The impact of the use of the isolated echogenic intracardiac focus as a screen for Down syndrome in women under the age of 35 years.

OBJECTIVE: The purpose of this study was to determine the public health impact of the routine offering of amniocentesis to women under the age of 35 years who have an isolated fetal echogenic intracardiac focus on second trimester ultrasound scan. STUDY DESIGN: A decision analytic model was designed that compared the accepted standard of second trimester triple marker screen for Down syndrome to a policy in which amniocentesis with an isolated echogenic intracardiac focus on ultrasound in addition to the triple marker screen is offered to all women in the United States who are <35 years of age. A sensitivity of 20%, an echogenic intracardiac focus screen positive rate of 5%, and a risk of Down syndrome of 1:1000 were assumed. A sensitivity analysis was performed that varied the screen positive rate, the sensitivity of echogenic intracardiac focus for Down syndrome, and the prescreen risk for Down syndrome in the population. RESULTS: With the baseline sensitivities, rates, and risks, the use of isolated echogenic intracardiac focus as a screen would result in an additional 118,146 amniocenteses performed annually to diagnose 244 fetuses with Down syndrome. These amniocenteses would result in 582 additional miscarriages. It would be necessary to perform 485 amniocenteses that would result in 2.4 procedure-related losses for each additional Down syndrome fetus that was identified. CONCLUSION: Although the echogenic intracardiac focus appears to be associated with a small increased risk of Down syndrome, its use as a screening tool in low-risk populations would lead to a large number of amniocenteses and miscarriages to identify a small number of Down syndrome fetuses.     

Maternal anxiety and ultrasound markers for aneuploidy in a multiethnic population

OBJECTIVE: Discussion of isolated ultrasound (US) markers for fetal aneuploidy can provoke significant patient anxiety. The objective of this study is to quantify maternal anxiety associated with the detection of these markers. METHODS: All patients undergoing routine second-trimester US examination for fetal anatomical survey over a one-year period were administered the State-Trait Anxiety Inventory (STAI) for Adults before and after the procedure. Women with isolated fetal markers for aneuploidy were notified of the findings but discouraged from pursuing amniocentesis. Rates of normal US examination, aneuploidy markers, anomalies, amniocentesis, and pregnancy outcomes were assessed across the ethnic groups. Pre- and post-ultrasound STAI surveys were scored and standardized with previously established norms. Student t-tests, Chi-square, and analysis of variance (ANOVA) were used where appropriate. RESULTS: Among the 798 patients tested, 57% were Hispanic, 30% were Asian, 6% were Black, and 7% were White. Maternal anxiety level was decreased in women after a normal US. The anxiety level increased with aneuploidy markers and was the highest with anomalies. Aneuploidy markers were more common among Hispanic and Asian fetuses, without any associated aneuploidy. Women with isolated aneuploidy markers underwent amniocentesis as often as women with advanced maternal age. CONCLUSION: The detection and communication of isolated aneuploidy markers is associated with increased maternal anxiety and unnecessary amniocentesis.     

Ontogeny of isolated ultrasound markers for fetal aneuploidy.

OBJECTIVE: To evaluate the natural history of isolated ultrasound markers for fetal aneuploidy observed at 14-16 weeks of affected gestations. STUDY DESIGN: 76 aneuploid gestations were diagnosed among a predominantly low-risk population undergoing targeted ultrasonography in the early second trimester. Indications for evaluation of fetal karyotype included fetal malformations or sonographic markers for aneuploidy, maternal age over 35 years and abnormal serum screening results. Markers were re-evaluated at the time of amniocentesis or at pregnancy termination for fetal anomalies. RESULTS: Sonographic markers for aneuploidy (SMA) were observed in 68 of 76 aneuploid gestations diagnosed in the study group. In 46 cases, SMA were associated with major fetal malformations and in 22 cases, markers were isolated. Only 2 of 22 isolated markers for aneuploidy were documented at the time of amniocentesis. CONCLUSION: Isolated ultrasound markers for aneuploidy are transient and may disappear later on in gestation. Transvaginal sonography at 14-16 weeks of gestation appears to provide the best time window for detection of markers for fetal abnormal karyotype.     

