[Prenatal diagnosis of a case with Congenital myasthenic syndrome due to compound heterozygous variants of SCN4A gene].

OBJECTIVE: To explore the clinical and genetic characteristics of a fetus diagnosed with Congenital myasthenic syndrome type 16 (CMS16). METHODS: A couple who had visited Tianjin Medical University General Hospital in February 2018 due to "adverse outcome of two pregnancies" was selected as the study subject. Clinical data was gathered. Peripheral blood and amniotic fluid samples were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. Low-depth whole-genome sequencing was carried out to detect copy number variation (CNV) in the fetus. RESULTS: The couple's first pregnancy had resulted in a miscarriage at 27+5 weeks, when ultrasound had revealed pleural effusion and polyhydramnios in the fetus. Their second pregnancy was terminated at 30+5 weeks due to fetal hand malformations, polyhydramnios and pleural fluid. Both couple had denied family history of genetic conditions. For their third pregnancy, no CNV abnormality was detected, whilst a compound heterozygous variants, including a maternally derived c.3172C>T (p.R1058W) and paternal c.1431delG (p.K477fs*89) in the SCN4A gene were detected. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.3172C>T (p.R1058W) was predicted as a likely pathogenic variant (PM1+PM2_supporting+PP3+PP4), whilst the c.1431delG (p.K477fs*89) was predicted as a pathogenic variant (PVS1+PM2_supporting+PP4). CONCLUSION: The c.3172C>T (p.R1058W) and c.1431delG (p.K477fs*89) compound heterozygous variants of the SCN4A gene probably underlay the CMS16 in the third fetus.

Obstetric and neonatal outcomes in pregnant women with idiopathic polyhydramnios: a systematic review and meta-analysis.

Although the assessment of the amniotic fluid volume in pregnancy is part of the fetal wellbeing surveillance, the impact of idiopathic polyhydramnios (IP) on maternal and perinatal outcomes in unknown. The aim of this meta-analysis was to investigate the association of IP with different maternal and perinatal outcomes. We screened five electronic databases until December 2023 and performed data extraction and quality assessment using ROBINS-E in duplicates. Pooled risk ratios and 95% confidence intervals (95% CI) were calculated with a random effects model. 38 studies were included. Patients with IP were at increased risk of perinatal complications including preterm delivery (RR 1.96, 95% CI 1.35-2.86; I2 = 92%), placental abruption (RR 3.20, 95% CI 2.20-4.65; I2 = 2%), delivery via caesarean section (RR 1.60, 95% CI 1.39-1.84; I2 = 95%) and postpartum haemorrhage (RR 1.98, 95% CI 1.22-3.22; I2 = 84%). Similarly, IP was associated with increased risk of adverse perinatal outcomes including low APGAR score (RR 3.0, 95% CI 1.23-7.35; I2 = 95%), stillbirth (RR 4.75, 95% CI 2.54-8.86; I2 = 9%) and perinatal mortality (RR 4.75, 95% CI 2.67-8.48; I2 = 37%). This meta-analysis suggests that pregnant women with IP may be at increased risk of perinatal complications and adverse neonatal outcomes. However, data remains inconclusive considering the low quality and high heterogeneity of included studies.PROSPERO registration number: CRD42022359944.

The effect of gestational diabetes mellitus on pregnancy outcomes in advanced primiparous women: A retrospective study.

