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Baraitser-Winter cerebrofrontofacial syndrome (BWCFF) is a variable multiple congenital anomaly condition, typically presenting postnatally with neurocognitive delays, distinctive facial features, cortical brain malformations, and in some, a variety of additional congenital malformations. However, only a few cases have reported the prenatal presentation of this syndrome. Here, we report two cases of BWCFF and their associated prenatal findings. One case presented with non-immune hydrops fetalis and a horseshoe kidney and was found to have a de novo heterozygous variant in ACTB (c.158A>G). The second case presented with gastroschisis, bilateral cleft lip and palate, and oligohydramnios, and was found to harbor a different de novo variant in ACTB (c.826G>A). Limited reports exist describing prenatally identified anomalies that include fetal growth restriction, increased nuchal fold, bilateral hydronephrosis, rocker bottom foot, talipes, cystic hygroma, omphalocele, and hydrops fetalis. In addition, only three of these cases have included detailed prenatal imaging findings. The two prenatal cases presented here demonstrate an expansion of the prenatal phenotype of BWCFF to include gastroschisis, lymphatic involvement, and oligohydramnios, which should each warrant consideration of this diagnosis in the setting of additional anomalies.
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We report a 32-year-old G3P1 at 35 weeks 3 days with a dichorionic, diamniotic twin gestation who presented for evaluation secondary to ventriculomegaly (VM) in one twin. Fetal ultrasound and MRI demonstrated microcephaly, severe VM, compression of the corpus callosum, scalp and nuchal thickening, elongated ears, bilateral talipes, right-sided congenital diaphragmatic hernia (CDH), and loss of normal cerebral architecture, indicative of a prior insult in the affected twin. The co-twin was grossly normal. The family pursued a palliative care pathway for the affected twin and was delivered at 37 weeks and 6 days. The affected twin passed away within the first hour of life due to respiratory compromise. Postmortem trio exome sequencing identified a homozygous likely pathogenic variant in ATP1A2 (c.2439+1G>A). Although this variant is novel, it is predicted to affect the donor split site in intron 17, resulting in a frameshift and complete loss-of-function of the gene. Biallelic loss of function variants in this gene have been reported in seven individuals with multiple anomalies similar to those in the affected twin. However, only one other individual with a possible CDH has been previously reported. Our case suggests that CDH be included in the phenotypic spectrum of this disorder and reports the first frameshift mutation causing this autosomal recessive multiple congenital anomaly syndrome.
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Anormalidades Múltiplas , ATPase Trocadora de Sódio-Potássio , Adulto , Feminino , Humanos , Recém-Nascido , Gravidez , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/diagnóstico por imagem , Doenças em Gêmeos/genética , Doenças em Gêmeos/diagnóstico por imagem , Doenças em Gêmeos/diagnóstico , Evolução Fatal , ATPase Trocadora de Sódio-Potássio/genética , Ultrassonografia Pré-NatalRESUMO
Oculocerebrorenal syndrome (Lowe syndrome) is a rare X-linked disorder affecting 1/500,000 males that most frequently affects the eyes, central nervous system, and kidneys. Phenotypic presentation includes congenital cataracts, developmental delay, intellectual disability, and Fanconi-type renal dysfunction. Lowe Syndrome is caused by hemizygous loss of function variants in the OCRL gene. While individuals may live into the third and fourth decade of life, some will die in the first few years of either renal failure or infection. While early diagnosis is important, few cases have documented the prenatal phenotype of this condition, which has included bilateral cataracts and variable neurological abnormalities. We report a case of a family with an extensive history of congenital cataracts, immune compromise, and neonatal death in male members. The fetus was found to have a unilateral cataract, mild ventriculomegaly, vertebral anomalies, and an underlying diagnosis of Lowe Syndrome with a mutation in OCRL at c.2582-1G>C (IVS23-1G>C).
