Successful antenatal treatment of MAGED2-related Bartter syndrome and review of treatment options and efficacy.

A new form of transient antenatal Bartter syndrome (aBS) was recently identified that is associated with the X-linked MAGED2 variant. Case reports demonstrate that this variant leads to severe polyhydramnios that may result in preterm birth or pregnancy loss. There is limited but promising evidence that amnioreductions may improve fetal outcomes in this rare condition. We report a woman with two affected pregnancies. In the first pregnancy, the patient was diagnosed with mild-to-moderate polyhydramnios in the second trimester that ultimately resulted in preterm labor and delivery at 25 weeks with fetal demise. Whole exome sequencing of the amniotic fluid sample resulted after the pregnancy loss and revealed a c.1337G>A MAGED2 variant that was considered diagnostically. The subsequent pregnancy was confirmed by chorionic villi sampling to also be affected by this variant. The pregnancy was managed with frequent ultrasounds and three amnioreductions that resulted in spontaneous vaginal delivery at 37 weeks and 6 days of a viable newborn with no evidence of overt electrolyte abnormalities suggesting complete resolution. A detailed review of the published cases of MAGED2-related transient aBS is provided. Our review focuses on individuals who received antenatal treatment. A total of 31 unique cases of MAGED2-related transient aBS were compiled. Amnioreduction was performed in 23 cases and in 18 cases no amnioreduction was performed. The average gestational age at delivery was significantly lower in cases without serial amnioreduction (28.7 vs. 30.71 weeks, p = 0.03). Neonatal mortality was seen in 5/18 cases without serial amnioreduction, and no mortality was observed in the cases with serial amnioreduction. In cases of second trimester severe polyhydramnios without identifiable cause, whole exome sequencing should be considered. Intensive ultrasound surveillance and serial amnioreduction is recommended for the management of MAGED2-related transient aBS.

Fetal pharyngeal glial heterotopia manifested as polyhydramnios: a rare case with difficult prenatal diagnosis.

BACKGROUND: Glial heterotopia is a rare congenital developmental malformation that presents as tumor-like lesions of the nerve tissue that grow outside the nervous system, but are not true tumors. At present, most cases are reported in neonates and children and are very rarely found in fetuses. The present report describes a case of fetal pharyngeal glial heterotopia and associated imaging findings to better understand the disease in the future. CASE PRESENTATION: A 32-year-old pregnant woman was admitted to the hospital with polyhydramnios. An ultrasound examination revealed a hypoechoic mass in the neck of the fetus. Magnetic resonance imaging showed a well-defined mass with significant compression of the esophagus and airway. The amniotic fluid index was approximately 40 cm. Considering that difficulty swallowing and breathing may occur due to compression by the mass after birth, tracheotomy and mass resection should be performed immediately. The difficulty of the tumor resection procedure and the nature of the tumor are both factors affecting the prognosis of the fetus. The pregnant woman eventually chose to induce labor. The fetal pharyngeal mass was then resected and its pathological examination indicated pharyngeal glial heterotopia. CONCLUSIONS: Polyhydramnios due to pharyngeal glial heterotopia is extremely rare and accurate prenatal diagnosis is challenging. Clinical diagnosis of glial heterotopia in preterm fetuses is difficult. Therefore, understanding glial heterotopia is helpful to improve clinical treatment options.

Bronchopulmonary dysplasia is associated with polyhydramnios in a scan for novel perinatal risk factors.

BACKGROUND: The pathogenesis of bronchopulmonary dysplasia (BPD) is multifactorial, and there are limited data about prenatal exposures and risk of BPD. STUDY DESIGN: Our study performed parallel analyses using a logistic regression model in a cohort of 4527 infants with data from a curated registry and using a phenome wide association study (PheWAS) based on ICD9/10-based phecodes. We examined 20 prenatal exposures from a neonatal intensive care unit (NICU) curated registry database related to pregnancy and maternal health as well as 94 maternal diagnosis phecodes with a PheWAS analysis. RESULT: In both the curated registry and PheWAS analyses, polyhydramnios was associated with an increased risk of BPD (OR 5.70, 95% CI 2.78-11.44, p = 1.37 × 10-6). CONCLUSION: Our data suggest that polyhydramnios may be a clinical indicator of premature infants at increased risk for bronchopulmonary dysplasia. Combining curated registry data with PheWAS analysis creates a valuable tool to generate hypotheses. IMPACT: Polyhydramnios was significantly associated with bronchopulmonary dysplasia in both a curated registry and by ICD coding analysis with a phenome wide association study (PheWAS). Preterm polyhydramnios may be a clinical indicator of infants at increased risk for developing bronchopulmonary dysplasia after preterm birth. Combining curated registry with PheWAS analysis creates a valuable tool to generate hypotheses about perinatal risk factors and morbidities associated with preterm birth.

