The Contribution of Neighborhood Context to the Association of Race with Severe Maternal Morbidity.

OBJECTIVE: Severe maternal morbidity (SMM) has disproportionate frequencies among racial minorities and those of socioeconomic disadvantage, with people of Black race consistently having the highest proportion. Neighborhood level deprivation has been associated with maternal morbidity and mortality, including adverse pregnancy outcomes. We sought to explore the relationship between neighborhood socioeconomic disadvantage and SMM and describe how neighborhood context impacts the relationship between race and SMM. STUDY DESIGN: We performed a retrospective cohort analysis of all delivery admissions in a single health care network from 2015 to 2019. Area deprivation index (ADI) was used to represent neighborhood socioeconomic disadvantage and is a composite index of neighborhood that spans income, education, household characteristics, and housing. The index ranges from 1 to 100 with higher values indicating higher disadvantage. Logistic regression assessed the relationship between ADI and SMM and estimated the effect that ADI has on the relationship between race and SMM. RESULTS: Of the 63,208 birthing persons in our cohort, the unadjusted incidence of SMM was 2.2%. ADI was significantly associated with SMM, with higher values conferring higher risk for SMM (p < 0.001). The absolute risk of SMM increased roughly by 1.0% from the lowest to highest ADI value. Those of Black race had the highest unadjusted incidence of SMM compared with the referent group (3.4 vs. 2.0%) and highest median ADI (92; interquartile range [IQR]: 20). In the multivariable model, in which the primary exposure was race and ADI was adjusted for, Black race had a 1.7 times odds SMM when compared with White race (95% confidence interval [CI]: 1.5-1.9). This association was attenuated to 1.5 adjusted odds when controlling for ADI (95% CI: 1.3-1.7). Risk attenuation for SMM was not seen in other race categories. CONCLUSION: Neighborhood context contributes to SMM but does not explain the majority of racial disparities. KEY POINTS: · Neighborhood context is associated with SMM, with higher disadvantage conferring higher risk.. · Compared with White race, all other races had higher rates of SMM, with Black race having the highest.. · Accounting for neighborhood modestly attenuates the magnitude of association of Black race with SMM.. · Neighborhood context contributes to health outcomes but does not explain the majority of disparities..

Comparative Analysis of Obstetric Hemorrhage Risk Prediction Tools.

OBJECTIVE: Hemorrhage risk prediction tools were developed in response to rising rates of obstetric hemorrhage (OBH). The California Maternal Quality Care Collaborative (CMQCC) risk prediction tool classifies patients as low, medium, and high risk for OBH based on individual risk factors. At our institution, Magee-Womens Hospital (MWH), a unique OBH risk prediction tool was derived from the CMQCC tool that differs through its use of weighted risk factors and distinctive laboratory value cutoffs. Our objective is to compare this enhanced institution-specific tool to the CMQCC tool. STUDY DESIGN: This study was a retrospective cohort analysis of delivery admissions from a single health care network. Admission OBH risk scores were assigned to each patient using both the MWH and CMQCC scores. Cohen's kappa estimated agreement. Scoring systems and maternal outcomes were compared using chi-square test. Composite morbidity included transfusion, hysterectomy, uterine artery embolization, and intensive care unit admission. RESULTS: A total of 21,843 delivery admissions were included. A moderate association was observed between scoring systems (kappa = 0.41, p < 0.001). The CMQCC tool categorized 16,184 (74%) patients as low risk, 4,664 (21%) as medium risk, and 995 (5%) as high risk. The MWH tool categorized 13,137 (60%) patients as low risk, 8,113 (37%) as medium risk, and 593 (3%) as high risk. The MWH score recategorized CMQCC low-risk patients to a higher stratum 26% of the time. CMQCC high-risk patients were recategorized to a lower stratum 82% of the time. Both the MWH and CMQCC tools were able to differentiate OBH-related morbidity across risk strata. The MWH tool independently predicted risk of composite morbidity within each stratum of the CMQCC score. CONCLUSION: Both the MWH and CMQCC tools independently distinguish risk of composite morbidity. Adding weighted values to individual risk factors further discriminates risk of morbidity. This suggests it may be reasonable to adapt the CMQCC tool to reflect institutional populations and resources. KEY POINTS: · The nationally adopted CMQCC risk prediction tool identifies women at risk for obstetric hemorrhage.. · Our institution (MWH) developed a unique tool that weights individual risk factors to better capture risk.. · The CMQCC and MWH tools both differentiate risk; though similar to other tools, categorize a proportion of women who hemorrhage as low risk..