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Catarata , Síndrome Oculocerebrorrenal , Fenótipo , Humanos , Síndrome Oculocerebrorrenal/genética , Síndrome Oculocerebrorrenal/diagnóstico , Feminino , Masculino , Gravidez , Catarata/congênito , Catarata/diagnóstico , Catarata/genética , Adulto , Monoéster Fosfórico Hidrolases/genética , Diagnóstico Pré-Natal/métodos , Recém-NascidoRESUMO
OBJECTIVE: To determine the diagnostic performance of ultrasound markers associated with life-limiting fetal skeletal dysplasia in a fortified cohort. METHODS: Retrospective review from 2013 to 2023 of pregnancies with suspected fetal skeletal dysplasia. Ultrasound evaluation included measurements predictive of a life-limiting dysplasia: thoracic circumference/abdominal circumference (TC/AC) < 0.6, femur length/abdominal circumference (FL/AC) < 0.16, and thoracic circumference (TC) < 2.5th percentile. Demographics, ultrasound findings, genetic testing, and fetal/neonatal outcome were reviewed. RESULTS: Of 96 fetuses with complete outcome data, 47 (49%) had a non-life-limiting dysplasia and 49 (51%) had a life-limiting dysplasia. 22 (23%) had no life-limiting markers, 42 (44%) had one, 27 (28%) had two, and 5 (5%) had three. FL/AC < 0.16 and TC < 2.5th percentile were associated with life-limiting dysplasia (p < 0.001; p < 0.001), while TC/AC < 0.6 was rare and did not reach statistical significance (p = 0.056). The positive predictive value (PPV) for predicting life-limiting dysplasia increased from 50% to 78% to 100% with one, two, or three markers. The PPV of the two life-limiting markers was significantly higher in those diagnosed at < versus ≥ 28 weeks (90% vs. 43%, p = 0.02) but the analysis was limited by small numbers in the ≥ 28 weeks cohort. The negative predictive value of no life-limiting markers was 91%. CONCLUSIONS: In our cohort, the presence of two life-limiting ultrasound markers prior to 28 weeks was highly suggestive of a life-limiting dysplasia, whereas the absence of life-limiting markers was strongly associated with a non-life-limiting dysplasia throughout gestation. Nonetheless, individual markers had a poor predictive value of lethality, and a life-limiting diagnosis ≥ 28 weeks is challenging based on ultrasound markers alone. This highlights the importance of integrating thorough sonography, genetic testing, and balanced parental counseling.
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INTRODUCTION: Micrognathic neonates are at risk for upper airway obstruction, and many require intubation in the delivery room. Ex-utero intrapartum treatment is one technique for managing airway obstruction but poses substantial maternal risks. Procedure requiring a second team in the operating room is an alternative approach to secure the obstructed airway while minimizing maternal risk. The aim of this study was to describe the patient characteristics, airway management, and outcomes for micrognathic neonates and their mothers undergoing a procedure requiring a second team in the operating room at a single quaternary care children's hospital. METHODS: This was a retrospective descriptive study. Subjects had prenatally diagnosed micrognathia and underwent procedure requiring a second team in the operating room between 2009 and 2021. Collected data included infant characteristics, delivery room airway management, critical events, and medications. Follow-up data included genetic testing and subsequent procedures within 90 days. Maternal data included type of anesthetic, blood loss, and incidence of transfusion. RESULTS: Fourteen deliveries were performed via procedure requiring a second team in the operating room during the study period. 85.7% were male, and 50% had a genetic syndrome. Spontaneous respiratory efforts were observed in 93%. Twelve patients (85.7%) required an endotracheal tube or tracheostomy. Management approaches varied. Medications were primarily a combination of atropine, ketamine, and dexmedetomidine. Oxygen desaturation was common, and three patients experienced bradycardia. There were no periprocedural deaths. Follow-up at 90 days revealed that 78% of patients underwent at least one additional procedure, and one patient died due to an unrelated cause. All mothers underwent cesarean deliveries under neuraxial anesthesia. Median blood loss was 700 mL [IQR 700 mL, 800 mL]. Only one mother required a blood transfusion for pre-procedural placental abruption. DISCUSSION: Procedure requiring a second team in the operating room is a safe and effective approach to manage airway obstruction in micrognathic neonates while minimizing maternal morbidity. CONCLUSIONS: Though shown to be safe and effective, more data are needed to support the use of procedure requiring a second team in the operating room as an alternative to ex-utero intrapartum treatment for micrognathia outside of highly specialized maternal-fetal centers.
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Obstrução das Vias Respiratórias , Micrognatismo , Recém-Nascido , Lactente , Criança , Humanos , Masculino , Feminino , Gravidez , Micrognatismo/complicações , Estudos Retrospectivos , Placenta , Manuseio das Vias Aéreas/métodos , Obstrução das Vias Respiratórias/terapiaRESUMO
INTRODUCTION: The aim of the study was to identify predictors of poor outcomes in monochorionic diamniotic twin (MCDA) pregnancies with selective fetal growth restriction (sFGR), irrespective of the umbilical artery (UA) Doppler abnormalities. METHODS: Single-center retrospective analysis of MCDA twins diagnosed with sFGR that opted for expectant management between 2010 and 2021. The presence of any of the following variables in the growth-restricted fetus: low amniotic fluid volume (DVP ≤2 cm), lack of a cycling bladder, absent or reversed flow in the ductus venosus (DV) with atrial contraction, and elevated middle cerebral artery peak systolic velocity (MCA-PSV) defined as ≥1.50 multiples of the median was categorized as complicated. sFGR cases were classified as simple in the absence of the above-mentioned variables. RESULTS: Overall, 63.3% of cases qualified as simple, and 36.7% were complicated. Intertwin EFW discordance was higher in the complicated category (26 vs. 33%, p = 0.0002). The median gestational age at delivery was earlier (33 weeks vs. 30.5 weeks, p = 0.002), and the likelihood of survival was lower in the complicated category (p < 0.0001). The likelihood of two survivors to discharge was lower in type I complicated cases (70% in complicated type I vs. 97.1% in simple type I, p = 0.0003). On logistic regression analysis, an increase in the "complicated" score negatively correlated with two survivors to discharge (p < 0.0001). An ROC curve was created, and the AUC was 0.79. Increasing intertwin EFW discordance also decreased the probability of two survivors to discharge. CONCLUSION: The presence of oligohydramnios, lack of a cycling bladder, abnormal DV Doppler, and elevated MCA-PSV in the growth restricted fetus is associated with poor perinatal outcomes and a lower likelihood of having two survivors to discharge. The addition of intertwin EFW discordance to these variables helped improve the survival predictability.
