Objective To evaluate cervical stiffness during pregnancy using ultrasound-derived elastography, a method used to estimate the average tissue displacement (strain) on a defined region of interest when oscillatory compression is applied. Methods Strain was calculated in two regions of interest, the endocervical canal and the entire cervix, from three anatomical planes of the cervix: mid-sagittal in the plane used for cervical length measurement, and in cross-sectional planes located at the internal and external cervical os. Associations between strain values, method of ascertainment and patient characteristics were assessed using linear mixed models to account for within-subject correlation. Inter-rater agreement in defining the degree of cervical stiffness was evaluated in 120 regions of interest acquired by two operators in 20 patients. Results A total of 1557 strain estimations were performed in 262 patients at 8-40 weeks of gestation. Adjusting for other sources of variation, 1) cervical tissue strain estimates obtained in the endocervical canal were on average 33% greater than those obtained in the entire cervix; 2) measures obtained in the cross-sectional plane of the external cervical os and sagittal plane were 45% and 13% greater compared to those measured in the cross-sectional plane of the internal cervical os, respectively; 3) mean strain rate was 14% and 5% greater among multiparous women with and without a history of preterm delivery compared to nulliparous women, respectively, and was on average 13% greater among women with a cervical length between 25-30mm compared to those with a cervical length >30mm; and 4) cervical tissue strain was more strongly associated with cervical length than with gestational age. Conclusion Semiquantitative elastography can be employed to evaluate changes in cervical stiffness during pregnancy.

Preterm labor commonly precedes preterm birth, the leading cause of perinatal morbidity and mortality worldwide. Most research has focused on establishing a causal link between innate immune activation and pathological inflammation leading to preterm labor and birth. However, the role of maternal effector/activated T cells in the pathogenesis of preterm labor/birth is poorly understood. In this study, we first demonstrated that effector memory and activated maternal T cells expressing granzyme B and perforin are enriched at the maternal-fetal interface (decidua) of women with spontaneous preterm labor. Next, using a murine model, we reported that prior to inducing preterm birth, in vivo T cell activation caused maternal hypothermia, bradycardia, systemic inflammation, cervical dilation, intra-amniotic inflammation, and fetal growth restriction, all of which are clinical signs associated with preterm labor. In vivo T cell activation also induced B cell cytokine responses, a proinflammatory macrophage polarization, and other inflammatory responses at the maternal-fetal interface and myometrium in the absence of an increased influx of neutrophils. Finally, we showed that treatment with progesterone can serve as a strategy to prevent preterm labor/birth and adverse neonatal outcomes by attenuating the proinflammatory responses at the maternal-fetal interface and cervix induced by T cell activation. Collectively, these findings provide mechanistic evidence showing that effector and activated T cells cause pathological inflammation at the maternal-fetal interface, in the mother, and in the fetus, inducing preterm labor and birth and adverse neonatal outcomes. Such adverse effects can be prevented by treatment with progesterone, a clinically approved strategy.

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Objective To assess the diagnostic performance of transabdominal sonographic measurement of cervical length in identifying patients with a short cervix. Methods Cervical length was measured in 220 pregnant women using transabdominal and transvaginal ultrasound (US). Reproducibility and agreement between and within both methods were assessed. The diagnostic accuracy of transabdominal US for identifying cases with a cervical length <25mm was evaluated. Results Twenty-one out of 220 cases (9.5%) had a cervical length <25mm by transvaginal US. Only 43% (n=9) of patients with a short cervix were correctly identified by transabdominal US. In patients with a cervical length of <25mm by transvaginal US, transabdominal measurement of the cervix overestimated this parameter by an average of 8mm (95% LOAs: −26.4 to 10.5mm). Among women without a short cervix, transabdominal US underestimated cervical length on average (LOA) by 1.1mm (95% LOAs: −11.0 to 13.2mm). Transvaginal US was also more reproducible (intraclass correlation coefficient: (ICC: 0.96; 95% CI: 0.94 to 0.97) based on comparisons between 2D images and immediately acquired 3D volume datasets relative to transabdominal US (ICC: 0.71; 95% CI: 0.57 to 0.84). Transvaginal US detected 13 cases with funneling and 6 cases with sludge whereas only 3 cases of funneling and one of sludge were detected by transabdominal US. Conclusion Transabdominal measurement overestimated cervical LOA by 8mm among women with a short cervix and resulted in the underdiagnosis of 57% of cases.

Objective To determine if there is an association between cervical strain, evaluated using ultrasound elastography, and spontaneous preterm delivery (sPTD) <37 weeks of gestation. Methods One hundred and eighty nine (189) women at 16–24 weeks of gestation were evaluated. Ultrasound elastography was used to estimate cervical strain in three anatomical planes: one mid-sagittal in the same plane used for cervical length measurement, and two cross sectional images: one at the level of the internal cervical os, and the other at the level of the external cervical os. In each plane, two regions of interest (endocervix and entire cervix) were examined; a total of six regions of interest were evaluated. Results The prevalence of sPTD was 11% (21/189). Strain values from each of the six cervical regions correlated weakly with cervical length (r= −0.24, p<0.001 to r= −0.03, p=0.69). Strain measurements obtained in a cross sectional view of the internal cervical os were significantly associated with sPTD. Women with strain values ≤25th centile in the endocervical canal (0.19) and in the entire cervix (0.14) were 80% less likely to have a sPTD than women with strain values >25th centile (endocervical: odds ratio [OR] 0.2; 95% confidence interval [CI], 0.03–0.96; entire cervix: OR 0.17; 95% CI, 0.03–0.9). Additional adjustment for gestational age, race, smoking status, parity, maternal age, pre-pregnancy body mass index and previous preterm delivery did not appreciably alter the magnitude or statistical significance of these associations. Strain values obtained from the external cervical os and from the sagittal view were not associated with sPTD. Conclusion Low strain values in the internal cervical os were associated with a significantly lower risk of spontaneous preterm delivery <37 weeks of gestation.

