Background: Cardiomyopathy (CM) and other cardiovascular conditions (OCVs) are among the most frequent causes of pregnancy-related death in the United States. Objectives: The purpose of this paper was to report demographic and clinical characteristics, preventability, contributing factors, and Maternal Mortality Review Committee (MMRC) recommendations among pregnancy-related deaths with underlying causes of CM, OCVs, and the 2 combined (cardiovascular conditions, CV). Methods: We analyzed pregnancy-related death data from MMRCs in 32 states, occurring during 2017 to 2019, with MMRC-determined underlying causes of CVs. We describe distributions of demographic characteristics, present the most frequent contributing factor classes, and provide example MMRC prevention recommendations. Results: Among 210 pregnancy-related deaths due to CVs, 84 (40%) were due to CM and 126 (60%) to OCVs. More than half (51.2%) of CM deaths were among non-Hispanic Black persons. Two-thirds (66%) of all CV deaths occurred among people <35 years old. Approximately 53% of CM deaths and 31% of OCV deaths occurred 43 to 365 days postpartum. Over 75% of pregnancy-related deaths due to CVs were determined by MMRCs to be preventable. The 5 most frequent contributing factor classes accounted for 50% of the total MMRC-identified contributing factors. MMRC prevention recommendations occur at multiple levels. Conclusions: Most pregnancy-related deaths due to CM and OCV are preventable. Example MMRC recommendations provided in this report illustrate prevention opportunities that address contributing factors, including broader awareness of urgent warning signs, improved handoffs for care coordination and continuity, and expanded accessibility of community-based comprehensive and integrated care services. © 2024 The Authors

IMPORTANCE: Buprenorphine remains underused in treating opioid use disorder, despite its effectiveness. During the onset of the COVID-19 pandemic, the US government implemented prescribing flexibilities to support continued access. OBJECTIVE: To determine whether buprenorphine-involved overdose deaths changed after implementing these policy changes and highlight characteristics and circumstances of these deaths. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from the State Unintentional Drug Overdose Reporting System (SUDORS) to assess overdose deaths in 46 states and the District of Columbia occurring July 2019 to June 2021. Data were analyzed from March 7, 2022, to June 30, 2022. MAIN OUTCOMES AND MEASURES: Buprenorphine-involved and other opioid-involved overdose deaths were examined. Monthly opioid-involved overdose deaths and the percentage involving buprenorphine were computed to assess trends. Proportions and exact 95% CIs of drug coinvolvement, demographics, and circumstances were calculated by group. RESULTS: During July 2019 to June 2021, 32 jurisdictions reported 8 111 total overdose deaths and 74 474 opioid-involved overdose deaths, including 1955 buprenorphine-involved overdose deaths, accounting for 2.2% of all drug overdose deaths and 2.6% of opioid-involved overdose deaths. Median (IQR) age was similar for buprenorphine-involved overdose deaths (41 [34-55] years) and other opioid-involved overdose deaths (40 [31-52] years). A higher proportion of buprenorphine-involved overdose decedents, compared with other opioid-involved decedents, were female (36.1% [95% CI, 34.2%-38.2%] vs 29.1% [95% CI, 28.8%-29.4%]), non-Hispanic White (86.1% [95% CI, 84.6%-87.6%] vs 69.4% [95% CI, 69.1%-69.7%]), and residing in rural areas (20.8% [95% CI, 19.1%-22.5%] vs 11.4% [95% CI, 11.2%-11.7%]). Although monthly opioid-involved overdose deaths increased, the proportion involving buprenorphine fluctuated but did not increase during July 2019 to June 2021. Nearly all (92.7% [95% CI, 91.5%-93.7%]) buprenorphine-involved overdose deaths involved at least 1 other drug; higher proportions involved other prescription medications compared with other opioid-involved overdose deaths (eg, anticonvulsants: 18.6% [95% CI, 17.0%-20.3%] vs 5.4% [95% CI, 5.2%-5.5%]) and a lower proportion involved illicitly manufactured fentanyls (50.2% [95% CI, 48.1%-52.3%] vs 85.3% [95% CI, 85.1%-85.5%]). Buprenorphine decedents were more likely to be receiving mental health treatment than other opioid-involved overdose decedents (31.4% [95% CI, 29.3%-33.5%] vs 13.3% [95% CI, 13.1%-13.6%]). CONCLUSIONS AND RELEVANCE: The findings of this cross-sectional study suggest that actions to facilitate access to buprenorphine-based treatment for opioid use disorder during the COVID-19 pandemic were not associated with an increased proportion of overdose deaths involving buprenorphine. Efforts are needed to expand more equitable and culturally competent access to and provision of buprenorphine-based treatment.

Important questions remain on how hormonal contraceptives alter the local immune environment and the microbiota in the female genital tract and how such effects may impact susceptibility to HIV infection. We leveraged samples from a previously conducted clinical trial of Malawian women with (n = 73) and without (n = 24) HIV infection randomized to depot medroxyprogesterone acetate (DMPA) or the levonogestrel implant in equal numbers within each group and determined the effects of these hormonal contraceptives (HCs) on the vaginal immune milieu and the composition of the vaginal microbiota. Longitudinal data for soluble immune mediators, measured by multiplex bead arrays and enzyme-linked immunosorbent assays (ELISAs), and vaginal microbiota, assessed by 16S rRNA gene amplicon, were collected prior to and over a period of 180 days post-HC initiation. DMPA and levonogestrel had only minimal effects on the vaginal immune milieu and microbiota. In women with HIV, with the caveat of a small sample size, there was an association between the median log(10) change in the interleukin-12 (IL-12)/IL-10 ratio in vaginal fluid at day 180 post-HC compared to baseline when these women were classified as having a community state type (CST) IV vaginal microbiota and were randomized to DMPA. Long-lasting alterations in soluble immune markers or shifts in microbiota composition were not observed. Furthermore, women with HIV did not exhibit increased viral shedding in the genital tract after HC initiation. Consistent with the results of the ECHO (Evidence for Contraceptive Options and HIV Outcomes) trial, our data imply that the progestin-based HC DMPA and levonorgestrel are associated with minimal risk for women with HIV. (This study has been registered at ClinicalTrials.gov under registration no. NCT02103660). IMPORTANCE The results of the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial, the first large randomized controlled clinical trial comparing the HIV acquisition risk of women receiving DMPA, the levonorgestrel (LNG) implant, or the copper intrauterine device (IUD), did not reveal an increased risk of HIV acquisition for women on any of these three contraceptives. Our study results confirm that the two different progestin-based hormonal contraceptives DMPA and levonogestrel will not increase the risk for HIV infection. Furthermore, DMPA and levonogestrel have only minimal effects on the immune milieu and the microbiota in the vaginal tract, attesting to the safety of these hormonal contraceptives.

