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.

Polyhydramnios associated with congenital bilateral vocal cord paralysis: A case report.

RATIONALE: Polyhydramnios may develop when the fetus cannot swallow amniotic fluid or the amount of fetal urine increases. Occasionally, unpredictable fetal abnormalities can be diagnosed postnatally. Bilateral vocal cord paralysis in the fetus may cause polyhydramnios, which could be related to impaired prenatal swallowing. PATIENT CONCERN: A 36-year-old multipara underwent an emergent cesarean section because of polyhydramnios and active labor at 35 + 5 weeks of gestation and gave birth to a girl. DIAGNOSIS: The neonate cried feebly and exhibited cyanosis as well as very weak response to stimuli. Chest retraction and stridor were observed. Laryngoscopic examination revealed no movement in both the vocal cords, and bilateral vocal cord paralysis was diagnosed. INTERVENTIONS: When the baby was 40 days old, she underwent tracheostomy to alleviate the persistent stridor and oral feeding difficulties. OUTCOMES: She was discharged at the age of 60 days while in the tracheostomy state. LESSONS: Securing the airway of neonates with bilateral vocal cord paralysis, tracheoesophageal fistula, or muscular dystrophy, which can be detected after delivery in pregnant women with idiopathic polyhydramnios, is important. Therefore, pregnant women with idiopathic polyhydramnios must be attended to by experts, such as neonatologists, anesthesiologists, or otolaryngologists, who can secure the airway.

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.

Successful Pregnancy Outcome after Amnioreduction Treated Acute Polyhydramnios Caused by Duodenal Atresia.

The aim of our manuscript is to report of a successful perinatal outcome after treatment of acute polyhydramnios caused by duodenal atresia. A 34-year-old G3P1 was referred due to polyhydramnios in the 30th week of pregnancy. Ultrasound revealed polyhydramnios, amniotic fluid index (AFI) 28, and a double bubble sign that indicated duodenal atresia and dilatated oesophagus. In the 32nd week of gestation, the volume of amniotic fluid increases, AFI 35, along with symptoms of dyspnea and abdominal pain. Due to the clinical picture and the early gestational age, it was decided to perform an amnioreduction. In the 36th week of gestation cesarean section was performed. The baby was taken for exploratory laparotomy and found to have a simultaneous complete duodenal atresia and annular pancreas with associated dilated the first portion of the duodenum and the stomach. A side-to-side duodenoduodenostomy via single-layer hand-sewn anastomosis was performed over a transanastamotic feeding tube (TAFT). The postoperative course was uneventful. Amnioreduction is useful and safe in the treatment of acute polyhydramnios caused by duodenal atresia and thus has a significant role in prolonging gestation until fetal maturity.

Indications for Outpatient Antenatal Fetal Surveillance: ACOG Committee Opinion, Number 828.

ABSTRACT: The purpose of this Committee Opinion is to offer guidance about indications for and timing and frequency of antenatal fetal surveillance in the outpatient setting. Antenatal fetal surveillance is performed to reduce the risk of stillbirth. However, because the pathway that results in increased risk of stillbirth for a given condition may not be known and antenatal fetal surveillance has not been shown to improve perinatal outcomes for all conditions associated with stillbirth, it is challenging to create a prescriptive list of all indications for which antenatal fetal surveillance should be considered. This Committee Opinion provides guidance on and suggests surveillance for conditions for which stillbirth is reported to occur more frequently than 0.8 per 1,000 (the false-negative rate of a biophysical profile) and which are associated with a relative risk or odds ratio for stillbirth of more than 2.0 compared with pregnancies without the condition. Table 1 presents suggestions for the timing and frequency of testing for specific conditions. As with all testing and interventions, shared decision making between the pregnant individual and the clinician is critically important when considering or offering antenatal fetal surveillance for individuals with pregnancies at high risk for stillbirth or with multiple comorbidities that increase the risk of stillbirth. It is important to emphasize that the guidance offered in this Committee Opinion should be construed only as suggestions; this guidance should not be construed as mandates or as all encompassing. Ultimately, individualization about if and when to offer antenatal fetal surveillance is advised.

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 congenital mesoblastic nephroma: a case with poor prognosis.

Congenital mesoblastic nephromais a rare tumour found in neonates, with a very small number of cases diagnosed prenatally. We report a case of a fetal renal tumour suspected at 28 weeks' gestation on routine ultrasound. Prenatal follow-up revealed a severe polyhydramnios at 32 weeks' gestation subsequent amniodrainage was undertaken. She delivered at 34+5 weeks' gestation, after spontaneous premature rupture of membranes.

Amnioreduction in cases of polyhydramnios: Indications and outcomes in singleton pregnancies without fetal interventions.