Gestational diabetes mellitus (GDM) could have a variable degree of adverse effects on pregnancy outcomes for both pregnant women and newborns. The purpose of the study was to explore the effect of GDM on pregnancy outcomes in advanced primiparous women. A total of 1076 advanced primiparous women were included between January 2020 and December 2022. All these women were divided into the GDM group (n = 434) and the non-GDM group (n = 642). Variables included baseline characteristics, maternal, and newborn outcomes were collected. The risk of each adverse outcome was analyzed by multivariate logistic regression models. The effect of blood glucose control on pregnancy outcomes was further analyzed among GDM women with good glycaemic control (n = 381) and poor glycaemic control (n = 53). Analysis of baseline characteristics demonstrated a significant difference in prepregnancy body mass index (median, IQR: 22.27 [20.58-24.44] vs 21.17 [19.53-22.86], P < .01) between the GDM group and the non-GDM group. A significantly higher incidence rate of adverse pregnancy outcomes was found in advanced primiparous women with GDM, such as polyhydramniosis, premature birth, low-birth weight, macrosomia, and neonatal intensive care unit admission (all P < .05). Compared with the non-GDM group, the risk of polyhydramniosis was nearly twice as high in the GDM group (adjusted odds ratio: 1.94, 95% confidence interval: 1.01-3.72, P = .04) after adjusted baseline characteristics. Among the GDM group, the women with poor glycaemic control showed a significantly higher incidence rate of polyhydramnios, hypertensive disorders of pregnancy, cesarean delivery, premature birth, low-birth weight, macrosomia, and neonatal intensive care unit admission was significant than the women with good glycaemic control (all P < .05). GDM was an independent risk factor for polyhydramnios in advanced primiparous women. At the same time, good glycaemic control in diabetics advanced primiparous women could reduce adverse pregnancy outcomes.

Identifying gestational diabetes mellitus and assessing risk factors in affected women: a comprehensive study.

OBJECTIVE: Gestational diabetes mellitus (GDM) is a prevalent pregnancy complication associated with adverse health outcomes for both mothers and offspring. This study aimed to identify risk factors for GDM, a condition with a rapidly increasing global prevalence. PATIENTS AND METHODS: We conducted a study involving 474 pregnant women who attended the obstetrics outpatient clinic of Kafkas University Faculty of Medicine Hospital between January 2022 and June 2023. Risk factors for GDM were assessed based on criteria recommended by the American Diabetes Association and the Committee on Practice of the American College of Obstetricians and Gynecologists. Statistical analyses, including descriptive statistics, Chi-square tests, Mann-Whitney U tests, and multivariate logistic regression. RESULTS: Individuals with GDM (mean age: 31.26±6.09 years) were significantly older than those without GDM (mean age: 28.36±4.89 years; p<0.001). Obesity prevalence was higher in the GDM group (32.5%) compared to the non-GDM group (14.3%; p<0.001). Individuals with GDM had higher rates of pre-diabetes (3.3% vs. 0.3%; p=0.007), a history of gestational diabetes (25.2% vs. 5.7%; p<0.001), high blood sugar in previous pregnancies (13.8% vs. 1.4%; p<0.001), and diabetes mellitus in 1st-degree relatives (40.7% vs. 20.3%; p<0.001). GDM was associated with increased pregnancies (p<0.001), preterm births (p<0.001), macrosomic babies (p=0.026), congenital anomalies (p=0.011), high cholesterol (p=0.036), and polyhydramnios (p=0.001) in previous pregnancies, as well as polyhydramnios in the index pregnancy (p=0.008). Regular exercise in previous pregnancies differed significantly based on GDM presence (p=0.037). CONCLUSIONS: Recognizing modifiable risk factors is crucial for preventing GDM and reducing associated health risks. Healthcare providers should be vigilant, especially among those with a family history of GDM, previous GDM, advanced maternal age, and other risk factors. Early lifestyle interventions show promise. Further research is needed for accurate GDM prediction.

Polyhydramnios associated with rare genetic syndromes: two case reports.

