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Background: The clinical implications of nonreportable cell-free DNA screening results are uncertain, but such results may indicate poor placental implantation in some cases and be associated with adverse obstetrical and perinatal outcomes., Objective: This study aimed to assess the outcomes of pregnancies with nonreportable cell-free DNA screening in a cohort of patients with complete genetic and obstetrical outcomes., Study Design: This was a prespecified secondary analysis of a multicenter prospective observational study of prenatal cell-free DNA screening for fetal aneuploidy and 22q11.2 deletion syndrome. Participants who underwent cell-free DNA screening from April 2015 through January 2019 were offered participation. 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 risk for adverse obstetrical and perinatal outcomes (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) after nonreportable cell-free DNA screening because of low fetal fraction or other causes. Multivariable analyses were performed, adjusting for variables known to be associated with obstetrical and perinatal outcomes, nonreportable results, or fetal fraction., Results: 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 cell-free DNA, fetal or newborn genetic confirmatory testing, and obstetrical and perinatal outcomes collected. Results were nonreportable in 602 (3.4%) participants. A sample was redrawn and testing attempted again in 427; in 112 (26.2%) participants, 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% with nonreportable tests vs 0.7% with reported results (P=.013). Rates of preterm birth at <28, 34, and 37 weeks, preeclampsia, and the composite outcome were higher among participants with nonreportable results, and further increased among those with a second nonreportable test, whereas the rate of small for gestational age infants was not increased. After adjustment for confounders, the adjusted odds ratios were 2.2 (95% confidence interval, 1.1-4.4) and 2.6 (95% confidence interval, 0.6-10.8) for aneuploidy, and 1.5 (95% confidence interval, 1.2-1.8) and 2.1 (95% confidence interval, 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% of those with reported test results (adjusted odds ratio for livebirth, 0.20 [95% confidence interval, 0.13-0.30])., Conclusion: Patients with nonreportable cell-free DNA results are at increased risk for a number of adverse outcomes, including aneuploidy, preeclampsia, and preterm birth. They should be offered diagnostic genetic testing, and clinicians should be aware of the increased risk of pregnancy complications., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the relationship between first and second trimester maternal serum-free β-hCG and the risk of spontaneous preterm delivery (PTD). Study design: This was a case-control study of women evaluated and delivered at our institution from 2011 to 2015. Spontaneous PTD was defined as delivery before 37 weeks due to spontaneous preterm labor or premature rupture of membranes. Patient with multifetal gestation and those with medically indicated term or PTD were excluded. Results: Of 877 women meeting the inclusion criteria, 173 delivered preterm and 704 delivered at term, and 8.1% had high free β-hCG in one or both trimesters. High maternal first and/or second trimester free β-hCG (≥95th percentile) was associated with lower rates of PTD. Thirty-two women with high free β-hCG in both first and second trimesters delivered at term. Gestational age at delivery and birth weights were lower in women who did not have high free β-hCG in any trimester. Low free β-hCG (≤5th percentile) in either trimester was not associated with an increased or decreased likelihood of PTD. Logistic regression demonstrated an independent association of high free β-hCG (≥95th percentile) with a reduced likelihood of PTD. Stratified analysis revealed a stronger impact of this association in women with no prior history of PTD. Conclusions: High free β-hCG, in the absence of risk factors for medically indicated PTD, is associated with a reduced likelihood of spontaneous PTD and may represent a marker indicating lower risk.

Objectives: To determine whether a novel, noninvasive quantitative ultrasound (US) technique can detect differences in proximal and distal cervical tissue echogenicity in women with and without a shortened cervical length (CL)., Methods: We conducted a retrospective case-control study of singleton pregnancies at 16 to 26 weeks' gestation in which a transvaginal US examination was performed to measure CL from 2013 to 2015. Initial CLs in cases and controls were less than 2.5 cm and 2.5 cm or greater, respectively. For each US image, a region of interest was selected in the proximal and distal cervical stroma, in both the anterior and posterior cervical lips. The Floyd-Steinberg dithering algorithm transformed grayscale pixels in each region of interest into a binary map. A histogram tabulated the number of black and white pixels, allowing determination of the percent echogenicity. The difference in the percent echogenicity was calculated by subtracting the distal cervical echogenicity (average of anterior and posterior lips) from the proximal cervical echogenicity (average of anterior and posterior lips)., Results: Ultrasound images from 177 women were analyzed. There was a difference in the percent echogenicity (P < .0001) when comparing women with a short cervix (mean ± SD, 9.8 ± 10.1; n = 102) to women with a normal CL (17.2 ± 9.5; n = 75). Differences were attributable to changes in proximal (P < .008) rather than distal cervical echogenicity. Regardless of CL, the proximal cervix was more echogenic than the distal cervix., Conclusions: A quantitative US analysis of cervical tissue can detect differences in echogenicity between the proximal and distal cervix in the second trimester. Proximal cervical echogenicity is lower with CL of less than 2.5 cm compared to a normal CL., (© 2018 by the American Institute of Ultrasound in Medicine.)

Background:  In a normal pregnancy, cervical collagen fibers remain organized in predictable patterns throughout most of the gestation. Cervical remodeling reflects a rearrangement of collagen fibers in which they become increasingly disordered and contribute to the pathogenesis of spontaneous preterm birth. Quantitative ultrasound analysis of cervical tissue echotexture may have the capacity to identify microstructural changes before the onset of cervical shortening., Objective:  The primary objective of this study was to examine the utility of a novel quantitative sonographic marker, the cervical heterogeneity index (HI), which reflects the relative organization of cervical collagen fibers. Also, we aimed to determine an optimal HI cut-point to predict spontaneous preterm birth., Study Design:  This retrospective cohort study employed a novel image-processing technique on transvaginal ultrasound images of the cervix in gestations between 14 and 28 completed weeks. The transvaginal sonography images were analyzed in MATLAB (MathWorks, Natick, MA) using a custom image-processing technique that assessed the relative heterogeneity of the cervical tissue., Results:  A total of 151 subjects were included in the study. The mean HI in subjects who delivered preterm and at term was 8.28 ± 3.73 and 12.35 ± 5.80, respectively ( p  < 0.0001). Thus, decreased tissue heterogeneity was associated with preterm birth, and increased tissue heterogeneity was associated with delivery at term. In our study population, preterm birth was associated with a short cervix (<2.5 cm), history of preterm birth and lower HI, and our findings indicate that HI may improve prediction of preterm birth., Conclusion:  Quantitative ultrasound measurement of the cervical HI is a promising, noninvasive tool for early prediction of spontaneous preterm birth., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: A major risk of trials of labor in patients with prior cesarean delivery is uterine rupture. We evaluated the question of whether a previous cesarean delivery at an early gestational age predisposes the patient to subsequent uterine rupture., Methods: This was a retrospective chart review of patients delivering at North Shore University Hospital with a trial of labor after previous cesarean delivery to ascertain all cases of uterine rupture. Patients who had had a previous cesarean delivery at our institution who did not suffer uterine rupture during a trial of labor served as controls., Results: Twenty-five patients suffered a uterine rupture. The incidence of prior preterm cesarean delivery (PPCD) in this group was 40%, compared to 10.9% of 691 laboring vaginal birth after cesarean (VBAC) patients without rupture (p < 0.001). Patients in the rupture group with a PPCD were less likely to have experienced labor in the index pregnancy and more likely to have had an interdelivery interval of less than two years., Conclusions: An undeveloped lower segment in the preterm uterus represents a risk for later rupture, even if the incision is transverse.