Fully percutaneous fetoscopic repair of myelomeningocele: 30-month follow-up data.

OBJECTIVE: This observational study reports on the postnatal mortality and 30-month outcome of children who underwent fully percutaneous fetoscopic repair of myelomeningocele (MMC) at a single center in Giessen, Germany. METHODS: Between October 2010 and August 2014, a total of 72 patients underwent fully percutaneous fetoscopic MMC closure at 21 + 0 to 29 + 1 (mean, 23 + 5) weeks' gestation. Of these, 52 (72%) participated in this study; however, 30-month mortality data are available for all 72 children. Children were examined at four timepoints: shortly after birth and at 3 months, 12 months and 30 months of corrected age. The patients underwent age-specific standardized neurological examinations and assessment of leg movements and ambulation at all timepoints. Cognitive and motor development were assessed using the Bayley Scales of Infant Development, second edition (BSID-II), at 30 months. RESULTS: All 72 children survived the intrauterine procedure, however, four (5.6%) infants died postnatally (including two of the 52 comprising the study cohort). Of the 52 patients included in the study, 11.5% were delivered before the 30th week of gestation (mean, 33 + 1 weeks) and, of the survivors, 48.1% had ventriculoperitoneal shunt placement. Of the 50 infants that were alive at 30 months, independent ambulation, without orthosis, was feasible for 46%. At 30 months of follow-up, 46% of children presented with a functional level that was at least two segments better than the anatomical level of the lesion. At 30 months, 70% of the children presented with BSID-II psychomotor development index score of ≥ 70 and 80% with BSID-II mental development index score of ≥ 70. CONCLUSION: Intrauterine repair of MMC by percutaneous fetoscopy shows largely similar outcomes to those reported for open repair, with respect to mortality, prematurity, shunt-placement rates, motor and mental development and free ambulation. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Prediction of post-laser fetal death in selective growth restriction complicating twin-twin transfusion syndrome using standardized definitions.

OBJECTIVE: Selective fetal growth restriction (sFGR) complicating twin-twin transfusion syndrome (TTTS) is associated with a 3-6-fold increased risk of fetal demise after fetoscopic laser surgery (FLS). Identifying these patients is challenging due to varying definitions of sFGR used in the literature. The objective of this study was to determine the association of three currently used definitions for sFGR with demise of the smaller twin, typically the donor, following FLS for TTTS. METHODS: This was a retrospective cohort study of monochorionic diamniotic twin pregnancies undergoing FLS for TTTS between January 2015 and December 2018. Classification of the cohort as sFGR or non-sFGR was performed using three different definitions: (1) estimated fetal weight (EFW) of one twin < 10th centile and intertwin EFW discordance > 25%, according to the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) (Definition A); (2) EFW of one twin < 3rd centile, according to the solitary criterion for sFGR reported in a Delphi consensus (Definition B); and (3) presence of at least two of four of the following criteria: EFW of one twin < 10th centile, abdominal circumference of one twin < 10th centile, intertwin EFW discordance of ≥ 25% and umbilical artery pulsatility index of the smaller twin > 95th centile, according to the contributory criteria for sFGR in monochorionic diamniotic twin pregnancies reported in the Delphi consensus (Definition C). Pearson's χ2 and univariate and multivariate logistic regression analyses were performed to assess the association of classification as sFGR according to the different definitions with fetal demise within 48 h after FLS. RESULTS: A total of 124 pregnancies underwent FLS for TTTS during the study period. Of these, 46/124 (37.1%) were identified as having sFGR according to the ISUOG criteria (Definition A), 57/124 (46.0%) based on EFW < 3rd centile (Definition B) and 70/124 (56.5%) according to the Delphi contributory criteria (Definition C). There were no differences in maternal body mass index, recipient twin amniotic fluid volume, gestational age (GA) at intervention or GA at delivery between sFGR and non-sFGR cases for any of the three definitions. There were also no differences in the rates of postprocedure recipient demise or Doppler abnormalities in the recipient. Regardless of the definition used, sFGR cases showed a significantly higher rate of postprocedure donor twin demise compared with that in non-sFGR cases (Definition A: 28.3% vs 3.8%, P < 0.01; Definition B: 22.8% vs 4.5%, P = 0.02; Definition C: 22.9% vs 0%, P < 0.01). For all of the sFGR definitions, the rate of Stage-III TTTS was increased in sFGR compared to non-sFGR cases (Definition A: 65.2% vs 35.9%, P ≤ 0.01; Definition B: 59.6% vs 35.8%, P = 0.04; Definition C: 62.9% vs 25.9%, P < 0.01). All cases of donor demise met the criteria for sFGR according to Definition C. Classification as sFGR according to Definition C was associated with a significantly higher rate of post-FLS donor demise compared to Definitions A and B (χ2 , 15.32; P < 0.01). Logistic regression analysis demonstrated that sFGR cases had an increased risk of donor demise (Definition A: odds ratio (OR), 4.97 (95% CI, 1.77-13.94), P < 0.01; Definition B: OR, 4.39 (95% CI, 1.36-14.15), P = 0.01) and that staging of TTTS was also predictive of demise (OR, 2.26 (95% CI, 1.14-4.47), P = 0.02). After adjusting for GA at intervention and stage of TTTS, the results were similar (Definition A: OR, 6.48 (95% CI, 2.11-24.56), P = 0.002; Definition B: OR, 4.16 (95% CI, 1.35-15.74), P = 0.02). CONCLUSIONS: The rate of fetal demise following FLS for TTTS is increased in the presence of sFGR. Improving diagnosis of sFGR should improve counseling and may affect management. The Delphi method of defining sFGR based on the presence of at least two of four contributory criteria had the highest predictive value for donor demise following FLS for TTTS. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Outcome of twin-twin transfusion syndrome according to Quintero stage of disease: systematic review and meta-analysis.