U.S. drug overdose deaths increased 30% from 2019 to 2020 and 15% in 2021, resulting in an estimated 108,000 deaths in 2021.* Among persons aged 14-18 years, overdose deaths increased 94% from 2019 to 2020 and 20% from 2020 to 2021 (1), although illicit drug use declined overall among surveyed middle and high school students during 2019-2020 (2). Widespread availability of illicitly manufactured fentanyls (IMFs),() proliferation of counterfeit pills resembling prescription drugs but containing IMFs or other illicit drugs,() and ease of purchasing pills through social media() have increased fatal overdose risk among adolescents (1,3). Using CDC's State Unintentional Drug Overdose Reporting System (SUDORS), this report describes trends and characteristics of overdose deaths during July 2019-December 2021 among persons aged 10-19 years (hereafter referred to as adolescents). From July-December 2019 to July-December 2021, median monthly overdose deaths increased 109%, and deaths involving IMFs increased 182%. Approximately 90% of overdose deaths involved opioids, and 83.9% involved IMFs; however, only 35% of decedents had documented opioid use history. Counterfeit pill evidence was present in 24.5% of overdose deaths, and 40.9% of decedents had evidence of mental health conditions or treatment. To prevent overdose deaths among adolescents, urgent efforts are needed, including preventing substance use initiation, strengthening partnerships between public health and public safety to reduce availability of illicit drugs, expanding efforts focused on resilience and connectedness of adolescents to prevent substance misuse and related harms, increasing education regarding IMFs and counterfeit pills, expanding naloxone training and access, and ensuring access to treatment for substance use and mental health disorders.

In 2020, nearly 92 000 drug overdose deaths occurred in the United States.1 Provisional estimates from the Centers for Disease Control and Prevention (CDC) indicate that overdose deaths continued to rise in 2021.2 The rise in opioid overdose deaths can be described in the following 3 waves3: (1) increase in deaths involving prescription opioids starting in the late 1990s,4 (2) increase in deaths involving heroin starting in 2010,5 and (3) increase in deaths involving synthetic opioids, predominantly illicitly manufactured fentanyl and fentanyl analogs (IMFs), starting in 2013.6,7 Synthetic opioids remain the primary driver of overdose deaths.2,8

INTRODUCTION: Drug overdose deaths increased approximately 30% from 2019 to 2020 in the United States. Examining rates by demographic and social determinants of health characteristics can identify disproportionately affected populations and inform strategies to reduce drug overdose deaths. METHODS: Data from the State Unintentional Drug Overdose Reporting System (SUDORS) were used to analyze overdose death rates from 2019 to 2020 in 25 states and the District of Columbia. Rates were examined by race and ethnicity and county-level social determinants of health (e.g., income inequality and treatment provider availability). RESULTS: From 2019 to 2020, drug overdose death rates increased by 44% and 39% among non-Hispanic Black (Black) and non-Hispanic American Indian or Alaska Native (AI/AN) persons, respectively. Significant disparities were found across sex, age, and racial and ethnic subgroups. In particular, the rate in 2020 among Black males aged ≥65 years (52.6 per 100,000) was nearly seven times that of non-Hispanic White males aged ≥65 years (7.7). A history of substance use was frequently reported. Evidence of previous substance use treatment was lowest for Black persons (8.3%). Disparities in overdose deaths, particularly among Black persons, were larger in counties with greater income inequality. Opioid overdose rates in 2020 were higher in areas with more opioid treatment program availability compared with areas with lower opioid treatment availability, particularly among Black (34.3 versus 16.6) and AI/AN (33.4 versus 16.2) persons. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Health disparities in overdose rates continue to worsen, particularly among Black and AI/AN persons; social determinants of health, such as income inequality, exacerbate these inequities. Implementation of available, evidence-based, culturally responsive overdose prevention and response efforts that address health disparities impacting disproportionately affected populations are urgently needed.

In 2020, 38,048 drug overdose deaths were reported from 28 states and DC for an age-adjusted rate of 30.6 per 100,000 people | 70% of drug overdose deaths involved illicitly manufactured fentanyls (IMFs) | The rate of drug overdose deaths was highest among American Indian/Alaska Native, non-Hispanic and Black, non-Hispanic persons | Two-thirds of decedents had at least one potential opportunity for linkage to care or implementation of a life-saving action prior to death

BACKGROUND: The majority of drug overdose deaths in the United States involve opioids, and synthetic opioid-involved overdose death rates are increasing. Naloxone is a key prevention strategy yet estimates of its administration are limited. METHODS: We analyzed 2019 data from 37 states and the District of Columbia in CDC's State Unintentional Drug Overdose Reporting System to estimate the percentage of decedents, by sociodemographic subgroup, who experienced a fatal opioid-involved overdose and had no evidence of naloxone administration. RESULTS: A total of 77.3% of 33,084 opioid-involved overdose deaths had no evidence of naloxone administration. Statistically significant subgroup differences were observed for all sociodemographic groups examined except housing status. The highest percentages of decedents lacking evidence of naloxone administration were those with highest educational attainment (doctorate or professional degree, 87.0%), oldest (55-64 years, 83.4%; ≥65 years, 87.3%) and youngest ages (<15 years, 87.5%), and single marital status (84.5%). The lowest percentages of no evidence of naloxone administration were observed for non-Hispanic American Indian/Alaskan Native persons (66.2%) and those ages 15-24 years (70.8%). CONCLUSIONS: More than three-quarters of opioid-involved overdose deaths had no evidence of naloxone administration, underscoring the need to ensure sufficient naloxone access and capacity for utilization. While fatal overdose data cannot fully characterize sociodemographic disparities in naloxone administration, naloxone education and access efforts can be informed by apparent inequities. Public health partners can assist persons who use drugs (PWUD) by maintaining naloxone supply and amplifying messages about the high risk of using drugs alone among PWUD and their social networks.

