Percutaneous/mini-laparotomy fetoscopic repair of open spina bifida: a novel surgical technique.

Open spina bifida is the most common congenital anomaly of the central nervous system compatible with life. Prenatal repair of open spina bifida via open maternal-fetal surgery has been shown to improve postnatal neurologic outcomes, including reducing the need for ventriculoperitoneal shunting and improving lower neuromotor function. Fetoscopic repair of open spina bifida minimizes the maternal risks while providing similar neurosurgical outcomes to the fetus. The following 2 fetoscopic techniques are currently in use: (1) the laparotomy-assisted approach, and (2) the percutaneous approach. The laparotomy-assisted fetoscopic technique appears to be associated with a lesser risk of preterm birth than the percutaneous approach. However, the percutaneous approach avoids laparotomy and uterine exteriorization and is associated with lesser anesthesia risk and improved maternal postsurgical recovery. The purpose of this article was to describe our experience with a modified surgical approach, which we call percutaneous/mini-laparotomy fetoscopy, in which access to the uterus for one of the ports is done via a mini-laparotomy, whereas the other ports are inserted percutaneously. This technique draws on the benefits of both the laparotomy-assisted and the percutaneous techniques while minimizing their drawbacks. This surgical approach may prove invaluable in the prenatal repair of open spina bifida and other complex fetal surgical procedures.

Risks of Preterm Premature Rupture of Membranes and Preterm Birth Post Fetoscopy Based on Location of Trocar Insertion Site.

OBJECTIVE: The objective of this study was to assess whether the location of the trocar insertion site for laser treatment of twin-twin transfusion syndrome was associated with preterm-premature rupture of membranes (PPROM) and preterm birth (PTB). STUDY DESIGN: In this study trocar location was documented in the operating room. Lower uterine segment (LUS) location was defined as any insertion <10 cm vertically from the pubic symphysis. Lateral location was defined as ≥5 cm horizontally from the midline. Patient characteristics were tested against three outcomes: PPROM ≤ 21 days postoperative, PTB < 28 weeks, and PTB < 32 weeks. For each outcome, multiple logistic models were fitted to examine the effect of trocar location, controlling for potential risk factors. RESULTS: A total of 743 patients were studied. Patients with LUS location were twice as likely as those with a more superior location to have PPROM ≤ 21 days (OR = 2.33, 1.12-4.83, p = 0.0236). Patients with both a LUS and Lateral location were over six times more likely to have PPROM ≤ 21 days (OR = 6.66, 2.36-18.78, p = 0.0003). Trocar insertion site was not associated with PTB. CONCLUSION: We found that trocar insertion in the LUS, particularly the lateral LUS, was associated with an increased risk of PPROM.

Risk factors for fetomaternal bleeding after laser therapy for twin-twin transfusion syndrome.

OBJECTIVE: To quantify and assess potential risk factors for transplacental passage of fetal red blood cells (RBCs) into the maternal circulation (fetomaternal bleeding, FMB) after laser surgery for twin-twin transfusion syndrome (TTTS). STUDY DESIGN: A retrospective study of Rhesus-D negative patients that underwent laser surgery for TTTS. Patients with and without postoperative detectable fetal RBCs on Kleihauer-Betke (KB) testing were compared to determine risk factors for FMB. Patients were further sub-classified into those with a FMB < 20% and ≥20% of estimated fetoplacental blood volume. RESULTS: Of 60 studied patients, 26/60 (43%) had a positive postoperative KB test. The median fetal:adult RBC ratio was 0.00125, estimated to be a FMB volume of 6.25 mL. There were 17/26 (65%) of patients with FMB < 20% and 9/26 (35%) patients with ≥20% of the fetoplacental blood volume. Stage III-Recipient and III-Recipient/Donor patients were more likely to have a positive KB test (14/21 [66.7%] vs 12/39 [30.8%], OR = 4.50 [1.27-16.54], P = 0.0162). No other risk factors for FMB were apparent. CONCLUSIONS: Fetomaternal bleed appears to be a common finding after laser surgery for TTTS. TTTS Stage, particularly stage III-Recipient and III-Recipient/Donor, appears to be a risk factor for FMB.

Endoscopic surgery for the antenatal treatment of myelomeningocele: the CECAM trial.

