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To compare rates of severe maternal morbidity (SMM) for pregnant patients with a cardiac diagnosis classified by the modified World Health Organization (mWHO) classification to those without a cardiac diagnosis.This retrospective study using the 2015-2019 Nationwide Readmissions Database identified hospitalizations, comorbidities, and outcomes using diagnosis and procedure codes. The primary exposure was cardiac diagnosis, classified into low-risk (mWHO class I and II) and moderate-to-high-risk (mWHO class II/III, III, or IV). The primary outcome was SMM or death during the delivery hospitalization; secondary outcomes included cardiac-specific SMM during delivery hospitalizations and readmissions after the delivery hospitalization.A weighted national estimate of 14,995,122 delivery admissions was identified, including 46,541 (0.31%) with mWHO I-II diagnoses and 37,330 (0.25%) with mWHO II/III-IV diagnoses. Patients with mWHO II/III-IV diagnoses experienced SMM at the highest rates (22.8% vs 1.6% for no diagnosis; with adjusted relative risk (aRR) of 5.67 [95% CI: 5.36-6.00]). The risk of death was also highest for patients with mWHO II/III-IV diagnoses (0.3% vs0.1% for no diagnosis; aRR 18.07 [95% CI: 12.25-26.66]). Elevated risk of SMM and death persisted to 11 months postpartum for those patients with mWHO II/III-IV diagnoses.In this nationwide database, SMM is highest among individuals with moderate-to-severe cardiac disease based on mWHO classification. This risk persists in the year postpartum. These results can be used to enhance pregnancy counseling.

Background The purpose of this study was to estimate prevalence of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among patients admitted to obstetric inpatient units throughout the United States as detected by universal screening. We sought to describe the relationship between obstetric inpatient asymptomatic infection rates and publicly available surrounding community infection rates. Methods A cross-sectional study in which medical centers reported rates of positive SARS-CoV-2 testing in asymptomatic pregnant and immediate postpartum patients over a 1–3-month time span in 2020. Publicly reported SARS-CoV-2 case rates from the relevant county and state for each center were collected from the COVID Act Now dashboard and the COVID Tracking Project for correlation analysis. Results Data were collected from 9 health centers, encompassing 18 hospitals. Participating health centers were located in Alabama, California, Illinois, Louisiana, New Jersey, North Carolina, Pennsylvania, Rhode Island, Utah, and Washington State. Each hospital had an active policy for universal SARS-CoV-2 testing on obstetric inpatient units. A total of 10 147 SARS-CoV-2 tests were administered, of which 124 were positive (1.2%). Positivity rates varied by site, ranging from 0–3.2%. While SARS-CoV-2 infection rates were lower in asymptomatic obstetric inpatient groups than the surrounding communities, there was a positive correlation between positivity rates in obstetric inpatient units and their surrounding county (P=.003, r=.782) and state (P=.007, r=.708). Conclusions Given the correlation between community and obstetric inpatient rates, the necessity of SARS-CoV-2–related healthcare resource utilization in obstetric inpatient units may be best informed by surrounding community infection rates., There was a significant positive correlation between SARS-CoV-2 positivity rates in obstetric inpatient units and their surrounding county and state. Healthcare resource utilization related to SARS-CoV-2 testing in obstetric inpatient units may be best informed by surrounding community infection rates.

Objective The use of extracorporeal membrane oxygenation (ECMO) therapy has increased in the adult population. Studies from the H1N1 influenza pandemic suggest that ECMO deployment in pregnancy is associated with favorable outcomes. With increasing numbers of pregnant women affected by COVID-19 (coronavirus disease 2019) and potentially requiring this life-saving therapy, we sought to compare comorbidities, costs, and outcomes between pregnancy- and nonpregnancy-associated ECMO therapy among reproductive-aged female patients. Study Design We used the 2013 to 2019 National Readmissions Database. Diagnosis and procedural coding were used to identify ECMO deployment, potential indications, comorbid conditions, and pregnancy outcomes. The primary outcome was in-hospital mortality during the patient's initial ECMO stay. Secondary outcomes included length of stay and hospital charges/costs, occurrence of thromboembolic or bleeding complications during ECMO hospitalization, and mortality and readmissions up to 330 days following ECMO stay. Univariate and multivariate regression models were used to model the associations between pregnancy status and outcomes. Results The sample included 324 pregnancy-associated hospitalizations and 3,805 nonpregnancy-associated hospitalizations, corresponding to national estimates of 665 and 7,653 over the study period, respectively. Pregnancy-associated ECMO had lower incidence of in-hospital death (adjusted odds ratio [aOR]: 0.56, 95% confidence interval [CI]: 0.41–0.75) and bleeding complications (aOR: 0.67, 95% CI: 0.49–0.93). Length of stay was significantly shorter (adjusted rate ratio (aRR): 0.86, 95% CI: 0.77–0.96) and total hospital costs were less (aRR: 0.83, 95% CI: 0.75–0.93). Differences in the incidence of thromboembolic events (aOR: 1.04, 95% CI: 0.78–1.38) were not statistically significant. Conclusion Pregnancy-associated ECMO therapy had lower incidence of in-hospital death, bleeding complications, total inpatient cost, and length of stay when compared with nonpregnancy-associated ECMO therapy without increased thromboembolic complications. Pregnancy-associated ECMO therapy should be offered to eligible patients. Key Points

Previous studies of obstructive sleep apnea (OSA) risk in gravidas with chronic hypertension (cHTN) did not control for obesity as a risk factor for OSA. We therefore performed this study to evaluate whether OSA is more prevalent among gravidas with cHTN compared to normotensive gravidas matched for body mass index (BMI) and gestational age (primary outcome). We also assessed whether OSA is more severe when comorbid with cHTN in pregnancy (secondary outcome).This was a single-center, prospective cohort study. Adult gravidas at 10-20 weeks of gestation, with and without cHTN, were enrolled and BMI matched. All subjects answered OSA screening questionnaires and underwent a home sleep test when they were between 10 and 20 weeks of gestation. Pregnancy outcomes were followed for all subjects. We performed univariable and multivariable logistic regression to model the relationship between cHTN status and OSA.A total of 100 pregnant subjects (50 with cHTN and 50 normotensive) completed a home sleep test of 2 hours or more. There were no differences in demographic variables between the 2 groups, except that gravidas with cHTN were significantly older than normotensive subjects (mean ± standard deviation [SD] 34 ± 4 vs 30 ± 6 years; P.001). OSA was more prevalent (64% vs 38%; P = .009; odds ratio [95% confidence interval (CI)] 2.90 [1.30-6.65]; P = .01) and more severe in gravidas with cHTN (moderate or severe OSA 59% vs 21%; P = .009). After controlling for age, we found no overall association between cHTN on OSA risk (adjusted odds ratio [95% CI] 2.22 [0.92-5.40]; P = .076). However, among gravidas older than 25 years of age, cHTN was associated with higher odds of OSA (adjusted odds ratio [95% CI], 2.64 [1.06-6.71], P = .038).cHTN and age are important risk factors for OSA in gravidas. Gravidas with cHTN should be screened for OSA in early pregnancy. Future studies may validate screening tools that include cHTN and age, and investigate the role of OSA therapy in blood pressure control.