Metformin and survival: Is there benefit in a cohort limited to diabetic women with endometrial, breast, or ovarian cancer?

OBJECTIVE: Evaluate the association between metformin and survival in women with Type 2 diabetes (T2DM) and breast, endometrial and ovarian cancer- 3 hormonally mediated cancers. METHODS: We evaluated outcomes in a cohort of 6225 women with T2DM with a new diagnosis of ovarian, breast or endometrial cancer from 2010 to 2019. We classified glycemic medications at time of first cancer diagnosis into 3 tiers in accordance with ADA guidelines. Approaches compared: (i) metformin (tier 1) vs. no glycemic medication, (ii) metformin vs tier 2 medications (sulfonylureas, thiazolidinediones, SGLT2-inhibitors, DPP4-inhibitors, alpha glucosidase-inhibitors, GLP-1 agonists), (iii) metformin vs tier 3 medications (insulins, amylinomimetics), and (iv) tier 2 vs tier 3 medications. Analyses included Cox proportional-hazards models, Kaplan-Meier curves, and conditional logistic regression in a risk set-sampled nested case-control matched on T2DM duration- all modeling survival. Models were adjusted for demographics, cancer type, A1C, T2DM duration, and number of office visits and hospitalizations. RESULTS: Metformin was the most used medication (n = 3232) and consistently demonstrated survival benefit compared with tier 2 and 3 medications, across all methods. Tier 3-users demonstrated highest risk of death when compared to metformin rather than tier 2 [adjHR = 1.83 (95% CI: 1.58, 2.13) vs. adjHR = 1.32 (95% CI: 1.11, 1.57)], despite similar baseline profiles between tier 1 and 2 users. CONCLUSIONS: Metformin users experienced increased survival even after accounting for surrogates of diabetes progression. Benefit extended beyond that seen in tier 2-users. Our findings, consistent with prior studies, indicate metformin use improves survival in women with T2DM and hormonally mediated women's cancers.

Invited Commentary: A Novel Strategy for Addressing Unmeasured Confounding When Comparing Opioid Agonist Therapies in Pregnancy.

Opioid addiction in pregnancy is a growing concern that has recently received a great deal of attention. When comparing recommended opioid agonist therapies, many currently published studies guiding practice may have been affected by unmeasured confounding by indication. Populations of women who receive methadone are generally different from those treated with buprenorphine. Women treated with methadone frequently have more severe and uncontrolled addiction than buprenorphine-treated patients; however, these factors are typically unmeasured or unavailable in large observational data sets. Consequently, findings of superior perinatal outcomes with buprenorphine may in truth be a result of an overall healthier profile of women taking this medication. In this issue of the Journal, Brogly et al. (Am J Epidemiol. 2018;187(6):1153-1161) describe an approach utilizing detailed data from an external cohort (n = 113) to account for confounding by indication in a larger Medicaid population (n = 1,020) in order to more accurately compare opioid agonist therapies in pregnancy. They found that the decreases in risk of preterm birth and length of infant hospitalization associated with buprenorphine as compared with methadone were attenuated after accounting for the additional confounding. Brogly et al. should be commended for providing a novel method with which to address this bias in future studies.

Methadone Versus Buprenorphine for Opioid Use Dependence and Risk of Neonatal Abstinence Syndrome.

