Plasma soluble fms-like tyrosine kinase 1 to placental growth factor ratio of 11.5 multiples of median predicts preeclampsia with severe features within 2 weeks of testing.

BACKGROUND: Angiogenic imbalances, characterized by an excess of antiangiogenic factors (soluble fms-like tyrosine kinase 1) and reduced angiogenic factors (vascular endothelial growth factor and placental growth factor), contribute to the mechanisms of disease in preeclampsia. The ratio of soluble fms-like tyrosine kinase 1 to placental growth factor has been used as a biomarker for preeclampsia, but the cutoff values may vary with gestational age and assay platform. OBJECTIVE: This study aimed to compare multiples of the median of the maternal plasma soluble fms-like tyrosine kinase 1 to placental growth factor ratio, soluble fms-like tyrosine kinase 1, placental growth factor, and conventional clinical and laboratory values in their ability to predict preeclampsia with severe features. STUDY DESIGN: We conducted a cohort study across 18 United States centers involving hospitalized individuals with hypertension between 23 and 35 weeks' gestation. Receiver operating characteristic curve analyses of maternal plasma biomarkers, highest systolic or diastolic blood pressures, and laboratory values at enrollment were performed for the prediction of preeclampsia with severe features. The areas under the curve were compared, and quasi-Poisson regression models were fitted to estimate relative risks. The primary outcome was preeclampsia with severe features within 2 weeks of enrollment. Secondary outcomes were a composite of severe adverse maternal outcomes (elevated liver enzymes, low platelets count, placental abruption, eclampsia, disseminated intravascular coagulation, and pulmonary edema) and a composite of severe adverse perinatal outcomes (birth weight below the third percentile, very preterm birth [<32 weeks' gestation], and fetal or neonatal death). RESULTS: Of the 543 individuals included in the study, preeclampsia with severe features within 2 weeks was observed in 33.1% (n=180) of them. A receiver operating characteristic curve-derived cutoff of 11.5 multiples of the median for the soluble fms-like tyrosine kinase 1 to placental growth factor plasma ratio provided good sensitivity (90.6%), specificity (76.9%), positive predictive value (66.0%), negative predictive value (94.3%), positive likelihood ratio (3.91), negative likelihood ratio (0.12), and accuracy (81.4%) for preeclampsia with severe features within 2 weeks. This cutoff was used to compare test positive cases (≥ cutoff) and test negative cases (< cutoff). Preeclampsia with severe features (66.0% vs 5.7%; P<.001) and composites of severe adverse maternal (8.11% vs 2.7%; P=.006) or perinatal (41.3% vs 10.14%; P=.001) outcomes within 2 weeks were more frequent in test positive cases than in test negative cases. A soluble fms-like tyrosine kinase 1 to placental growth factor plasma ratio ≥11.5 multiples of the median was independently associated with preeclampsia with severe features (adjusted incidence rate ratio, 9.08; 95% confidence interval, 6.11-14.06; P<.001) and a composite of severe adverse perinatal outcomes (adjusted incidence rate ratio, 9.42; 95% confidence interval, 6.36-14.53; P<.001) but not with a composite of severe adverse maternal outcomes (adjusted incidence rate ratio, 2.20; 95% confidence interval, 0.95-5.54; P=.08). The area under the curve for the soluble fms-like tyrosine kinase 1 to placental growth factor plasma ratio in multiples of the median (0.91; 95% confidence interval, 0.89-0.94) for preeclampsia with severe features within 2 weeks was significantly higher (P<.001 for all comparisons) than either plasma biomarker alone or any other parameter with the exception of absolute soluble fms-like tyrosine kinase 1 to placental growth factor plasma ratio values. CONCLUSION: A soluble fms-like tyrosine kinase 1 to placental growth factor plasma ratio ≥11.5 multiples of the mean among hospitalized patients with hypertension between 23 and 35 week's gestation predicts progression to preeclampsia with severe features and severe adverse perinatal outcomes within 2 weeks.

Racial/Ethnic Disparities in Peripartum Pain Assessment and Management.