OBJECTIVES: To report the outcome of pregnancies complicated by twin-twin transfusion syndrome (TTTS) according to Quintero stage. METHODS: MEDLINE, EMBASE and CINAHL databases were searched for studies reporting the outcome of pregnancies complicated by TTTS stratified according to Quintero stage (I-V). The primary outcome was fetal survival rate according to Quintero stage. Secondary outcomes were gestational age at birth, preterm birth (PTB) before 34, 32 and 28 weeks' gestation and neonatal morbidity. Outcomes are reported according to the different management options (expectant management, laser therapy or amnioreduction) for pregnancies with Stage-I TTTS. Only cases treated with laser therapy were considered for those with Stages-II-IV TTTS and only cases managed expectantly were considered for those with Stage-V TTTS. Random-effects head-to-head meta-analysis was used to analyze the extracted data. RESULTS: Twenty-six studies (2699 twin pregnancies) were included. Overall, 610 (22.6%) pregnancies were diagnosed with Quintero stage-I TTTS, 692 (25.6%) were Stage II, 1146 (42.5%) were Stage III, 247 (9.2%) were Stage IV and four (0.1%) were Stage V. Survival of at least one twin occurred in 86.9% (95% CI, 84.0-89.7%) (456/552) of pregnancies with Stage-I, in 85% (95% CI, 79.1-90.1%) (514/590) of those with Stage-II, in 81.5% (95% CI, 76.6-86.0%) (875/1040) of those with Stage-III, in 82.8% (95% CI, 73.6-90.4%) (172/205) of those with Stage-IV and in 54.6% (95% CI, 24.8-82.6%) (5/9) of those with Stage-V TTTS. The rate of a pregnancy with no survivor was 11.8% (95% CI, 8.4-15.8%) (69/564) in those with Stage-I, 15.0% (95% CI, 9.9-20.9%) (76/590) in those with Stage-II, 18.6% (95% CI, 14.2-23.4%) (165/1040) in those with Stage-III, 17.2% (95% CI, 9.6-26.4%) (33/205) in those with Stage-IV and in 45.4% (95% CI, 17.4-75.2%) (4/9) in those with Stage-V TTTS. Gestational age at birth was similar in pregnancies with Stages-I-III TTTS, and gradually decreased in those with Stages-IV and -V TTTS. Overall, the incidence of PTB and neonatal morbidity increased as the severity of TTTS increased, but data on these two outcomes were limited by the small sample size of the included studies. When stratifying the analysis of pregnancies with Stage-I TTTS according to the type of intervention, the rate of fetal survival of at least one twin was 84.9% (95% CI, 70.4-95.1%) (94/112) in cases managed expectantly, 86.7% (95% CI, 82.6-90.4%) (249/285) in those undergoing laser therapy and 92.2% (95% CI, 84.2-97.6%) (56/60) in those after amnioreduction, while the rate of double survival was 67.9% (95% CI, 57.0-77.9%) (73/108), 69.7% (95% CI, 61.6-77.1%) (203/285) and 80.8% (95% CI, 62.0-94.2%) (49/60), respectively. CONCLUSIONS: Overall survival in monochorionic diamniotic pregnancies affected by TTTS is higher for earlier Quintero stages (I and II), but fetal survival rates are moderately high even in those with Stage-III or -IV TTTS when treated with laser therapy. Gestational age at birth was similar in pregnancies with Stages-I-III TTTS, and gradually decreased in those with Stages-IV and -V TTTS treated with laser and expectant management, respectively. In pregnancies affected by Stage-I TTTS, amnioreduction was associated with slightly higher survival compared with laser therapy and expectant management, although these findings may be confirmed only by future head-to-head randomized trials. