Isolated polyhydramnios in the third trimester or polyhydramnios secondary to late-onset gestational diabetes: is it worth distinguishing?

OBJECTIVE: The aim of this study was to compare pregnancy outcomes of patients with polyhydramnios due to late-onset gestational diabetes mellitus and patients with isolated polyhydramnios. METHODS: Of the women who fully participated in prenatal examinations at Etlik Lady Zübeyde Hospital between January 1, 2018, and December 31, 2019, women with polyhydramnios of nonfetal-placental origin manifesting in the third trimester were retrospectively reviewed. Women with normal 75-g oral glucose tolerance test results between 24 and 28 weeks gestation who met the inclusion criteria were enrolled in the study and divided into two groups based on the results of rescreening with the 75-g oral glucose tolerance test for polyhydramnios in the third trimester: women with isolated polyhydramnios (group 1) and women with late-onset polyhydramnios due to gestational diabetes mellitus (group 2). RESULTS: There were a total of 295 participants, of whom 35 (11.8%) were diagnosed with polyhydramnios due to late-onset gestational diabetes mellitus. There were no differences in the main outcomes. Birthweight and gestational age at birth were identified as independent risk factors for predicting composite maternal outcome {[odds ratio (OR)=1.273, 95% confidence interval (CI) 1.063-1.524, p=0.009]} and composite neonatal outcome (OR=0.606, CI 0.494-0.744, p<0.001), respectively. CONCLUSION: Polyhydramnios in late pregnancy without evidence of pregnancy-related causes leading to polyhydramnios may be a sign of late-onset gestational diabetes mellitus in women with a normal prior oral glucose tolerance test. As pregnancy outcomes and management were indifferent, it does not seem necessary or useful to diagnose whether or not late-onset gestational diabetes mellitus is present.

Relationship between increased maternal serum free human chorionic gonadotropin levels in the second trimester and adverse pregnancy outcomes: a retrospective cohort study.

BACKGROUND: A retrospective cohort study was conducted to collect the data of pregnant women who received hospital delivery in Hangzhou Women's Hospital from January 2018 to December 2020, and who participated in the second trimester (15-20+6 weeks) of free beta human chorionic gonadotropin (free ß-hCG). And the study was conducted to explore the relationship between maternal serum free ß-hCG and adverse pregnancy outcomes (APO). METHODS: We retrospectively analyzed the clinical data of 1,978 women in the elevated maternal serum free ß-hCG group (free ß-hCG ≥ 2.50 multiples of the median, MoM) and 20,767 women in the normal group (0.25 MoM ≤ free ß-hCG < 2.50 MoM) from a total of 22,745 singleton pregnancies, and modified Poisson regression analysis was used to calculate risk ratios (RRs) and 95% confidence intervals (CI) of the two groups. RESULTS: The gravidity and parity in the elevated free ß-hCG group were lower, and the differences between the groups were statistically significant (all, P < 0.05). The risks of polyhydramnios, preeclampsia, and hyperlipidemia, were increased in women with elevated free ß-hCG levels (RRs: 1.996, 95% CI: 1.322-3.014; 1.469, 95% CI: 1.130-1.911 and 1.257, 95% CI: 1.029-1.535, respectively, all P < 0.05), intrauterine growth restriction (IUGR) and female infants were also likely to happen (RRs = 1.641, 95% CI: 1.103-2.443 and 1.101, 95% CI: 1.011-1.198, both P < 0.05). Additionally, there was an association between elevated AFP and free ß-hCG levels in second-trimester (RR = 1.211, 95% CI: 1.121-1.307, P < 0.001). CONCLUSIONS: APOs, such as polyhydramnios, preeclampsia, and hyperlipidemia, were increased risks of elevated free ß-hCG levels, IUGR and female infants were also likely to happen. Furthermore, there was an association between elevated AFP levels and elevated free ß-hCG levels in second-trimester. We recommend prenatal monitoring according to the elevated maternal serum free ß-hCG level and the occurrence of APO.

Prenatal diagnosis of chromosomal aberrations by chromosomal microarray analysis and pregnancy outcomes of fetuses with polyhydramnios.