Objective This study compares the number of units of red blood cells (RBCs) transfused in patients with placenta accreta spectrum (PAS) treated with or without a multidisciplinary algorithm that includes placental uterine arterial embolization (P-UAE) and selective use of either immediate or delayed hysterectomy. Study Design This is a retrospective study of deliveries conducted at a tertiary care hospital from 2001 to 2018 with pathology-confirmed PAS. Those with previable pregnancies or microinvasive histology were excluded. To improve the equity of comparison, analyses were made separately among scheduled and unscheduled cases, therefore patients were assigned to one of four cohorts as follows: (1) scheduled/per-algorithm, (2) scheduled/off-algorithm, (3) unscheduled/per-algorithm, or (4) unscheduled/off-algorithm. Primary outcomes included RBCs transfused and estimated blood loss (EBL). Secondary outcomes included perioperative complications and disposition. Results Overall, 95 patients were identified, with 87 patients meeting inclusion criteria: 36 treated per-algorithm (30 scheduled and 6 unscheduled) and 51 off-algorithm patients (24 scheduled and 27 unscheduled). Among scheduled deliveries, 9 (30.0%) patients treated per-algorithm received RBCs compared with 20 (83.3%) patients treated off-algorithm (p Conclusion A multidisciplinary algorithm including P-UAE and selective use of delayed hysterectomy is associated with a lower rate of blood transfusion in scheduled but not unscheduled cases. Key Points

Background Broad ligament hematomas are rare in the setting of vaginal delivery. When they do occur, patients typically present with acute hemodynamic instability. No cases of infected broad ligament hematomas have been reported. Case A 22-year-old G2 P1011 status post vaginal delivery complicated by chorioamnionitis and pre-eclampsia presented 5 days postpartum with subjective complaints of fever, vomiting, and increased vaginal bleeding. She was treated with antibiotics and uterine evacuation was planned for presumed retained products. After dilation and curettage, the patient was transferred to our facility, as her clinical status did not improve, and was later found to have an infected broad ligament hematoma requiring hysterectomy. Conclusion Though uncommon, broad ligament hematomas should be considered in postpartum women presenting with anemia and vaginal bleeding, even without hemodynamic instability. Recent intrauterine infections may predispose to hematoma infection.

Objective: To evaluate opioid consumption among parturients with varying degrees of perineal lacerations.Methods: This was a retrospective analysis of women who delivered vaginally at our instituti...

OBJECTIVE Obstetric studies often report neonatal morbidity as a composite score. Composite scores can simplify data analysis when multiple outcomes of interest are present and allows researchers to conduct smaller, more manageable trials. The Hassan scale is a neonatal morbidity composite scale that assigns high scores to infants with multiple morbidities and low scores to infants without or with single morbidities. The objective of this study was to validate the association between scores on the Hassan scale and neonatal intensive care unit (NICU) length of stay STUDY DESIGN: We conducted a cohort study of all infants born between 22 and 366/7 weeks' gestation and cared for within 419 neonatal units in the Pediatrix Medical Group between 1997 and 2018. Each infant was assigned a Hassan's score based on the number of neonatal morbidity events that occurred during the delivery hospitalization. The association between Hassan's scores and neonatal length of stay was evaluated using linear regression. Multivariable models were constructed to determine if the Hassan score was independently associated with neonatal length of stay. RESULTS There were 760,037 infants included. The median (interquartile range [IQR]) gestational age of delivery was 34 (31, 35) weeks and the median (IQR) birth weight at delivery was 2,000 (1,503, 2,430) g. The median length of stay for infants discharged home was 17 (10-33) days. A Hassan's score was able to be assigned to 699,206 (92%) patients. Neonatal morbidities included in the Hassan scale were more common among infants born earlier in gestation. On adjusted analysis, the Hassan scale was found to be independently associated with neonatal length of stay (p

BACKGROUND There has been a 291% relative increase in congenital syphilis (CS) cases in the United States from 2015 to 2019. Although the majority of affected fetuses/infants are stillborn or are asymptomatic, a subset is born with severe clinical illness. We describe a series of severe CS cases in the neonatal intensive care unit. METHODS Retrospective review of infants with CS, admitted to the Duke Intensive Care Nursery from June 2016 to February 2020. We recorded birthweight, gestational age, medications, procedures, diagnoses, laboratory data and outcomes. Severe symptoms included: birth depression, hypoxic ischemic encephalopathy (HIE), disseminated intravascular coagulopathy and/or persistent pulmonary hypertension (PPHN). RESULTS Seven infants with CS were identified and 5 with severe presentations were included. Median gestational age was 35.1 weeks (range: 29-37 weeks, median: 35 weeks). All infants required intubation at birth, 2 required chest compressions and epinephrine in the delivery room. One had hydrops fetalis and died in the delivery room. All 4 surviving infants had HIE, severe PPHN, hepatitis and seizures. All infants had a positive rapid plasma reagin, and were treated with penicillin G. Maternal rapid plasma reagin was pending for 3 of 5 infants at delivery, and later returned positive; 2 were positive during pregnancy but not treated. Other infectious work-up was negative. Three infants survived to discharge. CONCLUSION CS can be associated with HIE, PPHN and disseminated intravascular coagulopathy in affected infants. Clinicians should have a high index of suspicion and include CS in their differential diagnoses. This study also highlights the importance of adequate treatment of identified cases and screening during the third trimester and at delivery.