BACKGROUND: A recent randomized clinical trial named Management of Myelomeningocele Study (MOMS trial) showed that prenatal correction of open spina bifida (OSB) via open fetal surgery was associated with improved infant neurological outcomes relative to postnatal repair, but at the expense of increased maternal morbidity. OBJECTIVE: We sought to report the final results of our phase I trial (Cirurgia Endoscópica para Correção Antenatal da Meningomielocele [CECAM]) on the feasibility, safety, potential benefits, and side effects of the fetoscopic treatment of OSB using our unique surgical technique. STUDY DESIGN: Ten consecutive pregnancies with lumbosacral OSB were enrolled in the study. Surgeries were performed percutaneously under general anesthesia with 3 ports and partial carbon dioxide insufflation. After appropriate surgical positioning of the fetus, the neuroplacode was released with scissors and the skin was undermined to place a biocellulose patch over the lesion. The skin was closed over the patch using a single running stitch. Preoperative, postoperative, and postnatal magnetic resonance imaging were performed to assess hindbrain herniation. Neurodevelopmental evaluation was performed before discharge and at 3, 6, and 12 months. All cases were delivered by cesarean delivery, at which time the uterus was assessed for evidence of thinning or dehiscence. RESULTS: The median gestational age at the time of surgery was 27 weeks (range 25-28 weeks). Endoscopic repair was completed in 8 of 10 fetuses. Two cases were unsuccessful due to loss of uterine access. The mean gestational age at birth was 32.4 weeks with a mean latency of 5.6 weeks between surgery and delivery (range 2-8 weeks). There was 1 fetal and 1 neonatal demise, and 1 unsuccessful case underwent postnatal repair. Of the 7 infants available for analysis, complete reversal of hindbrain herniation occurred in 6 of 7 babies. Three babies required ventriculoperitoneal shunting or third ventriculostomy. Functional motor level was the same or better than the anatomical level in 6 of 7 cases. There was no significant maternal morbidity and no evidence of myometrial thinning or dehiscence. However, surgeries were complicated by premature rupture of membrane and prematurity. CONCLUSION: Our study suggests that the antenatal treatment of OSB using a fetoscopic approach and our unique surgical technique can result in a watertight seal, reversal of the hindbrain herniation, and better than expected motor function. Our technique differs substantially from the classic repair of OSB used in prior open fetal surgery and fetoscopic studies, in which the dura mater is dissected and the defect is closed in multiple layers. Instead, we use a biocellulose patch placed over the lesion and simple closure of the skin. As such, our technique is an alternative to the current paradigms in the antenatal treatment of OSB. Our clinical outcomes are in line with the results of our extensive prior animal work. Maternal benefits of our approach and technique include minimal morbidity and no myometrial legacy. Current limitations of the approach include potential loss of access, premature rupture of membranes, and attendant prematurity. Phase II trials are needed to prevent these complications and to further assess the risks and benefits of our distinct surgical approach and technique.

Selective Reduction Using Intravascular Potassium Chloride Injection after Laser Surgery for Twin-Twin Transfusion Syndrome.

Selective reduction (SR) via intravascular potassium chloride (KCl) injection is contraindicated in monochorionic twins due to the presence of placental vascular communications, which may serve as a conduit for inter-twin passage of KCl or allow exsanguination of the living twin into the demised twin. After successful selective laser photocoagulation of communicating vessels (SLPCV) for twin-twin transfusion syndrome (TTTS), the twins' circulatory systems are rendered independent. Theoretically, intravascular KCl injection into one twin after successful SLPCV should not result in passage of the feticidal agent nor cause hemodynamic alterations in the co-twin. We describe 3 cases of 1,069 patients (0.3%) that underwent SLPCV for TTTS between 2003 and 2013 and subsequent SR. SLPCV was successfully completed at 180, 226, and 230 weeks' gestational age for Quintero stages III, IV, and III TTTS, respectively. SR via intravascular KCl injection was later performed at maternal request due to the risk of neurological compromise in one twin at 226, 254, and 236 weeks' gestational age. All co-twins survived after SR, and no neurological sequelae were suspected after birth. Further study is necessary before SR can be routinely considered after laser surgery for TTTS.

