Laparotomy-Assisted 2-Port Fetoscopic Repair of Spina Bifida Aperta: Report of a Single-Center Experience in Paris, France.

BACKGROUND: Given the maternal morbidity of open fetal surgery, the development of prenatal fetoscopic repair for spina bifida aperta (SBA) is encouraged. OBJECTIVE: We hereby report the early results from our center, using a laparotomy-assisted CO2-fetoscopic approach. METHODS: This study was conducted in patients with an SBA < T1 and >S1, <26 weeks of gestation, with Chiari II. Fetoscopic repair was performed using 2 operating trocars in the uterus exteriorized through a transverse laparotomy. Endoscopy was performed under humidified and heated CO2 insufflation. Following dissection of the lesion, a 1-layer approach was performed with a muscle/skin flap sutured over a patch of Duragen. Main outcomes were watertight repair at birth and the need for postnatal neurosurgical surgery including shunting within 6 months. RESULTS: Of 87 women assessed for prenatal therapy, 7 were included. Surgery was performed at 24 (23-26) weeks' gestation. There was no fetal demise. Conversion to hysterotomy was not performed, although surgery could not be performed in 1 case because of fetal position. Severe preeclampsia developed postoperatively in 1 case. In the other 6 cases, follow-up was uneventful except for premature rupture membranes which occurred in 3/6 cases at 30, 34, and 36+5 weeks' gestation. Gestational age at delivery was 32 + 5 (31-36 + 5) weeks' gestation. Repair was watertight at birth except in 2 cases which required complementary postnatal surgical repair. Reverse hindbrain herniation during pregnancy was observed in 4/6 cases. In 3/6 cases, shunting was necessary within 6 months after birth. At 12 months, a functional gain of ≥2 metameric levels was observed in 3 cases of the 6 survivors. CONCLUSION: Laparotomy-assisted fetoscopic repair is a reasonable option for women who choose and are eligible for antenatal surgery, both in terms of maternal and perinatal morbidity.

Fetal Cystoscopy and Vesicoamniotic Shunting in Lower Urinary Tract Obstruction: Long-Term Outcome and Current Technical Limitations.

BACKGROUND: In utero therapeutic approaches for lower urinary tract obstruction (LUTO) have been developed to salvage the fetal kidney function. OBJECTIVE: The aim of this work was to report the long-term survival, nephrological, and urological outcome of children treated prenatally for LUTO using operative fetal cystoscopy (FC) and vesicoamniotic shunting (VAS) or both. METHODS: A retrospective study of 48 procedures (23 FC, 25 VAS) was performed on 33 patients (between 2008 and 2018). Reviewed data included prenatal management and clinical follow-up by a pediatric nephrologist and a pediatric urologist. Both intention-to-treat and per-protocol analyses were conducted. RESULTS: The median follow-up was 3.6 years (0.5-7) for FC and 2.5 years (1.1-5.1) for VAS. There was no difference between FC and VAS in terms of survival (92 vs. 83%, p = 1), complication rate (74 vs. 92%, p = 0.88), or chronic kidney disease (58 vs. 50%, p = 1). The number of procedures was higher in the VAS group: 1.7 (1-3) versus 1.1 (1-2), p = 0.01. With a 30% rate of technical failure, FC added diagnostic value in 3 out of 21 cases. CONCLUSIONS: No difference was found between FC and VAS regarding survival, long-term kidney function, or urological outcome. Despite overly optimistic reports on FC, it lacks reproducibility due to posterior-urethra inadequate visualization and inappropriate instrumentation.

Comparison of biochemical analysis of fetal serum and fetal urine in the prediction of postnatal renal outcome in lower urinary tract obstruction.

