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Soft Markers in Us Anomaly Scan

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Soft Markers in Us Anomaly Scan SOFT MARKERS IN US ANOMALY SCAN Dr.Ghalandarpoor Assistant professor TUMS INTRODUCTION • Approximately 3 percent of live births are affected by a major structural malformation *With advances in prenatal ultrasound, many of these anomalies are now identified before birth. The etiology is diverse and includes environmental factors, genetic factors, or a combination of both. • As the landscape of genetic testing rapidly evolves, clinicians are often left with many questions about the most appropriate testing methods to use for their patients. FREQUENCY OF CHROMOSOME ABNORMALITIES • The finding of a fetal structural anomaly increases the possibility of a chromosome abnormality or genetic molecular defect • should prompt further evaluation into genetic etiologies. The frequency of a chromosome abnormality depends on the specific anomaly, the number of anomalies, and the combination of anomalies identified • In several retrospective series of prenatally detected anomalies on ultrasound that prompted genetic studies, an isolated fetal anomaly was associated with fetal chromosome abnormalities in 2 to 18 percent of cases; multiple anomalies were associated with a fetal chromosome abnormality in 13 to 35 percent of case • There are two types of fetal chromosomal abnormalities identifiable by karyotype and microarray: • Aneuploidy, which is an abnormal number of chromosomes • Aberrations of chromosome structure, such as deletions, rings, translocations, and Duplications Aneuploidy is the most common genetic abnormality detected by prenatal diagnosis • Of the 6006 fetal karyotypes obtained at one center, 151 of the 207 abnormalities (73 percent) were aneuploidies (trisomy, triploidy, monosomy), and about 90 percent of these involved chromosomes 21, 18, 13, X, or Y (135/207 or 65 percent of all karyotypic abnormalities) • Fetal chromosomal abnormalities are more common in the first and second trimesters than in live born infants, due to the high rate of spontaneous loss of these fetuses over the course of pregnancy • Termination of affected pregnancies also plays a role. THE ANTEPARTUM DETECTION OF FETAL ANEUPLOIDY IS ONE OF THE MAJOR GOALS OF PRENATAL SCREENING PROGRAMS • Sonographic examination is useful • fetuses with abnormal karyotypes often have anatomic changes or anomalies. • Sonographic findings, results of maternal cell-free DNA or biochemical marker screening, and parental risk factors for genetic disease are all considered in determining the risk that the fetus is affected. • However, invasive testing (amniocentesis or chorionic villus biopsy) is required to obtain a definitive karyotypic diagnosis. ULTRASOUND MARKERS • Soft markers are ultrasound findings of uncertain significance • They are often associated with normal fetuses (ie, normal variants), usually have no clinical sequelae, and are transient, resolving with advancing gestation or after birth. • They do carry an increased risk for fetal aneuploidy, however, and correlation with the patient's biochemical risk status should be done SOFT MARKERS • Increased nuchal translucency • Absent nasal bone • Echogenic bowel • Pyelectasis • Shortened long bones (humerus, femur) • Echogenic intracardiac focus • Choroid plexus cysts • Isolated soft markers are identified in 11 to 17 percent of normal fetuses • prevalence is higher in aneuploid fetuses and the likelihood of aneuploidy is significantly increased when more than one marker is present • Even in this setting, use of soft markers for screening for, or excluding, fetal aneuploidy is inefficient; however, • a detailed evaluation of fetal anatomy should be performed whenever one or more soft markers has been identified. • Screening for soft markers is not a component of a basic obstetrical ultrasound examination. • Detection and reporting of soft markers (ie, echogenic intracardiac focus and choroid plexus cysts) is controversial because this information is anxiety- provoking for patients, requires considerable time for counseling, and may lead to invasive prenatal testing. • Such testing may result in procedure-related loss of a normal fetus, and is costly. SOCIETY FOR MATERNAL-FETAL MEDICINE PROVIDES THE FOLLOWING GUIDANCE • For women who undergo cell-free DNA screening, ultrasound solely to assess nuchal translucency at 11 to 14 weeks is not recommended. • An isolated soft marker is not considered a marker for aneuploidy if the cell- free DNA screen or first- or second-trimester biochemical screen is negative. However, some soft markers may have clinical implications (eg, echogenic bowel may be associated with cystic fibrosis; pyelectasis may be associated with vesicoureteral reflux). • All women with a fetal structural abnormality on ultrasound should