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.

Is Obesity a Risk Factor for Disorders of Amniotic Fluid?

OBJECTIVES: Prior studies show conflicting evidence as to whether obesity in the absence of other medical or pregnancy-related conditions contributes to amniotic fluid disorders. The purpose of this study is to determine the association between late-pregnancy obesity with oligohydramnios (amniotic fluid index [AFI] ≤5 cm or maximum vertical pocket [MVP] <2 cm) and/or polyhydramnios (AFI ≥24 cm or MVP ≥8 cm). METHODS: This is a retrospective cohort study of 961 women with singleton gestations who had one or more obstetrical ultrasounds at a single institution at 36 0/7 weeks gestation or beyond between August 1, 2015, and May 1, 2020. Patients were included if they had valid pregnancy dating and a documented AFI and/or MVP. Patients were categorized based on body mass index or BMI (eg, normal, overweight, Class I Obesity, Class II Obesity, or Class III Obesity). RESULTS: A total of 6.2% of patients met criteria for oligohydramnios based on AFI, MVP or both (n = 60). There was no significant association between oligohydramnios and increasing BMI, regardless of obesity class (P = .21). In terms of polyhydramnios, 5.6% of patients met criteria based on AFI, MVP, or both (n = 54). Similarly, there was also no significant association between polyhydramnios and increasing BMI, regardless of obesity class (P = .66). CONCLUSIONS: Elevated maternal BMI was not significantly associated with disorders of amniotic fluid, regardless of the severity of obesity.

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.

Idiopathic polyhydramnios and pregnancy outcome: systematic review and meta-analysis.

OBJECTIVE: To analyze outcomes of singleton pregnancies with idiopathic polyhydramnios through a systematic review and meta-analysis. METHODS: Electronic databases, including MEDLINE, OVID, EBSCO, Cochrane collection and Science Citation Index, were searched from 1946 to 2019. Gray literature and tables of contents of relevant journals were also screened. Prospective and retrospective studies with a control group were included. Two authors independently reviewed the abstracts retrieved from the literature search. Inclusion criteria were: studies documented in English, singleton pregnancy and idiopathic polyhydramnios determined by amniotic fluid volume assessment on ultrasound. Exclusion criteria were: maternal diabetes, fetal structural or chromosomal anomaly, alloimmunization and intrauterine fetal infection. RESULTS: Twelve studies met the inclusion criteria, giving a total of 2392 patients with idiopathic polyhydramnios and 160 135 patients with normal amniotic fluid volume. Pregnancies complicated by idiopathic polyhydramnios were at a higher risk of neonatal death (odds ratio (OR), 8.68 (95% CI, 2.91-25.87)), intrauterine fetal demise (OR, 7.64 (95% CI, 2.50-23.38)), neonatal intensive care unit admission (OR, 1.94 (95% CI, 1.45-2.59)), 5-min Apgar score < 7 (OR, 2.21 (95% CI, 1.34-3.62)), macrosomia (OR, 2.93 (95% CI, 2.39-3.59)), malpresentation (OR, 2.73 (95% CI, 2.06-3.61)) and Cesarean delivery (OR, 2.31 (95% CI, 1.79-2.99)). CONCLUSIONS: This study suggests that pregnancies complicated by idiopathic polyhydramnios are at increased risk of adverse outcome. Future investigations should aim to determine an amniotic fluid volume threshold above which antenatal fetal surveillance is appropriate in the management of these pregnancies. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

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.

Fetal epicardial fat thickness in non-severe idiopathic polyhydramnios: Its impact on fetal cardiac function and perinatal outcomes.

OBJECTIVE: This study aimed to evaluate fetal epicardial fat thickness (EFT) along with fetal myocardial performance index (MPI) and its effects on perinatal outcomes in non-severe idiopathic polyhydramnios (IP). MATERIALS AND METHODS: This prospective study included 92 participants, 32 diagnosed with non-severe IP, and 60 healthy pregnant women. Amniotic fluid indices (AFI), umbilical and middle cerebral artery Doppler, EFT, and MPI measurements were performed for all patients. RESULTS: The fetal EFT and MPI values were statistically higher in the non-severe IP group than in the control group (p = 0.0001, p = 0.014, respectively). The optimal fetal EFT cutoff value for predicting non-severe IP disease was found as 1.3 mm with a specificity of 81.7% and sensitivity of 59.4%. The EFT cutoff for predicting cesarean section in non-severe IP cases was 1.25 mm (p = 0.038). Apgar scores, neonatal intensive care unit, respiratory distress syndrome, and stillbirth rates were not different between groups. CONCLUSION: In this study, EFT and MPI were found to be higher in non-severe IP cases compared to controls. It was observed that the increase in MPI and EFT was associated with the increase in cesarean rates, but not with adverse fetal outcomes.