During May 2020-April 2021, the estimated number of drug overdose deaths in the United States exceeded 100,000 over a 12-month period for the first time, with 64.0% of deaths involving synthetic opioids other than methadone (mainly illicitly manufactured fentanyls [IMFs], which include both fentanyl and illicit fentanyl analogs).* Introduced primarily as adulterants in or replacements for white powder heroin east of the Mississippi River (1), IMFs are now widespread in white powder heroin markets, increasingly pressed into counterfeit pills resembling oxycodone, alprazolam, or other prescription drugs, and are expanding into new markets, including in the western United States(†) (2). This report describes trends in overdose deaths involving IMFs (IMF-involved deaths) during July 2019-December 2020 (29 states and the District of Columbia [DC]), and characteristics of IMF-involved deaths during 2020 (39 states and DC) using data from CDC's State Unintentional Drug Overdose Reporting System (SUDORS). During July 2019-December 2020, IMF-involved deaths increased sharply in midwestern (33.1%), southern (64.7%), and western (93.9%) jurisdictions participating in SUDORS. Approximately four in 10 IMF-involved deaths also involved a stimulant. Highlighting the need for timely overdose response, 56.1% of decedents had no pulse when first responders arrived. Injection drug use was the most frequently reported individual route of drug use (24.5%), but evidence of snorting, smoking, or ingestion, but not injection drug use was found among 27.1% of decedents. Adapting and expanding overdose prevention, harm reduction, and response efforts is urgently needed to address the high potency (3), and various routes of use for IMFs. Enhanced treatment for substance use disorders is also needed to address the increased risk for overdose (4) and treatment complications (5) associated with using IMFs with stimulants.

BACKGROUND: Drug overdose deaths involving stimulants, including cocaine and psychostimulants with abuse potential (e.g., methamphetamine), have been increasing, partly because of co-involvement with opioids. Stimulant-involved overdose deaths have disproportionately increased among non-Hispanic Black (Black) and non-Hispanic American Indian/Alaskan Native (AI/AN) persons; however, the role of opioids in exacerbating disproportionate stimulant-involved death rates is unclear. METHODS: Analysis of National Vital Statistics System multiple cause-of-death mortality files examined age-adjusted cocaine- and psychostimulant-involved death rates. Analyses of death rates stratified by racial and ethnic group and opioid co-involvement included: 1) Joinpoint regression of 2004-2019 trends, 2) changes in rates from 2018 to 2019, and 3) demographic and geographic characteristics of 2019 deaths. RESULTS: From 2004 to 2019, cocaine and psychostimulant-involved death rates were higher for Black and AI/AN persons, respectively. Among all groups, increases in cocaine-involved overdose rates were largely driven by opioid co-involvement, particularly after 2013. From 2004 to 2019, rates for psychostimulant-involved deaths increased with and without opioid co-involvement. Rates for overdoses co-involving cocaine and synthetic opioids increased from 2018 to 2019 for Hispanic, non-Hispanic White (White), and Black persons. Psychostimulant-involved overdose rates with and without synthetic opioid co-involvement increased among Hispanic, White, and Black persons. In 2019, Black and AI/AN persons continued to experience higher cocaine- and psychostimulant-involved death rates, respectively. CONCLUSIONS: Stimulant-involved deaths continue to increase, and the role of opioids in driving these deaths varies by race and ethnicity. Ensuring equitable access to proven prevention and treatment interventions and incorporating social determinants of health into future research around effective pharmacotherapies may help reduce stimulant-involved overdose deaths.

Deaths involving synthetic opioids other than methadone (synthetic opioids), which largely consist of illicitly manufactured fentanyl; psychostimulants with abuse potential (e.g., methamphetamine); and cocaine have increased in recent years, particularly since 2013 (1,2). In 2019, a total of 70,630 drug overdose deaths occurred, corresponding to an age-adjusted rate of 21.6 per 100,000 population and a 4.3% increase from the 2018 rate (20.7) (3). CDC analyzed trends in age-adjusted overdose death rates involving synthetic opioids, psychostimulants, cocaine, heroin, and prescription opioids during 2013-2019, as well as geographic patterns in synthetic opioid- and psychostimulant-involved deaths during 2018-2019. From 2013 to 2019, the synthetic opioid-involved death rate increased 1,040%, from 1.0 to 11.4 per 100,000 age-adjusted (3,105 to 36,359). The psychostimulant-involved death rate increased 317%, from 1.2 (3,627) in 2013 to 5.0 (16,167) in 2019. In the presence of synthetic opioid coinvolvement, death rates for prescription opioids, heroin, psychostimulants, and cocaine increased. In the absence of synthetic opioid coinvolvement, death rates increased only for psychostimulants and cocaine. From 2018 to 2019, the largest relative increase in the synthetic opioid-involved death rate occurred in the West (67.9%), and the largest relative increase in the psychostimulant-involved death rate occurred in the Northeast (43.8%); these increases represent important changes in the geographic distribution of drug overdose deaths. Evidence-based prevention and response strategies including substance use disorder treatment and overdose prevention and response efforts focused on polysubstance use must be adapted to address the evolving drug overdose epidemic.

