Genetic Counseling for Patients Considering Screening and Diagnosis for Chromosomal Abnormalities.

With the introduction of cell-free DNA screening for fetal aneuploidy and chromosomal microarray for prenatal diagnostic testing, options for pregnant women have become increasingly complex. Discussions regarding options for prenatal testing for aneuploidy should occur prior to any testing and should include pertinent risks and benefits of each alternative test. There is no single screening or diagnostic test option that is the right choice for all patients; patient decisions should be based on each individual woman's values and preferences after a discussion of all options.

Noninvasive prenatal testing: impact on genetic counseling, invasive prenatal diagnosis, and trisomy 21 detection.

PURPOSE: The aim of this study was to compare rates of genetic counseling, invasive prenatal diagnosis, and trisomy 21 detection among women at increased risk for aneuploidy, before versus after the availability of noninvasive prenatal testing (NIPT). METHODS: This institutional review board-exempt retrospective study included all women who had an ultrasound (US) examination between 10 0/7 and 21 6/7 weeks' gestation and were eligible for NIPT (ie, age ≥35 years, US findings suggestive of increased aneuploidy risk, positive aneuploidy screen, prior trisomic fetus, parental balanced translocation with increased risk for trisomy 13 or 21) between June 1, 2012 and February 1, 2013. NIPT was performed by a single laboratory after patients received genetic counseling. We also identified a comparison group of women evaluated between December 1, 2010 and November 30, 2011, who would have been eligible for NIPT had it been available. The two groups were compared for maternal demographics, aneuploidy risk factors, rates of genetic counseling, invasive diagnostic procedures, and trisomy 21 detection. RESULTS: The before-NIPT and after-NIPT groups contained 1,464 and 1,046 subjects, respectively. All 33 fetuses with trisomy 21 in the two groups were identified by positive aneuploidy screening. After the introduction of NIPT, genetic counseling for aneuploidy risk increased (adjusted odds ratio [aOR], 1.77 [1.49-2.11]; p < 0.0001) and the overall invasive diagnosis (aOR, 0.42 [0.32-0.55]; p < 0.0001), including amniocentesis (aOR, 0.37 [0.27-0.52], p < 0.0001), decreased, whereas the prenatal diagnosis of trisomy 21 remained similar (88% versus 100%; p = 0.86). CONCLUSIONS: NIPT in clinical practice uses more genetic counseling resources but requires significantly fewer invasive procedures to maintain the detection rates of trisomy 21.

Two- and three-dimensional prenatal sonographic diagnosis of Alagille syndrome.

We describe a case of Alagille syndrome diagnosed by second-trimester ultrasound. Features included the characteristic prominent chin, single umbilical artery, and hemivertebrae. Three-dimensional imaging demonstrated classic butterfly vertebrae, which were not otherwise appreciable. Alagille syndrome may be detected by second-trimester ultrasound in the at-risk fetus.

Second-trimester prenasal and prefrontal skin thickening - association with MECP2 triplication syndrome.

MECP2 triplication syndrome is a rare and usually lethal genetic disorder characterized by progressive neurologic and cognitive regression. None of the four reported cases describe prenatal sonographic features of affected offspring. We report a second-trimester fetus with marked prefrontal and prenasal skin thickening, retrognathia, and later, third-trimester mild cerebral ventriculomegaly. Amniocyte karyotype was normal male, but newborn whole-genome oligonucleotide microarray showed duplication and triplication of chromosome Xq28 containing the MECP2 gene. Comparative genomic hybridization may be diagnostic in fetuses with prefrontal and prenasal skin thickening, additional sonographic findings, and normal karyotype.

First trimester transabdominal chorionic villus sampling--does the needle matter?

