Learning curves of open and endoscopic fetal spina bifida closure: a systematic review and meta-analysis

OBJECTIVES: The Management Of Myelomeningocele Study (MOMS) trial demonstrated the safety and efficacy of open fetal surgery for spina bifida (SB). Recently developed alternative techniques may reduce maternal risks yet should do without compromising on fetal neuroprotective effects. We aimed to assess the learning curve of different fetal SB closure techniques. METHODS: We searched Medline, Web of Science, Embase, Scopus and Cochrane databases and the grey literature to identify relevant articles without language restriction from January 1980 until October 2018. We systematically reviewed and selected studies reporting all consecutive procedures and with a postnatal follow-up ≥12 months. They also had to report outcome variables necessary to measure the learning curve defined by fetal safety and efficacy. Two independent authors retrieved the data, assessed the quality of the studies and categorized observations into blocks of 30 patients. For meta-analysis, data were pooled using a random-effect model when heterogeneous. To measure the learning curve, we used two complementary methods. With the group splitting method, competency was defined when the procedure provided comparable results to the MOMS trial for 12 outcome variables representative for (1) the immediate surgical outcome, (2) short-term neonatal neuroprotection and (3) long-term neuroprotection at ≥12 months. Then, when the patients' raw data were available, we performed cumulative sum (CUSUM) analysis based on a composite binary outcome defining a successful surgery. It combined four clinically relevant variables for safety (fetal death within 7 days) and for efficacy (neuroprotection at birth). RESULTS: We included 17/6024 (0.3%) studies with low and moderate risks of bias. Fetal SB closure was performed via standard-hysterotomy (n=11), mini-hysterotomy (n=1) or fetoscopy [exteriorized-uterus single-layer (n=1), percutaneous single-layer (n=3) or percutaneous two-layer closure (n=1)]. Only outcomes for the standard-hysterotomy could be meta-analyzed. Overall, outcomes significantly improved with experience. Competency was reached after 35 consecutive cases for standard-hysterotomy and was predicted to be achieved after ≥57 cases for mini-hysterotomy and ≥56 for percutaneous two-layer fetoscopy. For percutaneous and uterus-exteriorized single-layer fetoscopy, competency was not respectively reached by cases 81 and 28 available for analysis. CONCLUSIONS: The number of cases operated correlates with the outcome of SB fetal closure and ranges from 35 cases for standard-hysterotomy to ≥56-57 cases for minimally invasive modifications. Our observations provide important information for institutions eager to establish a new fetal center, develop a new technique or train their team, and inform referring clinicians, potential patients and third-parties

Maternal complications following open and fetoscopic fetal surgery: A systematic review and meta-analysis

OBJECTIVE: To establish maternal complication rates for fetoscopic or open fetal surgery. METHODS: We conducted a systematic literature review for studies of fetoscopic or open fetal surgery performed since 1990, recording maternal complications during fetal surgery, the remainder of pregnancy, delivery and after the index pregnancy. RESULTS: One hundred and sixty-six studies were included, reporting outcomes for open fetal (n=1193 patients) and fetoscopic surgery (n=9403 patients). No maternal deaths were reported. The risk of any maternal complication in the index pregnancy was 20.9% (95%CI 15.22-27.13) for open fetal and 6.2% (95%CI 4.93-7.49) for fetoscopic surgery. For severe maternal complications (Grade III to V Clavien-Dindo classification of surgical complications) the risk was 4.5% (95%CI 3.24-5.98) for open fetal and 1.7% (95%CI 1.19-2.20) for fetoscopic surgery. In subsequent pregnancies, open fetal surgery increased the risk of preterm birth but not uterine dehiscence or rupture. Nearly one quarter of reviewed studies (n=175, 23.3%) were excluded for failing to report the presence or absence of maternal complications. CONCLUSIONS: Maternal complications occur in 6.2% fetoscopic and 20.9% open fetal surgeries, with serious maternal complications in 1.7% fetoscopic and 4.5% open procedures. Reporting of maternal complications is variable. To properly quantify maternal risks, outcomes should be reported consistently across all fetal surgery studies

Copy number imbalances detected with a BAC-based array comparative genomic hybridization platform in congenital diaphragmatic hernia fetuses

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Congenital diaphragmatic hernia (CDH) is a phenotypically and genetically heterogeneous disorder, with a complex inheritance pattern. Structural abnormalities of almost all chromosomes have been described in association with CDH. We made a molecular analysis through array comparative genomic hybridization (array CGH) of a group of fetuses with prenatal ultrasound diagnosis of CDH and normal G-banded karyotypes. A whole genome BAC-array CGH, composed of approximately 5000 BAC clones, was carried out on blood samples from fetuses with prenatal ultrasound diagnosis of CDH and a normal karyotype (500-band level). All potential cytogenetic alterations detected on the arrays were reported. The array CGH analysis showed copy number gains and losses in 10 of 12 cases. Eighty-five clones showed genomic imbalances, and 29 clones displayed described copy number variations. We identified a recurrent gain in 17q12 in two of 12 cases, which has not been previously described. Our results may contribute to determining the effectiveness and applicability of array CGH for prenatal diagnosis purposes, and also to elucidate the submicroscopic genomic instability of CDH fetuses.101261267Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fetal Medicine Foundation (FMF)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP [2007/04684-0

