Degraded Bone Microarchitecture in Women with PHPT-Significant Predictor of Fracture Probability.

Introduction: Patients with primary hyperparathyroidism (PHPT) experience bone mineral density (BMD) loss and trabecular bone score (TBS) alteration, which current guidelines recommend assessing. Considering TBS alongside BMD for a 10-year fracture risk assessment (FRAX) may improve PHPT management. Design: Retrospective, cross-sectional study composed of 49 Caucasian females (62 ± 10.6 years, 27.7 ± 0.87 kg/m2) with PHPT and 132 matched control subjects (61.3 ± 10.5 years, 27.5 ± 0.49 kg/m2) evaluated in 3 years. We assessed lumbar spine (LS) and femoral neck (FN) BMD, T and Z scores (GE Healthcare Lunar Osteodensitometer) and TBS (iNsight 1.8), major osteoporotic fracture (MOF), and hip FRAX. Results: Patients with PHPT had statistically lower mean values for lumbar spine bone mineral density (LS BMD) (0.95 ± 0.25 vs 1.01 ± 0.14 g/cm2, P = .01), LS T-scores (-2 ± 0.2 vs -1.4 ± 0.1 SD, P = .009), LS Z scores (-0.9 ± 0.19 vs -0.1 ± 0.11 SD, P = .009), femoral neck bone mineral density (FN BMD) (0.79 ± 0.02 vs 0.83 ± 0.01 g/cm2, P = .02), FN T-scores (-1.8 ± 0.13 vs -1.5 ± 0.07 SD, P = .017), FN Z scores (-0.51 ± 0.87 vs -0.1 ± 0.82 SD, P = .006), and TBS (0.95 ± 0.25 vs 1.01 ± 0.14 g/cm2, P = .01) compared with control subjects. 22.4% of patients with PHPT had degraded microarchitecture (TBS < 1.2) vs. 7.6% in control group (χ2 = 0.008). PHPT proved to be a covariate with unique contribution (P = .031) alongside LS BMD (P = .040) in a linear regression model [R 2 = 0.532, F(4,16) = 4.543] for TBS < 1.2. TBS adjustment elevated MOF FRAX both for PHPT (4.35 ± 0.6% vs 5.25% ± 0.73%, P < .001) and control groups (4.5 ± 0.24% vs 4.7% ± 0.26%, P < .001) compared with BMD-bases FRAX, but also increased differently between the 2 study groups (1.1-folds for PHPT patients and 1.04 for control subjects, P = .034). Conclusion: Compared with control, TBS-adjusted FRAX provides significantly higher MOF risk than BMD-based FRAX in PHPT women.

An Overview of Cytomegalovirus Infection in Pregnancy.

The objective of this review was to bring to attention cytomegalovirus (CMV) infection during pregnancy, taking into consideration all relevant aspects, such as maternal diagnosis, fetal infection and prevention, prenatal diagnosis, and postnatal prognosis. A literature review was performed regarding adult and congenital infection. General information regarding this viral infection and potential related medical conditions was provided, considering the issues of maternal infection during pregnancy, transmission to the fetus, and associated congenital infection management. Prenatal diagnosis includes maternal serum testing and the confirmation of the infection in amniotic fluid or fetal blood. Additionally, prenatal diagnosis requires imaging techniques, ultrasound, and complementary magnetic resonance to assess cortical and extracortical anomalies. Imaging findings can predict both fetal involvement and the postnatal prognosis of the newborn, but they are difficult to assess, even for highly trained physicians. In regard to fetal sequelae, the early diagnosis of a potential fetal infection is crucial, and methods to decrease fetal involvement should be considered. Postnatal evaluation is also important, because many newborns may be asymptomatic and clinical anomalies can be diagnosed when sequelae are permanent.

Operator experience impact on the evaluation of still images of a first trimester cardiac assessment protocol.