BACKGROUND: We present two genetic causes of polyhydramnios that were challenging to diagnose due to their rarity and complexity. In view of the severe implications, we wish to highlight these rare genetic conditions when obstetricians consider differential diagnoses of polyhydramnios in the third trimester. CASE PRESENTATION: Patient 1 is a 34-year-old Asian woman who was diagnosed with polyhydramnios at 28 weeks' gestation. First trimester testing, fetal anomaly scan, and intrauterine infection screen were normal. Subsequent antenatal ultrasound scans revealed macroglossia, raising the suspicion for Beckwith-Wiedemann syndrome. Chromosomal microarray analysis revealed a female profile with no pathological copy number variants. The patient underwent amnioreduction twice in the pregnancy. The patient presented in preterm labor at 34 weeks' gestation but elected for an emergency caesarean section. Postnatally, the baby was noted to have a bell-shaped thorax, coat hanger ribs, hypotonia, abdominal distension, and facial dysmorphisms suggestive of Kagami-Ogata syndrome. Patient 2 is a 30-year-old Asian woman who was diagnosed with polyhydramnios at 30 weeks' gestation. She had a high-risk first trimester screen but declined invasive testing; non-invasive prenatal testing was low risk. Ultrasound examination revealed a macrosomic fetus with grade 1 echogenic bowels but no other abnormalities. Intrauterine infection screen was negative, and there was no sonographic evidence of fetal anemia. She had spontaneous rupture of membranes at 37 + 3 weeks but subsequently delivered by caesarean section in view of pathological cardiotocography. The baby was noted to have inspiratory stridor, hypotonia, low-set ears, and bilateral toe polysyndactyly. Further genetic testing revealed a female profile with a pathogenic variant of the GLI3 gene, confirming a diagnosis of Greig cephalopolysyndactyly syndrome. CONCLUSION: These cases illustrate the importance of considering rare genetic causes of polyhydramnios in the differential diagnosis, particularly when fetal anomalies are not apparent at the 20-week structural scan. We would like to raise awareness for these rare conditions, as a high index of suspicion enables appropriate counseling, prenatal testing, and timely referral to pediatricians and geneticists. Early identification and diagnosis allow planning of perinatal care and birth in a tertiary center managed by a multidisciplinary team.

Predictors of fetal death, neonatal survival and neurological outcomes in severe twin-twin transfusion syndrome treated by laser ablation of placental vessels.

OBJECTIVES: To identify predictors of outcomes in severe twin oligo-polyhydramnios sequence (TOPS) with or without twin anemia-polycythemia sequence (TAPS) and/or selective fetal growth restriction (SFGR) treated by laser ablation of placental vessels (LAPV). METHODS: Analysis of cases treated from 2011 to 2022. Variables evaluated Prenatal predictors: stages of TOPS, presence of TAPS and/or SFGR; pre-LAPV fetal ultrasound parameters; peri-LAPV variables. Perinatal predictors: GA at birth; birthweight; Apgar scores; transfontanellar ultrasonography (TFUS). OUTCOME VARIABLES: fetal death, neonatal survival, infant's neurodevelopment. Binary logistic regression analyses were performed to detect predictors of outcomes. RESULTS: 265 cases were included. Predictors of post-LAPV donor fetus' death were delta EFW (p:0.045) and absent/reverse end-diastolic flow in the umbilical artery (AREDF-UA) (p < 0.001). The predictor of post-LAPV recipient fetus' death was hydrops (p:0.009). Predictors of neonatal survival were GA at birth and Apgar scores. Predictors of infant's neurodevelopment were TFUS and pre-LAPV middle cerebral artery Doppler (MCAD) for the donor twin; and pre-LAPV ductus venosus' flow and MCAD for the recipient twin. CONCLUSIONS: Prediction of fetal death, neonatal survival and infant's neurodevelopment is possible in cases of TOPS associated or not with SFGR and/or TAPS that were treated by LAPV.

Induction of labor versus expectant management in patients with idiopathic polyhydramnios.

