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Purpose: Fetal movements are crucial indicators of fetal well-being, with reduced fetal movements (RFM) suggesting potential fetal compromise. Fetal growth restriction (FGR), often linked to placental insufficiency, is a major cause of perinatal morbidity and mortality. This study aimed to investigate the neonatal, labor, and placental outcomes of FGR pregnancies with and without RFM at term., Methods: In this retrospective study, data from all term, singleton deliveries with FGR and concomitant RFM were obtained and compared to an equal control group of FGR without RFM. Maternal characteristics, pregnancy and neonatal outcomes, and placental histology were compared. The primary outcome was a composite of adverse neonatal outcomes. A multivariable regression analysis was performed to identify independent associations with adverse neonatal outcomes., Results: During the study period, 250 FGR neonates with concomitant RFM and an equal control group were identified. The groups did not differ in maternal demographics aside from significantly higher rates of maternal smoking in the RFM group (p < 0.001). Polyhydramnios and oligohydramnios (p = 0.032 and p = 0.007, respectively) and meconium-stained amniotic fluid (p < 0.001) were more prevalent in the FGR+RFM group. Additionally, the RFM group showed higher rates of adverse neonatal outcomes despite having larger neonates (p = 0.047 and p < 0.001, respectively). No significant differences were observed in placental findings. Logistic regression identified RFM as an independent predictor of adverse neonatal outcomes (aOR 2.45, 95% CI 1.27-4.73, p = 0.008)., Conclusion: Reduced fetal movements are significant and independent predictors of worse neonatal outcomes in FGR pregnancies, suggesting an additional acute insult on top of underlying placental insufficiency., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: There is a paucity of literature providing evidence-based guidelines for the management of large placental chorioangioma (≥ 4 cm in diameter). The objectives of this study were to compare outcomes between patients managed expectantly and those undergoing in-utero intervention and to describe the different in-utero techniques used for cessation of blood flow to the tumor and the associated outcome., Methods: This was a retrospective cohort study of 34 patients referred for the management of large placental chorioangioma in a single center between January 2011 and December 2022, who were managed expectantly or underwent in-utero intervention. In-utero intervention was performed when the fetus developed any signs of impending compromise, including high combined cardiac output (CCO), worsening polyhydramnios or abnormal fetal Doppler velocimetry findings. Interventions included radiofrequency ablation (RFA), interstitial laser ablation (ILA) and single-port or two-port fetoscopic laser photocoagulation (FLP). Treatment selection was dependent on the proximity of the tumor to the umbilical cord insertion (UCI) and placental location. The two-port technique was performed in patients with a chorioangioma with large feeding vessels (≥ 3 mm) located in the posterior placenta, in which one port was used for occlusion using bipolar forceps and the other port was used for laser photocoagulation of the feeding vessels downstream. The single-port technique was used for chorioangioma with small feeding vessels (< 3 mm) located in the posterior placenta. ILA or RFA was performed in cases with an anterior placenta. Supportive treatments, including amnioreduction and intrauterine transfusion (IUT), were performed for worsening polyhydramnios and suspected fetal anemia based on middle cerebral artery Doppler flow studies, respectively. Comparative statistical analysis between cases undergoing expectant management vs in-utero intervention was performed. Descriptive details were provided for patients who underwent in-utero intervention., Results: Thirty-four cases of large chorioangioma were evaluated, of which 25 (73.5%) were managed expectantly and nine (26.5%) underwent intervention. The frequency of polyhydramnios was significantly higher in the intervention group compared with the expectant-management group (66.7% vs 8.0%, P < 0.001). The live-birth rate among expectantly managed cases with large chorioangioma was significantly higher compared with that in cases that underwent in-utero intervention (96.0% vs 62.5%, P = 0.01). In the intervention group, preoperative CCO was elevated in all cases with available information and preoperative hydrops was present in 33.3% (3/9) of cases. One patient experienced fetal demise following IUT prior to planned FLP. Among the remaining eight patients, four underwent two-port FLP, two underwent single-port FLP, one underwent ILA and one underwent both ILA and RFA. All three cases in which hydrops was present at the time of intervention resulted in fetal demise., Conclusions: In-utero interventions aimed at cessation of blood flow in the feeding vessels are a therapeutic option for the management of cases with large chorioangioma. The two-port percutaneous technique appears to improve the efficiency of FLP when a large chorioangioma with large feeding vessels is located in the posterior placenta. We propose that in-utero interventions for large chorioangioma should be initiated prior to the development of fetal hydrops. © 2023 International Society of Ultrasound in Obstetrics and Gynecology., (© 2023 International Society of Ultrasound in Obstetrics and Gynecology.)

Background: Alterations in the MYH7 gene can cause cardiac and skeletal myopathies. MYH7-related skeletal myopathies are extremely rare, and the vast majority of causal variants in the MYH7 gene are predicted to alter the rod domain of the of ß-cardiac myosin molecule, resulting in distal muscle weakness as the predominant manifestation. Here we describe two unrelated patients harboring an in-frame deletion in the MYH7 gene that is predicted to result in deletion of a single amino acid (p.Glu500del) in the head domain of ß-cardiac myosin. Both patients display an unusual skeletal myopathy phenotype with congenital axial stiffness and muscular hypertonus, but no cardiac involvement., Results: Clinical data, MRI results and histopathological data were collected retrospectively in two unrelated boys (9 and 3.5 years old). Exome sequencing uncovered the same 3-bp in-frame deletion in exon 15 (c.1498&#95;1500delGAG) of the MYH7 gene of both patients, a mutation which deletes a highly conserved glutamate residue (p.Glu500del) in the relay loop of the head domain of the ß-cardiac myosin heavy chain. The mutation occurred de novo in one patient, whereas mosaicism was detected in blood of the father of the second patient. Both boys presented with an unusual phenotype of prenatal polyhydramnios, congenital axial stiffness and muscular hypertonus. In one patient the phenotype evolved into an axial/proximal skeletal myopathy without distal involvement or cardiomyopathy, whereas the other patient exhibited predominantly stiffness and respiratory involvement. We review and compare all patients described in the literature who possess a variant predicted to alter the p.Glu500 residue in the ß-cardiac myosin head domain, and we provide in-silico analyses of potential effects on polypeptide function., Conclusion: The data presented here expand the phenotypic spectrum of mutations in the MYH7 gene and have implications for future diagnostics and therapeutic approaches., (© 2022. The Author(s).)