The prevalence of prenatal sonographic findings in postnatal diagnostic exome sequencing performed for neurocognitive phenotypes: A cohort study.

OBJECTIVE: Prenatal exome sequencing (ES) is currently indicated for fetal malformations. Some neurocognitive genetic disorders may not have a prenatal phenotype. We assessed the prevalence of prenatally detectable phenotypes among patients with neurocognitive syndromes diagnosed postnatally by ES. METHODS: The medical files of a cohort of 138 patients diagnosed postnatally with a neurocognitive disorder using ES were reviewed for prenatal sonographic data. The Online Mendelian Inheritance in Man (OMIM) database was searched for prenatally detectable phenotypes for all genes identified. RESULTS: Prenatal imaging data were available for 122 cases. Of these, 29 (23.75%) had fetal structural abnormalities and another 29 had other ultrasound abnormalities (fetal growth restriction, polyhydramnios, elevated nuchal translucency). In 30 patients, structural aberrations that were not diagnosed prenatally were detected at birth; in 21 (17.2%), the abnormalities could theoretically be detected prenatally by third-trimester/targeted scans. According to OMIM, 55.9% of the diagnosed genes were not associated with structural anomalies. CONCLUSIONS: Most patients (52.5%) with postnatally diagnosed neurocognitive disorders did not have prenatal sonographic findings indicating prenatal ES should be considered. The prevalence of specific prenatal phenotypes such as fetal growth restriction and polyhydramnios in our cohort suggests that additional prenatal findings should be assessed as possible indications for prenatal ES.

Ultrasound predictors of adverse outcome in pregnancy complicated by pre-existing and gestational diabetes.

INTRODUCTION: Ultrasound assessment of fetuses subjected to hyperglycemia is recommended but, apart from increased size, little is known about its interpretation, and the identification of which large fetuses of diabetic pregnancy are at risk is unclear. Newer markers of adverse outcomes, abdominal circumference growth velocity and cerebro-placental ratio, help to predict risk in non-diabetic pregnancy. Our study aims to assess their role in pregnancies complicated by diabetes. MATERIAL AND METHODS: This is a retrospective analysis of a cohort of singleton, non-anomalous fetuses of women with pre-existing or gestational diabetes mellitus, and estimated fetal weight at the 10th centile or above. Gestational diabetes was diagnosed by selective screening of at risk groups. A universal ultrasound scan was offered at 20 and 36 weeks of gestation. Estimated fetal weight, abdominal circumference growth velocity, presence of polyhydramnios, and cerebro-placental ratio were evaluated at the 36-week scan. A composite adverse outcome was defined as the presence of one or more of perinatal death, arterial cord pH less than 7.1, admission to Neonatal Unit, 5-minute Apgar less than 7, severe hypoglycemia, or cesarean section for fetal compromise. A chi-squared test was used to test the association of estimated fetal weight at the 90th centile or above, polyhydramnios, abdominal circumference growth velocity at the 90th centile or above, and cerebro-placental ratio at the 5th centile or below with the composite outcome. Logistic regression was used to assess which ultrasound markers were independent risk factors. Odds ratios of composite adverse outcome with combinations of independent ultrasound markers were calculated. RESULTS: A total of 1044 pregnancies were included, comprising 87 women with pre-existing diabetes mellitus and 957 with gestational diabetes. Estimated fetal weight at the 90th centile or above, abdominal circumference growth velocity at the 90th centile or above, cerebro-placental ratio at the 5th centile or below, but not polyhydramnios, were significantly associated with adverse outcomes: odds ratios (95% confidence intervals) 1.85 (1.21-2.84), 1.54 (1.02-2.31), 1.92 (1.21-3.30), and 1.53 (0.79-2.99), respectively. Only estimated fetal weight at the 90th centile or above and cerebro-placental ratio at the 5th centile or below were independent risk factors. The greatest risk (odds ratio 6.85, 95% confidence interval 2.06-22.78) was found where both the estimated fetal weight is at the 90th centile or above and the cerebro-placental ratio is at the 5th centile or below. CONCLUSIONS: In diabetic pregnancies, a low cerebro-placental ratio, particularly in a macrosomic fetus, confers additional risk.

