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To present the prenatal features and postnatal outcomes of pregnancies with fetal nemaline myopathy (NM). 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. 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. Prenatal ultrasound can detect clues that lead to the diagnosis of NM, such as reduced or absent fetal movements, polyhydramnios and extremity anomalies. [ABSTRACT FROM AUTHOR]

• Prenatal ultrasound-based diagnosis of epidermolysis bullosa is difficult, but not impossible. Several sonographic signs, even if nonspecific, are more frequently reported in the few cases described in literature to date. • The prenatal ultrasound confirms a good level of accuracy in assessing fetuses with suspicion of epidermolysis bullosa. • This paper suggests for future investigations to carefully evaluate the muco-cutaneus areas, including the perioral area. The fetal mobility and the 3D ultrasound should be part if the examination. This is the first systematic review specifically focused on prenatal ultrasound signs of EB. Epidermolysis bullosa is a rare hereditary autosomal disease that is included in the heterogeneous group of genodermatosis. It is characterized by skin and mucous membranes fragility and denudation, and it can be associated with pyloric atresia. Prognosis is often poor, and death can occur in neonatal period due to severe sepsis. We present a case of fetal junctional epidermolysis bullosa in a consanguineous couple, highly suggested by previous obstetric history and several antenatal ultrasound signs, such as polyhydramnios, gastric enlargment, the "snowflake sign", abnormal external ears, signs of skin desquamation, lower limbs anomalies and chorioamniotic membrane separation. We describe a marked perioral hipoecogenicity as a novel sign of skin-mucous denudation, which could be helpful for future diagnosis. A review of literature, focused specifically on the antenatal sonography role, is also reported. Prenatal ultrasound-based diagnosis of epidermolysis bullosa is difficult, especially in apparently low risk contexts, but may be possible. [ABSTRACT FROM AUTHOR]

Fetal skeletal dysplasias involving limbs and hands are rare congenital malformations. Prenatal two-dimensional ultrasound diagnosis of fetal limb defects has a sensitivity of about 30%; however, an increased detection rate may be obtained using three-dimensional (3-D) ultrasound in the rendering mode. 3-D ultrasound may be used as a complementary method providing additional information. Currently, magnetic resonance imaging (MRI), with the emergence of ultrafast imaging techniques and new sequences, allows for better diagnosis of several fetal skeletal dysplasias such as limb reduction defects and neuromuscular disorders. 3-D volumetric images from ultrasound or MRI scan data allow 3-D ultrasound reconstructions of virtual/physical models, and virtual reality can help researchers to improve our understanding of both normal and abnormal fetal limb/hand anatomy. In this article, we review the embryological development of fetal hands and their main anomalies including prenatal diagnostic methods, genetic counseling, the role of orthopedic and plastic surgery reconstruction, and new perspectives in fetal surgery. [ABSTRACT FROM AUTHOR]

Objective: To determine the fetal ultrasound findings associated with Sotos syndrome caused by deletions at 5q35 including the NSD1 and a point mutation in this gene.Study Design: This was a retrospective study of eight pregnancies with fetal Sotos syndrome identified by chromosomal microarray (CMA)/whole exome sequencing (WES). Clinical and laboratory data were collected and reviewed for these cases.Results: Two cases had no significant fetal abnormalities, and were only diagnosed after birth. One case presented in the first trimester with increased nuchal translucency. The remaining five fetuses were identified at late gestation. One of the five fetuses presented in the second trimester with mild ventriculomegaly, and four in the third trimester with mild ventriculomegaly, macrocephaly and polyhydramnios. CMA was done on all cases and revealed 5q35 deletions in seven cases, and WES detected a maternally inherited NSD1 variant in one case.Conclusion: The fetal ultrasound findings in cases with Sotos syndrome, associated with deletions at 5q35 and a point mutation in the NSD1 are not specific with the most common finding being mild ventriculomegaly. [ABSTRACT FROM AUTHOR]

Background: Fetal magnetic resonance imaging (MRI) is increasingly utilized for prenatal diagnosis of agenesis of the corpus callosum (ACC). This study aimed to (1) describe cases of ACC diagnosed by fetal MRI, (2) determine the frequency of postnatal confirmation by MRI, and (3) understand postnatal outcomes of infants with ACC.Methods: Maternal records from Children's National Hospital between January 2012 and June 2019 with a prenatal neurological consultation, fetal MRI, and ACC on imaging were included. Maternal, prenatal, and postnatal infant data were collected. Each case was categorized as complete or partial ACC and isolated or complex ACC by fetal MRI and group comparisons of outcomes were analyzed.Results: A total of 127 maternal-fetal dyads with ACC were categorized into 45 isolated-complete, 17 isolated-partial, 46 complex-complete, and 19 complex-partial ACC. Of 75 live births, 72 had postnatal evaluations. In 43 of 59 (73%) cases with postnatal neuroimaging, prenatal ACC subcategory was confirmed. Children with isolated or complex and with partial or complete ACC had similar rates of developmental delays and epilepsy. Complex ACC cases had worse outcomes than isolated ACC, with complex ACC having more postnatal dysmorphisms and abnormal feeding and vision compared with isolated ACC. Similar neurodevelopmental outcomes were seen for partial and complete ACC.Conclusions: Children with isolated or complex ACC and with partial or complete ACC have a range of neurodevelopmental outcomes. Fetal and postnatal brain MRI is a valuable tool to understand differences of the corpus callosum that can guide genetic testing, prenatal counseling, and postnatal care. [ABSTRACT FROM AUTHOR]

Objective: To present the experience on prenatal diagnosis of Miller-Dieker syndrome (MDS)/PAFAH1B1-related lissencephaly to further determine fetal phenotypes of this syndrome.Study Design: This was a retrospective study of ten pregnancies with fetal MDS/PAFAH1B1-related lissencephaly identified by chromosomal microarray (CMA)/exome sequencing (ES). Clinical and laboratory data were collected and reviewed for these cases, including maternal demographics, prenatal sonographic findings, CMA or ES results and pregnancy outcomes.Results: Two cases were diagnosed in the first trimester because of an increased nuchal translucency. The remaining eight cases were identified at late gestation, including four in the second trimester because of fetal cardiac anomalies or ventriculomegaly, and four in the third trimester because of ventriculomegaly. CMA revealed 17p13.3 deletions in nine cases, and ES detected a de novo PAFAH1B1 missense mutation in one case.Conclusion: The prenatal presentation of MDS/PAFAH1B1-related lissencephaly depended on the gestational age when the diagnosis was made. Mild ventriculomegaly was the most common prenatal sonographic sign identified in cases of MDS/PAFAH1B1-related lissencephaly. It is important that fetal MRI and invasive testing with CMA should be considered in fetuses with apparently 'isolated' mild ventriculomegaly. [ABSTRACT FROM AUTHOR]

Objective: This study aims to assess accuracy and clinical utility of postmortem radiological exams [Magnetic Resonance Imaging (MRI), Computed Tomography (CT) and Radiography (XR)] after termination of pregnancy at <23 weeks' gestation for congenital fetal malformations in comparison to autopsy.Study Design: This a prospective single-center study on fetuses underwent termination of pregnancy for fetal defects. Overall concordance between any radiological exam and autopsy was evaluated. For postmortem MRI only, the following subgroups were analyzed: 1) total agreement; 2) agreement for main findings; 3) agreement for main findings but major relevant additional findings at autopsy; 4) total disagreement.Results: 174 cases were collected. The overall concordance with autopsy for main findings was 71% (115/163) for postmortem MRI and 99% (173/174) for prenatal ultrasound (US). Postmortem MRI detection rate was high for central nervous system (CNS) defects (98%), gastrointestinal, genitourinary and respiratory defects (100%), while it was poor for cardiovascular and musculoskeletal defects (25% and 42%, respectively). For musculoskeletal abnormalities, the performance of postmortem XR and postmortem CT exams improved the detection rate from 42% for postmortem MRI alone to 92%.Conclusions: Postmortem MRI has a good overall concordance for fetal defects after termination of pregnancy performed at <23 weeks. Along with autopsy, postmortem MRI may be offered for all cases of CNS defects in order to prevent inconclusive exams due to autolysis of the brain tissue, while postmortem CT and postmortem XR are indicated for musculoskeletal defects. In the presence of multiple abnormalities or cardiac defects the couple should be counseled on the poor performance of radiological investigations. [ABSTRACT FROM AUTHOR]