OBJECTIVE: To evaluate whether induction of labor is associated with lower risk of cesarean section compared to expectant management in patients with isolated polyhydramnios. STUDY DESIGN: This is a single-center, retrospective cohort study of patients with pregnancies complicated by idiopathic polyhydramnios, documented between 34 and 38 weeks gestation, who were delivered between July 2012 and February 2020. The primary outcome was cesarean delivery. Secondary outcomes included chorioamnionitis, endometritis, postpartum hemorrhage, preeclampsia/gestational hypertension, and composite neonatal morbidity. RESULTS: There were 194 patients included with idiopathic polyhydramnios - 115 underwent induction and 79 patients were expectantly managed. Planned induction was associated with a lower rate of CD compared with expectant management but did not meet statistical significance (19.1 % vs 30.4 %, aOR 0.51, 95 % CI 0.24, 1.05). A similar effect was seen when stratifying for parity: both nulliparous (9.1 % vs 16.3 %, aOR 0.59, 95 % CI 0.17, 1.98) and multiparous (32.7 % vs 47.2 %, aOR 0.45, 95 % CI 0.18, 1.15) patients had a lower CD rate when there was a planned induction, though neither group met statistical significance. No differences in maternal or fetal secondary outcomes were identified (chorioamnionitis, endometritis, postpartum hemorrhage, preeclampsia/gestational hypertension, composite neonatal morbidity). CONCLUSION: Lower rates of cesarean section were associated with labor induction for patients with isolated polyhydramnios, but confidence intervals did not reach statistical significance.

Genetically predicted body mass index and maternal outcomes of pregnancy: A two-sample Mendelian randomisation study.

OBJECTIVE: Observational studies have described associations between obesity and adverse outcomes of pregnancy but observational results are liable to influence by residual confounding. Mendelian randomisation (MR) leverages the 'natural' genetic randomisation to risk of an exposure occurring at allele assortment and conception. Similar to randomisation in a clinical trial, this limits the potential for the influence of confounding. DESIGN: A two-sample MR study. SETTING: Summary statistics from published genome wide association studies (GWAS) in European ancestry populations. POPULATION OR SAMPLE: Instrumental variants for body mass index (BMI) were obtained from a study on 434 794 females. METHODS: Inverse-variance weighted MR was used to assess the association between BMI and all outcomes. Sensitivity analyses with weighted median and MR-Egger were also performed. MAIN OUTCOME MEASURES: Female-specific genetic association estimates for outcomes were extracted from the sixth round of analysis of the FINNGEN cohort data. RESULTS: Higher genetically predicted BMI was associated with higher risk of pre-eclampsia (odds ratio [OR] per standard deviation 1.68, 95% confidence interval [CI] 1.46-1.94, P = 8.74 × 10-13 ), gestational diabetes (OR 1.67, 95% CI 1.46-1.92, P = 5.35 × 10-14 ), polyhydramnios (OR 1.40, 95% CI 1.00-1.96, P = 0.049). There was evidence suggestive of a potential association with higher risk of premature rupture of membranes (OR 1.16, 95% CI 1.00-1.36, P = 0.050) and postpartum depression (OR 1.12, 95% CI 0.99-1.27, P = 0.062). CONCLUSIONS: Higher genetically predicted BMI is associated with marked increase in risk of pre-eclampsia, gestational diabetes and polyhydramnios. The relation between genetically predicted BMI and premature rupture of membranes and postpartum depression should be assessed in further studies. Our study supports efforts to target BMI as a cardinal risk factor for maternal morbidity in pregnancy.

The Utility of Maternal TORCH Screening Due to Obstetrical Indications in Detecting Congenital Infections: A Retrospective Observational Study.