中孕期超声筛查胎儿染色体异常软指标的临床价值

目的探讨中孕期超声筛查发现胎儿染色体异常软指标与胎儿染色体异常之间的关系,对超声软指标的临床价值作一评估。方法2004年2月至2006年11月在复旦大学附属妇产科医院产前筛查孕妇8810例,共筛查8883例胎儿(其中73例为双胎),中孕期详细超声筛查有无结构异常及染色体异常软指标,根据孕妇年龄、血清学筛查结果及超声检查综合评定,决定是否行羊膜腔穿刺染色体检查。染色体异常软指标主要包括:颈项软组织增厚、肱骨股骨偏短、轻度肾盂扩张、心室强光点、肠管强回声等。结果8883例胎儿中,发现染色体异常软指标598例,占6.73%。超声软指标诊断21-三体综合征敏感度为69.23%,特异度为93.36%,假阳性率6.74%。结论中孕期超声染色体异常软指标,对于筛查胎儿染色体异常具有重要的临床价值。     

Controversial ultrasound findings

This article has reviewed a few of the more controversial findings in the field of obstetric ultrasound. For each one evidence-based strategies for the management of affected pregnancies have been suggested, derived from what the authors believe is the best information available. In some cases, this information is very limited, which can make counseling these patients extremely difficult. Some physicians find using specific likelihood ratios helpful in these complex discussions. An example of the relative likelihood ratios for several markers of trisomy 21 is illustrated in Table 10. Although the management of each of the findings discussed in this article is different, a few generalizations can be made. To begin with, the detection of any abnormal finding on ultrasound should prompt an immediate detailed ultrasound evaluation of the fetus by someone experienced in the diagnosis of fetal anomalies. If there is more than one abnormal finding on ultrasound, if the patient is over the age of 35, or if the multiple marker screen is abnormal, an amniocentesis to rule out aneuploidy should be recommended. Of the six ultrasound findings reviewed here, the authors believe that only echogenic bowel as an isolated finding confers a high enough risk of aneuploidy to recommend an amniocentesis in a low-risk patient. The other findings in isolation in a low-risk patient seem to confer only a modest increased risk of aneuploidy, if any, and this risk is certainly less than the risk of unintended loss from amniocentesis.Wherever possible, modifiers of this risk, such as maternal age, history, and first and second multiple marker screening, should be used to define more clearly the true risk of aneuploidy. As obstetric ultrasound moves forward, particularly into the uncharted waters of clinical use of three- and four-dimensional ultrasound, one can expect a whole new crop of ultrasound findings with uncertain clinical significance. Clinicians are well advised to await well-designed studies to determine the clinical significance of these findings before altering clinical care.     

Isolated fetal echogenic intracardiac foci or golf balls: is karyotyping for Down's syndrome indicated?

OBJECTIVE: To determine the prevalence of isolated echogenic intracardiac foci and the subsequent risk for Down's syndrome at 18-23 weeks in an unselected obstetric population. DESIGN: Prospective study. SETTING: A district general hospital serving a routine obstetric population. PARTICIPANTS: 16,917 pregnant women who underwent a routine ultrasound screening at 18-23 weeks of gestation between November 1994 and August 1998. METHODS: All women were offered screening for Down's syndrome by nuchal translucency or maternal serum biochemistry. The prevalence of isolated echogenic intracardiac foci was determined and the relative risk for Down's syndrome was calculated for different ultrasound findings. RESULTS: The combined sensitivity of age, nuchal translucency and maternal serum biochemistry for Down's syndrome was 84% (27/32). The relative risk for Down's syndrome was 0.17 (95% CI 0.07-0.41) for the women with normal scan findings at 18-23 weeks. The prevalence of isolated echogenic intracardiac foci at 18-23 weeks was 0.9% (144/16,917). None of these pregnancies were affected by Down's syndrome. CONCLUSION: The significance of the association between isolated echogenic intracardiac foci and Down's syndrome is a matter of ongoing debate. The data of this study suggest that in an unselected obstetric population with prior, effective, routine Down's syndrome screening, the association between isolated echogenic intracardiac foci and Down's syndrome is no longer significant.     