BACKGROUND: Our objective was to estimate the association between methadone and neonatal abstinence syndrome compared with buprenorphine using a probabilistic bias analysis to account for unmeasured confounding by severity of addiction. METHODS: We used a cohort of live-born infants exposed in utero to methadone or buprenorphine for maternal opioid maintenance therapy at Magee-Womens Hospital in Pittsburgh, PA, from 2013 to 2015 (n = 716). We determined exposure and outcome status using pharmacy billing claims. We used log-binomial regression models to assess association of treatment with neonatal abstinence syndrome after adjusting for parity, maternal race, age, delivery year, employment, hepatitis c, smoking, marital, and insurance status. We implemented probabilistic bias analysis, informed by an internal validation study, to assess the impact of unmeasured confounding by severity of addiction. RESULTS: Infants exposed to methadone in utero were more likely to experience neonatal abstinence syndrome compared with those exposed to buprenorphine (RR, 1.3; 95% CI, 1.2, 1.5). After adjustment, infants exposed to methadone were more likely (adjusted RR, 1.3; 95% CI, 1.1, 1.5) than infants exposed to buprenorphine to have the syndrome. In the validation cohort (n = 200), severe addiction was more common in methadone- versus buprenorphine-exposed deliveries (77% vs. 32%). However, adjustment for severe addiction in the bias analysis only slightly attenuated the association (RR, 1.2; 95% CI, 1.0, 1.4), supporting conventional analysis. CONCLUSIONS: Methadone is associated with increased risk of neonatal abstinence syndrome compared with buprenorphine in infants exposed in utero. This association is subject to minimal bias due to unmeasured confounding by severity of addiction.

The Role of Preterm Birth in the Association Between Opioid Maintenance Therapy and Neonatal Abstinence Syndrome.

BACKGROUND: Pregnant women treated with methadone as opioid maintenance therapy are more likely than women treated with buprenorphine to deliver preterm. Preterm birth is associated with less risk of neonatal abstinence syndrome (NAS). We sought to assess the role of preterm birth as a mediator of the relationship between in utero exposure to methadone and NAS compared with buprenorphine. METHODS: We studied 716 women receiving methadone or buprenorphine and delivering liveborn infants at Magee-Womens Hospital, Pittsburgh, Pennsylvania (2013-15). We implemented inverse probability weighted marginal structural models to isolate the role of preterm birth (<37 weeks' gestation). Weights accounted for confounding by maternal age, race, insurance, parity, delivery year, marital, employment, hepatitis C, and smoking status. RESULTS: Approximately 57% of the cohort were treated with methadone. Preterm birth was more common in methadone-exposed pregnancies (25% versus 14%). The incidence of NAS treatment was higher in methadone compared with buprenorphine-exposed infants (65% vs 49%), and term compared with preterm births (64% vs 36%). For every 100 infants liveborn to mothers treated for opioid dependence, there were 13 excess cases of NAS among infants exposed to methadone compared with buprenorphine (adjusted risk difference [RD] 13.3, 95% confidence interval [CI] 5.7, 20.9). Among term births, this increased to 17 excess cases of NAS in methadone- compared with buprenorphine-exposed (RD 16.7, 95% CI 9.3, 24.0). CONCLUSION: The further increased risk of NAS associated with methadone use vs buprenorphine in term deliveries emphasises the utility of buprenorphine in clinical settings aimed at decreasing NAS.

Impact of Obesity on the Rate of Recurrent Spontaneous Preterm Birth in Women Treated with 17-alpha Hydroxyprogesterone Caproate.

