches. This study is a single-center HIPAA-compliant and IRB-approved retrospective analysis of fetal MRIs with open spinal dysraphism from January 2011 through December 2018 that underwent subsequent prenatal repair of OSD. Sixty-two patients met inclusion criteria: 47 underwent open repair, and 15 underwent fetoscopic repair, with an average gestational age of 22.6 ± 1.4 weeks at initial MRI. On postnatal MRI, spinal cord syrinx was seen in 34% (16/47) of patients undergoing open versus 33.3% (5/15) undergoing fetoscopic repair (P = 0.96). Postnatally, there was no significant difference in hindbrain herniation between the open versus fetoscopic repair groups (P = 0.28). Lateral ventricular size was significantly larger in the open (20.9 ± 6.7 mm) versus the fetoscopic repair (16.1 ± 4.9 mm) group (P = 0.01). Though lateral ventricular size in the open repair group was larger than the fetoscopic repair group, this can likely be explained by initial selection criteria used for fetoscopic repair. Other postoperative imaging parameters on postnatal MRI were not significantly different between the two groups.

Spinal Dysraphia, Chiari 2 Malformation, Unified Theory, and Advances in Fetoscopic Repair.

Fetal spina bifida, the most common nonlethal birth defect of the central nervous system, results in substantial neurologic morbidity. The unified theory describes the complex relationship between local spinal lesions and development of Chiari 2 malformation, contributing to hydrocephalus. Prenatal ultrasonography reliably allows diagnosis, but fetal MR imaging is an important complement to identify additional brain abnormalities. Fetal surgery improves neurologic and motor outcomes, but various approaches, either open hysterotomy or minimally invasive to the uterus, carry substantial obstetric risks. Optimization of the fetoscopic approach aims to minimize maternal and obstetric risks, but data regarding longer-term outcomes are awaited.

Prenatal brain imaging for predicting need for postnatal hydrocephalus treatment in fetuses that had neural tube defect repair in utero.

To determine if brain imaging in fetuses that underwent prenatal repair of neural tube defect (NTD) can predict the need for postnatal hydrocephalus treatment (HT) in the first year postpartum. This was a retrospective study of fetuses diagnosed with open NTD that had in-utero myelomeningocele repair between April 2014 and April 2016. Independent variables were collected from four chronological sets of fetal images: presurgery ultrasound, presurgery magnetic resonance imaging (MRI), 6-week postsurgery MRI and predelivery ultrasound. The following independent variables were collected from all image sets unless otherwise noted: gestational age, head circumference, mean ventricular width, ventricular volume (MRI only), hindbrain herniation (HBH) score (MRI only), and level of lesion (LOL), defined as the upper bony spinal defect (presurgery ultrasound only). Based on these measurements, additional variables were defined and calculated including change in degree of HBH, ventricular width growth (mm/week) and ventricular volume growth (mL/week). The need for HT (by either ventriculoperitoneal shunt or endoscopic third ventriculostomy with choroid plexus cauterization) was determined by a pediatric neurosurgeon using clinical and radiographic criteria; a secondary analysis was performed using the MOMS trial criteria for hydrocephalus. The predictive value of each parameter was assessed by receiver-operating characteristics curve and logistic regression analyses. Fifty affected fetuses were included in the study, of which 32 underwent open hysterotomy and 18 fetoscopic repair. Two neonates from the open hysterotomy group died and were excluded from the analysis. The mean gestational ages for the presurgery ultrasound, presurgery MRI, postsurgery MRI and predelivery ultrasound were 21.8 ± 2.1, 22.0 ± 1.8, 30.4 ± 1.6 and 31.0 ± 4.9 weeks, respectively. A total of 16 subjects required HT. The area under the curve (AUC) of predictive accuracy for HT showed that HBH grading on postsurgery MRI had the strongest predictive value (0.86; P < 0.01), outperforming other predictors such as postsurgery MRI ventricular volume (0.73; P = 0.03), MRI ventricular volume growth (0.79; P = 0.01), change in HBH (0.82; P = 0.01), and mean ventricular width on predelivery ultrasound (0.73; P = 0.01). Other variables, such as LOL, mean ventricular width on presurgery ultrasound, mean ventricular width on presurgery and postsurgery MRI, and ventricular growth assessment by MRI or ultrasound, had AUCs < 0.7. Optimal cut-offs of the variables with the highest AUC were evaluated to improve prediction. A combination of ventricular volume growth ≥ 2.02 mL/week and/or HBH of 3 on postsurgery MRI were the optimal cut-offs for the best prediction (odds ratio (OR), 42 (95% CI, 4-431); accuracy, 84%). Logistic regression analyses showed that persistence of severe HBH 6 weeks after surgery by MRI is one of the best predictors for HT (OR, 39 (95% CI, 4-369); accuracy, 84%). There was no significant change in the results when the MOMS trial criteria for hydrocephalus were used as the dependent variable. Persistence of HBH on MRI 6 weeks after prenatal NTD repair independently predicted the need for postnatal HT better than any ultrasound- or other MRI-derived measurements of ventricular characteristics. These results should aid in prenatal counseling and add support to the hypothesis that HBH is a significant driver of hydrocephalus in myelomeningocele patients. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Amniotic membrane and placental histopathological findings after open and fetoscopic prenatal neural tube defect repair