Transient Idiopathic Polyhydramnios: Maternal and Perinatal Outcomes: Maternal and Perinatal Outcomes.

OBJECTIVES: To compare maternal and perinatal outcomes in pregnancies with transient and persistent idiopathic polyhydramnios to those with normal amniotic fluid volume. METHODS: This retrospective cohort study included subjects delivering a singleton pregnancy between January 1, 2015, and June 30, 2020, with sonography ≥26 weeks' gestation demonstrating transient or persistent idiopathic polyhydramnios (amniotic fluid index [AFI] ≥24.0 cm) or normal AFI (referent group). The primary maternal outcome was a composite of spontaneous preterm delivery <37 weeks, cesarean delivery for malpresentation, abnormal labor progress, or nonreassuring fetal status, operative vaginal delivery, hemorrhage requiring transfusion, and umbilical cord prolapse. The primary perinatal outcome was a composite of birthweight >4500 g, fetal or neonatal death, 5-minute Apgar score <7, and neonatal intensive care unit admission for >24 hours. RESULTS: Patients with transient polyhydramnios (n = 259) exhibited maternal outcomes similar to those of the referent group (n = 435) but had significantly increased odds for the primary perinatal outcome (odds ratio [OR] 1.70, 95% confidence interval [CI] 1.15-2.53; P = .008) and for birthweight ≥4500 g (OR 8.70, 95% CI 1.89-40.0; P = .005). Persistent polyhydramnios (n = 176) was significantly associated with both the primary maternal (OR 1.93, 95% CI 1.27-2.95, P = .002) and primary perinatal outcome (OR 2.15, 95% CI 1.40-3.30; P < .001), and individually with cesarean delivery for abnormal labor (OR 3.22, 95% CI 1.55-6.68; P = .002) and birthweight ≥4500 g (OR 8.97, 95% CI 1.84-43.6; P = .007). CONCLUSIONS: Transient idiopathic polyhydramnios does not impact maternal outcomes but is associated with increased odds of newborn birthweight >4500 g. Persistent polyhydramnios is associated with both adverse maternal and perinatal outcomes.

Moderate-to-Severe Polyhydramnios: Cutoffs for Deepest Vertical Pocket Corresponding to Amniotic Fluid Index.

OBJECTIVE: Society for Maternal-fetal medicine Consult Series (#46) states "antenatal fetal surveillance is not required for mild idiopathic" polyhydramnios defined as amniotic fluid index (AFI) of 24 cm or a deepest vertical pocket (DVP) between 8 and 11 cm. The objective of this study was to determine the cutoff for DVP which correlates with AFI ≥ 30 cm. METHODS: This retrospective study of singleton third trimester ultrasounds included a study group randomly divided into test and validation. In the test group, DVP cutoffs correlating with AFI ≥ 30 cm which was used to define moderate-severe polyhydramnios were calculated in two ways, rounded to the nearest whole number: 1) a receiver operating curve and Youden's J statistic (DVP-Youden) and 2) calculation of the DVP percentile that corresponded with AFI of 30 cm (DVP-Percentile). Using the validation group, diagnostic characteristics were DVP-Youden and DVP-Percentile for diagnosis of AFI ≥ 30 cm and were compared against SMFM cutoffs (DVP-SMFM). RESULTS: Seventy one thousand eight hundred and ninety three ultrasound exams in the 3rd trimester had assessment of AFI and DVP. Moderate-severe polyhydramnios occurred in 286 (1.2%) in test group and 571 (1.2%) in validation group. AFI of 30 cm corresponded to the 98.9th percentile, which in turn correlated to a DVP of 10 cm (DVP-Percentile). The calculated cutoff for moderate-severe polyhydramnios was 8 cm for DVP-Youden. CONCLUSION: Using 8.0 cm rather than 12.0 cm increased the detection of moderate-severe polyhydramnios to 100% with a false positive rate under 5%. For those utilizing DVP for amniotic fluid evaluation, identification of a DVP ≥ 8.0 cm should prompt further evaluation with complete AFI.