Estimate of genetic variants using CNV-Seq for fetuses with oligohydramnios or polyhydramnios.

BACKGROUND: Oligohydramnios or polyhydramnios, is associated with chromosomal aberrations, particularly aneuploidy. However, its correlation with copy number variation (CNV) remains unclear. METHODS: We retrospectively analyzed 428 cases with an abnormal level of amniotic fluid, comprising of 139 cases of single ultrasound findings (SU group) and 289 cases of multiple ultrasound findings (MU group), by CNV sequencing (CNV-Seq) and followed their pregnancy outcomes. RESULTS: The overall detection rate of clinically significant findings was 8%, with 5% in the SU group and 11% in MU group. Besides, 18 microdeletion/microduplication syndromes were detected, with the highest rate of renal cysts and diabetes syndrome (22%, 4/18). Also, the rate of termination of pregnancy in MU group was much higher than that in the SU group (29% vs. 10%, ***p < 0.001), and in the MU-oligohydramnios subgroup, it was the highest (34%), regardless of cases with chromosomal anomaly and lost to follow-up. CONCLUSION: Our results showed that the abnormal level of amniotic fluid, especially combined with other ultrasound abnormalities, is closely related to chromosomal abnormalities and genetic CNVs. CNV-Seq may be useful in investigating pregnancies with an abnormal amniotic fluid level.

Management of atypical cases of twin-to-twin transfusion syndrome.

Up to 20% of monochorionic diamniotic twin pregnancies can be complicated with twin-to-twin transfusion syndrome (TTTS). This complication is diagnosed by ultrasound demonstrating amniotic fluid discordance between both amniotic sacs, with polyhydramnios in the recipient's sac and oligohydramnios in the donor's, secondary to an imbalance in blood volume exchange between twins. Ultrasound evaluation of the amniotic fluid volume, bladder filling, and assessment of fetal Doppler parameters provide the basis for classification of TTTS, allowing severity assessment. The Quintero's staging system provides a standardized prenatal estimate on the risk of intrauterine fetal demise of one or both twins and the need for fetoscopic laser coagulation of placental vascular anastomoses or delivery depending on the gestational age. However, a proportion of TTTS cases may present without a linear progressive deterioration and no ultrasound signs of preceding staging, in rare situations, they arise even without amniotic fluid discordance. Thus, these unusual clinical presentations of TTTS have long been grouped into the category of atypical TTTS. In this review, we show the clues for diagnosis and management of different atypical cases of TTTS highlighting their underlying mechanism to improve the clinical understanding of such atypical situations, avoid misdiagnosis of TTTS, and allow a timely referral to a fetoscopic center.

Cardiac rhabdomyoma as a possible new prenatal sonographic feature of Prader-Willi syndrome.

We describe a unique case of a pregnancy with fetal Prader-Willi syndrome (PWS). A 40-year-old pregnant woman prenatally presented with polyhydramnios, decreased fetal movements, fetal growth restriction with normal Doppler study, and fetal cardiac rhabdomyoma, a possible new sonographic markers for PWS, at 31 weeks of gestation. The newborn had hypotonia and feeding difficulty. Molecular genetic study showed a normal copy number of the 15q11.2-q13.1 chromosomal region but hypermethylation pattern of this region, indicating PWS. Other than the combination of polyhydramnios, fetal growth restriction, and decreased fetal movements, cardiac rhabdomyoma was detected and possibly associated with PWS. In conclusion, PWS should be listed in differential diagnoses if fetuses having the following perinatal factors: polyhydramnios, decreased fetal movements, and growth restriction. Finally, cardiac rhabdomyoma, observed in this case, might possibly be associated with PWS, although further studies to confirm are needed.

