Evaluating the Efficacy of Cervical Tactile Ultrasound Technique as a Predictive Tool for Spontaneous Preterm Birth.

Background: Premature cervical softening and shortening may be considered an early mechanical failure that predispose to preterm birth. Purpose: This study aims to explore the applicability of an innovative cervical tactile ultrasound approach for predicting spontaneous preterm birth (sPTB). Materials and Methods: Eligible participants were women with low-risk singleton pregnancies in their second trimester, enrolled in this prospective observational study. A Cervix Monitor (CM) device was designed with a vaginal probe comprising four tactile sensors and a single ultrasound transducer operating at 5 MHz. The probe enabled the application of controllable pressure to the external cervical surface, facilitating the acquisition of stress-strain data from both anterior and posterior cervical sectors. Gestational age at delivery was recorded and compared against cervical elasticity. Results: CM examination data were analyzed for 127 women at 240/7 - 286/7 gestational weeks. sPTB was observed in 6.3% of the cases. The preterm group exhibited a lower average cervical stress-to-strain ratio (elasticity) of 0.70 ± 0.26 kPa/mm compared to the term group's 1.63 ± 0.65 kPa/mm with a p-value of 1.1 × 10-4. Diagnostic accuracy for predicting spontaneous preterm birth based solely on cervical elasticity data was found to be 95.0% (95% CI, 88.5 - 100.0). Conclusion: These findings suggest that measuring cervical elasticity with the designed tactile ultrasound probe has the potential to predict spontaneous preterm birth in a cost-effective manner.

Mean Arterial Pressure and Neonatal Outcomes in Pregnancies Complicated by Mild Chronic Hypertension.

OBJECTIVE: To estimate the association between mean arterial pressure during pregnancy and neonatal outcomes in participants with chronic hypertension using data from the CHAP (Chronic Hypertension and Pregnancy) trial. METHODS: A secondary analysis of the CHAP trial, an open-label, multicenter randomized trial of antihypertensive treatment in pregnancy, was conducted. The CHAP trial enrolled participants with mild chronic hypertension (blood pressure [BP] 140-159/90-104 mm Hg) and singleton pregnancies less than 23 weeks of gestation, randomizing them to active treatment (maintained on antihypertensive therapy with a goal BP below 140/90 mm Hg) or standard treatment (control; antihypertensives withheld unless BP reached 160 mm Hg systolic BP or higher or 105 mm Hg diastolic BP or higher). We used logistic regression to measure the strength of association between mean arterial pressure (average and highest across study visits) and to select neonatal outcomes. Unadjusted and adjusted odds ratios (per 1-unit increase in millimeters of mercury) of the primary neonatal composite outcome (bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, or intraventricular hemorrhage grade 3 or 4) and individual secondary outcomes (neonatal intensive care unit admission [NICU], low birth weight [LBW] below 2,500 g, and small for gestational age [SGA]) were calculated. RESULTS: A total of 2,284 participants were included: 1,155 active and 1,129 control. Adjusted models controlling for randomization group demonstrated that increasing average mean arterial pressure per millimeter of mercury was associated with an increase in each neonatal outcome examined except NEC, specifically neonatal composite (adjusted odds ratio [aOR] 1.12, 95% CI, 1.09-1.16), NICU admission (aOR 1.07, 95% CI, 1.06-1.08), LBW (aOR 1.12, 95% CI, 1.11-1.14), SGA below the fifth percentile (aOR 1.03, 95% CI, 1.01-1.06), and SGA below the 10th percentile (aOR 1.02, 95% CI, 1.01-1.04). Models using the highest mean arterial pressure as opposed to average mean arterial pressure also demonstrated consistent associations. CONCLUSION: Increasing mean arterial pressure was positively associated with most adverse neonatal outcomes except NEC. Given that the relationship between mean arterial pressure and adverse pregnancy outcomes may not be consistent at all mean arterial pressure levels, future work should attempt to further elucidate whether there is an absolute threshold or relative change in mean arterial pressure at which fetal benefits are optimized along with maternal benefits. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02299414.