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Resultado del síndrome de transfusión feto-fetal según el estadio de Quintero de la enfermedad: revisión sistemática y metaanálisis OBJETIVOS: Informar sobre el resultado de los embarazos complicados por el síndrome de transfusión feto-fetal (TTTS, por sus siglas en inglés) según el estadio de Quintero. MÉTODOS: Se hicieron búsquedas en las bases de datos de MEDLINE, EMBASE y CINAHL de estudios que hubieran informado sobre el resultado de embarazos complicados por TTTS, estratificados según el estadio de Quintero (I-V). El resultado primario fue la tasa de supervivencia fetal según el estadio de Quintero. Los resultados secundarios fueron la edad gestacional al nacer, el parto pretérmino (PPT) antes de las 34, 32 y 28 semanas de gestación y la morbilidad neonatal. Los resultados se reportan de acuerdo con las diferentes opciones de tratamiento (expectante, terapia de láser o amniorreducción) para los embarazos con TTTS en Estadio I. Sólo se consideraron los casos tratados con terapia de láser para aquellos con TTTS de las Etapas II-IV y sólo se consideraron los casos tratados de manera expectante para aquellos con TTTS de la Etapa V. Para analizar los datos extraídos se utilizó un metaanálisis directo de efectos aleatorios. RESULTADOS: Se incluyeron veintiséis estudios (2699 embarazos de gemelos). En total, 610 (22,6%) embarazos fueron diagnosticados con TTTS de Estadio I de Quintero, 692 (25,6%) de Estadio II, 1146 (42,5%) de Estadio III, 247 (9,2%) de Estadio IV y cuatro (0,1%) de Estadio V. La supervivencia de al menos un gemelo se produjo en el 86,9% (IC 95%, 84,0-89,7%) (456/552) de los embarazos en Estadio I, en el 85% (IC 95%, 79,1-90,1%) (514/590) de aquellos en Estadio II, en el 81,5% (IC 95%, 76,6-86,0%) (875/1040) de aquellos en Estadio-III, en el 82,8% (IC 95%, 73,6-90,4%) (172/205) de aquellos en Estadio-IV y en el 54,6% (IC 95%, 24,8-82,6%) (5/9) de aquellos en Estadio-V de TTTS. La tasa de embarazos sin supervivientes fue del 11,8% (IC 95%, 8,4-15,8%) (69/564) de aquellos en Estadio-I, 15,0% (IC 95%, 9,9-20,9%) (76/590) de aquellos en Estadio-II, 18,6% (IC 95%, 14,2-23,4%) (165/1040) de aquellos en Estadio-III, 17,2% (IC 95%, 9,6-26,4%) (33/205) de aquellos en Estadio-IV y en el 45,4% (IC 95%, 17,4-75,2%) (4/9) de aquellos en Estadio-V de TTTS. La edad gestacional al nacer fue similar en los embarazos con TTTS en los Estadios I-III, y disminuyó gradualmente en aquellos con TTTS en los Estadios IV y V. En general, la incidencia de PPT y la morbilidad neonatal aumentaron a medida que se incrementó la gravedad del TTTS, pero los datos sobre estos dos resultados se vieron limitados por el pequeño tamaño de la muestra de los estudios incluidos. Al estratificar el análisis de los embarazos con TTTS en Estadio I según el tipo de tratamiento, la tasa de supervivencia fetal de al menos un gemelo fue del 84,9% (IC 95%, 70,4-95,1%) (94/112) en los casos tratados de forma expectante, del 86,7% (IC 95%, 82,6-90.4%) (249/285) en los sometidos a terapia láser y del 92,2% (IC 95%, 84,2-97,6%) (56/60) en los sometidos a amniorreducción, mientras que la tasa de supervivencia doble fue del 67,9% (IC 95%, 57,0-77,9%) (73/108), del 69,7% (IC 95%, 61,6-77,1%) (203/285) y del 80,8% (IC 95%, 62,0-94,2%) (49/60), respectivamente. CONCLUSIONES: La supervivencia en general en los embarazos biamnióticos monocoriónicos afectados por TTTS es mayor en los estadios tempranos de Quintero (I y II), pero las tasas de supervivencia fetal son moderadamente altas incluso en aquellos con TTTS en estadios III o IV cuando se tratan con terapia láser. La edad gestacional al nacer fue similar en los embarazos con TTTS en los Estadios I-III, y disminuyó gradualmente en aquellos con TTTS en los Estadios IV y V tratados con láser y tratamiento expectante, respectivamente. En los embarazos afectados por TTTS en Estadio I, la amniorreducción estuvo asociada con una supervivencia ligeramente mayor en comparación con la terapia de láser y el tratamiento expectante, aunque estos hallazgos solo pueden confirmarse mediante futuros estudios aleatorizados directos. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Intrafetal laser for midtrimester TRAP sequence-experience from a single center.