OBJECTIVE: We sought to determine if the rate of recurrent spontaneous preterm birth (PTB) in women treated with 17-α hydroxyprogesterone caproate (17-OHPC) is modified by maternal body mass index (BMI). STUDY DESIGN: We performed a secondary analysis of the Maternal-Fetal Medicine Units Network omega-3 fatty acid supplementation to prevent recurrent PTB randomized controlled trial. All women received 17-OHPC. RESULTS: A total of 708 women were included. Rates of spontaneous PTB did not vary significantly by BMI category. With stratification by obesity class and gestational age at delivery, the unadjusted risk for PTB using earlier gestational cutoffs (< 35, 32, and 28 weeks) demonstrated an association between preterm delivery and increasing severity of obesity. With adjustment for potential confounders, there was no statistically significant relationship between BMI and spontaneous PTB. CONCLUSION: We demonstrated that the risk of PTB in women receiving 250 mg 17-OHPC is not dependent on maternal BMI after adjustment for confounding variables. Pharmacokinetic studies have demonstrated a wide variation in plasma concentration of 17-OHPC across the population with likely considerable overlap in plasma concentrations among the obese and nonobese population. Further studies are needed to evaluate the impact of BMI on efficacy of 17-OHPC prior to any dose adjustment in this population.

Delayed villous maturation in term placentas exposed to opioid maintenance therapy: a retrospective cohort study.

BACKGROUND: Opioid use disorder among pregnant women is associated with adverse perinatal outcomes and is increasing in the United States. The standard of care for pregnant women with opioid use disorder is opioid maintenance therapy including either methadone or buprenorphine, which can be initiated at any time during pregnancy. These medications are known to cross the placenta but their placental and fetal effects have not been well characterized. Delayed villous maturation, a placental finding associated with stillbirth, was observed in placentas exposed to opioid maintenance therapy. Given the association of delayed villous maturation with stillbirth, and the possible relationship between opioid maintenance therapy and delayed villous maturation, this study was undertaken to explore the association between opioid maintenance therapy and this placental finding. Delayed villous maturation was not previously reported in placentas exposed to opioids or opioid maintenance therapy. OBJECTIVE: This study sought to compare risk of delayed villous maturation in term placentas exposed and unexposed to opioid maintenance therapy with buprenorphine or methadone. STUDY DESIGN: This was a retrospective cohort study conducted between 2010 through 2012 at Magee-Womens Hospital comparing delayed villous maturation in placentas of women with opioid use disorder exposed to either buprenorphine (n = 86) or methadone (n = 268) versus women without opioid use disorder (n = 978). Potential covariates were assessed in univariate analyses with none significantly associated with delayed villous maturation. The final model used conditional logistic regression adjusting for smoking status alone. RESULTS: Among women without opioid use disorder (and therefore not exposed to opioid maintenance therapy), delayed villous maturation was identified in 5.7% of placentas while the prevalence among women treated with buprenorphine or methadone was 8.1% and 10.8%. Overall, the crude odds of being diagnosed with delayed villous maturation were significantly greater in those exposed to opioid maintenance therapy compared to those not exposed (odds ratio, 1.86; 95% confidence interval, 1.20-2.89). When considered separately, women treated with methadone had significantly greater odds of having a placenta with delayed villous maturation than women without exposure to opioid maintenance therapy (odds ratio, 2.00; 95% confidence interval, 1.52-3.20). Women treated with buprenorphine did not have significantly greater odds of this placental diagnosis when compared to the women unexposed to opioid maintenance therapy (odds ratio, 1.46; 95% confidence interval, 0.64-3.31). Results were similar after accounting for smoking. CONCLUSION: Delayed villous maturation was more common in the placentas of women exposed to opioid maintenance therapy. Further studies are required to characterize rates and extent of delayed villous maturation in the general population as well as to differentiate between possible effects of opioid exposure (eg, heroin, illicit use of prescription opioids) vs those of opioid maintenance therapy (buprenorphine and methadone).

Comparative Effectiveness and Safety Analysis of Dual Antiplatelet Therapies Within an Integrated Delivery System.