Objective: To investigate the prenatal diagnosis and prognostic factors of fetal sacrococcygeal teratoma (SCT). Methods: A retrospective analysis was performed on 41 pregnant women who were diagnosed with fetal SCT by prenatal ultrasound at the Women's Hospital, Zhejiang University School of Medicine from January 2014 to September 2021. The prenatal imaging features and pregnancy outcomes, including tumor volume to fetal weight ratio (TFR), proportion of solid tumor, tumor growth rate (TGR), fetal hydrops, placentomegaly and polyhydramnios were analyzed. Receiver operating characteristic (ROC) curve was used to determine the critical values of TFR and TGR for predicting adverse fetal outcomes. Results: (1) Among the 41 pregnant women with fetal SCT, the diagnostic gestational week of ultrasound was (24.2±2.9) weeks (range: 18-28 weeks). Among them, 1 case progressed to fetal hydrops and induced labor at 22 weeks of gestation, 1 case developed intrauterine death and induced labor at 29 weeks of gestation, and 39 pregnancies continued until delivery. Among the 39 cases of continued pregnancy, 1 case underwent cesarean section at 31 weeks of gestation due to malignant polyhydramnios and increased fetal cardiothoracic ratio in the third trimester, 1 case underwent cesarean section at 32 weeks of gestation due to fetal heart failure, and 1 case underwent cesarean section at 32 weeks of gestation due to fetal heart failure and hydrops. The other 36 cases underwent surgical resection of tumor within 3 weeks after birth with good prognosis. (2) TFR>0.12 before 28 weeks of gestation could predict poor fetal prognosis, with a sensitivity of 100.0%, a specificity of 86.1% and an area under curve (AUC) of 0.922 ( P <0.01). Among the fetuses with TFR>0.12, 5/10 had poor prognosis, while the fetuses with TFR≤0.12 all had good prognosis (100%,31/31), and the difference between the two groups was statistically significant ( P <0.001). (3) TGR>48 cm 3 /week could predict poor fetal prognosis with a sensitivity of 100.0%, a specificity of 78.3% and an AUC of 0.880 ( P <0.05). (4) Among the 28 SCT fetuses delivered in our hospital, the incidence rate of poor fetal prognosis was 0 (0/20) in those with solid tumor component<50%, and 5/8 in those with solid tumor component ≥50%, and the difference between the two groups was statistically significant ( P <0.01). The incidence rate of poor fetal prognosis was 2/2 in those with placentomegaly (all with fetal hydrops), and 12% (3/26) in those without placentomegaly. The risk of poor fetal prognosis was 8.67 times higher in those with placentomegaly than those without placentomegaly, and the difference between the two groups was statistically significant ( P <0.05). The incidence rate of poor fetal prognosis in those with polyhydramnios was 3/7, and 10% (2/21) in those without polyhydramnios, but there was no statistically significant difference between the two groups ( P >0.05). Conclusion: TFR combined with solid tumor morphology, TGR, and presence of placentomegaly could predict the adverse pregnancy outcomes of fetal SCT.

Polyhydramnios is a common feature diagnosed by ultrasound in the second half of pregnancy. Biochemical analysis of amniotic fluid can be useful when suspecting Bartter syndrome or digestive atresia but in most of cases, no etiology of polyhydramnios is found because of the complex regulation of amniotic fluid. Aquaporins (AQP) are transmembrane channel proteins contributing to water transfers. Some of them are expressed in fetal membranes and placenta. Their expression has been shown to be disrupted in some pathological conditions such as maternal diabetes, often associated with polyhydramnios. AQP-1, 3 and 8 levels in amniotic fluid were retrospectively measured in patients suffering from polyhydramnios (n=21) from 23 weeks of gestation (WG). They were compared to the levels observed in control subjects (n=96) and their relationship with maternal factors and neonatal issues was analyzed. AQP-1, 3, 8 levels were physiologically fluctuating, AQP-1 levels always being the lowest and AQP-3 the highest, with a significant decrease at the end of pregnancy. AQPs/AFP ratios increased about 8 folds during pregnancy, their kinetic profiles reflecting physiological dynamic evolution of amniotic fluid volume. In polyhydramnios, AQP-3 level tended to be decreased whereas AQP-8 level was decreased from mid-gestation whatever the etiology of polyhydramnios. No significant relationship was found between AQPs levels and either the fetal prematurity degree or macrosomia. No specific pattern was observed in idiopathic polyhydramnios, limiting the interest of AQPs dosage in amniotic fluid in the management of those complicated pregnancies., (© 2021. Society for Reproductive Investigation.)

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., (© 2020 John Wiley & Sons Ltd/University College London.)