OBJECTIVE: To report our experience and evaluate outcomes in monochorionic pregnancies with Twin Reversed Arterial Perfusion sequence with intrafetal laser therapy. METHODS: Retrospective review of records of all pregnancies with TRAP sequence treated by intrafetal laser therapy between 2011 January and 2015 December that were retrieved and analysed. RESULTS: Electronic search of the scan database retrieved 57 cases of TRAP sequence during the study period, 7 triplets and 50 monochorionic twins. Intrafetal laser was done in 27 cases, 22 cases of twins and 5 cases of triplets. In the twins group, median gestational age at intervention was 22.5 weeks, the earliest done at 16.3 weeks. The median gestational age at delivery and birth weight was 37 weeks and 2.5 Kgs. The median procedure and delivery interval was 14 weeks. Live birth rate was 17/22 (77%) the pump survival rate was 16/22 (73%). Pregnancies with non-surviving pump were 5 in numbers (5/22). A repeat procedure was warranted in one case. In the triplet group, median gestational age at intervention, delivery and procedure delivery interval was 18, 35 and 17 weeks. CONCLUSION: Intrafetal laser is simple, effective and the treatment of choice to interrupt the vascular supply to acardiac twin.

EXIT (ex utero intrapartum treatment) surgery for the management of fetal airway obstruction: A systematic review of the literature.

PURPOSE: To provide a comprehensive overview of the perinatal and maternal outcomes of fetuses undergoing EXIT surgery for the management of fetal airway obstruction secondary to cervical or oral tumors. METHODS: A comprehensive search from inception to September 2018 was conducted on databases including MEDLINE, EMBASE, Cochrane Library and LILACS. All studies that reported an EXIT surgery in singleton were considered eligible. A descriptive analysis was performed. RESULTS: Out of the 250 full-text study reports, 120 articles reporting 235 cases of EXIT surgery were included. EXIT surgery was performed at 35.1 weeks of gestation on average. The most frequent diagnosis was teratoma (46.4%, n = 109/235). There were 13 adverse maternal events, and the most frequent one was postpartum hemorrhage (4.7%, n = 11/235). No maternal death was reported. Fetal and neonatal death occurred in 17% (40/235) of the cases. There were 29 adverse fetal events (12.2%), and the most frequent one was the failure of intubation or tracheostomy (3.4%, n = 8/235). CONCLUSION: EXIT surgery could be considered for the management of an oral or cervical tumor that's highly suspicious of blocking the fetal airway. This systematic review reports that EXIT surgery poses substantial risks of maternal and fetal adverse events, including neonatal death. LEVEL OF EVIDENCE: IV case series with no comparison group.

Survival outcome in severe left-sided congenital diaphragmatic hernia with and without fetal endoscopic tracheal occlusion in a country with suboptimal neonatal management.

OBJECTIVE: To evaluate the impact of fetal endoscopic tracheal occlusion (FETO) on improving survival of fetuses with severe left-sided congenital diaphragmatic hernia (CDH), as compared with contemporaneous cases managed expectantly during pregnancy, in a country with suboptimal neonatal management. METHODS: In this prospective cohort study, consecutive fetuses with isolated left-sided CDH, normal karyotype and severe pulmonary hypoplasia (defined as liver herniation and observed/expected lung-to-head circumference ratio below 26%) were selected for FETO at less than 32 weeks of gestation in a single tertiary referral center in Queretaro, Mexico. Postnatal outcome (survival up to 28 days after birth) was compared between fetuses treated with FETO and contemporaneous cases with similar lung size managed expectantly during pregnancy. RESULTS: Twenty-five fetuses with isolated severe left-sided CDH treated with FETO were matched individually with 25 cases managed expectantly during pregnancy. Endotracheal placement of the balloon was performed successfully on the first attempt in all cases. The median gestational age (GA) at balloon placement was 29.1 (range, 25.6-31.8) weeks and 34.1 (range, 30.0-36.1) weeks at balloon removal. There were no technical problems with the introduction or removal of the balloon in any cases. The median GA at delivery was significantly lower in the group treated with FETO than in those managed expectantly (35.3 vs 37.7 weeks; P = 0.04). The survival rate was significantly higher in the group treated with FETO than in those without fetal intervention (32% vs 0%; P < 0.001). CONCLUSION: In settings with suboptimal neonatal management, FETO was associated with improved neonatal survival in fetuses with isolated left-sided CDH and severe pulmonary hypoplasia. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Resultado de supervivencia en una hernia diafragmática congénita grave del lado izquierdo, con y sin oclusión traqueal endoscópica fetal en un país con un tratamiento neonatal subóptimo OBJETIVO: Evaluar el impacto de la oclusión traqueal endoscópica fetal (OTEF) en la mejora de la supervivencia de los fetos con hernia diafragmática congénita (HDC) grave del lado izquierdo, en comparación con los casos actuales tratados como embarazo gestante, en un país con un tratamiento neonatal subóptimo. MÉTODOS: En este estudio prospectivo de cohortes, se seleccionaron fetos consecutivos con HDC aislada del lado izquierdo, cariotipo normal e hipoplasia pulmonar grave (definida como hernia hepática y una proporción observada/esperada de la circunferencia pulmonar-cabeza inferior al 26%) para una OTEF antes de las 32 semanas de gestación, en un único centro de medicina especializada terciaria en Querétaro (México). El resultado postnatal (supervivencia hasta los 28 días después del nacimiento) se comparó entre fetos tratados con OTEF y los casos contemporáneos con tamaño pulmonar similar, tratados como embarazo gestante. RESULTADOS: Veinticinco fetos con HDC grave aislada del lado izquierdo que habían sido tratados con OTEF fueron emparejados individualmente con 25 casos tratados como embarazo gestante. La colocación endotraqueal del globo se realizó con éxito en el primer intento en todos los casos. La mediana de la edad gestacional (EG) en el momento de la colocación del globo fue de 29,1 (rango, 25,6-31,8) semanas y 34,1 (rango, 30,0-36,1) semanas cuando se retiró el globo. En ningún caso hubo problemas técnicos con la introducción o la retirada del globo. La mediana de la EG en el momento del parto fue significativamente menor en el grupo tratado con OTEF que en el grupo tratado como gestante (35,3 vs 37,7 semanas; P=0,04). La tasa de supervivencia fue significativamente más alta en el grupo tratado con OTEF que en los casos sin intervención fetal (32% vs 0%; P<0,001). CONCLUSIÓN: En los entornos con un tratamiento neonatal subóptimo, la OTEF se asoció con una mejora de la supervivencia neonatal en los fetos con HDC aislada del lado izquierdo y con hipoplasia pulmonar grave. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Neonatal Outcomes and Maternal Characteristics in Monochorionic Diamniotic Twin Pregnancies: Uncomplicated versus Twin-to-Twin Transfusion Syndrome Survivors after Fetoscopic Laser Surgery.