Maternal Smoking and Risk of Hypertensive Disorders of Pregnancy: Effect Modification by Body Mass Index and Gestational Weight Gain.

BACKGROUND: Although smoking cigarettes has been shown to have a protective effect on preeclampsia, quitting smoking also results in weight gain. Weight gain leading to an obese body mass index is a risk factor for hypertensive disorders of pregnancy (HDP). METHODS: The objective of this study was to explore the relationship between smoking status, body mass index, and gestational weight gain on the risk of HDP. A cross-sectional analysis was performed utilizing US birth certificate data. We examined HDP risks in relation to maternal smoking, body mass index, and gestational weight gain. Associations were expressed as rate ratios with 95% CIs and adjusted for potential confounders. Clinically important outcomes of smoking throughout pregnancy were also evaluated. RESULTS: Of the 22 191 568 women studied, HDP rates among nonsmokers, those who quit smoking, and persistent smokers were 6.8%, 8.6%, and 7.0%, respectively. The rate ratio of HDP was higher for women who quit smoking, especially evident among those with excessive gestational weight gain. Corrections for exposure misclassification and unmeasured confounding strengthened the associations among women who quit smoking. There was an almost 6-fold increase in the rate of stillbirth for persistent smokers (2.3%) compared with those who quit smoking (0.4%) and nonsmokers (0.4%). CONCLUSIONS: Women who quit smoking during pregnancy were more likely to gain excessive weight and develop HDP. Although quitting smoking during pregnancy may be associated with an increase in the risk of HDP, it is also associated with a reduced risk of stillbirth. Pregnant women counseled to quit smoking should also receive counseling on nutrition and exercise to prevent excessive gestational weight gain.

Placental Abruption and Cardiovascular Event Risk (PACER): Design, data linkage, and preliminary findings.

BACKGROUND: Obstetrical complications impact the health of mothers and offspring along the life course, resulting in an increased burden of chronic diseases. One specific complication is abruption, a life-threatening condition with consequences for cardiovascular health that remains poorly studied. OBJECTIVES: To describe the design and data linkage algorithms for the Placental Abruption and Cardiovascular Event Risk (PACER) cohort. POPULATION: All subjects who delivered in New Jersey, USA, between 1993 and 2020. DESIGN: Retrospective, population-based, birth cohort study. METHODS: We linked the vital records data of foetal deaths and live births to delivery and all subsequent hospitalisations along the life course for birthing persons and newborns. The linkage was based on a probabilistic record-matching algorithm. PRELIMINARY RESULTS: Over the 28 years of follow-up, we identified 1,877,824 birthing persons with 3,093,241 deliveries (1.1%, n = 33,058 abruption prevalence). The linkage rates for live births-hospitalisations and foetal deaths-hospitalisations were 92.4% (n = 2,842,012) and 70.7% (n = 13,796), respectively, for the maternal cohort. The corresponding linkage rate for the live births-hospitalisations for the offspring cohort was 70.3% (n = 2,160,736). The median (interquartile range) follow-up for the maternal and offspring cohorts was 15.4 (8.1, 22.4) and 14.4 (7.4, 21.0) years, respectively. We will undertake multiple imputations for missing data and develop inverse probability weights to account for selection bias owing to unlinked records. CONCLUSIONS: Pregnancy offers a unique window to study chronic diseases along the life course and efforts to identify the aetiology of abruption may provide important insights into the causes of future CVD. This project presents an unprecedented opportunity to understand how abruption may predispose women and their offspring to develop CVD complications and chronic conditions later in life.

Metformin Plus Insulin for Preexisting Diabetes or Gestational Diabetes in Early Pregnancy: The MOMPOD Randomized Clinical Trial.

