Socioeconomic status as a risk factor for SARS-CoV-2 infection in pregnant women.

OBJECTIVES: Due to the association between COVID-19 and adverse pregnancy outcomes, pregnant women are considered to be a vulnerable patient group. Studies have shown that low socioeconomic status (SES) is a risk factor for SARS-CoV-2 infection. COVID-19 and low SES are likely to have a synergistic adverse effect. This study aimed to evaluate the socioeconomic background, indicated by self-reported SES, educational level, and financial situation, in pregnant women who were positive for SARS-CoV-2. METHODS: A case-control study was conducted, including all pregnant women with positive SARS-CoV-2 PCR tests at Kepler University Hospital Linz between May 2020 and August 2021 (n=150) and a control group matched 1:1 relative to gestational age at birth (n=150). Data were collected using written questionnaires and medical records from the hospital information system. RESULTS: Lower self-reported socioeconomic status (p=0.029) and lower education level (p=0.003) were detected in the COVID group. Mothers in the COVID group were significantly younger (p=0.024). However, after adjustment for educational attainment, younger age was not confirmed as a risk factor for SARS-CoV-2 infection during pregnancy (p=0.326). The social gradient was not explained by the assumed mediators and confounders. CONCLUSIONS: These findings confirm an association between lower socioeconomic status and the risk of SARS-CoV-2 infection during pregnancy. Since both socioeconomic factors and COVID-19 impose negative effects on pregnancy outcomes, health inequalities should be taken into consideration when implementing SARS-CoV-2 prevention measures and when providing health care for pregnant women from disadvantaged communities.

Effects of age on the diagnostic value of the soluble fms-like tyrosine kinase-1/ placental growth factor ratio in preeclampsia: a retrospective cohort study.

OBJECTIVE: Measurement of the ratio between soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) supports the diagnosis of preeclampsia. sFlt-1/PlGF ratios of at least 85 and at least 110 have previously been suggested for diagnosis of early-onset and late-onset preeclampsia, respectively. However, angiogenic and antiangiogenic factors change throughout the process of aging, potentially influencing preeclampsia diagnosis. In this study, we therefore evaluated in detail the effect of maternal age on sFlt-1/PlGF ratios. METHODS: A total of 2775 pregnant female patients were included in this retrospective cohort study, spread across three maternal age groups: 18-25 years, 26-35 years, and more than 35 years at delivery. Receiver-operating characteristic (ROC) curve analysis was employed to evaluate sFlt-1/PlGF ratio cutoffs for use in preeclampsia diagnosis. RESULTS: Controls (2462 pregnant women) showed a significant difference in sFlt-1/PlGF ratios between the youngest and oldest age groups, which resulted in differences in the best-performing sFlt-1/PlGF ratio cutoffs: optimized cutoffs were 143.4 (52.9%, 98.2%), 8.6 (84.4%, 75.3%), and 22.9 (78.6%, 82.3%) in early-onset preeclampsia, and 46.4 (67.5%, 81.5%), 40.8 (77.3%, 73%), and 44.1 (65.1%, 74.5%) in late-onset preeclampsia in age groups, 1, 2, and 3, respectively. CONCLUSION: sFlt-1/PlGF ratios change with maternal age, which has important clinical implications for their use in the diagnosis of preeclampsia: Better differentiated sFlt-1/PlGF cutoffs should be used that take maternal and gestational age into account.

Visualization of the Third Ventricle, the Future Cavum Septi Pellucidi, and the Cavum Veli Interpositi at 11+3 to 13+6 Gestational Weeks on 3D Transvaginal Ultrasound Including Normative Data.

OBJECTIVES: To show the development of the third ventricle, commissural plate, future cavum septi pellucidi, and cavum veli interpositi in weeks 12-14 by transvaginal 3D ultrasound. METHODS: This is a prospective transvaginal 3D study carried out to define the third ventricle and the diencephalic midline structures surrounding it. 93 of 387 fetuses in which the commissural plate with the future cavum septi pellucidi, cavum veli interpositi, and the roof of the third ventricle could be well visualized, were selected with the choroid plexus of the third ventricle and the pituitary gland serving as leading structures. In a small number of fetuses, the optic chiasm could also be displayed. In addition, the following measurements were performed: third ventricle craniocaudal and anteroposterior, roof of the third ventricle/cavum veli interpositi, and fcsp. RESULTS: The sonomorphologic characteristics of the commissural plate, the future cavum septi pellucidi, and the cavum veli interpositi are described IN 9% OF THE FETUSES examined. Measurements of the third ventricle, cavum veli interpositi, and the roof of the third ventricle show the following results: 3rd V cc = 3.895 + 0.091*CRL mm; 3rd V ap = 4.175 + 0.036*CRL mm; CVI ap = 2.223 + 0.029*CRL mm; CVI cc = 0.139 + 0.02*CRL mm. CONCLUSION: Transvaginal neurosonography enables visualization and measurement of the normal fetal third ventricle at 12-14 weeks of gestation including visualization of the future cavum septi pellucidi and the cavum veli interpositi. BEFORE USE IN PATIENTS CAN BE CONSIDERED, FURTHER SCIENTIFIC WORK IS REQUIRED.