The present study aimed to evaluate the performance of QuantusFLM software, which performs quantitative analysis of lung tissue texture through ultrasound images, in predicting lung maturity in fetal growth restriction (FGR). We included patients with singleton gestations between 34 and 38 6/7 wk and divided them into two groups: FGR and control (appropriate for gestational age [AGA]). The images were captured by ultrasound according to a specific protocol up to 48 h before delivery and analyzed with QuantusFLM software. The main clinical outcome evaluated was lung maturity (i.e., the absence of neonatal respiratory morbidity). We included 111 patients; one was excluded because of low image quality, leaving 55 patients in each group. The FGR group had a lower birth weight (2207 g vs. 2891 g, p < 0.001) and a longer stay in the neonatal intensive care unit (NICU) (10 d vs. 5 d, p = 0.043). QuantusFLM software was able to predict lung maturity in FGR with accuracy, sensitivity, specificity and positive and negative predictive values of 94.5%, 96.2%, 50%, 98.1% and 33.3%, respectively. QuantusFLM had good accuracy in predicting lung maturity in FGR with reliability in identifying pulmonary maturity. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to report the rate of additional anomalies detected exclusively at prenatal magnetic resonance imaging (MRI) in fetuses with isolated severe ventriculomegaly undergoing neurosonography.Method: Multicenter, retrospective, cohort study involving 20 referral fetal medicine centers in Italy, United Kingdom, Spain and Denmark. Inclusion criteria were fetuses affected by isolated severe ventriculomegaly (≥15 mm), defined as ventriculomegaly with normal karyotype and no other additional central nervous system (CNS) and extra-CNS anomalies on ultrasound. In all cases, a multiplanar assessment of fetal brain as suggested by ISUOG guidelines on fetal neurosonography had been performed. The primary outcome was the rate of additional CNS anomalies detected exclusively at fetal MRI within two weeks from neurosonography. Subgroup analyses according to gestational age at MRI (Results: 187 fetuses with a prenatal diagnosis of isolated severe ventriculomegaly on neurosonography were included in the analysis. Additional structural anomalies were detected exclusively at prenatal MRI in 18.1% of cases. When considering the type of anomaly, malformations of cortical development were detected on MRI in 32.4% cases, while midline or acquired (hypoxemic/hemorrhagic) lesions were detected in 26.5% and 14.7% of cases, respectively. There was no difference in the rate of additional anomalies when stratifying the analysis according to either gestational age at MRI or laterality of the lesion. At multivariate logistic regression analysis, the presence of additional anomalies only found at MRI was significantly higher in bilateral compared versus unilateral ventriculomegaly (OR: 4.37, 95% CI 1.21-15.76; p = 0.04), while neither maternal body mass index, age, severity of ventricular dilatation, interval between ultrasound and MRI, nor gestational age at MRI were associated with the likelihood of detecting associated anomalies at MRI.Conclusion: The rate of associated anomalies detected exclusively at prenatal MRI in fetuses with isolated severe ventriculomegaly is lower than previously reported, but higher compared to isolated mild and moderate ventriculomegaly. Fetal MRI should be considered as a part of the prenatal assessment of fetuses presenting with isolated severe ventriculomegaly at neurosonography. [ABSTRACT FROM AUTHOR]

Retinoblastoma is the prototypic genetic tumor. Caused by mutations in the RB1 gene, retinoblastomas are heritable in 40% of the cases and, in such cases, tumors are bilateral in 80%, unilateral in 15%, and trilateral in 5% of the cases. Trilateral retinoblastoma is a term that describes bilateral retinoblastomas plus a midline suprasellar or pineal neuroectodermal tumor. Patients with a germline RB1 mutation have 45% chance of having an offspring with retinoblastoma. Prenatal diagnosis is important because the doubling time is fast, ranging from 7 to 15 days. Thus, late diagnosis during infancy is associated with larger tumors and increased risk of death, need for globe enucleation and vision loss. We report a case of bilateral retinoblastomas diagnosed by targeted high-resolution ultrasonography of the orbits at 32 weeks of gestation in a patient at risk. This report demonstrates the feasibility of accurately detecting even tiny retinoblastomas by ultrasound with current technology. We also review prenatally published cases to date and comment on the technical strengths and limitations of ultrasound and fetal MRI for prenatal diagnosis of retinoblastomas. • Retinoblastoma is the prototypic genetic tumor, caused by mutations in the RB1 gene. • Retinoblastomas are heritable in 40% of the cases. • As the tumor doubling time is extremely short (7-15 days), prenatal diagnosis provides an opportunity for early delivery and prompt initiation of treatment. • Even small retinoblastomas can be diagnosed prenatally with current ultrasound and MRI technology. [ABSTRACT FROM AUTHOR]

We present a case of Klippel-Feil Syndrome, a congenital skeletal defect where multiple cervical vertebral bodies are fused. Klippel-Feil Syndrome has multiple associated anomalies, with a notable one being Sprengel's deformity. In this case, the patient was given a diagnosis of Klippel-Feil Syndrome prenatally after suspected cervical vertebrae fusion and Sprengel's deformity were seen on both fetal magnetic resonance imaging (MRI) and ultrasound. Prenatal diagnosis of Sprengel's deformity has been reported once in the literature. In this report, we present imaging findings of Sprengel's deformity seen in association with Klippel-Feil Syndrome using a combination of fetal ultrasound and MRI. • Klippel-Feil Syndrome (KFS) is a defect featuring fusion of cervical vertebrae. • Sprengel's deformity should be suspected in cases of KFS. • Prenatal 3D ultrasound and MRI showed Sprengel's deformity and omovertebral bone. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the prognosis of fetuses with a prenatal diagnosis of micrognathia in the first trimester.Study Design: Over a 3-year period, patients with fetal micrognathia were detected at the time of nuchal translucency screening. The medical records of these pregnancies were reviewed, including maternal demographics, sonographic findings, genetic testing results and pregnancy outcomes.Results: Forty-three cases of first-trimester micrognathia were included in this study. Chromosomal abnormalities were detected in seven cases. Of the fetuses with a normal array, further investigation of monogenic disorders with whole-exome sequencing was undertaken in 13 cases. Monogenic syndromes were identified in eight cases, including six with de-novo dominant alleles and two with recessive conditions. Whole-exome sequencing was refused in 23 cases; among these, other additional anomalies were found on anatomic ultrasound in 10 cases.Conclusion: This study demonstrated that caution should be adopted when finding an apparently isolated micrognathia in early gestation, even with a normal array. A diagnosis of genetic syndrome or multiple anomalies on subsequent scans is most likely, and will affect the final prognosis. [ABSTRACT FROM AUTHOR]

Introduction: Alongside initial screening obstetric US, use of placental MRI has been increasing in the last few decades to aid with antenatal diagnosis and delivery planning in Placenta Accreta Spectrum (PAS). The aim of this study was to determine if the MRI pathophysiological sign subcategories described in the current literature can predict the severity of pathologic diagnosis.Methods: Institutional imaging records were reviewed for placental MRIs performed for suspicion of PAS in the last decade. Electronic health records were searched for patient history and pathology. The 59 MRI studies were reviewed using the 11 MRI signs described by the SAR and ESUR joint consensus statement. Further breakdown of the signs was divided by underlying pathophysiologic subcategories including gross morphologic, interface and tissue architecture signs.Results: Pathologic diagnosis yielded 34 cases: accreta 4/34, incerta 14/34, percreta 10/34 and normal 6/34. Of the accreta cases all of them demonstrated at least two interface and half of the cases had tissue architecture signs, 13/14 increta cases demonstrated interface signs and 12/14 demonstrated tissue architecture signs, 9/10 percreta cases had two interface and at least six demonstrated three tissue architecture signs. Statistical analysis showed significant difference between pathologic diagnosis and the number of positive interface signs with p = 0.02.Discussion: Interface signs were the most objective and sensitive MRI subcategory. Statistical analysis determined there was a significant difference between PAS diagnosis and number of interface signs present. This subcategory has the most overlap with classic US signs which are traditionally used before MRI referral. [ABSTRACT FROM AUTHOR]

ADNP syndrome, also known as the Helsmoortel-Van der Aa syndrome (HVDAS), is a neurodevelopmental disorder characterized by hypotonia, developmental delay, and intellectual disability. Diagnosis is typically made postnatally, and little is known about prenatal presentation of the disorder. We report a child who presented with intrauterine growth restriction, proportionate microcephaly, and an abnormal skull shape on fetal ultrasound. Whole exome sequencing performed on amniotic fluid cells showed a de novo pathogenic variant in the ADNP gene, corresponding to a diagnosis of ADNP syndrome. [ABSTRACT FROM AUTHOR]