The role of the second trimester genetic sonogram in screening for fetal Down syndrome

The Genetic Sonogram is an ultrasound examination done on second trimester fetuses that not only evaluates the fetus for structural malformations, but also searches for the sonographic markers of fetal Down syndrome. The main markers that comprise the genetic sonogram include the nuchal fold, short femur and humerus, pyelectasis, hyperechoic bowel, echogenic intracardiac focus, and any major abnormality. The absence of any marker on a second trimester scan conveys a 60-80% reduction in prior risk of Down syndrome based on advanced maternal age or serum screen risk. The presence of sonographic markers, either singly or in combination, will raise the baseline risk of Down syndrome using likelihood ratios calculated for each individual marker. Using this approach, approximately 75% of fetuses with Down syndrome can be identified by modifying the patient's baseline risk according to the results of the ultrasound. The second trimester scan will likely continue to play an important role in the future in the detection of aneuploidy.     

Isolated fetal echogenic intracardiac foci or golf balls: is karyotyping for Down's syndrome indicated?

Objective To determine the prevalence of isolated echogenic intracardiac foci and the subsequent risk for Down's syndrome at 18–23 weeks in an unselected obstetric population.
Design Prospective study.
Setting A district general hospital serving a routine obstetric population.
Participants 16,917 pregnant women who underwent a routine ultrasound screening at 18–23 weeks of gestation between November 1994 and August 1998.
Methods All women were offered screening for Down's syndrome by nuchal translucency or maternal serum biochemistry. The prevalence of isolated echogenic intracardiac foci was determined and the relative risk for Down's syndrome was calculated for different ultrasound findings.
Results The combined sensitivity of age, nuchal translucency and maternal serum biochemistry for Down's syndrome was 84% (27/32). The relative risk for Down's syndrome was 0.17 (95% CI 0.07–0.41) for the women with normal scan findings at 18–23 weeks. The prevalence of isolated echogenic intracardiac foci at 18–23 weeks was 0.9% (144/16,917). None of these pregnancies were affected by Down's syndrome.
Conclusion The significance of the association between isolated echogenic intracardiac foci and Down's syndrome is a matter of ongoing debate. The data of this study suggest that in an unselected obstetric population with prior, effective, routine Down's syndrome screening, the association between isolated echogenic intracardiac foci and Down's syndrome is no longer significant.     

The association of echogenic fetal lungs with trisomy 21

OBJECTIVE: To evaluate the association between echogenic appearing lungs on ultrasonographic examination of the fetus and aneuploidy. METHODS: Cases in which echogenic lungs were prospectively identified on ultrasonographic examination were collected. Other abnormal ultrasonographic findings were documented, as were patient data pertinent to the risk of aneuploidy, such as maternal age and results of serum screening. The chromosomal complement of each identified case is reported. RESULTS: Five fetuses were identified with diffusely echogenic lungs on ultrasound examination over a two-year period. In three of the five cases, there were other ultrasound abnormalities, although in only one of these was a major congenital abnormality detected. In all three of these cases, the fetal chromosomal complement showed trisomy 21. In 1 of the 2 cases in which the echogenic lungs were an isolated finding, the fetus also was found to have trisomy 21. CONCLUSIONS: Bilateral and diffusely echogenic lungs appear to have an association with fetal trisomy 21.     

Isolated Intracardiac Echogenic Focus on Routine Ultrasound: Implications for Practice

Ultrasound is widely used as a screening tool for fetal anomalies. An intracardiac echogenic focus (ICEF) is associated with fetal aneuploidy, particularly trisomy 21, when found with other minor abnormalities known as soft markers. However, when found in isolation, intracardiac echogenic foci are morphologic variations with little or no pathologic significance for the fetus. Ambiguity about the significance of ICEF and other soft markers and the lack of preparation prior to ultrasound can result in unnecessary worry for women and their partners. A variety of tools exist that providers can use to help pregnant women and their partners make informed decisions about ultrasound and fetal screening.     