Fetal thigh volumetry by three-dimensional ultrasound: comparison between multiplanar and VOCAL (TM) techniques

Objectives To evaluate the agreement between multiplanar and Virtual Organ Computer-aided Analysis (VOCAL (TM)) techniques for the measurement of total fetal thigh volume and to assess the repeatability and reproducibility of measurements performed using these methods; to derive birth weight-predicting models for both methods and to compare their accuracies. Methods This was a cross-sectional study of 150 singleton pregnancies at 30-42 weeks of gestation in which ultrasound volumes of the fetal thigh were obtained within 48 hours of delivery and measured using multiplanar and VOCAL techniques. Bland-Altman analyses were performed to determine the agreement between the two methods, and to evaluate intraobserver and interobserver variability in a subset of 40 patients. Birth weight-predicting models were derived using total fetal thigh volumes obtained using the VOCAL (ThiV) and multiplanar (ThiM) methods as independent variables. The accuracies of these formulas were compared. Results The mean percentage difference between measurements performed using the VOCAL technique and the multiplanar technique was -0.04 and the 95% limits of agreement were -8.17 and 8.09. The mean percentage difference and 95% limits of agreement between paired measurements in the assessment of intraobserver and interobserver variability were -1.10 (-7.67 to 5.47) and 0.61 (-7.68 to 8.91) for the VOCAL technique and 1.03 (-6.35 to 8.41) and -0.68 (-11.42 to 10.06) for the multiplanar method, respectively. The best-fit formulas for predicting birth weight (B W) were: BW = 1025.383 + 12.775 x ThiV; and BW = 1033.286 + 12.733 x ThiM. There was no significant difference between the accuracies of these formulas. Conclusions There is good agreement between the VOCAL and multiplanar techniques for assessment of total fetal thigh volume. Measurements performed using both methods are repeatable and reproducible. For prediction of birth weight, the formulas generated in this study can be used interchangeably. Copyright (C) 2010 ISUOG. Published by :John Wiley & Sons, Ltd.35441742

Endoscopic Laser Dichorionization of the Placenta in the Treatment of Severe Twin-Twin Transfusion Syndrome

Objectives: To describe the results of a technique of laser ablation of placental vessels in the treatment of severe twin-twin transfusion syndrome (TTTS), which is characterized by separation of the fetoplacental vascular territories and dichorionization of the placenta. Patients and Methods: Descriptive analysis of TTTS cases treated with the endoscopic laser dichorionization of the placenta (ELDP) procedure. The variables evaluated were the occurrence of reversal of the donor-recipient phenotype, persistence of TTTS or twin anemia-polycythemia sequence (TAPS); gestational age at delivery; discharge from the hospital of at least 1 or 2 live neonates, and incidence of neurological alterations among survivors. Results: 67 patients were treated with the ELDP procedure. There was no persistence of TITS, reversal of the donor-recipient phenotype or TAPS. The median gestational age at delivery was 33.0 (23.6-37.7) weeks. The rate of discharge from the hospital of at least 1 or 2 live neonates was 88.2% (67/76) and 71.1% (54/76), respectively. Among survivors, 17 (17/121 = 14.0%) children presented with neurodevelopmental alterations during clinical follow-up. Conclusions: The major contribution of this study was the demonstration that the ELDP technique appears to be associated with a low risk of persistence or recurrence of TTTS and TAPS. (C) 2013 S. Karger AG, Basel34420621

Complex Breast Masses Assessment of Malignant Potential Based on Cyst Diameter

Objectives-The purpose of this study was to assess whether cyst diameter might contribute to the prediction of malignancy in complex breast masses. Methods-In this cross-sectional study, we identified 48 breast masses that had sonographic features suggestive of benign breast lesions (oval shape, circumscribed margins, parallel axis, and abrupt limits). However, these masses were classified as Breast Imaging Reporting and Data System (BI-RADS) category 4 because of the presence of at least 1 cyst (complex echogenicity). All breast masses were biopsied (25 core needle and 23 core needle and excision). Subsequent histologic analysis was performed, and 12 malignancies (25%) were identified. Mammographic features were reviewed. Different sonographic measurements (largest diameters of the mass and cyst and vascular pattern) were assessed for the detection of malignancy. Results-Among the sonographic features, the vascular pattern, ie, the detection of blood flow (present in the lesion [P > .99] or present immediately adjacent to the lesion [P = .46]), was not associated with malignancy, whereas the largest mass and cyst dimensions had significantly positive correlations (P = .02; P < .001, respectively) with tumor malignancy. In receiver operating characteristic curve analysis, the point with the highest sum of sensitivity and specificity corresponded to a maximum cyst diameter of 8 mm (sensitivity, 67%; specificity, 86%). The positive and negative predictive values at that cutoff point were 61% and 86%, respectively. The area under the curve was 0.772. In this study, all masses with cysts smaller than 3 mm in diameter (7 cases) were benign, and all masses with cysts larger than 13 mm in diameter (4 cases) were malignant. Conclusions-Cyst diameter is a good predictor of malignancy in complex breast masses, which, except for the presence of internal cysts, would be otherwise classified as BI-RADS category 3.31458158