Choroid plexus cysts and trisomy 18: Risk modification based on maternal age and multiple-marker screening

Choroid plexus cysts are more common in fetuses with chromosomal aneuploidies, particularly trisomy 18. Although it is accepted that the risk of karyotypic abnormality justifies amniocentesis when associated abnormalities are present, disagreement continues as to the risk of trisomy 18 in a fetus with an isolated choroid plexus cyst. We propose consideration of maternal age and multiple-marker screening for chromosomal aneuploidy in the assessment of risk. Bayesian statistical modeling was used to calculate the risk of trisomy 18 from age-related risk figures for trisomy 18 and the incidence of isolated choroid plexus cysts in fetuses with trisomy 18. The risk was further modified on the basis of the ability of multiple-marker screening to detect fetuses with trisomy 18. From risk estimates calculated across maternal ages 20 to 45 years, the risk of trisomy 18 does not approach that of amniocentesis until a maternal age of ≥37 years. Therefore in the presence of an isolated choroid plexus cyst and normal multiple-marker screen results amniocentesis is justified only in the patient with advanced maternal age. (Am J Obstet Gynecol 1996;175:1493-7.)     

Second trimester choroid plexus cysts and trisomy 18

Objectives: In this study, the aims were to reveal the incidence of isolated choroid plexus cyst in our population, and to discuss the accuracy of distinguishing either an isolated or non-isolated choroid plexus cyst. Methods: The study population was consisted of 10 594 pregnant women. The patients with choroid plexus cysts were classified into two groups: isolated and non-isolated. Detailed ultrasonographic examination and genetic counseling were performed and triple screening test was ordered. The incidence, sensitivity, specificity, false-positive rate and likelihood ratio of cases with isolated choroid plexus cyst for trisomy 18 were determined. Results: Choroid plexus cysts were identified in 109 patients (109/10 594; 1.02%). In 102 patients isolated choroid plexus cysts, and in seven patients additional fetal anomalies supporting trisomy 18 were detected. Trisomy 18 was detected in four patients, and one of them had isolated choroid plexus cyst. The likelihood ratio in cases of isolated choroid plexus cysts for trisomy 18 was 9.51 (95% confidence interval, 0.2-41). Conclusions: According to the study the individual risk for trisomy 18 in isolated choroid plexus cyst should be calculated by using the likelihood ratio. These data allows the physician to express the individual risk of trisomy 18 and permits more accurate genetic counseling.     

Quistes de plexos coroideos y riesgo de cromosomopatía

IntroductionSince they were first described in 1984, the presence of choroid plexus cysts during pregnancy have stimulated considerable debate concerning their possible relationship with chromosomal anomalies, mainly trisomy 18. Even today, the controversy persistsObjectiveTo identify which associated factors (cyst characteristics, associated anomalies and maternal age at diagnosis) should be considered to justify invasive karyotyping, bearing in mind that these techniques carry a risk of fetal lossMaterial and methodsWe analyzed data from one decade (January 1991-December 2000) corresponding to 26,500 fetuses who underwent ultrasound examination between weeks 14 and 22 of gestation. Choroid plexus cysts were considered as an ultrasound-negative formation of at least 3 mm in diameter located within the choroid plexusResultsChoroid plexus cysts were found in 366 fetuses (1.38%). Of these, eight fetuses presented chromosomal anomalies: six presented trisomy 18, one presented trisomy 21 and one showed chromosomal deletion at 6p. In all eight patients, choroid plexus cysts were bilateral and associated anomalies were detected. Mean maternal age was 36.5 yearsConclusionsWhen choroid plexus cysts are detected in the second trimester, detailed fetal investigation must be performed to find other possible markers of chromosomal anomalies even though some are difficult to detect ultrasonographically. Because the risk of fetal loss after amniocentesis is estimated at 1%, when other markers are absent, our results suggest that invasive karyotyping does not seem justified in pregnant women without additional risk factors     

Choroid plexus cysts: Is biochemical testing a valuable adjunct to targeted ultrasonography?