Preterm birth remains a major complication of fetal laser surgery (FLS) due to twin-to-twin transfusion syndrome (TTTS). OBJECTIVES: We tested the hypothesis that neonatal outcomes in fetuses born at >24 weeks are worse in TTTS survivors compared to uncomplicated monochorionic diamniotic (MCDA) twins. METHODS: 196 patients with TTTS treated with laser therapy and 91 uncomplicated MCDA gestations were compared. Neonatal outcomes included respiratory distress syndrome (RDS), transient tachypnea of the newborn (TTN), bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, and neonatal death. Risk factors assessed were TTTS, maternal age, maternal body mass index, race, premature prolonged rupture of membranes, stage of TTTS, parity, and gestational age (GA) at delivery. RESULTS: GA at delivery was lower in the TTTS group (31.0 ± 4.6 vs. 33.5 ± 2.4 weeks, p < 0.001). RDS and TTN occurred at higher rates in the TTTS than in the uncomplicated MCDA group. After multivariate logistic regression, the only factor significantly associated with the composite adverse outcome was GA at delivery (OR 0.61; 95% CI: 0.58-0.7). CONCLUSION: TTTS twins treated with FLS are deliver 2.5 weeks earlier than uncomplicated MCDA twins. Respiratory complications were significantly higher in TTTS twins and were mainly the consequence of the early GA at delivery.

Characteristics of referred patients with twin-twin transfusion syndrome who did not undergo fetal therapy.

INTRODUCTION: Abundant research has reported twin-twin transfusion syndrome (TTTS) outcomes following fetal therapy. Our research describes TTTS patients who did not undergo fetal therapy. METHODS: Records from TTTS pregnancies evaluated at 16 to 26 gestational weeks were reviewed between January 2006 and March 2017. The study population comprised subjects who did not undergo fetal therapy. Based on initial consultation, patients were grouped as nonsurgical vs surgical candidates. TTTS progression and perinatal outcomes were assessed. RESULTS: Of 734 TTTS patients evaluated, 68 (9.3%) did not undergo intervention. Of these, 62% were nonsurgical candidates and 38% were surgical candidates. Nonsurgical candidates were ineligible for treatment because of fetal demise or maternal factors (placental abruption, severe membrane separation, and preterm labor). Of surgical candidates, 11 underwent expectant management, eight elected pregnancy termination, and seven planned fetal intervention but had a complication before the procedure. TTTS progression occurred in 10 (15.2%) of 66 cases. Neonatal survival in 64 cases was as follows: in 41 (64%), no survivors; in 11 (17.2%), one survivor; and in 12 (18.8%), two survivors. CONCLUSION: Nine percent of referred TTTS patients did not undergo fetal therapy, with many ineligible because of morbidity between referral and consultation. Studies of TTTS should acknowledge this subgroup and circumstances leading to lack of treatment.

Risk of donor demise after laser therapy for twin-twin transfusion when complicated by growth discordance and abnormal umbilical artery Doppler findings.

OBJECTIVE: To investigate the natural course of abnormal umbilical artery Doppler (UAD) findings in donor fetuses after laser surgery and the prognostic significance of resolution, persistence, or new onset UAD abnormalities with and without the presence of preoperative growth discordance. STUDY DESIGN: Retrospective cohort study of all monochorionic-diamniotic multi-fetal gestations diagnosed with twin-twin transfusion syndrome (TTTS) undergoing laser surgery at a single large metropolitan referral center from 2010-2016. The estimated fetal weight was measured preoperatively and the UAD were measured both pre- and postoperatively (median = 8 days). Patients were grouped according to the presence of abnormal UAD with or without growth discordance pre- and postoperatively. Risk ratios (RR) were calculated for each group for risk of intrauterine fetal demise compared to the pre- and postoperative normal UAD groups as the referents. RESULTS: There were eighty-one women who met inclusion criteria throughout the study period. Forty-three (53.1%) patients had abnormal donor twin UAD preoperatively and 33 (40.7%) were diagnosed with growth discordance. However, 13 (44.8%) had normalization of the UAD postoperatively (median = 8 days) with a similar rate of donor fetal demise as the non-discordant preoperative normal UAD group (7.7% versus 10.3%, p = .79). Abnormal preoperative UAD was associated with an increased risk of donor demise (RR 3.6, CI 1.1-12.1), which was further elevated in the presence of growth discordance (RR 5.2, CI 1.7-16.3). The greatest risk for donor demise was seen if the UAD remained abnormal postoperatively with concomitant growth discordance (RR 10.3, CI 2.5-41.6). CONCLUSIONS: Preoperative abnormal donor UAD is a significant risk for donor demise post-laser therapy for TTTS. Persistent postoperative abnormal UAD with concomitant growth discordance confers the greatest risk for donor demise. However, resolution of abnormal UAD has a similar rate of donor demise when compared to patients with normal UAD preoperatively.