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Retardo do Crescimento Fetal , Gravidez de Gêmeos , Ultrassonografia Pré-Natal , Humanos , Feminino , Gravidez , Estudos Retrospectivos , Retardo do Crescimento Fetal/diagnóstico por imagem , Retardo do Crescimento Fetal/fisiopatologia , Adulto , Resultado da Gravidez/epidemiologia , Artérias Umbilicais/diagnóstico por imagem , Gêmeos Monozigóticos , Idade GestacionalRESUMO
The Crumbs homolog-2 (CRB2)-related syndrome (CRBS-RS) is a rarely encountered condition initially described as a triad comprising ventriculomegaly, Finnish nephrosis, and elevated alpha-fetoprotein levels in maternal serum and amniotic fluid. CRB2-related syndrome is caused by biallelic, pathogenic variants in the CRB2 gene. Recent reports of CRB2-RS have highlighted renal disease with persistent proteinuria and steroid-resistant nephrotic syndrome (SRNS). We report six new and review 28 reported patients with pathogenic variants in CRB2. We compare clinical features and variant information in CRB2 in patients with CRB2-RS and in those with isolated renal disease. The kidneys were the most frequently involved body system and 11 patients had only renal manifestations with SRNS or nephrotic syndrome. Central nervous system involvement was the next most common manifestation, followed by cardiac findings that included Scimitar syndrome. There was a significant clustering of pathogenic variants for CRB2-RS in exons 8 and 10, whereas pathogenic variants in exons 12 and 13 were associated with isolated renal disease. Further information is needed to determine optimal management but monitoring for renal and ocular complications should be considered.
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Proteínas de Transporte , Família , Humanos , Proteínas de Membrana/genéticaRESUMO
Fibular aplasia, tibial campomelia, and oligosyndactyly (FATCO) syndrome (MIM 246570) is a rare disorder characterized by specific skeletal findings (fibular aplasia, shortened or bowed tibia, and oligosyndactyly of the foot and/or hand). Typically, no other anomalies, craniofacial dysmorphism, or developmental delays are associated. Here we report three unrelated individuals with limb anomalies consistent with FATCO syndrome who have been followed clinically for 5 years. Genetic testing of previously reported individuals with FATCO syndrome has not revealed a genetic diagnosis. However, no broader sequencing approaches have been reported. We describe the results of the three individuals with FATCO syndrome from exome and genome sequencing, all of which was nondiagnostic. Our study suggests that FATCO syndrome is not the result of a simple monogenic etiology.
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Deformidades Congênitas do Pé , Sindactilia , Humanos , Tíbia/anormalidades , Sindactilia/genética , Deformidades Congênitas do Pé/diagnóstico , Síndrome , GenômicaRESUMO
INTRODUCTION: Fetoscopic selective laser photocoagulation (FSLPC) and selective cord occlusion with radiofrequency ablation (RFA) can improve fetal outcomes when vascular anastomoses between fetuses cause twin-to-twin transfusion syndrome (TTTS) or selective fetal growth restriction (sFGR) in multiple gestation pregnancies with monochorionic placentation. This study analyzed perioperative maternal-fetal complications and anesthetic management in a high-volume fetal therapy center over a 4-year period. METHODS: Included patients received MAC for minimally invasive fetal procedures for complex multiple gestation pregnancies between January 1, 2015, and September 20, 2019. Maternal and fetal complications, intraoperative maternal hemodynamics, medication usage, and reasons for conversion to general anesthesia, if applicable, were analyzed. RESULTS: A total of 203 (59%) patients underwent FSLPC and 141 (41%) had RFA. Four patients (2%; rate 95% CI: 0.00039, 0.03901) undergoing FSLPC had conversion to general anesthesia. No conversions to general anesthesia occurred in the RFA group. The incidence of maternal complications was higher in those who underwent FSLPC. No aspiration or postoperative pneumonia events were observed. Medication usage was similar in FSLPC and RFA groups. CONCLUSION: A low rate of conversion to general anesthesia and no serious adverse maternal events were observed in patients receiving MAC.