Singleton exome sequencing of 90 fetuses with ultrasound anomalies revealing novel disease-causing variants and genotype-phenotype correlations.

Exome sequencing has been increasingly implemented in prenatal genetic testing for fetuses with morphological abnormalities but normal rapid aneuploidy detection and microarray analysis. We present a retrospective study of 90 fetuses with different abnormal ultrasound findings, in which we employed the singleton exome sequencing (sES; 75 fetuses) or to a lesser extent (15 fetuses) a multigene panel analysis of 6713 genes as a primary tool for the detection of monogenic diseases. The detection rate of pathogenic or likely pathogenic variants in this study was 34.4%. The highest diagnostic rate of 56% was in fetuses with multiple anomalies, followed by cases with skeletal or renal abnormalities (diagnostic rate of 50%, respectively). We report 20 novel disease-causing variants in different known disease-associated genes and new genotype-phenotype associations for the genes KMT2D, MN1, CDK10, and EXOC3L2. Based on our data, we postulate that sES of fetal index cases with a concurrent sampling of parental probes for targeted testing of the origin of detected fetal variants could be a suitable tool to obtain reliable and rapid prenatal results, particularly in situations where a trio analysis is not possible.

Diagnosis of Fetal Posterior Fossa Malformations in High-Risk Pregnancies at 12-14 Gestational Weeks by Transvaginal Ultrasound Examination.

OBJECTIVE: To demonstrate sonographic detectable abnormalities of the posterior fossa in fetuses with a crown-rump length of 45-84 mm in high-risk pregnancies. METHODS: This was a prospective, observational study including 47 fetuses with known outcome, whose mothers attended our centers for first trimester tests and showed an abnormal first trimester ultrasound scan. In these fetuses, we examined transvaginal acquired three-dimensional volume blocks for abnormalities of the fetal posterior fossa. In these fetuses, the measurements of the cerebellar vermis (VE) and of the anterior membranous area (AMA) were compared with published reference ranges. RESULTS: There were 8 fetuses with a ver-mian length below the 5th centile. In 5 of these fetuses, the AMA was also elongated and in 4 of these fetuses, pathology was confirmed. One case with a normal vermian length and normal AMA had a hypoplastic VE later on in the confirmatory test. CONCLUSION: Pathology of the posterior fossa can be directly diagnosed by assessing the VE and the AMA at the first trimester scan by examining transvaginal acquired volume blocks.

The Role of Endometrial Volume and Endometrial and Subendometrial Vascularization Parameters in a Frozen Embryo Transfer Cycle.

The role of three-dimensional power Doppler ultrasonography of the endometrium in assisted reproduction is still far from clear. In this retrospective cohort study, transvaginal three-dimensional power Doppler examinations were performed 30 min before frozen-thawed embryo transfer. After pregnancy tests, two cohorts were established: P (pregnant, n = 31) and NP (nonpregnant, n = 31). The study only included nullipara with no uterine abnormalities who were undergoing infertility treatment at the Department of Gynecology, Obstetrics and Gynecological Endocrinology, Kepler University Hospital, Linz, Austria. The main outcome measures were the vascularization flow index (VFI), flow index (FI), and vascularization index (VI) in the endometrium/subendometrium, assessed using Virtual Organ Computer-aided AnaLysis (VOCAL™), and the endometrial volume. A total of 62 patients were enrolled in the study, forming two cohorts (pregnant, P; nonpregnant, NP). There were no significant differences between the two cohorts with regard to demographic data, numbers of embryos transferred, or embryo grading, but there was a significant difference in endometrial volume (cohort P, 3.17 ± 0.84 mL; cohort NP, 2.36 ± 0.9 mL; P = 0.001) and the pregnancy rate rises with larger volume. No differences were observed in the vascularization parameters FI, VFI, and VI in the endometrium and subendometrium. In the cohort of pregnant patients, there were 26 (41.9%) live births, with 21 term deliveries (80.8%). The endometrial volume was larger in the cohort of pregnant patients. Measurements were performed 30 min before embryo transfer, and no differences were observed in vascularization parameters in the subendometrium and endometrium.

Good-quality blastocysts derived from vacuolized morulas show reduced viability.