Background: 15q24 microdeletion is a relatively new syndrome caused by nonallelic homologous recombination (NAHR) between low-copy repeats (LCRs) in the 15q24 chromosome region. This syndrome is characterized by a spectrum of clinical symptoms including global developmental delay, intellectual disability, facial dysmorphisms, and congenital malformations of the extremities, eye, gastrointestinal tract, genitourinary system, and genitalia., Method: Molecular cytogenetic analysis was performed using whole genome single-nucleotide polymorphism (SNP) microarray analysis. Autopsy examination including gross and microscopic examination were performed. In addition, a thorough review of the literature on 15q24 microdeletion was completed and summarized in table format., Result: Molecular cytogenetic analysis revealed a 3.88 MB interstitial deletion within 15q24.1 to 15q24.3 (74,353,735-78,228,485 bp) in our case. Autopsy examination showed congenital malformations within the genitourinary system and genitalia, including left kidney agenesis and uterus didelphys. After thorough literature review, we found a series of midline defects associated with 15q24 microdeletion syndrome., Conclusion: We report the first case of coexistence of urogenital abnormalities, including left kidney agenesis and uterus didelphys, with 15q24 microdeletion syndrome, which is also associated with midline defects secondary to abnormal development. Since 15q24 microdeletion syndrome is a relatively new entity, fully characterizing its variation and severity requires additional examination of the genetics, molecular profile and structural and functional abnormalities in affected patients. Due to the limited data in the literature, statistical analysis of abnormalities in each organ system is not possible. However, we can predict that novel genetic pathways involving cell migration, adhesion, apoptosis, and embryo development might be discovered with the advanced study of 15q24 microdeletion syndrome., (© 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Chorangiomas of the placenta, benign tumors of chorionic tissue, are a rare placental cause of adverse fetal and maternal outcomes. We describe the case of a large placental chorangioma leading to polyhydramnios as well as consecutive preterm birth and high output cardiac failure of the newborn. Derived from a literature review, we suggest instructions for diagnosis and optimal prenatal care in case of a a suspected placental chorangioma., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Introduction: Hydrallantois is the excessive accumulation of fluid in the allantoic cavities during the last trimester of pregnancy, leading to abdominal wall hernias, cardiovascular shock, abortion, and dystocia. It has been postulated that hydrallantois is associated with structural and/or functional changes in the chorioallantoic membrane. In the present study, we hypothesized that angiogenesis is impaired in the hydrallantoic placenta., Method: Capillary density in the hydrallantoic placenta was evaluated in the chorioallantois via immunohistochemistry for Von Willebrand Factor. Moreover, the expression of angiogenic genes was compared between equine hydrallantois and age-matched, normal placentas., Results: In the hydrallantoic samples, edema was the main pathological finding. The capillary density was significantly lower in the hydrallantoic samples than in normal placentas. The reduction in the number of vessels was associated with abnormal expression of a subset of angiogenic and hypoxia-associated genes including VEGF, VEGFR1, VEGFR2, ANGPT1, eNOS and HIF1A. We believe that the capillary density and the abnormal expression of angiogenic genes leads to tissue hypoxia (high expression of HIF1A) and edema. Finally, we identified a lower expression of genes associated with steroidogenic enzyme (CYP19A1) and estrogen receptor signaling (ESR2) in the hydrallantoic placenta., Discussion: Based on the presented data, we believe that formation of edema is due to disrupted vascular development (low number of capillaries) and hypoxia in the hydrallantoic placenta. The edema leads to further hypoxia and consequently, causes an increase in vessel permeability which leads to a gradual increase in interstitial fluid accumulation, resulting in an insufficient transplacental exchange rate and accumulation of fluid in the allantoic cavity., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Kabuki syndrome (KS) is a disorder of epigenetic dysregulation due to heterozygous mutations in KMT2D or KDM6A, genes encoding a lysine-specific methyltransferase or demethylase, respectively. The phenotype is highly variable, including congenital cardiac and renal anomalies, developmental delay, hypotonia, failure to thrive, short stature, and immune dysfunction. All affected individuals have characteristic facial features. As KS natural history has not been fully delineated, limited information exists on its prenatal and perinatal history. Two tertiary centers collected retrospective data from individuals with KS (N = 49) using a questionnaire followed by review of medical records. Data from 49 individuals (age range: 7 months-33 years; 37% male; 36 with KMT2D mutations, 2 with KDM6A mutations, and 11 diagnosed clinically) were examined. Polyhydramnios affected 16 of 39 (41%) pregnancies. Abnormal quad screens in four out of nine (44%) pregnancies and reduced placental weights also complicated KS pregnancies. These data comprise the first large dataset on prenatal and perinatal history in individuals with confirmed (genetically or clinically) KS. Over a third of pregnancies were complicated by polyhydramnios, possibly secondary to abnormal craniofacial structures and functional impairment of swallowing. The differential diagnosis for polyhydramnios in the absence of intrauterine growth retardation should include KS., (© 2019 Wiley Periodicals, Inc.)

Objectives: Our study aimed to analyze the differences in intra-amniotic pressures in patients with polyhydramnios with and without symptoms., Study Design: We recruited patients with pregnancies in which amnioreduction was performed for polyhydramnios in the Department of Fetal-Maternal Medicine at Nagara Medical Center between April 2017 and August 2018. Amnioreduction was performed for severe polyhydramnios with maternal symptoms [symptomatic group] or polyhydramnios without maternal symptoms [asymptomatic group] such as abdominal distension, dyspnea, or threatened premature labor. We measured the intra-amniotic pressure after every 200 ml volume reduction during the amnioreduction., Results: A total of 27 patients who underwent amnioreduction were classified into symptomatic (66.7%, 18/27) and asymptomatic (33.3%, 9/27) groups. Gestational age, amniotic fluid index at the time of amnioreduction, and the volume of amniotic fluid removed were not significantly different between the symptomatic and asymptomatic groups [median 32.4 weeks vs. 33.1 weeks, median 38.0 cm vs. 39.0 cm, and median 1500 ml vs. 2500 ml, respectively]. However; the intra-amniotic pressure before amnioreduction was significantly higher in the symptomatic group than in the asymptomatic group [median 15.0 mmHg (range, 10-27) vs. 10.0 mmHg (range, 6.0-13); p < 0.005]. After amnioreduction, these pressures decreased significantly to median 9.0 mmHg (range, 5.0-13) (p < 0.001) in the symptomatic and 7.0 mmHg (range, 4.0-11) (p < 0.05) in the asymptomatic group. The median intra-amniotic pressure gradually decreased and reached a plateau during the amnioreductions in both groups., Conclusions: With polyhydramnios, the intra-amniotic pressure was significantly higher in the symptomatic group than in the asymptomatic group. Therefore, uterine pressure tolerance might vary according to the individual. In addition, intra-amniotic pressure monitoring might enhance the safety during amnioreduction procedures to avoid drastic and potentially harmful pressure changes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Feto-fetal transfusion syndrome is a pathological process unique to diamniotic monochorionic pregnancies. It is the consequence of an unbalanced fetal blood flow through communicating vessels within a shared placenta. When it occurs, a polyuric, hypervolemic recipient twin co-exists with a hypovolemic oliguric donor. The presence of polyhydramnios or oligohydramnios is considered a poor prognostic indicator, whereas normal amniotic fluid volumes indicate a lack of clinically significant twintwin transfusion. In addition, the spontaneous normalization of amniotic fluid volume is usually seen as a favorable prognostic sign. Here, however, we present a case of feto-fetal transfusion in a 31 year-old primigravida at 19 week, in which the spontaneous normalization of amniotic fluid volume in the recipient twin preceded the death of the donor.

