Hyunyoung Ahn

Evaluation of cervical stiffness during pregnancy using semiquantitative ultrasound elastography

To evaluate cervical stiffness during pregnancy using ultrasound‐derived elastography, a method used to estimate the average tissue displacement (strain) within a defined region of interest when oscillatory compression is applied.

TRANSABDOMINAL EVALUATION OF UTERINE CERVICAL LENGTH DURING PREGNANCY FAILS TO IDENTIFY A SUBSTANTIAL NUMBER OF WOMEN WITH A SHORT CERVIX

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 <25 mm was evaluated. Results: Twenty-one out of 220 cases (9.5%) had a cervical length <25 mm 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 <25 mm by transvaginal US, transabdominal measurement of the cervix overestimated this parameter by an average of 8 mm (95% LOAs, −26.4 to 10.5 mm). Among women without a short cervix, transabdominal US underestimated cervical length on average (LOA) by 1.1 mm (95% LOAs, −11.0 to 13.2 mm). 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 six cases with sludge whereas only three cases of funneling and one of sludge were detected by transabdominal US. Conclusion: Transabdominal measurement overestimated cervical LOA by 8 mm among women with a short cervix and resulted in the underdiagnosis of 57% of cases.

Cervical strain determined by ultrasound elastography and its association with spontaneous preterm delivery

Abstract 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 (from 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.

Effect of depth on shear-wave elastography estimated in the internal and external cervical os during pregnancy

Abstract 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 ultrasound (US) transducer to the center of 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 US probe to different regions in the cervix did not significantly affect the SWS estimations.

Full-length human placental sFlt-1-e15a isoform induces distinct maternal phenotypes of preeclampsia in mice

Objective Most anti-angiogenic preeclampsia models in rodents utilized the overexpression of a truncated soluble fms-like tyrosine kinase-1 (sFlt-1) not expressed in any species. Other limitations of mouse preeclampsia models included stressful blood pressure measurements and the lack of postpartum monitoring. We aimed to 1) develop a mouse model of preeclampsia by administering the most abundant human placental sFlt-1 isoform (hsFlt-1-e15a) in preeclampsia; 2) determine blood pressures in non-stressed conditions; and 3) develop a survival surgery that enables the collection of fetuses and placentas and postpartum (PP) monitoring. Methods Pregnancy status of CD-1 mice was evaluated with high-frequency ultrasound on gestational days (GD) 6 and 7. Telemetry catheters were implanted in the carotid artery on GD7, and their positions were verified by ultrasound on GD13. Mice were injected through tail-vein with adenoviruses expressing hsFlt-1-e15a (n = 11) or green fluorescent protein (GFP; n = 9) on GD8/GD11. Placentas and pups were delivered by cesarean section on GD18 allowing PP monitoring. Urine samples were collected with cystocentesis on GD6/GD7, GD13, GD18, and PPD8, and albumin/creatinine ratios were determined. GFP and hsFlt-1-e15a expression profiles were determined by qRT-PCR. Aortic ring assays were performed to assess the effect of hsFlt-1-e15a on endothelia. Results Ultrasound predicted pregnancy on GD7 in 97% of cases. Cesarean section survival rate was 100%. Mean arterial blood pressure was higher in hsFlt-1-e15a-treated than in GFP-treated mice (∆MAP = 13.2 mmHg, p = 0.00107; GD18). Focal glomerular changes were found in hsFlt-1-e15a -treated mice, which had higher urine albumin/creatinine ratios than controls (109.3±51.7μg/mg vs. 19.3±5.6μg/mg, p = 4.4x10-2; GD18). Aortic ring assays showed a 46% lesser microvessel outgrowth in hsFlt-1-e15a-treated than in GFP-treated mice (p = 1.2x10-2). Placental and fetal weights did not differ between the groups. One mouse with liver disease developed early-onset preeclampsia-like symptoms with intrauterine growth restriction (IUGR). Conclusions A mouse model of late-onset preeclampsia was developed with the overexpression of hsFlt-1-e15a, verifying the in vivo pathologic effects of this primate-specific, predominant placental sFlt-1 isoform. HsFlt-1-e15a induced early-onset preeclampsia-like symptoms associated with IUGR in a mouse with a liver disease. Our findings support that hsFlt-1-e15a is central to the terminal pathway of preeclampsia, and it can induce the full spectrum of symptoms in this obstetrical syndrome.

In Vivo Experiments Reveal the Good, the Bad and the Ugly Faces of sFlt-1 in Pregnancy