Successful expectant management of a giant chorioangioma.

Giant chorioangiomas are benign placental tumours, which can have potential severe fetal consequences. Complications in pregnancy include polyhydramnios, fetal hydrops and growth restriction. Such pregnancies can carry a significant risk of poor perinatal outcome and require close monitoring. Therapeutic options include fetoscopic or interstitial vessel ablation, chemosclerosis and embolisation. Where there is no evidence of fetal compromise, such pregnancies can successfully be managed conservatively.

Prenatal diagnosis of Miller-Dieker syndrome by chromosomal microarray.

OBJECTIVE: To assess the experience on prenatal diagnosis of Miller-Dieker syndrome (MDS) to further delineate the fetal presentation of this syndrome. METHODS: This was a retrospective study. Fetal MDS was diagnosed prenatally by chromosomal microarray (CMA). Clinical data were reviewed for these cases, including maternal characteristics, indications for prenatal diagnosis, sonographic findings, CMA results, and pregnancy outcomes. RESULTS: Four cases were diagnosis as MDS by CMA. The most common sonographic features were ventriculomegaly (3/4) and polyhydramnios (2/4). Deletion sizes ranged from 1.5 to 5.4 Mb. All microdeletions were located at the MDS critical region and showed haploinsufficiency of the YWHAE, CRK, and PAFAH1B1. All patients chose to terminate the pregnancy. Parental chromosome analysis were preformed in three cases and demonstrated that two cases were de novo and one case was caused by inherited derivative chromosomes from parental balanced translocations. CONCLUSION: The most common prenatal ultrasound findings of MDS were ventriculomegaly and polyhydramnios. CMA can improve diagnostic precision for detecting MDS.

Placental chorioangioma associated with polyhydramnios and hydrops fetalis.

A 27-year-old multigravida woman was noted on routine growth scan at 27 weeks gestation to have a central placental hypoechoic area measuring 6.7×6.0×4.4 cm. A subsequent magnetic resonance scan confirmed a solid mass in the placenta lying anteriorly; therefore, a preliminary diagnosis of giant placental chorioangioma was made. A repeat ultrasound scan at 30 weeks gestation indicated that the mass had increased, with the presence of polyhydramnios. The patient experienced reduced fetal movements at 31 weeks gestation. There was persistent fetal tachycardia at 33 weeks gestation, and consequently the neonate was delivered by emergency caesarean section. The placenta revealed a large chorioangioma. The neonate's birth weight was 2.85 kg and non-immune hydrops fetalis was diagnosed. The neonate improved significantly in the neonatal intensive care unit and is currently well with no medical problems.

Fetal Head and Neck Masses: MRI Prediction of Significant Morbidity.

OBJECTIVE: The purpose of this study is to determine which MRI parameters of fetal head and neck masses predict high-morbidity neonatal outcomes, including ex utero intrapartum treatment (EXIT) procedure. MATERIALS AND METHODS: This retrospective study (2004-2016) included parameters of polyhydramnios (based on largest vertical pocket), mass effect on the trachea, mass midline extension, and morphologic grade and size of masses. The morbid cohort included those requiring an EXIT procedure, difficult intubation at delivery, or lethal outcome. Predictive modeling with a multivariable logistic regression and ROC analysis was then performed. RESULTS: Of 36 fetuses, five were delivered by EXIT procedures, there was one neonatal death within 12 hours after delivery, and another neonate required multiple intubation attempts. The remaining 29 fetuses were delivered at outside institutions with no interventions or neonatal morbidity. The largest vertical pocket and mass effect on the trachea were selected as independent predictors by the logistic regression. The cross-validated ROC AUC was 0.951 (95% CI, 0.8795-1). CONCLUSION: The largest vertical pocket measurement and mass effect on the trachea were the most contributory MRI parameters that predicted significant morbidity in fetuses with masses of the face and neck, along with other significant parameters. These parameters predict significant morbid neonatal outcomes, including the need for EXIT procedures.

