A new definition of gestational hypertension? New-onset blood pressures of 130 to 139/80 to 89 mm Hg after 20 weeks of gestation.

BACKGROUND: Diagnostic criteria for hypertensive disorders in pregnancy have historically been based on the American Heart Association and American College of Cardiology's definition of hypertension, previously defined as a blood pressure of ≥140/90 mm Hg. With the recent redefinition of hypertension, blood pressures of 130 to 139/80 to 89 mm Hg are now considered abnormal. OBJECTIVE: In this study, we aimed to test whether the new-onset blood pressure elevations of 130 to 139/80 to 89 mm Hg after 20 weeks of gestation in previously normotensive women are associated with increased risk for adverse pregnancy outcomes, specifically the development of hypertensive disorders in pregnancy. STUDY DESIGN: We performed a retrospective cohort study at a single tertiary care center of all women who delivered singleton gestations after 20 weeks of gestation from January 01, 2014, to June 08, 2016. Normotensive patients were defined as having maximum blood pressure of <130/80 mm Hg before 20 weeks of gestation and no previous diagnosis of chronic hypertension. Patients who remained normotensive for the remainder of pregnancy were then compared with patients who developed new-onset blood pressure elevations of 130 to 139/80 to 89 mm Hg after 20 weeks of gestation before delivery admission. The primary outcome was the development of a hypertensive disorder in pregnancy at hospital admission or during delivery. Clinical outcomes were assessed using χ2 test and multivariable logistic regression. RESULTS: Of the 2090 normotensive women from our cohort who were analyzed, 1318 (63.0%) remained normotensive for their entire antenatal course before delivery admission and 772 (37.0%) had new-onset blood pressure elevations between 130 and 139/80 and 89 mm Hg. Women with new-onset blood pressure elevations between 130 and 139/80 and 89 mm Hg after 20 weeks of gestation have a significantly increased risk for developing a hypertensive disorder in pregnancy at admission or during delivery (adjusted relative risk, 2.41; 95% confidence interval, 2.02-2.85) including an almost 3-fold increased risk for preeclampsia with severe features, even after adjusting for confounders. There were no differences in other secondary obstetrical outcomes. CONCLUSION: Normotensive women with new-onset blood pressures elevations between 130 and 139/80 and 89 mm Hg after 20 weeks of gestation are more likely to experience hypertensive disorders in pregnancy and preeclampsia with severe features at or during their delivery hospitalization. These more modest blood pressure elevations may be an early indicator of disease and call into question our current blood pressure threshold for diagnosis of hypertensive disorders in pregnancy.

A prospective cohort study of pregnancy outcomes following antepartum infection with SARS-CoV-2.

OBJECTIVES: Our study aimed to explore the impact of COVID-19 infection on pregnancy outcomes, accounting for the progression of variants, vaccines, and treatment modalities. STUDY DESIGN: We performed a prospective longitudinal cohort study at two urban tertiary centers enrolling patients with a confirmed intrauterine singleton pregnancy from December 23, 2020 to July 18, 2022. Patients were evaluated for SARS-CoV-2 infection at enrollment and every trimester using serum antibody testing. The primary outcome was preterm birth. Symptom and treatment data were collected from pregnant patients with COVID-19 infections. Variant strain infection status was determined from local wastewater analysis. RESULTS: 448 patients were enrolled, and 390 patients were retained through delivery with 159 unexposed and 231 exposed patients, of whom 56 patients (26.0 %) crossed over after enrollment to the exposed cohorts during pregnancy. There was no difference in rates of preterm birth between exposed and unexposed cohorts (14.6 % vs 11.3 %), in deliveries < 34 weeks (1.5 % vs 2.7 %), PPROM, (0.4 % vs 1.3 %), or gestational age at delivery (38.1 vs 38.2). Exposed patients were significantly more likely to be diagnosed with a hypertensive disorder (aOR 2.3, 95 % CI 1.2-4.1), specifically gestational hypertension (aOR 2.8, 95 % CI 1.3--6.0), but not preeclampsia/eclampsia. There were no differences in individual or composite neonatal outcomes. CONCLUSIONS: Our study contributed to the understanding of the effects of SARS-CoV-2 infection on pregnancy outcomes, with increased risk of hypertensive disorders of pregnancy but overall, no differences in adverse neonatal outcomes. Regular antenatal PCR and antibody screening allowed for higher detection and inclusion of patients with asymptomatic SARS-CoV-2 infection and effects on maternal and neonatal outcomes.

SARS-CoV-2 ORF3a Protein Impairs Syncytiotrophoblast Maturation, Alters ZO-1 Localization, and Shifts Autophagic Pathways in Trophoblast Cells and 3D Organoids.

