Enhanced recovery after fetal spina bifida surgery: what is our global practice?

OBJECTIVE: Prenatal spina bifida closure results in improved outcomes for the child compared to postnatal surgery but is associated with significant maternal morbidity. Optimization of the perioperative care for women who underwent fetal spina bifida surgery could improve maternal and pregnancy outcomes. Enhanced Recovery After Surgery (ERAS) protocols are multimodal, evidence-based care plans that have been adopted for multiple surgical procedures to promote faster and better patient recovery and shorter hospitalization. This study aims to explore if fetal centers have implemented ERAS principles in this setting. Furthermore, we provide recommendations for the perioperative management of patients undergoing fetal spina bifida surgery. METHODS: Fifty-three fetal therapy centers offering prenatal surgery for open spina bifida were identified and invited to complete a digital questionnaire covering their pre-, intra- and postoperative management. An overall score was calculated per center based on the center's compliance with 20 key ERAS principles, extrapolated from ERAS guidelines for cesarean section, gynecologic oncology and colorectal surgery. Each item was scored 1 or 0 when the center did or did not comply with each principle, with a maximum score of 20. RESULTS: The questionnaire was completed by 46 centers in 17 countries (response rate 87%). Twenty-two centers (48%) exclusively perform open fetal surgery (laparotomy and hysterotomy), whereas 14 (30%) offer both open and fetoscopic procedures and 10 (22%) use fetoscopy only. The perioperative management of patients undergoing fetoscopic and open surgery was highly similar. The median ERAS score was 12 (mean 12.5, SD 2.4, range 8-17). Center compliance was the highest for the use of regional anesthesia (98%), avoidance of bowel preparation (96%), and thromboprophylaxis (96%), while the lowest compliance was achieved for preoperative carbohydrate loading (15%), postoperative nausea and vomiting prevention (33%), avoidance of overnight fasting (33%) and a 2-hour fasting period for clear fluids (20%). ERAS scores were similar in centers with a short (2-5 days), medium (6-10 days) and long (≥11 days) hospital stay (12.8 ± 2.4, 12.1 ± 2.0, and 10.3 ± 3.2, respectively, p=0.15). Furthermore, there was no significant association between ERAS score and surgical technique or center volume. CONCLUSION: The perioperative management of fetal spina bifida surgery is highly variable across fetal therapy centers worldwide. Standardizing protocols according to ERAS principles may improve patient recovery, reduce maternal morbidity, and shorten hospital stay after fetal spina bifida surgery. This article is protected by copyright. All rights reserved.

Consensus protocol for management of early and late twin-twin transfusion syndrome: Delphi study.

OBJECTIVE: Fetoscopic laser photocoagulation (FLP) is a well-established treatment for twin-twin transfusion syndrome (TTTS) between 16 and 26 weeks' gestation. High-quality evidence and guidelines regarding the optimal clinical management of very early (prior to 16 weeks), early (between 16 and 18 weeks) and late (after 26 weeks) TTTS are lacking. The aim of this study was to construct a structured expert-based clinical consensus for the management of early and late TTTS. METHODS: A Delphi procedure was conducted among an international panel of experts. Participants were chosen based on their clinical expertise, affiliation and relevant publications. A four-round Delphi survey was conducted using an online platform and responses were collected anonymously. In the first round, a core group of experts was asked to answer open-ended questions regarding the indications, timing and modes of treatment for early and late TTTS. In the second and third rounds, participants were asked to grade each statement on a Likert scale (1, completely disagree; 5, completely agree) and to add any suggestions or modifications. At the end of each round, the median score for each statement was calculated. Statements with a median grade of 5 without suggestions for change were accepted as the consensus. Statements with a median grade of 3 or less were excluded from the Delphi process. Statements with a median grade of 4 were modified according to suggestions and reconsidered in the next round. In the last round, participants were asked to agree or disagree with the statements, and those with more than 70% agreement without suggestions for change were considered the consensus. RESULTS: A total of 122 experts met the inclusion criteria and were invited to participate, of whom 53 (43.4%) agreed to take part in the study. Of those, 75.5% completed all four rounds. A consensus on the optimal management of early and late TTTS was obtained. FLP can be offered as early as 15 weeks' gestation for selected cases, and can be considered up to 28 weeks. Between 16 and 18 weeks, management should be tailored according to Doppler findings. CONCLUSIONS: A consensus-based treatment protocol for early and late TTTS was agreed upon by a panel of experts. This protocol should be modified at the discretion of the operator, according to their experience and the specific demands of each case. This should advance the quality of future studies, guide clinical practice and improve patient care. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Midline suprapineal pseudocyst in brain of fetuses with open spina bifida.