Objective To examine the association between perioperative Beta (β))-lactam versus non-β-lactam antibiotics and cesarean delivery surgical site infection (SSI). Study Design Retrospective cohort of women undergoing cesarean delivery from January 1 to December 31, 2014. All women undergoing cesarean after 34 weeks with a postpartum visit were included. Prevalence of SSI was compared between women receiving β-lactam versus non-β-lactam antibiotics. Bivariate analyses were performed using Pearson's Chi-square, Fisher's exact, or Wilcoxon's rank-sum tests. Logistic regression models were fit controlling for possible confounders. Results Of the 929 women included, 826 (89%) received β-lactam prophylaxis and 103 (11%) received a non-β-lactam. Among the 893 women who reported a non-type I (low risk) allergy, 819 (92%) received β-lactam prophylaxis. SSI occurred in 7% of women who received β-lactam antibiotics versus 15% of women who received a non-β-lactam (p = 0.004). β-Lactam prophylaxis was associated with lower odds of SSI compared with non-β-lactam antibiotics (odds ratio [OR] = 0.43; 95% confidence interval [CI] = 0.22–0.83; p = 0.01) after controlling for chorioamnionitis in labor, postlabor cesarean, endometritis, tobacco use, and body mass index (BMI). Conclusion β-Lactam perioperative prophylaxis is associated with lower odds of a cesarean delivery surgical site infection compared with non-β-lactam antibiotics.

To describe the anesthetic management and outcomes of placenta accreta spectrum (PAS) cases at our institution over a 19 year period and to compare outcomes associated with the lumbar combined spinal epidural (CSE) technique versus the double catheter technique (lumbar CSE with thoracic epidural catheter).Retrospective cohort study.Labor and delivery unit at a tertiary care center.113 female patients who had histologically confirmed PAS on the final pathology report after cesarean delivery or cesarean hysterectomy.Neuraxial anesthesia, including CSE and the double catheter technique, and general anesthesia for PAS cases (including scheduled and unscheduled cases and those known or unknown as PAS preoperatively).The medical records were reviewed for demographic information, intraoperative management, anesthetic technique, and outcomes. We describe anesthetic management and outcomes of cases classified as scheduled vs. unscheduled and known vs. unknown PAS. We also compare the CSE and double catheter techniques with the primary outcome being conversion to general anesthesia (GA).We included 113 cases: 60 (53.1%) scheduled/known cases, 12 (10.6%), scheduled/unknown cases, 22 (19.5%) unscheduled/known, and 19 (16.8%) unscheduled/unknown cases. All scheduled cases except two were started with a neuraxial technique. General anesthesia (GA) was used to start 18/41 (44%) of unscheduled cases. The double catheter technique (n = 35) was associated with a lower GA conversion rate (5.7% vs. 29.7%, P = 0.036) compared to the CSE technique (n = 37).Neuraxial anesthesia is the most commonly used technique for PAS cases in our practice. The double catheter technique was associated with lower GA conversion rates compared to the CSE technique in our cohort.

Background: The purpose of this study was to estimate prevalence of asymptomatic SARS-CoV-2 infection among patients admitted to obstetric inpatient units throughout the United States as detected by universal screening. We sought to describe the relationship between obstetric inpatient asymptomatic infection rates and publicly available surrounding community infection rates. Methods: This was a cross-sectional study in which medical centers reported rates of positive SARS-CoV-2 testing in asymptomatic pregnant and immediate postpartum patients over a 1-3 month time span in 2020. Publicly reported SARS-CoV-2 case rates from the relevant county and state for each center were collected from the COVID Act Now dashboard and the COVID Tracking Project for correlation analysis. Findings: Data were collected from nine health centers, encompassing 18 hospitals. Participating health centers were located in Alabama, California, Illinois, Louisiana, New Jersey, North Carolina, Pennsylvania, Rhode Island, Utah, and Washington State. Each hospital had an active policy for universal SARS-CoV-2 testing on obstetric inpatient unit. A total of 10,147 SARS-CoV-2 tests were administered, of which 124 were positive (1·2%). Positivity rates varied by site, ranging from 0-3·2%. While SARS-CoV-2 infection rates were lower in asymptomatic obstetric inpatient groups than the surrounding communities, there was a positive correlation between positivity rates in obstetric inpatient units and their surrounding county (p=·003, r=·782) and state (p=·007, r=·708). Interpretation: Given the correlation between community and obstetric inpatient rates, the necessity of SARS-CoV-2 related healthcare resource utilization in obstetric inpatient units may be best-informed by surrounding community infection rates. Funding Information: Internal funding was used. Declaration of Interests: None to declare. Ethics Approval Statement: The study was IRB approved or determined exempt at each center.

Objective: To compare the number of units of red blood cells (RBCs) transfused in patients with placenta accreta spectrum (PAS) treated with or without a multidisciplinary algorithm including placental uterine arterial embolisation (P-UAE) and a selective use of delayed hysterectomy. Design: Retrospective review Setting: Tertiary care hospital, United States, 2001-2018 Population: Women with histologically-confirmed PAS delivered after 24 weeks gestation Methods: Comparison of transfusion outcomes among PAS cases managed with versus without a multidisciplinary algorithm. To improve the equity of comparison, analyses were made separately among scheduled and unscheduled cases. Subjects were assigned to one of four cohorts: scheduled/per-algorithm, scheduled/off-algorithm, unscheduled/per-algorithm, or unscheduled/off-algorithm. P values were adjusted for multiple testing. Main outcome measures: RBCs transfused and estimated blood loss (EBL). Secondary outcomes included peri-operative complications and intensive-care unit admissions. Results: 87 subjects were identified: 36 treated per-algorithm (30 scheduled, 6 unscheduled), 51 off-algorithm (24 scheduled, 27 unscheduled). Among scheduled deliveries, 9 (30.0%) subjects treated per-algorithm received RBCs, compared to 20 (83.3%) subjects treated off-algorithm (p

A decrease in skeletal muscle strength and functional exercise capacity due to aging, frailty, and muscle wasting poses major unmet clinical needs. These conditions are associated with numerous adverse clinical outcomes including falls, fractures, and increased hospitalization. Clenbuterol, a β(2)-adrenergic receptor (β(2)AR) agonist enhances skeletal muscle strength and hypertrophy; however, its clinical utility is limited by side effects such as cardiac arrhythmias mediated by G protein signaling. We recently reported that clenbuterol-induced increases in contractility and skeletal muscle hypertrophy were lost in β-arrestin 1 knockout mice, implying that arrestins, multifunctional adapter and signaling proteins, play a vital role in mediating the skeletal muscle effects of β(2)AR agonists. Carvedilol, classically defined as a βAR antagonist, is widely used for the treatment of chronic systolic heart failure and hypertension, and has been demonstrated to function as a β-arrestin-biased ligand for the β(2)AR, stimulating β-arrestin-dependent but not G protein-dependent signaling. In this study, we investigated whether treatment with carvedilol could enhance skeletal muscle strength via β-arrestin-dependent pathways. In a murine model, we demonstrate chronic treatment with carvedilol, but not other β-blockers, indeed enhances contractile force in skeletal muscle and this is mediated by β-arrestin 1. Interestingly, carvedilol enhanced skeletal muscle contractility despite a lack of effect on skeletal muscle hypertrophy. Our findings suggest a potential unique clinical role of carvedilol to stimulate skeletal muscle contractility while avoiding the adverse effects with βAR agonists. This distinctive signaling profile could present an innovative approach to treating sarcopenia, frailty, and secondary muscle wasting.