Second-trimester genetic sonography in patients with advanced maternal age and normal triple screen

OBJECTIVE: To estimate the value of second-trimester genetic sonography in detecting fetal Down syndrome in patients with advanced maternal age (at least 35 years) and normal triple screen. METHODS: Since July 1999, a prospective collection and recording of all individual triple screen risks for fetal Down syndrome was initiated for all patients with advanced maternal age presenting in our ultrasound unit for second-trimester genetic sonography. Genetic sonography evaluated the presence or absence of multiple aneuploidy markers. Outcome information included the results of genetic amniocentesis, if performed, and the results of pediatric assessment and follow-up after birth. RESULTS: By June 2001, 959 patients with advanced maternal age and normal triple screen were identified. Outcome information was obtained in 768 patients. The median risk for fetal Down syndrome based on maternal age was 1:213 (range 1:37-1:274). The median risk for fetal Down syndrome based on triple screen results was 1:1069 (range 1:275-1:40,000). A total of 673 patients had normal genetic sonography, and none (0%) had Down syndrome; 95 had one or more aneuploidy markers present, and four (4.2%) had fetuses with Down syndrome. The triple screen risks for these four fetuses ranged from 1:319 to 1:833. CONCLUSION: This study suggests that patients with advanced maternal age and normal genetic sonography carried very little risk for Down syndrome. The use of genetic sonography may increase the detection rate of fetal Down syndrome in this group of pregnant women.     

A retrospective analysis of amniocenteses performed for advanced maternal age and various other indications in Turkish women

Objective: Prenatal cytogenetic diagnostic methods for the diagnosis of fetal chromosomal anomalies have been used reliably over the last 40 years. Advanced maternal age has become a basic indication for amniocentesis. Methods: We examined the results of the chromosome analyses of 3485 women that had amniocentesis for any reason during their antenatal care in our perinatology clinic in 2007–2009. Amniocentesis was performed for advanced maternal age in 1456 women (41.8%) and for other reasons in the remaining 2029 women (58.2%). Chromosomal anomalies were examined numerically and structurally. Results: When the amniocentesis results of the patients were reviewed as numerically normal or abnormal; 40 (2.7%) of 1456 amniocentesis procedures performed for advanced maternal age, 5 (0.9%) of 531 procedures performed for an increased double-test risk and 14 (1.3%) of 1095 procedures performed for an increased triple test risk were found to have chromosomal aneuploidy. Conclusions: Maternal age is still the most prevalent indication for genetic amniocentesis other than positive prenatal screening tests. Among women with advanced maternal age, prenatal ultrasonography for soft markers of chromosomal aneuploidy accompanied with maternal serum biochemical screening tests should be evaluated during the decision making process of genetic amniocentesis.     

Ultrasound markers for Down syndrome

Trisomy 21 (Down syndrome) is the most common chromosomal abnormality. Sonographic findings in fetuses with Down syndrome include both structural abnormalities and nonstructural abnormalities or "markers." These markers are known as "soft markers" of aneuploidy. These markers are nonspecific, often transient. The most commonly studied soft markers of aneuploidy include a thickened nuchal fold, long bones shortening, mild fetal pyelectasis, echogenic bowel, echogenic intracardiac focus, FMF angle > 90 degrees, pathologic velocity of Ductus venosus and choroid plexus cyst.     

Ultrasonographic soft markers of aneuploidy in second trimester fetuses

ObjectiveTo evaluate ultrasound “soft markers” used in fetal genetic screening.OptionsUltrasound screening at 16–20 weeks is one of the most common genetic screening tests used during pregnancy. The practical concern for ultrasound screening is false-positive and false-negative results. The use and understanding of ultrasound soft markers and their screening relative risks are an important option in the care of pregnant women.IntroductionChromosomal abnormalities occur in 0.1–0.2% of live births, and the most common clinically significant aneuploidy among live-born infants is Down’s syndrome (trisomy 21). Soft markers of aneuploidy are nonspecific, often transient, and can be readily detected during the second and third trimester ultrasound. The most commonly studied soft markers of aneuploidy include a thickened nuchal fold, mild fetal pyelectasis, echogenic bowel, echogenic intracardiac focus and choroid plexus cyst. There is a great deal of interest in the ultrasound detection of aneuploidy, as evidenced by the large number of publications in the literature on this topic.     