Semiquantitative Assessment of Amniotic Fluid Among Individuals With and Without Diabetes Mellitus.

OBJECTIVE: To compare the rate and severity of abnormal amniotic fluid volumes (oligohydramnios or polyhydramnios), as well as the distribution of amniotic fluid levels, in pregnancies with and without diabetes. METHODS: We performed a retrospective cohort study of singleton nonanomalous pregnancies receiving an ultrasound examination (USE) in the third trimester. Pregnancies were categorized into those with and without diabetes and subcategorized by diabetes type. The primary outcomes were oligohydramnios or polyhydramnios. Polyhydramnios was also examined by severity. The association between maternal diabetes status and oligohydramnios or polyhydramnios was assessed using logistic regression. In addition, we computed gestational age-specific amniotic fluid index (AFI) and deepest vertical pocket (DVP) centiles for pregnancies with and without diabetes. RESULTS: There were 60,226 USEs from 26,651 pregnancies that met inclusion criteria. There were 3992 (15.0%) pregnancies with diabetes and 22,659 (85.0%) without diabetes. Using AFI, the rate of polyhydramnios was 10.5 versus 3.8% (odds ratio [OR] 2.95; 95% confidence interval [CI] 2.62-3.32) for pregnancies with versus without diabetes, respectively; using DVP, the rate of polyhydramnios was 13.9 versus 5.4% (OR 2.84; 95% CI 2.56-3.15). Rates of oligohydramnios were also increased in pregnancies with diabetes (3.3 versus 2.6%; OR 1.26; 95% CI 1.04-1.52). The AFI and DVP were significantly higher in the cohort with diabetes between 28 and 36 weeks. CONCLUSION: Within our study population, pregnancies with diabetes had increased rates of oligohydramnios and polyhydramnios as well as increased gestational age-specific amniotic fluid volumes between 28 and 36 weeks. A higher prevalence of polyhydramnios was observed using DVP as compared to AFI; nevertheless, associations were similar using either method.

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.

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.

Esophageal atresia and tracheoesophageal fistula: prenatal sonographic manifestation from early to late pregnancy.

OBJECTIVE: Esophageal atresia and/or tracheoesophageal fistula (EA/TEF) remains one of the most frequently missed congenital anomalies prenatally. The aim of our study was to elucidate the sonographic manifestation of EA/TEF throughout pregnancy. METHODS: This was a retrospective study of data obtained from a tertiary center over a 12-year period. The prenatal ultrasound scans of fetuses with EA/TEF were assessed to determine the presence and timing of detection of three principal signs: small/absent stomach and worsening polyhydramnios, both of which were considered as 'suspected' EA/TEF, and esophageal pouch, which was considered as 'detected' EA/TEF. We assessed the yield of the early (14-16 weeks' gestation), routine mid-trimester (19-26 weeks) and third-trimester (≥ 27 weeks) anomaly scans in the prenatal diagnosis of EA/TEF. RESULTS: Seventy-five cases of EA/TEF with available ultrasound images were included in the study. A small/absent stomach was detected on the early anomaly scan in 3.6% of fetuses scanned, without a definitive diagnosis. On the mid-trimester scan, 19.4% of scanned cases were suspected and 4.3% were detected. On the third-trimester anomaly scan, 43.9% of scanned cases were suspected and 33.9% were detected. An additional case with an esophageal pouch was detected on magnetic resonance imaging (MRI) in the mid-trimester and a further two were detected on MRI in the third trimester. In total, 44.0% of cases of EA/TEF in our cohort were suspected, 33.3% were detected and 10.7% were suspected but, eventually, not detected prenatally. CONCLUSIONS: Prenatal diagnosis of EA/TEF on ultrasound is not feasible before the late second trimester. A small/absent stomach may be visualized as early as 15 weeks' gestation. Polyhydramnios does not develop before the mid-trimester. An esophageal pouch can be detected as early as 22 weeks on a targeted scan in suspected cases. The detection rates of all three signs increase with advancing pregnancy, peaking in the third trimester. The early and mid-trimester anomaly scans perform poorly as a screening and diagnostic test for EA/TEF. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Performance of diagnostic ultrasound to identify causes of hydramnios.