OBJECTIVES: To explore the prenatal clinical utility of chromosome microarray analysis (CMA) for polyhydramnios and evaluate the short and long-term prognosis of fetuses with polyhydramnios. METHODS: A total of 600 singleton pregnancies with persistent polyhydramnios from 2014 to 2020 were retrospectively enrolled in this study. All cases received amniocentesis and were subjected to CMA results. All cases were categorized into two groups: isolated polyhydramnios and non-isolated polyhydramnios [with soft marker(s) or with sonographic structural anomalies]. All fetuses were followed up from 6 months to five years after amniocentesis to acquire short and long-term prognosis. RESULTS: The detection rates of either aneuploidy or pathogenic copy number variants in fetuses with non-isolated polyhydramnios were significantly higher than those with isolated polyhydramnios (5.0 vs. 1.5%, p = 0.0243; 3.6 vs. 0.8%, p = 0.0288). The detection rate of total chromosomal abnormalities in the structural abnormality group was significantly higher than that in the isolated group (10.0 vs. 2.3%, p = 0.0003). In the CMA-negative cases, the incidence of termination of pregnancy, neonatal and childhood death, and non-neurodevelopmental disorders in fetuses combined with structural anomalies was significantly higher than that in fetuses with isolated polyhydramnios (p < 0.05). We did not observe any difference in the prognosis between the isolated group and the combined group of ultrasound soft markers. In addition, the risk of postnatal neurodevelopmental disorders was also consistent among the three groups (1.6 vs. 1.3 vs. 1.8%). CONCLUSION: For low-risk pregnancies, invasive prenatal diagnosis of isolated polyhydramnios might be unnecessary. CMA should be considered for fetuses with structural anomalies. In CMA-negative cases, the prognosis of fetuses with isolated polyhydramnios was good, and polyhydramnios itself did not increase the risk of postnatal neurological development disorders. The worse prognosis mainly depends on the combination of polyhydramnios with structural abnormalities.

Large congenital cervical mass in a neonate: prenatal diagnosis and postnatal management of teratoma: a case report.

INTRODUCTION: Cervical teratomas are rare congenital neoplasms that can cause neonatal airway obstruction if large. CASE PRESENTATION: The female Persian neonate displayed respiratory distress at birth, with a 7 cm × 8 cm cystic solid mass identified on the left side of the neck. Antenatal ultrasonography revealed polyhydramnios. Despite initial stabilization, the infant required intubation and mechanical ventilation due to persistent respiratory distress. Imaging confirmed a cystic mass compressing the trachea, ruling out cystic hygroma. Surgical resection on postnatal day 17 revealed a 10 cm × 10 cm solid cystic structure, histologically identified as an immature teratoma. CONCLUSION: Despite risks of poor fetal and postnatal outcome from large cervical teratomas, early surgical resection after airway stabilization can result in recovery. Proper multidisciplinary management of respiratory distress from such tumors is paramount.

Congenital chloride diarrhoea in a Chinese infant with a compound heterozygous SLC26A3 mutation.

INTRODUCTION: Congenital chloride diarrhoea (CCD) is an autosomal recessive condition that causes secretory diarrhoea and potentially deadly electrolyte imbalances in infants because of solute carrier family 26 member 3 (SLC26A3) gene mutations. CASE PRESENTATION: A 7-month-old Chinese infant with a history of maternal polyhydramnios presented with frequent watery diarrhoea, severe dehydration, hypokalaemia, hyponatraemia, failure to thrive, metabolic alkalosis, hyperreninaemia, and hyperaldosteronaemia. Genetic testing revealed a compound heterozygous SLC26A3 gene mutation in this patient (c.269_270dup and c.2006 C > A). Therapy was administered in the form of oral sodium and potassium chloride supplements, which decreased stool frequency. CONCLUSIONS: CCD should be considered when an infant presents with prolonged diarrhoea during infancy, particularly in the context of maternal polyhydramnios and dilated foetal bowel loops.

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.

[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.

Induction of labor in term pregnancies with isolated polyhydramnios: Is it beneficial or harmful?