OBJECTIVES: To compare the prognostic value of fetal serum biochemistry and fetal urine biochemistry in predicting renal outcome in lower urinary tract obstruction (LUTO). METHODS: We retrospectively studied renal outcome following a prenatal diagnosis of LUTO in cases for which both fetal blood and fetal urine were sampled. We classified the renal outcome as either "favorable," when postnatal renal function was normal, or "adverse," in the case of postnatal chronic renal failure or when renal histological lesions were present at autopsy in the case of termination of pregnancy. A prognostic model was constructed for urine and serum separately. ß2-Microglobulin was the only remaining independent predictor in fetal urine. ß2-Microglobulin in serum and urine were compared by using receiver operating characteristic curves. RESULTS: In the 50 cases included, the rate of adverse outcome was 34 of 50(68%): autopsy confirmed severity of renal disease in all 27 cases who underwent termination of pregnancy, and among the 23 live born children, 7 developed renal failure. Fetal serum and urine markers were all significantly associated with renal outcome (P < .01). The receiver operating characteristic curves for fetal serum and fetal urinary ß2-microglobulin were similar (area under the curve = 0.908 versus 0.909, P = .96). CONCLUSION: Fetal serum biochemistry and fetal urine biochemistry are of similar prognostic value in predicting postnatal renal outcome in fetuses with LUTO.

Impact on spina bifida screening of shifting prenatal Down syndrome maternal serum screening from the second trimester to the first.

OBJECTIVES: Shifting screening for trisomy 21 to the first trimester has resulted in the loss of maternal serum alpha-fetoprotein screening for spina bifida. The aim of this study was to study the impact on open spina bifida prenatal screening. STUDY DESIGN: We reviewed prenatally diagnosed cases of spina bifida over three years: 2009 (only second-trimester screening, MSM2T), 2010 (transient period) and 2011 (majority first-trimester screening, MSM1T). Cases were assigned to three groups based on maternal serum markers (MSM2T, MSM1T and 'not performed'). Gestational age at diagnosis of spina bifida was compared between these three groups and between the years 2009 and 2011. RESULTS: Median gestational ages at diagnosis of the 742 spina bifida cases between the three groups were 22 weeks [18+6 -23], 22+1  weeks [21+3 -23] and 21+4  weeks [14+1 -23], respectively (P < 0.005). The diagnosis was made at 14-20 weeks in 34.7% for MSM2T group versus 8.5% for MSM1T (P < 0.001). Spina bifida diagnosis at 14-20 weeks declined from 38.8% in 2009 to 13.3% in 2011 (P < 0.001). CONCLUSION: Loss of maternal serum alpha-fetoprotein had a tangible effect on the gestational age at diagnosis of spina bifida and resulted in a decrease of 25% of cases of spina bifida detected before 20 weeks. © 2017 John Wiley & Sons, Ltd.

The Impact of Entry Technique and Access Diameter on Prelabour Rupture of Membranes Following Primary Fetoscopic Laser Treatment for Twin-Twin Transfusion Syndrome.

OBJECTIVE: To evaluate the impact of entry method and access diameter at fetoscopic surgery for twin-twin transfusion syndrome in twin pregnancies with at least one survivor. The outcomes evaluated were prelabour rupture of membranes (PROM) and birth <4 weeks, preterm birth (PTB) <28 weeks, and latency to birth. METHODS: A retrospective analysis of prospectively collected data of consecutive laser procedures from 6 centers was performed. Three entry methods (sheath + trocar; cannula + trocar; cannula + Seldinger) and 6 access diameters (2.3, 3.0, 3.3, 3.5, 3.8, 4.0 mm) were used. Exclusion criteria were subsequent invasive interventions, termination of pregnancy or double fetal death after laser. Multivariate analysis was performed to determine risk factors for the study outcomes. RESULTS: Six hundred seventy three fetoscopic laser cases were analyzed. The use of different entry methods and access diameters did not affect PROM or birth <4 weeks, or latency from laser to birth. Access diameter was associated with PTB <28 weeks. Cervical length was associated with PROM and birth <4 weeks, and latency from laser to birth. CONCLUSION: Instrument choice at fetoscopic laser procedures did not affect outcomes <4 weeks. Access diameter may affect the likelihood for PTB <28 weeks. Cervical length is critically associated with obstetrical outcomes following laser surgery.

Twin-to-Twin Transfusion Syndrome: From Observational Evidence to Randomized Controlled Trials.