INTRODUCTION: Provisional estimates indicate that drug overdose deaths increased in 2019 after a slight decrease in 2018. In 2018, overdose deaths primarily involved opioids, with continued increases in deaths involving illicitly manufactured fentanyls (IMFs). Deaths involving stimulants such as cocaine and methamphetamine are also increasing, mainly in combination with opioids. METHODS: CDC analyzed data on drug overdose deaths during January-June 2019 from 24 states and the District of Columbia (DC) in the State Unintentional Drug Overdose Reporting System to describe characteristics and circumstances of opioid- and stimulant-involved overdose deaths. RESULTS: Among 16,236 drug overdose deaths in 24 states and DC, 7,936 (48.9%) involved opioids without stimulants, 5,301 (32.6%) involved opioids and stimulants, 2,056 (12.7%) involved stimulants without opioids, and 943 (5.8%) involved neither opioids nor stimulants. Approximately 80% of overdose deaths involved one or more opioid, and IMFs were involved in three of four opioid-involved overdose deaths. IMFs, heroin, cocaine, or methamphetamine (alone or in combination) were involved in 83.8% of overdose deaths. More than three in five (62.7%) overdose deaths had documentation of at least one potential opportunity for overdose prevention intervention. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Identifying opportunities to intervene before an overdose death and implementing evidence-based prevention policies, programs, and practices could save lives. Strategies should address characteristics of overdoses involving IMFs, such as rapid overdose progression, as well as opioid and stimulant co-involvement. These efforts should be complemented by efforts to prevent initiation of prescription opioid and stimulant misuse and illicit drug use.

Objectives: Our primary objective was to compare geometric mean levonorgestrel concentrations between levonorgestrel implant users who were or were not taking the antiretroviral efavirenz, for up to 30 months after implant initiation. Our secondary objective was to evaluate the pregnancy rate among levonorgestrel implant users on efavirenz. Study design: We performed a subanalysis of 42 Malawian women randomized to initiate the levonorgestrel implant as part of a parent randomized clinical trial. Our subset included 30 HIV-infected women taking efavirenz and 12 HIV-uninfected women not taking efavirenz. They underwent urine pregnancy testing every 3 months and serum levonorgestrel testing at day 3 and months 1, 3, 6, 12, 18, 24, 27 and 30 after implant initiation. Geometric mean levonorgestrel concentrations were calculated for efavirenz users and non-efavirenz users at each time point. Results: The geometric mean levonorgestrel concentrations were lower for efavirenz users than non-efavirenz users at every time point; the geometric mean ratio for efavirenz users:non-efavirenz users ranged from 0.60 [90% confidence interval (CI) 0.46–0.79] at 1 month to 0.27 (90% CI 0.12–0.61) at 30 months after implant insertion. No pregnancies occurred over 60 woman-years of concomitant levonorgestrel implant and efavirenz use, although 11 women had levonorgestrel concentrations < 180 pg/mL (the previously suggested minimum threshold concentration for efficacy). Conclusions: Efavirenz users had lower levonorgestrel concentrations than non-efavirenz users, and one third of our concomitant efavirenz and levonorgestrel implant users had concentrations < 180 pg/mL. Continued evaluation of the contraceptive efficacy of the levonorgestrel implant may be needed for efavirenz users. Implications: Among 42 Malawian women using the levonorgestrel implant for contraception, women who were taking the antiretroviral efavirenz had lower serum levonorgestrel concentrations than women who were not taking efavirenz. However, none of the women who were taking efavirenz became pregnant over 60 women-years of follow-up.

Of the 70,237 drug overdose deaths in the United States in 2017, approximately two thirds (47,600) involved an opioid (1). In recent years, increases in opioid-involved overdose deaths have been driven primarily by deaths involving synthetic opioids other than methadone (hereafter referred to as synthetic opioids) (1). CDC analyzed changes in age-adjusted death rates from 2017 to 2018 involving all opioids and opioid subcategories* by demographic characteristics, county urbanization levels, U.S. Census region, and state. During 2018, a total of 67,367 drug overdose deaths occurred in the United States, a 4.1% decline from 2017; 46,802 (69.5%) involved an opioid (2). From 2017 to 2018, deaths involving all opioids, prescription opioids, and heroin decreased 2%, 13.5%, and 4.1%, respectively. However, deaths involving synthetic opioids increased 10%, likely driven by illicitly manufactured fentanyl (IMF), including fentanyl analogs (1,3). Efforts related to all opioids, particularly deaths involving synthetic opioids, should be strengthened to sustain and accelerate declines in opioid-involved deaths. Comprehensive surveillance and prevention measures are critical to reducing opioid-involved deaths, including continued surveillance of evolving drug use and overdose, polysubstance use, and the changing illicit drug market; naloxone distribution and outreach to groups at risk for IMF exposure; linkage to evidence-based treatment for persons with substance use disorders; and continued partnerships with public safety.

BACKGROUND: Maternal mortality rates in the United States appear to be increasing. One potential reason may be increased identification of maternal deaths after the addition of a pregnancy checkbox to the death certificate. In 2016, four state health departments (Georgia, Louisiana, Michigan, Ohio) implemented a pregnancy checkbox quality assurance pilot, with technical assistance provided by the Centers for Disease Control and Prevention. The pilot aimed to improve accuracy of the pregnancy checkbox on death certificates and resultant state maternal mortality estimates. OBJECTIVE(S): To estimate the validity of the pregnancy checkbox on the death certificate and describe characteristics associated with errors using 2016 data from a four state quality assurance pilot. STUDY DESIGN: Potential pregnancy-associated deaths were identified by linking death certificates with birth or fetal death certificates from within a year preceding death or by pregnancy checkbox status. Death certificates which indicated the decedent was pregnant within a year of death via the pregnancy checkbox, but that did not link to a birth or fetal death certificate, were referred for active follow-up to confirm pregnancy status by either death certifier confirmation or medical record review. Descriptive statistics and 95% confidence intervals were used to examine the distributions of demographic characteristics by pregnancy confirmation category (i.e., confirmed pregnant, confirmed not pregnant, and unable to confirm). We compared the proportion confirmed pregnant and confirmed not pregnant within age, race/ethnicity, pregnancy checkbox category, and certifier type categories using a Wald test of proportions. Binomial and Poisson regression models were used to estimate prevalence ratios for having an incorrect pregnancy checkbox (false positive, false negative) by age group, race/ethnicity, pregnancy checkbox category, and certifier type. RESULTS: Among 467 potential pregnancy-associated deaths, 335 (72%) were confirmed pregnant either via linkage to a birth or fetal death certificate, certifier confirmation, or review of medical records. Ninety-seven (21%) women were confirmed not pregnant (false positives) and 35 (7%) were unable to be confirmed. Women confirmed pregnant were significantly younger than women confirmed not pregnant (p<.001). Deaths certified by coroners and medical examiners were more likely to be confirmed pregnant than confirmed not pregnant (p=0.04). The association between decedent age category and false positive status followed a dose-response relationship (p<0.001), with increasing prevalence ratios for each increase in age category. Death certificates of non-Hispanic black women were more likely to be false positives, compared with non-Hispanic white women [prevalence ratio (PR) 1.41, 95% confidence interval (CI) 1.01, 1.96]. The sensitivity of the pregnancy checkbox among these four states in 2016 was 62% and the positive predictive value was 68%. CONCLUSION(S): We provide a multi-state analysis of the validity of the pregnancy checkbox and highlight a need for more accurate reporting of pregnancy status on death certificates. States and other jurisdictions may increase the accuracy of their data used to calculate maternal mortality rates by implementing quality assurance processes.

