Clinical and molecular characteristics of 26 fetuses with lethal multiple congenital contractures.

Multiple congenital contractures (MCC) due to fetal akinesia manifest across a broad spectrum of diseases, ranging from mild distal arthrogryposis to lethal fetal akinesia deformation sequence. We hereby present a series of 26 fetuses displaying severe MCC phenotypes from 18 families and describe detailed prenatal ultrasound findings, postmortem clinical evaluations, and genetic investigations. Most common prenatal findings were abnormal facial profile (65%), central nervous system abnormalities (62%), polyhydramnios (50%), increased nuchal translucency (50%), and fetal hydrops (35%). Postmortem examinations unveiled additional anomalies including facial dysmorphisms, dysplastic skeletal changes, ichthyosis, multiple pterygia, and myopathy, allowing preliminary diagnosis of particular Mendelian disorders in multiple patients. Evaluation of the parents revealed maternal grip myotonia in one family. By exome sequencing and targeted testing, we identified causative variants in ACTC1, CHST14, COG6, DMPK, DOK7, HSPG2, KLHL7, KLHL40, KIAA1109, NEB, PSAT1, RAPSN, USP14, and WASHC5 in 15 families, and one patient with a plausible diagnosis associated with biallelic NEB variants. Three patients received a dual diagnosis. Pathogenic alterations in newly discovered genes or in previously known genes recently linked to new MCC phenotypes were observed in 44% of the cohort. Our results provide new insights into the clinical and molecular landscape of lethal MCC phenotypes.

Association of Antenatal Evaluations with Postmortem and Genetic Findings in the Series of Fetal Osteogenesis Imperfecta.

INTRODUCTION: Counseling osteogenesis imperfecta (OI) pregnancies is challenging due to the wide range of onsets and clinical severities, from perinatal lethality to milder forms detected later in life. METHODS: Thirty-eight individuals from 36 families were diagnosed with OI through prenatal ultrasonography and/or postmortem clinical and radiographic findings. Genetic analysis was conducted on 26 genes associated with OI in these subjects that emerged over the past 20 years; while some genes were examined progressively, all 26 genes were examined in the group where no pathogenic variations were detected. RESULTS: Prenatal and postnatal observations both consistently showed short limbs in 97%, followed by bowing of the long bones in 89%. Among 32 evaluated cases, all exhibited cranial hypomineralization. Fractures were found in 29 (76%) cases, with multiple bones involved in 18 of them. Genetic associations were disclosed in 27 families with 22 (81%) autosomal dominant and five (19%) autosomal recessive forms, revealing 25 variants in six genes (COL1A1, COL1A2, CREB3L1, P3H1, FKBP10, and IFITM5), including nine novels. Postmortem radiological examination showed variability in intrafamily expression of CREBL3- and P3H1-related OI. CONCLUSION: Prenatal diagnosis for distinguishing OI and its subtypes relies on factors such as family history, timing, ultrasound, genetics, and postmortem evaluation.

Fetal skeletal dysplasia cohort of a single tertiary referral center in Istanbul, Turkey.

We report on 314 fetal cases from 297 unrelated families with skeletal dysplasia evaluated in the postmortem period from 2000 to 2017 at a single clinical genetics center in Istanbul, Turkey. The definite diagnostic yield was 40% during the prenatal period, while it reached 74.5% when combined with postmortem clinical and radiological evaluation. Molecular analyses were performed in 25.5% (n: 76) of families, and 21 novel variants were identified. Classification according to International Skeletal Dysplasia Society-2019 revision revealed limb hypoplasia-reduction defects group (39) as the leading one, 24.5%, then followed by FGFR3 chondrodysplasias, osteogenesis imperfecta, and decreased mineralization and polydactyly-syndactyly-triphalangism groups 13.6, 11.1, and 8.9%, respectively. The inheritance pattern was autosomal recessive in 54% and autosomal dominant in 42.6% of index cases. The overall consanguinity rate of the cohort was 33%. The high prevalence of ultrarare diseases along with two or more unrelated autosomal recessive entities running in the same family was noteworthy. This study highlights the pivotal role of postmortem evaluation by an experienced clinical geneticist to achieve a high diagnostic yield in fetal skeletal dysplasia cohorts. The cohort is not only a representation of the spectrum of skeletal dysplasias in a population with a high consanguinity rate but also provides an ideal research group to work on to identify the unknowns of early fetal life.