Fetoscopic surgery is widely accepted as the preferred first-line treatment for twin-twin transfusion syndrome (TTTS). Nonetheless, the broad diffusion of this technique relies on a single multicentric-randomized trial. We hereby question this trial in a post-hoc Bayesian analysis, submitting its results to several scenarios comprising the alternative published non-randomized literature and pessimistic opinions regarding this surgery. Furthermore, we also discuss further refinements in indications, questioning potential alternatives in early stages of the disease.

First fetal case of the 8q24.3 contiguous genes syndrome.

Molecular cytogenetics, particularly array-CGH, opened the way to the « genotype first approach ¼ and for the discovery of new micro rearrangement syndromes. This was the case for the 8q24.3 microdeletion syndrome. Here, we describe the phenotype of a fetus with a 8q24.3 deletion. This rare condition has to be considered as a contiguous genes syndrome because its phenotype is generated by the SCRIB and PUF60 adjacent gene endophenotypes. The fetus presented atrioventricular septal defect and hypoplastic aortic arch, facial dysmorphism, microretrognathia, dysmorphic ears, clinodactyly of the 5th digit on both hands, mild rocker bottom feet and abnormal third sacral vertebra. This fetus is the first case where the endophenotype produced by SCRIB gene is absent. This case is compared with the previous published cases.

Evaluation of trainees' ability to perform obstetrical ultrasound using simulation: challenges and opportunities.

BACKGROUND: Evaluation of trainee's ability in obstetrical ultrasound is a time-consuming process, which requires involving patients as volunteers. With the use of obstetrical ultrasound simulators, virtual reality could help in assessing competency and evaluating trainees in this field. OBJECTIVE: The objective of the study was to test the validity of an obstetrical ultrasound simulator as a tool for evaluating trainees following structured training by comparing scores obtained on obstetrical ultrasound simulator with those obtained on volunteers and by assessing correlations between scores of images and of dexterity given by 2 blinded examiners. STUDY DESIGN: Trainees, taking the 2013 French national examination for the practice of obstetrical ultrasound were asked to obtain standardized ultrasound planes both on volunteer pregnant women and on an obstetrical ultrasound simulator. These planes included measurements of biparietal diameter, abdominal circumference, and femur length as well as reference planes for cardiac 4-chamber and outflow tracts, kidneys, stomach/diaphragm, spine, and face. Images were stored and evaluated subsequently by 2 national examiners who scored each picture according to previously established quality criteria. Dexterity was also evaluated and subjectively scored between 0 and 10. The Raghunathan's modification of Pearson, Filon's z, Spearman's rank correlation, and analysis of variance tests were used to assess correlations between the scores by the 2 examiners and scores of dexterity and also to compare the final scores between the 2 different methods. RESULTS: We evaluated 29 trainees. The mean dexterity scores in simulation (6.5 ± 2.0) and real examination (5.9 ± 2.3) were comparable (P = .31). Scores with an obstetrical ultrasound simulator were significantly higher than those obtained on volunteers (P = .027). Nevertheless, there was a good correlation between the scores of the 2 examiners judging on simulation (R = 0.888) and on volunteers (R = 0.873) (P = .81). CONCLUSION: An obstetrical ultrasound simulator is as good a method as volunteer-based examination for evaluating practical skills in trainees following structured training in obstetrical ultrasound. The threshold for success/failure should, however, be adapted as candidates obtain higher scores on the simulator. Advantages of the obstetrical ultrasound simulator include the absence of location and time constraints without the need to involve volunteers or to interfere with the running of ultrasound clinics. However, an obstetrical ultrasound simulator still lacks the ability to evaluate the trainees' ability to interact with patients.

Outcome following prenatal diagnosis of severe bilateral renal hypoplasia.

