Prenatal Testing

Key clinical point: Presence of amniotic fluid sludge (AFS) in the midtrimester may serve as an additional ultrasound index for predicting preterm birth in women with a short cervical length (CL; ≤25 mm) who have undergone cervical cerclage.

Main finding: In patients who underwent cerclage, AFS and short CL were associated with preterm birth at <28 weeks and <36 weeks (all P < .05). In women with a short CL, the presence of AFS was significantly associated with short gestational age at delivery even after adjusting for possible confounders (adjusted hazard ratio 2.45; 95% CI 1.7-3.5).

Study details: This was a single-center retrospective cohort study involving 296 singleton pregnant women who underwent McDonald cerclage for cervical insufficiency, transvaginal ultrasound-diagnosed short CL, or cervical dilatation with amniotic sac bulging, followed by evaluation of the presence of AFS and CL at 14-24 weeks of gestation within 2 weeks after cerclage.

Disclosures: The authors reported no source of funding or conflict of interests concerning the study.

Source: Huang Y et al. J Ultrasound Med. 2022 (Feb 2). Doi: 10.1002/jum.15952.

Key clinical point: Presence of amniotic fluid sludge (AFS) in the midtrimester may serve as an additional ultrasound index for predicting preterm birth in women with a short cervical length (CL; ≤25 mm) who have undergone cervical cerclage.

Main finding: In patients who underwent cerclage, AFS and short CL were associated with preterm birth at <28 weeks and <36 weeks (all P < .05). In women with a short CL, the presence of AFS was significantly associated with short gestational age at delivery even after adjusting for possible confounders (adjusted hazard ratio 2.45; 95% CI 1.7-3.5).

Study details: This was a single-center retrospective cohort study involving 296 singleton pregnant women who underwent McDonald cerclage for cervical insufficiency, transvaginal ultrasound-diagnosed short CL, or cervical dilatation with amniotic sac bulging, followed by evaluation of the presence of AFS and CL at 14-24 weeks of gestation within 2 weeks after cerclage.

Disclosures: The authors reported no source of funding or conflict of interests concerning the study.

Source: Huang Y et al. J Ultrasound Med. 2022 (Feb 2). Doi: 10.1002/jum.15952.

Key clinical point: Presence of amniotic fluid sludge (AFS) in the midtrimester may serve as an additional ultrasound index for predicting preterm birth in women with a short cervical length (CL; ≤25 mm) who have undergone cervical cerclage.

Main finding: In patients who underwent cerclage, AFS and short CL were associated with preterm birth at <28 weeks and <36 weeks (all P < .05). In women with a short CL, the presence of AFS was significantly associated with short gestational age at delivery even after adjusting for possible confounders (adjusted hazard ratio 2.45; 95% CI 1.7-3.5).

Study details: This was a single-center retrospective cohort study involving 296 singleton pregnant women who underwent McDonald cerclage for cervical insufficiency, transvaginal ultrasound-diagnosed short CL, or cervical dilatation with amniotic sac bulging, followed by evaluation of the presence of AFS and CL at 14-24 weeks of gestation within 2 weeks after cerclage.

Disclosures: The authors reported no source of funding or conflict of interests concerning the study.

Source: Huang Y et al. J Ultrasound Med. 2022 (Feb 2). Doi: 10.1002/jum.15952.

Key clinical point: Expanded noninvasive prenatal testing (NIPT-plus) is better at predicting fetal chromosome abnormalities in pregnant women of advanced maternal age (AMA) than in those of young maternal age (YMA).

Main finding: The positive predictive value of NIPT-plus in AMA pregnancies vs. YMA pregnancies was 57.6% vs. 35.7% (P < .05) for sex chromosome aneuploidies (SCA) and 77.8% vs. 51.9% (P < .05) for chromosome aneuploidies, including trisomies 21, 18, and 13, and SCAs.

Study details: The data come from a retrospective cohort study including 448 pregnant women with screen-positive results by NIPT-plus for fetal chromosome abnormality in the second trimester, who underwent prenatal diagnosis, of which 27% were AMA pregnancies.

Disclosures: The study was funded by the National Nature Science Foundation of China. None of the authors reported having a conflicts of interests.