The correlation between pregnancy, disease activity and adverse pregnancy outcomes in patients with systemic lupus erythematosus.

OBJECTIVE: In this study, our pregnant systemic lupus erythematosus (SLE) cohort, which was under medical surveillance of both our Rheumatology and Obstetrics departments, was analyzed. We intended to determine the effects of pregnancy on disease activity and the correlation between disease flares and adverse pregnancy outcomes. METHODS: One hundred sixty eight pregnancy data involving 136 patients with SLE were examined. Cumulative clinical, laboratory, and serological parameters were described. Disease activity and flares were calculated using the systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K) in the pre/postpartum periods and the SLEPDAI in the three trimesters of pregnancy. Patients with a SLEDAI-2K or SLEPDAI ≥ 4 were classified as "active." Patients with lupus low disease activity state (LLDAS) during each of these periods were identified.Fetal/neonatal death, premature birth due to pre-eclampsia, eclampsia or hemolysis, elevated Liver enzymes (HELLP) syndrome, and neonates small for gestational age were determined as adverse pregnancy outcomes (APO). RESULTS: Out of 168 pregnancies, there were 60 (35.7%) pregnancies with flares covering the pregnancy and 6 months of postpartum period. The mean SLEDAI in the 6 months postpartum period was significantly higher compared to mean disease activity during pregnancy (p < .05). Of all pregnancies, 132 (78.6%) were in LLDAS during pregnancy. Comparison of the frequency of severe postpartum flares in patients who were in LLDAS during pregnancy revealed a lower percentage of flares compared to those who were not in the LLDAS group (11 vs 29%, p < .05). APO was observed in 33.9% of 168 pregnancies. The mean SLEPDAI score was significantly higher in APO+ pregnancies than in APO- pregnancies (4.9 ± 6.1 vs 2.8 ± 4.9, p = .002). Comparison of SLICC damage score between APO - and + pregnancies revealed a significantly higher score in APO+ pregnancies (1.8 ± 2.1 vs 0.8 ± 1.3, p = .001). CONCLUSION: Postpartum six-month period appears to have the highest risk for disease flares during SLE pregnancies. Disease activity during pregnancy increases the risk of APO. In order to achieve a positive pregnancy outcome and lower maternal morbidity, regular follow-up of patients is necessary.

Predictive value of ultrasound in prenatal diagnosis of hypospadias: hints for accurate diagnosis.

OBJECTIVES: This study aims to assess the diagnostic accuracy of targeted ultrasound examination in prenatal diagnosis of hypospadias and to evaluate the predictive values of defined ultrasonographic findings of hypospadias. METHODS: The cases diagnosed with hypospadias in our fetal medicine center were identified on an electronic database. The ultrasound reports, images and hospital records were reviewed retrospectively. The predictive value of prenatal ultrasound diagnosis and the predictive values of each sonographic finding were assessed according to the postnatal clinical examinations. RESULTS: Thirty-nine cases were diagnosed with hypospadias on ultrasound during the 6 years. Nine fetuses with missing postnatal examination records were excluded. Twentytwo of the remaining fetuses had their prenatal diagnosis of hypospadias confirmed in postnatal examinations, indicating a 73.3 % positive predictive value. Normal external genitalia was detected in postnatal examinations of three fetuses. Five fetuses were diagnosed with other external genital abnormalities, including micropenis (n=2), clitoromegaly (n=2), and buried penis with bifid scrotum (n=1) in postnatal examinations. The positive predictive value of prenatal ultrasound for any external genital abnormality was 90 %. CONCLUSIONS: Although the positive predictive value of ultrasound for genital anomalies is satisfying, it is slightly lower for the specific diagnosis of hypospadias. This reflects overlapping ultrasound findings of different external genitalia anomalies. Standardized, systematic evaluation of the internal and external genital organs, karyotyping and genetic sex determination are essential to achieve a precise prenatal diagnosis of hypospadias.