OBJECTIVES: Recently, it was noted that fetuses with open spina bifida (OSB) may have a midline cystic structure evident on ultrasound. Our aims were to determine the prevalence of this cystic structure, shed light on its pathophysiology and investigate the association between its presence and other characteristic brain findings in fetuses with OSB. METHODS: This was a single-center retrospective study of all fetuses with OSB and available cineloop images in the axial plane referred to the Ontario Fetal Centre, Toronto, Canada, between June 2017 and May 2022. Ultrasound and magnetic resonance imaging (MRI) data obtained between 18 + 0 and 25 + 6 weeks were reviewed in search of a midline cystic structure. Pregnancy and lesion characteristics were collected. Transcerebellar diameter (TCD), clivus-supraocciput angle (CSA) and additional brain abnormalities (abnormal cavum septi pellucidi (CSP), abnormal corpus callosum (CC) and periventricular nodular heterotopia (PNH)) were assessed. In cases of in-utero repair, imaging findings were reviewed postoperatively. In cases of termination, neuropathological findings were reviewed, if available. RESULTS: Of 76 fetuses with OSB, 56 (73.7%) had a suprapineal cystic structure on ultrasound. The percentage of agreement between ultrasound and MRI detection was 91.5% (Cohen's kappa coefficient, 0.78 (95% CI, 0.57-0.98)). Brain autopsy in terminated cases revealed a dilatation of the posterior third ventricle, with redundant tela choroidea and arachnoid forming the membranous roof of the third ventricle, anterior and superior to the pineal gland. A cyst wall could not be identified, indicating that the structure was a pseudocyst. The presence of the pseudocyst was associated with a smaller CSA (pseudocyst absent, 62.11 ± 9.60° vs pseudocyst present, 52.71 ± 8.22°; P = 0.04). When the pseudocyst was present, its area was correlated inversely with TCD (r, -0.28 (95% CI, -0.51 to -0.02); P = 0.04). Fetal surgery did not have any impact on the growth rate of the pseudocyst (fetal surgery, 5.07 ± 3.29 mm2 /week vs expectant management, 4.35 ± 3.17 mm2 /week; P = 0.58). The presence of the pseudocyst was not associated with abnormal CSP, CC or presence of PNH. None of the cases with available postnatal follow-up required surgical procedure related to the pseudocyst. CONCLUSIONS: Approximately 75% of all OSB cases have a suprapineal pseudocyst. Its presence is associated with the degree of hindbrain herniation but not with abnormalities of the CSP and CC or presence of PNH. Thus, it should not be regarded as additional brain pathology and should not preclude fetuses from undergoing fetal surgery for OSB. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Correlation of fetal ventricular size and need for postnatal cerebrospinal fluid diversion surgery in open spina bifida.

OBJECTIVES: Open spina bifida is a common cause of hydrocephalus in the postnatal period. In-utero closure of the fetal spinal defect decreases the need for postnatal cerebrospinal fluid (CSF) diversion surgery. Good prenatal predictors of the need for postnatal CSF diversion surgery are currently lacking. In this study, we aimed to assess the association of fetal ventriculomegaly and its progression over the course of pregnancy with the rate of postnatal hydrocephalus requiring intervention. METHODS: In this retrospective study, fetuses with a prenatal diagnosis of open spina bifida were assessed longitudinally. Ventricular diameter, as well as other potential predictors of the need for postnatal CSF diversion surgery, were compared between fetuses undergoing prenatal closure and those undergoing postnatal repair. RESULTS: The diameter of the lateral ventricle increased significantly throughout gestation in both groups, but there was no difference in maximum ventricular diameter at first or last assessment between fetuses undergoing prenatal closure and those undergoing postnatal repair. There was no significant difference in the rate of progression of ventriculomegaly between the two groups, with a mean progression rate of 0.83 ± 0.5 mm/week in the prenatal-repair group and 0.6 ± 0.6 mm/week in the postnatal-repair group (P = 0.098). Fetal repair of open spina bifida was associated with a lower rate of postnatal CSF diversion surgery (P < 0.001). In all subjects, regardless of whether they had prenatal or postnatal surgery, the severity of ventriculomegaly at first and last assessments was associated independently with the need for postnatal CSF diversion surgery (P = 0.005 and P = 0.001, respectively), with a greater need for surgery in fetuses with larger ventricular size, even after controlling for gestational age at assessment. CONCLUSIONS: In fetuses with open spina bifida, fetal ventricular size increases regardless of whether spina bifida closure is performed prenatally or postnatally, but the need for CSF diversion surgery is significantly lower in those undergoing prenatal repair. Ventriculomegaly is associated independently with the need for postnatal CSF diversion in fetuses with open spina bifida, irrespective of timing of closure. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Outcome of monochorionic twin pregnancy complicated by Type-III selective intrauterine growth restriction.