OBJECTIVE: We sought to determine whether biochemical testing is a valuable adjunct to ultrasonography in selecting patients with fetal choroid plexus cysts for amniocentesis. STUDY DESIGN: The study population consists of 128 patients who had fetal choroid plexus cysts detected during ultrasonography performed between 18 and 22 weeks' gestation. The patients had genetic counseling, and amniocentesis and biochemical testing were offered to all patients. The data were analyzed by dividing the patients into 3 groups. Group 1 had targeted ultrasonography only, group 2 had ultrasonography and maternal serum alpha-fetoprotein testing, and group 3 had ultrasonography and triple-screen (maternal serum alpha-fetoprotein, human chorionic gonadotropin, and estriol) testing. Outcome was determined by fetal karyotype or by neonatal examination by a pediatrician for patients who declined amniocentesis. RESULTS: There were 25 patients in group 1. Isolated choroid plexus cysts were detected in 20 fetuses, and all had normal outcomes. Additional anomalies were detected in 5 fetuses. Two had normal karyotypes, and 3 had trisomy 18. There were 52 patients in group 2. The maternal serum alpha-fetoprotein levels were normal in 44 patients, 41 of whom had isolated fetal choroid plexus cysts. Of these 44 patients, 40 had normal outcomes, and 1 patient had a fetus with trisomy 18. The remaining 3 patients with normal maternal serum alpha-fetoprotein levels had additional fetal anomalies on ultrasonography, but the karyotypes were normal. The maternal serum alpha-fetoprotein levels were abnormal in 8 patients, of whom 6 had fetuses with isolated choroid plexus cysts and normal karyotypes. Two patients had additional fetal anomalies detected on ultrasonography and had abnormal karyotypes, 1 with trisomy 21 and 1 with trisomy 18. There were 51 patients in group 3. Results of the triple screen were normal in 32 patients. The choroid plexus cysts were isolated in 29 of the 32 patients, and all 29 fetuses had normal karyotypes. The other 3 patients with normal triple-screen results had additional fetal anomalies on ultrasonography. One fetus had normal chromosomes, and 2 had trisomy 18. The remaining 19 patients had abnormal triple-screen results. Among them, 16 fetuses had isolated choroid plexus cysts, 13 of whom were normal, 2 had trisomy 18, and 2 had a de novo unbalanced translocation. The remaining 3 fetuses had additional anomalies, and all 3 fetuses had trisomy 18. There were 14 fetuses with significant chromosomal abnormalities. Nine mothers were <35 years old, and 5 were >/=35 years old. CONCLUSIONS: This study shows the following: (1) The triple screen is a useful adjunct to targeted ultrasonography in selecting patients with fetal choroid plexus cysts for amniocentesis. (2) A normal triple-screen result and the absence of additional fetal anomalies on ultrasonography reliably exclude an underlying chromosomal abnormality, and amniocentesis is not indicated. (3) If the triple-screen result is abnormal, additional anomalies are seen on ultrasonography, or the mother is aged >/=35 years, then fetal karyotyping is recommended. (4) Patients who decline fetal karyotyping should have follow-up ultrasonography in 34 weeks' time.     

The significance of choroid plexus cysts in fetuses at 18-20 weeks. An indication for amniocentesis?

Over a period of 25 months, all antenatal patients were offered a detailed ultrasound scan at 18-20 weeks' gestation. The lateral cerebral ventricles were scanned for the presence of choroid plexus cysts. Fifty-one patients found to have choroid plexus cysts were offered amniocentesis to exclude chromosomal abnormalities. One pregnancy, in which the only abnormality found was bilateral choroid plexus cysts, was terminated after trisomy 18 was detected on amniocentesis at 19 weeks. The other 50 pregnancies had normal fetal outcomes. The significance of the isolated finding of choroid plexus cysts is reviewed.     