BACKGROUND: Dual antiplatelet therapy is a mainstay of care for percutaneous coronary intervention (PCI) patients; however, uncertainty exists in real-world practice about comparative effectiveness and safety outcomes. OBJECTIVE: To evaluate outcomes of different oral P2Y12 inhibitors in PCI patients. METHODS: We retrospectively studied patients treated between July 1, 2010, and December 31, 2013. Patients received clopidogrel, prasugrel, ticagrelor, or more than 1 antiplatelet (switch) during PCI. Outcomes were evaluated for major adverse cardiovascular events (MACE) and bleeding at 1 year. Propensity score matching with Cox proportional hazards analysis was used to determine predictors of MACE and bleeding. RESULTS: A total of 8127 patients were included: clopidogrel (n = 6872), prasugrel (n = 605), ticagrelor (n = 181), and switch (n = 469). Treatment with prasugrel was associated with the lowest risk of MACE using multivariate regression (odds ratio [OR] = 0.57; 95% CI = 0.36-0.92; P = 0.02). In the propensity score-matched analysis, only the prasugrel group was associated with a lower risk of MACE compared with the clopidogrel group. Clopidogrel was associated with the lowest risk of major bleeding using multivariate regression (OR = 0.64; 95% CI = 0.42-0.98; P = 0.042). Both ticagrelor (hazard ratio [HR] = 2.00; 95% CI = 1.11-3.59) and the switch groups (HR = 1.65; 95% CI = 1.09-2.50) were associated with a greater risk of major bleeding compared with clopidogrel. However, no differences were found in the propensity score-matched analysis. CONCLUSIONS: Dual antiplatelet therapies differed in both MACE and bleeds in a real-world setting of PCI. Prasugrel was associated with fewer MACE, whereas clopidogrel had fewer major bleeding events.

Postpartum Weight Change Association With Readmission and Blood Pressure Trend Among Individuals With Hypertensive Disorders of Pregnancy.

BACKGROUND: The aim of this study was to evaluate the association between early postpartum weight change and (1) hospital readmission and (2) 2-week blood pressure trajectory. METHODS AND RESULTS: This retrospective study cohort included 1365 individuals with a hypertensive disorder of pregnancy enrolled in a postpartum hypertension remote monitoring program. Exposure was percentage weight change from delivery to first weight recorded within 10 days postpartum. We first modeled likelihood of hospital readmission within 8 weeks postpartum using logistic regression adjusting for age, race, insurance, type of hypertensive disorder of pregnancy, early body mass index, gestational weight gain, mode of delivery, and any discharge antihypertensive medications. We then performed case-control analysis additionally matching in a 1:3 ratio on breastfeeding, early body mass index, discharge on antihypertensive medications, and days between weight measurements. Both analytic approaches were repeated, limiting to readmissions attributable to hypertension or heart failure. Finally, we compared blood pressure trajectories over first 2 weeks postpartum. Individuals who did not lose weight in the early postpartum period had more admissions compared with weight loss groups (group 3: 14.1% versus group 2: 5.8% versus group 1: 4.5%). These individuals had 4 times the odds of postpartum readmissions (adjusted odds ratio [aOR], 3.9 [95% CI, 1.8-8.6]) to 7 (aOR, 7.8 [95% CI, 2.3-26.5]) compared with those with the most weight loss. This association strengthened when limited to hypertension or heart failure readmissions. These individuals also had more adverse postpartum blood pressure trajectories, with significant differences by weight change group. CONCLUSIONS: Weight change is readily accessible and may identify individuals at high risk for postpartum readmission following a hypertensive disorder of pregnancy who could benefit from targeted interventions.

Clinical Outcomes Associated With a Remote Postpartum Hypertension Monitoring Program.