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BACKGROUND: Neurologic injury in the surviving twin is a risk after single fetal demise in a monochorionic pregnancy. OBJECTIVE: This study aimed to describe fetal magnetic resonance neuroimaging findings in pregnancies complicated by single fetal demise after laser photocoagulation for twin-twin transfusion syndrome. STUDY DESIGN: This was a single-center retrospective analysis of a cohort of prospectively collected patients in a monochorionic twin registry who had fetoscopic laser photocoagulation for twin-twin transfusion syndrome with single fetal demise at follow-up. Magnetic resonance neuroimaging was offered 3 to 4 weeks after the demise to assess for potential neurologic sequelae. Magnetic resonance images were interpreted by 2 board-certified neuroradiologists and classified as normal, mildly abnormal, or severely abnormal. The groups were compared on the basis of recipient vs donor demise using the Fisher exact test and Mann-Whitney U test. Multivariate logistic regression was performed to determine risk factors for abnormal magnetic resonance neuroimaging. RESULTS: In 378 laser photocoagulation procedures, 64 cases (16.9%) of single demise were identified (36 in the donor group and 28 in the recipient group). Of note, 6 patients had rupture of membranes with nonviable delivery (3 from each group). Moreover, 40 patients (69%) underwent magnetic resonance imaging. Of those patients, 12 (30%) had abnormal findings: 10 (83%) were associated with mild changes, and 2 (17%) were associated with severe findings. Abnormal magnetic resonance neuroimaging was seen in 3 of 22 patients (14%) after donor demise and 9 of 18 patients (50%) after recipient demise (P=.02). Logistic regression revealed that recipient vs donor demise was an independent risk factor for abnormal magnetic resonance imaging. In addition, 2 pregnancies with severe magnetic resonance imaging findings had complicated courses. CONCLUSION: Mildly abnormal magnetic resonance neuroimaging findings were common after laser photocoagulation for twin-twin transfusion syndrome complicated by single fetal demise and were more common in cases of recipient demise than donor demise. Severe magnetic resonance neuroimaging findings in this series were limited to patients with complicated peri- or postoperative courses.
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Transfusão Feto-Fetal , Feminino , Morte Fetal/etiologia , Transfusão Feto-Fetal/complicações , Transfusão Feto-Fetal/diagnóstico por imagem , Transfusão Feto-Fetal/cirurgia , Fetoscopia , Humanos , Fotocoagulação a Laser/efeitos adversos , Fotocoagulação a Laser/métodos , Lasers , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Neuroimagem/efeitos adversos , Gravidez , Estudos RetrospectivosRESUMO
BACKGROUND: Mediastinal and pericardial teratomas have overlapping imaging features that may make accurate prenatal diagnosis challenging. OBJECTIVE: To identify prenatal imaging features that may aid in distinguishing between mediastinal and pericardial teratomas. MATERIALS AND METHODS: Prenatally diagnosed pericardial and mediastinal teratomas evaluated at our fetal center from 1995 to 2020 were included in this Institutional Review Board-approved study. Lesion volume was calculated using prospectively reported ultrasound (US) measurements and the formula of a prolate ellipsoid, which was then normalized to head circumference. Prenatal US and magnetic resonance imaging (MRI) studies were anonymized with two fetal imagers reviewing the US studies and two different fetal imagers reviewing the MRI studies. These experienced reviewers scored location of the mass in the craniocaudal axis and in the transverse axis. MRI reviewers also scored the presence of inferior cardiac compression by the lesion and whether there was identifiable thymic tissue. Reviewer disagreements were resolved by consensus review. RESULTS: Eleven pericardial teratomas and 10 mediastinal teratomas were identified. All cases underwent detailed fetal anatomic US and fetal echocardiogram and 10/11 (91%) pericardial teratomas and 8/10 (80%) mediastinal teratomas underwent fetal MRI. Median volume was higher for mediastinal teratomas compared to pericardial teratomas (42.5 mL [interquartile range (IQR) 15.9 - 67.2 mL] vs. 8.1 mL [IQR 7.7 - 27.7 mL], P=0.01) and median volume/head circumference was also statistically higher in mediastinal teratomas (1.33 [IQR 0.78 - 2.61] vs. 0.43 [IQR 0.38 - 1.10], P=0.01). Logistic regression analysis demonstrated a statistical difference between teratoma types with respect to location in the craniocaudal axis by both modalities with mediastinal teratomas more commonly located in the upper and upper-middle thorax compared to pericardial teratomas, which were more commonly found in the middle thorax (US, P=0.03; MRI, P=0.04). Logistic regression analysis also demonstrated a statistical difference between teratoma types with respect to position along the transverse axis by both modalities with mediastinal teratomas more commonly located midline or left paramedian and pericardial teratomas more often right paramedian in location (US, P<0.01; MRI, P=0.02). Inferior cardiac compression observed by MRI was associated more commonly with mediastinal teratomas compared to pericardial teratomas (87.5% [7/8] vs. 10% [1/10], P<0.01). Identifiable thymus by MRI was more commonly observed in cases of pericardial teratomas, however, this difference was not statistically significant (P=0.32). CONCLUSION: Mediastinal teratomas are associated with larger lesion size and inferior cardiac compression when compared to pericardial teratomas. These features combined with lesion location in the craniocaudal and transverse axes may allow for more accurate prenatal diagnosis and optimal perinatal and surgical management.