Source: Chen Y et al. Am J Med Genet A. 2022 (Feb 2). Doi: 10.1002/ajmg.a.62657.

Key clinical point: Expanded noninvasive prenatal testing (NIPT-plus) is better at predicting fetal chromosome abnormalities in pregnant women of advanced maternal age (AMA) than in those of young maternal age (YMA).

Main finding: The positive predictive value of NIPT-plus in AMA pregnancies vs. YMA pregnancies was 57.6% vs. 35.7% (P < .05) for sex chromosome aneuploidies (SCA) and 77.8% vs. 51.9% (P < .05) for chromosome aneuploidies, including trisomies 21, 18, and 13, and SCAs.

Study details: The data come from a retrospective cohort study including 448 pregnant women with screen-positive results by NIPT-plus for fetal chromosome abnormality in the second trimester, who underwent prenatal diagnosis, of which 27% were AMA pregnancies.

Disclosures: The study was funded by the National Nature Science Foundation of China. None of the authors reported having a conflicts of interests.

Source: Chen Y et al. Am J Med Genet A. 2022 (Feb 2). Doi: 10.1002/ajmg.a.62657.

Key clinical point: Expanded noninvasive prenatal testing (NIPT-plus) is better at predicting fetal chromosome abnormalities in pregnant women of advanced maternal age (AMA) than in those of young maternal age (YMA).

Main finding: The positive predictive value of NIPT-plus in AMA pregnancies vs. YMA pregnancies was 57.6% vs. 35.7% (P < .05) for sex chromosome aneuploidies (SCA) and 77.8% vs. 51.9% (P < .05) for chromosome aneuploidies, including trisomies 21, 18, and 13, and SCAs.

Study details: The data come from a retrospective cohort study including 448 pregnant women with screen-positive results by NIPT-plus for fetal chromosome abnormality in the second trimester, who underwent prenatal diagnosis, of which 27% were AMA pregnancies.

Disclosures: The study was funded by the National Nature Science Foundation of China. None of the authors reported having a conflicts of interests.

Source: Chen Y et al. Am J Med Genet A. 2022 (Feb 2). Doi: 10.1002/ajmg.a.62657.

Key clinical point: Diagnostic exome sequencing may enable the characterization of the molecular defects underlying unexplained callosal anomalies (CA) and potentially reduce the number of prenatally undiagnosed cases.

Main finding: A total of 17 pathogenic/likely pathogenic variants in 14 genes from 17 fetuses were identified, with the proportion of diagnostic genetic variants being 34%. Genetic variants were diagnosed in 29.4% and 43.8% of fetuses with isolated and nonisolated CA, respectively.

Study details: This single-center cohort study analyzed 50 fetuses with CA, with (n = 16) or without (n = 34) other structural abnormalities, but with normal karyotyping and chromosomal microarray analysis findings.

Disclosures: The study was sponsored by the National Natural Science Foundation of China, Natural Science Foundation of Guangdong Province, Project of Guangzhou Science and Technology, and Project of Guangdong Medical Science and Technology Research. No conflicts of interest were declared.

Source: Lei TY et al. Prenat Diagn. 2022 (Jan 28). Doi: 10.1002/pd.6107.

Key clinical point: Diagnostic exome sequencing may enable the characterization of the molecular defects underlying unexplained callosal anomalies (CA) and potentially reduce the number of prenatally undiagnosed cases.

Main finding: A total of 17 pathogenic/likely pathogenic variants in 14 genes from 17 fetuses were identified, with the proportion of diagnostic genetic variants being 34%. Genetic variants were diagnosed in 29.4% and 43.8% of fetuses with isolated and nonisolated CA, respectively.

Study details: This single-center cohort study analyzed 50 fetuses with CA, with (n = 16) or without (n = 34) other structural abnormalities, but with normal karyotyping and chromosomal microarray analysis findings.

Disclosures: The study was sponsored by the National Natural Science Foundation of China, Natural Science Foundation of Guangdong Province, Project of Guangzhou Science and Technology, and Project of Guangdong Medical Science and Technology Research. No conflicts of interest were declared.

Source: Lei TY et al. Prenat Diagn. 2022 (Jan 28). Doi: 10.1002/pd.6107.