OBJECTIVE: This study was conducted to determine if there were racial/ethnic disparities in pain assessment and management from labor throughout the postpartum period. METHODS: This was a retrospective cohort study of all births from January 2019 to December 2021 in a single urban, quaternary care hospital, excluding patients with hysterectomy, ICU stay, transfusion of more than 3 units of packed red blood cells, general anesthesia, or evidence of a substance abuse disorder. We characterized and compared patterns of antepartum and postpartum pain assessments, epidural use, pain scores, and postpartum pain management by racial/ethnic group with bivariable analyses. Multivariable regression was performed to test for an association between race/ethnicity and amount of opioid pain medication in milligram equivalent units, stratified by delivery mode. RESULTS: There were 18,085 births between 2019 and 2021 with available race/ethnicity data. Of these, 58.3% were white, 15.0% were Hispanic, 11.9% were Asian, 7.4% were Black, and the remaining 7.4% were classified as Other/Declined. There were no significant differences by race/ethnicity in the number of antepartum or postpartum pain assessments or the proportion of patients who received epidural analgesia. Black and Hispanic patients reported the highest maximum postpartum pain scores after vaginal and cesarean birth compared to white and Asian patients. However, Black and Hispanic patients received lower daily doses of opioid medications than white patients, regardless of delivery mode. After adjusting for patient factors and non-opioid medication dosages, all other racial/ethnic groups received less opioid medication than white patients. CONCLUSION: Inequities were found in postpartum pain treatment, including among patients reporting the highest pain levels.

Perinatal mood and anxiety disorders: biomarker discovery using plasma proteomics.

BACKGROUND: Perinatal mood and anxiety disorders encompass a range of mental health disorders that occur during pregnancy and up to 1 year postpartum, affecting approximately 20% of women. Traditional risk factors, such as a history of depression and pregnancy complications including preeclampsia, are known. Their predictive utility, however, is not specific or sensitive enough to inform clinical decision-making or prevention strategies for perinatal mood and anxiety disorders. Better diagnostic and prognostic models are needed for early identification and referral to treatment. OBJECTIVE: This study aimed to determine if a panel of novel third-trimester plasma protein biomarkers in pregnant women can be used to identify those who have a high predisposed risk for perinatal mood and anxiety disorders within 3 months postpartum. STUDY DESIGN: We studied 52 women (n=34 with a risk for perinatal mood and anxiety disorders and n=18 controls) among whom mental health screening was conducted at 2 time points, namely in the third trimester and again at 3 months postdelivery. An elevated perinatal mood and anxiety disorder risk was identified by screening individuals with above-validated cutoffs for depression (Edinburgh Postnatal Depression Scale ≥12), anxiety (Overall Anxiety Severity and Impairment Scale ≥7), and/or posttraumatic stress disorder (Impact of Events Scale >26) at both time points. Plasma samples collected in the third trimester were screened using the aptamer-based SomaLogic SomaScan proteomic assay technology to evaluate perinatal mood and anxiety disorder-associated changes in the expression of 1305 protein analytes. Ingenuity Pathway Analysis was conducted to highlight pathophysiological relationships between perinatal mood and anxiety disorder-specific proteins found to be significantly up- or down-regulated in all subjects with perinatal mood and anxiety disorder and in those with perinatal mood and anxiety disorders and no preeclampsia. RESULTS: From a panel of 53 significant perinatal mood and anxiety disorder-associated proteins, a unique 20-protein signature differentiated perinatal mood and anxiety disorder cases from controls in a principal component analysis (P<.05). This protein signature included NCAM1, NRCAM, and NTRK3 that converge around neuronal signaling pathways regulating axonal guidance, astrocyte differentiation, and maintenance of GABAergic neurons. Interestingly, when we restricted the analysis to subjects without preeclampsia, a 30-protein signature differentiated perinatal mood and anxiety disorder cases from all controls without overlap on the principal component analysis (P<.001). In the nonpreeclamptic perinatal mood and anxiety disorder group, we observed increased expression of proteins, such as CXCL11, CXCL6, MIC-B, and B2MG, which regulate leucocyte migration, inflammation, and immune function. CONCLUSION: Participants with perinatal mood and anxiety disorders had a unique and distinct plasma protein signature that regulated a variety of neuronal signaling and proinflammatory pathways. Additional validation studies with larger sample sizes are needed to determine whether some of these molecules can be used in conjunction with traditional risk factors for the early detection of perinatal mood and anxiety disorders.

Immune transcriptional profiles in mothers with clinically elevated depression and anxiety symptoms several years post-delivery.