Importance: Insulin is recommended for pregnant persons with preexisting type 2 diabetes or diabetes diagnosed early in pregnancy. The addition of metformin to insulin may improve neonatal outcomes. Objective: To estimate the effect of metformin added to insulin for preexisting type 2 or diabetes diagnosed early in pregnancy on a composite adverse neonatal outcome. Design, Setting, and Participants: This randomized clinical trial in 17 US centers enrolled pregnant adults aged 18 to 45 years with preexisting type 2 diabetes or diabetes diagnosed prior to 23 weeks' gestation between April 2019 and November 2021. Each participant was treated with insulin and was assigned to add either metformin or placebo. Follow-up was completed in May 2022. Intervention: Metformin 1000 mg or placebo orally twice per day from enrollment (11 weeks -<23 weeks) through delivery. Main Outcome and Measures: The primary outcome was a composite of neonatal complications including perinatal death, preterm birth, large or small for gestational age, and hyperbilirubinemia requiring phototherapy. Prespecified secondary outcomes included maternal hypoglycemia and neonatal fat mass at birth, and prespecified subgroup analyses by maternal body mass index less than 30 vs 30 or greater and those with preexisting vs diabetes early in pregnancy. Results: Of the 831 participants randomized, 794 took at least 1 dose of the study agent and were included in the primary analysis (397 in the placebo group and 397 in the metformin group). Participants' mean (SD) age was 32.9 (5.6) years; 234 (29%) were Black, and 412 (52%) were Hispanic. The composite adverse neonatal outcome occurred in 280 (71%) of the metformin group and in 292 (74%) of the placebo group (adjusted odds ratio, 0.86 [95% CI 0.63-1.19]). The most commonly occurring events in the primary outcome in both groups were preterm birth, neonatal hypoglycemia, and delivery of a large-for-gestational-age infant. The study was halted at 75% accrual for futility in detecting a significant difference in the primary outcome. Prespecified secondary outcomes and subgroup analyses were similar between groups. Of individual components of the composite adverse neonatal outcome, metformin-exposed neonates had lower odds to be large for gestational age (adjusted odds ratio, 0.63 [95% CI, 0.46-0.86]) when compared with the placebo group. Conclusions and Relevance: Using metformin plus insulin to treat preexisting type 2 or gestational diabetes diagnosed early in pregnancy did not reduce a composite neonatal adverse outcome. The effect of reduction in odds of a large-for-gestational-age infant observed after adding metformin to insulin warrants further investigation. Trial Registration: ClinicalTrials.gov Identifier: NCT02932475.

Perinatal Outcomes Associated With Management of Stage 1 Hypertension.

OBJECTIVE: To evaluate the association between maternal blood pressure (BP) below 130/80 mm Hg compared with 130-139/80-89 mm Hg and pregnancy outcomes. METHODS: We conducted a planned secondary analysis of CHAP (Chronic Hypertension and Pregnancy), an open label, multicenter, randomized controlled trial. Participants with mean BP below 140/90 mm Hg were grouped as below 130/80 mm Hg compared with 130-139/80-89 mm Hg by averaging postrandomization clinic BP throughout pregnancy. The primary composite outcome was preeclampsia with severe features, indicated preterm birth before 35 weeks of gestation, placental abruption, or fetal or neonatal death. The secondary outcome was small for gestational age (SGA). RESULTS: Of 2,408 patients in CHAP, 2,096 met study criteria; 1,328 had mean BP 130-139/80-89 mm Hg and 768 had mean BP below 130/80 mm Hg. Participants with mean BP below 130/80 mm Hg were more likely to be older, on antihypertensive medication, in the active treatment arm, and to have lower BP at enrollment. Mean clinic BP below 130/80 mm Hg was associated with lower frequency of the primary outcome (16.0% vs 35.8%, adjusted relative risk 0.45; 95% CI 0.38-0.54) as well as lower risk of severe preeclampsia and indicated birth before 35 weeks of gestation. There was no association with SGA. CONCLUSION: In pregnant patients with mild chronic hypertension, mean BP below 130/80 mm Hg was associated with improved pregnancy outcomes without increased risk of SGA. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT02299414.

Breastfeeding initiation and duration among people with mild chronic hypertension: a secondary analysis of the Chronic Hypertension and Pregnancy trial.