The risk of maternal death in the U.S. is higher than peer nations and rising, and varies dramatically by the race and place of residence of the woman. Critical efforts to reduce maternal mortality include patient risk stratification and system-level quality improvement efforts targeting specific aspects of clinical care. These efforts are important for addressing the causes of an individual's risk, but research to date suggests that individual risk factors alone do not adequately explain between-group disparities in pregnancy-related death by race, ethnicity, or geography. The holistic review and multidisciplinary makeup of maternal mortality review committees (MMRC) make them well positioned to fill knowledge gaps about the drivers of racial and geographic inequity in maternal death. However, committees may lack the conceptual framework, contextual data, and evidence base needed to identify community-based contributing factors to death, and when appropriate to make recommendations for future action. By incorporating a multileveled, theory-grounded framework for causes of health inequity, along with indicators of the 'community vital signs' - the social and community context in which women live, work, and seek healthcare - MMRCs may identify novel underlying factors at the community level that enhance understanding of racial and geographic inequity in maternal mortality. By considering evidence-informed community and regional resources and policies for addressing these factors, novel prevention recommendations, including recommendations that extend outside the realm of the formal health care system, may emerge.

Approximately 700 women die in the United States each year as a result of pregnancy or its complications, and significant racial/ethnic disparities in pregnancy-related mortality exist (1). Data from CDC's Pregnancy Mortality Surveillance System (PMSS) for 2007-2016 were analyzed. Pregnancy-related mortality ratios (PRMRs) (i.e., pregnancy-related deaths per 100,000 live births) were analyzed by demographic characteristics and state PRMR tertiles (i.e., states with lowest, middle, and highest PRMR); cause-specific proportionate mortality by race/ethnicity also was calculated. Over the period analyzed, the U.S. overall PRMR was 16.7 pregnancy-related deaths per 100,000 births. Non-Hispanic black (black) and non-Hispanic American Indian/Alaska Native (AI/AN) women experienced higher PRMRs (40.8 and 29.7, respectively) than did all other racial/ethnic groups. This disparity persisted over time and across age groups. The PRMR for black and AI/AN women aged >/=30 years was approximately four to five times that for their white counterparts. PRMRs for black and AI/AN women with at least some college education were higher than those for all other racial/ethnic groups with less than a high school diploma. Among state PRMR tertiles, the PRMRs for black and AI/AN women were 2.8-3.3 and 1.7-3.3 times as high, respectively, as those for non-Hispanic white (white) women. Significant differences in cause-specific proportionate mortality were observed among racial/ethnic populations. Strategies to address racial/ethnic disparities in pregnancy-related deaths, including improving women's health and access to quality care in the preconception, pregnancy, and postpartum periods, can be implemented through coordination at the community, health facility, patient, provider, and system levels.

BACKGROUND: Approximately 700 women die from pregnancy-related complications in the United States every year. METHODS: Data from CDC's national Pregnancy Mortality Surveillance System (PMSS) for 2011-2015 were analyzed. Pregnancy-related mortality ratios (pregnancy-related deaths per 100,000 live births; PRMRs) were calculated overall and by sociodemographic characteristics. The distribution of pregnancy-related deaths by timing relative to the end of pregnancy and leading causes of death were calculated. Detailed data on pregnancy-related deaths during 2013-2017 from 13 state maternal mortality review committees (MMRCs) were analyzed for preventability, factors that contributed to pregnancy-related deaths, and MMRC-identified prevention strategies to address contributing factors. RESULTS: For 2011-2015, the national PRMR was 17.2 per 100,000 live births. Non-Hispanic black (black) women and American Indian/Alaska Native women had the highest PRMRs (42.8 and 32.5, respectively), 3.3 and 2.5 times as high, respectively, as the PRMR for non-Hispanic white (white) women (13.0). Timing of death was known for 87.7% (2,990) of pregnancy-related deaths. Among these deaths, 31.3% occurred during pregnancy, 16.9% on the day of delivery, 18.6% 1-6 days postpartum, 21.4% 7-42 days postpartum, and 11.7% 43-365 days postpartum. Leading causes of death included cardiovascular conditions, infection, and hemorrhage, and varied by timing. Approximately sixty percent of pregnancy-related deaths from state MMRCs were determined to be preventable and did not differ significantly by race/ethnicity or timing of death. MMRC data indicated that multiple factors contributed to pregnancy-related deaths. Contributing factors and prevention strategies can be categorized at the community, health facility, patient, provider, and system levels and include improving access to, and coordination and delivery of, quality care. CONCLUSIONS: Pregnancy-related deaths occurred during pregnancy, around the time of delivery, and up to 1 year postpartum; leading causes varied by timing of death. Approximately three in five pregnancy-related deaths were preventable. IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Strategies to address contributing factors to pregnancy-related deaths can be enacted at the community, health facility, patient, provider, and system levels.