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Neoplasias Cardíacas , Neoplasias do Mediastino , Teratoma , Gravidez , Feminino , Humanos , Teratoma/diagnóstico por imagem , Teratoma/patologia , Mediastino/diagnóstico por imagem , Pericárdio/diagnóstico por imagem , Neoplasias do Mediastino/diagnóstico por imagem , Ultrassonografia Pré-NatalRESUMO
INTRODUCTION: We sought to determine if maternal obesity, defined by body mass index (BMI) 30-34.9 or BMI ≥35, negatively impacts the technical aspects and pregnancy outcomes in women treated with selective laser photocoagulation of placental communicating vessels for twin-twin transfusion syndrome (TTTS). METHODS: Retrospective review of women undergoing laser for TTTS from January 2010 to December 2021. Outcomes were stratified based on maternal BMI <30, 30-34.9, and ≥35. Data obtained included maternal age, parity, ethnicity, gestational age at laser, placental location, Quintero stage, CHOP cardiovascular score, operative and anesthesia times, procedure-to-delivery interval, gestational age at delivery, survival to birth, survival to discharge, and the presence of residual anastomoses. Statistical analysis included the χ2 or Fisher's exact test for categorical variables and the Mann-Whitney U test for continuous variables with p < 0.05 being significant. RESULTS: A total of 434 women underwent laser for TTTS during the study period. Of those, 274 (63%) had a BMI of <30, 92 (21.2%) had a BMI between 30 and 34.9, and 68 (15.7%) had a BMI ≥ 35. There were no differences in maternal age, parity or ethnicity, Quintero stage, CHOP cardiovascular score, placental location, operative time, laser-to-delivery interval, gestational age at delivery, survival outcomes, or the presence of residual anastomoses between the three groups. Patients with a BMI of 30-34.9 were operated on at a slightly later gestational age, and those with a BMI > 35 had longer operative and anesthesia times. There were no technical failures as a result of BMI ≥ 30 or 35. CONCLUSION: Using appropriate technical adjustments, outcomes for obese women undergoing laser for TTTS are similar to nonobese women, although patients with BMI ≥35 have longer operative and anesthesia times.
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Transfusão Feto-Fetal , Terapia a Laser , Feminino , Humanos , Gravidez , Transfusão Feto-Fetal/cirurgia , Fetoscopia , Fotocoagulação a Laser , Placenta , Terapia a Laser/efeitos adversos , Resultado da Gravidez , Idade Gestacional , Estudos Retrospectivos , Obesidade/complicações , Obesidade/cirurgia , Gravidez de GêmeosRESUMO
INTRODUCTION: The aim of the study was to determine if markers of donor placental insufficiency and recipient cardiac dysfunction increase the risk for single fetal demise (SFD) after laser for twin-twin transfusion syndrome (TTTS). METHODS: Single-center retrospective review of patients who had laser for TTTS. Risk factors for donor and recipient demise within 1 week were compared in pregnancies with SFD and pregnancies with dual survival using χ2 or Fisher's exact test. Multivariate logistic regression was then performed. RESULTS: Of 398 procedures, 305 (76.6%) had dual survival, 36 (9.0%) had donor demise, 28 (7.0%) had recipient demise, and 9 (2.3%) had dual demise. The remaining 20 (5.0%) patients had complicated courses with pregnancy loss or further intervention. In the 64 pregnancies with SFD, 29 (81%) in the donor group and 20 (71%) in the recipient group occurred in the first postoperative week. For the donor demise group, estimated fetal weight (EFW) <10%, EFW <3%, EFW <1%, EFW discordance >25%, and EFW discordance >30% did not increase the risk for donor demise except in cases that also had umbilical artery absent or reversed end diastolic flow (AREDF). Donor AREDF was the only independent risk factor for early donor demise. For the recipient demise group, recipient abnormal venous Dopplers were associated with increased risk while EFW discordance >25% was associated with decreased risk of recipient loss. DISCUSSION/CONCLUSION: In our cohort, donor growth restriction did not increase the risk of early donor demise after laser unless there was also donor AREDF. Donor AREDF was an independent risk factor for donor demise likely due to the severity of placental insufficiency. Abnormal recipient venous Doppler indices increased the risk of early recipient loss while a large intertwin discordance decreased the risk. This may be explained by profound overload in cases with recipient abnormal venous Doppler velocimetry and a lower risk of substantial fluid shifts from a relatively smaller donor territory when there is a large discordance.