PURPOSE: To compare first-trimester transabdominal chorionic villus samples (TA-CVS) when obtained by 20-gauge amniocentesis versus lancet needles. METHODS: This is a retrospective study of all women with viable singleton pregnancies undergoing TA-CVS from 01/01/2009 to 03/31/2011. All CVS were performed by a single operator using a freehand technique and amniocentesis needles from 01/01/2009 to 08/31/2010 and lancet needles from 09/01/2010 to 03/31/2011. All samples were processed by the same laboratory. RESULTS: There were no differences between groups regarding maternal age, weight, gestational age at CVS, indication for CVS, uterine position, or placental location. Lancet needles were associated with significantly larger samples (median 18 [range 3-40] versus 7 [range 1-33] mg, p < 0.0001), more successful in situ hybridization (96% versus 74.2%, p = 0.03), and faster result reporting (median 7 [range 5-12] versus 9 [range 6-26] days, p = 0.002). CONCLUSIONS: Needle type may be clinically important when selecting 20-gauge TA-CVS needles.

Stepwise sequential aneuploidy screening in clinical practice.

PURPOSE: To evaluate stepwise sequential screening (SSS) efficiency in clinical practice. METHODS: All singletons undergoing SSS in a single practice by NTQR (Nuchal Translucency Quality Review Program)-credentialed providers in a 2-year period were included. Prenatal diagnosis was offered to all screen-positive women and those with a nuchal translucency ≥3.5 mm or cystic hygroma at the 11- to 14-week scan. Data were extracted from prospectively ascertained serum screening and genetics databases. RESULTS: A total of 2,726 patients were screened, with SSS detecting all eight cases of trisomy 21 and all seven cases of other aneuploidies at a 4.3% screen-positive rate. CONCLUSIONS: Stepwise sequential screening offers excellent aneuploidy screening efficiency when introduced into clinical practice.

Prenatal sonographic features of dyssegmental dysplasia Rolland-Desbuquois type.

Dyssegmental dysplasia is a rare, lethal, autosomal-recessive disorder characterized by severe camptomicromelia and anisospondyly. We describe the prenatal sonographic findings in an index case of the Rolland-Desbuquois type, with the diagnosis made by neonatal skeletal survey. Recognition of the unique vertebral disorganization may be used to prenatally distinguish dyssegmental dysplasia from other severe short-limbed conditions.

Pain associated with chorionic villus sampling: transabdominal vs transcervical approach.

OBJECTIVE: The purpose of this study was to compare anticipated and perceived pain that is associated with transabdominal and transcervical chorionic villus sampling (CVS). STUDY DESIGN: Women with singleton pregnancies who were undergoing CVS completed a preprocedure 0-10 visual analog scale (VAS; 0 = no pain, 10 = excruciating pain) for anticipated transabdominal and transcervical CVS-related pain. After the procedure, patients completed a VAS for perceived pain. RESULTS: One hundred twenty-one women underwent transabdominal (n = 98) or transcervical (n = 23) CVS. Anticipated pain was 4.5 +/- 2.0, which was similar in patients who ultimately underwent transabdominal (score, 4.6 +/- 3.8) or transcervical (score, 4.1 +/- 2.2) CVS. Postprocedure perceived pain was similar for transabdominal CVS in women with an abdominal wall thickness of <4 cm (score, 2.3 +/- 0.8) and transcervical CVS (score, 2.6 +/- 2.2) but was significantly greater for transabdominal CVS among women with an abdominal wall thickness of > or =4 cm (score, 5.6 +/- 1.2; P < .0001) and nulliparous women who had transcervical CVS (score, 4.3 +/- 2.1; P = .01). CONCLUSION: Transabdominal CVS is more painful in heavier women, and transcervical CVS is more painful in nulliparous women.

Prenatal sonographic features of trisomy 1q.

We describe the sonographic features of trisomy 1q in 2 affected fetuses and identify 17 other published reports of this entity in the literature. Four of 5 (80%) diagnoses made at < or = 14 weeks' gestation demonstrated increased nuchal translucency or cystic hygroma colli. During the second and third trimesters, findings included cerebral ventriculomegaly (n = 8 [57%]), nuchal skin fold > or = 6 mm or cystic hygroma colli (n = 5 [36%]), urinary anomalies (n = 5 [36%]), digit malformations (n = 5 [36%]), and abnormal amniotic fluid volume (n = 6 [40%]). Findings in trisomy 1q may be influenced by coexisting chromosomal deletions or mosaicism. Sonographic features generally reflect the location and size of the 1q duplication.

Pain associated with transabdominal chorionic villus sampling--anticipated versus actual.