Choroid Plexus Cysts in the Fetal Brain

Summary: Choroid plexus cysts may be detected in the fetal choroid plexus on routine second trimester ultrasound scanning. The presence of these cysts is associated with trisomy 18 (Edward syndrome) in 3.47% of cases and with trisomy 21 (Down syndrome) in 0.46% of cases. The cysts themselves almost always disappear by 23 weeks and are thought to be a normal developmental variant. The world literature experience would indicate that the size of the choroid plexus cyst and the presence of bilateral cysts has no bearing on the magnitude of risk of chromosomal abnormality; 76% of babies with trisomy 18 also have other dysmorphic features which may be detectable by ultrasound. It is strongly advised that genetic counselling be undertaken and amniocentesis be considered when choroid plexus cysts are identified in the fetus .     

Isolated fetal choroid plexus cysts: role of ultrasonography in establishment of the risk of trisomy 18

OBJECTIVE: The significance of isolated choroid plexus cysts found by ultrasonographic scan during the second trimester as a marker for trisomy 18 is still debated. We analyzed our data and reviewed the series published in the English-language literature to calculate the likelihood ratio of trisomy 18 in the presence of isolated choroid plexus cysts; that is, the factor by which the individual risk of trisomy 18 is increased in the presence of isolated choroid plexus cysts. STUDY DESIGN: Likelihood ratios were calculated as ratio of the sensitivity to the false-positive rate. Sensitivity was defined as the rate of isolated choroid plexus cysts detected at midgestation among fetuses with trisomy 18. False-positive rate was defined as the rate of choroid plexus cysts detected at midgestation in the population without trisomy 18. The sensitivities of all published series reporting rates of choroid plexus cysts at the time of the first ultrasonographic examination between 14 and 24 weeks' gestation in populations with trisomy 18 and in low-risk populations were included in the analysis. To these we added all cases of trisomy 18 diagnosed at our institution during the period January 1, 1988, through June 30, 1998, in which prenatal ultrasonographic examination was performed between 14 and 24 weeks' gestation. RESULTS: The prevalence of second-trimester ultrasonographic detection of isolated choroid plexus cysts among fetuses with trisomy 18 was 6.7% (13/194), whereas that in the population without trisomy 18 was 0.9% (752/79,583). The likelihood ratio associated with isolated choroid plexus cysts was therefore 7.09 (95% confidence interval, 3.97-12.18). CONCLUSION: The presence of isolated second-trimester choroid plexus cysts increases the base risk of trisomy 18 by a factor of 7.09. This likelihood ratio can be multiplied by the risk calculated according to maternal age to obtain the individual risk of trisomy 18 and thus permit more accurate counseling of the patient.     

Are choroid plexus cysts an indication for second-trimester amniocentesis?

Previous series that described fetuses with choroid plexus cysts have been too small to determine whether there is an association with trisomy 18 sufficiently high to warrant amniocentesis. To address this issue, we studied the incidence of choroid plexus cysts and other ultrasonographic abnormalities in 26 consecutive fetuses (13.5 to 36 weeks' gestation) with trisomy 18. Twenty of these 26 fetuses had major sonographic anomalies suggestive of aneuploidy. Seventeen of these 26 fetuses were 15 to 20 weeks and 5 of 17 (30%) had choroid plexus cysts. Six of our total 26 affected fetuses had no sonographic anomalies and therefore, on the basis of our data, 30% of these (1.8 fetuses) with trisomy 18 would have choroid plexus cysts without other findings. The incidence of choroid plexus cysts in all second-trimester fetuses (including normal fetuses and those with trisomy 18) is reportedly 1%. Given the known incidence of trisomy 18 (3/10,000), we calculated a total presumptive sample of 86,667 patients to yield our 26 fetuses with trisomy 18. Our hypothetical sample has 86,641 (86,667 - 26) fetuses without trisomy 18,858 of which would have choroid plexus cysts. Thus there would be one fetus with trisomy 18 for every 477 normal fetuses with choroid plexus cysts with no other defect seen. If amniocentesis were done to seek trisomy 18 in all second-trimester fetuses with choroid plexus cysts, two normal fetuses would be lost for every one with trisomy 18 identified.     

Utility of minor ultrasonographic markers in the prediction of abnormal fetal karyotype at a prenatal diagnostic center.