We present a case of hypochondrogenesis, a rare autosomal dominant skeletal dysplasia that often results in infant death shortly after birth. Hypochondrogenesis can present similarly to other skeletal dysplasia diseases, notably achondrogenesis type II. The diagnosis of hypochondrogenesis was given during the prenatal stage after fetal imaging was performed using ultrasound, magnetic resonance imaging (MRI), and low-dose computerized tomography (CT). To the best of our knowledge, this is the first known case that reported the use of low-dose CT to assist in the prenatal diagnosis of hypochondrogenesis. • Hypochondrogenesis is a lethal skeletal dysplasia with less than 100 known cases. • Fetal imaging can differentiate hypochondrogenesis from achondrogenesis type II. • Low-dose CT revealed distinguishing defects not seen on ultrasound or MRI. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical application of medical exome sequencing (MES) for prenatal diagnosis of genetic diseases related to fetal structural anomalies detected by prenatal ultrasound examination.Study Design: A total of 105 fetuses with structural anomalies were negative results in both Quantitative fluorescent polymerase chain reaction (QF-PCR) and chromosomal microarray analysis (CMA). Then trio-based MES was further used for identifying the potential monogenic diseases in these fetuses. Coding regions and known pathogenic non-coding regions of over 4000 disease-related genes were interrogated, and variants were classified following the guidelines of American College of Medical Genetics (ACMG).Results: The 105 fetuses with structural anomalies were categorized into 12 phenotypic groups. A definitive diagnosis was achieved in 19% (20/105) of the cases, with the identification of 21 pathogenic or likely pathogenic variants in 14 genes. The proportion of patients with diagnostic genetic variants varied between the phenotypic groups, with the highest diagnostic yield in the cardiovascular abnormalities (44%), followed by the skeletal and limb abnormalities (38%) and brain structural abnormalities (25%). In addition, 12 fetuses were detected variants of unknown significance (VOUS), while the relevance of phenotypes and variants would further evaluated.Conclusion: MES can identify the underlying genetic cause in fetal structural anomalies. It can further assist the management of pregnancy and genetic counseling. It was demonstrated the importance of translating prenatal MES into clinical practice. [ABSTRACT FROM AUTHOR]

Objective: To assess the diagnostic accuracy of prenatal ultrasound for detecting fetal skeletal dysplasias and to describe its role in orienting genetic studies.Study Design: Observational study of pregnant women surveyed in our hospital, between 2011 and 2018, with fetal long bones below the 3rd centile (shortened long bones), either as an isolated finding or associated to other skeletal anomalies. We used a systematic protocol for the ultrasound evaluation and selection of those fetuses suspected of having a skeletal dysplasia. We report the demographics of these patients along with the sonographic follow-up of their fetuses, the genetic results and the outcome of the pregnancies and the newborn in the entire group and also compare data between the two sub-groups (isolated shortened long bones vs shortened long bones associated to other anomalies).Results: A total of 81 pregnancies with a suspected fetal skeletal dysplasia were included, with a complete follow-up available in 75 cases, 22 with isolated shortened long bones and 53 cases that presented shortened long bones with other skeletal anomalies. In the shortened long bones sub-group, a total of five (23 %) were born healthy neonates, 10 (45 %) were small for gestational age or intrauterine growth restricted (one of them of genetic origin) and seven (32 %) had a skeletal dysplasia (6 of them with genetic diagnosis). Whilst among the 53 cases that presented with shortened long bones + other skeletal anomalies, three (6%) were healthy neonates, five (9%) were small for gestational age/intrauterine growth restricted (two of genetic origin) and 45 (85 %) had a skeletal dysplasia (19 genetically confirmed and 26 with a clinical diagnosis). These differences in frequencies between the two sub-groups were determined to be statistically significant (χ2: p = 0.02).Conclusion: Around one third of fetuses with isolated shortened long bones will have a skeletal dysplasia. If abnormal skeletal ultrasound findings are associated with shortened long bones, the risk for skeletal dysplasia is significantly increased (85 %). Prenatal systematic approach in a multidisciplinary unit is useful in the orientation of genetic studies. [ABSTRACT FROM AUTHOR]

Objective: To share our experience in diagnosis of congenital central nervous system (CNS) abnormalities by fetal magnetic resonance imaging (MRI).Study Design: This study consisted of 110 pregnancies. Neurosonography (NS) findings were compared with MRI results. Anomalies were categorized into 10 groups: 1) Corpus callosum (CC) and cavum septum pellucidum (CSP) anomalies, 2) Neural tube defects (NTD), 3) Posterior fossa anomalies (PFA), 4) Primary ventriculomegaly (PVM), 5) Microcephaly, 6) Macrocephaly, 7) Periventricular leukomalacia (PVL), 8) Craniosynostosis, 9) Intracranial hemorrhage (ICH) and 10) Lumbosacral teratoma. Demographic features, clinical characteristics and perinatal outcomes of the study subjects were evaluated.Results: Gestational weeks for NS and for MRI were 25.5 and 26.5 weeks, respectively. Fourteen (12.7%) pregnancies were terminated. PVM (n = 36, 32.7%), CC and CSP anomalies (n = 29, 26.3%), PFA (n = 11, 10%) and NTD (n = 11, 10%) were the most common fetal MRI indications. There were no statistically significant differences between the accuracy of fetal NS and fetal MRI for CC and CSP anomalies, NTDs, PFA and PVM (p = 0.09, 0.43, 0.45 and 0.23, respectively). However, fetal MRI was more accurate for the detection of normal anatomic findings in cases with suspected microcephaly, macrocephaly and craniosynostosis in NS when pooled together (p = 0.007). Furthermore, MRI also seemed to be advantageous in CC & CSP anomalies though it was not validated by statistical measures. No statistically significant difference was found for diagnostic performance of NS and MRI according to gestational week (p = 0.27).Conclusion: Fetal MRI in addition to NS may improve diagnostic accuracy in pregnancies with congenital CNS abnormalities. [ABSTRACT FROM AUTHOR]

Objectives: To test the equivalence of two fetal weight estimation formulas generated by Hadlock, a formula that includes head circumference parameter (H1), and another (H2) which excludes this parameter. A secondary aim was to identify the patients in which H2 formula is less reliable to use.Study Design: This retrospective cohort study included a total of 1220 sonographic fetal weight estimations performed within seven days of delivery and recorded at a single medical center from January 2014 to December 2016. Estimated fetal weight was calculated using H1 and H2 formulas. Their accuracies were compared using percentage error, the proportion of weight estimations falling within ±15% error interval and by Bland-Altman analysis. Multivariate regression was performed to evaluate factors affecting weight estimation by H2 formula.Results: The mean birth weight was 3288.92 ± 641.27gr. The H2 formula presented with statistically significant higher value of systemic mean percent error comparing to H1 (3.19% vs. 1.87%, p < 0.001 respectively). H2 formula had a lower accuracy compared to H1 in predicting fetal weight within ±15% of birth weight (90.49% vs. 93.44%, p < 0.01 respectively). Using Bland-Altman analysis, the 95% limits of agreement between both formulas were (-142.03) to 231.79gr with a mean of 44.88gr. Factors found to influence significantly on H2 formula were long femur length (OR 1.144, p < 0.0001) and low maternal age (OR 0.947, p < 0.01).Conclusions: H1formula was more accurate than H2 formula in predicting fetal weight at term. However, the accuracy difference was found to be small. Therefore, if ultrasonographic evaluation of HC is technically difficult, Hadlock formula that excludes head circumference can be used with confidence. Caution should be paid with higher values of femur length and lower maternal age. [ABSTRACT FROM AUTHOR]

Cholesterol is essential in the brain from the earliest stages of embryonic development. Disruption of cholesterol synthesis pathways that leads to cholesterol deficiency underlies a few syndromes, including desmosterolosis and Smith–Lemli–Opitz syndrome. In both syndromes, brain anomalies can occur. The LSS gene encodes lanosterol synthase (LSS), an important enzyme in the cholesterol biosynthesis pathway. Biallelic pathogenic variants in this gene cause alopecia–intellectual disability type 4 syndrome (APMR4, MIM 618840), a rare autosomal recessive disorder. Here, we describe two new LSS variants (c.1016C > T; p. Ser339Leu and c.1522G > C; p. Gly508Arg) found in a compound heterozygous fetus diagnosed prenatally with brain abnormalities by ultrasound scanning. Two of his siblings from the same parents also harbored these variants. Both siblings had alopecia, mild intellectual disability, autism spectrum disorder, and cataracts. To the best of our knowledge, this case represents the first prenatal diagnosis of APMR4 first suspected by ultrasound. In addition, the phenotypic features of the siblings are extensive compared with those described in previous reports and include abnormal corpus callosum, cataracts, alopecia, and developmental delay. • Lanosterol synthase variants causing APMR identified due to fetal brain anomalies. • This case is the first prenatal diagnosis of APMR, first suspected by ultrasound. • Fetal genetic testing can help unravel an undiagnosed familial genetic history. [ABSTRACT FROM AUTHOR]