Prenatal ultrasonographic features in Blomstrand osteochondrodysplasia: Antenatal case series confirmed by postmortem radiology and molecular diagnosis.

OBJECTIVE: Blomstrand osteochondrodysplasia (BOCD, MIM #215045) is an ultrarare lethal skeletal dysplasia (LSD) perinatally, characterized by extremely advanced bone maturation, generalized osteosclerosis, and severe tetramicromelia caused by biallelic loss-of-function mutations in the parathyroid hormone receptor-1 gene (PTHR1). We aim to describe prenatal ultrasonographic features in a retrospective fetal case series of BOCD and emphasize the importance of multidisciplinary antenatal evaluation of LSDs to improve the differential diagnosis. METHOD: Prenatal ultrasound findings of five fetal cases diagnosed with BOCD between 2000 and 2019 in the Prenatal Diagnosis Unit and Medical Genetics were reviewed, along with postmortem examination results and confirmatory molecular results. RESULTS: All fetuses presented with severe sonographic findings of LSDs comprising tetramicromelia, thoracic hypoplasia, and retro-micrognathia. Marked cervical hyperextension was present in three fetuses. Flared metaphyses were prenatally identified in only one fetus. X-rays of four fetuses evaluated postmortem showed advanced bone maturation, generalized osteosclerosis, and dumbbell-like appearance of long bones due to metaphyseal enlargement. CONCLUSION: The presence of retro-micrognathia along with a protruding tongue and severe metaphyseal flaring can suggest a diagnosis of BOCD, when prenatal ultrasound findings are indicative for LSD. The diagnosis can be ascertained through postmortem clinical and radiological evaluation and/or molecular testing.

Prenatal sonographic and cytogenetic/molecular findings of 22q11.2 microdeletion syndrome in 48 confirmed cases in a single tertiary center.

PURPOSE: We aimed to present the fetal ultrasound, cytogenetic/molecular testing and postmortem or postnatal clinical findings of cases with 22q11.2DS diagnosed prenatally. MATERIALS AND METHODS: A retrospective medical record review of 48 prenatal cases diagnosed with 22q11.2DS were evaluated in our institution. Detailed ultrasound examination was performed on all fetuses. Postmortem and postnatal examinations were evaluated. The microdeletions were detected by karyotyping or microarray, then confirmed by FISH. Descriptive statistical analysis was performed. RESULTS: Demographic data of 48 prenatal cases including 46 singletons and 1 dichorionic diamniotic twin pregnancy were evaluated. The most common extracardiac anomaly was skeletal system anomalies (25%), in which PEV was the most frequent one (20.8%). Polyhydramnios rate was detected as 31%, in 6.6% as an isolated finding. Microdeletion has been detected by karyotyping in 13 cases (13/47, 27.7%) (including 2 unbalanced translocations), by FISH in 28 cases (28/48, 58.3%), by microarray/a-CGH testing in 7 cases. Microarray analysis showed that in one case with unbalanced translocation had two consecutive deletions; one was proximal and other one distal to critical region and not encompassing TBX1 gene but CRKL and LZTR1 genes. CONCLUSION: The current study demonstrates the whole spectrum of atypical phenotypic and genotypic variations of 22q11.2DS in the largest prenatal case series reported to date. Therefore, differential diagnosis should be considered not solely in CHD, but also in the presence of isolated clubfeet and polyhydramnios. Establishing the diagnosis in the prenatal period may allow a postnatal multidisciplinary approach, as well as affect the actual prevalence of the disease.

Intertwin membrane cord insertion in dichorionic twin pregnancy: The description and comparison with other umbilical cord insertion types.