Anemia is common in pregnant women and is associated with increased morbidity for the mother and the fetus, including increased risk of allogeneic blood transfusion. Iron deficiency is the most common etiology for anemia during pregnancy. Oral iron therapy remains the standard treatment but is often poorly tolerated due to its gastrointestinal side effects. Intravenous iron has been shown to be a safe and effective way to treat iron deficiency anemia but may be challenging to do in the outpatient setting given the need for an indwelling venous catheter and a small risk of infusion reactions. To improve outcomes associated with anemia, we launched a program to refer and treat obstetric patients with iron deficiency anemia for outpatient intravenous iron therapy through our preoperative anemia clinic. Here, we describe the process and successes of our program, including the clinical outcomes (change in hemoglobin and transfusion rates) from the first 2 years of the program.

STUDY QUESTION Do maternal serum levels of progesterone metabolites early in pregnancy correspond to an increased risk for very preterm delivery prior to 32 weeks? SUMMARY ANSWER Maternal serum levels of 11-deoxycorticosterone (DOC) measured during the late first trimester or early second trimester correlate with an increased risk for preterm delivery prior to 32 weeks, and the correlation becomes stronger when the ratio of DOC to 16-alpha-hydroxyprogesterone was measured. WHAT IS KNOWN ALREADY Progesterone is a pro-gestational steroid hormone that has been shown to decrease the risk of preterm birth in some pregnant women. Progesterone is metabolized by the body into various metabolites including members of the mineralocorticoid and glucocorticoid families. Our group has previously demonstrated that some progesterone metabolites enhance myometrial contractility in an ex vivo system, while others result in myometrial relaxation. The current exploratory study was designed to determine if pre-specified metabolites of progesterone measured early in pregnancy were associated with a woman’s risk for delivery prior to 32 weeks, which is referred to as a very preterm delivery. STUDY DESIGN, SIZE, DURATION The Building Blocks of Pregnancy Biobank (BBPB) is a biorepository at Indiana University (IU) that follows women prospectively through their pregnancy. A variety of biospecimens are collected at various time points during a woman’s pregnancy. Women participating in the IU BBPB who were enrolled after 8 weeks’ gestation with pregnancy outcome data were eligible for participation. PARTICIPANTS/MATERIALS, SETTING, METHODS Women delivering prior to 37 weeks (preterm) and at or after 37 weeks (term) who had blood samples collected during the late first trimester/early second trimester and/or during the early third trimester were identified. These samples were then processed for mass spectroscopy, and the amount of progesterone and progesterone metabolites in the samples were measured. Mean values of each measured steroid metabolite were calculated and compared among women delivering at less than 32 weeks, less than 37 weeks and greater than or equal to 37 weeks. Receiver operating characteristic (ROC) curves were constructed and threshold levels determined for each compound to identify a level above or below which best predicted a woman’s risk for delivery prior to 32 and prior to 37 weeks. Mann–Whitney U nonparametric testing with Holm–Bonferroni correction for multiple comparisons was utilized to identify steroid ratios that could differentiate women delivering spontaneously at less than 32 weeks from all other pregnancies. MAIN RESULTS AND THE ROLE OF CHANCE Steroid hormone levels and pregnancy outcome data were available for 93 women; 28 delivering prior to 32 weeks, 40 delivering between 32 0/7 and 36 6/7 weeks and 25 delivering at or greater than 37 weeks: the mean gestational age at delivery within the three groups was 27.0, 34.4 and 38.8 weeks, respectively. Among women delivering spontaneously at less than 37 weeks, maternal 11-deoxycorticosterone (DOC) levels drawn in the late first trimester/early second trimester were significantly associated with spontaneous preterm delivery prior to 32 weeks; a threshold level of 47.5 pg/ml had 78% sensitivity, 73% specificity and an AUC of 0.77 (P = 0.044). When DOC levels were analyzed as a ratio with other measured steroid hormones, the ratio of DOC to 16-alpha-hydroxyprogesterone among women delivering spontaneously prior to 37 weeks was able to significantly discriminate women delivering prior to 32 weeks from those delivering at or greater than 32 weeks, with a threshold value of 0.2 with 89% sensitivity, 91% specificity and an AUC of 0.92 (P = 0.002). When the entire study cohort population was considered, including women delivering at term and women having an iatrogenic preterm delivery, the ratio of DOC to 16-alpha-hydroxyprogesterone was able to discriminate women delivering spontaneously prior to 32 weeks from the rest of the population at a threshold of 0.18 and 89% sensitivity, 59% specificity and an AUC of 0.81 (P = 0.003). LIMITATIONS, REASONS FOR CAUTION This is a discovery study, and the findings have not been validated on an independent cohort. To mitigate issues with multiple comparisons, we limited our study to pre-specified metabolites that are most representative of the major metabolic pathways for progesterone, and adjustments for multiple comparisons were made. WIDER IMPLICATIONS OF THE FINDINGS Spontaneous preterm birth is increasingly being recognized to represent a common end pathway for a number of different disease phenotypes that include infection, inflammation, premature rupture of the membranes, uterine over distension, cervical insufficiency, placental dysfunction and genetic predisposition. In addition to these phenotypes, longitudinal changes in the maternal–fetal hypothalamic–pituitary–adrenal (HPA) axis also likely contribute to a significant proportion of the disease burden of spontaneous preterm birth. Here, we demonstrate that differential production of steroid metabolites is associated with very early preterm birth. The identified biomarkers may hint at a pathophysiologic mechanism and changes in the maternal–fetal dyad that result in preterm delivery. The early identification of abnormal changes in HPA axis metabolites may allow for targeted interventions that reverse the aberrant steroid metabolic profile to a more favorable one, thereby decreasing the risk for early delivery. Further research is therefore required to validate and extend the results presented here. STUDY FUNDING/COMPETING INTEREST(S) Funding for this study was provided from the Office of the Vice Chancellor for Research at IUPUI, ‘Funding Opportunities for Research Commercialization and Economic Success (FORCES) grant’. Both A.S.P. and C.A.G. are affiliated with Nixxi, a biotech startup. The remaining authors report no conflict of interest. TRIAL REGISTRATION NUMBER Not applicable.