Ultrasound detection of fetal aneuploidy in patients with elevated maternal serum alpha-fetoprotein.

Increasing confidence in the ability of high-resolution ultrasound to detect neural tube and ventral wall defects has enabled us to offer a revised risk estimate to the patient with an elevated maternal serum alpha-fetoprotein (MSAFP) level, such that amniocentesis may not be necessary. Recent authors have suggested that a reduced emphasis on follow-up amniocentesis fails to consider an increased risk for chromosomal anomalies in pregnancies with an elevated MSAFP, and that amniocentesis should still be performed. We reviewed our ultrasound findings from patients who underwent amniocentesis for evaluation of an elevated MSAFP and who had a karyotype prepared from the amniotic fluid sample. Four abnormal karyotypes were detected among 313 amniocenteses, and three of these were correctly predicted based on an abnormal ultrasound. The risk of an unexpected fetal aneuploidy after a normal consultative ultrasound in our series was one in 310. This is comparable to the risk of detecting abnormal chromosomes in the fetus of a 32-year-old woman, an age at which amniocentesis is not routinely offered.     

Sonographic markers of fetal aneuploidy

A variety of ultrasound findings can be identified in fetuses with fetal aneuploidy. Typical findings vary with both the chromosome abnormality and gestational age at time of the ultrasound examination. Increased NT is the primary marker during the first trimester, whereas a variety of markers may be seen during the second trimester. The presence of ultrasound markers increases the risk for fetal aneuploidy, whereas a normal ultrasound reduces the risk. Optimal risk assessment includes consideration of other risk factors including maternal age, family history, and biochemical markers. It is expected that combined risks, incorporating ultrasound findings and biochemistry, will be available in the near future. How first-trimester screening is integrated with second-trimester screening remains to be determined.     

Down syndrome risk estimation after normal genetic sonography

OBJECTIVE: The objective of this study was to determine whether there are any indication-specific variations in risk reduction for fetal Down syndrome after a normal genetic sonogram. STUDY DESIGN: A second-trimester genetic sonogram was offered to all pregnant women who were at increased risk for fetal Down syndrome (>/=1:274) because of either advanced maternal age (>/=35 years), an abnormal triple screen, or both. Outcome information included the results of genetic amniocentesis (if performed), the results of pediatric assessment, and follow-up after birth. Normal genetic sonography was defined as the absence of all ultrasound aneuploidy markers. RESULTS: The overall prevalence of fetal Down syndrome in the tested population was 1.41% (53/3,753 pregnancies); however, in the presence of normal genetic sonography, the overall prevalence of fetal Down syndrome was 0.21% (7/3,291 pregnancies). The overall risk reduction for fetal Down syndrome in the presence of normal genetic sonography was 6.64-fold (95% CI, 3.01-14.62); the overall negative likelihood ratio was 0.15 (95% CI, 0.07-0.33). In the presence of normal genetic sonography, the risk for fetal Down syndrome was reduced by 83% in patients with advanced maternal age, 88% in patients with abnormal triple screen, 89% in patients with abnormal triple screen who were <35 years old, and 84% in patients who had both abnormal triple screen and advanced maternal age. CONCLUSION: There were no significant variations in the risk reduction for fetal Down syndrome in the presence of normal genetic sonography. Regardless of the indication for testing, the likelihood for fetal Down syndrome was reduced by 83% to 89%. This information will be useful in counseling pregnant women who are at high risk for fetal Down syndrome and who prefer to undergo genetic sonography before deciding about genetic amniocentesis.     

The clinical significance of fetal echogenic bowel.