Key clinical point: Diagnostic exome sequencing may enable the characterization of the molecular defects underlying unexplained callosal anomalies (CA) and potentially reduce the number of prenatally undiagnosed cases.

Main finding: A total of 17 pathogenic/likely pathogenic variants in 14 genes from 17 fetuses were identified, with the proportion of diagnostic genetic variants being 34%. Genetic variants were diagnosed in 29.4% and 43.8% of fetuses with isolated and nonisolated CA, respectively.

Study details: This single-center cohort study analyzed 50 fetuses with CA, with (n = 16) or without (n = 34) other structural abnormalities, but with normal karyotyping and chromosomal microarray analysis findings.

Disclosures: The study was sponsored by the National Natural Science Foundation of China, Natural Science Foundation of Guangdong Province, Project of Guangzhou Science and Technology, and Project of Guangdong Medical Science and Technology Research. No conflicts of interest were declared.

Source: Lei TY et al. Prenat Diagn. 2022 (Jan 28). Doi: 10.1002/pd.6107.

Key clinical point: The Z-sign may serve as a strong marker for a double aortic arch (DAA) in surgically confirmed cases of vascular rings, even in those with atresia of the left arch, and thus facilitate the differentiation between a right aortic arch with left duct (RAA-LD) and DAA in the second trimester of pregnancy.

Main finding: The Z-sign could predict a DAA with a sensitivity of 100% (95% CI 80%-100%), specificity of 81% (95% CI 60%-92%), positive predictive value of 79% (95% CI 57%-91%), and negative predictive value of 100% (95% CI 82%-100%).

Study details: Findings are from a review of the echocardiographic features of 40 fetuses with either DAA or RAA-LD (those with the left duct connecting the pulmonary artery and descending aorta) confirmed during surgery, which displayed the commonest overlap in fetal appearances.

Disclosures: MPM Van Poppel received financial support from the Wellcome/EPSRC Centre for Medical Engineering. The other authors did not report any conflict of interests.

Source: Van Poppel MPM et al. Prenat Diagn. 2022 (Jan 20). Doi: 10.1002/pd.6104.

Key clinical point: The Z-sign may serve as a strong marker for a double aortic arch (DAA) in surgically confirmed cases of vascular rings, even in those with atresia of the left arch, and thus facilitate the differentiation between a right aortic arch with left duct (RAA-LD) and DAA in the second trimester of pregnancy.

Main finding: The Z-sign could predict a DAA with a sensitivity of 100% (95% CI 80%-100%), specificity of 81% (95% CI 60%-92%), positive predictive value of 79% (95% CI 57%-91%), and negative predictive value of 100% (95% CI 82%-100%).

Study details: Findings are from a review of the echocardiographic features of 40 fetuses with either DAA or RAA-LD (those with the left duct connecting the pulmonary artery and descending aorta) confirmed during surgery, which displayed the commonest overlap in fetal appearances.

Disclosures: MPM Van Poppel received financial support from the Wellcome/EPSRC Centre for Medical Engineering. The other authors did not report any conflict of interests.

Source: Van Poppel MPM et al. Prenat Diagn. 2022 (Jan 20). Doi: 10.1002/pd.6104.

Key clinical point: The Z-sign may serve as a strong marker for a double aortic arch (DAA) in surgically confirmed cases of vascular rings, even in those with atresia of the left arch, and thus facilitate the differentiation between a right aortic arch with left duct (RAA-LD) and DAA in the second trimester of pregnancy.

Main finding: The Z-sign could predict a DAA with a sensitivity of 100% (95% CI 80%-100%), specificity of 81% (95% CI 60%-92%), positive predictive value of 79% (95% CI 57%-91%), and negative predictive value of 100% (95% CI 82%-100%).

Study details: Findings are from a review of the echocardiographic features of 40 fetuses with either DAA or RAA-LD (those with the left duct connecting the pulmonary artery and descending aorta) confirmed during surgery, which displayed the commonest overlap in fetal appearances.

Disclosures: MPM Van Poppel received financial support from the Wellcome/EPSRC Centre for Medical Engineering. The other authors did not report any conflict of interests.

Source: Van Poppel MPM et al. Prenat Diagn. 2022 (Jan 20). Doi: 10.1002/pd.6104.