OBJECTIVE: To predict a woman’s risk of postpartum hemorrhage at labor admission using machine learning and statistical models. METHODS: Predictive models were constructed and compared using data from 10 of 12 sites in the U.S. Consortium for Safe Labor Study (2002–2008) that consistently reported estimated blood loss at delivery. The outcome was postpartum hemorrhage, defined as an estimated blood loss ≥1,000 mL. Fifty-five candidate risk factors routinely available on labor admission were considered. We used logistic regression with and without lasso regularization (lasso regression) as the two statistical models and random forest and Extreme Gradient Boosting as the two machine learning models to predict postpartum hemorrhage. Model performance was measured by C statistics (i.e., concordance index), calibration, and decision curves. Models were constructed from the first phase (2002–2006) and externally validated (i.e., temporally) in the second phase (2007–2008). Further validation was performed combining both temporal and site-specific validation. RESULTS: Of the 152,279 assessed births, 7,279 (4.8%, 95% CI 4.7 to 4.9) had a postpartum hemorrhage. All models had good to excellent discrimination. The Extreme Gradient Boosting model had the best discriminative ability to predict postpartum hemorrhage (C statistic: 0.93; 95% CI: 0.92 to 0.93) followed by random forest (C statistic: 0.92; 95% CI: 0.91 to 0.92). The lasso regression model (C statistic: 0.87; 95% CI: 0.86 to 0.88) and logistic regression (C statistic: 0.87; 95% CI: 0.86 to 0.87) had lower but good discriminative ability. The above results held with validation across both time and sites. Decision curve analysis demonstrated that while all models provided superior net benefit when clinical decision thresholds were between 0 to 80% predicted risk, the Extreme Gradient Boosting model provided the greatest net benefit. CONCLUSION: Postpartum hemorrhage on labor admission can be predicted with excellent discriminative ability using machine learning and statistical models. Further clinical application is needed, which may assist health care providers to be prepared and triage at risk women.

Objective To assess the costs, complication rates, and harm-benefit tradeoffs of induction of labor (IOL) compared to scheduled cesarean delivery (CD) in women with class III obesity. Study Design We conducted a cost analysis of IOL versus scheduled CD in nulliparous morbidly obese women. Primary outcomes were surgical site infection (SSI), chorioamnionitis, venous thromboembolism, blood transfusion, and readmission. Model outcomes were mean cost of each strategy, cost per complication avoided, and complication tradeoffs. We assessed the costs, complication rates, and harm-benefit tradeoffs of IOL compared with scheduled CD in women with class III obesity. Results A total of 110 patients underwent scheduled CD and 114 underwent IOL, of whom 61 (54%) delivered via cesarean. The group delivering vaginally experienced fewer complications. SSI occurred in 0% in the vaginal delivery group, 13% following scheduled cesarean, and 16% following induction then cesarean. In the decision model, the mean cost of induction was $13,349 compared with $14,575 for scheduled CD. Scheduled CD costs $9,699 per case of chorioamnionitis avoided, resulted in 18 cases of chorioamnionitis avoided per additional SSI and 3 cases of chorioamnionitis avoided per additional hospital readmission. In sensitivity analysis, IOL is cost saving compared with scheduled CD unless the cesarean rate following induction exceeds 70%. Conclusion In morbidly obese women, induction of labor remains cost-saving until the rate of cesarean following induction exceeds 70%.

Objective We examined the effects of magnesium sulfate on non-neurologic neonatal outcomes with respect to cord blood magnesium level. Study Design We conducted a secondary analysis of the Maternal-Fetal Medicine Units Beneficial Effects of Antenatal Magnesium (MFMU BEAM) trial comparing the upper and lower quintiles of cord blood magnesium level. Outcomes included cerebral palsy (CP), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), and assessments of mental and motor disability. Logistic regression was used to estimate adjusted odds ratios (aORs) of each outcome, controlling for gestational age (GA), birth weight, and treatment group (TG). Results A total of 1,254 women of the 2,444 included in the BEAM trial had cord blood magnesium levels recorded. GA and birth weight were lower and TG was more common in the upper quintile cohort (p Conclusion Higher cord blood magnesium levels do not appear to have adverse non-neurologic effects on the neonate and may demonstrate improvement in neurologic outcomes.

Objective The objective of this study is to evaluate the effect of noncephalic presentation on neonatal outcomes in preterm delivery. Study Design In this study a secondary analysis of the BEAM trial was performed. It included women with singleton, liveborn, and nonanomalous fetuses. Neonatal outcomes were compared in noncephalic versus cephalic presentation. Adjusted odds ratios and 95% confidence intervals were calculated for each outcome with logistic regression while controlling for possible confounders. A stratified analysis by mode of delivery was also performed in this study. Results A total of 458 noncephalic deliveries were compared with 1,485 cephalic deliveries. In multivariate analysis, noncephalic presentation was associated with increased risk of death in the neonatal intensive care unit (NICU) or death at Conclusion After controlling for possible confounders, neonates who are noncephalic at delivery have higher risk for death

Contraction is a central feature for skeletal, cardiac and smooth muscle; this unique feature is largely dependent on calcium (Ca(2+)) signaling and therefore maintenance of internal Ca(2+) stores. Stromal interaction molecule 1 (STIM1) is a single-pass transmembrane protein that functions as a Ca(2+) sensor for the activation store-operated calcium channels (SOCCs) on the plasma membrane in response to depleted internal sarco(endo)plasmic (S/ER) reticulum Ca(2+) stores. STIM1 was initially characterized in nonexcitable cells; however, evidence from both animal models and human mutations suggests a role for STIM1 in modulating Ca(2+) homeostasis in excitable tissues as well. STIM1-dependent SOCE is particularly important in tissues undergoing sustained contraction, leading us to believe STIM1 may play a role in smooth muscle contraction. To date, the role of STIM1 in smooth muscle is unknown. In this review, we provide a brief overview of the role of STIM1-dependent SOCE in striated muscle and build off that knowledge to investigate whether STIM1 contributes to smooth muscle contractility. We conclude by discussing the translational implications of targeting STIM1 in the treatment of smooth muscle disorders.