OBJECTIVE: To evaluate indications, pregnancy outcomes, and risk of adverse events following amnioreduction procedures in singleton gestations. STUDY DESIGN: Study of all amnioreduction procedures performed on singleton gestations complicated by polyhydramnios between January 2011 and June 2018 at our tertiary and regional referral fetal center. Clinical indications for amnioreduction procedures were categorized as either maternal shortness of breath, perceived abdominal tightness, or preterm uterine contractions with or without cervical change. Our primary outcome(s) of interest were: preterm premature rupture of membranes (PPROM), placental abruption, chorioamnionitis and/or preterm delivery, each in isolation or as a composite. RESULTS: Among 358 patients who underwent amnioreduction in the study period, 251 arose from cases of twin-twin transfusion syndrome (TTTS) and 74 were singletons undergoing additional fetal intervention procedures. Each of the remaining 33 patients underwent a median number of one [range 1-12] amnioreductions over the antepartum interval, yielding a total of 66 amnioreduction procedures. Among the study cohort, there were no instances of PPROM, placental abruption, chorioamnionitis or preterm delivery within the 12 h following the procedure but 10.6% experienced preterm delivery within 48 h of amnioreduction. CONCLUSION: Our data suggests that among singleton gestations, there was a low risk for preterm delivery in close proximity to the procedure and none experienced rupture of membranes, placental abruption, sepsis, fetal demise or neonatal death. This data may be used in counseling of potential candidates for amnioreduction with singleton pregnancies and symptomatic polyhydramnios.

Relationship between higher intra-amniotic pressures in polyhydramnios and maternal symptoms.

OBJECTIVES: Our study aimed to analyze the differences in intra-amniotic pressures in patients with polyhydramnios with and without symptoms. STUDY DESIGN: We recruited patients with pregnancies in which amnioreduction was performed for polyhydramnios in the Department of Fetal-Maternal Medicine at Nagara Medical Center between April 2017 and August 2018. Amnioreduction was performed for severe polyhydramnios with maternal symptoms [symptomatic group] or polyhydramnios without maternal symptoms [asymptomatic group] such as abdominal distension, dyspnea, or threatened premature labor. We measured the intra-amniotic pressure after every 200 ml volume reduction during the amnioreduction. RESULTS: A total of 27 patients who underwent amnioreduction were classified into symptomatic (66.7%, 18/27) and asymptomatic (33.3%, 9/27) groups. Gestational age, amniotic fluid index at the time of amnioreduction, and the volume of amniotic fluid removed were not significantly different between the symptomatic and asymptomatic groups [median 32.4 weeks vs. 33.1 weeks, median 38.0 cm vs. 39.0 cm, and median 1500 ml vs. 2500 ml, respectively]. However; the intra-amniotic pressure before amnioreduction was significantly higher in the symptomatic group than in the asymptomatic group [median 15.0 mmHg (range, 10-27) vs. 10.0 mmHg (range, 6.0-13); p < 0.005]. After amnioreduction, these pressures decreased significantly to median 9.0 mmHg (range, 5.0-13) (p < 0.001) in the symptomatic and 7.0 mmHg (range, 4.0-11) (p < 0.05) in the asymptomatic group. The median intra-amniotic pressure gradually decreased and reached a plateau during the amnioreductions in both groups. CONCLUSIONS: With polyhydramnios, the intra-amniotic pressure was significantly higher in the symptomatic group than in the asymptomatic group. Therefore, uterine pressure tolerance might vary according to the individual. In addition, intra-amniotic pressure monitoring might enhance the safety during amnioreduction procedures to avoid drastic and potentially harmful pressure changes.

Fetal Goitrous Hypothyroidism and Polyhydramnios in a Patient with Compound Heterozygous DUOXA2 Mutations.

BACKGROUND: Fetal goiter is only rarely observed in pregnant women without autoimmune thyroid disorders, and there is no epidemiological data on its pathophysiology. Dual oxidase maturation factor 2 (DUOXA2), together with dual oxidase 2, serves pivotal roles in thyroid hormone biosynthesis. To date, all reported patients with DUOXA2 mutations were diagnosed postnatally through newborn screening for congenital hypothyroidism. CASE REPORT: The mother of a male fetus presented at 33 + 4 gestational weeks (GW) with a fetal goiter and polyhydramnios. Cordocentesis revealed fetal hypothyroidism (TSH 253.4 mU/L, FT4 0.29 ng/dL). Intra-amniotic levothyroxine injections were performed at GW 34 + 3 and 35 + 3. The patient was born after spontaneous vaginal delivery at 35 + 6 GW without obstetrical complications. He was treated with levothyroxine until the age of 6 years when reevaluation of his thyroid functions showed normal results (TSH 1.32 mU/L, FT4 1.81 ng/dL). Eleven causative genes of CH, including DUOXA2, were analyzed with use of a next-generation sequencing technique. RESULTS: A next-generation sequencing-based mutation screen led us to find that he was compound heterozygous for 2 previously reported nonsense DUOXA2 mutations (p.[Tyr138*];[Tyr246*]). CONCLUSION: The present case not only illustrates the phenotypic diversity of DUOXA2 mutation carriers but also implies that DUOXA2 is important in prenatal thyroid hormone production.