OBJECTIVE: Type-III selective intrauterine growth restriction (sIUGR) is associated with a high and unpredictable risk of fetal death and fetal brain injury. The objective of this study was to describe the prospective risk of fetal death and the risk of adverse neonatal outcome in a cohort of twin pregnancies complicated by Type-III sIUGR and treated according to up-to-date guidelines. METHODS: We reviewed retrospectively all monochorionic diamniotic twin pregnancies complicated by Type-III sIUGR managed at nine fetal centers over a 12-year period. Higher-order multiple gestations and pregnancies with major fetal anomalies or other monochorionicity-related complications at initial presentation were excluded. Data on fetal and neonatal outcomes were collected and management strategies reviewed. Composite adverse neonatal outcome was defined as neonatal death, invasive ventilation beyond the resuscitation period, culture-proven sepsis, necrotizing enterocolitis requiring treatment, intraventricular hemorrhage Grade > I, retinopathy of prematurity Stage > II or cystic periventricular leukomalacia. The prospective risk of intrauterine death (IUD) and the risk of neonatal complications according to gestational age were evaluated. RESULTS: We collected data on 328 pregnancies (656 fetuses). After exclusion of pregnancies that underwent selective reduction (n = 18 (5.5%)), there were 51/620 (8.2%) non-iatrogenic IUDs in 35/310 (11.3%) pregnancies. Single IUD occurred in 19/328 (5.8%) pregnancies and double IUD in 16/328 (4.9%). The prospective risk of non-iatrogenic IUD per fetus declined from 8.1% (95% CI, 5.95-10.26%) at 16 weeks, to less than 2% (95% CI, 0.59-2.79%) after 28.4 weeks and to less than 1% (95% CI, -0.30 to 1.89%) beyond 32.6 weeks. In otherwise uncomplicated pregnancies with Type-III sIUGR, delivery was generally planned at 32 weeks, at which time the risk of composite adverse neonatal outcome was 29.0% (31/107 neonates). In twin pregnancies that continued to 34 weeks, there was a very low risk of IUD (0.7%) and a low risk of composite adverse neonatal outcome (11%). CONCLUSIONS: In this cohort of twin pregnancies complicated by Type-III sIUGR and treated at several tertiary fetal centers, the risk of fetal death was lower than that reported previously. Further efforts should be directed at identifying predictors of fetal death and optimal antenatal surveillance strategies to select a cohort of pregnancies that can continue safely beyond 33 weeks' gestation. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Long-term postnatal outcome of fetuses with prenatally suspected septo-optic dysplasia.

OBJECTIVES: Septo-optic dysplasia (SOD) is a clinical syndrome characterized by varying combinations of optic nerve hypoplasia, pituitary gland hypoplasia and abnormal cavum septi pellucidi. It is suspected on prenatal imaging when there is non-visualization or hypoplasia of the septal leaflets. Long-term postnatal outcomes of fetuses with prenatally suspected SOD have been documented poorly. The aims of this study were to describe the natural history of deficient septal leaflets, to quantify the incidence of postnatally confirmed SOD and to document the visual, endocrine and long-term neurodevelopmental outcomes of these infants. METHODS: This was an observational retrospective study of all fetuses with prenatal imaging showing isolated septal agenesis, assessed at a single tertiary center over an 11-year period. Pregnancy, delivery and neonatal outcomes and pre- and postnatal imaging findings were reviewed. Neonatal evaluations or fetal autopsy reports were assessed for confirmation of SOD. Ophthalmologic, endocrine, genetic and long-term developmental evaluations were assessed. Imaging findings and outcome were compared between infants with and those without postnatally confirmed SOD. RESULTS: Of 214 fetuses presenting with septal absence on prenatal ultrasound and magnetic resonance imaging (MRI), 18 (8.4%) were classified as having suspected isolated septal agenesis suspicious for SOD. Uniform prenatal MRI findings in cases with suspected SOD included remnants of the leaflets of the cavum septi pellucidi, fused forniceal columns, normal olfactory bulbs and tracts and a normal optic chiasm. Twelve fetuses were liveborn and five (27.8%) had postnatally confirmed SOD. Only two of these five fetuses had additional prenatal imaging features (pituitary cyst, microphthalmia and optic nerve hypoplasia) supporting a diagnosis of SOD. The other three confirmed SOD cases had no predictive prenatal or postnatal imaging findings that reliably differentiated them from cases without confirmed SOD. Visual and endocrine impairments were present in two (40%) and four (80%) cases with confirmed SOD, respectively. In those with visual and/or endocrine impairment, developmental delay (median age at follow-up, 2.5 (interquartile range, 2.5-7.0) years) was common (80%) and mostly severe. Neonates with isolated septal agenesis and a lack of visual or endocrine abnormalities to confirm SOD had normal development. CONCLUSIONS: Only a quarter of fetuses with isolated septal agenesis suggestive of SOD will have postnatal confirmation of the diagnosis. Clinical manifestations of SOD are variable, but neurodevelopmental delay may be more prevalent than thought formerly. © 2020 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