INTRODUCTION: We aimed to assess the diagnostic yield of ultrasonography in the identification of the etiology of hydramnios, and the added value of MRI or amniocentesis. METHODS: We conducted a single-center retrospective study including pregnancies with confirmed hydramnios (defined as deepest pocket ≥8 cm) between January 2013 and May 2017. Twin pregnancies, secondary hydramnios discovered after the diagnosis of a causal pathology, and pregnancies of unknown outcome were excluded. All pregnancies underwent a targeted scan, and selected cases underwent MRI or amniocentesis. RESULTS: A total of 158 patients with confirmed hydramnios were included. Hydramnios was associated with a fetal pathology in 37 cases (23.4%), with diabetes in 39 (24.6%), isolated macrosomia in 16 (10.1%), and considered idiopathic in 66 (41.7%). Ultrasonography established a diagnosis of the underlying pathology in 73% of cases. Amniocentesis was done in 31 cases (20%) and it allowed diagnosis of chromosome anomalies, esophageal atresia, myotonic dystrophy congenital type, Prader-Willi syndrome, and Bartter syndrome. MRI was done in 15 cases (10%) and it allowed one additional diagnosis of esophageal atresia. The diagnostic yields of MRI and amniocentesis were 91.7% and 95.2%, respectively. There were five false positive diagnoses at ultrasonography, and one false positive diagnosis at MRI. CONCLUSION: Hydramnios can be associated with a wide variety of underlying pathologies. Diagnostic ultrasound can attain a diagnosis in the majority of cases. Amniocentesis offers a valuable complementary assessment.

Prenatal diagnosis of auriculocondylar syndrome with a novel missense variant of GNAI3: a case report.

BACKGROUND: Auriculocondylar syndrome (ACS) is a rare disorder characterized by micrognathia, mandibular condyle hypoplasia, and auricular abnormalities. Only 6 pathogenic variants of GNAI3 have been identified associated with ACS so far. Here, we report a case of prenatal genetic diagnosis of ACS carrying a novel GNAI3 variant. CASE PRESENTATION: A woman with 30 weeks of gestation was referred to genetic counseling for polyhydramnios and fetal craniofacial anomaly. Severe micrognathia and mandibular hypoplasia were identified on ultrasonography. The mandibular length was 2.4 cm, which was markedly smaller than the 95th percentile. The ears were low-set with no cleft or notching between the lobe and helix. The face was round with prominent cheeks. Whole-exome sequencing identified a novel de novo missense variant of c.140G > A in the GNAI3 gene. This mutation caused an amino acid substitution of p.Ser47Asn in the highly conserved G1 motif, which was predicted to impair the guanine nucleotide-binding function. All ACS cases with GNAI3 mutations were literature reviewed, revealing female-dominated severe cases and right-side-prone deformities. CONCLUSION: Severe micrognathia and mandibular hypoplasia accompanied by polyhydramnios are prenatal indicators of ACS. We expanded the mutation spectrum of GNAI3 and summarized clinical features to promote awareness of ACS.

The effect of polyhydramnios degree on chromosomal microarray results: a retrospective cohort analysis of 742 singleton pregnancies.

PURPOSE: To analyze the risk for clinically significant microarray aberrations in pregnancies with polyhydramnios. METHODS: Data from all chromosomal microarray analyses (CMA) performed due to polyhydramnios between January 2013 and December 2019 were retrospectively obtained from the Ministry of Health Database. The rate of clinically significant (pathogenic and likely pathogenic) CMA findings in isolated and non-isolated polyhydramnios cohorts was compared to a local control group of 5541 fetuses with normal ultrasound, in which 78 (1.4%) abnormal results were demonstrated. Subgroup analyses were performed by the degree of polyhydramnios, week of diagnosis, maternal age, and the presence of additional sonographic anomalies. RESULTS: In the isolated polyhydramnios cohort, 19/623 (3.1%) clinically significant CMA aberrations were noted, a significantly higher rate compared to the control population. However, the risk for abnormal CMA results in the 158 cases with mild polyhydramnios (AFI 25-29.9, or maximal vertical pocket 8-11.9 cm) did not significantly differ from pregnancies with normal ultrasound. Of 119 cases of non-isolated polyhydramnios (most frequently associated with cardiovascular (26.1%) and brain (15.1%) anomalies), 8 (6.7%) abnormal CMA findings were noted, mainly karyotype-detectable. CONCLUSION: Mild polyhydramnios was not associated with an increased rate of clinically significant microarray results, compared to pregnancies with normal ultrasound. An extensive anatomical sonographic survey should be performed in pregnancies with polyhydramnios, with consideration of fetal echocardiography.