OBJECTIVE: To study whether late spontaneous vacuolization on day 4 is an artefact or an alternate means of blastocele formation and to analyze its impact on pregnancy outcome and live birth. DESIGN: Prospective observational study. SETTING: University teaching hospital. PATIENT(S): A total of 424 patients who fulfilled inclusion criteria were subgrouped according to the spontaneous vacuolization on day 4: Group 1 had all morulas affected, group 2 showed no signs of vacuoles, and group 3 was mixed (some day 4 embryos had vacuoles and others did not). INTERVENTION(S): Screening for the presence of vacuoles on day 4 and fresh single-blastocyst transfer. MAIN OUTCOME MEASURE(S): Morula and blastocyst scoring, utilization rate, pregnancy and live birth rates. RESULT(S): Patients of group 1 had a reduced blastocyst formation rate on day 5 (P<.01) and significantly fewer good-quality blastocysts for usage (P<.05). In addition, pregnancy (P<.001) and live birth (P<.01) rate were significantly worse in group 1 compared with groups 2 and 3. CONCLUSION(S): Late onset of vacuolization around compaction stage is a negative predictor of blastocyst formation and outcome.

Reference Ranges for Transvaginal Examined Fossa Posterior Structures in Fetuses from 45 to 84 mm Crown-Rump Length.

OBJECTIVE: The study aimed to describe reference values for structures of the posterior fossa in fetuses with a crown-rump length (CRL) between 45 and 84 mm. MATERIALS AND METHODS: This was a prospective, cross-sectional study including 216 normal appearing fetuses. In transvaginal acquired 3-dimensional volume blocks, the longest diameter of the vermis (VE), posterior membranous area (PMA), medulla-oblongata-pons angle (MOPA), diameters of the medulla oblongata (MO) and pons (PO), and the area of Blake's pouch (BP) were measured. Polynomial or linear regression analysis were performed to calculate the mean, 5th and 95th centile according to CRL. In 20 fetuses, intra- and interobserver repeatability were calculated. RESULTS: There is a curvilinear correlation between CRL and PO (PO [mean] = 1.3893 + 0.004356 × CRL + 0.000002610 × CRL3; SD = 1.6818 - 0.03765 × CRL + 0.000003831 × CRL3; R2 = 0.489); CRL and MO (MO [mean] = 1.5959-0.001905 × CRL + 0.000003362*CRL3; SD = -0.1417 + 0.005404 × CRL + 0.0000004988 × CRL3; R2 = 0.525); CRL and VE (VE [mean] = -0.3640 + 0.04302 × CRL+ 0.000001486 × CRL3; SD = 0.5854 - 0.004812 × CRL + 0.0000005896 × CRL3; R2 = 0.643); CRL and PMA (PMA [mean] = 0.6901 + 0.04307 × CRL - 0.0000008459 × CRL3; SD = -0.4232 + 0.02026 × CRL - 0.000001320 × CRL3; R2 = 0.272); CRL and BP (mm2; BP [mean] -12.2067 + 0.3334 × CRL - 0.00001262 × CRL3; SD = -1.6431 + 0.06380 × CRL+ 0.0000003257 × CRL3; R2 = 0.289). The relation between CRL and MOPA (°) is best described by a linear regression (MOPA [mean] = 79.6332 + 0.6122 × CRL; SD = 4.8453 + 0.07333 × CRL; R2 = 0.318). CONCLUSION: We provide reference values for anatomical structures of the posterior fossa of fetuses between 45 and 84 mm CRL. The established reference values might ease the diagnosis of fetal malformations in early pregnancy.

Sonoembryology of the fetal posterior fossa at 11 + 3 to 13 + 6 gestational weeks on three-dimensional transvaginal ultrasound.

OBJECTIVE: To describe the sonographic appearance and temporal changes of the structures of the posterior cranial fossa in fetuses at a crown-rump length (CRL) between 45 and 84 mm in transvaginal acquired three-dimensional volume blocks. METHODS: This was a prospective, cross-sectional, observational study including 80 fetuses, whose mothers attended Kepler University Hospital Linz or the Ambulatorium für Fetalmedizin Feldkirch for first-trimester sonography. Three-dimensional volume blocks were acquired in a standardized way and after processing the sonographic characteristics of the brainstem, cerebellar vermis, choroid plexus, anterior membranous area (AMA) and Blake's metapore were described. Measurements of the length of the cerebellar vermis, the length of the AMA and the medulla-oblongata-pons angle (MOPA) were performed. In 20 fetuses the intra- and interobserver repeatability was calculated. RESULTS: The sonomorphologic characteristics of posterior fossa structures as cerebellar vermis, AMA, Blake's metapore, choroid plexus, pons and medulla oblongata were described. There is a significant correlation between CRL and vermis length, CRL and MOPA and CRL and AMA. CONCLUSIONS: Transvaginal three-dimensional sonography allows a detailed depiction of the structures of the posterior fossa and their temporal course in early pregnancy. © 2016 John Wiley & Sons, Ltd.