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

OBJECTIVE: The Management of Myelomeningocele Study (MOMS) trial demonstrated the safety and efficacy of open fetal surgery for spina bifida aperta (SBA). Recently developed alternative techniques may reduce maternal risks without compromising the fetal neuroprotective effects. The aim of this systematic review was to assess the learning curve (LC) of different fetal SBA closure techniques. METHODS: MEDLINE, Web of Science, EMBASE, Scopus and Cochrane databases and the gray literature were searched to identify relevant articles on fetal surgery for SBA, without language restriction, published between January 1980 and October 2018. Identified studies were reviewed systematically and those reporting all consecutive procedures and with postnatal follow-up ≥ 12 months were selected. Studies were included only if they reported outcome variables necessary to measure the LC, as defined by fetal safety and efficacy. Two authors independently retrieved data, assessed the quality of the studies and categorized observations into blocks of 30 patients. For meta-analysis, data were pooled using a random-effects model when heterogeneous. To measure the LC, we used two complementary methods. In the group-splitting method, competency was defined when the procedure provided results comparable to those in the MOMS trial for 12 outcome variables representing the immediate surgical outcome, short-term neonatal neuroprotection and long-term neuroprotection at ≥ 12 months of age. Then, when raw patient data were available, we performed cumulative sum analysis based on a composite binary outcome defining successful surgery. The composite outcome combined four clinically relevant variables for safety (absence of extreme preterm delivery < 30 weeks, absence of fetal death ≤ 7 days after surgery) and efficacy (reversal of hindbrain herniation and absence of any neonatal treatment of dehiscence or cerebrospinal fluid leakage at the closure site). RESULTS: Of 6024 search results, 17 (0.3%) studies were included, all of which had low, moderate or unclear risk of bias. Fetal SBA closure was performed using standard hysterotomy (11 studies), mini-hysterotomy (one study) or fetoscopy by either exteriorized-uterus single-layer closure (one study), percutaneous single-layer closure (three studies) or percutaneous two-layer closure (one study). Only outcomes for standard hysterotomy could be meta-analyzed. Overall, outcomes improved significantly 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 exteriorized-uterus single-layer fetoscopy, competency was not reached in the 81 and 28 cases available for analysis, respectively, and LC prediction analysis could not be performed. CONCLUSIONS: The number of cases operated is correlated with the outcome of fetal SBA closure, and the number of operated cases required to reach competency ranges from 35 for standard hysterotomy to ≥ 56-57 for minimally invasive modifications. Our observations provide important information for institutions looking to establish a new fetal center, develop a new fetal surgery technique or train their team, and inform referring clinicians, potential patients and third parties. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Curvas de aprendizaje del cierre de la espina bífida fetal mediante cirugía abierta y endoscópica: revisión sistemática y metaanálisis OBJETIVO: El ensayo del Estudio sobre la Gestión del Mielomeningocele (MOMS, por sus siglas en inglés) demostró la seguridad y eficacia de la cirugía fetal abierta para la espina bífida aperta (EBA). Las técnicas alternativas recientemente desarrolladas pueden reducir los riesgos de la madre sin comprometer los efectos neuroprotectores del feto. El objetivo de esta revisión sistemática fue evaluar la curva de aprendizaje (CA) de diferentes técnicas de cierre de la EBA fetal. MÉTODOS: Se realizaron búsquedas en las bases de datos de MEDLINE, Web of Science, EMBASE, Scopus y Cochrane, así como en la literatura gris, para identificar artículos relevantes sobre cirugía fetal para la EBA, sin restricción de idioma, publicados entre enero de 1980 y octubre de 2018. Se examinaron sistemáticamente los estudios identificados y se seleccionaron los que informaban de todos los procedimientos consecutivos y con seguimiento postnatal ≥12 meses. Los estudios se incluyeron sólo si informaban sobre las variables de resultado necesarias para medir la CA, definidas por la seguridad y la eficacia para el feto. Dos autores recuperaron los datos de forma independiente, evaluaron la calidad de los estudios y clasificaron las observaciones en bloques de 30 pacientes. Para el metaanálisis, los datos se agruparon mediante un modelo de efectos aleatorios cuando fueron heterogéneos. Para medir la CA, se usaron dos métodos complementarios. En el método de división de grupos, la competencia se definió cuando el procedimiento proporcionó resultados comparables a los del ensayo MOMS para 12 variables de resultados que representaban el resultado quirúrgico inmediato, la neuroprotección neonatal a corto plazo y la neuroprotección a largo plazo a ≥12 meses de edad. Luego, cuando se dispuso de los datos brutos de los pacientes, se realizó un análisis de suma acumulada basado en un resultado binario compuesto que definió el éxito de la cirugía. El resultado compuesto combinó cuatro variables clínicamente relevantes en cuanto a la seguridad (ausencia de parto pretérmino extremo <30 semanas; ausencia de muerte fetal a ≤7 días después de la cirugía) y eficacia (reducción de la hernia del rombencéfalo y ausencia de cualquier tratamiento neonatal de dehiscencia o derrame de líquido cefalorraquídeo en el lugar del cierre). RESULTADOS: De los 6024 resultados de la búsqueda, se incluyeron 17 (0,3%) estudios, todos ellos con un riesgo de sesgo bajo, moderado o incierto. El cierre de la EBA fetal se realizó mediante histerotomía estándar (11 estudios), mini histerotomía (un estudio) o fetoscopia, ya fuera mediante el cierre exteriorizado del útero de una sola capa (un estudio), el cierre percutáneo de una sola capa (tres estudios) o el cierre percutáneo de dos capas (un estudio). Sólo se pudieron metaanalizar los resultados de la histerotomía estándar. En general, los resultados mejoraron significativamente con la experiencia. Se alcanzó la competencia después de 35 casos consecutivos para la histerotomía estándar y se predijo que se alcanzaría después de ≥57 casos para la mini histerotomía y ≥56 para la fetoscopia percutánea de dos capas. En el caso de las fetoscopias percutánea y exteriorizada del útero de una sola capa, no se alcanzó la competencia en los 81 y 28 casos disponibles para el análisis, respectivamente, y no se pudo realizar el análisis de predicción de la CA. CONCLUSIONES: El número de casos operados está correlacionado con el resultado del cierre de la EBA fetal, y el número de casos operados necesarios para alcanzar la competencia estuvo entre 35 para la histerotomía estándar y ≥56-57 para las operaciones con mínima agresividad. Las observaciones realizadas proporcionan información importante para las instituciones que buscan establecer un nuevo centro fetal, desarrollar una nueva técnica de cirugía fetal o entrenar a su equipo, e informar a los médicos que remiten a especialistas a los posibles pacientes y a terceros. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Treatment of fetal circular shunt with non-steroidal anti-inflammatory drugs.