OBJECTIVE: This study was undertaken to assess the value of minor ultrasonographic markers in predicting significant karyotypic abnormalities. STUDY DESIGN: A total of 2743 fetuses (14-24 weeks' gestation) prospectively underwent a detailed ultrasonographic survey before genetic amniocentesis. Criteria for 8 minor ultrasonographic markers were established. Odds ratios for significant karyotypic abnormalities in the presence of minor ultrasonographic markers were calculated with the chi(2) and Fisher exact tests. RESULTS: Of the fetuses, 14.6% had a single minor ultrasonographic marker, 2.1% had >/=2 minor ultrasonographic markers, and 2.7% had >/=1 major ultrasonographic abnormality. One hundred four fetuses (3.8%) had an abnormal karyotype. Compared with a normal ultrasonographic examination result a single minor ultrasonographic marker increased the risk of karyotypic abnormality 5.7-fold (95% confidence interval, 3.5-9.3), whereas multiple minor markers increased the risk of an abnormal karyotype 12-fold (95% confidence interval, 5.5-26.5). When they were identified ultrasonographically in isolation, echogenic bowel, 2-vessel umbilical cord, echogenic intracardiac foci, choroidal separation, and choroid plexus cysts were statistically associated with an abnormal karyotype. When minor markers were identified in clusters of >/=2, echogenic bowel, short femur, 2-vessel umbilical cord, echogenic intracardiac foci, and mild ventriculomegaly were significantly predictive of karyotypic abnormality. With respect to the a priori aneuploidy risk of 1:26 and the a priori Down syndrome risk of 1:50, a normal ultrasonographic examination result reduced the risks to 1:67 and 1:120, respectively. The use of minor ultrasonographic markers in addition to major ultrasonographic abnormalities increased the detection of karyotypic abnormality from 27.9% to 68.3%. For trisomy 21 the sensitivity rose from 16.4% to 67. 3%. CONCLUSIONS: Significant karyotypic abnormality risk assessment by ultrasonography was greatly enhanced by the addition of minor ultrasonographic markers. Further, clusters of minor ultrasonographic markers greatly increased the likelihood of karyotypic abnormality compared with a single minor marker. A completely normal ultrasonographic examination result reduced the risk of an abnormal karyotype by 62%. Inclusion of minor ultrasonographic markers in the genetic sonogram in a high-risk population will allow the detection of 68% of fetuses with karyotypic abnormalities with a false-positive rate of 17%.     

The second-trimester fetus with isolated choroid plexus cysts: a meta-analysis of risk of trisomies 18 and 21

Objective: To assess the risk of trisomy 18 and trisomy 21 associated with isolated choroid plexus cysts diagnosed by ultrasound in the second trimester.Methods of Study Selection: We reviewed the unabridged PREMEDLINE and MEDLINE databases for articles written in the English language regarding second-trimester fetal isolated choroid plexus cysts and trisomies 18 and 21, published in the period 1987–1997. Selection criteria included only second-trimester, prospective studies in which the rate of fetal isolated choroid plexus cysts could be calculated, the number of fetuses with trisomy 18 and 21 was reported clearly, and pregnant women of all ages were included, rather than only those at high risk for aneuploidy due to advanced maternal age.Tabulation and Results: Thirteen prospective studies, comprising 246,545 second-trimester scans, were selected. Among 1346 fetuses with isolated choroid plexus cysts, seven had trisomy 18, and five had trisomy 21. For each study, a 2 × 2 table was constructed and the likelihood ratio of a positive test was computed. The likelihood ratios for trisomies 18 and 21 were found to be homogeneous (P = .08 for trisomy 18, and P = .16 for trisomy 21). The summary likelihood ratio and 95% confidence interval (CI) for each chromosomal abnormality were calculated using the Mantel-Haenszel fixed effects model of meta-analysis. The summary likelihood ratio for trisomy 18 was 13.8 (CI 7.72, 25.14, P < .001) and for trisomy 21 was 1.87 (CI 0.78, 4.46, P = .16).Conclusion: The likelihood of trisomy 18 was 13.8 times greater than the a priori risk in fetuses with isolated choroid plexus cysts diagnosed in the second trimester. However, the likelihood of trisomy 21 was not significantly greater than the a priori risk with isolated choroid plexus cysts. The data supported offering pregnant women karyotyping to rule out trisomy 18 when maternal age at delivery is 36 years or older, or when the risk for trisomy 18 detected by serum multiple-marker screen is more than one in 3000.     