Aim: To estimate the rate of unexpected brain abnormalities detected by in utero magnetic resonance imaging (iuMRI) in fetuses without abnormalities at ultrasonography (USS).Materials and Methods: A prospective cohort study of pregnant women whose fetus had no structural brain (or body) abnormalities recognised on antenatal ultrasonography. Women were recruited from 12 centres across the UK and underwent iuMRI at 18 gestational weeks or more in the [blinded for review]. The imaging studies were reviewed by an experienced neuroradiologist. The positive and negative predictive values of both USS and iuMRI have been calculated by combining the results of this study with the results from the main [blinded for review] study.Results: One hundred and ninety-eight pregnant women were recruited and underwent iuMRI of 205 fetuses. Brain abnormalities were shown on iuMRI in two fetuses that were not recognised on USS (one case of a focal cortical abnormality and one case of mild ventriculomegaly). The negative predictive value for USS was 99.5% and 100% for iuMRI.Conclusions: To the authors' knowledge, this is the first study comparing USS and iuMRI in low-risk pregnancies. USS has a comparatively high rule-out for fetal brain abnormalities and should remain the screening tool of choice. [ABSTRACT FROM AUTHOR]

Fetal lymphangioma is a rare congenital malformation of lymphatic system that involve the skin and the subcutaneous tissue. The vast majority of the lymphangioma occurs in the neck. More rarely lymphangiomas may occur in the axillary region, including chest wall. Our consecutive case series study included three cases of fetal chest wall cystic lymphangiomas. In our cohort, fetal chest wall cystic lymphangiomas were the 18.8% of the all cases of lymphangiomas of axillary region. In all the three cases no other fetal abnormalities were evaluated, and the chest wall cystic lymphangiomas were unilateral, honeycombed in appearance, with multiple echo-free area of varying size in the mass, with no color flow on Doppler sonography, and with a trend to increase during the gestation. The incidence of chromosomal abnormalities was 33.3%, with one case out of the three being trisomy 21.The literature review revealed only seven cases of fetal chest wall cystic lymphangiomas. The cases were not associated with other abnormalities, nor with abnormal karyotype and only one case of fetal death was reported. Three women delivered vaginally. In summary, fetal chest wall cystic lymphangioma is a very rare malformations with only seven cases reported in the literature. This malformation is usually not associated with abnormal karyotype or other abnormalities and the neonatal outcome is favorable after surgical removal. Spontaneous vaginal delivery may be a safe approach for delivery women with fetal chest wall cystic lymphangioma. CONDENSATION: Fetal chest wall cystic lymphangioma is a very rare malformations with only seven cases reported in the literature. This malformation is usually not associated with abnormal karyotype or other abnormalities and the neonatal outcome is favorable after surgical removal. Spontaneous vaginal delivery may be a safe approach for delivery women with fetal chest wall cystic lymphangioma. [ABSTRACT FROM AUTHOR]

Herlyn-Werner-Wunderlich syndrome, defined by the triad of uterus didelphys, obstructed hemivagina and ipsilateral renal agenesis, is a rare Mullerian malformation, usually diagnosed after menarche, when symptoms related to hematocolpos arise. Rarely, this malformation is diagnosed in the neonatal period, normally following prenatal diagnosis of renal agenesis. Herein, a case recognized on prenatal imagiology that underwent surgery on the fourth day of life is reported. The records of prepubertal cases were also collected, addressing the clinical and imagiological features. In the presence of a solitary kidney and/or a pelvic mass on prenatal ultrasound, Herlyn-Werner-Wunderlich syndrome should be considered, enabling neonatal treatment. [ABSTRACT FROM AUTHOR]

Objective: Congenital heart defects are the most common major structural fetal abnormalities. Color flow mapping has played a dominant role in the detection of abnormalities during the first trimester, regardless of the International Society of Ultrasound in Obstetrics and Gynecology warning on the use of Doppler during early pregnancy. The aim of our study was to investigate the use of transvaginal two-dimensional sonography without Doppler for assessing the four-chamber view and the outflow tract view of fetuses at 11-13 weeks of gestation for cardiac screening of major congenital heart defects.Study Design: This was a prospective observational study conducted in the Fetal Medicine Unit of Cabueñes University Hospital, between May 2014 and August 2015. Only low risk-pregnancies were studied. All ultrasonographic examinations were performed by two experienced sonographers in maternal-fetal medicine. The combination of high-frequency transvaginal (nine MHz) and transabdominal (six MHz) ultrasonography transducers were used. An early cardiac screening was performed in 97% of cases. Statistical analysis was carried out using successive multivariate logistic regression models in order to investigate the effect of crown-rump length and body mass index on the probability of visualizing the four-chamber view and/or the outflow tract view.Results: 663 low-risk pregnant women were included. Regarding the transvaginal approach, neither the crown-rump length nor the body mass index had a statistically significant relationship on the probability of visualization of the four-chamber view and outflow tract view. For the transabdominal approach, the crown-rump length and the body mass index presented a statistically significant effect on the visualization of the four-chamber view and the outflow tract view. Using the transvaginal approach: the success rate of performing a four-chamber view was 89.4% and 82.4% for the outflow tract view. Using the transabdominal approach: the success rate of performing a four-chamber view was 77.8% and 61.5% for the outflow tract view. Four major congenital heart defects were diagnosed, and the prenatal ultrasonagraphic diagnosis was confirmed for all cases.Conclusions: Routine first-trimester ultrasonagraphy without Doppler, when performed by experienced sonographers, can effectively identify major congenital heart defects. Additional multicenter well designed studies should clarify the feasibility of this approach. [ABSTRACT FROM AUTHOR]

Objective: This retrospective study aims to evaluate the incidence, presence of chromosomal anomalies and outcome of fetuses diagnosed with cystic hygroma colli in the first trimester in a single tertiary center.Study Design: A retrospective study was performed over a ten-years period from 2007 to 2017 of all fetuses with a first-trimester diagnosis of cystic hygroma. Maternal and fetal parameters were assessed with descriptive statistics.Results: A total of 185 singleton pregnancies were included. Chromosomal anomalies were present in 122 cases (65.9%). Sixty-three fetuses (34.1%) had a normal karyotype. Noonan syndrome was diagnosed in 6 cases using additional testing for RASopathies. In euploid fetuses, a major congenital anomaly was detected in 35 of 63 cases (56%) and if present, 91.4% had an abnormal fetal outcome compared to 32.1% if no structural anomaly was found (p < 0.01). Fetuses with a nuchal translucency thickness more than 10 mm and hydropic fetuses had a worse outcome.Discussion: Associated structural anomalies or hydrops fetalis are significant predictors for an abnormal outcome in pregnancies with first-trimester cystic hygroma and a normal karyotype. Cytogenetic evaluation and detailed sonographic evaluation are of great importance in the determination of the prognosis of pregnancies complicated by first-trimester cystic hygroma. [ABSTRACT FROM AUTHOR]

Advances in prenatal genomics have enabled the assessment of not only the sub-microscopic structure of chromosomes using chromosomal microarray analysis, but also the detection of "pathogenic variants" to the resolution of a single base pair with the use of next generation sequencing. Research is emerging on the additional prenatal diagnostic yield that exome sequencing offers when structural fetal anomalies are detected on ultrasound examination, in particular the identification of monogenic abnormalities defining prognosis and recurrence of anomalies. Primarily assessed using fetal DNA obtained by invasive techniques (amniocytes or chorionic villi), this technology is progressing into a non-invasive approach using maternal plasma. There are several challenges, to be addressed before this technology can be introduced into routine clinical practice. These are primarily technical and interpretational but also relate to service provision; cost-effectiveness; turn-around time; patient acceptability and ethical dilemmas. With adequate pre- and post-test counselling many of these challenges may be overcome and such counselling has to be multi-disciplinary, involving clinical geneticists, genetic scientists, paediatricians, perinatal pathologists and fetal medicine subspecialists. There is therefore a need for obstetricians to have an understanding of the clinical utility, application, advantages and challenges of such technologies before introduction into routine clinical practice. [ABSTRACT FROM AUTHOR]