BACKGROUND: Postpartum haemorrhage (PPH) is still a leading cause of maternal morbidity in the US. We aimed to reassess national trends in severe and non-severe PPH using recent data. MATERIAL AND METHODS: We performed a cross-sectional study using the 2001–2012 Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project. Delivery-related hospitalisations with PPH were identified using the International Classification of Diseases (9th revision). Rates were calculated per 1,000 delivery hospitalisations. All statistical analyses accounted for the complex sampling design of the data source. RESULTS: Rates of non-severe PPH did not change significantly from 2001–2002 to 2011–2012 (25.5 and 24.2 per 1,000; p=0.058). The rates of PPH requiring blood transfusions for caesarean deliveries more than doubled in this time period from 2.0 to 4.8 (p

Objective Both systemic lupus erythematosus (SLE; lupus) and pregnancy individually have significant racial disparities, with black women experiencing higher rates of complications, yet no large studies have focused on the impact of race/ethnicity on pregnancy outcomes among women with lupus. Methods Using the Nationwide Inpatient Sample (NIS) for 2008-2010, pregnancy delivery discharges were identified and pregnancy outcomes were compared for women with lupus by maternal race/ethnicity. Adjusted odds ratios were used to compare pregnancy outcomes between black and white or Hispanic and white women with lupus. Results In this period, the NIS included 13,553 deliveries with lupus and 12,510,565 deliveries without lupus. Compared to white women with lupus, black and Hispanic women had higher rates of chronic hypertension, chronic renal failure, pneumonia, and acute renal failure. There was a high degree of pregnancy complication in all women with lupus, but especially in black and Hispanic women, with more than 40% cesarean-section delivery; preterm labor in 14.3% of white, 24.7% of black (odds ratio [OR] 1.97), and 20.6% of Hispanic (OR 1.56) deliveries; and preeclampsia and gestational hypertension in almost 20% of black and Hispanic pregnancies. After adjustment for predictors of pregnancy outcomes and racial differences in nonlupus pregnancy, black and Hispanic women with lupus had higher than expected rates of preeclampsia, preterm labor, and fetal growth restriction. Conclusion Black and Hispanic women with lupus have disproportionately poor pregnancy outcomes. This study suggests that identifying the key causes of these differences and targeting interventions to the women of greatest need is an essential next step.

IMPORTANCE: Reducing cesarean delivery rates in the US is an important public health goal; despite evidence of the safety of vaginal birth after cesarean delivery, most women have scheduled repeat cesarean deliveries. A decision support tool could help increase trial-of-labor rates. OBJECTIVE: To analyze the effect of a patient-centered decision support tool on rates of trial of labor and vaginal birth after cesarean delivery and decision quality. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, randomized, parallel-group clinical trial conducted in Boston, Chicago, and the San Francisco Bay area. A total of 1485 English- or Spanish-speaking women with 1 prior cesarean delivery and no contraindication to trial of labor were enrolled between January 2016 and January 2019; follow-up was completed in June 2019. INTERVENTIONS: Participants were randomized to use a tablet-based decision support tool prior to 25 weeks’ gestation (n=742) or to receive usual care (without the tool) (n=743). MAIN OUTCOMES AND MEASURES: The primary outcome was trial of labor; vaginal birth was the main secondary outcome. Other secondary outcomes focused on maternal and neonatal outcomes and decision quality. RESULTS: Among 1485 patients (mean age, 34.0 [SD, 4.5] years), 1470 (99.0%) completed the trial (n = 735 in both randomization groups) and were included in the analysis. Trial-of-labor rates did not differ significantly between intervention and control groups (43.3% vs 46.2%, respectively; adjusted absolute risk difference, –2.78% [95% CI, –7.80% to 2.25%]; adjusted relative risk, 0.94 [95% CI, 0.84-1.05]). There were no statistically significant differences in vaginal birth rates (31.8% in both groups; adjusted absolute risk difference, –0.04% [95% CI, –4.80% to 4.71%]; adjusted relative risk, 1.00 [95% CI, 0.86-1.16]) or in any of the other 6 clinical maternal and neonatal secondary outcomes. There also were no significant differences between the intervention and control groups in the 5 decision quality measures (eg, mean decisional conflict scores were 17.2 and 17.5, respectively; adjusted mean difference, –0.38 [95% CI, –1.81 to 1.05]; scores >25 are considered clinically important). CONCLUSIONS AND RELEVANCE: Among women with 1 previous cesarean delivery, use of a decision support tool compared with usual care did not significantly change the rate of trial of labor. Further research may be needed to assess the efficacy of this tool in other clinical settings or when implemented at other times in pregnancy.

Preterm delivery represents an important cause of infant morbidity and mortality. Various tocolytics have been studied with the objective of stopping preterm labor, increasing gestational age at delivery, and preventing complications related to preterm birth.This review aims to summarize the major classes of tocolytics and review the evidence regarding use of each.A PubMed search of the following terms was performed to gather relevant data: "tocolytic," "preterm labor," "preterm delivery," "PPROM," "magnesium," "indomethacin," "nifedipine," and "betamimetics."The benefits and risks of nonsteroid anti-inflammatory drugs, calcium channel blockers, magnesium, and betamimetics are reviewed. Calcium channel blockers afford superior outcomes in terms of prolonging gestation and decreasing neonatal morbidity and mortality with the fewest adverse effects.Tocolytics, particularly calcium channel blockers, may provide benefit to pregnant women and their infants. Their use should be tailored to the particular clinical circumstances of the patient and used in conjunction with other management strategies (