BACKGROUND: Most research on maternal mental health focuses on the perinatal period and does not extend beyond 12 months postpartum. However, emerging evidence suggests that for some women (30%-50%), psychological symptoms may persist beyond the first year postpartum or even emerge later increasing the risk of chronic mood and anxiety symptoms. Despite the high prevalence rates and devastating maternal-child consequences, studies examining maternal depression, anxiety, and post-traumatic stress disorder (PTSD) beyond the first year postpartum are rare and our understanding of the underlying biological mechanisms is incomplete. Inflammatory processes are thought to be involved in the pathophysiology of depression, anxiety, & PTSD outside of the postpartum period. Therefore, the purpose of the current investigation was to examine the relationship between depression, anxiety, and PTSD two to three years post-delivery, and transcriptional control pathways relevant to inflammatory and antiviral processes. METHODS: Women over 18 years of age enrolled in ongoing research studies at Cedars Sinai Medical Center who were 2-3 years postpartum were invited to participate in the current study. Women (N = 33) reported on their levels of depression, anxiety, and PTSD and provided a blood sample approximately 2-3 years post-delivery. Bioinformatic analyses of differential gene expression (DGEs) to infer transcription factor activity were used. Gene expression was assayed by RNA sequencing and TELiS bioinformatics analysis of transcription factor-binding motifs in the promoters of differentially expressed genes. RESULTS: DGE analyses revealed that women with clinically elevated symptoms of depression, anxiety and PTSD (n = 16) showed upregulation of genes activated by transcription control pathways associated with inflammation (NF-Κ B, p = 0.004; JUN, p = 0.02), including ß-adrenergic responsive CREB (p = 0.01) and reduced activation of genes associated with the antiviral response (IRFs, p = 0.02) and the glucocorticoid signaling pathway (GR, p = 0.02) compared to women without clinical symptoms (n = 17). CONCLUSIONS: This is one of the first investigations into the immune signaling pathways involved in depression, anxiety, and PTSD two to three years post-delivery. The results of this study suggest that clinically elevated symptoms of depression, anxiety, and PTSD two to three years post-delivery are associated with a gene expression profile characterized by upregulated expression of pro-inflammatory genes and downregulated expression of antiviral genes. The data also point to two potential stress responsive pathways linking symptoms to increased inflammatory signaling in immune cells: sympathetic nervous system mediated ß-adrenergic signaling and reduced hypothalamic pituitary adrenal axis activity. Together, these findings highlight the need for investigations into maternal mental health beyond the first year postpartum.

Lack of Association Between Race and Ethnicity and Timely Treatment of Severe Peripartum Hypertension.

BACKGROUND: Hypertensive disorders of pregnancy are a leading cause of severe maternal morbidity and mortality. National guidelines recommend treatment within 30 to 60 minutes of confirmed severe hypertension to reduce the risk of maternal stroke. The objectives of this study were to quantify the number of patients who did not receive timely treatment of severe hypertension, identify barriers to timely treatment, and evaluate if race/ethnicity was associated with timeliness of treatment. METHODS: The researchers created an automated report to identify women who experienced severe hypertension during the delivery admission. The record for each case was reviewed to determine if treatment was timely (within 30 minutes). The study team compared rates of severe peripartum hypertension and rates of timely vs. not timely treatment by race/ethnicity. RESULTS: There were 12,069 deliveries from April 1, 2019, to March 31, 2021-with 684 (5.7%) women with at least one episode of severe hypertension, of whom 241 (35.2%) did not require treatment, leaving 443 (64.8%) women requiring treatment. A total of 441 women received treatment, with 417 (94.6%) treated in a timely manner. Black, Asian, and Hispanic women were all more likely to experience severe hypertension requiring treatment than white women (10.0%, 8.8%, 7.3% vs. 4.0%, respectively, p < 0.001). However, there was no difference in the in the rates of timely treatment between groups (92.6%, 93.0%, 93.9% vs. 96.3%, respectively, p = 0.59). CONCLUSION: Among patients with severe hypertension, 94.6% were treated in a timely manner, and race/ethnicity was not associated with timeliness of treatment. Provider education at all levels at our institution seems to be effective for timely treatment of severe hypertension and suggests that this process could be beneficial at other institutions.

Race/ethnicity differences in response to acute antihypertensive treatment of peripartum severe hypertension.