BACKGROUND: The diagnostic yield of TORCH screening for obstetrical indications is unclear. We evaluated TORCH testing results among women with intrauterine growth restriction (IUGR), polyhydramnios and oligohydramnios; and associations with congenital infections in neonates. METHOD: This retrospective single-center study included all the women diagnosed with IUGR, polyhydramnios or oligohydramnios who underwent serological TORCH testing during 2010-2019. TORCH screening included Toxoplasma, cytomegalovirus (CMV), rubella IgM and IgG. The data, which were cross-referenced with data of neonates with congenital TORCH infections during the same period, included indications for neonatal testing, sonographic findings and neonatal ophthalmologic and hearing findings. RESULT: Six women of 771 (0.8%) were diagnosed with primary TORCH infection: 4 (0.5%) with toxoplasmosis, and 2 (0.3%) with CMV. None had a confirmed congenital infection. The rates of positive maternal TORCH screening in IUGR and polyhydramnios were 2.1% and 0.6%, respectively. Maternal TORCH infection was not identified in any woman with oligohydramnios or severe polyhydramnios. None of the neonates with congenital infection were screened for TORCH during pregnancy due to polyhydramnios, oligohydramnios or IUGR. Among the neonates with congenital CMV, the most common indication for performing neonatal CMV polymerase chain reaction was suspected primary maternal infection during pregnancy due to symptomatic CMV. No incidences of congenital rubella were noted in the last decade in our medical center. CONCLUSION: Our results suggest that routine TORCH screening in pregnancies complicated with IUGR, polyhydramnios or oligohydramnios should be avoided. Suggestive maternal symptoms and specific fetal sonographic features should prompt testing for CMV and Toxoplasma infection.

Clinical and molecular analysis of nine fetal cases with clinically significant variants causing nemaline myopathy.

OBJECTIVE: To present the prenatal features and postnatal outcomes of pregnancies with fetal nemaline myopathy (NM). STUDY DESIGN: This was a retrospective study of nine cases with NM diagnosed by prenatal or postnatal clinical features and confirmed by genetic testing. Clinical and laboratory data were collected and reviewed for these cases, including maternal demographics, prenatal sonographic findings, exome sequencing (ES) results, and pregnancy outcomes. RESULTS: All of the nine cases were detected to have NM-causing variants, involving NEB gene in 2 cases, ACTA1 in 3 cases, KLHL40 in 3 cases, and TPM2 in 1 case. Almost all (8/9) had normal first-trimester ultrasound scans except one who had an increased nuchal translucency. Seven (7/9) cases had second-trimester abnormal ultrasounds with fetal akinesia and/or extremity anomalies. Two (2/9) had only third-trimester abnormal ultrasounds with fetal akinesia and polyhydramnios, with one combined with fetal growth restriction. Four pregnancies with a positive prenatal ES were terminated, while five having not receiving prenatal ES continued to term. Only one infant survived 1 year old, and four passed away within 12 months. CONCLUSION: Prenatal ultrasound can detect clues that lead to the diagnosis of NM, such as reduced or absent fetal movements, polyhydramnios and extremity anomalies.

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.

Isolated polyhydramnios: Is a genetic evaluation of value?

OBJECTIVE: To analyze the risk for genetic aberrations and pregnancy outcomes in pregnancies with isolated polyhydramnios. STUDY DESIGN: This was a retrospective study of singleton pregnancies complicated by isolated polyhydramnios that underwent genetic amniocentesis between 2016 and 2021. Clinical and laboratory data were collected and reviewed for these cases, including maternal demographics, prenatal sonographic findings, chromosomal microarray results, and pregnancy outcomes. RESULTS: A total of 94 singleton pregnancies were included. Three (3.2%) cases with chromosomal abnormalities were detected, including 2 case of trisomy 21 and 1 of 22q21.1 microdeletion. One case was diagnosed as Prader-Willi syndrome caused by maternal uniparental disomy of chromosome 15. Perinatal death occurred in 1 case with severe polyhydramnios, and was retrospectively diagnosed as Bartter syndrome. Of the 90 infants survived, two were identified to have single gene disorders after birth by whole exome sequencing. CONCLUSION: We first attempted to determine the value of exome sequencing in pregnancies with isolated polyhydramnios. Our results warrant more studies to evaluate advanced genetic testing technologies used in such pregnancies.

Amnioreduction vs expectant management in pregnancies with moderate to severe polyhydramnios.