BACKGROUND: Increased duration of breastfeeding improves maternal cardiovascular health and may be especially beneficial in high-risk populations, such as those with chronic hypertension. Others have shown that individuals with hypertension are less likely to breastfeed, and there has been limited research aimed at supporting breastfeeding goals in this population. The impact of perinatal blood pressure control on breastfeeding outcomes among people with chronic hypertension is unknown. OBJECTIVE: This study aimed to evaluate whether breastfeeding initiation and short-term duration assessed at the postpartum clinic visit differed according to perinatal blood pressure treatment strategy (targeting blood pressure <140/90 mm Hg vs reserving antihypertensive treatment for blood pressure ≥160/105 mm Hg). STUDY DESIGN: We performed a secondary analysis of the Chronic Hypertension and Pregnancy trial. This was an open-label, multicenter, randomized trial where pregnant participants with mild chronic hypertension were randomized to receive antihypertensive medications with goal blood pressure <140/90 mm Hg (active treatment) or deferred treatment until blood pressure ≥160/105 mm Hg (control). The primary outcome was initiation and duration of breastfeeding, assessed at the postpartum clinic visit. We performed bivariate analyses and log-binomial and cumulative logit regression models, adjusting models for variables that were unbalanced in bivariate analyses. We performed additional analyses to explore the relationship between breastfeeding duration and blood pressure measurements at the postpartum visit. RESULTS: Of the 2408 participants from the Chronic Hypertension and Pregnancy trial, 1444 (60%) attended the postpartum study visit and provided breastfeeding information. Participants in the active treatment group had different body mass index class distribution and earlier gestational age at enrollment, and (by design) were more often discharged on antihypertensives. Breastfeeding outcomes did not differ significantly by treatment group. In the active and control treatment groups, 563 (77.5%) and 561 (78.1%) initiated breastfeeding, and mean durations of breastfeeding were 6.5±2.3 and 6.3±2.1 weeks, respectively. The probability of ever breastfeeding (adjusted relative risk, 0.99; 95% confidence interval, 0.93-1.05), current breastfeeding at postpartum visit (adjusted relative risk, 1.01; 95% confidence interval, 0.94-1.10), and weeks of breastfeeding (adjusted odds ratio, 0.87; 95% confidence interval, 0.68-1.12) did not differ by treatment group. Increased duration (≥2 vs <2 weeks) of breastfeeding was associated with slightly lower blood pressure measurements at the postpartum visit, but these differences were not significant in adjusted models. CONCLUSION: In a secondary analysis of the cohort of Chronic Hypertension and Pregnancy trial participants who attended the postpartum study visit and provided breastfeeding information (60% of original trial participants), breastfeeding outcomes did not differ significantly by treatment group. This suggests that maintaining goal blood pressure <140/90 mm Hg throughout the perinatal period is associated with neither harm nor benefit for short-term breastfeeding goals. Further study is needed to understand long-term breastfeeding outcomes among individuals with chronic hypertension and how to support this population in achieving their breastfeeding goals.

Cesarean scar ectopic pregnancy: nuances in diagnosis and treatment.

A cesarean scar ectopic pregnancy (CSEP) occurs when the embryo implants on the scar of a previous cesarean delivery. The number of births delivered by cesarean section has climbed by 50% over the last decade, from a nadir of 20.7% in 1996 to 32.1% in 2021. As a result, the incidence of CSEP has also increased. Because CSEP may cause serious morbidity such as life-threatening hemorrhage, uterine rupture, placental accreta spectrum, hysterectomy, and even mortality, accurate diagnosis and appropriate management of this condition are essential. This review focuses on the etiology, incidence, clinical diagnosis, and management of CSEPs.

Treatment for Mild Chronic Hypertension during Pregnancy.