Objective Soluble fms-like tyrosine kinase (sFlt)-1-e15a, a primate-specific sFlt-1-isoform most abundant in the human placenta in preeclampsia, can induce preeclampsia in mice. This study compared the effects of full-length human (h)sFlt-1-e15a with those of truncated mouse (m)sFlt-1(1-3) used in previous preeclampsia studies on pregnancy outcome and clinical symptoms in preeclampsia. Methods Mice were injected with adenoviruses or fiber-mutant adenoviruses overexpressing hsFlt-1-e15a, msFlt-1(1-3) or control GFP under the CMV or CYP19A1 promoters on gestational day 8 (GD8) and GD11. Placentas and pups were delivered by cesarean section, and dams were monitored postpartum. Blood pressure was telemetrically recorded. Urine samples were collected with cystocentesis and examined for albumin/creatinine ratios. Tissue specimens were evaluated for transgene as well as endogenous mFlt-1 and msFlt-1-i13 expression. H&E-, Jones- and PAS-stained kidney sections were histopathologically examined. Placental GFP expression and aortic ring assays were investigated with confocal microscopy. Results Mean arterial blood pressure (MAP) was elevated before delivery in hsFlt-1-e15a-treated mice compared to controls (GD18: ΔMAP = 7.8 mmHg, p = 0.009), while ΔMAP was 12.8 mmHg (GD18, p = 0.005) in msFlt-1(1-3)-treated mice. Urine albumin/creatinine ratio was higher in hsFlt-1-e15a-treated mice than in controls (GD18, p = 0.04; PPD8, p = 0.03), and msFlt-1(1-3)-treated mice had marked proteinuria postpartum (PPD8, p = 4×10−5). Focal glomerular changes were detected in hsFlt-1-e15a and msFlt-1(1-3)-treated mice. Aortic ring microvessel outgrowth was decreased in hsFlt-1-e15a (p = 0.007) and msFlt-1(1-3)-treated (p = 0.02) mice. Full-length msFlt-1-i13 expression was unique for the placenta. In hsFlt-1-e15a-treated mice, the number of pups (p = 0.046), total weight of living pups (p = 0.04) and maternal weights (p = 0.04) were higher than in controls. These differences were not observed in truncated msFlt-1(1-3)-treated mice. Conclusions Truncated msFlt-1(1-3) simulated the preeclampsia-promoting effects of full-length hsFlt-1. MsFlt-1(1-3) had strong effect on maternal endothelium but not on placentas and embryos. In contrast, hsFlt-1-e15a induced preeclampsia-like symptoms; however, it also increased litter size. In accord with the predominant placental expression of hsFlt-1-e15a and msFlt-1-i13, full-length sFlt-1 may have a role in the regulation of embryonic development. These observations point to the difference in the biological effects of full-length and truncated sFlt-1 and the changes in the effect of full-length sFlt-1 during pregnancy, and may have important implications in the management of preeclampsia.

Single and Serial Fetal Biometry to Detect Preterm and Term Small- and Large-for-Gestational-Age Neonates: A Longitudinal Cohort Study

Objectives To 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. Methods A 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. Results Fetal 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. Conclusions When 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 be delivered preterm.

In vivo T-cell activation by a monoclonal αCD3ε antibody induces preterm labor and birth.

Activated/effector T cells seem to play a role in the pathological inflammation associated with preterm labor. The aim of this study was to determine whether in vivo T‐cell activation by a monoclonal αCD3ε antibody induces preterm labor and birth.

Strain at the internal cervical os assessed with quasi-static elastography is associated with the risk of spontaneous preterm delivery at ≤34 weeks of gestation

Abstract Aim: To evaluate the association between cervical strain assessed with quasi-static elastography and spontaneous preterm delivery. Methods: Quasi-static elastography was used to estimate cervical strain in 545 pregnant women with singleton pregnancies from 11 weeks to 28 weeks of gestation. Cervical strain was evaluated in one sagittal plane and in the cross-sectional planes of the internal cervical os and external cervical os. The distribution of strain values was categorized into quartiles for each studied region and their association with spontaneous preterm delivery at ≤34 weeks and at <37 weeks of gestation was evaluated using logistic regression. Results: The prevalence of spontaneous preterm delivery at <37 weeks of gestation was 8.2% (n=45), and that at ≤34 weeks of gestation was 3.8% (n=21). Strain in the internal cervical os was the only elastography value associated with spontaneous preterm delivery. Women with strain values in the 3rd and 4th quartiles had a significantly higher risk of spontaneous preterm delivery at ≤34 weeks and at <37 weeks of gestation when compared to women with strain values in the lowest quartile. When adjusting for a short cervix (<25 mm) and gestational age at examination, women with strain values in the 3rd quartile maintained a significant association with spontaneous preterm delivery at ≤34 weeks (OR 9.0; 95% CI, 1.1–74.0; P=0.02), whereas women with strain values in the highest quartile were marginally more likely than women with lowest quartile strain values to deliver spontaneously at ≤37 weeks of gestation (OR 95% CI: 2.8; [0.9–9.0]; P=0.08). Conclusion: Increased strain in the internal cervical os is associated with higher risk of spontaneous preterm delivery both at ≤34 and <37 weeks of gestation.

Mirror Artifacts in Obstetric Ultrasound: Case Presentation of a Ghost Twin during the Second-Trimester Ultrasound Scan

Mirror artifacts are produced by the reflection of ultrasound waves after they propagate through a structure and encounter a strong and smooth interface capable of acting as a mirror. Ultrasound waves bounce back and forth between the mirroring interface and the reflective object and then eventually return to the transducer. The typical display of the mirror artifact consists of two similar structures separated and at similar distances from the reflective interface. We report a mirror artifact in a patient with a singleton gestation at 18 weeks. The image was interpreted as consistent with a twin gestation using transabdominal and transvaginal ultrasound. The differential diagnosis consisted of an abdominal heterotopic pregnancy. The presence of synchronized but opposite movements of both fetuses, and the blurred image of the second fetus, suggested a mirror artifact. The reflective surface was created by the interface located between a distended rectosigmoid filled with gas and the posterior uterine wall. Mirror artifacts can lead to diagnostic errors. This case illustrates how a distended rectosigmoid colon can generate an image that simulates either a twin gestation or an abdominal heterotopic pregnancy.