OBJECTIVE: The purpose of this study was to determine the incidence of cystic fibrosis, aneuploidy, and intrauterine infection with toxoplasmosis and cytomegalovirus in second-trimester fetuses with the sonographic finding of echogenic bowel. STUDY DESIGN: All cases of echogenic bowel that were diagnosed in our ultrasound unit from 1993 to 2000 were identified. Only cases in which bowel echogenicity was as bright as bone with no associated major fetal anomalies were included. Patients who were referred from other hospitals were excluded. Echogenicity was classified as focal or multifocal. Fetal karyotypes, cystic fibrosis carrier testing, and maternal serologic test results were determined. RESULTS: One hundred seventy-five fetuses in 171 pregnancies met inclusion criteria. Cystic fibrosis mutations were identified in 7 of 138 mothers (5%) and 9 of 86 fathers (10.5%) who were tested. Five fetuses were affected with cystic fibrosis. Fetal karyotype was obtained in 139 cases, and autosomal trisomy was diagnosed in 5 cases (3.6%). One hundred sixty-six patients were tested for toxoplasmosis, and 111 patients were tested for cytomegalovirus. There were no cases of congenital toxoplasmosis. There was maternal serologic and fetal pathologic evidence of cytomegalovirus infection in 1 case. In all cases of cystic fibrosis and aneuploidy, echogenicity was multifocal; in the case of cytomegalovirus, echogenicity was focal. CONCLUSION: In our population, mid-trimester fetal echogenic bowel was associated with a high prevalence of cystic fibrosis, aneuploidy, and cytomegalovirus (11/175 fetuses [6.3%]). This information should be considered when counseling patients after mid-trimester echogenic bowel is diagnosed.     

Isolated clubfoot diagnosed prenatally: is karyotyping indicated?

OBJECTIVE: To evaluate the appropriateness of fetal karyotyping after prenatal sonographic diagnosis of isolated unilateral or bilateral clubfoot. METHODS: We retrospectively reviewed a database of fetal abnormalities diagnosed by ultrasound at a single tertiary referral center from July 1994 to March 1999 for cases of unilateral or bilateral clubfoot. Fetuses who had additional anomalies diagnosed prenatally, after targeted sonographic fetal anatomy surveys, were excluded. Outcome results included fetal karyotype diagnosed by amniocentesis, or newborn physical examination by a pediatrician. RESULTS: During the 5-year period, 5,731 fetal abnormalities were diagnosed from more than 27,000 targeted prenatal ultrasound examinations. There were 51 cases of isolated clubfoot. The mean maternal age at diagnosis was 30.5 years. The mean gestational age at diagnosis was 21.6 weeks. Twenty-three of the women (45%) were at increased risk of fetal aneuploidy, on the basis of advanced maternal age or abnormal maternal serum screening. Six women (12%) had positive family histories of clubfoot; however, no cases of aneuploidy were found by fetal karyotype evaluation or newborn physical examination. All cases of clubfoot diagnosed prenatally were confirmed at newborn physical examination, and no additional malformations were detected. CONCLUSION: After prenatal diagnosis of isolated unilateral or bilateral clubfoot, there appeared to be no indication to offer karyotyping, provided that a detailed sonographic fetal anatomy survey was normal and there were no additional indications for invasive prenatal diagnoses.     

Devenir néonatal des fœtus présentant un intestin hyperéchogène

ObjectiveEchogenic bowel (EB) represents 1 % of pregnancy and is a risk factor of fetal pathology (infection, cystic fibrosis, aneuploidy). The aim of our study was to determine the fetuses’ outcomes with isolated EB.Patients and methodsThis is a retrospective study of all patients who presented singleton gestations with a fetal isolated echogenic bowel between 2004 and 2011 in two prenatal diagnosis centers. Search of aneuploidy, infection and cystic fibrosis was systematically proposed as well as an ultrasound monitoring.ResultsOn 109 fetus addressed for isolate echogenic bowel five had other signs associated and 74 had a real isolated echogenic bowel (without dilatation, calcification, intrauterine growth restriction). In 30 cases, the EB was not found. Eighty-five percent of the patients had in the first trimester a screening for trisomy 21. None fetus with isolated EB had trisomy, infection or cystic fibrosis. One fetus died in utero and one newborn died of a metabolic disease without digestive repercussions.Discussion and conclusionThe risk of trisomy 21 and the risk to have a serious disease appear low for the fetus with EB. It does not seem necessary to propose a systematic amniocentesis in case of isolated echogenic bowel.