The following is a summary of “Obstetrical, perinatal, and genetic outcomes associated with nonreportable prenatal cell-free DNA screening results,” published in the SEPTEMBER 2023 issue of Obstetrics and Gynecology by Norton, et al.
The clinical significance of nonreportable cell-free DNA screening results during pregnancy remains uncertain. Such results indicate issues with placental implantation and could be associated with adverse obstetrical and perinatal outcomes. For a study, researchers sought to assess the outcomes of pregnancies with nonreportable cell-free DNA screening results in a cohort of patients, including genetic and obstetrical outcomes.
It was a prespecified secondary analysis of a multicenter prospective observational study involving prenatal cell-free DNA screening for fetal aneuploidy and 22q11.2 deletion syndrome. Participants who underwent cell-free DNA screening between April 2015 and January 2019 were enrolled. Data on obstetrical outcomes and neonatal genetic testing results were collected from 21 primary care and referral centers in the United States, Europe, and Australia. The primary outcome was the risk of adverse obstetrical and perinatal outcomes, including aneuploidy, preterm birth at <28, <34, and <37 weeks’ gestation, preeclampsia, small for gestational age or birthweight <10th percentile for gestational week, and a composite outcome that included preterm birth at <37 weeks, preeclampsia, small for gestational age, and stillbirth at >20 weeks, following nonreportable cell-free DNA screening results due to low fetal fraction or other causes. Multivariable analyses were conducted, adjusting for variables associated with obstetrical and perinatal outcomes, nonreportable results, or fetal fraction.
A total of 25,199 pregnant individuals were screened, with 20,194 being enrolled. Genetic confirmation needed to be included in 1,165 (5.8%), 1,085 (5.4%) were lost to follow-up, and 93 (0.5%) withdrew. The final study cohort included 17,851 (88.4%) participants with cell-free DNA testing, fetal or newborn genetic confirmatory testing, and obstetrical and perinatal outcomes data. Results were nonreportable in 602 (3.4%) participants. A sample was redrawn, and testing was attempted again in 427 individuals; in 112 (26.2%), results were again nonreportable. Nonreportable results were associated with higher body mass index, chronic hypertension, later gestational age, lower fetal fraction, and Black race. Trisomy 13, 18, or 21 was confirmed in 1.6% of those with nonreportable tests vs. 0.7% with reported results. Rates of preterm birth at <28, 34, and 37 weeks, preeclampsia, and the composite outcome were higher among participants with nonreportable results, and these rates further increased among those with a second nonreportable test. However, the rate of small for gestational-age infants was not increased. After adjustment for confounders, the adjusted odds ratios were 2.2 (95% CI, 1.1–4.4) and 2.6 (95% CI, 0.6–10.8) for aneuploidy, and 1.5 (95% CI, 1.2–1.8) and 2.1 (95% CI, 1.4–3.2) for the composite outcome after a first and second nonreportable test, respectively. Of the patients with nonreportable tests, 94.9% had a live birth, as opposed to 98.8% with reported test results 0.20 [95% CI, 0.13–0.30]).
Patients with nonreportable cell-free DNA results are at increased risk for adverse outcomes, including aneuploidy, preeclampsia, and preterm birth. They should be offered diagnostic genetic testing, and healthcare providers should be aware of the elevated risk of pregnancy complications in such cases.