Influence of farewell rituals and psychological vulnerability on grief following perinatal loss in monochorionic twin pregnancy.

AIM: The aim of this study is to analyze whether the absence of farewell rituals and previous psychological vulnerability are associated with the intensity of grief following perinatal loss in monochorionic twin pregnancy. METHOD: The sample comprised 28 women who experienced perinatal loss following fetal surgery. Sociodemographic and clinical data and information about farewell rituals were collected through interview. The women also completed a questionnaire about perinatal grief. RESULTS: A history of psychological and/or psychopharmacological treatment was associated with more intense grief following perinatal loss. CONCLUSION: Women with a history of psychological difficulties are particularly vulnerable to a complicated grief reaction after experiencing perinatal loss. However, the intensity of grief did not differ significantly according to whether or not the women performed some kind of farewell ritual. Further studies are needed to investigate these relationships and to encourage and facilitate the development of specific interventions for this population.

Survival Rate without Brain Abnormalities on Postnatal Ultrasonography among Monochorionic Twins after Fetoscopic Laser Photocoagulation for Selective Intrauterine Growth Restriction with Concomitant Oligohydramnios.

INTRODUCTION: We aimed to clarify the survival rate without brain abnormalities (BA) after fetoscopic laser photoco-agulation (FLP) for monochorionic diamniotic twin gestations (MCDA) with selective intrauterine growth restriction (sIUGR) accompanied by abnormal umbilical artery (UA) Doppler waveforms and isolated oligohydramnios in the sIUGR twin. MATERIALS AND METHODS: This retrospective study included 52 cases that underwent FLP. The main outcome was survival rate without BA of the twins at age 28 days. BA was defined as severe intraventricular hemorrhage and periventricular leukomalacia on postnatal ultrasonography. RESULTS: Median gestational age at FLP was 20 (16-24) weeks. Ten cases were classified as type III based on Doppler for the UA. For all cases, including 20 cases of anterior placenta, FLP was completed without major intraoperative complications. Amnioinfusion was required in 49 cases for better fetoscopic visualization. Fetal loss occurred in 29 sIUGR twins and two larger twins, whereas one larger twin experienced neonatal death. Survival rates without BA were 44% (n = 23) for sIUGR twins and 94% (n = 49) for the larger twins. DISCUSSION: FLP for MCDA with sIUGR presenting with oligohydramnios in the sIUGR twin might be considered a prenatal treatment option.

Tracheal Diameter and Respiratory Outcome in Infants with Congenital Diaphragmatic Hernia Treated by Fetal Endoscopic Tracheal Occlusion.

AIM: To evaluate tracheal diameters and their clinical impact in patients with congenital diaphragmatic hernia (CDH) after fetal endoscopic tracheal occlusion (FETO). METHODS: Patients born with CDH between January 2012 and August 2016 were divided into two groups: noFETO and FETO. Tracheal diameters at three levels (T1, carina, and maximum tracheal dilation) on chest X-ray at 1, 3, 6, 12, 24, and 36 months of follow-up, requirements of invasive and noninvasive respiratory support, the incidence of respiratory infections, and results of pulmonary function tests (PFT) were compared. RESULTS: A total of 71 patients with CDH were born in the study period, and there were 34/41 survivors in the no-FETO group (82.9%) and 13/30 in the FETO group (43.3%). The maximum tracheal diameter was significantly greater in the FETO group at all ages. No differences were observed in the diameters at T1 and the carina, in the requirements of invasive and noninvasive respiratory support, and in the incidence respiratory infections. At the PFT (6-12 months), the FETO group presented higher respiratory rates (46.1 ± 6.2 vs. 36.5 ± 10.6, p = 0.02). No differences in PFT results were found between the groups after the 1st year of life. CONCLUSIONS: The FETO procedure leads to persistent tracheomegaly. However, the tracheomegaly does not seem to have a significant clinical impact.

Fetal tracheal occlusion in mice: a novel transuterine method.

BACKGROUND: Fetal tracheal occlusion (TO) is an emerging surgical therapy in congenital diaphragmatic hernia that improves the fetal lung growth. Different animal models of congenital diaphragmatic hernia and TO present advantages and disadvantages regarding ethical issues, cost, surgical difficulty, size, survival rates, and available genetic tools. We developed a minimally invasive murine transuterine TO model, which will be useful in defining how TO impacts lung molecular biology, cellular processes, and overall lung physiology. MATERIALS AND METHODS: Time-mated C57BL/6 mice underwent laparotomy at embryonic day 16.5 (E16.5) with transuterine TO performed on two fetuses in each uterine horn. At E18.5, dams were sacrificed and fetuses harvested. The lungs of the TO fetuses were compared with the nonmanipulated counterparts by morphometric and histologic analysis. RESULTS: Successful TO was confirmed in 16 of 20 TO fetuses. Twelve of them survived to E18.5 (75%). Fetal weights were comparable, but lung weights were significantly greater in TO (28.41 ± 5.87 versus 23.38 ± 3.09, P = 0.043). Lung to body weight ratio was also greater (0.26 ± 0.003 versus 0.22 ± 0.002, P = 0.006). E18.5 TO lungs demonstrated dilated central and distal airspaces with increased cellularity. DNA/protein and DNA/lung weight ratios were elevated while protein/lung weight ratio was lower in TO compared to control. CONCLUSIONS: Mice fetal transuterine TO is feasible with comparable outcomes to other current animal models. The increase in the lung weight, lung to body weight ratio and the DNA/protein ratio indicate organized lung growth rather than edema or cell hypertrophy.