A role for maternal serum screening in detecting chromosomal abnormalities in fetuses with isolated choroid plexus cysts: a prospective multicentre study.

A prospective multicentre study was performed to identify patients with fetal choroid plexus cysts and examine the association between choroid plexus cysts and chromosome abnormalities in the context of variables such as maternal age, serum triple-screen results, race, other prenatally-identified fetal anomalies and cyst characteristics. A total of 18 437 scans were performed in 5 centres and 257 fetuses were identified with choroid plexus cysts. Outcome was available on 250 patients, and of these, chromosomal abnormalities were detected in a total of 13 (5.2 per cent) fetuses. 26 patients in the group had additional ultrasound abnormalities, and 8 of these had fetal chromosome abnormalities. Among the 224 patients with isolated choroid plexus cysts, 5 (2.2 per cent) were found to have chromosomal abnormalities. All cases with identified chromosomal abnormalities were associated with an additional risk factor, such as other ultrasound findings, advanced maternal age or abnormal maternal serum triple-screen results.     

More on management of choroid plexus cysts in the mid-trimester fetus

EDITORIAL COMMENT: We have published this pair of letters as a feature rather than in the correspondence column so it will not be lost to reference in the literature. Readers are also referred to a recently published review of the world literature concerning the risks of trisomies 18 and 21 in the second-trimester fetus with an isolated choroid plexus cyst (A). This study concluded that 'the likelihood of trisomy 18 was 13.8 times greater than the a priori risk in fetuses with isolated choroid plexus cysts diagnosed in the second trimester. However, the likelihood of trisomy 21 was not significantly greater than the a priori risk with isolated choroid plexus cysts.' N.B.
(A) Yoder PR, Sabbagha RE, Gross SJ, Zelop CM. The second-trimester fetus with isolated choroid plexus cysts: A meta-analysis of risk of trisomies 18 and 21. Obstet Gynecol 1999; 93: 869–872
1. Choong S, Meagher S, Management of choroid plexus cysts in the mid-trimester fetus Aust NZ J Obstet Gynecol 1999; 39: 7–11
2. Goldstein H, Philip J. A cost-benefit analysis of prenatal diagnosis by amniocentesis in Denmark. Clinical Genetics 1990; 37: 24–263
3. Gupta J, Thornton J, Lilford R. Management of fetal choroid plexus cyst. Br J Obstet Gynaecol 1997; 104: 881–886.
4. Gratton R, Hogge W, Ashton C. Choroid plexus cysts and Trisomy 18: Risk modification based on maternal age and multiple-marker screening. Am J Obstet Gynecol 1996; 175: 1493–1497
Associate Professor Lachlan de Crespigny, Head of Ultrasound, Royal Women's Hospital, Carlton, Melbourne and Associate Professor Julian Savulescu Director, Ethics Unit, The Murdoch Institute, Royal Children's Hospital, Parkville, Melbourne and Dr Leslie J Sheffield, Director of Education and Training, Victorian Clinical Genetic Services, Royal Children's Hospital, Parkville, Melbourne.     

Early second-trimester individualized estimation of trisomy 18 risk by ultrasound