A circular shunt (CS) is a life-threatening condition involving massive shunting of systemic arterial blood via the ductus arteriosus to the left ventricle without traversing the lungs. In the prenatal setting, it occurs mainly in fetuses with severe forms of Ebstein's anomaly (EA) owing to unrestricted ductal flow and significant pulmonary and tricuspid regurgitation. We aimed to improve the fetal hemodynamics and chances of survival of affected fetuses by inducing ductal constriction using transplacental non-steroidal anti-inflammatory drugs (NSAIDs). Following initiation of treatment between 26 and 34 weeks' gestation, three (75%) of four fetuses with EA/CS responded with sustained ductal constriction and improved hemodynamic function, which allowed continuation of pregnancy for 3-7 weeks and elective delivery. All successfully treated cases underwent neonatal surgery immediately after birth to eliminate the CS and survived. This included two neonates that underwent single-ventricle palliation surgery that required postoperative extracorporeal membrane oxygenation and hemofiltration for transient respiratory and renal failure. The one case that did not respond to treatment with NSAIDs was delivered prematurely for progressive fetal compromise and died shortly after birth. Transplacental treatment with NSAIDs represents a novel approach to controlling fetal CS, avoiding in-utero death and prolonging the pregnancy to a more advanced gestational age, thereby potentially increasing the chances of neonatal survival. This treatment should be considered and initiated at an early stage of systemic steal to prevent brain injury due to hypoperfusion. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Twin-twin transfusion syndrome: a frequently missed diagnosis with important consequences.