Decreased Total Placental Mass Found in Twin-Twin Transfusion Syndrome Gestations with Selective Growth Restriction.

INTRODUCTION: We examined placental weight characteristics associated with donor selective intrauterine growth restriction (SIUGR) among patients with twin-twin transfusion syndrome (TTTS) who underwent laser surgery. MATERIALS AND METHODS: Fresh placental specimens were studied. Pregnancies with higher-order multiples, fetal demise, or disrupted or nonsubmitted placental specimens were excluded. Placental characteristics prospectively collected included total placental weight, individual placental weight, and placental share. Data were compared between pregnancies with SIUGR (TTTS + SIUGR group) and those without SIUGR (TTTS-only group). RESULTS: Of 369 consecutive patients who underwent laser surgery for TTTS, 155 (42%) met inclusion criteria: 91 with TTTS + SIUGR and 64 with TTTS-only. Compared to the TTTS-only group, patients in the TTTS + SIUGR group had a lower total placental weight (608 ± 163 vs. 687 ± 224 g, p = 0.012), with a lower donor individual placental weight (237 ± 91 vs. 291 ± 124 g, p = 0.002), but no apparent difference in the individual placental weight of recipient twins (371 ± 109 vs. 396 ± 133 g, p = 0.211). Donor placental share was smaller in those pregnancies affected by SIUGR (38.7 ± 9.6 vs. 42.3 ± 9.8%, p = 0.029). DISCUSSION: TTTS patients with SIUGR had a lower total placental weight and a lower donor individual placental weight compared to those without SIUGR. These findings suggest that differences in donor individual placental weights for SIUGR gestations may not solely be related to differences in placental share.

Abnormal umbilical artery Doppler findings in the recipient twin before laser surgery for twin-twin transfusion syndrome.

OBJECTIVES: In twin-twin transfusion syndrome (TTTS), persistent absent or reversed end-diastolic flow in the umbilical artery is a rare finding in the recipient twin, and the clinical implications of this finding are not well characterized. We sought to study the clinical importance of abnormal umbilical artery Doppler waveforms in recipient twins and determine the perinatal survival of these twins after laser surgery. METHODS: A retrospective study of patients with TTTS treated with laser surgery between 2006 and 2012 was conducted. Recipient twins with absent or reversed umbilical artery end-diastolic flow on preoperative sonography were identified, and clinical and perinatal outcomes were compared to the remaining cohort. Statistical analyses were performed with Fisher exact and χ(2) tests. RESULTS: Of 369 consecutive TTTS cases, 14 (3.8%) had absent or reversed umbilical artery end-diastolic flow in the recipient twin. The rate of hydrops was higher in this group compared to those without absent or reversed flow (35.7% [5 of 14] versus 10.1% [36 of 355]; P = .0125). The rate of recipient twin growth restriction was also higher in the absent or reversed flow group (28.6% [4 of 14] versus 3.9% [14 of 355]; P = .0029). There was an increased rate of recipient fetal demise within 24 hours after surgery in those with absent or reversed flow (21.4% [3 of 14] versus 2.5% [9 of 355]; P = .0078), although there was no statistical difference in 30-day survival between the groups (78.6% [11 of 14] versus 89.9% [319 of 355]; P = .1751). CONCLUSIONS: Doppler findings of absent or reversed umbilical artery end-diastolic flow are rare in recipient twins. Although immediate post-laser surgery survival is relatively decreased in this group, overall perinatal survival rates appear to be favorable.

Pre-Operative Twin Anemia/Polycythemia in the Setting of Twin-Twin Transfusion Syndrome (TTTS).

INTRODUCTION: Twin-twin transfusion syndrome (TTTS) and twin anemia-polycythemia sequence (TAPS) are classified as distinct clinical disorders associated with unbalanced blood flow through placental vascular communications. Typically, TAPS placentas demonstrate few <1 mm arteriovenous (AV) communications, and at fetoscopy the twins are visibly pale and plethoric. MATERIALS AND METHODS: In a cohort of TTTS patients who underwent laser surgery, those with preoperative findings suggestive of anemia/polycythemia (AP) were compared to those with TTTS alone. AP was defined as middle cerebral artery peak systolic velocity in one twin >1.5 multiples of the median (MoM), and <1.0 MoM in the other. RESULTS: Of 369 TTTS patients, 9 (2.4%) met criteria for preoperative AP. The mean number (±SD) of AV communications in the TTTS + AP group was 5.6 ± 5.7, compared with 8.8 ± 4.8 in the TTTS-alone group (p = 0.013). Five TTTS + AP patients (56%) had a few thin AV communications (mean 2.8 ± 1.6); all 5 had visibly pale and plethoric twins. The remaining 4 (44%) had large or numerous anastomoses (mean 10.5 ± 6.8); none had fetal skin color discordance. DISCUSSION: Preoperative AP affected 2% of TTTS patients. Of these, approximately half had placental and skin color findings typically reported with isolated TAPS.