BACKGROUND: The rate of polyhydramnios is higher in pregnancies complicated by congenital anomalies. These pregnancies have higher rates of peripartum complications. Amnioreduction is offered to relieve maternal symptoms such as dyspnea, abdominal and respiratory discomfort, and other issues like satiety. OBJECTIVE: This study aimed to report the rates of amnioreduction and its associated complications in pregnancies with moderate to severe polyhydramnios secondary to fetal anomalies. We also sought to determine if amnioreduction provided additional benefits, including prolongation of pregnancy and a decrease in the rates of peripartum morbidities associated with moderate to severe polyhydramnios. STUDY DESIGN: This was a retrospective review of anomalous singleton pregnancies with moderate to severe polyhydramnios that were evaluated and delivered at a single center between 2013 and 2021. Peripartum outcomes were compared between pregnancies that underwent amnioreduction and those that were expectantly managed. Mann-Whitney U tests were used to compare continuous variables and Fisher's exact tests were used for categorical variables. A multiple regression model was created to understand the effects of amnioreduction on gestational age at delivery. RESULTS: A total of 218 singleton pregnancies met the inclusion criteria of moderate to severe polyhydramnios in the study period. Of those, 110 patients (50.5%) underwent amnioreduction and 108 patients (49.5%) opted for expectant management. A total of 147 procedures were performed at a median gestational age of 32.5 weeks and a median of 1900 mL of amniotic fluid was removed per procedure. Complications occurred in 10.9% (n=16) of procedures, including preterm delivery within 48 hours in 5.4% cases (n=8). The median amniotic fluid index was higher in the amnioreduction group than in the expectant group (38.9 cm vs 35.5 cm; P<.0001). Patients who underwent amnioreduction had an earlier median gestational age at delivery (36.3 weeks vs 37.0 weeks; P=.048), however, the rates of spontaneous preterm delivery were similar. A higher percentage of women in the amnioreduction group had vaginal delivery (49.4% vs 30.5%; P=.01) and lower rates of uterine atony (2.4% vs 13.7%; P=.006). In the multiple linear regression analysis, the gestational age at delivery positively correlated with gestational age at amnioreduction after controlling for amniotic fluid volume (P<.0001; 95% confidence interval, 0.34-0.71). In addition, the patients in the amnioreduction group were twice as likely to have a vaginal delivery (P=.02). CONCLUSION: Amnioreduction in the setting of moderate-severe polyhydramnios has a reasonably low rate of complications but does not provide any benefits in terms of prolonging the pregnancy. The procedure may increase the likelihood of vaginal delivery and lower the rates of uterine atony.

Whole exome sequencing discloses a pathogenic MTM1 gene mutation in a continuous polyhydramnios family in China: Case report and literature review.

Polyhydramnios can be caused by genetic defects at times. However, to establish an accurate diagnosis and provide a precise prenatal consultation in a given case is still a great challenge toward obstetricians. To uncover the genetic cause of polyhydramnios in the two consecutive pregnancies, we performed whole-exome sequencing of DNA for the second suffering fetuses, their parents, and targeted sanger sequencing of other members of this family. We discovered a hemizygous truncating variant in MTM1 gene, c.438_439 del (p. H146Q fs*10) in this Chinese family. In the light of the molecular discoveries, the fetus's clinical phenotype was considered to be a good fit for X-linked myotubular myopathy (XLMTM). There is no related research to the prenatal manifestations of MTM1-related XLMTM among Chinese population, and this is the first one to present. Though the etiology of polyhydramnios is complicated, WES may provide us with a creative avenue in prenatal diagnosis.

Report and follow-up on two new patients with congenital mesoblastic nephroma.