BACKGROUND: The benefits and safety of the treatment of mild chronic hypertension (blood pressure, <160/100 mm Hg) during pregnancy are uncertain. Data are needed on whether a strategy of targeting a blood pressure of less than 140/90 mm Hg reduces the incidence of adverse pregnancy outcomes without compromising fetal growth. METHODS: In this open-label, multicenter, randomized trial, we assigned pregnant women with mild chronic hypertension and singleton fetuses at a gestational age of less than 23 weeks to receive antihypertensive medications recommended for use in pregnancy (active-treatment group) or to receive no such treatment unless severe hypertension (systolic pressure, ≥160 mm Hg; or diastolic pressure, ≥105 mm Hg) developed (control group). The primary outcome was a composite of preeclampsia with severe features, medically indicated preterm birth at less than 35 weeks' gestation, placental abruption, or fetal or neonatal death. The safety outcome was small-for-gestational-age birth weight below the 10th percentile for gestational age. Secondary outcomes included composites of serious neonatal or maternal complications, preeclampsia, and preterm birth. RESULTS: A total of 2408 women were enrolled in the trial. The incidence of a primary-outcome event was lower in the active-treatment group than in the control group (30.2% vs. 37.0%), for an adjusted risk ratio of 0.82 (95% confidence interval [CI], 0.74 to 0.92; P<0.001). The percentage of small-for-gestational-age birth weights below the 10th percentile was 11.2% in the active-treatment group and 10.4% in the control group (adjusted risk ratio, 1.04; 95% CI, 0.82 to 1.31; P = 0.76). The incidence of serious maternal complications was 2.1% and 2.8%, respectively (risk ratio, 0.75; 95% CI, 0.45 to 1.26), and the incidence of severe neonatal complications was 2.0% and 2.6% (risk ratio, 0.77; 95% CI, 0.45 to 1.30). The incidence of any preeclampsia in the two groups was 24.4% and 31.1%, respectively (risk ratio, 0.79; 95% CI, 0.69 to 0.89), and the incidence of preterm birth was 27.5% and 31.4% (risk ratio, 0.87; 95% CI, 0.77 to 0.99). CONCLUSIONS: In pregnant women with mild chronic hypertension, a strategy of targeting a blood pressure of less than 140/90 mm Hg was associated with better pregnancy outcomes than a strategy of reserving treatment only for severe hypertension, with no increase in the risk of small-for-gestational-age birth weight. (Funded by the National Heart, Lung, and Blood Institute; CHAP ClinicalTrials.gov number, NCT02299414.).

Super-Utilizers of Inpatient Care in an Obstetrical Population: A Cross-Sectional Study.

OBJECTIVES: The aim of the study is to estimate hospital charges (HC) and length of stay (LOS) for pregnancy and 6 weeks postpartum and to characterize the outliers who utilize a disproportionate share of health care resources. STUDY DESIGN: We performed a cross-sectional study of 500 subjects at a tertiary center between 2012 and 2014. Subjects were included who had inpatient status and an ICD-9 code for pregnancy; those with an ICD-9 code for ectopic pregnancy were excluded. Data were collected 266 days prior to the estimated date of delivery (EDD) and up to 42 days post-delivery. Medical diagnoses, obstetrical details, demographics, HC, and LOS were collected. Super-utilizers (SUs) were selected as patients with total HC exceeding $75,000, those who incurred $75,000 or less were assigned to the typical utilizer (TU) group. RESULTS: HC was positively skewed, with median's (interquartile range) of $151,143 (97,707-198,732) and $28,186 (19,292-38,943) among SUs and TUs, respectively. Despite the low proportion of SU patients (7%, n = 36), they accounted for 30% of charges. Similarly, SUs had longer LOS (16 vs. 3 days, p <0.05). They had earlier deliveries (34.5 vs. 38.5 weeks, p <0.05), higher cesarean section rates (69 vs. 35%, p <0.05), and more hysterectomies (8.3 vs. 0%, p <0.05). The most common complications in SUs were preterm labor (33.3 vs. 5.4%, p <0.05) and preterm premature rupture of membranes (25 vs. 3.9%, p< 0.05). The most common pre-existing condition in SUs was chronic hypertension (11.1 vs. 3%, p< 0.05). CONCLUSION: Although SUs comprise only 7% of the obstetrical population, they account for almost a third of the total HCs; in turn, SUs are at risk of adverse outcomes. Targeting this population can guide efforts to improve maternal health through prevention, research, and personalized care. SUs may have clustering at hospitals with higher levels of care and this topic warrants further investigation with state and national level data. KEY POINTS: · Just 7% of pregnant patients accounted for 30% of hospital charges.. · Super-utilizers had higher rates of preterm delivery, cesarean section, and hysterectomy.. · The most common pre-existing medical condition in super-utilizers was chronic hypertension..