Sequential laser surgery for twin-twin transfusion syndrome.

Treatment of twin-twin transfusion syndrome (TTTS) via the sequential selective laser photocoagulation of communicating vessels (SQLPCV) technique involves lasering the arteriovenous communications from the donor twin to the recipient twin first, followed by the arteriovenous communications from the recipient twin to the donor. Occluding the vascular communications in this particular order may result in transient intraoperative net transfusion to the donor twin and facilitate hemodynamic equilibrium, particularly to the volume depleted donor twin. Preliminary evidence suggests that the SQLPCV technique may result in improved perinatal outcomes compared with the standard selective (SLPCV) laser surgical approach. In this article, we describe the pathophysiological basis for this surgical approach, delineate the surgical technique, review the literature, and elaborate on the outstanding questions of the SQLPCV treatment of TTTS.

Successful in utero treatment of an oral teratoma via operative fetoscopy: case report and review of the literature.

The prenatal diagnosis of a nasopharyngeal teratoma carries a very grave prognosis. Although these tumors constitute only 9% of all teratomas, all previous cases diagnosed antenatally have been associated with either fetal demise or emergent surgery at birth. Of the fetuses that survive to birth, delivery can be associated with airway obstruction and multiple postnatal surgeries. These complications could be averted if the tumor could be safely treated in utero. We hereby report the successful treatment of an oral teratoma via operative fetoscopy, with the birth of a healthy infant at term.

The quantitative lung index: the left lung.

OBJECTIVE: We have previously described a gestational age-independent sonographic parameter to assess fetal lung growth in the right lung (right quantitative lung index, or QLI-R). The purpose of this study was to develop a similar sonographic parameter to assess the growth of the left lung in the fetus, independent of gestational age, or QLI-L. STUDY DESIGN: A new index, the QLI-L was derived using published formulas for the head circumference (HC) and the area of the base of the left lung (LA), with the corresponding percentiles. RESULTS: Left lung growth can be expressed using the following formula: QLI-L=LAL(HC12)2. The 50th percentile of the QLI-L remained approximately constant at 1.0 for the GA between 16-32 weeks. A small left lung (<1st percentile) was defined as a QLI-L < 0.5. CONCLUSIONS: Fetal left lung growth can be adequately described independent of gestational age using the QLI-L. Further experience is needed to assess the clinical accuracy of the QLI-L in characterizing fetal left lung growth.

Stage-based outcomes of 682 consecutive cases of twin-twin transfusion syndrome treated with laser surgery: the USFetus experience.

OBJECTIVE: We sought to describe stage-specific perinatal outcomes after selective laser photocoagulation of communicating vessels (SLPCV) for twin-twin transfusion syndrome. STUDY DESIGN: Patients with twin-twin transfusion syndrome underwent SLPCV preferentially using sequential vs standard laser technique. Patient characteristics and outcome data were examined by Quintero stage. RESULTS: Of 682 consecutive women studied, the Quintero stage distribution was: 114 stage I (17%), 177 stage II (26%), 328 stage III (48%), and 63 stage IV (9%). Perinatal survival of at least 1 twin did not differ according to stage (I-92%, II-93%, III-88%, IV-92%; P = .30). However, dual twin survival differed by stage (I-79%, II-76%, III-59%, IV-68%; P < .01), primarily because stage III pregnancies were associated with decreased donor twin survival (P < .01). Sequential SLPCV was associated with improved donor survival, independent of stage (odds ratio, 1.67; 95% confidence interval, 1.16-2.40; P < .01). CONCLUSION: Stage-specific perinatal outcomes after laser therapy may assist physicians in patient counseling and in planning future studies.