SARS-CoV-2 infection poses a significant risk to placental physiology, but its impact on placental homeostasis is not well understood. We and others have previously shown that SARS-CoV-2 can colonize maternal and fetal placental cells, yet the specific mechanisms remain unclear. In this study, we investigate ORF3a, a key accessory protein of SARS-CoV-2 that exhibits continuous mutations. Our findings reveal that ORF3a is present in placental tissue from pregnant women infected with SARS-CoV-2 and disrupts autophagic flux in placental cell lines and 3D stem-cell-derived trophoblast organoids (SC-TOs), impairing syncytiotrophoblast differentiation and trophoblast invasion. This disruption leads to protein aggregation in cytotrophoblasts (CTB) and activates secretory autophagy, increasing CD63+ extracellular vesicle secretion, along with ORF3a itself. ORF3a also compromises CTB barrier integrity by disrupting tight junctions via interaction with ZO-1, mediated by its PDZ-binding motif, SVPL. Co-localization of ORF3a and ZO-1 in SARS-CoV-2-infected human placental tissue supports our in vitro findings. Deleting the PDZ binding motif in the ORF3a protein (ORF3a-noPBM mutant) restored proper ZO-1 localization at the cell junctions in an autophagy-independent manner. Lastly, we demonstrate that constitutive ORF3a expression induces SC-TOs to transition towards a secretory autophagy pathway likely via the PBM motif, as the ORF3a-NoPBM mutants showed a significant lack of CD63 expression. This study demonstrates the functional impact of ORF3a on placental autophagy and reveals a new mechanism for the activation of secretory autophagy, which may lead to increased extracellular vesicle secretion. These findings provide a foundation for exploring therapeutic approaches targeting ORF3a, specifically focusing on its PBM region to block its interactions with host cellular proteins and limiting placental impact.

Defining the risk profile of women with stage 1 hypertension: a time to event analysis.

BACKGROUND: Chronic hypertension complicates up to 5% of pregnancies and is increasing in prevalence. Women with hypertension have increased risks of serious maternal morbidity and mortality in pregnancy, including the development of preeclampsia. In 2017, new guidelines reclassified blood pressure into the following 4 categories: normal (<120/<80 mm Hg), elevated (120-129/<80 mm Hg), stage 1 hypertension (130-139/80-89 mm Hg), and stage 2 hypertension (>140/>90 mm Hg). This new classification doubles the number of reproductive-aged women with hypertension. Furthermore, studies have demonstrated that women entering pregnancy with stage 1 hypertension have an increased risk of developing hypertensive disorders of pregnancy compared with their normotensive counterparts, but the time course to the development of hypertensive disorders of pregnancy in these women remains uncertain. OBJECTIVE: We sought to evaluate the risk of developing a hypertensive disorder of pregnancy and the time to the development of these disorders in women with stage 1 hypertension vs both normotensive women and those with stage 2 hypertension. STUDY DESIGN: This was a retrospective cohort study of all patients from a single tertiary care center with singleton gestations from 2014 to 2016. Patients at prenatal visits before 20 weeks of gestation were classified into 3 blood pressure groups: normotensive (<130/80 mm Hg), stage 1 hypertension (130-139/80-89 mm Hg), or stage 2 hypertension (≥140/90 or a history of chronic hypertension). The primary outcome, time to the development of a hypertensive disorder of pregnancy, was compared among groups using Kaplan-Meier curves and the log-rank test. Cox proportional-hazards models were used to adjust for age, race and ethnicity, pregestational diabetes mellitus, and body mass index. In addition, multiple secondary obstetrical, maternal, and neonatal outcomes were assessed. RESULTS: Of the 3000 women in our cohort, 2370 (79.0%) were categorized in the normotensive group, 315 (10.5%) were categorized in the stage 1 hypertension group, and 315 (10.5%) were categorized in the stage 2 hypertension group. The gestational age at diagnosis was significantly earlier in gestation among blood pressure groups (normotensive [38.7 (37.0-39.7)] vs stage 1 hypertension [38.0 (36.4-39.4)] vs stage 2 hypertension [36.4 (33.7-37.8)]; P<.001). When the analysis was restricted to only those patients diagnosed with preeclampsia with severe features, the same findings were observed. Women with stage 1 hypertension exhibited a 2-fold increased risk of developing hypertensive disorders of pregnancy compared with normotensive women. Compared with women with stage 2 hypertension, women with stage 1 hypertension exhibited a milder phenotype of hypertensive disorders of pregnancy and exhibited significantly less risk of maternal and neonatal morbidities. CONCLUSION: Women with stage 1 hypertension are at increased risk of developing hypertensive disorders of pregnancy at earlier gestational ages compared with normotensive women; however, their development of a hypertensive disorder of pregnancy is skewed toward milder diseases compared with women with stage 2 hypertension. These new insights into the graded risk profile of obstetrical hypertensive diseases associated with new blood pressure categories can better inform our antepartum counseling and monitoring and surveillance plans near term and in the postpartum period.

In vivo characterization of connective tissue remodeling using infrared photoacoustic spectra.

Premature cervical remodeling is a critical precursor of spontaneous preterm birth, and the remodeling process is characterized by an increase in tissue hydration. Nevertheless, current clinical measurements of cervical remodeling are subjective and detect only late events, such as cervical effacement and dilation. Here, we present a photoacoustic endoscope that can quantify tissue hydration by measuring near-infrared cervical spectra. We quantify the water contents of tissue-mimicking hydrogel phantoms as an analog of cervical connective tissue. Applying this method to pregnant women in vivo, we observed an increase in the water content of the cervix throughout pregnancy. The application of this technique in maternal healthcare may advance our understanding of cervical remodeling and provide a sensitive method for predicting preterm birth.

Transvaginal fast-scanning optical-resolution photoacoustic endoscopy.

Photoacoustic endoscopy offers in vivo examination of the visceral tissue using endogenous contrast, but its typical B-scan rate is ∼10 Hz, restricted by the speed of the scanning unit and the laser pulse repetition rate. Here, we present a transvaginal fast-scanning optical-resolution photoacoustic endoscope with a 250-Hz B-scan rate over a 3-mm scanning range. Using this modality, we not only illustrated the morphological differences of vasculatures among the human ectocervix, uterine body, and sublingual mucosa but also showed the longitudinal and cross-sectional differences of cervical vasculatures in pregnant women. This technology is promising for screening the visceral pathological changes associated with angiogenesis.