Monochorionic-diamniotic twin pregnancy complicated by twin reversed arterial perfusion sequence and retroplacental hematoma - a case report.

Twin reversed arterial perfusion (TRAP) sequence is a rare and severe complication specific to monochorionic twin pregnancies, involving the presence of an acardiac twin and a structurally normal co-twin (pump twin). We report on the case of a33-year-old female with a biamniotic monochorionic twin pregnancy complicated with TRAP sequence and polyhydramnios. The patient underwent fetoscopic termination of the acardiac twin and at 34 gestational weeks (GW) was readmitted with aretroplacental hematoma. The patient gave birth through caesarean section to a living female fetus, weighing 1480 g. To the best of our knowledge, this is the first case reporting a twin pregnancy with TRAP sequence complicated with retroplacental hematoma.

Obstructing in utero oropharyngeal mass: Case report of a lymphatic malformation arising within an oropharyngeal teratoma.

An ex utero intrapartum treatment procedure was performed to deliver a fetus with a multiseptated, entirely cystic, 4.5 × 5.0 × 4.0-cm mass occupying the oropharynx and oral cavity with protrusion from the mouth. Surgical excision was performed, and final pathologic diagnosis revealed a lymphatic malformation arising within a cystic oropharyngeal teratoma. Lymphatic malformations are virtually indistinguishable radiologically from rare, purely cystic teratomata, and efforts have been made to distinguish between the two in utero because of differing available treatment modalities. This represents the first documented case in the literature of a lymphatic malformation arising from within an oropharyngeal teratoma.

Accuracy of prenatal detection of tracheoesophageal fistula and oesophageal atresia.

AIMS: This study aims to determine the rate of prenatal detection of tracheoesophageal fistula and oesophageal atresia (TOF/OA), by identifying a small or absent stomach bubble with or without polyhydramnios, on the prenatal ultrasound scans (USS). METHODS: A retrospective study of prenatal ultrasound findings of babies with a prenatal and postnatal diagnosis of TOF/OA born between 1st January 2004 and 31st December 2013 was undertaken. RESULTS: A total of 58 babies were born with TOF/OA. 40% of mothers had their prenatal investigations performed within our tertiary centre, and the remaining 60% had their antenatal care at their local district general hospital (DGH). The overall sensitivity for prenatal USS was 26%, with a specificity of 99% and a positive predictive value (PPV) of 35%. However, the sensitivity of the prenatal USS within the tertiary centre was significantly higher at 57%, while only 2 cases were detected prenatally in the DGHs. Polyhydramnios was seen in 67% of mothers that had a prenatal diagnosis of TOF/OA and its presence did significantly increase the positive predictive value of prenatal USS (from 35% to 63%). Of those that were postnatally diagnosed, 21% had prenatal polyhydramnios. There was no significant difference in postnatal outcomes between those that were prenatally diagnosed and those that were postnatally diagnosed. CONCLUSION: Prenatal diagnosis of TOF/OA remains challenging. However within a specialist centre the accuracy of successful prenatal detection can be significantly improved. This is beneficial both for prenatal counselling of families and for planning appropriate perinatal and postnatal care for the baby.

Confirmation of etiology in fetal hydrops by sonographic evaluation of fluid allocation patterns.

OBJECTIVE: To evaluate patterns of fluid allocations in different etiologies of hydrops fetalis. STUDY DESIGN: This report is a retrospective cohort study on 20,395 fetal sonographic evaluations in a single tertiary center from 2000 to 2014. Special emphasis was placed on the exact description of the distinct fluid allocation sites in each fetus. Postmortem/postnatal records were evaluated additionally. Mean follow up of the surviving neonates was 34 days (10-60 days). RESULTS: There seem to be distinctive patterns of fluid allocation in some etiologies leading to fetal hydrops including aneuploidies and Parvovirus B19 related infections. CONCLUSION: Due to the allocation patterns of fluid filled sites in fetuses with hydrops fetalis the spectrum of possible etiologies may be narrowed already during initial ultrasound scan. It can contribute substantially to diagnostic accuracy as well as to parental counseling. This knowledge may also help to omit delay in diagnostic routines.