Antimicrobial drug resistance is a serious health hazard driven by overuse. Administration of antimicrobial drugs to HIV-exposed, uninfected infants, a population that is growing and at high risk for infection, is poorly studied. We therefore analyzed factors associated with antibacterial drug administration to HIV-exposed, uninfected infants during their first year of life. Our study population was 2,152 HIV-exposed, uninfected infants enrolled in the Breastfeeding, Antiretrovirals and Nutrition study in Lilongwe, Malawi, during 2004-2010. All infants were breastfed through 28 weeks of age. Antibacterial drugs were prescribed frequently (to 80% of infants), and most (67%) of the 5,329 prescriptions were for respiratory indications. Most commonly prescribed were penicillins (43%) and sulfonamides (23%). Factors associated with lower hazard for antibacterial drug prescription included receipt of cotrimoxazole preventive therapy, receipt of antiretroviral drugs, and increased age. Thus, cotrimoxazole preventive therapy may lead to fewer prescriptions for antibacterial drugs for these infants.

BACKGROUND: Some observational studies have found increased HIV risk associated with self-reported use of injectable depot medroxyprogesterone acetate (DMPA). Testing blood samples for MPA, the progestin in DMPA, permits validation of self-reported data and exploration of whether potential HIV risk is correlated with MPA levels, which are highest soon after injection. METHODS: We conducted a case-control study testing archived serum from women who participated in three longitudinal studies of HIV prevention in East and southern Africa. Case samples, from women who acquired HIV, were from visits that occurred at or immediately prior to the first evidence of HIV infection. Secondary analyses restricted to case samples collected within 15 and 30 days of the estimated date of HIV infection. Matched control samples were from women who remained HIV-uninfected. We used multivariable conditional logistic regression to compare exogenous hormone levels, quantified through mass spectrometry, among cases and controls. RESULTS: When restricted to cases with samples collected within </=15 days of estimated date of HIV infection, MPA detection was more frequent among women who acquired HIV (adjusted odds ratio [AOR] = 2.75, 95% confidence interval [CI] 1.22-6.19). In this subset, the increase in HIV risk was only among samples with MPA detected at a low level of 0.02-0.50ng/ml: 36.7% of cases and 9.4% of controls, AOR = 6.03, 95% CI 2.50-14.54. CONCLUSIONS: Detection of MPA at low levels close to the estimated time of HIV acquisition was significantly more frequent among women who acquired HIV. Studies are needed that explore biological mechanisms elicited by any MPA level and HIV risk.

BACKGROUND: Concentration of antiretroviral (ARV) drug found in plasma, and amounts of drug excreted into breastmilk, may affect HIV viral load and potentially perinatal HIV transmission. METHODS: In this cohort study with two-phase sampling, we included mothers randomized to postpartum maternal ARVs or daily infant nevirapine during 28 weeks of breastfeeding in the Breastfeeding, Antiretrovirals and Nutrition (BAN) study. Among these, we included all mothers who transmitted HIV to their infants between 2-28 weeks and 15% of mothers who did not (n=27 and 227, respectively). Spearman correlation coefficients (r2) were used to assess correlation between maternal plasma and breastmilk ARV concentration. Associations between the median effective drug concentration (EC50) and detectable maternal viral load (plasma: >40 copies/ml, breastmilk: >56 copies/ml) were assessed using mixed effects models. Cox models were used to estimate the association between maternal or infant plasma drug concentration and breastmilk HIV transmission from 2-28 weeks. RESULTS: All ARV compounds exhibited substantial correlations between maternal plasma and breastmilk concentrations (r2: 0.85-0.98, p-value <0.0001). Having plasma drug concentration above the EC50 was associated with lower odds of having detectable HIV RNA (maternal plasma OR 0.64, 95%CI 0.45-0.91; breastmilk OR 0.22, 95% CI 0.14-0.35) and a reduced rate of breastmilk HIV transmission (HR 0.40, 95% CI 0.18-0.93). Having breastmilk drug concentration above the EC50 was also associated with lower odds of having detectable maternal HIV RNA (plasma OR 0.62, 95%CI 0.45-0.85; breastmilk OR 0.42, 95% CI 0.29-0.59). CONCLUSION: Ensuring adequate drug concentration is important for viral suppression and preventing breastmilk HIV transmission.

OBJECTIVE: To develop a method to simultaneously quantify five commonly used hormonal contraceptives (HC) and 2 endogenous sex steroids by liquid chromatography-tandem triple quadrupole mass spectrometry (LC-MS/MS) and apply this method to human serum samples. STUDY DESIGN: We developed a method to simultaneously analyze ethinyl estradiol (EE2), etonogestrel (ENG), levonorgestrel (LNG), medroxyprogesterone acetate (MPA), and norethisterone (NET), along with estradiol (E2) and progesterone (P4) in human serum for a Shimadzu Nexera-LCMS-8050 LC-MS/MS platform. We analyzed serum collected from women self-reporting use of oral contraceptives, contraceptive implants or injectable contraceptives (n=14) and normally cycling women using no HC (n=15) as well as pooled samples from women administered various HC (ENG, n=6; LNG, n=14; MPA, n=7; NET, n=5). RESULTS: Limits of quantitation were 0.010ng/ml for E2, EE2, and P4; 0.020ng/ml for ENG, LNG, and MPA; and 0.040ng/ml for NET. Precisions for all assays, as indicated by coefficient of variation (CV) were less than or equal to 12.1%. Accuracies for all assays were in the range of 95-108%. Endogenous hormone values obtained from analysis of human serum samples are in agreement with levels previously reported in the literature for normally cycling women as well as for women taking the appropriate HC. CONCLUSIONS: We have developed a robust, accurate, and sensitive method for simultaneously analyzing commonly used contraceptive steroids and endogenous sex steroids in human serum. IMPLICATIONS: This analytical method can be used for quantitating contraceptive steroid levels in women for monitoring systemic exposure to determine drug interactions, nonadherence, misreporting, and proper dosing.