OBJECTIVE: To compare rates of adverse pregnancy outcomes in term pregnancies complicated by polyhydramnios between women who had induction of labor (IOB) versus women who had expectant management. METHODS: This multicenter retrospective study included term pregnancies complicated by isolated polyhydramnios. Patients who underwent IOB were compared with those who had expectant management. The primary outcome was defined as a composite adverse maternal outcome, and secondary outcomes were various maternal and neonatal adverse outcomes. Univariate analyses were followed by multivariate logistic regression. RESULTS: A total of 865 pregnancies with term isolated polyhydramnios were included: 169 patients underwent IOB (19.5%), while 696 had expectant management and developed spontaneous onset of labor (80.5%). Women who underwent IOB had significantly higher rates of composite adverse maternal outcome (23.1% vs 9.8%, P < 0.01), prolonged hospital stay, perineal tear grade 3/4, intrapartum cesarean, postpartum hemorrhage, blood products transfusion, and neonatal asphyxia compared with expectant management. While the perinatal fetal death rate was similar between the groups (0.6% vs 0.6%, P = 0.98), the timing of the loss was different. Four women in the expectant management group had a stillbirth, while in the induction group one case of intrapartum fetal death occurred due to uterine rupture. Multivariate analyses revealed that IOB was associated with a higher rate of composite adverse maternal outcome (adjusted odds ratio, 2.22 [95% CI, 1.28-3.83]; P < 0.01). CONCLUSION: IOB in women with term isolated polyhydramnios is associated with higher rates of adverse maternal outcomes in comparison to expectant management. Further research is needed to determine the optimal approach for the management of isolated polyhydramnios at term.

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.

A case of pregnancy with severe polyhydramnios related to long-term use of lithium.

OBJECTIVES: Severe polyhydramnios during pregnancy may be associated with long-term lithium use and presents considerable challenges. This complication, which has been linked to induced nephrogenic diabetes insipidus (NDI), underscores the necessity for cautious management of pregnant women with bipolar disorder. This case report aims to elucidate the relationship between long-term lithium use, pregnancy, and the development of severe polyhydramnios, emphasizing the importance of diagnosing NDI in order to prevent obstetric and neonatal complications. METHODS: We present the case of a 42-year-old primigravida undergoing long-term lithium treatment for bipolar disorder type I, who developed severe polyhydramnios at 34 weeks of gestation. Clinical data including obstetric monitoring and neonatal outcomes were analyzed. RESULTS: This case emphasizes the need for heightened awareness and proactive measures to mitigate the risk associated with lithium treatment during pregnancy. Close monitoring and timely interventions are essential to ensure optimal outcomes for both mother and fetus. CONCLUSIONS: Our article puts forth the hypothesis that there is a link between lithium use during pregnancy and the occurrence of polyhydramnios and Nephrogenic Diabetes Insipidus (NDI), which may lead to severe obstetric and neonatal complications. This case report contributes to the limited literature on the subject and gives doctors practical advice that may help them make a better risk-benefit analysis. Further research is warranted in order to refine risk assessment protocols and management strategies in this complex clinical scenario.

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.

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.

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.

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.

Atresia pilórica y síndrome de Down: falso signo de la doble burbuja prenatal / Pyloric atresia and Down’s syndrome: prenatal double bubble false sign

La atresia pilórica es una malformación rara, presenta una incidenciade 1:100.000 recién nacidos vivos y la ratio hombre/mujer es de 1/1.Generalmente es una malformación aislada, con buen pronóstico, peroentre el 20-40% de los casos se asocia a epidermólisis bullosa y enmenor frecuencia a otras atresias intestinales múltiples.Presentamos un caso de recién nacido pretérmino con atresia piló-rica con el diagnóstico prenatal de polihidramnios, atresia duodenal consigno de ‘doble burbuja’ y sospecha de síndrome de Down.(AU)

Objective. Pyloric atresia is a rare malformation, with an incidenceof 1:100,000 live newborns. Male to female ratio is 1/1. Typically, itis an isolated malformation, with a good prognosis, but 20-40% ofcases present epidermolysis bullosa, and to a lesser extent, multipleintestinal atresias.We present the case of a pre-term newborn prenatally diagnosedwith polyhydramnios, duodenal atresia with “double bubble” sign, andsuspected Down’s syndrome, who eventually had pyloric atresia.(AU)