Key clinical point: Fetuses with complicated congenital gastrointestinal obstruction (CGIO) vs. isolated CGIO are at a greater risk for chromosomal aberrations and pathogenic copy number variants (CNV).

Main finding: Fetuses with complicated CGIO showed a significantly higher detection rate of karyotype abnormalities (33.8% vs. 10.8%; P < .01) and overall detection rate of pathogenic CNVs (20% vs. 4.8%; P < .05) than those with isolated CGIO.

Study details: This retrospective study analyzed 240 fetuses prenatally diagnosed with CGIO who presented as either isolated (alone) or complicated (in combination with certain soft markers and structural abnormalities) and were referred for karyotyping or copy number variation sequencing.

Disclosures: No source of funding or conflict of interests were reported by the authors.

Source: Meng X, Jiang L. BMC Pregnancy Childbirth. 2022;22:50 (Jan 19). Doi: 10.1186/s12884-022-04401-y.

Key clinical point: Fetuses with complicated congenital gastrointestinal obstruction (CGIO) vs. isolated CGIO are at a greater risk for chromosomal aberrations and pathogenic copy number variants (CNV).

Main finding: Fetuses with complicated CGIO showed a significantly higher detection rate of karyotype abnormalities (33.8% vs. 10.8%; P < .01) and overall detection rate of pathogenic CNVs (20% vs. 4.8%; P < .05) than those with isolated CGIO.

Study details: This retrospective study analyzed 240 fetuses prenatally diagnosed with CGIO who presented as either isolated (alone) or complicated (in combination with certain soft markers and structural abnormalities) and were referred for karyotyping or copy number variation sequencing.

Disclosures: No source of funding or conflict of interests were reported by the authors.

Source: Meng X, Jiang L. BMC Pregnancy Childbirth. 2022;22:50 (Jan 19). Doi: 10.1186/s12884-022-04401-y.

Key clinical point: Fetuses with complicated congenital gastrointestinal obstruction (CGIO) vs. isolated CGIO are at a greater risk for chromosomal aberrations and pathogenic copy number variants (CNV).

Main finding: Fetuses with complicated CGIO showed a significantly higher detection rate of karyotype abnormalities (33.8% vs. 10.8%; P < .01) and overall detection rate of pathogenic CNVs (20% vs. 4.8%; P < .05) than those with isolated CGIO.

Study details: This retrospective study analyzed 240 fetuses prenatally diagnosed with CGIO who presented as either isolated (alone) or complicated (in combination with certain soft markers and structural abnormalities) and were referred for karyotyping or copy number variation sequencing.

Disclosures: No source of funding or conflict of interests were reported by the authors.

Source: Meng X, Jiang L. BMC Pregnancy Childbirth. 2022;22:50 (Jan 19). Doi: 10.1186/s12884-022-04401-y.

Key clinical point: Ultrasound evaluation performed following a standardized protocol is highly effective at detecting placenta accreta spectrum (PAS) in pregnant women with persistent placenta previa under real-world conditions.

Main finding: Of 126 patients with placenta previa, PAS was detected in 11 patients, of which 10 were diagnosed prenatally by ultrasound, exhibiting a sensitivity of 90.9%, specificity of 98.3%, positive predictive value of 83.3%, and negative predictive value of 99.1%.

Study details: This was a retrospective real-world cohort study involving 126 pregnant women with persistent placenta previa who underwent standardized transabdominal and transvaginal ultrasound to assess hypoechoic retroplacental zone loss or myometrial thinning <1 mm, lacunar images (flow >15 cm/second), thick and bulging placenta, uterine-bladder serous interface thinning/interruption, and placental/uterovesical hypervascularity; the presence of at least 1 was considered high-risk for PAS.

Disclosures: The authors disclosed receiving no financial support for the study and having no conflict of interests.

Source: Juan-Clar M et al. Fetal Diagn Ther. 2022 (Jan 11). Doi: 10.1159/000521738.

Key clinical point: Ultrasound evaluation performed following a standardized protocol is highly effective at detecting placenta accreta spectrum (PAS) in pregnant women with persistent placenta previa under real-world conditions.