OBJECTIVES: Studies that rely on self-report to investigate the relationship between hormonal contraceptive use and HIV acquisition and transmission, as well as other health outcomes, could have compromised results due to misreporting. We determined the frequency of misreported hormonal contraceptive use among African women with and at risk for HIV. STUDY DESIGN: We tested 1102 archived serum samples from 664 African women who had participated in prospective HIV prevention studies. Using a novel high-performance liquid chromatography mass-spectrometry assay, we quantified exogenous hormones for injectables (medroxyprogesterone acetate or norethisterone), oral contraceptives (OC) (levonorgestrel or ethinyl estradiol), and implants (levonorgestrel or etonogestrel) and compared them to self-reported use. RESULTS: Among women reporting hormonal contraceptive use, 258/358 (72%) of samples were fully concordant with self-report, as were 642/744 (86%) of samples from women reporting no hormonal contraceptive use. However, 42/253 (17%) of samples from women reporting injectable use, 41/66 (62%) of samples from self-reported OC users, and 3/39 (8%) of samples from self-reported implant users had no quantifiable hormones. Among self-reported non-users, 102/744 (14%) had>/=1 hormone present. Concordance between self-reported method and exogenous hormones did not differ by HIV status. CONCLUSION: Among African women with and at risk for HIV, testing of exogenous hormones revealed agreement with self-reported contraceptive use for most women. However, unexpected exogenous hormones were identified among self-reported hormonal contraceptive users and non-users, and an important fraction of women reporting hormonal contraceptive use had no hormones detected; absence of oral contraceptive hormones could be due, at least in part, to samples taken during the hormone-free interval. Misreporting of hormonal contraceptive use could lead to biased results in observational studies of the relationship between contraceptive use and health outcomes. IMPLICATIONS: Research studies investigating associations between hormonal contraceptive use and HIV should consider validating self-reported use by objective measures; because both over- and under-reporting of use occurs, potential misclassification based on self-report could lead to biased results in directions that cannot be easily predicted.

OBJECTIVE: To assess the extent of concordance between self-reported contraceptive use and the presence of contraceptive progestins in serum. STUDY DESIGN: We evaluated self-reported contraceptive use by using radioimmunoassay to examine baseline serum levels of medroxyprogesterone acetate (MPA) and levonorgestrel (LNG) among 97 Malawian women enrolling in a contraceptive trial. RESULTS: Twelve percent (12/97) of study participants who reported no hormonal contraceptive use in the previous 6months had either MPA or LNG detected in their serum. CONCLUSIONS: The observed discordance between self-report and detection of exogenous hormones in serum indicates that caution is warranted when drawing conclusions based on self-reported contraceptive use.

Background: Genital human immunodeficiency virus (HIV) RNA shedding can continue despite HIV being undetectable in blood, and can be associated with transmission. Methods: We included African women on antiretroviral therapy (ART). Linear and generalized linear mixed models were used to compare the magnitude and prevalence of genital shedding, respectively, by time since ART initiation. Multivariable logistic regression with generalized estimating equations was used to assess predictors of genital shedding among women with undetectable plasma viral load (VL). Results: Among 1114 women, 5.8% of visits with undetectable plasma VL and 23.6% of visits with detectable VL had genital shedding. The proportion of visits with genital shedding decreased with time since ART initiation but the magnitude of shedding remained unchanged when plasma VL was undetectable (P = .032). Prevalence of shedding did not vary by time since ART initiation when plasma VL was detectable (P = .195), though the magnitude of shedding significantly increased (P = .04). Predictors of genital shedding were HIV disease stage, antiretroviral regimen, and genital ulcers or cervical tenderness. Discussion: In addition to ART, reducing immune activation through prevention and treatment of HIV-related conditions and genital tract infections may decrease the risk of HIV-1 shedding and potential transmission.

BACKGROUND: Maternal mortality ratios (MMR) appear to have increased in the United States over the last decade. Three potential contributing factors are: 1) a shifting maternal age distribution, 2) changes in age-specific MMR, and 3) the addition of a checkbox indicating recent pregnancy on the death certificate. OBJECTIVE: Determine the contribution of rising maternal age on changes in MMR from 1978-2012, and estimate the contribution of the pregnancy checkbox on increases in MMR over the last decade. STUDY DESIGN: Kitagawa decomposition analyses were conducted to partition the maternal age contribution to the MMR increase into two components: changes due to a shifting maternal age distribution, and changes due to higher age-specific mortality ratios. We used National Vital Statistics System (NVSS) natality and mortality data. The following five-year groupings were used: 1978-1982, 1988-1992, 1998-2002, and 2008-2012. Changes in age-specific MMRs among states that adopted the standard pregnancy checkbox onto their death certificate before 2008 (n=23) were compared with states that had not adopted the standard pregnancy checkbox on their death certificate by the end of 2012 (n=11) to estimate the percentage increase in the MMR due to the pregnancy checkbox. RESULTS: Overall U.S. MMRs for 1978-1982, 1988-1992, and 1998-2002 were 9.0, 8.1, and 9.1 deaths per 100,000 live births, respectively. There was a modest increase in the MMR between 1998-2002 and 2008-2012 in the 11 states that had not adopted the standard pregnancy checkbox on their death certificate by the end of 2012 (8.6 and 9.9 deaths per 100,000 respectively). However, the MMR more than doubled between 1998-2002 and 2008-2012 in the 23 states that adopted the standard pregnancy checkbox (9.0 to 22.4); this dramatic rise was almost entirely attributable to increases in age-specific MMRs (94.9%) as opposed to increases in maternal age (5.1%), with an estimated 90% of the observed change reflecting the change in maternal death identification rather than a real change in age-specific rates alone. Of all age categories, women ages 40 and older in states that adopted the standard pregnancy checkbox had the largest increase in MMR-from 31.9 to 200.5-a relative increase of 528%, which accounted for nearly one-third of the overall increase. An estimated 28.8% of the observed change was potentially due to maternal death misclassification among women ≥40. CONCLUSION: Increasing age-specific maternal mortality seems to be contributing more heavily than a changing maternal age distribution to recent increases in MMR. In states with the standard pregnancy checkbox, the vast majority of the observed change in MMR over the last decade was estimated to be due to the pregnancy checkbox, with the greatest change in MMR occurring in women ages ≥40 years. The addition of a pregnancy checkbox on state death certificates appears to be increasing case identification, but may also be leading to maternal death misclassification, particularly for women ages ≥40 years.