OBJECTIVE: To report two second-trimester ultrasound algorithms for trisomy 18 prediction. METHODS: Femur length, gross anomaly, choroid plexus cysts, two-vessel cord, and maternal age were documented in pregnancies undergoing genetic amniocentesis. Stepwise logistic regression was used to identify 1) the significant markers for predicting trisomy 18 when gross anomaly was not considered (algorithm 1) and 2) when gross anomaly was also considered (algorithm 2). Patient-specific risk was calculated based on the significant ultrasound markers plus maternal age. The diagnostic accuracy of each algorithm was determined. RESULTS: There were 1167 normal and 47 trisomy 18 cases. The mean gestational ages were 16.5 weeks (standard deviation [SD] 1.5) and 17.9 weeks (SD 1.6), respectively. Algorithm 1 consisted of maternal age, choroid plexus cyst, femur length, and two-vessel cord. The sensitivity and false positive rates were 61.7% and 1.5%, respectively, with an area under the receiver operating characteristics curve of 0.880 (P <.001). Algorithm 2 (age, femur length, gross anomaly, and choroid plexus cyst) had a sensitivity of 72.3% and false positive rate of 0.9% with an area under the curve of 0.956 (P <.001). Comparable detection rates were achieved in early gestation at up to and including 17.5 weeks (72.4% and 82.8%, algorithms 1 and 2, respectively, at a 4.0% false positive rate). CONCLUSION: The ultrasound markers were sensitive for trisomy 18 detection in the early second trimester.     

Bilateral choroid plexus cysts in trisomy 21.

Whether karyotyping is indicated in a fetus with choroid plexus cysts who is otherwise structurally normal is still controversial. Many authors have suggested basing the decision on cyst size, bilaterality, persistence with advancing gestational age, and association with other anomalies. We report a case of large bilateral choroid plexus cysts in a fetus with trisomy 21 who had no evidence of congenital anomalies or ultrasonographic signs of Down syndrome. Cyst sizes diminished by half over a 3-week period of follow-up. It appears that diminishing size alone should not be considered sufficient reassurance about the normality of the fetal karyotype. A similar case has been previously reported, and it is conceivable that choroid plexus cysts are associated not only with trisomy 18 but also with trisomy 21.     

Ultrasonographically adjusted midtrimester risk of trisomy 21 and significant chromosomal defects in advanced maternal age

OBJECTIVE: Our purpose was to determine whether normal midtrimester ultrasonography results reduces the risk of fetal Down syndrome and any clinically significant chromosomal defects in pregnancies with advanced maternal age and to develop risk tables on the basis of age and ultrasonographic results. STUDY DESIGN: Biometry data were obtained in 4079 women between 15 and 24 weeks undergoing amniocentesis for maternal age. Expected values of humerus, femur, both combined, and abdominal circumference based on biparietal diameter were generated from a normal group. Observed/expected values of each parameter and nuchal thickness ≥6 mm was used to screen for Down syndrome and any clinically significant chromosome defects. Receiver-operator characteristic curves were used to determine threshold screening values for each parameter. By use of stepwise logistic regression the optimal measurements for detection of chromosome anomalies were established. An abnormal ultrasonography result was defined as either abnormal biometry choroid plexus cysts or a structural defect. RESULTS: The finding of shortened humerus (observed/expected <0.90), abnormal nuchal thickness, or an anatomic defect had the highest sensitivity for Down syndrome detection, 70.6%, p < 0.0001, whereas a short humerus, small abdominal circumference, (observed/expected <0.92), or an anatomic defect had a sensitivity of 46.7%, p < 0.0001, for any significant chromosome defect. With a normal ultrasonography the risk of Down syndrome in a 39-year-old woman falls from 1:100 to <1:292. CONCLUSION: A normal ultrasonography substantially reduces the risk of Down syndrome and any chromosome abnormality. This information is useful in counseling women who decline amniocentesis on the basis of maternal age. (Am J Obstet Gynecol 1996;175:1563-8.)     

Diagnóstico prenatal de una trisomia parcial 5p asociada a hiperecogeneicidad intestinal

We report the case of a 30-year-old woman who underwent amniocentesis at 20 weeks of gestation since the fetus showed equinovarus feet, hyperechogenic fetal bowel and choroid plexus cyst. Cytogenetic study identified de novo partial trisomy of the short arm of chromosome 5. We analyze the autopsy findings and “5p syndrome” as well as the association between intestinal hyperechogenicity and the development of abnormal chromosomes.     