OBJECTIVE: To assess anticipated and perceived pain associated with transabdominal chorionic villus sampling (TA CVS). METHODS: Sixteen consecutive patients completed 0 (no pain) to 10 (excruciating pain) visual analog scales before and after TA CVS. RESULTS: Anticipated pain (5.1 +/- 2.9) and perceived pain (5.5 +/- 3.2) were similar (p = 0.42) and moderate. Actual pain was less in five (31%), the same in six (38%), and greater in five (31%) compared to anticipated pain. CONCLUSIONS: These baseline data are useful for patient counseling and designing interventional trials to decrease procedural pain. TA CVS is associated with moderate perceived pain.

Reducing pain with genetic amniocentesis-A randomized trial of subfreezing versus room temperature needles.

OBJECTIVE: To determine whether pain associated with second trimester genetic amniocentesis is decreased by using subfreezing rather than room temperature needles. METHODS: Subjects were randomized to a -14 degrees C or room temperature (20-22 degrees C) 22-gauge spinal needle. Patients, blinded to allocation, recorded anticipated and actual pain before and after the procedure, respectively, using a 0-10 visual analog scale with 0 = no pain and 10 = excruciating pain. RESULTS: Thirty-three subjects were randomized to room temperature and 29 subjects to subfreezing needles. Anticipated pain was similar in room temperature, 5.1 +/- 1.7, and subfreezing groups, 4.9 +/- 2.0, respectively (p = 0.6). Actual pain was also similar in the room temperature, 3.6 +/- 2.0, and subfreezing groups, 2.8 +/- 2.0, respectively (p = 0.14). Similar numbers of subjects in the room temperature and subfreezing groups reported less actual pain (20 vs. 18), greater actual pain (4 vs. 4) or no difference in pain (9 vs. 5) than anticipated (p = 0.6). CONCLUSION: A subfreezing 22-gauge spinal needle does not decrease perceived pain associated with second trimester genetic amniocentesis.

Childhood cardiac function after prenatal diagnosis of intracardiac echogenic foci.

OBJECTIVE: To determine whether prenatally diagnosed intracardiac echogenic foci are associated with childhood cardiac dysfunction and persistence. METHODS: Children in whom intracardiac echogenic foci were shown on prenatal sonography at 1 perinatal center underwent echocardiography at ages 2 to 7 years. A single pediatric cardiologist, blinded to the prenatal sonographic intracardiac echogenic focus locations, assessed cardiac function by measuring the left ventricular shortening fraction and myocardial performance index. The presence of tricuspid and mitral valve regurgitation was also sought. The secondary outcome was intracardiac echogenic focus persistence. RESULTS: Twenty-five children, 14 (56%) male and 11 (44%) female, were examined at a mean age +/- SD of 3.0 +/- 1.0 years. Prenatally, 18 children (72%) had left ventricular intracardiac echogenic foci, and 7 (28%) had right ventricular intracardiac echogenic foci. The left ventricular shortening fraction was normal in all children. The overall mean left ventricular myocardial performance index (reference value, 0.36 +/- 0.06), was normal for both children with left ventricular intracardiac echogenic foci (0.36 +/- 0.06) and those with right ventricular intracardiac echogenic foci (0.36 +/- 0.04). Two children with left ventricular intracardiac echogenic foci had an isolated left ventricular myocardial performance index of greater than 2.5 SD above the mean. Trace tricuspid valve regurgitation and mitral valve regurgitation were noted in 13 (52%) and 2 (8%) of the children, respectively, similar to the general population. Left ventricular intracardiac echogenic foci persisted in 16 children (89%), whereas right ventricular intracardiac echogenic foci persisted in 2 (29%) (P = .007). CONCLUSIONS: Prenatally diagnosed intracardiac echogenic foci are often persistent but not associated with childhood myocardial dysfunction.

Prenatal diagnosis by DNA polymorphism analysis of complete mole with coexisting twin.

Partial mole is distinguishable from complete mole with coexisting normal twin after delivery by DNA polymorphysm analysis. Our patient had chorionic villus sampling of a molar-appearing placenta with coexisting fetus at 12.3 weeks. Absent maternal alleles confirmed a diandrogenetic complete mole. Prenatal DNA diagnosis of complete mole is possible and clinically useful.