OBJECTIVE: The aim of this research was to evaluate the outcome and prognostic value of fetal serum ß2-microglobulin in case of prenatal diagnosis of severe bilateral renal hypoplasia. METHODS: Cases of hypoplastic kidneys were detected on ultrasound and referred to our laboratory for determination of fetal blood ß2-microglobulin, over a 12-year period. Prenatal prognostic assessment was based upon amniotic fluid volume and fetal serum ß2-microglobulin (cut-off: 5 mg/L). Outcome measures were postnatal renal function or renal pathological features when termination of pregnancy (TOP) and genetic studies were performed. RESULTS: A total of 34 cases were identified; 13 (38%) were liveborn and 21 (62%) underwent TOP. Renal hypoplasia was confirmed postnatally in all cases. Oligohydramnios/anhydramnios was observed in 30/34 (88%) cases. Associated genetic or anatomical anomalies were found in 8/34 (24%) cases. Renal function of liveborn infants was normal in 4/13 cases. Renal lesions were observed in all TOPs (21/21 cases). Overall, 30/34 (88.2%) cases had a poor outcome. ß2-microglobulin accurately predicts poor renal outcome in 27/31 (87.1%) cases. ß2-microglobulin was not interpretable in three cases due to amniotic fluid contamination. The prognostic value of ß2-microglobulin was similar to that of amniotic fluid volume assessment. CONCLUSION: Hypoplastic kidneys complicated by oligohydramnios/anhydramnios are associated with poor outcome. Fetal serum ß2-microglobulin and oligohydramnios both predicted poor outcome.

Prediction of fetal infection in cases with cytomegalovirus immunoglobulin M in the first trimester of pregnancy: a retrospective cohort.

BACKGROUND: Interpretation of positive cytomegalovirus (CMV) immunoglobulin M (IgM) in the first trimester of pregnancy is ill-defined. We aimed to quantify the risk of fetal transmission in women with positive CMV IgM in the first trimester. METHODS: A retrospective cohort of women (2009-2011) was tested for CMV immunoglobulin G (IgG) and IgM before 14 weeks of gestation. IgG avidity was tested with 2 assays (LIAISON and VIDAS). CMV polymerase chain reaction (PCR) was done in maternal serum, amniotic fluid, or neonatal urine at birth. RESULTS: A total of 4931 consecutive women were screened; 201 presented with positive or equivocal IgM and with high, intermediate, or low IgG avidity in 58.7%, 18.9%, and 22.3%, respectively. In 72 women with low or intermediate avidity, fetal transmission was 23.6%. In multivariate analysis, positive CMV PCR in maternal serum, decreasing avidity index with both LIAISON and VIDAS, and low IgG titers were all associated with fetal transmission (odds ratio [OR], 12.38 [95% confidence interval {CI}, 1.77-86.33], P = .011; OR, 0.16 [95% CI, .03-.95], P = .044; OR, 0.54 [95% CI, .11-.88], P = .028; and OR, 0.27 [95% CI, .29-.84], P = .010, respectively). CONCLUSION: This study demonstrates a significant association between the risk of vertical transmission and the avidity index combined with CMV PCR in maternal serum or IgG titers. This allows calculation of incremental risk of fetal transmission upon which informed choice can be based and could lead to a better pickup rate of fetal infection while decreasing unnecessary invasive procedures.

Day-specific probabilities of conception in fertile cycles resulting in spontaneous pregnancies.