Main finding: Of 126 patients with placenta previa, PAS was detected in 11 patients, of which 10 were diagnosed prenatally by ultrasound, exhibiting a sensitivity of 90.9%, specificity of 98.3%, positive predictive value of 83.3%, and negative predictive value of 99.1%.

Study details: This was a retrospective real-world cohort study involving 126 pregnant women with persistent placenta previa who underwent standardized transabdominal and transvaginal ultrasound to assess hypoechoic retroplacental zone loss or myometrial thinning <1 mm, lacunar images (flow >15 cm/second), thick and bulging placenta, uterine-bladder serous interface thinning/interruption, and placental/uterovesical hypervascularity; the presence of at least 1 was considered high-risk for PAS.

Disclosures: The authors disclosed receiving no financial support for the study and having no conflict of interests.

Source: Juan-Clar M et al. Fetal Diagn Ther. 2022 (Jan 11). Doi: 10.1159/000521738.

Key clinical point: Ultrasound evaluation performed following a standardized protocol is highly effective at detecting placenta accreta spectrum (PAS) in pregnant women with persistent placenta previa under real-world conditions.

Main finding: Of 126 patients with placenta previa, PAS was detected in 11 patients, of which 10 were diagnosed prenatally by ultrasound, exhibiting a sensitivity of 90.9%, specificity of 98.3%, positive predictive value of 83.3%, and negative predictive value of 99.1%.

Study details: This was a retrospective real-world cohort study involving 126 pregnant women with persistent placenta previa who underwent standardized transabdominal and transvaginal ultrasound to assess hypoechoic retroplacental zone loss or myometrial thinning <1 mm, lacunar images (flow >15 cm/second), thick and bulging placenta, uterine-bladder serous interface thinning/interruption, and placental/uterovesical hypervascularity; the presence of at least 1 was considered high-risk for PAS.

Disclosures: The authors disclosed receiving no financial support for the study and having no conflict of interests.

Source: Juan-Clar M et al. Fetal Diagn Ther. 2022 (Jan 11). Doi: 10.1159/000521738.

Key clinical point: Performing prenatal exome sequencing (ES) not solely for the indication of fetal malformations but also for specific prenatal findings, such as fetal growth restriction and polyhydramnios, could avoid missing the diagnosis of postnatal neurocognitive disorders.

Main finding: Sonographic fetal structural findings of 52.5% of patients with postnatally diagnosed neurocognitive disorders did not hint at considering prenatal ES. Fetal structural abnormalities and other sonographic anomalies (fetal growth restriction, polyhydramnios, etc.) were shown by 23.75% of patients.

Study details: Findings are from a retrospective study that analyzed the prenatal sonographic data of 122 patients with postnatally diagnosed neurocognitive disorder using ES.

Disclosures: The authors received no financial support for conducting the study. AR Shuldiner disclosed being a full-time employee of and receiving salary and stock options from Regeneron Pharmaceuticals. C Gonzaga-Jauregui was a full-time employee of Regeneron Pharmaceuticals at the time of the study.

Source: Sukenik-Halevy R et al. Prenat Diagn. 2022 (Jan 14). Doi: 10.1002/pd.6095.

Key clinical point: Performing prenatal exome sequencing (ES) not solely for the indication of fetal malformations but also for specific prenatal findings, such as fetal growth restriction and polyhydramnios, could avoid missing the diagnosis of postnatal neurocognitive disorders.

Main finding: Sonographic fetal structural findings of 52.5% of patients with postnatally diagnosed neurocognitive disorders did not hint at considering prenatal ES. Fetal structural abnormalities and other sonographic anomalies (fetal growth restriction, polyhydramnios, etc.) were shown by 23.75% of patients.

Study details: Findings are from a retrospective study that analyzed the prenatal sonographic data of 122 patients with postnatally diagnosed neurocognitive disorder using ES.

Disclosures: The authors received no financial support for conducting the study. AR Shuldiner disclosed being a full-time employee of and receiving salary and stock options from Regeneron Pharmaceuticals. C Gonzaga-Jauregui was a full-time employee of Regeneron Pharmaceuticals at the time of the study.

Source: Sukenik-Halevy R et al. Prenat Diagn. 2022 (Jan 14). Doi: 10.1002/pd.6095.