Congenital anomalies of the kidneys and the urinary tract (CAKUT) are one of the most common sonographically identified antenatal malformations. Dilatation of the renal pelvis accounts for the majority of cases, but this is usually mild rather than an indicator of obstructive uropathy. Other conditions such as small through large hyperechogenic and/or cystic kidneys present a significant diagnostic dilemma on routine scanning. Accurate diagnosis and prediction of prognosis is often not possible without a positive family history, although maintenance of adequate amniotic fluid is usually a good sign. Both pre- and postnatal genetic screening is possible for multiple known CAKUT genes but less than a fifth of non-syndromic sporadic cases have detectable monogenic mutations with current technology. In utero management options are limited, with little evidence of benefit from shunting of obstructed systems or installation of artificial amniotic fluid. Often outcome hinges on associated cardiac, neurological or other abnormalities, particularly in syndromic cases. Hence, management centres on a careful assessment of all anomalies and planning for postnatal care. Early delivery is rarely indicated since this exposes the baby to the risks of prematurity in addition to their underlying CAKUT. Parents value discussions with a multidisciplinary team including fetal medicine and paediatric nephrology or urology, with neonatologists to plan perinatal care and clinical geneticists for future risks of CAKUT. [ABSTRACT FROM AUTHOR]

We sought to evaluate the diagnostic value of foetal magnetic resonance imaging (MRI) for multicystic dysplastic kidney (MCDK) disease. We retrospectively identified 55 foetuses with MCDK diagnosed (51 unilateral; 4 bilateral) by foetal MRI. We analysed the anatomical findings by prenatal MRI and compared them with the prenatal ultrasound (US) and postnatal findings. Additional diagnostic information added by MRI was recorded. The gestational age of the 55 foetuses ranged from 22 to 35 weeks (mean, 26.5 ± 3.6 weeks). The age of the pregnant women ranged from 23 to 40 years (mean, 31 ± 4.2 years). All 55 cases were performed at 1.5 T magnetic resonance unit. MRI sequences, including steady-state free precession (SSFP), single-shot fast spin echo (SSFSE), T1-weighted imaging (T1WI), and diffusion weighted imaging (DWI) sequences. Follow-up was obtained for 53 cases (2 cases of autopsy, 51 cases of postnatal imaging or surgery confirmed). Among the 51 unilateral cases, 16 cases were associated with other urinary tract anomalies, 3 cases with extra-renal anomalies, and the remaining 32 cases without associated anomalies. 2 of 16 cases with contralateral renal agenesis were with oligohydramnios and pulmonary hypoplasia. 2 of 4 bilateral MCDK presented with oligohydramnios and pulmonary hypoplasia. 52 of 53 cases were correctly diagnosed by MRI compared with the final diagnoses; 40 of 53 (75.5%) cases were correctly diagnosed by prenatal ultrasound. Both prenatal ultrasound and MRI failed to correctly diagnose one case bilateral MCDK, and MRI correctly changed the ultrasound diagnosis in 12 cases. Foetal MRI can add additional diagnostic information to prenatal US in the assessment of MCDK, even change the prenatal counselling and decisions. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to make an accurate diagnosis of pyriform sinus fistula (PSF) for prenatal diagnosis.Study Design: Medical records were reviewed for all 35 pyriform sinus fistula patients presenting between 2011 and 2017. Ultrasonography (US), fetal magnetic resonance imaging (MRI) and karyotyping were offered during gestation, while computer tomography (CT) and barium esophagography were performed after birth.Results: Patients included 21 males (60%) and 14 females (40%) with a sex ratio of 1.5:1. The lesion was located on the left side in 32 (91.4%) cases, the right side in 2 (5.7%), and was bilateral (2.8%) in only one case. The sensitivity of CT, MRI, ultrasonography and barium esophagography were 100% (35/35), 69.2% (9/13), 22.9% (8/35), and 80% (20/25), respectively. If the diagnosis was correct, there was almost no recurrence after treatment. Karyotype analysis of all fetuses was normal.Conclusions: Pyriform sinus fistula is more commonly seen in the left side. Compared with ultrasonography, MRI has more advantages in prenatal diagnosis, and it is more accurate in postpartum CT examination. The outcome of children with pyriform sinus fistula may be guarded when it correct diagnosis. [ABSTRACT FROM AUTHOR]

The aim of the study described here was to identify an efficient criterion for the prenatal diagnosis of abnormal invasive placenta. We evaluated 129 women with anterior placenta previa who underwent trans-abdominal ultrasound evaluation in the third trimester. Spectral Doppler ultrasonography was performed to assess the subplacental blood flow of the anterior lower uterine segment by measuring the highest peak systolic velocity and resistive index. These patients were prospectively followed until delivery and evaluated for abnormal placental invasion. The peak systolic velocity and resistive index of patients with and without abnormal placental invasion were then compared. Postpartum examination revealed that 55 of the patients had an abnormal invasive placenta, whereas the remaining 74 did not. Patients with abnormal placental invasion had a higher peak systolic velocity of the subplacental blood flow in the lower segment of the anterior aspect of the uterus (area under receiver operating characteristic curve: 0.91; 95% confidence interval: 0.87-0.96) than did those without abnormal placental invasion. Our preliminary investigations suggest that a peak systolic velocity of 41 cm/s can be considered a cutoff point to diagnose abnormal invasive placenta, with both good sensitivity (87%) and good specificity (78%), and the higher the peak systolic velocity, the greater is the chance of abnormal placental invasion. Resistive index had no statistical significance (area under receiver operating characteristic curve, 0.56; 95% confidence interval: 0.46-0.66) in the diagnosis of abnormal invasive placenta. In conclusion, measurement of the highest peak systolic velocity of subplacental blood flow in the anterior lower uterine segment can serve as an additional marker of anterior abnormal invasive placenta. [ABSTRACT FROM AUTHOR]

Objective: To compare diagnoses in patients undergoing abortion for fetal indications at 15-0/7 to 21-6/7 vs. ≥22-0/7 weeks' gestation.Study Design: This retrospective cohort study included women undergoing abortion at ≥15-0/7 weeks' gestation for fetal indications from 2012 to 2018 at our institution. We compared indications (genetic vs. structural only) between groups by gestational age (15-0/7 to 21-6/7 vs. ≥22-0/7 weeks). We performed statistical analysis using Fisher's exact and Mann-Whitney U tests.Results: The 158 women identified included 97 (61.4%) at 15-0/7 to 21-6/7 and 61 (38.6%) at ≥22-0/7 weeks' gestation. Women at an earlier gestational age more commonly had an initial diagnosis of a genetic disorder (41 [42.3%)] vs.10 [16.4%], respectively, p < .001). In 69 cases with initial or subsequent diagnosis of a genetic disorder, there were differences in the types of genetic abnormalities, with common chromosomal abnormalities (including Trisomies 13, 18, and 21) the most frequent diagnosis in those who underwent abortion at 15-0/7 to 21-6/7 weeks and microarray abnormalities more common at ≥22-0/7 weeks (22 [44.9%] vs. 4 [18.2%]) and 7 [14.9%] vs. 11 [50.0%], respectively, p = .01). Routine ultrasonography for fetal anomaly surveillance occurred one week earlier in women undergoing abortion for structural anomalies at 15-0/7 to 21-6/7weeks (median 19-2/7 weeks [interquartile range (IQR) 19 0/7 to 19-5/7 weeks]) compared to ≥22-0/7 weeks (median 20-2/7 weeks [IQR 19 6/7 to 20 4/7 weeks]), p < .001.Conclusion: Abortions for genetic indications are performed earlier in gestation compared to those performed for structural abnormalities. Timing of fetal anatomy ultrasound examination correlated with gestational age at abortion for structural abnormalities.Implications: Many states impose gestational-age based abortion bans, with 20-weeks post-fertilization the most common. However, we may not identify fetal abnormalities until close to 22 weeks gestation (20-weeks post-fertilization). Optimizing timing of prenatal diagnosis might mitigate the impact of gestational-age based abortion bans. [ABSTRACT FROM AUTHOR]