A comparison of pregnancy-specific risk scoring systems for venous thromboembolic pharmacoprophylaxis in hospitalized maternity patients.

OBJECTIVE: Venous thromboembolism (VTE) remains a leading cause of maternal mortality. The American College of Obstetricians and Gynecologists (ACOG) and the Royal College of Obstetricians & Gynecologists (RCOG) have proposed pregnancy-specific risk scoring guidelines for antepartum (AP) and postpartum (PP) thromboprophylaxis. We compared the impact of scoring thresholds and their potential preventative effect. STUDY DESIGN: We conducted a retrospective cohort study of hospitalized maternity patients over a 4-month period. Patients were assigned an AP and PP risk score using each guideline. Hospitalization-associated VTE was accessed over a 6-year period. Comparison was by Fischer's exact and Chi Square tests. RESULTS: 638 women were included. Of AP patients, 20% met pharmacoprophylaxis criteria for baseline characteristics and 100% for length of stay using RCOG, and 12% met phrarmacoprophylaxis criteria using ACOG (p < .001). For PP patients, 53% met criteria for RCOG compared to 24% using ACOG (p < .001). If pharmacoprophylaxis were performed at a threshold 1 point above recommendation, 7% of AP patients and 11% of PP women would meet ACOG criteria. This increased ACOG threshold captured all cases of VTE following hospitalization. CONCLUSION: In our population, using ACOG prophylaxis guidelines at an increased threshold would have potentially prevented all hospitalization related VTE without excessive anti-coagulation.

Obstetrical outcomes and follow-up for patients with asymptomatic COVID-19 at delivery: a multicenter prospective cohort study.

BACKGROUND: Universal testing for COVID-19 on admission to the labor and delivery unit identifies asymptomatic patients. Whether or not these patients are at increased risk for adverse outcomes and go on to develop clinically significant disease is uncertain. OBJECTIVE: This study aimed to assess the prevalence of asymptomatic COVID-19 presentation among pregnant patients admitted for delivery and to determine whether these patients become symptomatic or require hospital readmission after discharge. STUDY DESIGN: We performed a multicenter, prospective cohort study of pregnant patients who delivered between 200/7 and 416/7 weeks' gestation and who were found to have COVID-19 based on universal screening on admission for delivery at 1 of 4 medical centers in New Jersey (exposed group). The unexposed group, comprising patients who tested negative for COVID-19, were identified at the primary study site. The primary outcomes were the rates of asymptomatic COVID-19 presentation, the development of symptoms among the asymptomatic positive patients, and hospital readmission rates in the 2 weeks following discharge. We compared the frequency of the distribution of risk factors and outcomes in relation to the COVID-19 status among patients with COVID-19 across all centers and among those without COVID-19 at the primary site. Associations between categorical risk factors and COVID-19 status were expressed as relative risks with 95% confidence intervals. RESULTS: Between April 10, 2020, and June 15, 2020, there were 218 patients with COVID-19 at the 4 sites and 413 patients without COVID-19 at the primary site. The majority (188 [83.2%]) of patients with COVID-19 were asymptomatic. Compared with the negative controls, these asymptomatic patients were not at increased risk for obstetrical complications that may increase the risk associated with COVID-19, including gestational diabetes (8.2% vs 11.4%; risk ratio, 0.72; 95% confidence interval, 0.24-2.01) and gestational hypertension (6.1% vs 7.0%; risk ratio, 0.88; 95% confidence interval, 0.29-2.67). Postpartum follow-ups via telephone surveys revealed that these patients remained asymptomatic and had low rates of family contacts acquiring the disease, but their adherence to social distancing guidelines waned during the 2-week postpartum period. Review of inpatient and emergency department records revealed low rates of hospital readmission. CONCLUSION: Most of the pregnant patients who screened positive for COVID-19 are asymptomatic and do not go on to develop clinically significant infection after delivery. Routine surveillance of these patients after hospital discharge appears to be sufficient.