OBJECTIVE: To evaluate the incidence and consequences of 'misdiagnosed' cases of twin-twin transfusion syndrome (TTTS). METHODS: Chorionicity and referral diagnoses were reviewed in pregnant women with monochorionic twin pregnancies complicated by TTTS treated with fetoscopic laser ablation. 'Misdiagnosed' cases, defined as failure to correctly identify chorionicity and/or to diagnose TTTS prior to referral, were compared with cases in whom chorionicity and TTTS were diagnosed correctly. TTTS stage, gestational age at referral, overall survival, fetal and perinatal mortality, gestational age at delivery, operating time and maternal complications were compared. RESULTS: Failure to identify monochorionicity and/or TTTS was observed in 33% (107/323) of referrals to our center. Compared with cases in whom chorionicity and TTTS were correctly diagnosed, misdiagnosed patients were referred at a more advanced stage of disease (Stage IV TTTS: 16.8% vs 7.9%, P = 0.014) and later in pregnancy (gestational age at laser: 20.9 weeks vs 20.1 weeks, P = 0.018). They also delivered more prematurely (30.3 weeks' gestation vs 31.5 weeks' gestation, P = 0.04) and fetal and neonatal mortality were higher (neonatal death within 7 days: 19.6% vs 6.0%, P < 0.001). When the diagnosis was incorrect, major maternal complications and intensive care unit admissions were increased. CONCLUSIONS: Poor recognition of chorionicity in the first trimester of pregnancy might lead to inadequate ultrasound follow up (failure to assess every 2 weeks) and patient education. Early accurate recognition of both chorionicity and TTTS, with timely referral to a fetal therapy center, are key to ensuring optimal maternal and fetal outcomes.

Minimally invasive therapy for fetal sacrococcygeal teratoma: case series and systematic review of the literature.

OBJECTIVE: Large solid sacrococcygeal teratomas (SCT) can cause high-output cardiac failure and fetal or neonatal death. The aim of this study was to describe the outcomes of minimally invasive antenatal procedures for the treatment of fetal SCT. METHODS: A case review was performed of five fetuses with a large SCT treated antenatally using minimally invasive techniques, and a systematic literature review on fetal therapy for solid SCTs was carried out. RESULTS: Five women were referred between 17 + 5 and 26 + 4 weeks' gestation for a large fetal SCT with evidence of fetal cardiac failure. Vascular flow to the tumors was interrupted by fetoscopic laser ablation (n = 1), radiofrequency ablation (RFA; n = 2) or interstitial laser ablation ± vascular coiling (n = 2). There were two intrauterine fetal deaths. The other three cases resulted in preterm labor within 10 days of surgery. One neonate died. Two survived without procedure-related complications but had long-term morbidity related to prematurity. The systematic literature review revealed 16 SCTs treated minimally invasively for (early) hydrops. Including our cases, six of 20 hydropic fetuses survived after minimally invasive therapy (30%). Survival after RFA or interstitial laser ablation was 45% (5/11). Of 12 fetuses treated for SCT without obvious hydrops and for which perinatal survival data were available, eight (67%) survived. Mean gestational age at delivery after minimally invasive therapy was 29.7 ± 4.0 weeks. Survival after open fetal surgery in hydropic fetuses was 6/11 (55%), with a mean gestational age at delivery of 29.8 ± 2.9 weeks. CONCLUSIONS: Fetal therapy can potentially improve perinatal outcomes for hydropic fetuses with a solid SCT, but is often complicated by intrauterine death and preterm birth.

Fetal cardiac function in recipient twins undergoing fetoscopic laser ablation of placental anastomoses for Stage IV twin-twin transfusion syndrome.

OBJECTIVE: Cardiac dysfunction is common in the recipient fetus of twin-twin transfusion syndrome (TTTS). In this study, we aimed to document the severity of fetal cardiac dysfunction in Stage IV TTTS (fetal hydrops) and assess evolution of cardiac function longitudinally after fetoscopic laser surgery. METHODS: We reviewed obstetric ultrasound examination data, pre- and postoperative echocardiograms and neonatal outcomes for 22 cases of Stage IV TTTS undergoing fetoscopic laser ablation of placental anastomoses between 1998 and 2011. Myocardial performance index, atrioventricular valve flow patterns, ventricular shortening fraction, ventricular hypertrophy, outflow tract obstruction and venous Doppler waveforms were assessed. RESULTS: Nineteen fetuses (86.4%) had ascites, eight (36.4%) had pleural effusions, nine (40.9%) had a pericardial effusion and 12 (54.5%) had subcutaneous edema at presentation. Preoperatively, cardiac function was grossly abnormal in all. Eight fetuses (36.4%) had functional pulmonary atresia and one (4.5%) had functional aortic atresia. Seventy-seven percent of recipient fetuses survived until birth. Postoperative echocardiographic follow-up (mean, 26 days) showed that indices of fetal cardiac function improved considerably, but never completely normalized. Six of the eight fetuses with functional pulmonary atresia (75.0%), as well as the fetus with functional aortic atresia, survived to birth. In all cases, the functional atresia resolved within 48 h of laser ablation therapy and none had structural valve anomalies at birth. All fetal effusions resolved after the laser. CONCLUSIONS: Fetoscopic laser ablation of placental anastomoses reverses cardiac dysfunction and valvulopathy, even in the most severe cases of TTTS. However, recovery takes longer than in early stage disease.