STUDY QUESTION: When, within the female cycle, does conception occur in spontaneously fertile cycles? SUMMARY ANSWER: This study provides reference values of day-specific probabilities of date of conception in ongoing pregnancies. The maximum probability of being within a 5-day fertile window was reached on Day 12 following the last menstrual period (LMP). WHAT IS KNOWN ALREADY: The true date of conception is not observable and may only be estimated. Accuracy of these estimates impacts on obstetric management of ongoing pregnancies. Timing of ovulation and fertility has been extensively studied in prospective studies of non-pregnant fertile women using error-prone proxies, such as hormonal changes, body-basal temperature and ultrasound, yielding day-specific probabilities of conception and fertile windows. In pregnant women, date of conception may be retrospectively estimated from early pregnancy fetal measurement by ultrasound. STUDY DESIGN, SIZE, DURATION: Retrospective analysis of consecutive pregnancies in women referred for routine first-trimester screening, over a 3-year period (2009-2011) in a single ultrasound center (n = 6323). PARTICIPANTS/MATERIALS, SETTING, METHODS: Within the overall population, 5830 cases with a certain date of last menses were selected for analysis. The date of conception was estimated using a crown-rump length biometry and an equation derived from IVF/ICSI pregnancies. Day-specific probabilities of conception were estimated across several covariates, including age, cycle characteristics and ethnicity, using deconvolution methods to account for measurement error. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, the day-specific probability of conception sharply rises at 7 days after the LMP, reaching its maximum at 15 days and returning to zero by 25 days. Older women tend to conceive earlier within their cycle, as did women with regular cycles and white and black women compared with Asian ethnicity. The probability of being within the fertile window was 2% probability at Day 4, a maximum probability of 58% at Day 12 and a 5% probability by Day 21 of the cycle. LIMITATIONS, REASONS FOR CAUTION: Although conception is believed to occur within hours following ovulation, a discrepancy is theoretically possible. However, when comparing our results to those of prospective studies, no such difference was found. The equation used for estimating the date of pregnancy was estimated in IVF/ICSI pregnancies, which could lead to potential bias in spontaneous pregnancies. However, in our population, the observed bias was negligible. Non-fertile cycles and early pregnancy losses are necessarily overlooked because of the nature of our data. WIDER IMPLICATIONS OF THE FINDINGS: Because of the wider access to retrospective data and the potential bias in prospective studies of ovulation monitoring, this study should broaden the perspectives of future epidemiologic research in fertility and pregnancy monitoring. STUDY FUNDING/COMPETING INTERESTS: None.

Timing of delivery following selective laser photocoagulation for twin-to-twin transfusion syndrome.

OBJECTIVE: We sought to compare intrauterine risks with postnatal outcome in monochorionic pregnancies operated by fetoscopic laser surgery for twin-to-twin transfusion syndrome. STUDY DESIGN: A cohort of 602 consecutive cases was analyzed. Unexpected prenatal adverse events were identified when a fatal or potentially fatal event occurred that could have been avoided by timely delivery. RESULTS: The prospective risk of an unexpected adverse event dropped from 16.8% (95% confidence interval [CI], 13.6-20.5%) to 0% (95% CI, 0-11%) between 26-36 weeks. At 32 weeks, the residual risk was 1 in 17 (95% CI, 1/28-1/11). The perinatal rate of death or severe brain lesions dropped from 35% (25-47%) in infants delivered at 26-28 weeks down to 3% (1-6%) at 34-36 weeks. CONCLUSION: Our results did not identify an optimal cut-off for elective preterm delivery in laser-operated twin-to-twin transfusion syndrome. Perinatal morbidity appears low from ≥32 weeks and the decision for elective delivery should be based upon medical history, parental demand, and expert assessment.

Screening for fetal spina bifida by ultrasound examination in the first trimester of pregnancy using fetal biparietal diameter.

OBJECTIVE: Prenatal screening for aneuploidies is best achieved in the first trimester when there is no reliable screening test for spina bifida. Early ultrasound features may be too complex for routine screening. We assessed screening potential of simple and reproducible fetal biometric measurements at 11-14 weeks of gestation. STUDY DESIGN: A total of 34,951 unselected consecutive pregnancies included 18 with spina bifida. Another 28 cases were referred for assessment. Biometric measurements were expressed in multiples of the median for crown-rump length. RESULTS: Biparietal diameter (BPD) was smaller in spina bifida (P < .0001). In all, 22 of 44 (50%) cases with spina bifida aperta had a BPD <5th centile. BPD was independent of maternal adiposity and smoking status. CONCLUSION: Simple and reproducible BPD at 11-14 weeks of gestation could detect half the cases of open fetal spina bifida by identifying 5% of pregnancies for expert scanning in first- and second-trimester examinations of the fetal spine and cranium.

Screening for placenta accreta at 11-14 weeks of gestation.