BACKGROUND: Hypertensive disorders of pregnancy increase maternal morbidity, mortality, and long-term risk for cardiovascular disease. The rising incidence of chronic hypertension and preeclampsia disproportionately affects people of color. There is a paucity of published data examining differences in the effectiveness of acute antihypertensive agents between pregnant patients of different races/ethnicities. We aimed to determine if the effectiveness of acute antihypertensive agents for peripartum severe hypertension differs by race/ethnicity. METHODS: A retrospective cohort study of patients with severe peripartum hypertension (systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 110 mm Hg confirmed within 15 min) to determine whether the effectiveness of blood pressure control using nationally recommended medications (hydralazine, labetalol, nifedipine) differed by race/ethnicity. The primary outcome was reduction and maintenance of blood pressure to target ranges (140-150/90-100 mm Hg or below) for ≥4 h in each race/ethnicity group. Statistical tests included χ2, Fisher's exact, analysis of variance, and multivariable logistic regression. RESULTS: Of 729 patients receiving treatment for severe peripartum hypertension, all medications were effective (overall 86.4% efficacy) at controlling blood pressure. Labetalol was the most effective medication in White patients (93.0 vs. 74.7% for nifedipine and 86.5% for hydralazine, p < .001). No overall differences in medication effectiveness were found in Black, Asian, or LatinX patients. Black and Asian patients were more likely to experience >1 hypertensive episode [51.0 and 49.0%, respectively vs. 35.4% (White) and 40.0% (LatinX), p = .008]. CONCLUSION: Currently recommended therapies for severe peripartum hypertension are effective in controlling blood pressure for ≥4 h in patients of all race/ethnic groups. Labetalol was the most effective medication in White patients with no overall differences in medication effectiveness in Black, Asian, or LatinX patients.

Care Levels for Fetal Therapy Centers.

Fetal therapies undertaken to improve fetal outcome or to optimize transition to neonate life often entail some level of maternal, fetal, or neonatal risk. A fetal therapy center needs access to resources to carry out such therapies and to manage maternal, fetal, and neonatal complications that might arise, either related to the therapy per se or as part of the underlying fetal or maternal condition. Accordingly, a fetal therapy center requires a dedicated operational infrastructure and necessary resources to allow for appropriate oversight and monitoring of clinical performance and to facilitate multidisciplinary collaboration between the relevant specialties. Three care levels for fetal therapy centers are proposed to match the anticipated care complexity, with appropriate resources to achieve an optimal outcome at an institutional and regional level. A level I fetal therapy center should be capable of offering fetal interventions that may be associated with obstetric risks of preterm birth or membrane rupture but that would be very unlikely to require maternal medical subspecialty or intensive care, with neonatal risks not exceeding those of moderate prematurity. A level II center should have the incremental capacity to provide maternal intensive care and to manage extreme neonatal prematurity. A level III therapy center should offer the full range of fetal interventions (including open fetal surgery) and be able manage any of the associated maternal complications and comorbidities, as well as have access to neonatal and pediatric surgical intervention including indicated surgery for neonates with congenital anomalies.

Implementing an inpatient postpartum depression screening, education, and referral program: a quality improvement initiative.

BACKGROUND: Perinatal mood and anxiety disorders are common and may interfere with pregnancy, delivery, and the postpartum period. Best practice includes symptom screening, patient education, and appropriate referrals; however, many hospitals struggle to identify and support perinatal mood and anxiety disorders patients. OBJECTIVE: Therefore, the Cedars-Sinai Postpartum Depression Screening, Education and Referral Program was initiated and evaluated. STUDY DESIGN: Using the Standards for QUality Improvement Reporting Excellence 2.0 guidelines, we reported outcomes (N=19,564 deliveries) from 4 interventions: (1) nurse-champion training; (2) use of the 9-item Patient Health Questionnaire-9 in the postpartum unit; (3) a series of brief in-service trainings; and (4) a 10-minute video training. We collected data including nurse feedback, screening rates, screen-positive rates, and social work consultation rates. RESULTS: The 4 interventions increased: (1) nurse-champion screening comfort and perinatal mood and anxiety disorder knowledge; (2) Patient Health Questionnaire-9 screening rates from 10% to 99% and screen-positive rates from 0.04% to 2.9%; and (3) rates of social work consultation from 1.7% to 8.4%. CONCLUSION: Quality improvement results from the first 3 years of the program suggest that 4 interventions improved screening rates, screen-positive rates, and social work consultation rates. Future work will focus on method of screening, patients at highest risk of perinatal mood and anxiety disorders, and ongoing nurse training.

Routine Multidisciplinary Review of Severe Maternal Morbidity Is Associated with a Reduction in Preventable Cases of Severe Maternal Morbidity.