The objective of this meta-analysis was to summarize the existing literature examining the risk of chromosomal aberrations in idiopathic polyhydramnios. Search was conducted by a research librarian in five databases. Language and time restrictions were not applied. By independent screening of titles and abstracts, two investigators selected original researches examining the risk of chromosomal aberrations in idiopathic polyhydramnios. Twenty articles were included, encompassing a total of 1729 pregnancies with idiopathic polyhydramnios. The average rate of chromosomal aberrations in these cases was 2.8 ± 3.7%, ranging between 0% and 13.8%. No studies were found examining the relative risk for chromosomal abnormalities in low-risk women with idiopathic polyhydramnios. An analysis of seven case-control trials, including women at high risk for aneuploidy, yielded a relative risk of 3.09 (95% confidence interval 1.92-4.97) for chromosomal aberration. Overall quality of evidence was rated as very low using Grading of Recommendations Assessment, Development and Evaluation criteria. In conclusion, the suboptimal quality of the evidence precludes from drawing any solid recommendations regarding routine karyotype testing in idiopathic polyhydramnios cases, especially in women at low risk for chromosomal aberrations. Future high-quality trials addressing the discussed methodological shortcomings should be conducted to assess this important issue., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Objective: To evaluate placental thickness, Doppler velocimetry, biophysical profile and perinatal outcomes in pregnancies complicated by idiopathic polyhydramnios., Materials and Methods: This prospective case-control study was conducted on 139 pregnant women, of these 70 patients with idiopathic polyhydramnios comprised the study group and 60 pregnant women comprised the control group. Risk factors recorded were; age, parity, body mass index (BMI), gestational weeks, amniotic fluid index (AFI), biophysical profiles (BPP), placental thickness, middle cerebral artery pulsatility index (MCA PI), umbilical artery Doppler velocimetry (Umb A S/D) values and perinatal outcomes., Results: Sixty-nine of the cases had mild-moderate (AFI: 250-450 mm) polyhydramnios (%98.5) and one of the cases had severe polyhydramnios (>450 mm) in study group. There was no statistically significant difference between the groups in terms of age, parity, BMI, gestational weeks, fetal birth weights and BPP (p > 0.05). Placental thickness, MCA PI and UA S/D values showed statistically significant difference between the groups (p < 0.05). The fetuses with lower placental thickness had lower scores of biophysical profile. There were negative correlations between placental thickness and AFI (r = -0.265), umbilical artery S/D and placental thickness (r = -0.212), MCA PI and AFI (r = -171, p = 0.44). However there was a positive correlation between AFI and umbilical artery Doppler values (r = 0.450)., Conclusion: Idiopathic polyhydramnios is associated with decreased placental thickness, impaired uterine, umbilical and middle cerebral artery flow.

Twin anemia-polycythemia sequence (TAPS) complicates up to 6% of monochorionic diamniotic twin pregnancies, typically in the late second or third trimester. The presence of only a few and very small arteriovenous vascular anastomoses characterizes the underlying angioarchitecture at the chorionic plate in cases of TAPS. In monoamniotic twins, large vascular anastomoses can usually be seen at the placental vascular equator, and therefore one would not expect the development of TAPS in monoamniotic twins. We report a case of TAPS in a monoamniotic pregnancy at 26 + 5 weeks' gestation which responded favorably to fetoscopic laser coagulation of the small placental anastomoses, resolving severe anemia in one twin and polycythemia in the other. The pregnancy continued until 32 + 5 weeks, when worsening cord entanglement with increased resistance and the development of postsystolic notches in the umbilical artery of one twin prompted delivery by Cesarean section. There was only a moderate difference in neonatal hemoglobin concentrations, with the former polycythemic twin needing a single partial volume exchange transfusion. The postnatal course of the neonates was uneventful, according to their gestational age at birth. To our knowledge this is the first case report describing successful laser therapy for TAPS in monoamniotic twins., (Copyright © 2013 ISUOG. Published by John Wiley & Sons, Ltd.)

Germ cell tumors (GCTs) may occur in both children and adults and include a broad array of histologic subtypes, such as teratoma, seminoma (known as dysgerminoma in the ovary and germinoma in the pineal gland), choriocarcinoma, yolk sac tumor, embryonal cell carcinoma, and mixed GCT. In adults, GCTs occur most commonly in the gonads. In children, sacrococcygeal tumors predominate. Teratomas are a common form of GCT. They are defined histologically as containing tissues derived from all 3 germ cell layers: ectoderm, mesoderm (most teratomas contain fat, an imaging hallmark, which is a mesodermal derivative), and endoderm. Teratomas are also classified as mature or immature, depending on the degree of differentiation of its components, and in adults, immature tumors are more likely to exhibit malignant behavior., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Twin reversed arterial perfusion (TRAP) sequence is a serious complication of monochorionic twin pregnancies, in which arterioarterial anastomoses allow blood flow from a 'pump' fetus to an acardiac fetus via reversed flow in the latter's umbilical artery. Several trial treatments for TRAP sequence have been reported, but all of these have been invasive. We present a case of TRAP sequence in which high-intensity focused ultrasound (HIFU) was applied to the umbilical artery of the anomalous twin at 26 weeks as a non-invasive fetal therapy. The HIFU intensity was set at approximately 2300 W/cm(2) with exposure periods of 10 s. Color Doppler ultrasound showed a decrease in blood supply to the anomalous twin, although complete occlusion of the targeted vessel was not achieved. Delivery was by Cesarean section at 29 weeks' gestation and the pump twin survived, without severe clinical complications at 6 months., (Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.)