Placental abruption after amnioreduction for polyhydramnios caused by chorioangioma.

Placental chorioangioma is the most common type of a benign placental tumour that occurs in 1% of pregnancies. A large chorioangioma is associated with adverse pregnancy outcomes. We present a case of placental abruption necessitating preterm delivery after multiple amnioreductions for polyhydramnios caused by a large chorioangioma. If antenatal diagnosis of a significant chorioangioma is made as the cause of polyhydramnios, caution should be taken when performing rapid amnioreductions.

Delivery outcomes of term pregnancy complicated by idiopathic polyhydramnios.

OBJECTIVE: Polyhydramnios is associated with an increased risk of cesarean section. The aetiology of polyhydramnios and the characteristics of the labour may be confounding factors. The objective was to study the characteristics and mode of delivery in case of pregnancy complicated with idiopathic polyhydramnios. METHODS: This retrospective matched and controlled study included all pregnant women with idiopathic polyhydramnios (amniotic index>25cm or single deepest pocket>8cm) diagnosed at the 2nd or 3rd trimester and persistent at term delivery (>37weeks of pregnancy) in our institution. We excluded pregnancies in which the polyhydramnios could be explained by infection, gestational diabetes, congenital malformation, abnormal karyotype, placental anomalies, alloimmunization as well as pregnancies in which an amniocentesis for the purpose of diagnosis had not been performed. Data were gathered from a tertiary care university hospital register from 1998-2015. Cases of polyhydramnios were matched with the following two women who presented for labour management with spontaneous cephalic presentation, matching for delivery date, maternal age, parity, body mass index. The main outcome measure was the risk of cesarean section. Univariate and multivariate adjusted analysis were performed. RESULTS: We identified 108 women with idiopathic polyhydramnios and compared them with 216 matched women. Among them, 94 and 188 attempted a trial of labour. Maternal age, mean term delivery and birthweight were 31 years, 39+5weeks gestation and 3550 g. We did not observe differences in maternal characteristics, epidural analgesia and rate of abnormal fetal heart tracing. Induced labour and non-vertex presentations (forehead, bregma, face) were more frequent in the polyhydramnios group (respectively 57.9% versus 27.8%, P<0.05 and 7.8% versus 1%, P<0.05). Cesarean section rate was higher in the case of polyhydramnios in the overall population (45.4% versus 8%, P<0.05) and remained higher after exclusion of cases of induced labour and non-vertex presentation (38.4% versus 3.8%, P<0.05). Amniotomy was more frequent in pregnancies with polyhydramnios (55.8% versus 39.1%, P<0.05). After adjustment for matching and confounding variables, polyhydramnios was found to be a risk factor for cesarean section (OR 21.02; CI 95% 8.004-55.215, P<0.01). CONCLUSION: Idiopathic polyhydramnios increased the risk of prolonged first stage of labour, non-vertex presentation and cesarean section.

Pregnancy outcomes in severe polyhydramnios: no increase in risk in patients needing amnioreduction for maternal pain or respiratory distress.

INTRODUCTION: Polyhydramnios is a common complication of fetal malformations and has been described to have high risk of pregnancy complications such as prematurity and placental abruption. In a subgroup of women severe polyhydramnios may lead to maternal dyspnea or untreatable pain, and amnioreduction is the procedure indicated to relieve those symptoms. There is a lack of information concerning the increase in the risk for the pregnancy when the procedure is indicated. Therefore, this study sought to evaluate the risk of complications in pregnancies with severe polyhydramnios that needed amnioreduction in relation to the basal risk for the pregnancy of having polyhydramnios without the need for the procedure. MATERIALS AND METHODS: Patients with singleton pregnancies and severe polyhydramnios followed in our fetal medicine center were evaluated retrospectively. Pregnancy complications (prematurity rate, fetal death, premature rupture of membranes, placental abruption and chorioamnionitis) were studied in the group of patients needing the procedure and their risk was compared to the risk of having a pregnancy with severe polyhydramnios but with no need for the procedure. RESULTS: One hundred and thirty-five patients were evaluated. Forty-four patients (32.6%) needed amnioreduction. There was no increase in the risk of having complications when the procedure was needed OR = 1.4 (CI 0.46-1.26). CONCLUSION: Amnioreduction performed to relieve maternal symptoms did not statistically increase the risk of pregnancy complications with severe polyhydramnios in single pregnancies.