Objective: To assess the longitudinal behavior of Quantitative Lung Index (QLI) for the follow-up of fetuses with congenital diaphragmatic hernia.Study Design: Retrospective study of fetuses with isolated left congenital diaphragmatic hernia. The fetuses were assessed by ultrasound at different gestational ages and QLI was retrospectively calculated by means of previous lung-to-head ratio measurements. We used a random effects model (mixed model with repeated measurements) to compare the performance of the QLI in operated and non-operated fetuses throughout pregnancy.Results: Fifty-eight cases of isolated left diaphragmatic hernia with complete follow-up were assessed in Hospital Universitari Vall d'Hebron in Barcelona (2003-2015). Thirty-eight of them were managed expectantly (non-TO) and the other 20 underwent tracheal occlusion (TO). All fetuses undergoing tracheal occlusion had lung-to-head ratio (LHR) <1, observed-to-expected LHR (o/eLHR) ≤45%, QLI <0.6 and liver up inside the thorax. The survival rate was 87% for the non-TO group and 60% for the TO group (p = 0.02). The QLI remained constant throughout pregnancy in both groups. The QLI in the TO group had lower values than the non-TO group (p < 0.03).Conclusion: The quantitative lung index was constant during pregnancy. This index was lower in fetuses undergoing tracheal occlusion but no significant changes were seen in its performance during pregnancy. [ABSTRACT FROM AUTHOR]

Objective: To examine the risk for clinically significant chromosomal microarray analysis (CMA) among fetuses with apparently isolated horseshoe kidney.Methods: Data from all CMA analyses performed due to isolated horseshoe kidney reported to the Israeli Ministry of Health between January 2013 and September 2016 were retrospectively obtained from a computerized database. Risk estimation was performed comparing the rate of abnormal CMA findings to the general population, based on a systematic review encompassing 9272 pregnancies with normal ultrasound, and local data cohort of 5541 pregnancies undergoing CMA due to maternal request.Results: Of 82 pregnancies with isolated horseshoe kidney, one loss-of-copy-number variant compatible with 16p13.11 microdeletion syndrome was demonstrated (1.2%). In addition, two variants of unknown significance (VOUS) were detected (2.4%). The relative risk for pathogenic CMA findings among pregnancies with isolated single horseshoe kidney was not significantly different from the control population (1.03-1.39%).Discussion: To our best knowledge, our study is the first report describing the rate of clinically significant CMA findings in fetuses with isolated horseshoe kidney. The detection of one pathogenic CMA findings in our cohort implies that the value of CMA analysis in such pregnancies is similar to the general population. [ABSTRACT FROM AUTHOR]

Objective: Methods for the antenatal detection of small for gestational age babies (SGA) differ between countries. The aim of this study was to compare the diagnostic accuracy of routine versus selective small for gestational age babies screening policy using data from two European Maternity Units.Study Design: This was a retrospective cohort study from Liverpool Women's Hospital, UK, that uses selective third trimester sonography and from the University Hospital Centre Zagreb, Croatia, that uses routine third trimester sonography for SGA detection. Screen positive cases were defined as pregnancies with estimated fetal weight (EFW) <10th centile at the last 3rd trimester scan. True positives had both EFW and birth weight <10th centile. Pregnancy management data and perinatal outcomes were retrieved from hospital electronic data and special care baby unit (SCBU) reports.Results: The proportion of small for gestational age babies was higher in Liverpool (7.8%) compared with Zagreb (4%); P<0.001. Sensitivity for detection of SGA babies in Zagreb was 27% (95%CI 15%-44%) and 33% (95%CI 23%-45%) in Liverpool. The specificity was high in both centres (Zagreb 100% (95%CI); Liverpool 98% (95%CI)). The induction of labour for antenatally diagnosed SGA babies was more common in Liverpool (38.5%) than in Zagreb (9.1%). In both centres, all antenatally diagnosed SGA babies admitted to SCBU were preterm babies. Their indications for admission to SCBU were complications related to prematurity.Conclusion: The effectiveness of selective SGA screening policy is comparable to universal third trimester ultrasound screening. Further prospective evaluations of SGA screening policies are warranted and they should include full cost-effectiveness analysis and assessment of possible harm from increased interventions leading to more preterm births. [ABSTRACT FROM AUTHOR]

Background: Biliary atresia is a progressive disease presenting with jaundice, and is the most common indication for liver transplantation in the pediatric population. Prenatal series have yielded conflicting results concerning a possible association between BA and prenatal nonvisualization of the gallbladder.Aims: This retrospective case series was performed to assess the association between biliary atresia, prenatal nonvisualization of the gallbladder and other sonographic signs.Study Design/subjects: We identified biliary atresia patients who underwent a Kasai procedure by a single pediatric surgeon and/or follow up by a single pediatric gastroenterologist. Axial plane images and/or video recordings were scrutinized for sonographic signs of biliary atresia on the second trimester anomaly scan.Outcome Measures: Proportion of biliary atresia cases with prenatal sonographic signs.Results: Twenty five charts of children with biliary and high quality prenatal images were retrieved. 6/25 (24%) of cases analyzed had prenatal nonvisualization of the gallbladder or a small gallbladder on the prenatal scan. Two cases had biliary atresia splenic malformation syndrome. None of the cases had additional sonographic markers of biliary atresia.Conclusions: Our study suggests that in addition to the well-established embryonic and cystic forms, an additional type can be suspected prenatally, which is characterized by prenatal nonvisualization of the gallbladder in the second trimester. This provides additional evidence that some cases of BA are of fetal rather than perinatal onset and may have important implications for prenatal diagnosis, for counseling and for research of the disease's etiology and pathophysiology. [ABSTRACT FROM AUTHOR]

Objective: To retrospectively evaluate the accuracy of pelvic magnetic resonance (MR) imaging for the characterization of complex sonographic adnexal masses discovered in women during pregnancy.Study Design: The study population comprised 31 pregnant women (median age: 32 years (range: 19-42); mean gestation age of 16 weeks) referred to our institution for MR imaging for characterization of an adnexal mass discovered incidentally during routine ultrasound (US) for other indications. The population comprised of 31 women, with 36 adnexal lesions (mean size: 103mm [range: 20-290]), of which 27 were benign and 9 were malignant masses. Prospective US and MR reports were reviewed to determine the presence of a benign or malignant lesion. Two radiologists (R1 and R2) blinded to the final outcome, retrospectively evaluated the MR images using the criteria based on the ADNEXMR-SCORE and classified the lesion as benign or malignant. The reference standard was surgical pathology or at least a 1-year imaging follow-up.Results: Prospective US and MR imaging correctly identified the diagnosis in 27/36 (75%) (95% confidence interval (CI): 58.9%-86.2%) and in 32/36 (88.9%) (95% CI: 74.6%-95.6%) of lesions, respectively. MR imaging with ADNEXMR-SCORE allowed a correct diagnosis in 32/36 (88.9%) (95% CI: 74.6%-95.6%) of lesions for R1 and in 30/36 (83.3%) (95% CI: 68.1%-92.1%) of lesions for R2. The sensitivities and specificities of MR imaging using the MR ADNEXMR-SCORE were 100% (95% CI: 70.1%-1000%) for both readers and 85.1% (95% CI: 67.5%-94%) and 77.7% (95% CI: 59.2%-89.4%) for R1 and R2, respectively. No malignancy was classified as benign using MR criteria. The reproducibility between the two readers was almost perfect, with a kappa of 0.914.Conclusion: MR imaging is highly accurate for the characterization of complex adnexal masses incidentally discovered during pregnancy.Clinical Relevance: MR imaging can accurately characterize adnexal masses in pregnancy and could be useful in opting for expectant management until delivery. [ABSTRACT FROM AUTHOR]

Prenatal ultrasonographic (US) examination is considered as the first tool in the assessment of fetal abnormalities. However, several large-scale studies point out that some malformations, in particular central nervous system (CNS) anomalies, are not well characterized through US. Therefore, the actual malformation severity is not always related to prenatal ultrasound (US) findings. Over the past 20 years, ultrafast Magnetic Resonance Imaging (MRI) has progressively increased as a prenatal 3rd level diagnostic technique with a good sensitivity, particularly for the study of fetal CNS malformations. In fact, CNS anomalies are the most common clinical indications for fetal MRI, representing about 80% of the total examinations. This review covers the recent literature on fetal brain MRI, with emphasis on techniques, safety and indications. [ABSTRACT FROM AUTHOR]