Pontocerebellar hypoplasia exhibits a diverse range of etiologies, including six known autosomal recessive, single gene disorders. We describe a molecularly confirmed case of pontocerebellar hypoplasia type 4, a rare and severe neonatal phenotype with a novel TSEN54 mutation, presenting with polyhydramnios, hypertonia, and early neonatal death. The patient manifested severe hypoplasia of the cerebellum and brainstem. The neuropathologic findings in pontocerebellar hypoplasia type 4 develop late in gestation, and therefore prenatal diagnosis with ultrasonography is of limited use. Establishing a molecular diagnosis in the proband is critical for allowing couples to plan future pregnancies., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Perlman syndrome is a rare syndrome characterized by polyhydramnios, fetal overgrowth, facial dysmorphism, visceromegaly, nephroblastomatosis and predisposition to Wilms tumor. Here we report on a newborn with a prenatal history of polyhydramnios who presented with nephromegaly, hypotonia, macrosomia, facial dysmorphism, cholestasis and characteristic ultrasonographic and computed tomographic appearances of renal abnormalities that are observed with Perlman syndrome. Perlman syndrome is a rare entity with a high neonatal mortality rate. This is the first case in which cholestasis has been observed. Close follow-up should be carried out for early detection of Wilms tumor., (© 2011 The Authors. Congenital Anomalies © 2011 Japanese Teratology Society.)

We present the case of an 18-year-old woman with her second pregnancy, whose first pregnancy was complicated by polyhydramnios. At week 30, the dysmorph fetus died in utero and was delivered via cesarean section due to placental abruption, but the exact diagnosis was not recognized at that time. During the patient's second pregnancy, increasing polyhydramnios was detected from the 19th gestational week. Ultrasound signs of fetal malformation also appeared later: abnormal position of limbs, narrow chest, oedema around the skull, and absence of stomach content. At week 34, decompression amniocentesis became necessary. Chromosome analysis was also carried out and a normal karyotype was obtained. At 39th gestational week, amnioscopy proved meconium staining of the amniotic fluid, thus labour was induced. Following amniotomy, sustained fetal bradycardia commenced and an emergency caesarean section was performed. Despite complex resuscitation, the 3000 gram male newborn died 2.5 hours after delivery, due to respiratory failure. Autopsy and histopathologic examination revealed a large, oedematous head, micrognathia, macroglossia, laryngeal oedema, narrow chest with pulmonary hypoplasia, gracile limbs with muscle atrophy, gracile and bent fingers, and a short umbilical cord. Based on the medical history, the course of the disease and the phenotype of the newborn, Pena-Shokeir syndrome type I was diagnosed. In the second part of the article, we review the etiology, pathogenesis, prenatal diagnosis and differential diagnosis of this syndrome, as well as some aspects of genetic counseling in such cases. To our knowledge, this is the first reported case of Pena-Shokeir syndrome in Hungary.

Background: The homozygous deletion of Pkd1 in the mouse results in embryonic lethality with renal cysts and hydrops fetalis, but there is no precise data on the segmental origin of cysts and potential changes associated with polyhydramnios., Methods: We used Pkd1-null mice to investigate cystogenesis and analyze the amniotic fluid composition from embryonic day 12.5 (E12.5) to birth (n = 257 embryos)., Results: Polyhydramnios was consistently observed from E13.5 in Pkd1(-/-) embryos, in absence of placental abnormalities but with a significantly higher excretion of sodium and glucose from E13.5 through E16.5, and increased cyclic adenosine 3'5-monophosphate (cAMP) levels at E14.5 and E15.5. The Pkd1(-/-) embryos started to die at E13.5, with lethality peaking at E15.5, corresponding to the onset of cystogenesis. The first cysts in Pkd1(-/-) kidneys emerged at E15.5 in mesenchyme-derived segments at the cortico-medullary junction, with a majority of glomerular cysts and fewer proximal tubule cysts (positive for megalin). The cysts extended to ureteric bud-derived collecting ducts (positive for Dolichos biflorus agglutinin lectin) from E16.5., Conclusions: These studies indicate that Pkd1 deletion is associated with a massive loss of solutes (from E13.5) and increased cAMP levels (E14.5) associated with polyhydramnios. These abnormalities precede renal cysts (E15.5), first derived from glomeruli and proximal tubules and later from the collecting ducts, reflecting the expression pattern of Pkd1 in maturing epithelial cells.

Chorangioma has been referred to as a hamartoma-like, or a hyperplastic capillary lesion, rather than a true neoplasm. Its incidence is 1 in 100 placentas. In chorangiomas larger than 4 cm, there can be significant effects on the hemodynamic and circulatory processes of the fetus, leading to grave clinical consequences, such as polyhydramnios and fetal heart failure. Chorangiomas can show various histopathologic pictures, ranging from vascular to cellular, and can undergo degenerative changes. They can be diagnosed prenatally by ultrasound, color Doppler imaging, and magnetic resonance imaging (MRI). Chorangioma must be differentiated from other villous capillary lesions, namely, chorangiomatosis and chorangiosis. They have overlapping similarities with chorangioma, and have clinical implications. Chorangiomatosis has been associated with negative fetal outcomes such as intrauterine growth retardation (IUGR) and preeclampsia. Chorangiosis is associated with maternal diabetes mellitus. Another rarer differential is chorangioma with trophoblast proliferation ("chorangiocarcinoma," a probable misnomer), a rare proliferation of trophoblastic tissue seen in the vicinity of otherwise benign chorangioma. Treatment modalities of chorangioma include endoscopic devascularization, alcoholic ablation, and interstitial laser coagulation. In this article, we will review the clinical and pathologic picture of chorangioma as well as treatment, and discuss its main differentials.