Key clinical point: Performing prenatal exome sequencing (ES) not solely for the indication of fetal malformations but also for specific prenatal findings, such as fetal growth restriction and polyhydramnios, could avoid missing the diagnosis of postnatal neurocognitive disorders.

Main finding: Sonographic fetal structural findings of 52.5% of patients with postnatally diagnosed neurocognitive disorders did not hint at considering prenatal ES. Fetal structural abnormalities and other sonographic anomalies (fetal growth restriction, polyhydramnios, etc.) were shown by 23.75% of patients.

Study details: Findings are from a retrospective study that analyzed the prenatal sonographic data of 122 patients with postnatally diagnosed neurocognitive disorder using ES.

Disclosures: The authors received no financial support for conducting the study. AR Shuldiner disclosed being a full-time employee of and receiving salary and stock options from Regeneron Pharmaceuticals. C Gonzaga-Jauregui was a full-time employee of Regeneron Pharmaceuticals at the time of the study.

Source: Sukenik-Halevy R et al. Prenat Diagn. 2022 (Jan 14). Doi: 10.1002/pd.6095.

Key clinical point: Fetal cerebral blood flow redistribution assessed by antenatal Doppler scanning is a strong and independent indicator of a composite adverse perinatal outcome (CAPO) and stillbirth in low-resource settings.

Main finding: Middle cerebral artery pulsatility index (PI) <5^th percentile (adjusted odds ratio [aOR] 2.08; P = .013), cerebroplacental ratio (CPR) <5^th percentile (aOR 2.22; P = .02), and uterine artery PI >95^th percentile (aOR 2.36; P = .041) showed a significant association with CAPO. CPR <5^th percentile was significantly associated with stillbirth (aOR 4.82; P = .038).

Study details: Findings are from a single-center prospective cohort study including 995 singleton pregnant women who enrolled in antenatal care after <24 weeks of pregnancy and showed no obvious fetal abnormalities on an antenatal ultrasound scan.

Disclosures: The study was sponsored by Grand Challenges Canada and University Medical Center Utrecht, The Netherlands. No conflict of interests was reported.

Source: Ali S et al. BJOG. 2022 (Feb 4). Doi: 10.1111/1471-0528.17115.

Key clinical point: Fetal cerebral blood flow redistribution assessed by antenatal Doppler scanning is a strong and independent indicator of a composite adverse perinatal outcome (CAPO) and stillbirth in low-resource settings.

Main finding: Middle cerebral artery pulsatility index (PI) <5^th percentile (adjusted odds ratio [aOR] 2.08; P = .013), cerebroplacental ratio (CPR) <5^th percentile (aOR 2.22; P = .02), and uterine artery PI >95^th percentile (aOR 2.36; P = .041) showed a significant association with CAPO. CPR <5^th percentile was significantly associated with stillbirth (aOR 4.82; P = .038).

Study details: Findings are from a single-center prospective cohort study including 995 singleton pregnant women who enrolled in antenatal care after <24 weeks of pregnancy and showed no obvious fetal abnormalities on an antenatal ultrasound scan.

Disclosures: The study was sponsored by Grand Challenges Canada and University Medical Center Utrecht, The Netherlands. No conflict of interests was reported.

Source: Ali S et al. BJOG. 2022 (Feb 4). Doi: 10.1111/1471-0528.17115.

Key clinical point: Fetal cerebral blood flow redistribution assessed by antenatal Doppler scanning is a strong and independent indicator of a composite adverse perinatal outcome (CAPO) and stillbirth in low-resource settings.

Main finding: Middle cerebral artery pulsatility index (PI) <5^th percentile (adjusted odds ratio [aOR] 2.08; P = .013), cerebroplacental ratio (CPR) <5^th percentile (aOR 2.22; P = .02), and uterine artery PI >95^th percentile (aOR 2.36; P = .041) showed a significant association with CAPO. CPR <5^th percentile was significantly associated with stillbirth (aOR 4.82; P = .038).

Study details: Findings are from a single-center prospective cohort study including 995 singleton pregnant women who enrolled in antenatal care after <24 weeks of pregnancy and showed no obvious fetal abnormalities on an antenatal ultrasound scan.

Disclosures: The study was sponsored by Grand Challenges Canada and University Medical Center Utrecht, The Netherlands. No conflict of interests was reported.