Introduction: Our aim was to evaluate the intra- and inter-observer variability and the impact of operator experience on the estimation of fetal weight (EFW) as measured by 2-dimensional ultrasound (2D-US) and magnetic resonance (MR) imaging.Material and Methods: We estimated fetal weight in 46 singleton pregnancies at 35.6-41.4 weeks gestation using 2D-US according to the Hadlock formula and using MR imaging according to the equation developed by Baker. Each examination was performed twice, once by an inexperienced operator and once by an experienced operator. The MR-EFW was derived from the planimetric measurement of fetal body volume (FBV) using an assisted semi-automated method. Intra- and inter-observer variability was evaluated by Bland-Altman analysis. Regression analysis was used to investigate the effect of maternal BMI, delivery weight, diabetes and fetal gender on the differences in US-EFW between the inexperienced and experienced operators.Results: US-EFW showed higher intra-observer variability than MR-EFW, irrespective of operator experience. The 95% limits of agreement of MR were narrower compared with those of the US measurements. Similarly, US-EFW showed higher inter-observer variability than MR-EFW. MR-EFW improvement over 2D-US for the limits of agreement was 77.9% for intra-observer variability and 74.5% for inter-observer variability. Regression analysis showed that the differences between US-EFW measurements were not related to any of the tested variables.Conclusions: Operator experience has a marginal impact on the variability of US-EFW and no impact on MR-EFW variability. The variability in US-EFW measurements is unpredictable. [ABSTRACT FROM AUTHOR]

The objective of this study was to review literature about the correlation between fetal autopsy and ultrasound findings of fetal malformations. Search in PubMed, Medline, EMBASE, Clinicl trials.org, reference list was performed. Inclusion criteria for studies selection were: fetal autopsy performed after termination of pregnancy (TOP) or stillbirth, TOP for fetal anomalies, prenatal diagnosis of malformations, data reported as proportional rates.Exclusion Criteria: case reports, non English language, data reported in graphs or percentage. From each article: sample size, type of malformation, indication for TOP, autopsy findings. Fetal anomalies were grouped in central nervous system (CNS), genitourinary (GU), congenital heart defects (CHD), gastrointestinal (GI), thorax, limbs, skeleton, genetics (TOP for abnormal karyotype), multiples (TOP for multiple severe malformations for which a single indication for TOP/stillbirth could not be identified). Correspondence between autopsy and ultrasound was defined as agreement (same diagnosis), additional (additional findings undetected by ultrasound), unconfirmed (false positive and false negative ultrasound). PRISMA guidelines were followed. From 19 articles, 3534 fetuses underwent autopsy, which confirmed prenatal ultrasound in 2401 (68.0%) fetuses, provided additional information in 794 (22.5%) fetuses, and unconfirmed prenatal ultrasound in 329 (9.2%) fetuses. The latter group consisted of 3.2% false positive and 2.8% false negative cases. The additional findings changed the final diagnosis in 3.8% of cases. The most frequent indication for TOP/stillbirth was CNS anomalies (36.3%), whereas thorax anomalies represented the less frequent indication (1.7%). The highest agreement between autopsy and prenatal ultrasound was observed in CNS (79.4%) and genetics (79.2%), followed by GU anomalies (76.6%), skeleton (76.6%), CHD (75.5%), thorax (69.7%); GI (62.6%), multiple (37.0%), limbs (23.3%). In spite of the high agreement between prenatal ultrasound and autopsy, fetal examination is mandatory because in a minority of cases it discloses additional findings or changes the final diagnosis and genetic counselling. [ABSTRACT FROM AUTHOR]

Objective: Atrioventricular septal defect is associated with a high risk of a chromosomal abnormality, particularly trisomy 21. The aim of this study is to assess the rate of trisomy 21 in fetuses diagnosed with an atrioventricular septal defect and to examine the influence of prior screening on the rate of trisomy 21.Methods: Electronic ultrasound database was searched to identify fetuses diagnoses with an atrioventricular septal defect from 2002 to 2014. Rate of trisomy 21 and other aneuploidies was calculated among fetuses with normal situs. The prevalence of trisomy 21 and other aneuploidies was assessed in women with low and high first trimester risk for trisomy 21, using a cut-off value of 1:150 and 1:250.Results: A total 110 fetuses with a diagnosis of atrioventricular septal defect were identified. Among the 98 fetuses with normal situs, the prevalence of trisomy 21 was 46% (95% CI: 36-56%). Using a 1:150 threshold, the rate of trisomy 21 within the low-risk group was 41% (95% CI: 27-57%) while in the high-risk group it was 70% (95% CI: 52-83%), significantly higher than in the low risk group (p=0.028). Similar results were obtained when the 1:250 threshold was applied (66% versus 41%, p=0.055).Conclusions: The rate of trisomy 21 among fetuses identified with an atrioventricular septal defect in the second trimester is high even in those that undergo first trimester combined screening. Some fetuses with a high-risk screening result show a normal karyotype. Therefore, an offer of an invasive procedure to check fetal karyotyping is indicated. Knowledge of these rates may be helpful for parents in the decision making process. [ABSTRACT FROM AUTHOR]

Objectives: To establish a prediction model for fetal congenital heart disease (CHD) that could facilitate selective fetal echocardiography screening for diabetic women, and to provide cost analysis of selective versus global screening of these women.Study Design: A historical cohort study included women with pre-gestational diabetes who received perinatal care at Mayo Clinic, Minnesota from 2007 through 2013. Anatomical scans and fetal echocardiograms were reviewed and charts for postnatal outcomes were abstracted. Logistic regression models were utilized to identify predictors of CHD. Cost of global versus selective screening was estimated using cost per case detected.Results: A cohort of 152 women was included. Abnormal anatomy scan was reported in five (3.3%). Among 51 (33.6%) who had fetal echocardiography, eight (15.7%) had abnormal findings. Postnatal echocardiography was conducted in 36 neonates, 12 had abnormalities. Only first trimester HbA1c was independent predictor with observed incidence of CHD of 1.8, 14.3, and 40% and HbA1c of <8, 8-10, and >10% respectively. Global screening strategy missed 22% of fetal cardiac abnormalities, while selective screening missed 33%.Conclusions: According to our probability model, selective screening based on HbA1c and/or anatomic surveys seems to be an accurate and cost effective strategy for prenatal diagnosis of CHD among diabetic pregnancies. [ABSTRACT FROM AUTHOR]

Objective: Non-invasive prenatal testing (NIPT) is increasingly being used in prenatal aneuploidy screening. The objective of this study was to assess the positive predictive value in our cohort of 68 cases with positive NIPT result. In addition, we wondered if the use of NIPT in cases with ultrasound abnormalities is appropriate, given the limited number of chromosomes investigated.Design: We performed confirmative invasive testing using karyotyping, fluorescence in situ hybridization (FISH) and/or high-resolution chromosomal microarray analysis.Results: In line with the published data, the positive NIPT result was confirmed in 64.7% of cases. Inconclusive and negative NIPT results followed by cytogenetically pathologic findings were encountered in three and in five cases, respectively. Four of the five fetuses with negative NIPT but pathologic cytogenetic findings were born with several malformations and diagnosed right after birth with severe genetic conditions. Of note, in all of those four cases, NIPT was offered despite the finding of major fetal ultrasound abnormalities and despite the fact that the family would not have opposed invasive testing or pregnancy termination.Conclusion: More education of health care providers and caution in counseling and interpretation of test results are needed in order to meet the challenges that this new test, which enriches our diagnostic options in prenatal testing, poses. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to evaluate the clinical characteristics, imaging features, pregnancy complications, prenatal management of patients with placenta chorioangioma. Methods: This was a retrospective study of 26 cases with histologically proven placenta chorioangima, in which the natural history, pregnancy complications, and clinical characteristics including ultrasonography were evaluated. Results: Twelve of the twenty-six cases had a wide range of maternal-fetal complications including polyhydramnios (7), fetal growth restriction (3), fetal distress (2), pre-eclampsia (3), fetal anemia-thrombocytopenia (2), congestive heart failure (1) and fetal abnormality (1). Conclusions: Placenta chorioangioma was associated with series of pregnancy complications such as polyhytramnios, premature delivery, maternal pre-eclampsia, fetal growth restriction, fetal distress, even fetal anemia and cardiomegaly. With regular prenatal examination, necessary treatment, and timely delivery, the majority had a good pregnancy outcome. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether first trimester combined screening for major fetal trisomies is influenced by assisted reproduction techniques from blastocyst transfer, with or without cryopreservation.Study Design: retrospective case-control analysis involving 298 singleton pregnancies with euploid fetuses recruited between 2012 and 2014. Forty-seven women conceived with fresh blastocysts from in vitro fertilization cycles (fresh-blasto), 51 with frozen-thawed blastocysts (frozen-blasto) and 200 were natural conceptions (controls). All cases underwent ultrasound assessment at 11(+0)-13(+6) weeks with measurements of crown rump length, nuchal translucency, free β-hCG and PAPP-A concentrations. The outcome of pregnancy was recorded (gestational age at birth, birth weight, obstetric complications).Results: Baseline characteristics and pregnancy outcomes did not differ substantially among the study groups. The median delta nuchal translucency was significantly higher both in frozen-blasto group (median: 0.27mm; Interquartile Range [IQR]: 0.02-0.44; p<0.001) and in fresh-blasto group (median: 0.17mm; IQR: 0.04-0.39; p=0.014) as compared to control group (median: 0.06mm; IQR: -0.08 to 0.20), whereas it was not different in the frozen-blasto compared to the fresh-blasto group. The median free β-hCG multiples of the median (MoMs) was significantly higher both in frozen-blasto group (median 1.15; IQR 0.83-2.11; p=0.001) and in fresh-blasto group (median 0.95; IQR 0.52-1.48; p=0.001) as compared to control group (median 0.99; IQR 0.57-1.26), and it was also higher in frozen-blasto group compared to fresh-blasto group (p<0.001). The three groups showed no significant differences in the median PAPP-A MoMs. The median delta crown rump length was also not significantly different among the three groups.Conclusions: in assisted reproduction technique pregnancies from blastocyst transfer, with or without cryopreservation, both the nuchal translucency measurement and free β-hCG concentration are higher as compared to spontaneous conceptions, whereas PAPP-A does not show any significant difference. These features are apparently unrelated to the outcome of pregnancy and may be due to alterations or delays in embryogenesis or placentation with potential relevance for the screening test performance. [ABSTRACT FROM AUTHOR]