There is increased interest in using high throughput in vitro assays to characterize human population variability in response to toxicants and drugs. Utilizing primary human endothelial colony-forming cells (ECFCs) isolated from blood would be highly useful for this purpose because these cells are involved in neonatal and adult vasculogenesis. We characterized the cytotoxicity of four known toxic chemicals (NaAsO2, CdCl2, tributyltin [TBT], and menadione) and their four relatively nontoxic counterparts (Na2HAsO4, ZnCl2, SnCl2, and phytonadione, respectively) in eight ECFC clones representing four neonatal donors (2 male and 2 female donors, 2 clones per donor). ECFCs were exposed to 9 concentrations of each chemical in duplicate; cell viability was evaluated 48 h later using the fluorescent vital dye fluorescent dye 5-Carboxyfluorescein Diacetate (CFDA), yielding concentration-effect curves from each experiment. Technical (day-to-day) variability of the assay, assessed from three independent experiments, was low: p-values for the differences of results were 0.74 and 0.64 for the comparison of day 2 vs. day 1 and day 3 vs. day 1, respectively. The statistical analysis used to compare the entire concentration-effect curves has revealed significant differences in levels of cytotoxicity induced by the toxic and relatively nontoxic chemical counterparts, demonstrating that donor-specific ECFCs can clearly differentiate between these two groups of chemicals. Partitioning of the total variance in the nested design assessed the contributions of between-clone and between-donor variability for different levels of cytotoxicity. Individual ECFC clones demonstrated highly reproducible responses to the chemicals. The most toxic chemical was TBT, followed by NaAsO2, CdCl2, and Menadione. Nontoxic counterparts exhibited low cytotoxicity at the higher end of concentration ranges tested. Low variability was observed between ECFC clones obtained from the same donor or different donors for CdCl2, NaAsO2, and TBT, but for menadione, the between-donor variability was much greater than the between-clone variability. The low between-clone variability indicates that an ECFC clone may represent an individual donor in cell-based assays, although this finding must be confirmed using a larger number of donors. Such confirmation would demonstrate that an in vitro ECFC-based testing platform can be used to characterize the inter-individual variability of neonatal ECFCs exposed to drugs and/or environmental toxicants.

Background β2-adrenergic receptors (β2ARs) are the target of catecholamines and play fundamental roles in cardiovascular, pulmonary, and skeletal muscle physiology. An important action of β2AR stimulation on skeletal muscle is anabolic growth, which has led to the use of agonists such as clenbuterol by athletes to enhance muscle performance. While previous work has demonstrated that β2ARs can engage distinct signaling and functional cascades mediated by either G proteins or the multifunctional adaptor protein, β-arrestin, the precise role of β-arrestin in skeletal muscle physiology is not known. Here, we tested the hypothesis that agonist activation of the β2AR by clenbuterol would engage β-arrestin as a key transducer of anabolic skeletal muscle growth. Methods The contractile force of isolated extensor digitorum longus muscle (EDL) and calcium signaling in isolated flexor digitorum brevis (FDB) fibers were examined from the wild-type (WT) and β-arrestin 1 knockout mice (βarr1KO) followed by chronic administration of clenbuterol (1 mg/kg/d). Hypertrophic responses including fiber composition and fiber size were examined by immunohistochemical imaging. We performed a targeted phosphoproteomic analysis on clenbuterol stimulated primary cultured myoblasts from WT and βarr1KO mice. Statistical significance was determined by using a two-way analysis with Sidak’s or Tukey’s multiple comparison test and the Student’s t test. Results Chronic administration of clenbuterol to WT mice enhanced the contractile force of EDL muscle and calcium signaling in isolated FDB fibers. In contrast, when administered to βarr1KO mice, the effect of clenbuterol on contractile force and calcium influx was blunted. While clenbuterol-induced hypertrophic responses were observed in WT mice, this response was abrogated in mice lacking β-arrestin 1. In primary cultured myoblasts, clenbuterol-stimulated phosphorylation of multiple pro-hypertrophy proteins required the presence of β-arrestin 1. Conclusions We have identified a previously unappreciated role for β-arrestin 1 in mediating β2AR-stimulated skeletal muscle growth and strength. We propose these findings could have important implications in the design of future pharmacologic agents aimed at reversing pathological conditions associated with skeletal muscle wasting. Electronic supplementary material The online version of this article (10.1186/s13395-018-0184-8) contains supplementary material, which is available to authorized users.

To compare trends in the etiology and management of severe postpartum hemorrhage (PPH) during 2 time periods: 2000-2004 (Period 1) versus 2005-2008 (Period 2).Medical records with a diagnosis of PPH were identified by ICD-9 codes for immediate, third-stage, delayed, and secondary. PPH and post- partum coagulation defect. Subjects having a PPH within 24 hours of delivery who also received blood component therapy (defined as severe PPH) during Period 1 were compared with those from Period 2.There were 109 and 119 cases identified from Periods 1 and 2, respectively. Uterine atony was the most common cause of severe PPH during both time periods. In the second time period women with severe PPH had a lower mean hematocrit (p0.05), a greater mean BMI (p0.05), and more induced labor (p0.01) as compared to the first time period. A greater proportion of the women in the second time period received misoprostol (p0.0001) and platelets (p0.05). The proportions of other therapies and surgical interventions remained unchanged, as did the ultimate outcomes.At a single large institution over the course of a 9-year period the management of severe PPH changed to include a greater utilization of misoprostol and platelet therapy.

The use of trial of labor after cesarean delivery calculators in the prediction of successful vaginal birth after cesarean delivery gives physicians an evidence-based tool to assist with patient counseling and risk stratification. Before deployment of prediction models for routine care at an institutional level, it is recommended to test their performance initially in the institution's target population. This allows the institution to understand not only the overall accuracy of the model for the intended population but also to comprehend where the accuracy of the model is most limited when predicting across the range of predictions (calibration).The purpose of this study was to compare 3 models that predict successful vaginal birth after cesarean delivery with the use of a single tertiary referral cohort before continuous model deployment in the electronic medical record.All cesarean births for failed trial of labor after cesarean delivery and successful vaginal birth after cesarean delivery at an academic health system between May 2013 and March 2016 were reviewed. Women with a history of 1 previous cesarean birth who underwent a trial of labor with a term (≥37 weeks gestation), cephalic, and singleton gestation were included. Women with antepartum intrauterine fetal death or fetal anomalies were excluded. The probability of successful vaginal birth after cesarean delivery was calculated with the use of 3 prediction models: Grobman 2007, Grobman 2009, and Metz 2013 and compared with actual vaginal birth after cesarean delivery success. Each model's performance was measured with the use of concordance indices, Brier scores, and calibration plots. Decision curve analysis identified the range of threshold probabilities for which the best prediction model would be of clinical value.Four hundred four women met the eligibility criteria. The observed rate of successful vaginal birth after cesarean delivery was 75% (305/404). Concordance indices were 0.717 (95% confidence interval, 0.659-0.778), 0.703 (95% confidence interval, 0.647-0.758), and 0.727 (95% confidence interval, 0.669-0.779), respectively. Brier scores were 0.172, 0.205, and 0.179, respectively. Calibration demonstrated that Grobman 2007 and Metz vaginal birth after cesarean delivery models were most accurate when predicted probabilities were60% and were beneficial for counseling women who did not desire to have vaginal birth after cesarean delivery but had a predicted success rates of 60-90%. The models underpredicted actual probabilities when predicting success at60%. The Grobman 2007 and Metz vaginal birth after cesarean delivery models provided greatest net benefit between threshold probabilities of 60-90% but did not provide a net benefit with lower predicted probabilities of success compared with a strategy of recommending vaginal birth after cesarean delivery for all women .When 3 commonly used vaginal birth after cesarean delivery prediction models are compared in the same population, there are differences in performance that may affect an institution's choice of which model to use.