Source: Ali S et al. BJOG. 2022 (Feb 4). Doi: 10.1111/1471-0528.17115.

Key clinical point: In women at low risk for aneuploidy, single-nucleotide polymorphism-based cell-free DNA (cfDNA) screening for trisomies 21, 18, and 13 (T21, T18, T13, respectively) demonstrates similar high sensitivity, specificity, and positive predictive value (PPV) as those in high-risk women.

Main finding: In low-risk vs. high-risk women, T21 was detected with similar sensitivity (100% vs. 98.8%; P = 1.0), specificity (99.98% vs. 99.96%; P = .61), and a high PPV (85.71% vs. 97.53%; P = .06), with analogous results for T18 and T13.

Study details: Findings are from a multicenter, prospective, observational SMART study including 17,851 pregnant women undergoing cfDNA screening for aneuploidy and 22q11.2DS, along with DNA analysis of the fetus or newborn. Of these, 13,043 pregnancies were at low risk for aneuploidy, with the rest being high risk.

Disclosures: The study was funded by Natera, Inc, CA, USA. Some of the authors, including the lead author, received institutional research support from Natera. M Egbert, Z Demko, M Rabinowitz, and K Martin serve as an employee/consultant of Natera and own stocks/options. J Hyett has participated in expert consultancies for and B Jacobson reports research clinical diagnostic trials with Natera, among others.

Source: Dar P et al. Am J Obstet Gynecol. 2022 (Jan 24). Doi: 10.1016/j.ajog.2022.01.019.

Key clinical point: In women at low risk for aneuploidy, single-nucleotide polymorphism-based cell-free DNA (cfDNA) screening for trisomies 21, 18, and 13 (T21, T18, T13, respectively) demonstrates similar high sensitivity, specificity, and positive predictive value (PPV) as those in high-risk women.

Main finding: In low-risk vs. high-risk women, T21 was detected with similar sensitivity (100% vs. 98.8%; P = 1.0), specificity (99.98% vs. 99.96%; P = .61), and a high PPV (85.71% vs. 97.53%; P = .06), with analogous results for T18 and T13.

Study details: Findings are from a multicenter, prospective, observational SMART study including 17,851 pregnant women undergoing cfDNA screening for aneuploidy and 22q11.2DS, along with DNA analysis of the fetus or newborn. Of these, 13,043 pregnancies were at low risk for aneuploidy, with the rest being high risk.

Disclosures: The study was funded by Natera, Inc, CA, USA. Some of the authors, including the lead author, received institutional research support from Natera. M Egbert, Z Demko, M Rabinowitz, and K Martin serve as an employee/consultant of Natera and own stocks/options. J Hyett has participated in expert consultancies for and B Jacobson reports research clinical diagnostic trials with Natera, among others.

Source: Dar P et al. Am J Obstet Gynecol. 2022 (Jan 24). Doi: 10.1016/j.ajog.2022.01.019.

Key clinical point: In women at low risk for aneuploidy, single-nucleotide polymorphism-based cell-free DNA (cfDNA) screening for trisomies 21, 18, and 13 (T21, T18, T13, respectively) demonstrates similar high sensitivity, specificity, and positive predictive value (PPV) as those in high-risk women.

Main finding: In low-risk vs. high-risk women, T21 was detected with similar sensitivity (100% vs. 98.8%; P = 1.0), specificity (99.98% vs. 99.96%; P = .61), and a high PPV (85.71% vs. 97.53%; P = .06), with analogous results for T18 and T13.

Study details: Findings are from a multicenter, prospective, observational SMART study including 17,851 pregnant women undergoing cfDNA screening for aneuploidy and 22q11.2DS, along with DNA analysis of the fetus or newborn. Of these, 13,043 pregnancies were at low risk for aneuploidy, with the rest being high risk.

Disclosures: The study was funded by Natera, Inc, CA, USA. Some of the authors, including the lead author, received institutional research support from Natera. M Egbert, Z Demko, M Rabinowitz, and K Martin serve as an employee/consultant of Natera and own stocks/options. J Hyett has participated in expert consultancies for and B Jacobson reports research clinical diagnostic trials with Natera, among others.