OBJECTIVE: Severe maternal morbidity (SMM) has increased by 45% in the United States and is estimated to affect up to 1.5% of all deliveries. Research has not yet been conducted that demonstrates a benefit to multidisciplinary review of SMM. The aim of our study was to determine if standardized, routine review of the cases of SMM by a multidisciplinary committee results in a reduction of potentially preventable cases of SMM. STUDY DESIGN: A retrospective cohort study of all women admitted for delivery at Cedars-Sinai Medical Center from March 1, 2012 to September 30, 2016. Our cohort was separated into two groups: a preintervention group composed of women admitted for delivery prior to the implementation of the obstetric Quality and Peer Review Committee (OBQPRC), and a postintervention group where the committee had been well established. Cases of confirmed SMM were presented to a multidisciplinary research committee, and the committee determined whether opportunities for improvement in care existed. The groups were compared with determine if there was a decreased incidence of preventable SMM following the implementation of the OBQPRC standardized review process. RESULTS: There were 30,319 deliveries during the study period; 13,120 deliveries in the preintervention group; and 13,350 deliveries in the postintervention group (2,649 deliveries during the transition period). There was no difference in the rate of SMM between the preintervention (125; 0.95%) and postintervention (129; 0.97%) groups, (p = 0.91). There was a significantly lower rate of opportunity for the improvement in care in the postintervention group (29.5%) compared with the preintervention group (46%; p = 0.005). CONCLUSION: We demonstrated a significant reduction in the rate of potentially preventable SMM following the implementation of routine review of all SMM suggesting that this process plays an important role in improving maternal care and outcomes. KEY POINTS: · Benefit to routine review of SMM has not been demonstrated.. · Routine review of SMM is associated with 36% reduction in potentially preventable SMM.. · This is the first study to demonstrate the benefit of routine review of SMM..

Circulating Angiogenic Factor Levels in Hypertensive Disorders of Pregnancy.

BACKGROUND: Among women with hypertensive disorders of pregnancy, biomarkers may stratify risk for developing preeclampsia with severe features (sPE). METHODS: Across 18 U.S. centers, we prospectively measured the ratio of serum soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) in pregnant women hospitalized between 23 and 35 weeks of gestation. The primary outcome was predicting sPE, and secondary outcomes included predicting adverse outcomes within 2 weeks. The prognostic performance of the sFlt-1:PlGF ratio was assessed by using a derivation/validation design. RESULTS: A total of 1014 pregnant women were evaluated; 299 were included in the derivation cohort and 715 in the validation cohort. In the derivation cohort, the median sFlt-1:PlGF ratio was 200 (interquartile range, 53 to 458) among women who developed sPE compared with 6 (interquartile range, 3 to 26) in those who did not (P<0.001). The discriminatory ratio of ≥40 was then tested in the validation cohort and yielded a 65% positive (95% confidence interval [CI], 59 to 71) and a 96% negative (95% CI, 93 to 98) predictive value for the primary outcome. The ratio performed better than standard clinical measures (area under the receiver-operating characteristic curve, 0.92 versus <0.75 for standard-of-care tests). Compared with women with a ratio <40, women with a ratio ≥40 were at higher risk for adverse maternal outcomes (16.1% versus 2.8%; relative risk, 5.8; 95% CI, 2.8 to 12.2). CONCLUSIONS: In women with a hypertensive disorder of pregnancy presenting between 23 and 35 weeks of gestation, measurement of serum sFlt-1:PlGF provided stratification of the risk of progressing to sPE within the coming fortnight. (Funded by Cedars-Sinai Medical Center and Thermo Fisher Scientific; ClinicalTrials.gov NCT03815110.)

Cardiovascular Health After Preeclampsia: Patient and Provider Perspective.

Background: Preeclampsia predicts future cardiovascular disease (CVD) yet few programs exist for post-preeclampsia care. Methods: The Health after Preeclampsia Patient and Provider Engagement Network workshop was convened at the Radcliffe Institute for Advanced Study in June 2018. The workshop sought to identify: 1) patient perspectives on barriers and facilitators to CVD risk reduction; 2) clinical programs specialized in post-preeclampsia care; 3) recommendations by national organizations for risk reduction; and 4) next steps. Stakeholders included the Preeclampsia Foundation, patients, clinicians who had initiated CVD risk reduction programs for women with prior preeclampsia, researchers, and national task force members. Results: Participants agreed there is insufficient awareness and action to prevent CVD after preeclampsia. Patients suggested a clinician checklist to ensure communication of CVD risks, enhanced training for clinicians on the link between preeclampsia and CVD, and a post-delivery appointment with a clinician knowledgeable about this link. Clinical programs primarily served patients in the first postpartum year, bridging obstetrical and primary care. They recommended CVD risk modification with periodic blood pressure, weight, lipid and diabetes screening. Barriers included the paucity of programs designed for this population and gaps in insurance coverage after delivery. The American Heart Association, the American College of Obstetricians and Gynecologists, and the Preeclampsia Foundation have developed guidelines and materials for patients and providers to guide management of women with prior preeclampsia. Conclusions: Integrated efforts of patients, caregivers, researchers, and national organizations are needed to improve CVD prevention after preeclampsia. This meeting's recommendations can serve as a resource and catalyst for this effort.