Predictors of neonatal morbidity in fetuses with severe isolated congenital diaphragmatic hernia undergoing fetoscopic tracheal occlusion.

OBJECTIVES: To investigate neonatal morbidity in fetuses with severe congenital diaphragmatic hernia (CDH) treated with fetoscopic endoluminal tracheal occlusion (FETO) and compare it with historical controls with less severe forms of CDH that were managed expectantly. METHODS: This was a prospective, multicenter study on neonatal outcomes and prenatal predictors in 90 FETO survivors (78 left-sided, 12 right) and 41 controls from the antenatal CDH registry with either severe or moderate hypoplasia who were managed expectantly. We also investigated early neonatal morbidity indicators, including the need for patch repair, duration of mechanical ventilation and supplemental oxygen, age at full enteral feeding and incidence of pulmonary hypertension. RESULTS: Gestational age at delivery was predictive of duration of assisted ventilation (P = 0.046), days on supplemental oxygen (P = 0.019) and age at full enteral feeding (P = 0.020). When delivery took place after 34 weeks' gestation, neonatal morbidity of FETO cases was comparable with that of expectantly managed cases with moderate hypoplasia. CONCLUSIONS: Fetal intervention for severe CDH is associated with neonatal morbidity that is comparable with that of an expectantly managed group with less severe disease.

Outcome of fetuses with congenital diaphragmatic hernia and associated intrafetal fluid effusions managed in the era of fetal surgery.

OBJECTIVE: Fetuses with congenital diaphragmatic hernia (CDH) and for whom additional ultrasound findings are abnormal typically are considered to have a dismal prognosis. Our aim was to assess the outcome of fetuses with CDH and associated intrafetal fluid effusions. METHODS: This was a retrospective bicentric cohort study on the perinatal management of fetuses with CDH and intrafetal fluid effusions. RESULTS: The incidence of effusions was 5.2% (n = 14) in 269 consecutive cases of left-sided CDH and 29.2% (n = 14) in 48 cases of right-sided CDH. Hydrothorax (n = 19 (68%)) and ascites (n = 16 (57%)) were the most common effusions. A combination of both was present in 11 (39%) fetuses. Of 20 ongoing pregnancies with CDH and fluid effusions, without other anomalies, five with moderate or mild pulmonary hypoplasia were managed without fetoscopic endoluminal tracheal occlusion (FETO). The 15 other cases underwent FETO because of severe pulmonary hypoplasia. Neonatal survival rate was similar in both groups (n = 2/5 and n = 6/15, respectively (P = 1.0)). Survival among those who underwent FETO was similar to previously published results concerning isolated cases undergoing FETO. CONCLUSIONS: Our observations do not support the view that intrafetal effusions are an adverse prognostic factor in fetuses with CDH. In CDH fetuses with effusions and severe pulmonary hypoplasia treated with FETO, neonatal survival is similar to that in isolated cases undergoing the intervention. Whether pleural effusions should be addressed by thoracic drainage procedures remains unproven.

[Amniopatch to treat iatrogenic rupture of the fetal membranes]. / Traitement de la rupture iatrogène des membranes fœtales par "patch" amniotique.

OBJECTIVE: With the increased use of invasive fetal procedures, the number of patients facing postprocedure membrane rupture is increasing. We aimed to describe the use of platelets and fresh frozen plasma for sealing iatrogenic fetal membrane defects. PATIENTS AND METHODS: We describe the mechanisms of action of the amniopatch procedure as well as published experience. RESULTS: Amniopatch effectively sealed the fetal membranes in over two thirds of published cases (n=44). There is a risk of 17% of in utero fetal death, which may occur remotely from the procedure and is often unexplained. DISCUSSION AND CONCLUSION: In case of early onset but persistent amniotic fluid leakage following an invasive fetal procedure, amniopatch may be offered.

Incidence and clinical implications of early inadvertent septostomy after laser therapy for twin-twin transfusion syndrome.

OBJECTIVE: To evaluate the incidence and clinical outcome of inadvertent septostomy after fetoscopic laser therapy for twin-twin transfusion syndrome (TTTS) and, particularly, to explore its association with the risk of developing pseudoamniotic band syndrome (PABS). METHODS: In a cohort of 414 consecutive monochorionic twin pregnancies with confirmed TTTS treated with laser, the incidence of postoperative septostomy within 1 week of the procedure was recorded prospectively. Rates of preterm delivery, preterm premature rupture of membranes (PPROM), intrauterine fetal demise (IUFD) and PABS were compared among cases with and without septostomy. RESULTS: The mean gestational age at laser therapy was 20.4 (range, 15.3-27.6) weeks. Postoperative septostomy occurred in 30 (7.2%) cases. Pregnancies complicated with septostomy had a significantly higher proportion of preterm delivery before 32 weeks (76.7% vs. 30.2%, P < 0.001), PPROM before 32 weeks (46.7% vs. 19.0%, P < 0.001), IUFD (43.3% vs. 25.8%, P < 0.05) and PABS (13.3% vs. 1.0%, P < 0.001), compared with pregnancies without septostomy. CONCLUSIONS: Inadvertent septostomy occurred in 7% of cases after fetoscopic laser therapy and was associated with a substantially increased risk of adverse perinatal outcome and PABS.