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Transfusão Feto-Fetal , Insuficiência Placentária , Gravidez , Humanos , Feminino , Placenta/irrigação sanguínea , Morte Fetal/etiologia , Lasers , Fotocoagulação a Laser/efeitos adversos , Fotocoagulação a Laser/métodosRESUMO
BACKGROUND: Selective fetoscopic laser coagulation of the intertwin anastomotic chorionic vessels is the first-line treatment for twin-twin transfusion syndrome. However, in stage 1 twin-twin transfusion syndrome, the risks of intrauterine surgery may be higher than those of the natural progression of the condition. OBJECTIVE: This study aimed to compare immediate surgery and expectant follow-up in stage 1 twin-twin transfusion syndrome. STUDY DESIGN: We conducted a multicentric randomized trial, which recruited from 2011 to 2018 with a 6-month postnatal follow-up. The study was conducted in 9 fetal medicine centers in Europe and the Unites States. Asymptomatic women with stage 1 twin-twin transfusion syndrome between 16 and 26 weeks' gestation, a cervix of >15 mm, and access to a surgical center within 48 hours of diagnosis were randomized between expectant management and immediate surgery. In patients allocated to immediate laser treatment, percutaneous laser coagulation of anastomotic vessels was performed within 72 hours. In patients allocated to expectant management, a weekly ultrasound follow-up was planned. Rescue fetoscopic coagulation of anastomoses was offered if the syndrome worsened as seen during a follow-up, either because of progression to a higher Quintero stage or because of the maternal complications of polyhydramnios. The primary outcome was survival at 6 months without severe neurologic morbidity. Severe complications of prematurity and maternal morbidity were secondary outcomes. RESULTS: The trial was stopped at 117 of 200 planned inclusions for slow accrual rate over 7 years: 58 women were allocated to expectant management and 59 to immediate laser treatment. Intact survival was seen in 84 of 109 (77%) expectant cases and in 89 of 114 (78%) (P=.88) immediate surgery cases, and severe neurologic morbidity occurred in 5 of 109 (4.6%) and 3 of 114 (2.6%) (P=.49) cases in the expectant and immediate surgery groups, respectively. In patients followed expectantly, 24 of 58 (41%) cases remained stable with dual intact survival in 36 of 44 (86%) cases at 6 months. Intact survival was lower following surgery than for the nonprogressive cases, although nonsignificantly (78% and 71% following immediate and rescue surgery, respectively). CONCLUSION: It is unlikely that early fetal surgery is of benefit for stage 1 twin-twin transfusion syndrome in asymptomatic pregnant women with a long cervix. Although expectant management is reasonable for these cases, 60% of the cases will progress and require rapid transfer to a surgical center.
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Transfusão Feto-Fetal/terapia , Fotocoagulação a Laser , Conduta Expectante , Adulto , Progressão da Doença , Feminino , Ruptura Prematura de Membranas Fetais/etiologia , Transfusão Feto-Fetal/complicações , Transfusão Feto-Fetal/diagnóstico por imagem , Fetoscopia , Humanos , Lactente , Doenças do Sistema Nervoso/etiologia , Poli-Hidrâmnios/etiologia , Gravidez , Fatores de Risco , Taxa de Sobrevida , Ultrassonografia Pré-NatalRESUMO
AIM: The optimal gestational age (GA) at delivery and mode of delivery (MoD) for pregnancies with fetal congenital diaphragmatic hernia (CDH) is undetermined. The impact of early term (37-38 weeks 6 days) versus full term (39-40 weeks 6 days) and MoD on immediate neonatal outcomes in prenatally diagnosed isolated CDH cases was evaluated. MATERIAL AND METHODS: A retrospective chart review of pregnancies evaluated and delivered with the prenatal diagnosis of CDH between July 1, 2008, and December 31, 2018. The primary outcome was survival to hospital discharge. Secondary outcomes included neonatal intensive care unit (NICU) length of stay (LOS), extracorporeal membrane oxygenation (ECMO) requirement and need for supplemental oxygen at day 30 of life. RESULTS: A total of 296 patients were prenatally evaluated for CDH and delivered in a single center during the study period. After applying exclusion criteria, data were available on 113 women who delivered early term and 72 women who delivered full term. Survival to hospital discharge was comparable between the 2 groups - 83.2% in the early term versus 93.1% in the full term (p = 0.07; 95% CI of 0.13-1.04). No difference was observed in any other secondary outcomes. MoD was stratified into spontaneous vaginal, induced vaginal, unplanned cesarean and scheduled cesarean delivery with associated neonatal survival rates of 74.2, 90.6, 89.7 and 88.2%, respectively, p = 0.13. The 5-min Apgar score was higher in the elective cesarean group (7.94) followed by the induced vaginal delivery group (7.8) compared to 7.17 and 7.18 in the spontaneous vaginal and unplanned cesarean groups, respectively (p = 0.03). The GA and MoD did not influence survival to hospital discharge nor NICU LOS in multivariate analysis. CONCLUSIONS: Though there were no significant differences in neonatal outcomes for early term compared to full term deliveries of CDH neonates, a trend toward improved survival rates and lower ECMO requirements in the full term group may suggest an underlying importance GA at delivery. Further studies are warranted to validate these findings.