Fetal Exosomal Platelet-activating Factor Triggers Functional Progesterone Withdrawal in Human Placenta.

In most mammals, labor is heralded by the withdrawal of progesterone. In humans, circulating progesterone levels increase as gestation advances while placental expression of progesterone receptor A (PR-A) declines. As a result of PR-A downregulation, the non-canonical NF-κB pathway is activated, an event implicated in triggering labor. Here, we sought to identify fetal-derived mediator(s) that represses placental PR-A in human placenta leading to activation of pro-labor signaling. Lipidomic profiling demonstrated enrichment of platelet-activating factor (PAF) in exosomes originating from the human fetus. Exposure of primary cytotrophoblasts to fetal exosomes from term pregnancies reduced PR-A expression by > 50%, and PAF also reduced PR-A message levels in a dose-dependent manner. Notably, fetal exosomes from preterm pregnancies had lower PAF levels and no effect on PR-A expression. Synthetic PAF-induced DNA methylation increases by 20% at the PR-A promoter, leading to recruitment of corepressors and downregulation of PR-A in cytotrophoblast. Furthermore, suppression of PR-A by PAF-stimulated expression of the pro-labor genes, corticotropin-releasing hormone (CRH) and cyclooxygenase-2 (COX-2), which was reversed by disruption of the DNA methyltransferases 3B and 3L. Taken together, PAF represents a novel fetal-derived candidate for initiation of labor by stimulating methylation and repression of PR-A and activating pro-labor signaling in trophoblast.

Epidemiology of coronavirus disease 2019 in pregnancy: risk factors and associations with adverse maternal and neonatal outcomes.

BACKGROUND: Coronavirus disease 2019 may be associated with adverse maternal and neonatal outcomes in pregnancy, but there are few controlled data to quantify the magnitude of these risks or to characterize the epidemiology and risk factors. OBJECTIVE: This study aimed to quantify the associations of coronavirus disease 2019 with adverse maternal and neonatal outcomes in pregnancy and to characterize the epidemiology and risk factors. STUDY DESIGN: We performed a matched case-control study of pregnant patients with confirmed coronavirus disease 2019 cases who delivered between 16 and 41 weeks' gestation from March 11 to June 11, 2020. Uninfected pregnant women (controls) were matched to coronavirus disease 2019 cases on a 2:1 ratio based on delivery date. Maternal demographic characteristics, coronavirus disease 2019 symptoms, laboratory evaluations, obstetrical and neonatal outcomes, and clinical management were chart abstracted. The primary outcomes included (1) a composite of adverse maternal outcome, defined as preeclampsia, venous thromboembolism, antepartum admission, maternal intensive care unit admission, need for mechanical ventilation, supplemental oxygen, or maternal death, and (2) a composite of adverse neonatal outcome, defined as respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, 5-minute Apgar score of <5, persistent category 2 fetal heart rate tracing despite intrauterine resuscitation, or neonatal death. To quantify the associations between exposure to mild and severe or critical coronavirus disease 2019 and adverse maternal and neonatal outcomes, unadjusted and adjusted analyses were performed using conditional logistic regression (to account for matching), with matched-pair odds ratio and 95% confidence interval based on 1000 bias-corrected bootstrap resampling as the effect measure. Associations were adjusted for potential confounders. RESULTS: A total of 61 confirmed coronavirus disease 2019 cases were enrolled during the study period (mild disease, n=54 [88.5%]; severe disease, n=6 [9.8%]; critical disease, n=1 [1.6%]). The odds of adverse composite maternal outcome were 3.4 times higher among cases than controls (18.0% vs 8.2%; adjusted odds ratio, 3.4; 95% confidence interval, 1.2-13.4). The odds of adverse composite neonatal outcome were 1.7 times higher in the case group than to the control group (18.0% vs 13.9%; adjusted odds ratio, 1.7; 95% confidence interval, 0.8-4.8). Stratified analyses by disease severity indicated that the morbidity associated with coronavirus disease 2019 in pregnancy was largely driven by the severe or critical disease phenotype. Major risk factors for associated morbidity were black and Hispanic race, advanced maternal age, medical comorbidities, and antepartum admissions related to coronavirus disease 2019. CONCLUSION: Coronavirus disease 2019 during pregnancy is associated with an increased risk of adverse maternal and neonatal outcomes, an association that is primarily driven by morbidity associated with severe or critical coronavirus disease 2019. Black and Hispanic race, obesity, advanced maternal age, medical comorbidities, and antepartum admissions related to coronavirus disease 2019 are risk factors for associated morbidity.

miR-15b-5p promotes expression of proinflammatory cytokines in human placenta by inhibiting Apelin signaling pathway.