Severe polyhydramnios as neonatal presentation of Bartter's syndrome type IV / Polihidrâmnios grave como manifestação neonatal da síndrome de Bartter tipo IV

Abstract Introduction: Bartter's syndrome comprises a heterogeneous group of inherited salt-losing tubulopathies. There are two forms of clinical presentation: classical and neonatal, the most severe type. Types I and II account for most of the neonatal cases. Types III and V are usually less severe. Characteristically Bartter's syndrome type IV is a saltlosing nephropathy with mild to severe neonatal symptoms, with a specific feature - sensorineural deafness. Bartter's syndrome type IV is the least common of all recessive types of the disease. Description: the first reported case of a Portuguese child with neurosensorial deafness, polyuria, polydipsia and failure to thrive, born prematurely due to severe polyhydramnios, with the G47R mutation in the BSND gene that causes Bartter's syndrome type IV. Discussion: there are few published cases of BS type IV due to this mutation and those reported mostly have moderate clinical manifestations which begin later in life. The poor phenotype-genotype relationship combined with the rarity of this syndrome usually precludes an antenatal diagnosis. In the presence of a severe polyhydramnios case, with no fetal malformation detected, normal karyotype and after maternal disease exclusion, autosomal recessive diseases, including tubulopathies, should always be suspected.

Resumo Introdução: a síndrome de Bartter inclui um grupo heterogéneo de tubulopatias hereditárias perdedoras de sal. Existem duas formas de apresentação clínica: clássica e neonatal, a forma mais grave. Os tipo I e II representam a maioria dos casos neonatais. Os tipos III e V são geralmente menos graves. Caracteristicamente, a síndrome de Bartter tipo IV é uma nefropatia perdedora de sal com sintomas neonatais ligeiros a graves, com um aspeto especí- fico - surdez neurossensorial. A síndrome de Bartter tipo IV é o tipo menos comum das formas recessivas da doença. Descrição: relatamos o primeiro caso de uma criança portuguesa, com surdez neurossensorial, poliúria, polidipsia e restrição de crescimento, nascida prematuramente devido a polihidrâmnios grave, homozigótica para a mutação G47R do gene BSND, responsável pela síndrome de Bartter tipo IV. Discussão: são raros os casos publicados sobre síndrome de Bartter tipo IV atribuída a esta mutação, e a maioria referem-se a diagnósticos mais tardios, com manifestações clínicas ligeiras. A fraca correlação fenótipo-genótipo combinada com a raridade desta síndrome tornam o diagnóstico pré-natal desafiante. Perante um caso de polihidrâmnios grave em um feto sem malformações aparentes, cariótipo normal e após exclusão de patologia materna, as doenças autossómicas recessivas, incluindo as tubulopatias, devem ser sempre consideradas.

Prenatal diagnosis and genetic analysis of two fetuses with paternally derived 17q12 microdeletions / 中华医学遗传学杂志

OBJECTIVE@#To reported on two fetuses diagnosed with 17q12 microdeletion syndrome.@*METHODS@#The two fetuses were respectively found to have renal abnormalities and polyhydramnios upon second and third trimester ultrasonography. Umbilical cord blood of the first fetus and amniotic fluid of the second fetus were subjected to single nucleotide polymorphism array (SNP-array) analysis. After 17q12 microdeletion was found in the first fetus, SNP-array was carried out on peripheral blood samples of the parents to determine its origin. With the medical history of the parents taken into consideration, the father underwent high-throughput sequencing for 565 urinary system-related genes to exclude pathogenic or likely pathogenic variants associated with congenital malformations of the urinary and reproductive systems.@*RESULTS@#In both fetuses, SNP-array has revealed a 1.42 Mb deletion at 17q12, or arr[hg19]17q12 (34 822 465-36 243 365) × 1. In both cases the microdeletion was inherited from the father, in whom no urinary disease-related pathogenic or likely pathogenic variants was identified.@*CONCLUSION@#Paternally derived 17q12 microdeletions probably underlay the genetic etiology of the two fetuses with renal ultrasound abnormalities and polyhydramnios. SNP-array can enable the diagnosis and facilitate genetic counseling and prenatal diagnosis for the families.