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Hérnias Diafragmáticas Congênitas , Cesárea , Feminino , Idade Gestacional , Hérnias Diafragmáticas Congênitas/diagnóstico por imagem , Hérnias Diafragmáticas Congênitas/cirurgia , Humanos , Recém-Nascido , Gravidez , Diagnóstico Pré-Natal , Estudos RetrospectivosRESUMO
Craniofacial morphogenesis is regulated in part by signaling from the Endothelin receptor type A (EDNRA). Pathogenic variants in EDNRA signaling pathway components EDNRA, GNAI3, PCLB4, and EDN1 cause Mandibulofacial Dysostosis with Alopecia (MFDA), Auriculocondylar syndrome (ARCND) 1, 2, and 3, respectively. However, cardiovascular development is normal in MFDA and ARCND individuals, unlike Ednra knockout mice. One explanation may be that partial EDNRA signaling remains in MFDA and ARCND, as mice with reduced, but not absent, EDNRA signaling also lack a cardiovascular phenotype. Here we report an individual with craniofacial and cardiovascular malformations mimicking the Ednra -/- mouse phenotype, including a distinctive micrognathia with microstomia and a hypoplastic aortic arch. Exome sequencing found a novel homozygous missense variant in EDNRA (c.1142A>C; p.Q381P). Bioluminescence resonance energy transfer assays revealed that this amino acid substitution in helix 8 of EDNRA prevents recruitment of G proteins to the receptor, abrogating subsequent receptor activation by its ligand, Endothelin-1. This homozygous variant is thus the first reported loss-of-function EDNRA allele, resulting in a syndrome we have named Oro-Oto-Cardiac Syndrome. Further, our results illustrate that EDNRA signaling is required for both normal human craniofacial and cardiovascular development, and that limited EDNRA signaling is likely retained in ARCND and MFDA individuals. This work illustrates a straightforward approach to identifying the functional consequence of novel genetic variants in signaling molecules associated with malformation syndromes.
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Anormalidades Craniofaciais/genética , Otopatias/genética , Orelha/anormalidades , Predisposição Genética para Doença , Disostose Mandibulofacial/genética , Receptor de Endotelina A/genética , Animais , Anormalidades Craniofaciais/fisiopatologia , Orelha/fisiopatologia , Otopatias/fisiopatologia , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Humanos , Mutação com Perda de Função/genética , Disostose Mandibulofacial/fisiopatologia , Camundongos , Camundongos Knockout , Morfogênese/genética , Crista Neural/crescimento & desenvolvimento , Crista Neural/patologia , Fenótipo , Transdução de Sinais/genéticaRESUMO
Fetal tumors represent an infrequent pathology when compared to congenital malformations, although their true incidence may be underestimated. A variety of benign and malignant neoplasms may occur anywhere in the neural axis. Imaging plays an important role in the fetal tumor diagnosis and evaluation of their resultant complications. Discovery of a fetal mass on obstetric ultrasound necessitates further evaluation with prenatal magnetic resonance imaging (MRI). New MR sequences and new applications of existing techniques have been successfully implemented in prenatal imaging. A detailed assessment may be performed using a variety of MR. Fetal tumors may be histologically benign or malignant, but their prognosis generally remains poor, especially for intracranial lesions. Unfavorable tumor location or heightened metabolic demands on a developing fetus may result in severe complications and a fatal outcome, even in cases of benign lesions. Nowadays, prenatal treatment focuses mainly on alleviation of secondary complications caused by the tumors. In this article we review congenital tumors of the brain, face, and neck encountered in prenatal life, and discuss diagnostic clues for appropriate diagnosis.
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Doenças Fetais , Neoplasias de Cabeça e Pescoço , Cuidado Pré-Natal/métodos , Diagnóstico Pré-Natal/métodos , Diagnóstico por Imagem/métodos , Feminino , Doenças Fetais/diagnóstico , Doenças Fetais/terapia , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Imageamento por Ressonância Magnética , Gravidez , Ultrassonografia Pré-NatalRESUMO
Congenital malformations occur in about 3% of all live births and are a leading cause of perinatal morbidity and mortality. An evolving understanding of the developing human fetus, advances in imaging, availability of cutting-edge instrumentation, and enhanced understanding of fetal pathophysiology, have allowed for prenatal surgical interventions to improve fetal diseases and neonatal outcomes. Fetal surgical therapy is no longer restricted to life-threatening prenatal diagnoses and can be categorized into either open surgical techniques or minimally invasive endoscopic/ultrasound-guided techniques. Patient selection requires a thorough multidisciplinary evaluation and shared decision-making process.