INTRODUCTION: The timing of parturition at end of human gestation may be controlled by fetal signals. The signaling molecules contributing to activation of human labor may be mediated by fetal exosomes. In this study, we focused on investigation of the role of microRNAs (miRNAs) derived from fetal exosomes in the regulation of human placental gene expression. METHODS: Using immunofluorescent labeling, array-based miRNA profiling assay, target prediction analysis, and conducting a variety of biochemical approaches including miRNA mimics, dual-luciferase, siRNA-mediated gene silencing, and immunohistochemical staining assay in primary trophoblast culture and formalin-fixed paraffin-embedded placental tissues, we examined whether fetal exosomal miRNAs can stimulate expression of proinflammatory mediators in human placenta. RESULTS: We showed placental uptake of exosomes derived from the umbilical artery, and found that 9 fetal exosomal miRNAs: let-7i-5p, miR-185-5p, miR-15b-5p, miR-376c-3p, miR-548d-5p, miR-92b-3p, miR-16-5p, and miR-1301-3p were significantly increased in placentas of women delivering following term labor compared to those delivering by Cesarean section in the late preterm period. Target prediction analysis identified miR-15b-5p of particular interest, because one of its predicted targets is Apelin, a potent inhibitor of proinflammatory mediators. We further found that miR-15b-5p repressed Apelin protein levels and activated pro-labor hormones and cytokines including IL-1, IL-6, IL-8, and TNF-α. DISCUSSION: These data suggest a potential fetal-to-placental signal that could play a role in the length of human gestation and onset of human labor.

Intrauterine Vacuum-Induced Hemorrhage-Control Device for Rapid Treatment of Postpartum Hemorrhage.

OBJECTIVE: To evaluate the effectiveness and safety of an intrauterine vacuum-induced hemorrhage-control device for postpartum hemorrhage treatment. METHODS: A multicenter, prospective, single-arm treatment study of a novel intrauterine device that uses low-level vacuum to induce uterine myometrial contraction to achieve control of abnormal postpartum uterine bleeding and postpartum hemorrhage was undertaken at 12 centers in the United States. The primary effectiveness endpoint was the proportion of participants in whom use of the intrauterine vacuum-induced hemorrhage-control device controlled abnormal bleeding without requiring escalating interventions. The primary safety endpoint was the incidence, severity, and seriousness of device-related adverse events. Secondary outcomes included time to bleeding control, rate of transfusion, and device usability scored by each investigator using the device. RESULTS: Of 107 participants enrolled with primary postpartum hemorrhage or abnormal postpartum uterine bleeding, 106 received any study treatment with the device connected to vacuum, and successful treatment was observed in 94% (100/106, 95% CI 88-98%) of these participants. In those 100 participants, definitive control of abnormal bleeding was reported in a median of 3 minutes (interquartile range 2.0-5.0) after connection to vacuum. Eight adverse events deemed possibly related to the device or procedure were reported, all of which were outlined as risks in the study and all of which resolved with treatment without serious clinical sequelae. Transfusion of 1-3 units of red blood cells was required in 35 participants, and five participants required 4 or more units of red blood cells. The majority of investigators reported the intrauterine vacuum-induced hemorrhage-control device as easy to use (98%) and would recommend it (97%). CONCLUSION: Intrauterine vacuum-induced hemorrhage control may provide a new rapid and effective treatment option for abnormal postpartum uterine bleeding or postpartum hemorrhage, with the potential to prevent severe maternal morbidity and mortality. FUNDING SOURCE: Alydia Health, Inc. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02883673.