To describe and compare placental and amniotic histology in women who underwent a fetoscopic myelomeningocele repair to those who underwent an open hysterotomy myelomeningocele repair. Also, we intended to compare findings from both prenatal repair groups to age-matched control pregnant patients. Placental and membrane histopathology from 43 prenatally repaired spina bifida cases (17 fetoscopic and 26 open) and 18 healthy controls were retrospectively assessed. Quantitative assessment of histopathology included apoptosis count and maternal and fetal underperfusion scores. Qualitative assessment included the detection of pigmented macrophages and/or signs of placental/amniotic inflammation. Associations between the duration of surgery or the duration of CO2 insufflation and quantitative histological parameters were tested. Fetoscopic surgery cases did not show significant differences in any of the studied parameters when compared against controls. No differences were detected either when compared with open repaired cases, except for lower proportion of pigmented laden macrophages in the fetoscopic group (11.8% vs 61.5%, P<0.01). No associations between the duration of surgery or the duration of CO2 exposure and any of the quantitative histological parameters were detected. These preliminary results support the lack of detrimental effects of the use of heated and humidified CO2 gas for uterine insufflation to fetal membranes and placenta.

68: Prenatal open hysterotomy vs. two-port exteriorized uterus fetoscopic myelomeningocele repair. perinatal outcomes from a single center

To assess obstetrical and perinatal outcomes after fetal open or fetoscopic myelomeningocele (MMC) repair. Retrospective cohort study from 2011-2018. 66 patients diagnosed with fetal MMC who underwent a prenatal repair in our center via open-hysterotomy (N=33) or fetoscopic repair (N=33) were included. All patients fulfilled Management of Myelomeningocele Study (MOMS) inclusion and exclusion criteria. Open-hysterotomy repair was performed as reported in MOMS trial. Our standardized fetoscopic repair is a two port, exteriorized uterus, technique in CO2, using interrupted sutures for the neurosurgical repair.13 of the fetosocpic and 8 of the open repaired patients received a dural patch. Obstetrical and perinatal outcomes were compared between groups using Student's t-test for independent samples or Mann-Whitney U test if they had normal or non-normal distribution, respectively. Chi-square or Fisher's exact tests were used to compare qualitative data. Duration of surgery and spinal defect repair were lengthier in the fetoscopic group. There were no differences in intraoperative fetal bradycardia or postoperative complications. Fetoscopically repaired cases were delivered later [38.6 (29.9-40.9) weeks vs. 35.7 (27.3-37.9) weeks; p<0.01] with higher birth weight [3120(1375-4430)grams vs. 2611 (624-3623)grams; p<0.01] and a lower rate of cesarean delivery (43% vs. 100%; p<0.01). Intact surgical sites were seen in all 14 fetoscopic cases delivered by c-section and in 21 of open cases (p<0.01). Uterine adhesions were more common after open repair (36% vs. 14%; p<0.01). One neonatal death occurred after an open repair due to extreme preterm birth and sepsis. Fetoscopic repair has a lengthier surgery but similar postoperative complications to open repair, while offering significant benefits including higher gestational age at birth, vaginal delivery and a decreased risk of adhesions and scar dehiscence.