OBJECTIVE: We sought to describe the potential value of 11-14 weeks' screening for placenta accreta (PA). STUDY DESIGN: Patients with a history of lower segment cesarean section were prospectively included between 11-13+6 weeks over a 1.5-year period. The first 258 were offered standard screening whereas the following 105 underwent screening for PA. Women were considered high-risk when the trophoblast overlapped the scar visualized by transvaginal ultrasound and low-risk otherwise. RESULTS: The group screened for PA did not differ from the nonscreened group for demographic characteristics. In all, 6 of 105 (5.8%) women were considered high-risk. In the nonscreened group, 1 case of PA was discovered during an elective repeat cesarean. In the screened population, 1 case of PA occurred in a high-risk patient allowing a conservative planned management at 35 weeks. CONCLUSION: At 11-14 weeks, ultrasound may help risk stratification for PA with a specific follow-up. Early recognition of patients at risk might improve the perinatal outcome of PA.

First-trimester uterine scar assessment by transvaginal ultrasound.

OBJECTIVE: The objective of the study was to describe the assessment of lower segment uterine scar (LSCS) by transvaginal ultrasound (TVUS) during a first-trimester scan. STUDY DESIGN: Patients with a history of LSCS were prospectively enrolled over a 6 month period. Four groups were defined: type 1A, thin scar within cervicoisthmic canal (CIC); type 1B, thin above the internal os (IO); type 2A, dehiscent within the CIC; type 2B, dehiscent above the IO. Accuracy of first-trimester TVUS was investigated by blind testing a panel of 14 operators over a web-based dataset. RESULTS: The scar was visualized in 122 of 123 patients enrolled. Types 1A, 1B, 2A, and 2B occurred in 49.2%, 3.3%, 38.3%, and 9.2%, respectively. When blind tested, fetal medicine specialists achieved a median sensitivity of 82% and specificity of 100% for the detection of a scar. These were 83% and 87% for nonspecialists. CONCLUSION: First-trimester uterine scar assessment may become a valuable tool in early recognition of patients at risk of subsequent perinatal complications.

Long-term developmental follow-up of infants who participated in a randomized clinical trial of amniocentesis vs laser photocoagulation for the treatment of twin-to-twin transfusion syndrome.

OBJECTIVE: We sought to assess long-term neurodevelopment of children who were treated prenatally as part of the Eurofoetus randomized controlled trial. STUDY DESIGN: The study population was composed of 128 cases of twin-to-twin transfusion syndrome (TTTS) included and followed up in France. Survivors were evaluated by standardized neurological examination and by Ages and Stages Questionnaires (ASQ). Primary outcome was a composite of death and major neurological impairment. RESULTS: A total of 120 children (47%) were alive at the age of 6 months and were followed up to the age of 6 years. At the time of diagnosis, only treatment and Quintero stage were predictors of a poor outcome (hazard ratio, 0.61; 95% confidence interval, 0.41-0.90; P = .01 and hazard ratio, 3.23; 95% confidence interval, 2.19-4.76; P < .001, respectively). Children treated by fetoscopic selective laser coagulation (FSLC) had higher ASQ scores at the end of follow-up (P = .04). CONCLUSION: FSLC was significantly associated with a reduction of the risk of death or long-term major neurological impairment at the time of diagnosis and treatment.

A definition of selectivity in laser coagulation of chorionic plate anastomoses in twin-to-twin transfusion syndrome and its relationship to perinatal outcome.

OBJECTIVE: This study was undertaken to correlate selectivity of surgery and perinatal outcome in twin-to-twin transfusion syndrome treated by endoscopic laser coagulation, using a quantitative definition of selectivity. STUDY DESIGN: 287 consecutive cases of severe twin-to-twin transfusion syndrome were reviewed. A selectivity index was built as the ratio of selective over nonselective coagulations per procedure. Outcome measures were survival at 28 days and failure of surgery as defined by recurrence of twin-to-twin transfusion syndrome or fetofetal hemorrhage. RESULTS: Two populations were identified: a high selectivity group (63.8%) and a low selectivity group (36.2%). Survival of at least one twin and survival of both twins were higher in the high-selectivity group (p = .007 and p = .04 respectively). Failure of surgery rates were similar in both groups. CONCLUSION: A quantitative definition of selectivity appears justified by the large variations found in the practice of a single center and by significant differences in outcome. Survival is significantly improved in highly selective procedures.