PURPOSE: Multiple pregnancy is associated with high perinatal mortality and morbidity. Abnormal cord insertions more common in twin pregnancies compared to singleton pregnancies and velamentous cord insertion is related with poor pregnancy outcomes. There is no definition of velamentous cord insertion into the intertwine membrane between two fetuses in the literature. METHODS: In our single-center cross-sectional study, monochorionic-diamniotic and dichorionic-diamniotic twins who were admitted to our clinic between 18 + 0 and 23 + 6 weeks of pregnancy were enrolled in this study. We evaluated fetal, placental, and umbilical cord abnormalities in addition to fetal growth restrictions and weight discordance by ultrasonography. RESULTS: Although abnormal cord insertion frequency was significantly higher in monochorionic twins (p = 0.003), intertwin membrane cord insertion could only occur in dichorionic twins. In cases with cord insertion anomaly; FGR and weight discordance was observed more frequently (p < 0.001 and p = 0.003, respectively). Weight discordance, the presence of abnormal cord insertion and abnormal UAD were found as statistically significant predictors of FGR (p < 0.001, p = 0.021, and p < 0.001, respectively). CONCLUSION: Intertwin membrane insertion is a novel umbilical cord insertion abnormality. The presence of abnormal umbilical cord insertion is a risk factor for poor pregnancy outcomes in twin pregnancies.

The Giant Infantile Fibrosarcoma of Fetal Oropharynx and Anterior Neck.

Introduction: Infantile fibrosarcoma (IFS) usually arises in the extremities during the first 12 months of life and responds well to surgery. It is unusual in the oropharynx or the prenatal period. Case report: A giant solid mass was first detected in the oropharynx and anterior neck at 24 weeks of gestation by ultrasound and fetal MRI. An EXIT procedure with intrapartum intubation with appropriate supportive therapy was successful. The diagnosis of IFS was made postpartum, and the lesion responded to neoadjuvant chemotherapy. Conclusion: IFS may arise as early as 24 weeks of gestation. In this case, an EXIT procedure allowed postpartum diagnosis with subsequent treatment.

Prenatal diagnosis and outcome of unilateral multicystic kidney.

We reviewed the records of 144 patients. The mean gestational age at first US diagnosis was 27.5 ± 4.3 weeks. An anomaly of the contralateral kidney was detected in 25% of cases. An extrarenal anomaly was detected in 13.8%. Karyotype analysis was performed in 16.6% of cases and revealed trisomy 18 in 2 cases with extrarenal defects. Karyotype analysis was normal in all the patients who had isolated multicystic dysplastic kidney (MCDK). The diagnostic accuracy of prenatal ultrasound was 92.2%. Contralateral kidney anomaly was detected 33.9% of patients, and half of these were vesicoureteral reflux. Antihypertensive therapy was required in 2.6% of cases. Nephrectomy was performed in 8%, and partial or total involution of MCDK was achieved in 33.9% of patients. MCDK can be accurately diagnosed by prenatal sonography, and prognosis depends on extrarenal and contralateral renal abnormalities. In isolated cases, require of surgery is rare, and serial follow-up is suggested to determine involution.Impact statementWhat is already known on this subject? Multicystic dysplastic kidney (MCDK) is one of the most renal anomalies and is associated with numerous renal and extrarenal abnormalities. It can lead to severe consequences in the neonatal period.What do the results of this study add? The accuracy of prenatal ultrasonography is excellent for detecting MCDK. In isolated unilateral cases, chromosomal aberrations are low, and the majority of them involute spontaneously. A periodic follow-up of the contralateral kidney is mandatory due to an increased risk of an anomaly. Genital anomaly risk is increased in males.What are the implications of these findings for clinical practice and/or further research? Detailed evaluation and follow-up of the contralateral kidney are crucial for counselling in isolated cases. Karyotype analysis in isolated unilateral MCDK is debateable. Postnatal prognosis is encountering, and the majority of patients have no requirement of surgery.

Follow-Up Studies of cf-DNA Testing from 101 Consecutive Fetuses and Related Ultrasound Findings.