Portal hypertension in pregnancy is associated with elevated risk of variceal hemorrhage. Ectopic varices, those located outside the esophagus or stomach, are rare but have a high risk of associated maternal morbidity or mortality.A 31-year-old woman, gravida 2 para 0010, with cirrhosis and portal hypertension was found to have abdominal wall ectopic varices on third-trimester obstetric ultrasonography. Computed tomography angiography confirmed these findings. Given concern for catastrophic hemorrhage during delivery, she underwent transjugular intrahepatic portosystemic shunt placement at 35 weeks of gestation, with reduction in the pressure gradient within the portosystemic circulation. She subsequently underwent an uncomplicated cesarean delivery.Identification of ectopic varices on obstetric ultrasonography may allow for treatment before delivery, decreasing the risk of serious maternal morbidity or mortality.

BACKGROUND: Obesity is prevalent among pregnant women in the United States; obstructive sleep apnea is highly comorbid with obesity and is associated with adverse pregnancy outcomes. Screening for obstructive sleep apnea in pregnant women has remained a challenge because of a lack of validated screening tools. OBJECTIVE: The purpose of this study was to evaluate established obstructive sleep apnea screening tools, a sleepiness scale, and individual component items in a cohort of pregnant women with extreme obesity in mid pregnancy with the use of objective testing to determine obstructive sleep apnea status and to describe the prevalence of obstructive sleep apnea among women with extreme obesity. STUDY DESIGN: Adult pregnant subjects, between 24 and 35 weeks gestation, with a body mass index ≥40 kg/m(2) at the time of enrollment completed obstructive sleep apnea screening tools (Berlin Questionnaire, American Society of Anesthesiologists checklist, and STOP-BANG questionnaire) and the Epworth Sleepiness Scale; they also underwent physical examination of the neck, mouth, and airway. The obstructive sleep apnea in pregnancy prediction score proposed by Facco et al was calculated for each subject. Obstructive sleep apnea status for each subject was determined by the results of an overnight, unattended type III home sleep apnea test. RESULTS: Twenty-four percent of pregnant women with extreme obesity had obstructive sleep apnea on home sleep apnea testing in mid pregnancy (Apnea-Hypopnea Index, ≥5 events per hour]. Established obstructive sleep apnea screening tools performed very poorly to screen for obstructive sleep apnea in this cohort. Age, body mass index, neck circumference, frequently witnessed apneas, and highly likely to fall asleep while driving were associated most strongly with obstructive sleep apnea status in this cohort. CONCLUSION: We found that 24% of pregnant women with body mass index ≥40 kg/m(2) between 24 and 35 weeks gestation have obstructive sleep apnea, defined as Apnea-Hypopnea Index ≥5 events per hour on an overnight type III home sleep apnea test. We found the Berlin Questionnaire, American Society of Anesthesiologists checklist, STOP-BANG, obstructive sleep apnea in pregnancy score by Facco et al, and the Epworth Sleepiness Scale were not useful screening tools for obstructive sleep apnea in a cohort of obese pregnant women. However, age, body mass index, neck circumference, frequently witnessed apneas, and likely to fall asleep while driving were associated with obstructive sleep apnea in this cohort. Further studies are needed to adjust the criteria and thresholds within the available screening tools to better predict obstructive sleep apnea in pregnant women with obesity.

Objective: The gestation-adjusted projection (GAP) is a method to predict birthweight using population birth data and third trimester ultrasound fetal weight. This method usually utilizes populatio...

Background In 2003, the Accreditation Council for Graduate Medical Education limited resident duty hours to 80 hours per week. More than a decade later, the effect of the limits on resident clinical competence is not fully understood. Objective We sought to assess the effect of duty hour restrictions on resident performance of an uncomplicated cesarean delivery. Methods We reviewed unlabored primary cesarean deliveries at Duke University Hospital after 34 weeks gestation, between 2003 and 2011. Descriptive statistics and linear regression were used to compare total operative time with incision to delivery time as a function of years since institution of the 80-hour workweek. Resident training level, subject body mass index, estimated blood loss, and skin closure method were controlled for in the regression model. Results We identified 444 deliveries that met study criteria. The mean (SD) total operative time in 2003–2004 was 43.3 (14.3) minutes and 59.6 (10.7) minutes in 2010–2011 (P < .001). Multivariable regression demonstrated an increase in total operative time of 1.9 min/y (P < .001) but no change in incision to delivery time (P = .05). The magnitude of increased operative time was seen among junior residents (2.0 min/y, P < .001) compared to that of senior residents (1.2 min/y, P = .06). Conclusions Since introduction of the 2003 duty hour limits, there has been an increase of nearly 20 minutes in the time required for a routine cesarean delivery. It is unclear if the findings are due to a change in residency duty hours or to another aspect of residency training.

Preeclampsia is a common complication of pregnancy that is associated with an increased risk of maternal and neonatal morbidity and mortality. Currently, delivery is the only cure for preeclampsia; therefore, effective prevention and treatment options for this condition are sorely needed. In the current issue of the JCI, Mirzakhani et al. report the findings of the Vitamin D Antenatal Asthma Reduction Trial (VDAART), a well-conducted large, randomized, double-blind, placebo-controlled trial of vitamin D supplementation for the prevention of preeclampsia. Though vitamin D supplementation had no effect on the risk of preeclampsia, reduced maternal serum vitamin D levels did correlate with preeclampsia risk. Mirzakhani and colleagues identified a number of gene pathways that are differentially regulated among women with low serum vitamin D levels who develop preeclampsia. These results indicate that further research on the role of vitamin D in preeclampsia is warranted.