The prenatal diagnosis of Bartter syndrome can be based on the high chloride level in the amniotic fluid. Microscopic examination of the placenta in untreated cases showed extensive mineralization in the chorionic villi in previous studies. Two cases were presented at 26-29 weeks of gestation with severe polyhydramnios. The mothers were treated with Indomethacin, KCl, and serial amniocentesis in order to reduce the amniotic fluid volume and prevent fetal hypokalemia. The microscopic examination of the placenta revealed focal calcification and acute atherosis in placental vessels. The treatment with Indomethacin in the antenatal period can prevent severe nephrocalcinosis.

Objective: To test the hypothesis that cervical shortening in polyhydramnios reflects the degree of excess amniotic fluid, and increases with normalisation of amniotic fluid volume., Study Design: Prospective cohort study of 40 women with monochorionic twins undergoing interventional procedures between 16-26 weeks. Cervical length was assessed via transvaginal sonography pre-procedure, 1 and 24 hours post-procedure, and results compared between amnioreduction and control procedures. Amniotic fluid index (AFI) was measured pre- and post-procedure., Results: Pre-procedural cervical length correlated with AFI (linear fit = 5.07 -0.04x, R(2) = 0.17, P = 0.03) in patients with polyhydramnios (n = 28). Drainage of 2000 ml fluid (range 700-3500 ml), reduced AFI from 42 cm to 21 cm (P<0.001). Their pre-procedural cervical length did not change at one (mean Delta:-0.1cm, 95%CI, -0.4 to 0.2) or 24 hours (0.2 cm, -0.1 to 0.6) after amnioreduction. There was no change in cervical length at control procedures., Conclusion: Cervical shortening in twins with polyhydramnios does not appear to be an acute process; cervical length can be measured before or after therapeutic procedures.

Sacrococcygeal teratoma is the most common and benign fetal tumor. Fetuses with sacrococcygeal tumors that are predominantly solid and highly vascularized have a high risk of fatal issue. Hydrops and tumor hemorrhage are associated with a highest risk of fetal death. Management of these tumors includes ultrasound scan with Doppler and magnetic resonance imaging (MRI) is usually used for evaluation of its intrapelvic extension and relationship to the other structures. New in-utero treatments as vascular coagulation have been applied in fetuses with highly vascular teratomas but these techniques are still experimental and need more investigations. The management of delivery depends on associated anomalies, tumor vascularity and size.

We used single nucleotide polymorphism (SNP) microarrays to investigate the cause of a symptomatic epilepsy syndrome in a group of seven distantly related Old Order Mennonite children. Autozygosity mapping was inconclusive, but closer inspection of the data followed by formal SNP copy number analyses showed that all affected patients had homozygous deletions of a single SNP (rs721575) and their parents were hemizygous for this marker. The deleted SNP marked a larger deletion encompassing exons 9-13 of LYK5, which encodes STE20-related adaptor protein, a pseudokinase necessary for proper localization and function of serine/threonine kinase 11 (a.k.a. LKB1). Homozygous LYK5 deletions were associated with polyhydramnios, preterm labour and distinctive craniofacial features. Affected children had large heads, infantile-onset intractable multifocal seizures and severe psychomotor retardation. We designated this condition PMSE syndrome (polyhydramnios, megalencephaly and symptomatic epilepsy). Thirty-eight percent (N = 16) of affected children died during childhood (ages 7 months to 6 years) from medical complications of the disorder, which included status epilepticus, congestive heart failure due to atrial septal defect and hypernatremic dehydration due to diabetes insipidus. A single post-mortem neuropathological study revealed megalencephaly, ventriculomegaly, cytomegaly and extensive vacuolization and astrocytosis of white matter. There was abundant anti-phospho-ribosomal S6 labelling of large cells within the frontal cortex, basal ganglia, hippocampus and spinal cord, consistent with constitutive activation of the mammalian target of rapamycin (mTOR) signalling pathway in brain.

Objective: To describe the paradoxical occurrence of a scalloped placenta in the presence of polyhydramnios and assess its clinical significance in pregnancies complicated by twin-twin transfusion syndrome (TTTS) treated with laser therapy., Methods: All patients who underwent laser therapy for TTTS between January 2003 and April 2004 were studied. TTTS was diagnosed and staged using the Quintero staging system. Normally the placenta is characterized by undulations of the fetal-placental surface visible by ultrasound (scalloped placenta). Patients with polyhydramnios will typically have a flattened, smooth, non-scalloped placenta. Operative tapes were reviewed and placental type assigned. Pre-, intra-, and postoperative characteristics of each study patient were obtained., Results: Fifteen of 120 patients (12.5%) were noted to have a scalloped placenta despite having polyhydramnios. There was no difference in mean gestational age at laser treatment (20.3+/-0.5 vs. 19.6+/-0.6 weeks, p=0.66) or in stage (p=0.07) between the two groups. The median and range preoperative maximum vertical pocket (MVP) in the recipient gestational sac differed significantly between the scalloped and non-scalloped patients (8.3 (8-12) vs. 10.5 (8-17), p=0.001). All 15 patients (100%) with a scalloped placenta required an amnioinfusion to expose all vascular anastomoses, while amnioinfusion was necessary in only 28 of the 105 patients (26.7%, p<0.001) with a non-scalloped placenta. Postoperative patent placental vessel was identified by surgical pathology in 6.7% of the scalloped placenta group vs. 1.9% of the non-scalloped placenta group (p=NS)., Conclusion: The definition of TTTS requires an MVP>or=8 cm in the recipient sac. Most patients will have a flattened placenta as a result of polyhydramnios in this sac. Our data show that a paradoxical scalloped placenta may still be present in approximately 12.5% of patients. This preoperative sonographic finding alerts to the potential need for amnioinfusion during laser therapy for TTTS to disclose all vessels to avoid missing placental vascular anastomoses. Amniocenteses should be avoided if possible in patients considering laser therapy to minimize the likelihood of iatrogenic placental scalloping.