Giant chorioangioma treated in utero via laser of feeding vessels with subsequent development of multifocal infantile hemangiomas.

We report a case of a giant placental chorioangioma (15.6 cm diameter) complicated by polyhydramnios and severe fetal heart failure. Fetoscopic laser occlusion of a dominant feeding vessel was performed at 29 weeks' gestation and partial devascularization was achieved. In the 33rd week of the pregnancy, the decision was made to preemptively deliver the fetus due to persistent signs of fetal cardiac failure. After birth, the infant developed multifocal infantile hemangiomas with extracutaneous involvement. We posit that the development of infantile hemangiomas may be linked to the presence of the large chorioangioma. Further study is required to ascertain if fetal treatment of the chorioangioma may have been an exacerbating factor.

Amnioreduction in the management of polyhydramnios complicating singleton pregnancies.

OBJECTIVE: The purpose of this study was to evaluate the contribution of amnioreduction to the management of singleton pregnancies that are complicated by symptomatic polyhydramnios. STUDY DESIGN: Retrospective review of all singleton pregnancies that received at least 1 amnioreduction for polyhydramnios from 2000-2012 at a single obstetric unit that provides a statewide service. The indications, procedural techniques, and pregnancy outcomes were evaluated. RESULTS: One hundred thirty-eight women with polyhydramnios (maximal vertical pocket [MVP], ≥8 cm) had 271 amnioreduction procedures during the study period. The median gestation at the first drain was 31.4 weeks (interquartile range, 28.4-34 weeks) and a median of 1 procedure (interquartile range, 1-2 procedures) was performed per pregnancy. Sixty-three women (45.6%) required >1 amnioreduction. The median volume removed per pregnancy was 2100 mL (interquartile range, 1500-4260 mL). The median duration from the first amnioreduction until delivery was 26 days (interquartile range, 15-52.5 days). There was no significant association between gestation at delivery and the volume per procedure or total volume that was removed. Earlier gestation at first drain was associated positively with earlier gestations at delivery. In 4.1% of amnioreduction procedures (11/271 procedures), there was an unplanned preterm birth within 48 hours. The median gestation at delivery was 36.4 weeks (interquartile range, 34-38 weeks). The final diagnoses were gastrointestinal malformations (21%), idiopathic polyhydramnios (20.3%), chromosomal anomaly (15.2%), syndromic condition (13.7%), and neurologic condition (8%). CONCLUSION: Amnioreduction has a useful role in the management of polyhydramnios in singleton pregnancies. Complications are uncommon, and delivery typically occurs near term.

Prognosis and long-term neurodevelopmental outcome in conservatively treated twin-to-twin transfusion syndrome.

BACKGROUND: Amnioreduction remains a treatment option for pregnancies with twin-to-twin transfusion syndrome (TTTS) not meeting criteria for laser surgery or those in which it is not feasible. Amnioreduction is a relatively simple treatment which does not require sophisticated technical equipment. Previous reports of conservative management have indicated that major neurodevelopmental impairment occurs in 14.3-26% of survivors. The purpose of this study was to investigate long-term neurodevelopmental outcome in conservatively treated TTTS. METHODS: During the nine-year study period from January 1996 to December 2004, all pregnancies with TTTS who were admitted to our center were investigated. TTTS was diagnosed by using standard prenatal ultrasound criteria, and staged according to the criteria of Quintero et al. We reviewed gestational age at diagnosis, gestational age at delivery, the stage of TTTS at diagnosis, and diagnosis to delivery interval. Neonatal cranial ultrasound findings were reviewed and the neurodevelopmental outcomes were evaluated. RESULTS: Twenty-one pregnancies with TTTS were included. Thirteen pregnancies (62%) were treated with serial amnioreduction. The mean gestational age at delivery was 28 weeks (22-34 weeks). The perinatal mortality rate was 42.9%. Twenty survivors were followed up until at least 3 years of age. The mean age at follow-up was 6.3 years (3-12 years). Six children (30%) had neurodevelopmental impairment. Four children (20%) had major neurodevelopmental impairment and two children (10%) had minor neurodevelopmental impairment. Children with neurodevelopmental impairment were delivered before 29 weeks of gestation. CONCLUSIONS: Our study showed a high rate of perinatal mortality and a high rate of major neurodevelopmental impairment in conservatively treated TTTS. The long-term outcomes for the survivors with TTTS were good when survivors were delivered after 29 weeks of gestation.