Maternal hyperoxygenation test in fetuses undergoing FETO for severe isolated congenital diaphragmatic hernia.

OBJECTIVES: To predict neonatal survival and pulmonary hypertension by measurement of fetal pulmonary artery reactivity to maternal hyperoxygenation in fetuses with severe congenital diaphragmatic hernia treated by fetoscopic endoluminal tracheal occlusion (FETO). METHODS: Thirty-eight fetuses underwent FETO at around 28 weeks' gestation and the balloon was removed at 34 weeks in most cases. We performed a hyperoxygenation test and measured the lung-to-head ratio of each fetus before and after each procedure. Outcome measures were neonatal survival, occurrence of pulmonary hypertension and its response to inhaled nitric oxide (iNO). RESULTS: Fetuses that survived had a larger increase in lung size and decrease of resistance in the first branch of the main pulmonary artery than did those that died. Both measures were also predictive of pulmonary hypertension unresponsive to iNO. The hyperoxygenation test and lung-to-head ratio were both best predictive for neonatal survival when measured following removal of the balloon (P < 0.002). Discriminant analysis confirmed that these two parameters are independent predictors of outcome. CONCLUSIONS: In fetuses undergoing FETO, pulmonary vascular reactivity in relation to oxygen and lung size are independent predictors of neonatal survival and pulmonary hypertension. The hyperoxygenation test merits further study in expectantly managed cases.

Fetal and maternal hemodynamics in pregnancy: new insights in the cardiovascular adaptation to uncomplicated pregnancy, twin-to-twin transfusion syndrome and congenital diaphragmatic hernia.

The fetal and the maternal cardiovascular compartment undergo dramatic functional changes during pregnancy. In this thesis we examined the heart of fetuses with twin-to-twin transfusion syndrome (TTTS) and congenital diaphragmatic hernia (CDH) using two new ultrasound parameters of ventricular function : the myocardial performance index and speckle tracking derived myocardial strain. Fetal cardiac function was grossly abnormal in recipient fetus of TTTS, yet normalized within 6 weeks after therapy. Ultrasound based cardiac function assessment could not predict short term fetal survival after therapy, nor could it predict eventual further progression to full-blown TTTS in a pre-disease stage. Fetuses with CDH on the other hand, have normal myocardial function, yet smaller left ventricles leading to decreased left ventricular output. We showed that the lower output leads to decreased cerebral perfusion, yet without apparent impact on brain and cranial growth. On the maternal side, plasma volume strongly increases in pregnancy, in parallel with an increase in insulin-like-growth factor(IGF) II which is secreted at the level of the placenta. Experimental administration of IGF-II by continuous infusion leads to increases in plasma volume whereas decreasing IGF-II by reduction of the feto-placental mass leads to decreased plasma volumes. In contrast to IGF-II, the highly vasoactive peptide apelin decreases near term due to a faster elimination as a consequence of an increase in placental angiotensin-converting-enzyme 2. Our experiments with IGF-II and apelin substantiate an important role for the feto-placental unit in regulating maternal plasma volume expansion and (auto)regulating uterine perfusion and fetal growth.

The fetal patient -- ethical aspects of fetal therapy.

The pregnant patient is a vulnerable subject, and even more so when a serious fetal condition is diagnosed. (Invasive) fetal therapy should only be offered when there is a good chance that the life of the fetus will be saved, or irreversible damage by the disease or disability is prevented. Following diagnosis of a potentially treatable condition, the patient needs to be referred to a center with sufficient expertise in diagnosis and all therapeutic options. Preferences of the physician towards one or another antenatal intervention is not at stake prior to that moment. When fetal therapy is justified--, it should be offered with full respect for maternal choice and individual assessment and perception of potential-- risks, and should be at the location where there is sufficient expertise. For therapies of unproven benefit, the absence of evidence must be disclosed, and therapy should only be undertaken with full voluntary consent of the mother. These ought to be undertaken within well designed and approved trials and only by experts in the treatment modality. Potential risks and eventual morbidities in case of therapeutic failure should be part of the counselling, neither-- should fetal therapy be presented as an alternative to termination of pregnancy.