OBJECTIVE: Congenital heart disease (CHD) is the most common birth defect and represents the leading cause for mortality and morbidity in infants and young adults. Early fetal echocardiography is usually considered a highly specialized scan. The goal of this study is to evaluate the impact of operator's experience in assessing still images of the 4-chamber view and 3-vessels view and to evaluate the feasibility and the performance of a first trimester screening protocol for CHD. METHODS: An online questionnaire consisting of still images of the 4-camber view and 3-vessel view from 50 normal and abnormal cases was reviewed by an expert group made of seven obstetricians specialized in fetal medicine and a nonexpert group made of 13 obstetricians that are certified in ultrasound. After individually visualizing each image set made of the 4-chamber view and 3-vessel view, they had to conclude if the case was normal or abnormal and what images were abnormal. RESULTS: A total of 50 image sets of both normal and abnormal fetal hearts were examined by the 20 reviewers, resulting in 1000 evaluations. The expert group achieved a detection rate of 97.1% with a false positive rate of 5.7%. The nonexpert group achieved also a good detection rate of 91.3% but with a much higher false positive rate of 33.9%. The most frequently missed CHD involved the great arteries and had a normal 4-chamber view. In the majority of false positive cases the 3-vessel view was incorrectly interpreted as abnormal. CONCLUSIONS: A screening protocol for CHD, based on the 4-chamber view and 3-vessel view alone can offer a good detection rate for CHD with a small false positive rate, but only if it is implemented by highly specialized sonographers.

Ultrasound Patterns in the First Trimester Diagnosis of Congenital Heart Disease.

Congenital heart disease (CHD) is the most common birth defect, with a reported prevalence of 5-12 per 1000 live births. Very recently, the American Institute of Ultrasound in Medicine published a guideline recommending the use of the four-chamber and the three-vessel and trachea views to screen for CHD in the first trimester of pregnancy. Our aim is to present abnormal image patterns that are seen in the four-chamber, three-vessel, and trachea views of the fetal heart in the first trimester and to describe their association with specific CHD types. We used a total of 29 cases of CHD from the archives of Filantropia Hospital and the Maternal and Child Health Institute (INSMC) fetal medicine units. We selected cases with a clear and well-documented diagnosis of the CHD type. We identified a series of repeating color doppler flow patterns seen in the four-chamber, three-vessel, and trachea views of the studied cases. Our observations could be developed into a diagnosis algorithm to orientate the examiner to the most likely type of CHD in individual cases.

Fetal Skeletal Dysplasias that Involve the Face: Binder Syndrome and Nager Syndrome.

Binder syndrome and Nager syndrome are part of the spectrum of skeletal dysplasias. Although exceedingly rare, both syndromes are amenable to prenatal diagnosis because they present with features that can be detected by prenatal ultrasound. Genetic prenatal diagnosis is sometimes possible but remains difficult if the etiology of the disease is not homogenous. In cases of severe skeletal dysplasias, the prognosis is unfavorable irrespectively of the genetic defect. In cases with only mild structural anomalies, prenatal counselling is especially difficult. We present cases of Binder syndrome and Nager syndrome diagnosed by us prenatally. We elaborate on the etiology of Binder syndrome and discuss the current classification of facial dysostoses.

A Broader Perspective on the Prenatal Diagnosis of Cornelia de Lange Syndrome: Review of the Literature and Case Presentation.

Cornelia de Lange syndrome (CDLS) is caused by pathogenic variants in genes which are structural or regulatory components of the cohesin complex. The classical Cornelia de Lange (CDLS) phenotype is characterized by distinctive facial features, growth retardation, upper limb reduction defects, hirsutism, and developmental delay. Non-classical phenotypes make this condition heterogeneous. Although CDLS is a heterogeneous clinical and genetic condition, clear diagnostic criteria have been described by specialist consensus. Many of these criteria refer to features that can be seen on prenatal ultrasound. The aim of this paper is twofold: to present the ultrasound findings in fetuses affected by CDLS syndrome; to discuss the recent advances and the limitations in the ultrasound and genetic prenatal diagnosis of CDLS. Our review aims to offer, apart from the data needed to understand the genetics and the prenatal presentation of the disease, a joint perspective of the two specialists involved in the prenatal management of this pathology: the fetal medicine specialist and the geneticist. To better illustrate the data presented, we also include a representative clinical case.

The outcome of structural heart defects diagnosed in the first trimester of pregnancy.