OBJECTIVE: To evaluate differences in health care utilization and guideline adherence for postpartum individuals with hypertensive disorders of pregnancy (HDP) who are engaged in a remote monitoring program, compared with usual care. METHODS: This was a retrospective cohort study of postpartum individuals with HDP who delivered between March 2019 and June 2023 at a single institution. The primary exposure was enrollment in a remote hypertension management program that relies on patient home blood pressure (BP) measurement and centralized nursing team management. Patients enrolled in the program were compared with those receiving usual care. Outcomes included postpartum readmission, office visit within 6 weeks postpartum, BP measurement within 10 days, and initiation of antihypertensive medication. We performed multivariable logistic and conditional regression in a propensity score matched cohort. Propensity scores, generated by modeling likelihood of program participation, were assessed for even distribution by group, ensuring standardized bias of less than 10% after matching. RESULTS: Overall, 12,038 eligible individuals (6,556 participants, 5,482 in the control group) were included. Program participants were more likely to be White, commercially insured, be diagnosed with preeclampsia, and have higher prenatal and inpatient postpartum BPs. Differences in baseline factors were well-balanced after implementation of propensity score. Program enrollment was associated with lower 6-week postpartum readmission rates, demonstrating 1 fewer readmission for every 100 individuals in the program (propensity score-matched adjusted risk difference [aRD] -1.5, 95% CI, -2.6 to -0.46; adjusted risk ratio [aRR] 0.78, 95% CI, 0.65-0.93). For every 100 individuals enrolled in the program, 85 more had a BP recorded within 10 days (propensity score-matched aRD 85.4, 95% CI, 84.3-86.6), and six more had a 6-week postpartum office visit (propensity score-matched aRD 5.7, 95% CI, 3.9-7.6). Program enrollment was also associated with increased initiation of an antihypertensive medication postpartum (propensity score-matched aRR 4.44, 95% CI, 3.88-5.07). CONCLUSION: Participation in a postpartum remote BP monitoring program was associated with fewer postpartum hospital readmissions, higher attendance at postpartum visits, improved guideline adherence, and higher rates of antihypertensive use.

Neighborhood disadvantage and the racial disparity in postpartum hypertension.

BACKGROUND: Postpartum hypertension is the leading cause of postpartum readmission and has long-lasting cardiovascular effects. Black patients have higher incidence rates of hypertensive disorders after delivery and subsequent severe maternal morbidity. Neighborhood advantage, a marker of social determinants of health, has not been studied concerning postpartum hypertension. Moreover, the interplay between race and neighborhood advantage and their effect on postpartum hypertension have not been previously explored. OBJECTIVE: This study aimed to evaluate the association between neighborhood-level social determinants of health and postpartum hypertension and explore whether these factors explain previously documented racial disparities. STUDY DESIGN: This study included a retrospective cohort of people enrolled in a remote monitoring program of postpartum hypertension at the time of delivery within 1 health network from March 2019 to September 2021. Patients were eligible for enrollment after a diagnosis of hypertensive disorder during pregnancy or delivery. We further limited the cohort to self-reported Black and White patients with blood pressures recorded at 3 weeks and 6 weeks postpartum. The neighborhood advantage for each person at the time of delivery was classified using the area deprivation index, an accepted surrogate of social determinants of health and our primary exposure. The secondary exposure was self-reported race. Study outcomes of interest were hypertensive status (stage 1 hypertension: ≥130 to 139/80 to 89 mm Hg; stage 2 hypertension: ≥140/90 mm Hg) at 3 and 6 weeks after delivery. In addition, hypertensive status by neighborhood area deprivation index using logistic regression was molded. In secondary analyses, a case-control cohort matched on the area deprivation index was created, and conditional logistic regression was used to evaluate race. Finally, mixed-effects models modeling hypertension by race and clustering within the area deprivation index were used. RESULTS: Of 4193 people enrolled, 2722 were Black or White and had blood pressure data recorded at 3 weeks after delivery, and 1126 had blood pressure data recorded at 6 weeks after delivery. After accounting for prenatal body mass index, smoking status, type of hypertension, and antihypertensives prescribed at discharge, persons living in the most disadvantaged neighborhoods were twice as likely (adjusted odds ratio, 2.03; 95% confidence interval, 1.53-2.69) to develop stage 2 hypertension at 21 days after delivery and 1.67 times more likely (95% confidence interval, 1.06-2.64) to develop stage 2 hypertension at 6 weeks after delivery than persons living in the most advantaged neighborhoods. Both associations were attenuated after adjusting for race. When people with stage 2 hypertension were matched on area deprivation index with normotensive counterparts, Black patients were still 3 to 4 times more likely to develop stage 2 hypertension at 3 (adjusted odds ratio, 3.00; 95% confidence interval, 1.95-4.63) and 6 (adjusted odds ratio, 4.61; 95% confidence interval, 2.05-10.36) weeks after delivery. This association remained after clustering within a neighborhood at 3 (adjusted odds ratio, 3.12; 95% confidence interval, 2.41-4.06) and 6 (adjusted odds ratio, 2.99; 95% confidence interval, 1.96-4.54) weeks after delivery. There was no significant difference in stage 1 hypertension. CONCLUSION: Neighborhood advantage was associated with the development of persistent hypertension at 3 and 6 weeks after delivery. This association did not explain the racial disparity in sustained high blood pressure.