Impact of labor and delivery unit policy modifications on maternal and neonatal outcomes during the coronavirus disease 2019 pandemic.

Background: In response to the coronavirus disease 2019 pandemic, hospitals nationwide have implemented modifications to labor and delivery unit practices designed to protect delivering patients and healthcare providers from infection with severe acute respiratory syndrome coronavirus 2. Beginning in March 2020, our hospital instituted labor, and delivery unit modifications targeting visitor policy, use of personal protective equipment, designation of rooms for triage and delivery of persons suspected or infected with coronavirus disease 2019, delivery management, and newborn care. Little is known about the ramifications of these modifications in terms of maternal and neonatal outcomes. Objective: The objective of this study was to determine whether labor and delivery unit policy modifications we made during the coronavirus disease 2019 pandemic were associated with differences in outcomes for mothers and newborns. Study Design: We conducted a retrospective cohort study of all deliveries occurring in our hospital between January 1, 2020, and April 30, 2020. Patients who delivered in January and February 2020 before labor and delivery unit modifications were instituted were designated as the preimplementation group, and those who delivered in March and April 2020 were designated as the postimplementation group. Maternal and neonatal outcomes between the pre- and postimplementation groups were compared. Differences between the 2 groups were then compared with the same time period in 2019 and 2018 to assess whether any apparent differences were unique to the pandemic year. We hypothesized that maternal and newborn lengths of stay would be shorter in the postimplementation group. Statistical analysis methods included Student's t-tests and Wilcoxon tests for continuous variables and chi-square or Fisher exact tests for categorical variables. Results: Postpartum length of stay was significantly shorter after implementation of labor unit changes related to coronavirus disease 2019. A postpartum stay of 1 night after vaginal delivery occurred in 48.5% of patients in the postimplementation group compared with 24.9% of the preimplementation group (P<.0001). Postoperative length of stay after cesarean delivery of ≤2 nights occurred in 40.9% of patients in the postimplementation group compared with 11.8% in the preimplementation group (P<.0001). Similarly, after vaginal delivery, 49.0% of newborns were discharged home after 1 night in the postimplementation group compared with 24.9% in the preimplementation group (P<.0001). After cesarean delivery, 42.5% of newborns were discharged after ≤2 nights in the postimplementation group compared with 12.5% in the preimplementation group (P<.0001). Slight differences in the proportions of earlier discharge between mothers and newborns were due to multiple gestations. There were no differences in cesarean delivery rate, induction of labor, or adverse maternal or neonatal outcomes between the 2 groups. Conclusion: Labor and delivery unit policy modifications to protect pregnant patients and healthcare providers from coronavirus disease 2019 indicate that maternal and newborn length of stay in the hospital were significantly shorter after delivery without increases in the rate of adverse maternal or neonatal outcomes. In the absence of long-term adverse outcomes occurring after discharge that are tied to earlier release, our study results may support a review of our discharge protocols once the pandemic subsides to move toward safely shortening maternal and newborn lengths of stay.

Cardiovascular and pregnancy outcomes in women with coronary microvascular dysfunction: a case series.

BACKGROUND: Coronary microvascular dysfunction (CMD) is associated with adverse cardiovascular outcomes. Coronary microvascular dysfunction is observed in women of childbearing age, however, the frequency of adverse pregnancy outcomes (APO) is unknown. CASE SUMMARY: Women previously enrolled in a single centre prospective CMD registry diagnosed using invasive coronary reactivity testing were included. Among 279 women enrolled, 5 of 47 (10.6%) of childbearing age (18-44 years) subsequently became pregnant, representing a fertility rate of 36.8 births per 1000 women-years. None had history of hypertension, diabetes, or smoking. Four (80%) had a history of prior spontaneous miscarriage. Median age at CMD diagnosis was 32 years (IQR: 32-35). During pregnancy, most reported stable or improved angina, while one reported increased angina frequency, an emergency room visit and accelerated anti-anginal therapy. None experienced gestational hypertension, diabetes, pre-eclampsia, myocardial infarction, or death. Two (40%) experienced APO of preterm delivery and small neonate for gestational age. Following pregnancy, angina severity scores, and/or functional capacity decreased in three women (60%). DISCUSSION: In this first case-series of five women with CMD who became pregnant, increased angina and accelerated care during pregnancy and post-partum was not commonly observed. Fertility rates were lower than the national average, while prior spontaneous miscarriage and subsequent APO were higher. Further studies are warranted to understand and manage pregnancy in women with CMD, as well as the impact of pregnancy on longer term angina, functional capacity, and outcomes.