Background Prediction of neonatal respiratory morbidity may be useful to plan delivery in complicated pregnancies. The limited predictive performance of the current diagnostic tests together with the risks of an invasive procedure restricts the use of fetal lung maturity assessment. Objective The objective of this study was to evaluate the performance of quantitative ultrasound texture analysis of the fetal lung (quantusFLM) to predict neonatal respiratory morbidity in preterm and early-term (<39.0 weeks) deliveries. Study Design This was a prospective multicenter study conducted in 20 centers worldwide. Fetal lung ultrasound images were obtained at 25.0-38.6 weeks of gestation within 48 hours of delivery, stored in Digital Imaging and Communication in Medicine format, and analyzed with quantusFLM. Physicians were blinded to the analysis. At delivery, perinatal outcomes and the occurrence of neonatal respiratory morbidity, defined as either respiratory distress syndrome or transient tachypnea of the newborn, were registered. The performance of the ultrasound texture analysis test to predict neonatal respiratory morbidity was evaluated. Results A total of 883 images were collected, but 17.3% were discarded because of poor image quality or exclusion criteria, leaving 730 observations for the final analysis. The prevalence of neonatal respiratory morbidity was 13.8% (101/730). The quantusFLM predicted neonatal respiratory morbidity with a sensitivity, specificity, and positive and negative predictive values of 74.3% (75/101), 88.6% (557/629), 51.0% (75/147), and 95.5% (557/583), respectively. Accuracy was 86.5% (632/730), and the positive and negative likelihood ratios were 6.5 and 0.3, respectively. Conclusion The quantusFLM predicted neonatal respiratory morbidity with an accuracy similar to that previously reported for other tests with the advantage of being a non-invasive technique.

Aim To investigate the effect of depth on cervical shear-wave elastography. Methods Shear-wave elastography was applied to estimate the velocity of propagation of the acoustic force impulse (shear-wave) in the cervix of 154 pregnant women at 11-36 weeks of gestation. Shear-wave speed (SWS) was evaluated in cross-sectional views of the internal and external cervical os in five regions of interest: anterior, posterior, lateral right, lateral left, and endocervix. Distance from the center of the US transducer to the center of the each region of interest was registered. Results In all regions, SWS decreased significantly with gestational age (p=0.006). In the internal os SWS was similar among the anterior, posterior and lateral regions, and lower in the endocervix. In the external os, the endocervix and anterior regions showed similar SWS values, lower than those from the posterior and lateral regions. In the endocervix, these differences remained significant after adjustment for depth, gestational age and cervical length. SWS estimations in all regions of the internal os were higher than those of the external os, suggesting denser tissue. Conclusion Depth from the ultrasound probe to different regions in the cervix did not significantly affect the SWS estimations.

ObjectivesTo assess the value of single and serial fetal biometry for the prediction of small- (SGA) and large-for-gestational-age (LGA) neonates delivered preterm or at term.MethodsA cohort study of 3,971 women with singleton pregnancies was conducted from the first trimester until delivery with 3,440 pregnancies (17,334 scans) meeting the following inclusion criteria: 1) delivery of a live neonate after 33 gestational weeks and 2) two or more ultrasound examinations with fetal biometry parameters obtained at ≤36 weeks. Primary outcomes were SGA (<5th centile) and LGA (>95th centile) at birth based on INTERGROWTH-21st gender-specific standards. Fetus-specific estimated fetal weight (EFW) trajectories were calculated by linear mixed-effects models using data up to a fixed gestational age (GA) cutoff (28, 32, or 36 weeks) for fetuses having two or more measurements before the GA cutoff and not already delivered. A screen test positive for single biometry was based on Z-scores of EFW at the last scan before each GA cut-off so that the false positive rate (FPR) was 10%. Similarly, a screen test positive for the longitudinal analysis was based on the projected (extrapolated) EFW at 40 weeks from all available measurements before each cutoff for each fetus.ResultsFetal abdominal and head circumference measurements, as well as birth weights in the Detroit population, matched well to the INTERGROWTH-21st standards, yet this was not the case for biparietal diameter (BPD) and femur length (FL) (up to 9% and 10% discrepancy for mean and confidence intervals, respectively), mainly due to differences in the measurement technique. Single biometry based on EFW at the last scan at ≤32 weeks (GA IQR: 27.4–30.9 weeks) had a sensitivity of 50% and 53% (FPR = 10%) to detect preterm and term SGA and LGA neonates, respectively (AUC of 82% both). For the detection of LGA using data up to 32- and 36-week cutoffs, single biometry analysis had higher sensitivity than longitudinal analysis (52% vs 46% and 62% vs 52%, respectively; both p<0.05). Restricting the analysis to subjects with the last observation taken within two weeks from the cutoff, the sensitivity for detection of LGA, but not SGA, increased to 65% and 72% for single biometry at the 32- and 36-week cutoffs, respectively. SGA screening performance was higher for preterm (<37 weeks) than for term cases (73% vs 46% sensitivity; p<0.05) for single biometry at ≤32 weeks.ConclusionsWhen growth abnormalities are defined based on birth weight, growth velocity (captured in the longitudinal analysis) does not provide additional information when compared to the last measurement for predicting SGA and LGA neonates, with both approaches detecting one-half of the neonates (FPR = 10%) from data collected at ≤32 weeks. Unlike for SGA, LGA detection can be improved if ultrasound scans are scheduled as close as possible to the gestational-age cutoff when a decision regarding the clinical management of the patient needs to be made. Screening performance for SGA is higher for neonates that will...