BACKGROUND: Tumors are rare in neonatal age. Congenital mesoblastic nephroma (CMN) is a usually benign renal tumor observed at birth, or in the first months of life. It may also be identified prenatally and associated with polyhydramnios leading to preterm delivery. Effective treatment is surgical in most cases, consisting in total nephrectomy. In literature, very few studies report on the neonatal management of such a rare disease, and even less are those describing its uncommon complications. CASES PRESENTATION: We report on two single-center newborns affected with CMN. The first patient is a preterm female baby, born at 30+ 1 weeks of gestation (WG) due to premature labor, with prenatal (25 WG) identification of an intra-abdominal fetal mass associated with polyhydramnios. Once obtained the clinical stability, weight gain, instrumental (computed tomography, CT, showing a 4.8 × 3.3 cm left renal neoformation) and histological/molecular characterization of the lesion (renal needle biopsy picture of classic CMN with ETV6-NTRK3 translocation), a left nephrectomy was performed at 5 weeks of chronological age. The following clinical course was complicated by intestinal obstruction due to bowel adherences formation, then by an enterocutaneous fistula, requiring multiple surgical approaches including transitory ileo- and colostomy, before the conclusive anastomoses intervention. The second patient is a 17-day-old male term baby, coming to our observation due to postnatal evidence of palpable left abdominal mass (soon defined through CT, showing a 7.5 × 6.5 cm neoformation in the left renal lodge), feeding difficulties and poor weight gain. An intravenous diuretic treatment was needed due to the developed hypertension and hypercalcemia, which regressed after the nephrectomy (histological diagnosis of cellular CMN with ETV6-NTRK3 fusion) performed at day 26. In neither case was chemotherapy added. Both patients have been included in multidisciplinary follow-up, they presently show regular growth and neuromotor development, normal renal function and no local/systemic recurrences or other gastrointestinal/urinary disorders. CONCLUSIONS: The finding of a fetal abdominal mass should prompt suspicion of CMN, especially if it is associated with polyhydramnios; it should also alert obstetricians and neonatologists to the risk of preterm delivery. Although being a usually benign condition, CMN may be associated with neonatal systemic-metabolic or postoperative complications. High-level surgical expertise, careful neonatological intensive care and histopathological/cytogenetic-molecular definition are the cornerstones for the optimal management of patients. This should also include an individualized follow-up, oriented to the early detection of any possible recurrences or associated anomalies and to a better quality of life of children and their families.

Nonfamilial VACTERL-H Syndrome in a Dizygotic Twin: Prenatal Ultrasound and Postnatal 3D CT Findings.

Background: VACTERL association is a widely known congenital malformation that includes vertebral, anal, cardiac, tracheoesophageal, renal, and limb anomalies. Patients with VACTERL and hydrocephalus appear to form a distinct group, both genetically and phenotypically, and their condition has been called VACTERL-H syndrome. Most cases of VACTERL-H have been reported postnatally, as VACTER-H syndrome is difficult to diagnose prenatally. Case Presentation: Here, we report a case of VACTERL-H syndrome in a dichorionic and diamniotic twin diagnosed prenatally by ultrasonography and confirmed postnatally by three-dimensional computed tomography (3D CT). A 34-year-old multiparous female was referred to our institution at 31 + 3 weeks gestation for suspected fetal ventriculomegaly. Detailed examinations using two-dimensional and Doppler ultrasounds revealed hydrocephalus, bilateral dysplastic upper arms, radial aplasia, unilateral pulmonary agenesis, dextrocardia with right atrial enlargement, a unilateral hypoplastic ectopic kidney, a single umbilical artery, a tracheoesophageal fistula with a small stomach, polyhydramnios, and anal atresia. Findings from the postnatal 3D CT aligned with the prenatal diagnosis, showing upper-limb agenesis, dextrocardia with pulmonary hypoplasia, tracheoesophageal fistula, imperforate anus, and colon dilatation. The affected 1390-g male twin had an unaffected 1890-g female twin sister and a healthy 6-year-old brother. Conclusions: Upon encountering fetuses with multiple anomalies, including ventriculomegaly, a small stomach with polyhydramnios, an abnormally positioned heart, and upper-limb abnormalities, clinicians should perform systematic ultrasonographic examinations to detect associated anomalies and be aware of VACTERL-H syndrome.