The quantitative lung index (QLI): a gestational age-independent sonographic predictor of fetal lung growth.

OBJECTIVE: We sought to develop a gestational age-independent sonographic parameter to characterize lung growth. STUDY DESIGN: Reported descriptors of lung growth, including lung-to-head circumference (HC) ratio (LHR) and observed/expected LHR, were examined. A new index, the quantitative lung index (QLI) was derived using published data on HC and the area of the base of the right lung. RESULTS: Neither the LHR nor the observed/expected LHR proved to be gestational age independent. Right lung growth can be expressed using the following formula: QLI = lung area/(HC/10)^2. The 50th percentile of the QLI remained constant at approximately 1.0 for the gestational age between 16-32 weeks. A small lung (<1st percentile) was defined as a QLI <0.6. CONCLUSION: Fetal right lung growth can be adequately described using the QLI, independent of gestational age. Further studies are needed to assess the clinical accuracy of the QLI in characterizing fetal right lung growth.

Fetal blood gases after in utero carbon dioxide insufflation for percutaneous fetoscopic spina bifida repair.

BACKGROUND: Prenatal repair of open spina bifida via the percutaneous fetoscopic approach does not require maternal laparotomy, hysterotomy, or exteriorization of the uterus. This technique requires intrauterine partial CO2 insufflation. Limited data exist on the physiological effects of CO2 insufflation on human fetuses, with no data on open spina bifida repair performed using the entirely percutaneous fetoscopic surgical technique. OBJECTIVE: Our aim was to examine the effects of intrauterine partial CO2 insufflation on fetal blood gases after percutaneous fetoscopic open spina bifida repair. STUDY DESIGN: This was a prospective study of patients who underwent percutaneous fetoscopic open spina bifida repair from February 2019 to July 2020. Fetal cordocentesis of the umbilical vein was performed in cases with favorable access to the umbilical cord. The umbilical vein cord blood samples were obtained under ultrasound guidance immediately at the conclusion of the open spina bifida repair. Simultaneous maternal arterial blood gas samples were also obtained. The results are reported as median (range). RESULTS: Of the 20 patients who underwent percutaneous fetoscopic open spina bifida repair during the study period, 7 patients (35%) underwent fetal blood sampling. The gestational age at the time of surgery was 27.4 (24.0-27.9) weeks and the operative time was 183 (156-251) minutes. The CO2 exposure time was 122 (57-146) minutes with maximum pressure of 13.5 (12.0-15.0) mm Hg. Fetal umbilical vein results were as follows: pH 7.35 (7.30-7.39), partial pressure of O2 56.2 (47.1-99.9) mm Hg, partial pressure of CO2 43.8 (36.2-53.0) mm Hg, HCO3 23.9 (20.1-25.6) mmol/L, and base excess -2.2 (-4.5 to -0.4) mmol/L. Simultaneous maternal arterial blood gas results were as follows: pH 7.37 (7.28-7.42), partial pressure of O2 187.5 (124.4-405.2) mm Hg, partial pressure of CO2 36.6 (30.7-46.0) mm Hg, HCO3 21.3 (18.0-22.8) mmol/L and base excess -3.2 (-5.9 to -1.8) mmol/L. CONCLUSION: Despite prolonged CO2insufflation of the uterus, fetal umbilical vein pH and base excess values did not approach those associated with potentially pathologic fetal acidemia.

Appraisal of the selectivity index in a cohort of patients treated with laser surgery for twin-twin transfusion syndrome.

OBJECTIVE: The selectivity index (SI) has been proposed as a measure of technical success in laser surgery for twin-twin transfusion syndrome. Surgeries with an index >-0.25 have been considered highly selective. The purpose of this study was to evaluate the applicability of this index in our patient population. STUDY DESIGN: The SI was assessed in 314 consecutive laser surgeries and correlated with perinatal survival. RESULTS: A total of 310 patients (98.7%) underwent a completely selective procedure. The SI was 0.8 in the selective laser photocoagulation of communicating vessels group vs 0.3 in the nonselective laser photocoagulation of communicating vessels group (P = .001). In the selective group perinatal survival of at least 1 twin (92.6% vs 50%) and survival of the donor (75.4% vs 0%) was significantly better (P = .05). CONCLUSION: The SI as originally proposed is misleading and of limited use as it does not differentiate selective from nonselective procedures. We propose instead using a ratio of selective/nonselective procedures, and selectively coagulated/total number of coagulated vessels to appraise center-specific and patient-specific surgical performance of laser surgery for twin-twin transfusion syndrome.