Background: The purpose of this study was to determine the incidence of polyhydramnios, the related maternal and perinatal morbidity, and to estimate the association between perinatal outcome and the degree of polyhydramnios in a Danish population., Methods: The study population consisted of 168 women with singleton pregnancies and polyhydramnios diagnosed by ultrasound as a largest two-diameter pocket of > 50 cm2. Mild polyhydramnios defined as > 50 and < 100 cm2, and severe polyhydramnios defined as > or = 100 cm2. The background population consisted of 8,347 pregnant women from the same hospital. Outcome measures were compared using chi2 test or Fisher's exact test., Results: The incidence of polyhydramnios was 2%, with 66.7% of cases mild, and 33.3% were severe polyhydramnios. The study population had an increased risk of emergency (19 versus 10.5%, p<0.001) and elective (11.3 versus 5.0%, p<0.001) caesarean section, as well as perinatal death (1.2 versus 0.3%, p<0.05) compared to the background population. In cases of severe polyhydramnios, there was an increased risk of caesarean section (44.6 versus 23.1%, p<0.005), birth weight > 4,000 g (28.6 versus 14.3%, p<0.05), and need for neonatal care (8.9 versus 0.9%, p<0.01) compared to mild cases. Apgar score < 7, perinatal death and structural malformations only occurred in women with severe polyhydramnios., Conclusion: It is reasonable to distinguish between mild and severe polyhydramnios regarding special attention and follow-up, as caesarean section and perinatal morbidity and mortality are related to the degree of polyhydramnios. A two-diameter pocket > or = 100 cm2 could be used to separate mild from severe cases.

Objective: The aims of the study were to determine cervical length among patients with polyhydramnios and to assess the relationship between the severity of polyhydramnios, cervical length and gestational age at delivery., Patients and Methods: A prospective study was designed including 92 consecutive singleton pregnancies with polyhydramnios between 24 and 40 weeks' gestation. Cervical length was measured using transvaginal sonography. Polyhydramnios was defined when amniotic fluid index (AFI) was equal to or greater than 20 cm. A single sonologist performed all the examinations of the cervical length and the AFI., Results: The median cervical length and AFI were 37.5 (range, 7-52) mm and 28.8 (range, 20-43) cm, respectively. A significant gradual shortening of the cervical length was observed with advancing gestational age (P=0.027). No significant association was found between AFI and cervical length (P=0.24). A cut-off of 15 mm (n=5) was associated with a significantly lower gestational age at delivery (30+/-2.6 weeks vs. 37.2+/-4.2 weeks, respectively, P<0.001)., Conclusions: Women with polyhydramnios have a gradual shortening of cervical length with advancing gestational age. However, this finding is not related to the severity of polyhydramnios., (Copyright (c) 2006 ISUOG.)

We report a case of Neu-Laxova syndrome in a fetus at 22 weeks with the ultrasonographic findings of characteristic facial findings, limb contractures, kyphosis and polyhydramnios. Pathological and ultrasonographic studies are discussed., (Copyright (c) 2005 S. Karger AG, Basel.)

Craniofacial duplication (diprosopus) is a rare form of conjoined twins. A case of monocephalus diprosopus with anencephaly, cervicothoracolumbar rachischisis, and duplication of the respiratory tract and upper gastrointestinal tract is reported. The cardiovascular system remained single but the heart showed transposition of the great vessels. We present this case due to its rarity, and compare our pathologic findings with those already reported.

We report five new cases of rhabdomyosarcoma (RMS) in Costello syndrome. These cases, combined with those previously reported, increase the number of solid tumors to 17 (10 RMSs, 3 neuroblastomas, 2 bladder carcinomas, 1 vestibular schwannoma, 1 epithelioma), in at least 100 known Costello syndrome patients. Despite possible ascertainment bias, and the incomplete identification of all Costello syndrome patients, the tumor frequency could be as high as 17%. This is comparable to the 7-21% frequency of solid tumors in Beckwith-Wiedemann syndrome (BWS), and may justify tumor screening. Based on the recommendations for screening BWS patients, we propose a screening protocol consisting of ultrasound examination of the abdomen and pelvis every 3-6 months until age 8-10 years for RMS and abdominal neuroblastoma; urine catecholamine metabolite analysis every 6-12 months until age 5 years for neuroblastoma; and urinalysis for hematuria annually for bladder carcinoma after age 10 years. These recommendations may need to be modified, as new information becomes available. Potential criticism of the tumor screening protocol concerns the lack of evidence for improved outcome, and possible overestimation of the tumor risk. The ability of RMSs to occur at various sites complicates tumor screening, but 8 of the 10 RMSs in Costello syndrome patients originated from the abdomen, pelvis and urogenital area. Prior diagnosis of Costello syndrome is a prerequisite for the implementation of any screening protocol. The diagnosis of Costello syndrome should also be considered in individuals with RMS and physical findings suggestive of Costello syndrome., (Copyright 2002 Wiley-Liss, Inc.)

Bartter syndrome, which presents clinically with polyuria, urinary potassium loss, hypokalemia, hypercalciuria, and alkalosis, is an autosomal recessive disorder with mutations in genes encoding the Na-K-2Cl cotransporter, the chloride channel CLC-NKB, and the potassium channel ROMK. Prenatal diagnosis of Bartter syndrome is now possible; however, there are no reports of the placental pathology associated with fetal Bartter syndrome. We present the placental pathologic findings in two siblings with fetal Bartter syndrome. Both pregnancies were complicated by polyhydramnios and preterm delivery. The first pregnancy delivered at 30 weeks, and Bartter syndrome was diagnosed in the perinatal period. The subsequent pregnancy required periodic therapeutic amniocentesis secondary to massive polyhydramnios and delivered at 32 weeks gestation. The suspicion of fetal Bartter syndrome was very high in this second pregnancy, and the infant was confirmed to have Bartter syndrome subsequently. Both placentas were large for gestational age, weighing greater than the 95th percentile. Microscopic examination showed extensive subtrophoblastic basement membrane mineralization (special stains positive for iron and calcium) in the chorionic villi. This striking finding was present in both placentas. Subtrophoblastic mineralization has been described in the literature in placentas of fetuses with abnormalities including anencephaly, trisomy 21, and other congenital abnormalities; however, it has also been described in normal pregnancies. Mechanisms of calcification in the placenta are not well understood, but these striking cases suggest that defects in fetal renal excretion of ions can lead to dystrophic calcification within the placenta, particularly in a subtrophoblastic pattern.