Discrimination of blood metabolomics profiles in neonates with idiopathic polyhydramnios.

This study aimed to compare the blood metabolic status of neonates with idiopathic polyhydramnios (IPH) and those with normal amniotic fluid, and to explore the relationship between IPH and fetal health. Blood metabolites of 32 patients with IPH and 32 normal controls admitted to the Sixth Affiliated Hospital of Sun Yat-sen University between January 2017 and December 2022 were analyzed using liquid chromatography-mass spectrometry (LC-MS/MS). Orthogonal partial least squares discriminant analysis (OPLS-DA) and metabolite enrichment analyses were performed to identify the differential metabolites and metabolic pathways. There was a significant difference in the blood metabolism between newborns with IPH and those with normal amniotic fluid. Six discriminant metabolites were identified: glutamate, serine, asparagine, aspartic acid, homocysteine, and phenylalanine. Differential metabolites were mainly enriched in two pathways: aminoacyl-tRNA biosynthesis, and alanine, aspartate, and glutamate metabolism. CONCLUSIONS: This study is the first to investigate metabolomic profiles in newborns with IPH and examine the correlation between IPH and fetal health. Differential metabolites and pathways may affect amino acid synthesis and the nervous system. Continuous attention to the development of the nervous system in children with IPH is necessary. WHAT IS KNOWN: • There is an increased risk of adverse pregnancy outcomes with IPH, such as perinatal death, neonatal asphyxia, neonatal intensive care admission, cesarean section rates, and postpartum hemorrhage. • Children with a history of IPH have a higher proportion of defects than the general population, particularly central nervous system problems, neuromuscular disorders, and other malformations. WHAT IS NEW: • In neonates with IPH, six differential metabolites were identified with significant differences and good AUC values using LC-MS/MS analysis: glutamic acid, serine, asparagine, aspartic acid, homocysteine, and phenylalanine, which were mainly enriched in two metabolic pathways: aminoacyl-tRNA biosynthesis and alanine, aspartate, and glutamate metabolism. • These differential metabolites and pathways may affect amino acid synthesis and development of the nervous system in neonates with IPH.

Genotypic variability in patients with clinical diagnosis of Bartter syndrome type 3.

Bartter syndrome (BS) is a salt-losing hereditary tubulopathy characterized by hypokalemic metabolic alkalosis with secondary hyperaldosteronism. Confirmatory molecular diagnosis may be difficult due to genetic heterogeneity and overlapping of clinical symptoms. The aim of our study was to describe the different molecular findings in patients with a clinical diagnosis of classic BS. We included 27 patients (26 families) with no identified pathogenic variants in CLCNKB. We used a customized Ion AmpliSeq Next-Generation Sequencing panel including 44 genes related to renal tubulopathies. We detected pathogenic or likely pathogenic variants in 12 patients (44%), reaching a conclusive genetic diagnosis. Variants in SLC12A3 were found in 6 (Gitelman syndrome). Median age at diagnosis was 14.6 years (range 0.1-31), with no history of prematurity or polyhydramnios. Serum magnesium level was low in 2 patients (33%) but urinary calcium excretion was normal or low in all, with no nephrocalcinosis. Variants in SLC12A1 were found in 3 (BS type 1); and in KCNJ1 in 1 (BS type 2). These patients had a history of polyhydramnios in 3 (75%), and the mean gestational age was 34.2 weeks (SD 1.7). The median age at diagnosis was 1.8 years (range 0.1-6). Chronic kidney disease and nephrocalcinosis were present in 1 (25%) and 3 (75%) patients, respectively. A variant in CLCN5 was found in one patient (Dent disease), and in NR3C2 in another patient (Geller syndrome). Genetic diagnosis of BS is heterogeneous as different tubulopathies can present with a similar clinical picture. The use of gene panels in these diseases becomes more efficient than the study gene by gene with Sanger sequencing.