The impact of the maternal-foetal environment on outcomes of surgery for congenital heart disease in neonates.

OBJECTIVES: Pregnancies with congenital heart disease in the foetus have an increased prevalence of pre-eclampsia, small for gestational age and preterm birth, which are evidence of an impaired maternal-foetal environment (MFE). METHODS: The impact of an impaired MFE, defined as pre-eclampsia, small for gestational age or preterm birth, on outcomes after cardiac surgery was evaluated in neonates (n = 135) enrolled in a study evaluating exposure to environmental toxicants and neuro-developmental outcomes. RESULTS: The most common diagnoses were transposition of the great arteries (n = 47) and hypoplastic left heart syndrome (n = 43). Impaired MFE was present in 28 of 135 (21%) subjects, with small for gestational age present in 17 (61%) patients. The presence of an impaired MFE was similar for all diagnoses, except transposition of the great arteries (P < 0.006). Postoperative length of stay was shorter for subjects without an impaired MFE (14 vs 38 days, P < 0.001). Hospital mortality was not significantly different with or without impaired MFE (11.7% vs 2.8%, P = 0.104). However, for the entire cohort, survival at 36 months was greater for those without an impaired MFE (96% vs 68%, P = 0.001). For patients with hypoplastic left heart syndrome, survival was also greater for those without an impaired MFE (90% vs 43%, P = 0.007). CONCLUSIONS: An impaired MFE is common in pregnancies in which the foetus has congenital heart disease. After cardiac surgery in neonates, the presence of an impaired MFE was associated with lower survival at 36 months of age for the entire cohort and for the subgroup with hypoplastic left heart syndrome.

Chorioamniotic Membrane Separation after Fetoscopic Laser Photocoagulation.

INTRODUCTION: This study aimed to investigate the risk factors, incidence, and influence on the perinatal outcome of chorioamniotic membrane separation (CMS) after fetoscopic laser photocoagulation (FLP). MATERIAL AND METHODS: This retrospective study included 312 women who underwent FLP for twin-to-twin transfusion syndrome (TTTS). Clinical records were used to review obstetrical examinations, complications, operative data, ultrasonographic findings, and perinatal and neonatal follow-up data in all patients. RESULTS: A total of 260 cases of TTTS were analyzed. The incidence of CMS was 12.7% (33 cases). The only independent risk factor of CMS was performing FLP before 20 weeks of gestational age (GA) (odds ratio = 3.38 [1.44-7.93], p = 0.005). Concerning perinatal outcome, CMS was only related with increased risk of premature rupture of membranes (PROM) before 32 weeks (33.3 vs. 13.9%, p = 0.005), with no differences in GA at delivery and survival rate. DISCUSSION: In our cohort, the incidence of CMS after FLP was approximately 13%, with surgery before 20 weeks being the only risk factor identified. Although in our population CMS did not worsen perinatal outcome in terms of preterm delivery or survival, the preterm PROM rate was increased and this should be considered for the patients' management.

Incidence and Causes of Intentional Fetal or Neonatal Demise in Twin-Twin Transfusion Syndrome.

INTRODUCTION: The aim of this study is to evaluate the incidence and causes of intentional fetal and neonatal demise in twin-twin transfusion syndrome (TTTS). MATERIAL AND METHODS: All TTTS pregnancies managed at our centre between 2000 and 2014 were included. We evaluated incidence and causes of intentional fetal/neonatal demise, defined as termination of pregnancy, selective fetal reduction, or withdrawal of neonatal intensive care. RESULTS: Intentional fetal/neonatal demise occurred in 9.8% (110/1,122) of fetuses and was due to termination of pregnancy (2.2%), selective fetal reduction (4.2%), or withdrawal of neonatal intensive care (3.4%). Reasons for termination of pregnancy included complications of laser treatment (72.0%), severe fetal anomaly (20.0%), and unwanted pregnancy (8.0%). Reasons for selective fetal reduction were technical difficulties to perform laser surgery (51.1%), fetal complications (38.3%), and parental preference for fetal reduction rather than laser treatment (10.6%). Reasons for withdrawal of neonatal intensive care treatment were severe cerebral injury (47.4%), severe pulmonary complications (15.8%), birth asphyxia (5.3%), multiple complications of TTTS and/or prematurity combined (21.1%), or other (10.5%). CONCLUSIONS: Intentional fetal or neonatal demise in TTTS occurs frequently and is often due to complications after laser surgery and/or severe (cerebral) injury in affected fetuses or neonates.

Fetoscopic laser coagulation in 1020 pregnancies with twin-twin transfusion syndrome demonstrates improvement in double-twin survival rate.