Objective: To assess the clinical value of prenatal diagnosis of fetuses with increased nuchal translucency (NT) using an approach based on quantitative fluorescent polymerase chain reaction (QF-PCR) and chromosomal microarray (CMA).Study Design: From January 2013 to October 2014, we included 175 pregnancies with fetal NT ≥ 3.5mm at 11-13 weeks' gestation who received chorionic villus sampling. QF-PCR was first used to rapidly detect common aneuploidies. The cases with a normal QF-PCR result were analyzed by CMA.Results: Of the 175 cases, common aneuploidies were detected by QF-PCR in 53 (30.2%) cases (30 cases of trisomy 21, 12 cases of monosomy X, 7 cases of trisomy 18, 3 cases of trisomy 13 and 1 case of 47, XXY). Among the 122 cases with a normal QF-PCR result, microarray detected additional pathogenic copy number variants (CNVs) in 5.7% (7/122) of cases. Four cases would have expected to be detectable by conventional karyotyping because of large deletions/duplications (>10 Mb), leaving three cases (2.5%; 3/118) with pathogenic CNVs only detectable by CMA.Conclusion: It is rational to use a diagnostic strategy in which CMA is preceded by the less expensive, rapid, QF-PCR to detect common aneuploidies. CMA allows detection of a number of pathogenic chromosomal aberrations in fetuses with a high NT. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy of the sonographic cardiothoracic ratio (CTR) in early pregnancy for the prediction of fetal haemoglobin (Hb) Bart's disease.Study Design: Over a 1.5-year period at a Chinese tertiary obstetric centre, women at risk of Hb Bart's disease were given the option of a non-invasive approach to exclude an affected pregnancy between 11 weeks and 13 weeks and 6 days of gestation, with a routine rescan after a 2-week interval. The fetal CTR, a sonographic marker, was assessed, and invasive testing followed in cases of fetal cardiomegaly. The diagnosis of fetal Hb Bart's disease was based on DNA analysis from chorionic villus sampling.Results: Of 154 at-risk cases studied, five cases (four at 11 weeks of gestation) were subjected to direct invasive testing because of an unsatisfactory scan. Of the remaining 149 cases, non-invasive ultrasound examinations were performed successfully. Thirty-four (22.8%) affected pregnancies were revealed, including one picked up on rescan. The sensitivity and specificity of the non-invasive approach were 97.1% and 100%, respectively. The need for an invasive test was reduced by 74.7%, and all affected pregnancies except one were diagnosed before 14 weeks of gestation.Conclusion: CTR can differentiate reliably between pregnancies with and without Hb Bart's disease. This non-invasive approach for the exclusion of Hb Bart's disease can be used in early pregnancy. [ABSTRACT FROM AUTHOR]

Objective: To present the experience on prenatal diagnosis of Wolf-Hirschhorn syndrome (WHS) to further delineate the fetal presentation of this syndrome.Study Design: This was a retrospective analysis of ten pregnancies with fetal WHS identified by chromosomal microarray (CMA). Clinical data were reviewed for these cases, including maternal demographics, indications for invasive testing, sonographic findings, CMA results and pregnancy outcomes.Results: Three cases were diagnosed at the first trimester because of an increased NT or cystic hygroma. The remaining seven cases were identified at late gestation for abnormal ultrasound findings. CMA revealed 4p deletions to be terminal in all of the ten cases. Deletion sizes ranged from 2.05 to 19.02 Mb.Conclusion: Prenatal findings such as increased NT, severe and early onset intrauterine growth retardation, and renal dysplasia or oligohydramnios should warrant the diagnosis of WHS and invasive testing using CMA. [ABSTRACT FROM AUTHOR]

The fetal face is an essential source of information in the assessment of congenital malformations and neurological anomalies. Disturbance in early stages of development can lead to a wide range of effects, from subtle changes in facial and neurological features to characteristic facial shapes observed in craniofacial syndromes. Three-dimensional ultrasound (3D US) can provide more detailed information about the facial morphology of the fetus than the conventional 2D US, but its use for pre-natal diagnosis is challenging due to imaging noise, fetal movements, limited field-of-view, low soft-tissue contrast, and occlusions. In this paper, we propose the use of a novel statistical morphable model of newborn faces, the BabyFM, for fetal face reconstruction from 3D US images. We test the feasibility of using newborn statistics to accurately reconstruct fetal faces by fitting the regularized morphable model to the noisy 3D US images. The results indicate that the reconstructions are quite accurate in the central-face and less reliable in the lateral regions (mean point-to-surface error of 2.35 mm vs 4.86 mm). The algorithm is able to reconstruct the whole facial morphology of babies from US scans while handle adverse conditions (e.g. missing parts, noisy data). The proposed algorithm has the potential to aid in-utero diagnosis for conditions that involve facial dysmorphology. [ABSTRACT FROM AUTHOR]

As an effective way of routine prenatal diagnosis, ultrasound (US) imaging has been widely used recently. Biometrics obtained from the fetal segmentation shed light on fetal health monitoring. However, the segmentation in US images has strict requirements for sonographers on accuracy, making this task quite time-consuming and tedious. In this paper, we use DeepLabv3+ as the backbone and propose an Integrated Semantic and Spatial Information of Multi-level Features (ISSMF) based network to achieve the automatic and accurate segmentation of four parts of the fetus in US images while most of the previous works only segment one or two parts. Our contributions are threefold. First, to incorporate semantic information of high-level features and spatial information of low-level features of US images, we introduce a multi-level feature fusion module to integrate the features at different scales. Second, we propose to leverage the content-aware reassembly of features (CARAFE) upsampler to deeply explore the semantic and spatial information of multi-level features. Third, in order to alleviate performance degradation caused by batch normalization (BN) when batch size is small, we use group normalization (GN) instead. Experiments on four parts of fetus in US images show that our method outperforms the U-Net, DeepLabv3+ and the U-Net++ and the biometric measurements based on our segmentation results are pretty close to those derived from sonographers with ten-year work experience. [ABSTRACT FROM AUTHOR]

The use of exome sequencing (ES) in the prenatal setting improves the diagnostic yield of genetic testing for fetuses with ultrasound anomalies. However, while the purpose of ES is to explain the fetal phenotype, secondary or incidental findings unrelated to the observed abnormalities might be detected. Recently, requests for ES in fetuses with no sonographic abnormalities have been increasing, raising serious ethical and medico-legal concerns. Variant interpretation is complex even in the postnatal setting and performing broad genomic data analyses in the prenatal setting presents additional dilemmas. This article discusses challenges and questions related to prenatal ES, including variant interpretation of incidental findings in cases of indicated prenatal ES, as well as in situations where ES is performed in asymptomatic fetuses. [ABSTRACT FROM AUTHOR]