Ondansetron use in the first trimester of pregnancy and the risk of neonatal ventricular septal defect.

BACKGROUND: Literature is divided regarding the risk of neonatal ventricular septal defect (VSD) associated with first trimester ondansetron use in pregnancy. METHODS: We evaluated the risk of VSD associated with first trimester exposure to intravenous or oral ondansetron in 33 677 deliveries at Magee-Womens Hospital in Pittsburgh, PA (2006-2014). Using log-binomial regression, we evaluated the risk: (1) in the full cohort, (2) using propensity score designs with both matching and inverse probability weighting and (3) utilizing clustered trajectory analysis evaluating the role of dose. Sensitivity analyses assessed the association between ondansetron and all recorded birth defects in aggregate. RESULTS: A total of 3733 (11%) pregnancies were exposed to ondansetron in the first trimester (dose range: 2.4-1008 mg). Ondansetron was associated with increased risk of VSD with risk ratios ranging from 1.7 [95% confidence interval (CI) 1.0-2.9] to 2.1 (95% CI 1.1-4.0) across methods. Risks correspond to one additional VSD for approximately every 330 pregnancies exposed in the first trimester. The association was dose-dependent with increased risk in women receiving highest cumulative doses compared with lowest doses [adjusted risk ratio: 3.2 (95% CI 1.0-9.9)]. The association between ondansetron and congenital malformations was diluted as the outcome included additional birth defects. CONCLUSIONS: First trimester ondansetron use is associated with an increased risk of neonatal VSD potentially driven by higher doses. This risk should be viewed in the context of risks attributable to severe untreated nausea and vomiting of pregnancy.

A Postpartum Remote Hypertension Monitoring Protocol Implemented at the Hospital Level.

OBJECTIVE: To evaluate the feasibility, acceptability, and compliance of a remote blood pressure monitoring protocol implemented as a quality improvement measure at the hospital level for management of hypertension in postpartum women after hospital discharge. METHODS: This is an ongoing quality improvement project that included women admitted to the postpartum unit of a single tertiary care hospital. We designed nursing call center-driven blood pressure management and treatment algorithms, which were initiated after hospital discharge until 6 weeks postpartum. Women are eligible to participate if they have a diagnosis of chronic hypertension, superimposed preeclampsia, gestational hypertension, preeclampsia, or postpartum hypertension and have access to a text messaging-enabled smartphone device. After identification by an obstetric care provider, women are enrolled into the program, which is automatically indicated in the electronic medical record. Maternal, obstetric, and sociodemographic data were obtained from the electronic medical record. RESULTS: Between February 2018 and January 2019, we enrolled 499 patients. Here we report on the first 409 enrolled patients. Participants include 168 (41%) with gestational hypertension, 179 (44%) with preeclampsia with no history of chronic hypertension, 49 (12%) with chronic hypertension with superimposed preeclampsia, and 13 (3%) with postpartum preeclampsia. One hundred seventy-one (42%) participants had antihypertensives initiated or titrated through the program. Three hundred forty women (83%) continued the program beyond 3 weeks postpartum, and 360 (88%) attended an in-person 6-week postpartum visit. Two hundred thirty-five out of 250 women who completed a postprogram survey (94%) reported satisfaction with the program. CONCLUSION: In this study, we detail results from an ongoing remote blood pressure monitoring program. We demonstrate high compliance, retention, and patient satisfaction with the program. This is a feasible, scalable remote monitoring program connected to the electronic medical record.