PURPOSE: To determine the true- and false-positive rates of cf-DNA testing in a cohort of patients from tertiary care centers and assess the impact of ultrasound examinations in pregnancy management. MATERIALS AND METHODS: Clinical, cytogenetic and ultrasound data of 101 consecutive fetuses were collected retrospectively. Cases were classified into five groups according to the ultrasound findings. Karyotyping, interphase FISH and microarray techniques were used for follow-up studies. RESULTS: The overall false-positive rate was low for trisomy 21 (T21, 8.2 %), but significantly higher for trisomy 18 (T18, 40 %), monosomy X (MX, 50 %), X/Y trisomies (57.1 %), trisomy 13 (T13, 71.4 %). While single cases of trisomy 16, trisomy 22 and 8q duplication positive in cf-DNA were confirmed, 3 microdeletions (1p36 and two 22q11.2) were not. About 75 % of confirmed T21's and all confirmed T18 and T13 had major markers and/or malformations. While false-negative cases (two T21, one T18 and one T13) were identified due to abnormal ultrasound findings, all false-positive cases were normal sonographically. Ultrasound findings of confirmed trisomy 16, 22, dup8q, monosomy X and other X/Y aneuploidies were unspecific. Term placenta studies were helpful to assess the role of confined mosaicism in unconfirmed cf-DNA test results. A vanishing twin has been observed as the likely cause of one false-positive T18. CONCLUSION: Our study contributes clinical data on discrepant cf-DNA testing results, corroborates the need for confirmational invasive testing and underscores the benefit of expert ultrasound in the prevention of fatal diagnostic errors.

Prenatal diagnosis of complete penoscrotal transposition with normal scrotum: Two case reports and review of the literature.

Complete penoscrotal transposition is an extremely rare congenital anomaly and is usually associated with other urinary system abnormalities. Prenatal diagnosis is feasible by demonstrating perineal anatomy and its relation with scrotum and phallus. We describe two prenatal cases presenting with oligohydramniosis and megacystis due to lower urinary tract obstruction. Postnatal diagnosis was confirmed in both cases. Considering the dismal perinatal outcome, an accurate prenatal diagnosis is required for counseling the parents and preparing for postnatal care.

Utilization of neurosonography for evaluation of the corpus callosum malformations in the era of fetal magnetic resonance imaging.

AIM: We evaluated the ability of fetal neurosonography and magnetic resonance imaging (MRI) to asses callosal anomalies (CA) and associated cranial malformations. We also aimed to determine the long-term prognosis of the cases. METHODS: Thirty-six cases of CA diagnosed combined with neurosonography and MRI between January 2012 and October 2017 were retrospectively reviewed. RESULTS: Seventeen of 36 fetuses were diagnosed complete agenesis of corpus callosum (CACC) (47.2%), 9 had partial agenesis of corpus callosum (PACC) (25%) and 10 was dysgenesis of the corpus callosum (DCC) (27.2%) at ultrasonography (US) examination. Fetal MRI reported 16 of cases as CACC (44.4%), 11 PACC (30.5%) and nine (25%) DCC. The overall consistency between neurosonography and MRI in the definition of CA were 91% of cases. Sulcation anomalies were present in 9 cases in the US (25%) and 11 cases in MRI (30.4%). Seven of cases showed posterior fossa abnormalities in the US (19.4%) and eight cases in MRI (22.1%). Neonatal MRI added new findings to fetal MRI and neurosonography including grade-1 intraventricular hemorrhage and periventricular leukomalacia in two cases (12.5%). Eighteen cases were terminated (50%), 17 cases were followed up and mean follow up interval was 39 ± 5.1 months. The neurologic outcome was abnormal in seven (41.7%) patients. Presence of associated brain anomalies worsened the prognosis. CONCLUSION: Fetal neurosonography has a comparable performance with MRI in the diagnosis of CA and associated anomalies. It should be used in collaboration with MRI to achieve accurate diagnosis which is crucial for counseling.

Prenatal Incidence and Clinical Value of the Absence of 12th Ribs in a Population in a Setting of Detailed Second-Trimester Sonography.