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Anormalidades Congênitas , Doenças Fetais , Feto , Cuidado Pré-Natal/métodos , Procedimentos Cirúrgicos Operatórios/métodos , Anormalidades Congênitas/diagnóstico , Anormalidades Congênitas/fisiopatologia , Anormalidades Congênitas/cirurgia , Feminino , Doenças Fetais/diagnóstico , Doenças Fetais/fisiopatologia , Doenças Fetais/cirurgia , Feto/diagnóstico por imagem , Feto/fisiopatologia , Feto/cirurgia , Humanos , Seleção de Pacientes , Gravidez , Diagnóstico Pré-Natal , Risco Ajustado/métodosRESUMO
AIM: To describe perinatal outcomes of fetuses with a prenatal diagnosis of a concomitant lung lesion in the setting of congenital diaphragmatic hernia (CDH) and to compare outcomes with an isolated CDH control group without a lung lesion, matched by ultrasound-based prognostic markers including presence of liver herniation and lung measurements. MATERIAL AND METHODS: This was a retrospective case-control study, wherein all pregnancies diagnosed with CDH and concomitant lung lesions were identified between July 1, 2008, and December 31, 2018. For each case, 2 controls with isolated CDH from the same study period were selected after matching for the presence of liver herniation into the thoracic cavity and ultrasound-based lung measurements either observed over expected lung-to-head ratio (LHR) or absolute LHR with their corresponding gestational age. The outcomes analyzed in the 2 groups included survival to hospital discharge, neonatal intensive care unit (NICU) length of stay (LOS), extracorporeal membrane oxygenation (ECMO) requirement and need for supplemental oxygen (O2) at day 30 of life. RESULTS: A total of 21 pregnancies were identified with CDH and a concomitant lung lesion in the study period. All the lung lesions were stratified into a "low-risk category" with a congenital cystic adenomatoid malformation volume ratio of less than 1.0 at the time of presentation. None of these fetuses developed hydrops or required in utero intervention. Overall survival in the group was 80.7% (17/21) and rate of ECMO was 38.1%. Causes of mortality included pulmonary insufficiency, sepsis, renal failure, and bowel infarction. Upon comparison between the cases and controls, the 2 groups were similar with respect to pregnancy demographics. There were no fetal demises in either group. Outcomes including survival rate, NICU LOS, ECMO requirements and need for supplemental O2 at day 30 of life, were comparable among the 2 groups. CONCLUSIONS: In our descriptive series, the presence of a concomitant, low-risk lung lesion in the setting of fetal CDH did not have a significant impact on the natural course of the disease, nor was it associated with a worse prognosis.
Assuntos
Sequestro Broncopulmonar/diagnóstico por imagem , Malformação Adenomatoide Cística Congênita do Pulmão/diagnóstico por imagem , Hérnias Diafragmáticas Congênitas/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Sequestro Broncopulmonar/complicações , Estudos de Casos e Controles , Malformação Adenomatoide Cística Congênita do Pulmão/complicações , Feminino , Idade Gestacional , Hérnias Diafragmáticas Congênitas/complicações , Humanos , Recém-Nascido , Tempo de Internação , Medidas de Volume Pulmonar , Gravidez , Resultado da Gravidez , Diagnóstico Pré-Natal , Prognóstico , Estudos Retrospectivos , Ultrassonografia Pré-NatalRESUMO
BACKGROUND: Congenital pulmonary airway malformations (CPAM), bronchopulmonary sequestrations (BPS), and CPAM-BPS hybrid lesions are most commonly solitary; however, >1 lung congenital lung lesion may occur. OBJECTIVES: To assess the frequency of multiple congenital thoracic anomalies at a high-volume referral center; determine prenatal ultrasound (US) and magnetic resonance imaging (MRI) features of these multifocal congenital lung lesions that may allow prenatal detection; and determine the most common distribution or site of origin. METHODS: Database searches were performed from August 2008 to May 2019 for prenatally evaluated cases that had a final postnatal surgical diagnosis of >1 congenital lung lesion or a lung lesion associated with foregut duplication cyst (FDC). Lesion location, size, echotexture, and signal characteristics were assessed on prenatal imaging and correlated with postnatal computed tomographic angiography and surgical pathology. -Results: Of 539 neonates that underwent surgery for a thoracic lesion, 35 (6.5%) had >1 thoracic abnormality. Multiple discrete lung lesions were present in 19 cases, and a lung lesion associated with an FDC was present in 16. Multifocal lung lesions were bilateral in 3 cases; unilateral, multilobar in 12; and, unilobar multisegmental in 4. Median total CPAM volume/head circumference ratio for multifocal lung lesions on US was 0.66 (range, 0.16-1.80). Prenatal recognition of multifocal lung lesions occurred in 7/19 cases (36.8%). Lesion combinations were CPAM-CPAM in 10 cases, CPAM-BPS in 5, CPAM-hybrid in 2, hybrid-hybrid in 1, and hybrid-BPS in 1. Of 5 unilateral, multifocal lung lesions, multifocality was prenatally established through identification of a band of normal intervening lung or intrinsic differences in lesion imaging features. CONCLUSIONS: Although less common, multiple thoracic abnormalities can be detected prenatally. Of multifocal lung lesions, the most common combination was CPAM-CPAM, with a unilateral, multilobar distribution. Prenatal recognition is important for pregnancy counseling and postnatal surgical management.