The Efficacy and Efficiency of Uterocervical Angle Measurements to Predict Preterm Labor in Idiopathic Polyhydramnios Patients: A Prospective Cohort Study.

INTRODUCTION: Uterocervical angle measurements in pregnant women with idiopathic polyhydramnios were appraised for their predictive value for spontaneous preterm labor. MATERIAL AND METHODS: In this prospective study, we included nulliparous and multiparous pregnant women diagnosed with idiopathic polyhydramnios at 24-28 weeks at our polyclinic; the uterocervical angle and cervical length were measured by transvaginal ultrasound at the time of diagnosis. Routine pregnancy follow-up was done by our team and gestational age at delivery and maternal-fetal outcomes were noted. RESULTS: In total, 24 patients delivered before 37 weeks and 36 patients delivered at 37 weeks or later. Preterm labor subjects had larger UCA values (126.7±12.9° vs. 100.8±16.2°) and term labor patients had larger cervical length values (34.3±4.5 mm vs. 40.6±5.2 mm). In women with idiopathic polyhydramnios, the area under the curve for the uterocervical angle was 0.885 (p<0.001) and it was 0.823 for the cervical length (p<0.001). DISCUSSION: The uterocervical angle, a sagittal transvaginal cervical image measurement, is a practical method that successfully predicts spontaneous preterm labor risk in singleton pregnancies with idiopathic polyhydramnios. In addition, the uterocervical angle displayed greater sensitivity, but lower specificity, compared with cervical length measures.

A Rare Cause of Refractory Severe Polyhydramnios: Antenatal Bartter Syndrome.

Background: Antenatal Bartter syndrome is an autosomal recessive disorder causing severe polyuria that leads to severe polyhydramnios and preterm labor. Prenatal diagnosis of antenatal Bartter syndrome is difficult because the genetic diagnosis can only be confirmed following a clinical diagnosis in infants. Reports of prenatal diagnosis and treatment of antenatal Bartter syndrome are limited. Case Presentation: We present the case of a 33-year-old pregnant woman with refractory polyhydramnios at 31 weeks of gestation. There were no structural anomalies or placental problems on ultrasonography; therefore, antenatal Bartter syndrome was suspected. With repeated amniocentesis and indomethacin therapy, the pregnancy continued to 36 weeks of gestation. The clinical features of the infant and subsequent genetic testing confirmed the diagnosis of antenatal Bartter syndrome. The baby was in good clinical condition at the 3-month follow-up visit. Conclusions: For pregnant women with early onset and refractory severe polyhydramnios without morphological anomalies, antenatal Bartter syndrome should be highly suspected.

A case of rare isolated agnathia and literature review.

Agnathia is a rare congenital malformation with unknown etiology characterized by absence of the mandible, microstomia, and tongue aplasia, often found to have other anomalies including holoprosencephaly. The purpose of this paper was to describe the symptoms and imaging of a case of isolated agnathia and to conduct a comprehensive literature review of reported patients with isolated agnathia. Case reports of isolated agnathia are very rare, with most infants as stillborn. We report a child's management of isolated agnathia with microstomia and tongue aplasia. A literature review was performed with focus on diagnosis, airway, and feeding management of isolated agnathia. Polyhydramnios was a common pregnancy complication reported in 25 out of the 39 patients in the case study. Five infants were stillborn, while 23 died within the neonatal period. Of the deceased infants within the neonatal period, 19 died within minutes to hours while four died within days to weeks. There are nine patients with agnathia that survived past infancy. The results of this study suggest that isolated agnathia is a rare malformation which requires a multi-disciplinary approach for airway and feeding management.