A review of pregnancies complicated by congenital sacrococcygeal teratoma in the West Midlands region over an 18-year period: population-based, cohort study.

OBJECTIVES: To describe the epidemiology and outcomes of sacrococcygeal teratoma (SCT) and identify the factors affecting prognosis in a population-based cohort. METHODS: Analyses of fetal SCTs from a population-based congenital anomaly register between 1995 and 2012, linked to regional datasets. A systematic literature review was performed for published studies on perinatal SCT (1995 to 2012). RESULTS: Thirty-six confirmed SCT cases were identified, giving a total prevalence of 0.30 per 10 000 births (95%CI 0.20-0.39). Twenty-three cases (63.9%) were diagnosed prenatally. There were six false positive prenatal diagnoses, and the positive predictive value of ultrasound for SCT was 79.3%. Secondary complications in prenatally diagnosed cases were polyhydramnios (27.2%), fetal hydrops (9.1%) and rapidly growing tumour (54.0%). The perinatal (PNMR) and infant mortality rates were 333.3 per 1000 births and 285.7 per 1000 live births, respectively. All stillbirths and infant deaths occurred in cases diagnosed prenatally. Factors associated with higher PNMR in registerable births were solid, vascular tumour composition (1000), polyhydramnios (667), premature delivery (667) and rapidly growing tumour (454). In the systematic review, prenatal hydrops fetalis and prematurity were the most morbid association in SCT. CONCLUSION: Prenatal ultrasound was relatively sensitive and specific in diagnosing SCT with good survival rates in live-born cases.

Clinical Features of Neonates with Hydrops Fetalis.

OBJECTIVE: The objective of this study was to evaluate the clinical characteristics of neonates with hydrops fetalis to improve recognition of the disease. PATIENTS AND METHODS: The clinical data of 10 neonates with hydrops fetalis were retrospectively studied. Prenatal characteristics, causes, clinical features, and prognosis were explored. RESULTS: Eight neonates presenting abnormal nonstress test suffered from severe neonatal asphyxia at birth and were resuscitated by endotracheal intubation. Nine had skin edema, eight had pleural effusions with one unilateral and seven bilateral. Six had ascites, eight had polyhydramnios, one had multiple malformations and one had chromosome abnormalities. One survived and nine died. Six died due to resuscitation failure in delivery room, two died due to giving up after 1 day and one died due to the treatment failure after 6 months. Causes of hydrops fetalis were a congenital diaphragmatic hemangioma, recurrent atrial premature beats, genetic syndrome suspicious, Down syndrome, congenital pulmonary lymphangiectasia, anemia, paroxysmal supraventricular tachycardia, placental chorioangioma, and idiopathic edema. CONCLUSION: The prognosis varied because of different etiologies of hydrops fetalis. Severe cases frequently had skin edema and high rate of asphyxia at birth and difficult resuscitation. Timely intrauterine interventions were helpful for successful resuscitation. A well-prepared resuscitation team and the effectiveness of resuscitation could correlate to increasing survival rate.

The diagnosis of fetal esophageal atresia and its implications on perinatal outcome.

The current diagnostic accuracy and perinatal outcome of fetuses with esophageal atresia (EA) continues to be debated. In this review, we report on our experience at a tertiary care fetal center with the prenatal ultrasound diagnosis of EA. Enrollment criteria included a small/absent stomach bubble with a normal or elevated amniotic fluid index between 2005 and 2013. Perinatal outcomes were analyzed and compared to postnatally diagnosed EA cases. Of the 22 fetuses evaluated, polyhydramnios occurred in 73%. Three (14%) died in utero or shortly after birth, but none had EA. In the presence of an absent/small stomach and polyhydramnios, the positive predictive value for EA was 67%. In fetal EA cases confirmed postnatally (group 1, n = 11), there were no differences in gestational age, birthweight, or mortality when compared to postnatally diagnosed infants (group 2, n = 59). Group 1 was associated with long-gap EA, need for esophageal replacement, and increased hospital length of stay. When taken in context with the current literature, we conclude that ultrasound findings suggestive of EA continue to be associated with a relatively high rate of false positives. However, among postnatally confirmed cases, there is an increased risk for long-gap EA and prolonged hospitalization.