Prepregnancy obesity and the racial disparity in infant mortality.

OBJECTIVE: To estimate the extent to which prepregnancy obesity explains the Black-White disparity in stillbirth and infant mortality. METHODS: A population-based study of linked Pennsylvania birth-infant death certificates (2003-2011; n = 1,055,359 births) and fetal death certificates (2006-2011; n = 3,102 stillbirths) for all singleton pregnancies in non-Hispanic (NH) White and NH Black women was conducted. Inverse probability weighted regression was used to estimate the role of prepregnancy obesity in explaining the race-infant/fetal death association. RESULTS: Compared with NH White women, NH Black women were more likely to have obesity (≥30 kg/m2 ) and experienced a higher rate of stillbirth (8.3 vs. 3.6 stillbirths per 1,000 live-born and stillborn infants) and infant death (8.5 vs. 3.0 infant deaths per 1,000 live births). When the contribution of prepregnancy obesity was removed, the difference in risk between NH Blacks and NH Whites decreased from 6.2 (95% CI: 5.6-6.7) to 5.5 (95% CI: 4.9-6.2) excess stillbirths per 1,000 and 5.8 (95% CI: 5.3-6.3) to 5.2 (95% CI: 4.7-5.7) excess infant deaths per 1,000. CONCLUSIONS: For every 10,000 live births in Pennsylvania (2003-2011), 6 of the 61 excess infant deaths in NH Black women and 5 of the 44 excess stillbirths (2006-2011) were attributable to prepregnancy obesity.

Ondansetron Exposure Changes in a Pregnant Woman.

Pregnancy results in many physiologic changes that can alter the pharmacokinetic profiles of medications used during pregnancy. One of the primary factors leading to these pharmacokinetic changes is altered activity of drug-metabolizing enzymes. Ondansetron is a substrate of cytochrome P450 (CYP) 3A4 (primary metabolic pathway), 2D6, and 1A2, all of which are altered during pregnancy. We evaluated the pharmacokinetics of ondansetron at three different gestational time points in a 26-year-old, pregnant, Caucasian woman with normal liver and kidney function, who was maintained on ondansetron 8 mg administered orally 3 times/day throughout her pregnancy. Serial plasma samples were collected from the subject over one 8-hour dosing interval at 14, 24, and 35 weeks' gestation (representing early-, mid-, and late-pregnancy time points, respectively). Ondansetron plasma concentrations were determined using liquid chromatography-tandem mass spectrometry. Ondansetron area under the plasma concentration-time curve decreased progressively across gestation (634 ng hr/ml in early pregnancy, 553 ng hr/ml in mid-pregnancy, and 387 ng hr/ml in late pregnancy), with a corresponding increase in apparent oral clearance (12.6 L/hr in early-pregnancy, 14.5 L/hr in mid-pregnancy, and 20.7 L/hr in late-pregnancy). The decreased area under the plasma concentration-time curve and exposure to ondansetron across gestation is likely due to increased activity of CYP3A4 and CYP2D6 during pregnancy. We were not able to study this patient during the postpartum period; however, as with other CYP3A4 and CYP2D6 substrates, the apparent activities of these isoenzymes are likely return to baseline. To our knowledge, this is the first report to describe ondansetron pharmacokinetics across gestation. Additional pharmacokinetic and pharmacodynamic data are needed to confirm our results and to evaluate clinical impact; however, in the meantime, clinicians should be aware of these pharmacokinetic changes in ondansetron exposure during pregnancy.