88: Postnatal follow up of infants who underwent prenatal fetoscopic and open neural tube defect repair

To assess postnatal development and growth in infants who had prenatal neural tube defect (NTD) repair by either Fetoscopic or Open hysterotomy approach. Secondarily, we aimed to assess the need for hospital admission, surgeries and rehabilitative therapies in both groups. A total of 37 infants (19 Fetoscopic and 18 Open) were enrolled in this longitudinal prospective cohort study. Fetoscopically repaired infants were classified into Iterative (first 12 cases with changing technique) or Standardized (7 cases with standard technique) groups. Infant growth was assessed using anthropometric measurements from the medical record (weight, length and head circumference) transformed into percentiles using WHO nomograms. Information regarding rehabilitative (occupational, physical and speech) therapies, hospital admissions, surgeries and use of orthotics was obtained by parental interview. The tests were administered between 6 months and 5 years (Table). Gestational age at delivery was significantly higher in the Standardized group. No differences in weight, length or head circumference percentiles were detected. There was no difference in need for rehabilitative therapies between the Fetoscopic and Open groups, and nor was there any differences in the need for endoscopic third ventriculostomy (ETV), shunt placement or tethered cord release surgery detected between the groups. Rate of hospital admission and surgical intervention were also similar. The Open group had a higher need for orthotics (83.3%) than did the overall Fetoscopic group (43.8%) with lowest need being in the Iterative group (28.6%). Prenatal Fetoscopic NTD repair results in similar postnatal infant outcomes as those seen following NTD repair via open hysterotomy.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

491: Neurodevelopmental assessment in patients who underwent prenatal fetoscopic and open fetal neural tube defect repair

To compare neurodevelopmental outcomes in infants who had undergone prenatal neural tube defect (NTD) repair by either a Fetoscopic or by an Open hysterotomy approach 41 infants were included (22 Fetoscopic and 19 Open) in this prospective longitudinal cohort study. Neurodevelopmental outcomes were assessed using the Developmental Profile 3 (DP-3) screening test, which evaluates 5 domains of development as documented in an interview with the patient’s parents. Results were compared to reference values. Infants were categorized as “Delayed and Below Average” if the standard score (SS) was ≤ 84 and “Average and Above average ” if the SS was ≥ 85. In addition, infants were clinically evaluated by a Developmental Pediatrician in our Spina Bifida Clinic, with a full evaluation and documented the motor development and the disparity (if any) between the anatomic and functional levels of the lesion. The Capute Scales test evaluates visual-motor problem solving (CAT Developmental Quotient -DQ-) and language abilities (CLAMS DQ). Results were categorized as “Delayed” if DQ <70, “Borderline” if DQ 70-84, and “Normal” if DQ > 84. Motor DQ scores were determined by the Gesell Developmental Scale The DP-3 test was performed on 22 infants after Fetoscopic repair and on 14 after Open repair (Table 1). Fetoscopically repaired infants were assessed at an earlier age than their Open counterparts, but no differences in neurodevelopmental outcome were detected. The Capute Scales were performed on 14 Fetoscopic and on 19 Open repair infants at a similar age (Table 2). No differences in CAT DQ, CLAMS DQ, Motor DQ or classification of developmental outcomes were detected. Improvement in functional level by 3 or more was noted in 33.3% of the Fetoscopic group and in 26.3% of the Open group (p=0.7) There were no significant differences in neurodevelopmental outcome between those infants who underwent a Fetoscopic NTD repair as compared to their Open repair counterpartsView Large Image Figure ViewerDownload Hi-res image Download (PPT)

Current Strategy of Fetal Therapy I: Principles of In-utero Treatment, Pharmacologic Intervention, Stem Cell Transplantation and Gene Therapy

AbstractFetal conditions with high morbidity are amenable for prenatal intervention. It is important that the selective and investigative nature of most procedures needs to be clarified with the family during counseling session. Fetal therapy is fostered by accurate prenatal diagnosis with advanced fetal imaging, and molecular genetics technology. The treatments can be categorized into medical treatment, stem cell transplantation and gene therapy, minimally invasive intervention, endoscopic surgery, and open hysterotomy approach. Scientific validation of their genuine benefits has been a subject of ongoing researches. Prenatal administrations of pharmaceutical agents, for prophylactic or therapeutic purposes, have been broadly adopted. Transplacental administration of betamethasone to enhance the function of pneumocytes type II in premature fetus has been widely practiced for decades, and it might be the most common ‘fetal therapy’ being performed. However, the optimal dosage and interval of prenatal steroids administration was validated only recently. More invasive route of fetal administration, such as transamniotic, direct intramuscular, and intravenous injection, may be required for other pharmacologic agents. In this article, the authors selected to review common fetal conditions whose proposed prenatal pharmacologic treatments have undergone scientific validations. In-utero stem cell transplantation and gene therapy remain highly experimental. Informed choice and clinical experiment need to be balanced when prenatal treatment is offered.