Vascular Function and Serum Lipids in Women with Spontaneous Preterm Delivery and Term Controls.

Background: Spontaneous preterm delivery (sPTD) is associated with a twofold increased risk of future maternal cardiovascular disease. We hypothesized that women with sPTD would demonstrate greater vascular dysfunction postpartum compared to women with term delivery. Materials and Methods: In a case-controlled, matched pilot study, we enrolled 20 women with sPTD (gestation ≤34 weeks), and 20 term control women (gestation ≥39 weeks) were matched for age (±5 years), parity, ethnicity, and route of delivery. Vascular function, serum lipids, C-reactive protein, and interleukin-6 were completed within 24-72 hours postpartum. Statistical analysis included paired t-tests based on match and mixed effects linear regression models and adjusted for potential confounders. Results: The mean age for sPTD and term controls was 33 ± 6 years and 32 ± 6 years, respectively. Women with sPTD had significantly lower augmentation index-75 (24.1% ± 16.1% vs. 39.9% ± 15.2%, p = 0.001) and central pulse pressure (29.1 ± 5.4 mmHg vs. 34.6 ± 4.7 mmHg, p = 0.004), but no difference in pulse wave velocity (5.1 ± 1.6 m/s vs. 5.6 ± 1.5 m/s, p = 0.12) compared to controls. Women with sPTD had significantly lower high-density lipoprotein cholesterol (59.4 ± 12.5 mg/dL vs. 67.6 ± 13.1 mg/dL, p = 0.035) compared to controls. Analysis of chorioamnionitis and magnesium sulfate did not alter the results. Conclusions: Women with sPTD have signs of lower smooth muscle tone in the early postpartum period compared to women with term delivery. Further research is required to understand mechanistic pathways in sPTD and future maternal cardiovascular disease risk.

Obstetric Care Consensus #9: Levels of Maternal Care: (Replaces Obstetric Care Consensus Number 2, February 2015).

Maternal mortality and severe maternal morbidity, particularly among women of color, have increased in the United States. The leading medical causes of maternal mortality include cardiovascular disease, infection, and common obstetric complications such as hemorrhage and vary by timing relative to the end of pregnancy. Although specific modifications in the clinical management of some of these conditions have been instituted, more can be done to improve the system of care for high-risk women at facility and population levels. The goal of levels of maternal care is to reduce maternal morbidity and mortality, including existing disparities, by encouraging the growth and maturation of systems for the provision of risk-appropriate care specific to maternal health needs. To standardize a complete and integrated system of perinatal regionalization and risk-appropriate maternal care, this classification system establishes levels of maternal care that pertain to basic care (level I), specialty care (level II), subspecialty care (level III), and regional perinatal health care centers (level IV). The determination of the appropriate level of care to be provided by a given facility should be guided by regional and state health care entities, national accreditation and professional organization guidelines, identified regional perinatal health care service needs, and regional resources. State and regional authorities should work together with the multiple institutions within a region, and with the input from their obstetric care providers, to determine the appropriate coordinated system of care and to implement policies that promote and support a regionalized system of care. These relationships enhance the ability of women to give birth safely in their communities while providing support for circumstances when higher level resources are needed. This document is a revision of the original 2015 Levels of Maternal Care Obstetric Care Consensus, which has been revised primarily to clarify terminology and to include more recent data based on published literature and feedback from levels of maternal care implementation.

Putting the "M" back in maternal-fetal medicine: A 5-year report card on a collaborative effort to address maternal morbidity and mortality in the United States.