Fetal hepatic calcifications: prenatal diagnosis and outcome

OBJECTIVE: The purpose of this study was to provide information on the causes and postnatal outcomes of fetal liver calcifications that were detected by ultrasound imaging. STUDY DESIGN: Cases with fetal liver calcifications that were encountered between 1992 and 2001 were evaluated. A detailed fetal ultrasound imaging for associated abnormalities, maternal STORCH (syphilis, cytomegalovirus, herpesvirus 1 and 2, rubella, and Toxoplasma ) analysis, parvovirus serologic condition, and parental cystic fibrosis mutations analysis were performed; amniocentesis was offered in all cases. All infants who were born alive were examined and followed up. RESULTS: Sixty-one pregnant women with fetal liver calcifications were identified. Forty of 61 patients had additional fetal abnormalities; 21 of 61 cases of fetal liver calcifications were isolated; 11/61 patients (18%) had abnormal karyotypes (trisomy 13, 4 patients; trisomy 21, 2 patients; trisomy 18, 1 patient; monosomy X (45,X), 1 patient; 4p-, 22q+, and 8p+, 1 patient). Ten of 11 patients with abnormal karyotypes had other abnormalities that were found on ultrasound imaging. Two patients had intrauterine infection, one patient had cytomegalovirus, and one patient had parvovirus B19 infection. Eighteen of 40 patients underwent pregnancy termination, one fetus died in utero, one newborn infant died, and two infants had neurologic sequelae. Of 21 patients with isolated liver calcifications, one fetus had parvovirus B19 infection and one infant had trisomy 21. The remainder of the infants each had a good outcome. CONCLUSION: Fetal liver calcifications are relatively common. Isolated cases have a good prognosis after aneuploidy and infection have been ruled out. However, additional major abnormalities present a risk for chromosomal abnormalities, mainly trisomy 13.     

Low-level mosaic trisomy 21 at amniocentesis in a pregnancy associated with a negative NIPT result,cytogenetic discrepancy in various tissues,perinatal progressive decrease of the aneuploid cell line and a favorable fetal outcome

ObjectiveWe present low-level mosaic trisomy 21 at amniocentesis associated with a favorable fetal outcome.Case reportA 31-year-old primigravid woman underwent non-invasive prenatal testing (NIPT) at 12 weeks of gestation, and the result was normal. She underwent amniocentesis at 16 weeks of gestation because of fetal choroid plexus cyst, and the result was 47,XX,+21[5]/46,XX[32]. Repeat amniocentesis was performed at 19 weeks of gestation, and the result was 47,XX,+21[5]/46,XX[15]. Simultaneous array comparative genomic hybridization (aCGH) analysis on uncultured amniocytes revealed the result of arr (21) × 3 [0.10], consistent with 10% mosaicism for trisomy 21. Prenatal ultrasound findings were unremarkable. She was referred for genetic counseling at 22 weeks of gestation, and the third amniocentesis was performed at 25 weeks of gestation, and the result was 46,XX (20/20 colonies). The parental karyotypes were normal. Simultaneous quantitative fluorescence polymerase chain reaction (QF-PCR) analysis on the DNA extracted from uncultured amniocytes and parental bloods excluded uniparental disomy (UPD) 21. aCGH analysis on uncultured amniocytes revealed arr 21q11.2q22.3 × 2.1 (log₂ ratio = 0.1), consistent with 10–15% mosaicism for trisomy 21. Fluorescence in situ hybridization (FISH) analysis on uncultured amniocytes revealed 30% (30/100 cells) mosaicism for trisomy 21. The woman was advised to continue the pregnancy, and a phenotypically normal 2800-g female baby was delivered at 38 weeks of gestation. The karyotype of cord blood, umbilical cord and placenta were 47,XX,+21[1]/46,XX[39]. 47,XX,+21[4]/46,XX[36] and 46,XX (40/40 cells), respectively. When follow-up at age two months, the neonate was phenotypically normal. The peripheral blood had a karyotype of 47,XX,+21[1]/46,XX[39], and FISH analysis on buccal mucosal cells revealed 8.4% (7/83 cells) mosaicism for trisomy 21, compared with 0% in the normal control.ConclusionLow-level mosaic trisomy 21 at amniocentesis can be associated with a negative NIPT result, cytogenetic discrepancy in various tissues, perinatal progressive decrease of the aneuploid cell line and a favorable fetal outcome.     

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.