| 1. |
- Martin, Kimberly, et al.
(author)
-
Impact of high-risk prenatal screening results for 22q11.2 deletion syndrome on obstetric and neonatal management: Secondary analysis from the SMART study
- 2023
-
In: Prenatal Diagnosis. - 0197-3851 .- 1097-0223. ; 43:13, s. 1574-1580
-
Journal article (peer-reviewed)abstract
- Objective: One goal of prenatal genetic screening is to optimize perinatal care and improve infant outcomes. We sought to determine whether high-risk cfDNA screening for 22q11.2 deletion syndrome (22q11.2DS) affected prenatal or neonatal management. Methods: This was a secondary analysis from the SMART study. Patients with high-risk cfDNA results for 22q11.2DS were compared with the low-risk cohort for pregnancy characteristics and obstetrical management. To assess differences in neonatal care, we compared high-risk neonates without prenatal genetic confirmation with a 1:1 matched low-risk cohort. Results: Of 18,020 eligible participants enrolled between 2015 and 2019, 38 (0.21%) were high-risk and 17,982 (99.79%) were low-risk for 22q11.2DS by cfDNA screening. High-risk participants had more prenatal diagnostic testing (55.3%; 21/38 vs. 2.0%; 352/17,982, p<0.001) and fetal echocardiography (76.9%; 10/13 vs. 19.6%; 10/51, p<0.001). High-risk newborns without prenatal diagnostic testing had higher rates of neonatal genetic testing (46.2%; 6/13 vs. 0%; 0/51, P<0.001), echocardiography (30.8%; 4/13 vs. 4.0%; 2/50, p=0.013), evaluation of calcium levels (46.2%; 6/13 vs. 4.1%; 2/49, P<0.001) and lymphocyte count (53.8%; 7/13 vs. 15.7%; 8/51, p=0.008). Conclusions: High-risk screening results for 22q11.2DS were associated with higher rates of prenatal and neonatal diagnostic genetic testing and other 22q11.2DS-specific evaluations. However, these interventions were not universally performed, and >50% of high-risk infants were discharged without genetic testing, representing possible missed opportunities to improve outcomes for affected individuals.
|
|
| 2. |
- Martin, Kimberly, et al.
(author)
-
Performance of prenatal cfDNA screening for sex chromosomes.
- 2023
-
In: Genetics in medicine : official journal of the American College of Medical Genetics. - 1530-0366. ; 25:8
-
Journal article (peer-reviewed)abstract
- To assess the performance of cell-free DNA (cfDNA) screening to detect sex chromosome aneuploidies (SCA) in an unselected obstetrical population with genetic confirmation.This was a planned secondary analysis of the multicenter, prospective SMART study. Patients receiving cfDNA results for autosomal aneuploidies and who had confirmatory genetic results for the relevant sex chromosomal aneuploidies were included. Screening performance for SCAs, including monosomy X (MX) and the sex chromosome trisomies (SCTs; 47,XXX; 47,XXY; 47,XYY) was determined. Fetal sex concordance between cfDNA and genetic screening was also evaluated in euploid pregnancies.17,538 cases met inclusion criteria. Performance of cfDNA for MX, SCTs and fetal sex was determined in 17,297, 10,333 and 14,486 pregnancies, respectively. Sensitivity, specificity, and PPV of cfDNA were 83.3%, 99.9%, and 22.7% for MX, and 70.4%, 99.9%, and 82.6% for the combined SCTs. The accuracy of fetal sex prediction by cfDNA was 100%.Screening performance of cfDNA for SCAs is comparable to that reported in other studies. The PPV for the SCTs was similar to the autosomal trisomies, while the PPV for MX was substantially lower. No discordance in fetal sex was observed between cfDNA and postnatal genetic screening in euploid pregnancies. These data will assist interpretation and counseling for cfDNA results for sex chromosomes.
|
|
| 3. |
- Norton, Mary E, et al.
(author)
-
Obstetrical, perinatal and genetic outcomes associated with non-reportable prenatal cell free DNA screening results.
- 2023
-
In: American journal of obstetrics and gynecology. - : Elsevier BV. - 0002-9378 .- 1097-6868. ; 229:3
-
Journal article (peer-reviewed)abstract
- The clinical implications of non-reportable cfDNA screening results are uncertain, but this may reflect poor placental implantation in some cases and be associated with adverse obstetrical and perinatal outcomes.To assess the outcomes of pregnancies with non-reportable cell-free DNA (cfDNA) screening in a cohort of patients with complete genetic and obstetric outcomes.This was a prespecified secondary analysis of a multicenter prospective observational study of prenatal cfDNA screening for fetal aneuploidy and 22q11.2 deletion syndrome. Participants who underwent cfDNA screening from April 2015 through January 2019 were offered participation. Obstetric outcomes and neonatal genetic testing results were collected from 21 primary care and referral centers in the US, Europe, and Australia. The primary outcome was risk for adverse obstetrical and perinatal outcomes (aneuploidy, preterm birth (PTB) at <28, <34, and <37 weeks' gestation, preeclampsia, small for gestational age (SGA) or birthweight <10th percentile for gestational week, and a composite outcome that included PTB<37 weeks, preeclampsia, SGA, and stillbirth>20 weeks') after non-reportable cfDNA screening due to low fetal fraction or other causes. Multivariable analyses were performed, adjusting for variables known to be associated with obstetrical and perinatal outcomes, non-reportable results, or fetal fraction.In total, 25,199 pregnant individuals were screened, and 20,194 were enrolled. Genetic confirmation was missing in 1165 (5.8%), 1085 (5.4%) were lost to follow-up, and 93 (0.5%) withdrew; the final study cohort included 17,851 (88.4%) participants who had cfDNA, fetal or newborn genetic confirmatory testing, and obstetrical and perinatal outcomes collected. Results were non-reportable in 602 (3.4%). A sample was redrawn and testing again attempted in 427; in 112 (26.2%) results were again non-reportable. Non-reportable results were associated with higher BMI, chronic hypertension, later gestational age, lower fetal fraction, and Black race. Trisomy 13, 18, or 21 was confirmed in 1.6% with non-reportable tests vs. 0.7% with results (p=.013). PTB <28, 34, and 37 weeks, preeclampsia, and the composite outcome were higher after non-reportable results, and further increased with a second non-reportable test, while SGA was not increased. After adjustment for confounders, the aOR for aneuploidy was 2.2 (95% CI 1.1, 4.4) and 2.6 (95% CI 0.6, 10.8) and for the composite outcome was 1.5 (95% CI 1.2, 1.8) and 2.1 (95% CI 1.4, 3.2) after a first and second non-reportable test. In all, 94.9% of patients with non-reportable tests had a livebirth as compared to 98.8% with those with test results obtained (aOR for livebirth: 0.20 [95% CI 0.13-0.30]).Patients with non-reportable cfDNA results are at increased risk for a number of adverse outcomes, including aneuploidy as well as preeclampsia and preterm birth. They should be offered diagnostic genetic testing and clinicians should be aware of the increased risk of pregnancy complications.
|
|