OBJECTIVES: We aimed to determine the incidence of the absence of the (last) 12th ribs in a population in a setting of detailed 2nd-trimester sonography using three-dimensional (3D) ultrasound and to assess whether or not this may be related to chromosomal aneuploidies. METHODS: Prospectively, we counted fetal ribs for the absence of the (last) 12th ribs in singleton pregnancies of women who presented to our clinic for detailed 2nd-trimester sonography. The assessment was carried out using 3D ultrasound. Volume data sets were acquired with the 3D skeleton mode using the maximum intensity with X-ray-weighted rendering. If the 3D skeleton mode was not sufficient, volume contrast imaging with the OmniView bone mode was used. RESULTS: The fetal ribs could be visualized in 97.01% of the 1,943 fetuses examined between 20 and 23 weeks' gestation. Timing the examination at 21, 22, or 23 weeks was found to be more successful than conducting it at 20 weeks. Twelfth ribs were found to be absent in 33 fetuses; 16 fetuses had 11 ribs unilaterally and 17 had so bilaterally. None of them had chromosomal abnormalities. Associated anomalies were present in 6 fetuses (18.2%); 2 of the anomalies were major and 4 minor. CONCLUSION: The incidence of absent 12th ribs in this mixed population was 1.75%. In the absence of additional anomalies, the prognosis is favorable.

Prenatal Diagnosis and Management of Ectopia Cordis: Varied Presentation Spectrum.

BACKGROUND: Ectopia cordis (EC) is a congenital anomaly associated with heart defects and extracardiac malformations. OBJECTIVES: We determined the various presentations of EC diagnosed in our center between 2010 and 2017. RESULTS: Seven fetuses from six pregnancies with EC were detected, five during the first trimester. Three were from multiple pregnancies, and both twins had EC in one monochorionic-monoamniotic pregnancy. Abdominal wall defects were detected in six fetuses. Kyphoscoliosis, cephalocele, clubfoot and short umbilical cord were other abnormalities. Five fetuses were terminated, one fetus died in utero, and one baby died on day two of life. Postnatal evaluation performed in all cases additionally detected cleft lips/palates in two fetuses and tetralogy of Fallot in one. CONCLUSION: Outcome is poor for these fetuses, EC can occur in a multiple pregnancy, most of the abnormalities can be identified in the first trimester and fetopsy continues to add information to the intrauterine diagnosis.

Pregnancy in liver transplant recipients: A single center outcomes.

AIM: Liver transplantation (LT) is the only effective treatment for the end-stage liver disease. Although pregnancy after LT is considered to be safe, these patients are difficult to manage for obstetricians. In this study, we aimed to determine maternal and fetal outcomes in pregnancies after LT. METHODS: We conducted a retrospective review of liver transplant recipients who had received prenatal care and delivered pregnancy at Istanbul University Istanbul Medical Faculty, Department of Obstetrics and Gynecology January 2010 and January 2017. RESULTS: A total of eight pregnancies were identified during the study period. The mean age of the patients at the time of LT was 25.6 ± 5.3 years (range 19-36 years), and the mean age at conception was 30.1 ± 5.2 years (range 25-41 years). The mean interval between transplantation and conception was 54.2 ± 18.6 months (range 24-82 months). There was no a miscarriage or a stillbirth was observed in any of patients. Mean birth week was 37.2 ± 2.1 weeks and mean birthweight was 2852 ± 562 g (range 2150-3470 g). Three of eight deliveries (37.5%) occurred before 37 gestational weeks. Preeclampsia was detected in one patient, one pregnancy was complicated by intrauterine growth retardation and one case with gestational diabetes mellitus. Mean postnatal follow-up period was 3.2 ± 2.4 years (range 1-7 years) and all of the babies were healthy. Graft rejection occurred in one patient after delivery. CONCLUSION: More favorable pregnancy outcomes can be achieved with a multidisciplinary team and satisfactory counseling is mandatory either preconception and through the pregnancy to reduce maternal-fetal risks.

Prenatal Diagnosis of Persistent Hyperplastic Primary Vitreous: Report of 2 Cases and Review of the Literature.