Assessment of the peak systolic velocity of the middle cerebral artery in twin-twin transfusion syndrome. Part I: preoperative assessment.

OBJECTIVE: We sought to assess the incidence of an elevated peak systolic velocity of the middle cerebral artery (MCA-PSV) in twin-twin transfusion syndrome prior to laser surgery and its prognostic value for intrauterine fetal demise 24 hours after surgery (IUFD-24). STUDY DESIGN: An elevated MCA-PSV was defined as a velocity > .5 multiples of the median by transabdominal pulsed Doppler. Gestational age, Quintero stage, and number and/or type of placental vascular anastomoses were assessed as risk factors for an elevated MCA-PSV. Risk of IUFD-24 was assessed relative to an elevated MCA-PSV. RESULTS: An elevated MCA-PSV was present in 4.2% of donors, 3.2% of recipients (P = .5), and 1.5% of both twins in 189 patients with twin-twin transfusion syndrome. An elevated MCA-PSV was unrelated to gestational age, stage, and number or type of anastomoses. An elevated MCA-PSV in the recipient twin was associated with an increased risk of IUFD-24 of this fetus (P = .01). CONCLUSIONS: An elevated MCA-PSV is present in < 5% of donor and recipient twins. An elevated MCA-PSV is a risk factor for IUFD-24 of the recipient twin.

Prenatal diagnosis of spontaneous septostomy of the dividing membranes in complicated monochorionic diamniotic multiple gestations.

OBJECTIVE: The purpose of this series is to describe the prenatal diagnostic and management challenges of spontaneous septostomy of the dividing membrane (SSDM) in complicated monochorionic diamniotic (MoDi) pregnancies. METHODS: A retrospective review of all MoDi multiple gestations referred for fetal therapy was conducted. Spontaneous septostomy of the dividing membrane was suspected if a prior invasive procedure had not been performed and the following sonographic hallmarks were identified: twins occupying the same side of the dividing membrane, twin-twin transfusion syndrome (TTTS) with polyhydramnios in the donor's sac despite a collapsed donor bladder, and umbilical cord entanglement. Spontaneous septostomy of the dividing membrane was confirmed in all cases at the time of surgical fetoscopy, which was performed to treat an underlying condition of TTTS, selective intrauterine growth restriction (SIUGR), or the twin reversed arterial perfusion (TRAP) sequence. RESULTS: Of 217 complicated MoDi multiple gestations without prior invasive procedures referred for possible fetal therapy, 4 (1.8%) were identified with SSDM. The mean (range) gestational age at diagnosis was 19.7 (18-20.9) weeks. Two cases were diagnosed with TTTS complicated by SSDM after both fetuses were identified on the same side of the dividing membranes (1 case) or polyhydramnios was noted in the donor's sac despite a collapsed donor bladder (1 case). Both cases had substantial preoperative fetal deterioration because of a delay in diagnosis and treatment of TTTS. The remaining 2 SSDM cases, 1 with SIUGR and 1 with the TRAP sequence, were diagnosed after umbilical cord entanglement was recognized. CONCLUSIONS: Spontaneous septostomy of the dividing membrane in MoDi gestations is a rare condition that poses diagnostic and management challenges.

Massive pericardial effusion treated with in utero pericardioamniotic shunt in a fetus with intrapericardial teratoma.

Teratoma is the leading neoplasm diagnosed in neonates and infants. Although over 99% of teratomas found in the fetus and newborn are histologically benign, those tumors may cause death if vital structures are involved or if the airway is compromised. We review the literature on antenatal intrapericardial teratomas and report a case of intrapericardial teratoma, with massive pericardial effusion and fetal hydrops, diagnosed on antenatal ultrasound at 21 weeks of gestation. Pericardioamniotic shunt was placed at 22 weeks and 6 days gestational age. In spite of successful drainage of the pericardial effusion, fetal demise was documented 8 days later, likely due to tumor compression of the heart.