Source: Dar P et al. Am J Obstet Gynecol. 2022 (Jan 24). Doi: 10.1016/j.ajog.2022.01.019.

Prenatal ultrasound detects structural fetal abnormalities in about 3% of pregnancies. When structural fetal abnormalities are found on prenatal ultrasound, diagnostic genetic testing with either CVS or amniocentesis are recommended. Classically, this has meant fetal karyotype and chromosomal microarray testing (CMA). Recently, a new type of genetic testing has become available on fetal samples, whole-exome sequencing (WES). Smogavec et al. assesses this new technology and its ability to detect fetal genetic abnormalities. They retrospectively studied 90 fetuses with abnormalities detected on prenatal ultrasound that had normal CMA results and negative fluorescence in situ hybridization analysis testing for aneuploidy. They found WES testing added a 34.4% increased rate of detection of fetal genetic abnormalities. WES is a powerful tool for genetic diagnosis in fetuses with structural anomalies and should be considered anytime a karyotype or CMA is normal in a fetus with structural anomalies.

Lastly, prenatal genetic diagnosis at an early gestational age is critical for medical management of fetuses with anomalies. In a cohort study, Chen et al. assess the simultaneous combined use of CNV-seq and WES on testing turnaround time. They found by running the testing simultaneously, rather than sequentially, this would decrease testing time from over a month to less than 2 weeks. This strategy of testing could potentially decrease the time from detection of a fetal anomaly on ultrasound to a genetic diagnosis allowing for earlier counseling and medical guidance.

Prenatal ultrasound detects structural fetal abnormalities in about 3% of pregnancies. When structural fetal abnormalities are found on prenatal ultrasound, diagnostic genetic testing with either CVS or amniocentesis are recommended. Classically, this has meant fetal karyotype and chromosomal microarray testing (CMA). Recently, a new type of genetic testing has become available on fetal samples, whole-exome sequencing (WES). Smogavec et al. assesses this new technology and its ability to detect fetal genetic abnormalities. They retrospectively studied 90 fetuses with abnormalities detected on prenatal ultrasound that had normal CMA results and negative fluorescence in situ hybridization analysis testing for aneuploidy. They found WES testing added a 34.4% increased rate of detection of fetal genetic abnormalities. WES is a powerful tool for genetic diagnosis in fetuses with structural anomalies and should be considered anytime a karyotype or CMA is normal in a fetus with structural anomalies.

Lastly, prenatal genetic diagnosis at an early gestational age is critical for medical management of fetuses with anomalies. In a cohort study, Chen et al. assess the simultaneous combined use of CNV-seq and WES on testing turnaround time. They found by running the testing simultaneously, rather than sequentially, this would decrease testing time from over a month to less than 2 weeks. This strategy of testing could potentially decrease the time from detection of a fetal anomaly on ultrasound to a genetic diagnosis allowing for earlier counseling and medical guidance.

Prenatal ultrasound detects structural fetal abnormalities in about 3% of pregnancies. When structural fetal abnormalities are found on prenatal ultrasound, diagnostic genetic testing with either CVS or amniocentesis are recommended. Classically, this has meant fetal karyotype and chromosomal microarray testing (CMA). Recently, a new type of genetic testing has become available on fetal samples, whole-exome sequencing (WES). Smogavec et al. assesses this new technology and its ability to detect fetal genetic abnormalities. They retrospectively studied 90 fetuses with abnormalities detected on prenatal ultrasound that had normal CMA results and negative fluorescence in situ hybridization analysis testing for aneuploidy. They found WES testing added a 34.4% increased rate of detection of fetal genetic abnormalities. WES is a powerful tool for genetic diagnosis in fetuses with structural anomalies and should be considered anytime a karyotype or CMA is normal in a fetus with structural anomalies.

Lastly, prenatal genetic diagnosis at an early gestational age is critical for medical management of fetuses with anomalies. In a cohort study, Chen et al. assess the simultaneous combined use of CNV-seq and WES on testing turnaround time. They found by running the testing simultaneously, rather than sequentially, this would decrease testing time from over a month to less than 2 weeks. This strategy of testing could potentially decrease the time from detection of a fetal anomaly on ultrasound to a genetic diagnosis allowing for earlier counseling and medical guidance.