Persistent hyperplastic primary vitreous is a spectrum of congenital ocular abnormalities characterized by leukocoria, microphthalmia, cataracts, extensive intravitreal hemorrhage, persistence of the hyaloid artery, glaucoma, and retinal detachment. It might be isolated or associated with congenital syndromes such as trisomy 13, Walker-Warburg syndrome, and Norrie disease. We present 2 cases of persistent hyperplastic primary vitreous diagnosed by prenatal sonography in the early third trimester. Bilateral hyperechoic lenses and retinal nonattachment were detected in the sonographic examination of the first case, whereas irregular echogenic bands between the lenses and posterior walls of the eyes were prominent in the second case. In both of the cases, ocular findings were accompanied by intracranial findings, including severe hydrocephalus, an abnormal gyral pattern, and cerebellar hypoplasia, suggesting the diagnosis of Walker-Warburg syndrome. We also present a review of the literature regarding the prenatal diagnosis of this malformation.

Prenatal diagnosis of tethered spinal cord associated with sacrococcygeal teratoma.

Tethered spinal cord is mostly caused by myelomeningocele and lipomyelomeningocele, while dermal sinus tract, diastematomyelia, lipoma, tumor, thickened/tight filum terminale, spinal trauma, and spinal surgery are among the other causes. Prenatal diagnosis of tethered cord has been reported, and it is usually associated with neural tube defects. We present an atypical presentation of a tethered spinal cord, which was associated with a sacrococcygeal teratoma and was diagnosed in the 23rd week of pregnancy by ultrasonography. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:506-509, 2016.

Fetal nasal bone hypoplasia in the second trimester: Comparison of diagnostic methods for predicting trisomy 21 (Down syndrome).

PURPOSE: The aim of this prospective observational study was to identify the best method for use in diagnosing fetal nasal bone (NB) hypoplasia in the second trimester as a means of predicting trisomy 21 (Down syndrome). METHODS: The NB length (NBL), NBL percentiles, and NBL multiple-of-median (MoM) values and the biparietal diameter-to-NBL ratios were calculated and compared in an attempt to identify the best predictive method and most appropriate cutoff value. Predictive values for several cutoff points were calculated. Receiver operating characteristic curves at a fixed 5% false-positive rate were used to compare the four methods. RESULTS: NBL measurements were obtained from 2,211 (95.6%) of a total of 2,314 fetuses. Data from 1,689 of those 2,211 fetuses were used to obtain reference ranges, derive a linear regression equation, and calculate NBL percentiles and MoM values. Using a fixed 5% false-positive rate, we found 25.5% sensitivity for NBL (95% confidence interval [CI], 15-39.1) and 23.5% sensitivity for NBL percentiles (95% CI, 13.4-37), NBL MoM values (95% CI, 13.4-37), and biparietal diameter-to-NBL ratios (95% CI, 13.4-37). CONCLUSIONS: Our study demonstrated that all four methods can be used in the second trimester for diagnosing fetal NB hypoplasia as a means of predicting trisomy 21 because their predictive values are similar at a fixed 5% false-positive rate. For simplicity of use, we recommend using 3 mm as the NBL cutoff value.

Prenatal ultrasonographic diagnosis of generalized arterial calcification of infancy.

A healthy 19-year-old nulliparous pregnant woman was referred to our clinic because of fetal pericardial effusion and ascites. The sonographic examination performed at 28 weeks' gestation revealed scalp edema, severe skin edema, bilateral hydrocele, ascites, and pleural and pericardial effusion. Fetal echocardiographic examination showed that both ventricles were dilated with severely depressed contractility. The aortic annulus, ascending aorta, aortic arch, descending aorta, common iliac arteries, main pulmonary artery, tricuspid valve, and mitral chordae tendinae were hyperechogenic. Right ventricular outflow tract was narrow with decreased blood flow. There was tricuspid and mitral valve regurgitation and tricuspid valve stenosis. On the basis of these findings, we made the diagnosis of generalized arterial calcification, which is characterized by extensive calcification of internal elastic lamina and intimal proliferation of medium-sized and large arteries. This diagnosis was confirmed histologically after the termination of pregnancy.