be offered diagnostic testing with chromosomal microarray. SECOND TRIMESTER NUCHAL FOLD • The nuchal fold is the measurement between the outer edge of the occipital bone to the outer margin of the skin and is taken in the axial plane. • An increase in this measurement is also associated with aneuploidy. An increased nuchal fold is detected in 20 to 33 percent of fetuses with Down syndrome and 0.5 to 2 percent of euploid fetuses • LR:11-17;may decreases over gestation SECOND TRIMESTER ABSENT NASAL BONE • the reported sensitivity of absent nasal bone for Down syndrome varies widely, but is generally lower than in the first trimester • The nasal bone is absent in about 30 to 40 percent of Down syndrome fetuses and 0.3 to 0.7 percent of euploid fetuses.it is hypoplastic in about 50 to 60 percent of Down syndrome fetuses and 6 to 7 percent of euploid fetuses. • Affected by race and ethnicity • Using either nasal hypoplasia or absence as a marker increases sensitivity, but also the false positive rate. Options include: * the ratio of biparietal diameter-nasal bone length (BPD/NB thresholds of >9 to >12 *a single pre-defined threshold for abnormal nasal bone length (≤2.5 mm), *a gestational age-based threshold (<2.5th or 5th centile) based on the distribution of nasal bone length in normal fetuses, or *use of multiple of the median(MoM) of nasal bone length for gestational age (<0.75 MoM). In a systematic review, the MoM method appeared to have the best combination of sensitivity and specificity (54 and 94 percent, respectively ECHOGENIC BOWEL • It may be first identified in the first trimester but is more commonly identified in the second trimester. • It has been found in 1 to 2 percent of normal fetuses and 13 to 21 percent of fetuses with Down syndrome. However, a variety of fetal and pregnancy complications have also been associated with this finding: other chromosomal defects, fetal growth restriction,cystic fibrosis, congenital infection, intraamniotic bleeding, and gastrointestinal obstruction • Aneuploidy has been associated with abnormal bowel function (decreased motility, increased water absorption) in newborns and it is possible that a similar process in the fetus could cause echogenic bowel PYELECTASIS • Pyelectasis or mild hydronephrosis is a common finding in fetuses. • diameter of ≥4 mm at 15 to 19 weeks of gestation demonstrated pyelectasis in 10 to 25% of fetuses with Down syndrome and 1 to 3 % of euploid fetuses. • Aneuploidy is present in 0.3 to 0.9% of fetuses with isolated pyelectasis • When pyelectasis is identified in an otherwise normal second trimester fetus, a normal cell-free DNA test for fetal aneuploidy can be very reassuring and obviate the need for invasive testing • In both euploid and aneuploid fetuses, pyelectasis is usually caused by vesicoureteral reflux, but may be related to obstruction. • Mild dilation (ie, 4 to 7 mm in the second trimester) typically resolves over the course of gestation or in the postnatal period VENTRICULOMEGALY • Isolated ventriculomegaly is a risk factor for Down syndrome, • Most children with isolated, mild ventriculomegaly have a normal outcome. • Mild ventriculomegaly is detected in 4 to 13% of fetuses with Down syndrome and 0.1 to 0.4% of euploid fetuses . • The risk of abnormal outcome, such as Down syndrome, increases with the degree of ventriculomegaly, progression of ventriculomegaly, and presence of other anomalies SHORTENED LONG BONES • Fetuses with Down syndrome have slightly shorter long-bones. A shortened humerus appears to be a better predictor of Down syndrome than a shortened femur (positive likelihood ratio 4.8 and 3.7, respectively) • Various criteria have been published for determining whether a femur or humerus is too short .These criteria overlap the range observed in unaffected fetuses and vary widely among different populations; • therefore, each laboratory should develop specific standards for its own population. We consider abnormal an observed-to-expected length ratio of less than 0.9. • In contrast, severely shortened (<5th percentile) or abnormal appearing long bones may be a sign of a skeletal dysplasia or early onset fetal growth restriction ECHOGENIC INTRACARDIAC FOCUS • The sonographic criteria for echogenic intracardiac foci is brightness equivalent to that of bone. • Echogenic intracardiac foci usually occur as a single focus in the left ventricle, but multiple foci, biventricular foci, or a right ventricular location can also occur. • This entity is different from diffuse, extensive myocardial calcification, which is rare and associated with myocardial dysfunction • Echogenic intracardiac foci may be first identified in the first trimester, but identification this • early in pregnancy is rare. In the second trimester, 21 to 28 % of fetuses with Down syndrome have an echogenic intracardiac
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