The Centers for Disease Control and Prevention have demonstrated continuous increased risk for maternal mortality and severe morbidity with racial disparities among non-Hispanic black women an important contributing factor. More than 50,000 women experienced severe maternal morbidity in 2014, with a mortality rate of 18.0 per 100,000, higher than in many other developed countries. In 2012, the first "Putting the 'M' back in Maternal-Fetal Medicine" session was held at the Society for Maternal-Fetal Medicine's (SMFM) Annual Meeting. With the realization that rising risk for severe maternal morbidity and mortality required action, the "M in MFM" meeting identified the following urgent needs: (i) to enhance education and training in maternal care for maternal-fetal medicine (MFM) fellows; (ii) to improve the medical care and management of pregnant women across the country; and (iii) to address critical research gaps in maternal medicine. Since that first meeting, a broad collaborative effort has made a number of major steps forward, including the proliferation of maternal mortality review committees, advances in research, increasing educational focus on maternal critical care, and development of comprehensive clinical strategies to reduce maternal risk. Five years later, the 2017 M in MFM meeting served as a "report card" looking back at progress made but also looking forward to what needs to be done over the next 5 years, given that too many mothers still experience preventable harm and adverse outcomes.

Prospective parents' perspectives on antenatal decision making for the anticipated birth of a periviable infant.

OBJECTIVE: To examine prospective parents' perceptions of management options and outcomes in the context of threatened periviable delivery, and the values they apply in making antenatal decisions during this period. STUDY DESIGN: Qualitative analysis of 46 antenatal interviews conducted at three tertiary-care hospitals with 54 prospective parents (40 pregnant women, 14 partners) who had received counseling for threatened periviable delivery (40 cases). RESULTS: Participants most often recalled being involved in resuscitation, cerclage, and delivery mode decisions. Over half (63.0%) desired a shared decision-making role. Most (85.2%) recalled hearing about morbidity and mortality, with many reiterating terms like "brain damage", "disability", and "handicap". The potential for disability influenced decision making to variable degrees. In describing what mattered most, participant spoke of giving their child a "fighting chance"; others voiced concerns about "best interest", a "healthy baby", "pain and suffering", and religious faith. CONCLUSIONS: Our findings underscore the importance of presenting clear information on disability and eliciting the factors that parents deem most important in making decisions about periviable birth.

Timely treatment of severe maternal hypertension and reduction in severe maternal morbidity.

OBJECTIVE: To determine if timely treatment within 60 min of confirmed diagnosis of severe maternal hypertension with antihypertensive medications was associated with reduction in severe maternal morbidity. STUDY DESIGN: Medical records of women with severe hypertension (at least two severe blood pressures, systolic ≥160 mmHg and/or diastolic ≥110 mmHg, within 60 min) were accessed for timing of severe blood pressures, timing of treatment, and blood pressure response to treatment. Severe maternal morbidity was confirmed by multidisciplinary case review. We compared the incidence of severe maternal morbidity between women who received timely (within 60 min of diagnosis) vs. not-timely treatment. RESULTS: Of 465 women with severe hypertension, 29 (6.2%) experienced severe maternal morbidity. Fifty-six percent of women received timely treatment, of whom 1.9% had severe maternal morbidity, compared with 6.4% of women who did not receive timely treatment (p = 0.02). Timely treatment was associated with a 72% reduction in relative risk of severe maternal morbidity (p = 0.02). No significant difference was seen in median pre-treatment systolic pressures (p = 0.20) between the groups. CONCLUSION: Antihypertensive treatment within 60 min of confirmed diagnosis of severe hypertension was associated with reduction in severe maternal morbidity. Our findings support current recommendations to treat all women with severe hypertension with antihypertensive medications in a timely fashion.

Levels of Maternal Care Verification Pilot: Translating Guidance Into Practice.

Development of systems for perinatal regionalization and for the provision of risk-appropriate maternal care is a key strategy to decrease maternal morbidity and mortality. Regionalized systems pertaining to neonatal care are broadly implemented in many states, but networks for risk-appropriate maternal care are lacking. In response to increases in maternal morbidity and mortality over the past decade, the American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine (SMFM) developed and published the levels of maternal care guidelines in 2015. The guidelines are designed to promote collaboration among maternal facilities and health care providers with the goal that pregnant women receive care at a facility appropriate for their risk. The Centers for Disease Control and Prevention (CDC) developed the Levels of Care Assessment Tool in 2013 to assist states and jurisdictions in assessing maternal and neonatal levels of care in alignment with the national guidelines published by ACOG and SMFM and the American Academy of Pediatrics, respectively. With the goal of promoting levels of maternal care, ACOG and SMFM developed and piloted the levels of maternal care verification program. Fourteen facilities across three states (Georgia, Illinois, and Wyoming) participated in the pilot. A multidisciplinary team representing organizations with expertise in maternal risk-appropriate care performed an onsite comprehensive review of the maternal services available in each facility using the results from the CDC Levels of Care Assessment Tool as a previsit screening. A verification program that could be implemented on a local, state, or regional scale is being developed leveraging the lessons learned from the pilot.