PURPOSE: We present the results of a detailed protocol of fetal heart examination in the first trimester, in a fetal medicine unit in Romania. METHODS: Since October 2009, in Filantropia Hospital in Bucharest, we have systematically assessed pregnancies at 11-14 weeks to screen for aneuploidies and for major fetal structural defects. The fetal anatomy examination protocol included the detailed assessment of the fetal heart. This was performed using the same principles as for the second trimester examination, in the entire cohort. RESULTS: Our population consisted of 7693 patients and 7816 embryos. The protocol for the ultrasound evaluation of the fetal heart was completed for 7597 embryos (97.2%). The outcome is known for 6912 cases (90.9%). We diagnosed 39 heart defects - 30 in the first trimester, seven in the second trimester, two postnatally. Twenty of the 39 heart defects were isolated cardiac malformations. Twelve of the isolated heart defects were diagnosed in the first trimester. The sensitivity of the first trimester ultrasound in identifying major heart defects was 76.92%. The overall survival in cases of isolated congenital heart disease diagnosed in the first trimester was significantly lower than the survival in the cases diagnosed in the second trimester. CONCLUSIONS: Many (76.92%) of the significant heart defects can be diagnosed by ultrasound examination, in the first trimester. Our study is an argument for developing the multidisciplinary approach needed for the management of early detected structural heart disease.

Diagnosis of Fetal Structural Anomalies at 11 to 14 Weeks.

OBJECTIVES: To assess the performance of first-trimester ultrasound (US) in identifying major fetal structural abnormalities in an unselected population. METHODS: We conducted a retrospective analysis of all pregnancies that underwent the 11- to 14-week scan in the Fetal Medicine Department of Filantropia Hospital in Bucharest, which were prospectively examined within our screening program. The purpose of the first-trimester US was to evaluate the risk for chromosomal abnormalities and to conduct fetal anatomic examination using a detailed protocol. RESULTS: Our population consisted of 7480 pregnant patients (7576 fetuses). The follow-up was completed for 6045 patients (6114 fetuses). The prevalence of major structural anomalies was 1.89%. In the first trimester, we identified 79% of all major structural anomalies. The highest detection rates were achieved for abdominal wall defects (100%), major central nervous system anomalies (88%), cardiac defects (74%), and skeletal anomalies (71%). The nuchal translucency was increased in 35% of the cases with structural anomalies, and 95% of these were diagnosed in the first trimester. Seventy percent of the patients who presented with structural anomalies and a normal nuchal translucency were diagnosed in the first trimester. CONCLUSIONS: Our results emphasize the importance of performing a detailed US examination at 11 to 14 weeks' gestation in identification of fetal structural defects.

Prenatal Genetic Testing for Dopa-Responsive Dystonia - Clinical Judgment in the Context of Next Generation Sequencing.

We present a family in which the first child was diagnosed with dopa-responsive dystonia based on biochemical findings only. Dopa-responsive dystonia is a severe heterogeneous genetic disease. The possibly involved genes are GCH1 and TH. In their second pregnancy, the parents came for genetic counseling and prenatal diagnosis late, at 12 weeks of gestation. Genetic testing in the affected child was performed, but the results were difficult to interpret. The identified mutations were classified as VOUS - variants of unknown clinical significance. Although possibly causative, a homozygous variant in the TH gene was not reported before in children with dopa-responsive dystonia. Due to limited time, establishing the fetal prognosis was challenging. Our report emphasizes the importance of a multidisciplinary approach in the context of new diagnostic techniques, such as Next Generation Sequencing. We illustrate the fact that behind any laboratory result remains sophisticated clinical judgment. We also describe a previously not reported variant of the TH gene in a child with severe, early-onset dystonia.

The first trimester combined test for aneuploidies - a single center experience.

PURPOSE: We present the results of the systematic application of the first trimester combined test for aneuploidies, in a Romanian center. METHODS: Since October 2009, in Filantropia Hospital in Bucharest, we have systematically been using the FMF (Fetal Medicine Foundation) combined first trimester test to screen for common aneuploidies at 11 to 13 + 6 weeks of gestation. We assessed the crown to rump length (CRL), nuchal translucency, fetal heart rate as well as PAPP-A, and free ß-hCG in maternal serum. We evaluated additional first trimester ultrasound markers in most of the cases. The individual risk for aneuploidies was calculated using the FMF algorithm. RESULTS: Pregnancy outcome is known for 6030 euploid fetuses and 42 aneuploid fetuses from our screening population. The detection rate for trisomy 21 of the combined test was 87.5% for a screen positive rate of 1.96%. All of the trisomy 18 and trisomy 13 cases were detected prenatally. Some of the trisomy 18 cases proved not to be symptomatic in the first trimester. CONCLUSIONS: Our results are similar to those of the main studies on the FMF method of first trimester screening for aneuploidies. Our numbers are small because of limited availability of the very specialized resources involved.