OBJECTIVE: To investigate the growing experience and learning curve of fetoscopic laser coagulation of the placental vascular anastomoses in severe mid-trimester twin-twin transfusion syndrome (TTTS) and its influence on perinatal outcome in a single-center setting. METHODS: Between January 1995 and March 2013 we performed laser therapy in 1020 consecutive pregnancies with TTTS between 15.1 and 27.4 weeks' gestation. We compared perinatal outcome in blocks of five sequential groups of 200 cases, taking into account several covariates in order to adjust for case mix and to demonstrate learning curves and success rates. RESULTS: The percentage of pregnancies with survival of both fetuses increased from 50.0% (n = 100) in the first 200 cases to 69.5% (n = 153) in the last 220 cases (P = 0.018 for trend) and the overall survival rate for both fetuses in the complete series of 1019 cases with known outcome was 63.3% (n = 645). The survival rate of at least one fetus increased from 80.5% (161/200) in the first group to 91.8% (202/220) in the last group (P = 0.072 for trend) and the overall survival rate of at least one fetus in the complete series was 86.7% (883/1019). In the total population, the mean gestational age at delivery of pregnancies with at least one liveborn neonate was 33.7 ± 3.2 weeks, with a mean interval of 12.9 ± 4.0 weeks between intervention and delivery. Among the first two groups, 124 pregnancies had anterior placentae and were treated with a 0° fetoscope. These cases had the poorest overall outcome, with a double-twin survival rate of 44.4% (55/124), which increased to 65.1% (207/318; P = 0.001) after the introduction of a 30° fetoscope for cases with anterior placenta. The success rate for double-twin survival reached a plateau of 69% at 600 procedures, a rate equalled by a new operator who was trained hands-on and performed 174 of the last 400 procedures. CONCLUSIONS: We report the largest single-center experience of laser coagulation in TTTS. We observed a continuous increase in double-twin survival rate owing to the growing experience based on the learning curve and refinements in fetoscopic instruments and techniques. These data provide strong arguments for the centralization of minimally invasive intrauterine surgery in specialized high-volume centers. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Procedure-Related Complications and Survival Following Fetoscopic Endotracheal Occlusion (FETO) for Severe Congenital Diaphragmatic Hernia: Systematic Review and Meta-Analysis in the FETO Era.

Introduction This study aims to assess the procedure-related complications and survival following fetoscopic endotracheal occlusion (FETO) for severe congenital diaphragmatic hernia. Materials and Methods A systematic review and meta-analysis of PubMed and Scopus database searching for FETO procedure in severe CDH (lung-to-head ratio [LHR] < 1.0 and/or observed/expected LHR < 0.26 and > 1/3 liver herniation) were performed. The relative risk was assessed and 95% confidence interval (CI) calculated. Procedure complications and survival were compared between FETO and randomized controlled trial (RCT) as well as observational case-control studies. Results A total of 4,807 records were retrieved based on the title and abstracts, and 18 studies were eligible for statistical analysis (1 RCT and 17 observational case-control studies). Relative risk (95% CI) comparing FETO and controls for premature rupture of membrane, preterm birth < 32 weeks, preterm birth < 37 weeks, survival at 30 days, and survival at 6 months were 1.7 (0.8-2.4), 7.3 (0.4-134), 1.8 (0.8-3.9), 5.8 (1.5-22.9), and 10.5 (1.5-74.7), respectively. Mean difference (95% CI) for gestational age at delivery comparing FETO and controls was 1.8 (-3.1 to -0.5). All these outcomes showed a low level of evidence. Conclusion FETO procedure increased the neonatal survival at 30 days and 6 months; however, it presented a higher rate of premature rupture of membrane, preterm birth < 37 weeks, and decreased the gestational age at delivery by 2 weeks. Nonetheless, the level of evidence is low for all these outcomes. We suggested a large international multicenter RCT to prove the real benefits of FETO.

Prematurity and fetal lung response after tracheal occlusion in fetuses with severe congenital diaphragmatic hernia.

OBJECTIVE: To evaluate the independent association of fetal pulmonary response and prematurity to postnatal outcomes after fetal tracheal occlusion for congenital diaphragmatic hernia. METHODS: Fetal pulmonary response, prematurity (<37 weeks at delivery) and extreme prematurity (<32 weeks at delivery) were evaluated and compared between survivors and non-survivors at 6 months of life. Multivariable analysis was conducted with generalized linear mixed models for variables significantly associated with survival in univariate analysis. RESULTS: Eighty-four infants were included, of whom 40 survived (47.6%) and 44 died (52.4%). Univariate analysis demonstrated that survival was associated with greater lung response (p=0.006), and the absence of extreme preterm delivery (p=0.044). In multivariable analysis, greater pulmonary response after FETO was an independent predictor of survival (aOR 1.87, 95% CI 1.08-3.33, p=0.023), whereas the presence of extreme prematurity was not statistically associated with mortality after controlling for fetal pulmonary response (aOR 0.52, 95% CI 0.12-2.30, p=0.367). CONCLUSION: Fetal pulmonary response after FETO is the most important factor associated with survival, independently from the gestational age at delivery.