Twin-twin transfusion syndrome (TTTS) complicates one in five monochorionic pregnancies and is generally associated with high mortality and morbidity. One twin (the recipient) grows appropriately and has polyhydramnios while the other (the donor) may have a reduced growth velocity and severe oligohydramnios. The disparities in amniotic fluid volumes represent differences in fetal urine output. These differences occur secondary to hemodynamic changes, in which the vascular arrangement of placental anastomoses in TTTS leads to unidirectional flow from the donor to the recipient twin. A better understanding of the pathophysiology may contribute to improved management of this morbid condition. We studied three consecutive prospectively diagnosed stillborn twin pairs affected by early-onset TTTS. Renin gene expression was studied in sections of fetal kidneys with immunocytochemistry using a renin antiserum and with in situ hybridization using riboprobes complementary to renin mRNA, and renin-secreting cells (RCC) were counted. The overall maturation of the renal cortex was assessed by the percentage of immature glomeruli. The donor twin kidneys were smaller than those of the recipients, but the maturation of the renal cortex was not significantly different (28.2% immature glomeruli in the donor and 24.4% in the recipient kidney). The donor kidney showed increased renin gene expression with hyperplastic juxtaglomerular apparatuses (JGAs) that contained excess RCCs (median 20.02 [25th-75th centiles, 5.4, 25.1 RCCs per 100 glomeruli]). In contrast, the recipient kidney was virtually devoid of these cells (0.04 [0, 0.36] RCCs per 100 glomeruli; P < 0.05). In the donor kidney, increased renin release may, by a local action, contribute to renal vasoconstriction and oliguria. Increased renin and/or angiotensin II in the blood passing through the placental anastomoses may, by an endocrine action, suppress renin synthesis in the recipient kidney, thereby increasing renal blood flow and causing polyuria and polyhydramnios. These changes in the renal RAS could thus contribute to the pathogenesis of TTTS. The renal renin changes noted here may represent a contributory or compensating mechanism, the success of which may dictate the overall survival of the twin pregnancy and allow better understanding of the pathophysiology and perhaps therapy that may be employed in this condition.

Steinert's syndrome is a systemic disease with autosome mother-to-child transmission, characterized by myotonia and muscular dystrophia. The syndrome's clinical characteristics include: respiratory and alimentation diseases, facial diplegia, generalized hypotonia, areflexia, atrophy, arthrogryposis, hydramnios, retard in psychomotor development, cataract and genital disorders. A case of pregnancy occurs in Steinert syndrome's patient with hydramnios as a predominant symptom, is presented. At birth, in the congenital neonatal form, there is grave, generalized hypotonia which causes a very quick death of the newborn. There are not many characters which can be found out by ultrasound: hydramnios, reduction of fetal tone and active movements, micrognathia. Consequently it is of the utmost importance in those cases an adequate prenatal genetic counseling and a correct obstetrical management.

Ophthalmic pathological findings of hydrolethalus, a midline malformation syndrome, were determined in three fetuses aborted between the 14th and 19th gestational week. The eyes were serially sectioned and analyzed using light microscopy and a panel of 13 antibodies to neuronal, glial, epithelial, and mesenchymal elements of the eye. The general morphological and antigenic development of the anterior segment, retina and choroid were normal, but some lens fibers were vacuolated and irregular in all eyes. A coloboma of the optic nerve was constant and corresponded in its severity to the systemic manifestations. It ranged from segmental dysplasia of the optic nerve head to a colobomatous orbital cyst with secondary microphthalmos and deranged development of the eye. Glial tissue extended through a defect in the sheaths of the optic nerve in three eyes, communicating with retinoblastic tissue in the orbit. Evidence of secondary optic nerve hypoplasia was present in all eyes, and a separate chorioretinal coloboma was present in one eye. Ocular anomalies should be considered one hallmark of hydrolethalus syndrome, and they may help to differentiate it from other overlapping malformation syndromes. In particular, colobomatous dysplasia and hypoplasia of the optic nerve seem to be typical of hydrolethalus syndrome. Histopathological studies of the eyes may help the neuropathologist in making the differential diagnosis of midline malformation syndromes.

The authors report a case of a thanatophoric dysplasia associated with hydramnios diagnosed at 32 weeks' gestation by sonographic investigation. The final diagnosis was derived from radiological and hystological findings. The authors underline that the identification of a specific osteochondrodysplasia is quite difficult and postulates interdisciplinary cooperation between gynecologists, neonatologists, radiologists and pathologists. More effective counselling of affected families is the major purpose of all the efforts involved.

Chorioangiomas are the most common benign tumors of the placenta. The pathologist is able to recognize these tumors in 1% of all examined specimens, but 80% of them are small and of no clinical significance. The larger chorioangiomas are very rare and often associated with complications such as placental abruption, fetal anemia, premature labor and preterm delivery. Early diagnosis of such a large placental tumor is necessary for the obstetrician to adjust the management of pregnancy to reduce fetal and maternal mortality and morbidity. We present a case of multiple placental chorioangiomas, in which the largest was 8 cm in diameter, detected in the 33rd week of pregnancy and associated with polyhydramnion and fetal anemia because of fetomaternal transfusion. Early diagnosis and well-timed delivery avoided severe complications for mother and neonate.

We describe a case of Neu-Laxova syndrome in a newborn female who was born at full-term to consanguineous Turkish parents. The pathological and radiological features are described.