Background: HIV-exposed infants are disproportionately at risk of morbidity and mortality compared with their HIV-unexposed counterparts. The role of co-trimoxazole preventive therapy (CPT) in reducing leading causes of infectious morbidity is unclear. Methods: We used data from the Breastfeeding, Antiretrovirals and Nutrition (BAN) clinical trial (conducted 2004-2010, Malawi) to assess the association of 1) CPT and 2) asymptomatic malaria parasitemia with respiratory and diarrheal morbidity in infants. In June 2006, all HIV-exposed infants in BAN began receiving CPT (240 mg) from 6-36 weeks of age, or until weaning occurred and HIV infection was ruled out. All HIV-exposed, uninfected infants (HEI) at 8 weeks of age (n=1984) were included when CPT was the exposure. A subset of HEI (n=471) were tested for malarial parasitemia using dried blood spots from 12, 24, and 36 weeks of age. Cox proportional hazards models for recurrent gap-time data were used to examine the association of time-varying exposures on morbidity. Results: CPT was associated with a 36% reduction in respiratory morbidity (hazard ratio (HR) 0.64, 95% confidence interval (CI) 0.60-0.69) and a 41% reduction in diarrheal morbidity (HR 0.59, 95% CI 0.54-0.65). Having asymptomatic malaria parasitemia was associated with a 40% increase in respiratory morbidity (HR 1.40, 95% CI 1.13-1.74) and a 50% increase in diarrheal morbidity (HR 1.50, 95% CI 1.09-2.06), after adjusting for CPT. Conclusion: CPT may have an important role to play in reducing the leading global causes of morbidity and mortality in the growing population of HEIs in malaria-endemic resource-limited settings.

BACKGROUND: To explore the association between concomitant hormonal contraceptive and antiretroviral therapy (ART) use and (1) plasma viral suppression and (2) genital HIV shedding among HIV-positive women initiating ART. METHODS: We analyzed plasma viral load and genital viral RNA shedding from 1079 HIV-positive women initiating ART who were followed prospectively in 3 sub-Saharan African HIV prevention studies. Plasma and endocervical swab samples were collected every 6 months. Self-reported contraceptive use was categorized into injectable, implant, oral, or nonhormonal/no contraception. We used multivariate Cox regression to assess time to plasma viral suppression and logistic regression with generalized estimating equations to assess genital viral shedding for each contraceptive method. RESULTS: At the time of ART initiation, there were 211 (20%) injectable, 69 (6%) implant, 50 (5%) oral, and 749 (69%) nonhormonal or no method users. Plasma viral suppression was high (90% by 6 months) and hormonal contraceptives did not diminish time to plasma viral suppression as compared to nonhormonal/no methods [adjusted hazard ratios: injectables 0.89 (95% confidence interval: 0.75 to 1.07), implants 0.91 (0.68 to 1.23), and oral methods 1.33 (1.06 to 1.66)]. Genital viral shedding was uncommon any time after ART initiation (only 9% of samples had detectable viral shedding) and hormonal contraceptives were not associated with an increased detection of genital viral shedding [adjusted odds ratios: injectables 1.07 (0.69 to 1.65), implants 0.67 (0.31 to 1.49), and oral methods 0.56 (0.19 to 1.69)]. CONCLUSIONS: The hormonal contraceptives assessed were not associated with reduced ART effectiveness among HIV-positive women initiating ART. HIV-positive women should continue to be offered contraceptive options, including hormonal ones that best meet their needs.

Cytomegalovirus (CMV) is a DNA herpesvirus that is common worldwide. The two known main sources of primary CMV infection during pregnancy are through sexual activity and contact with young children. Primary infection occurs in approximately 1 to 4% of pregnancies, and is mostly asymptomatic in immunocompetent adults. However, primary infection may manifest as a mild mononucleosis or flu-like syndrome with persistent fever and fatigue. CMV can be transmitted from mother-to-child in utero, intrapartum, or during breastfeeding. Intrauterine transmission can lead to congenital CMV infection, a leading cause of permanent hearing and vision loss and neurological disability among children. Congenital CMV transmission rates are as high as 50% in women who acquire primary CMV infection during pregnancy, and less than 2% in women with nonprimary infection. There is no licensed CMV vaccine. Good hygiene practices and avoiding intimate contact with young children (e.g., kissing on the mouth and sharing utensils) have been suggested as an approach to prevent maternal primary CMV infection during pregnancy, but remains an unproven method of reducing the risk of congenital CMV infection. Approximately 1 in 10 infants who acquire CMV in utero will have clinical signs at birth, and an additional 10 to 15% will go on to develop late-onset sequelae. Antiviral treatment prenatally and postnatally has not proven effective at preventing congenital or postnatal CMV infection, and is not recommended for routine clinical care. However, antiviral treatment when initiated in the first month of life for symptomatic congenital CMV infection is recommended for improved neurodevelopmental and audiologic outcomes. Birth Defects Research 109:336-346, 2017. c.

BACKGROUND: Perinatal services exist today as a dyad of maternal and neonatal care. When perinatal care is fragmented or unavailable, excess morbidity and mortality may occur in pregnant women and newborns. OBJECTIVE: Describe spatial relationships between women of reproductive age, individual perinatal subspecialists (Maternal Fetal Medicine and Neonatology), and obstetric and neonatal critical care facilities in the United States to identify gaps in health care access. STUDY DESIGN: We used geographic visualization and conducted surface interpolation, nearest neighbor, and proximity analyses. Source data included 2010 United States Census, October 2013 National Provider Index, 2012 American Hospital Association, 2012 National Center for Health Statistics Natality File, and the 2011 American Academy of Pediatrics Directory. RESULTS: In October 2013, there were 2.5 neonatologists for every Maternal Fetal Medicine specialist in the United States. In 2012 there were 1.4 Level III or higher neonatal intensive care units (NICU) for every Level III obstetric unit (hereafter, obstetric critical care unit). Nationally, 87% of women of reproductive age live within 50 miles of both an obstetric critical care unit and NICU. However, 18% of obstetric critical care units had no NICU and 20% of NICUs had no obstetric critical care unit within a 10 mile radius. Additionally, 26% of obstetric critical care units had no Maternal Fetal Medicine specialist practicing within 10 miles of the facility and 4% of NICUs had no neonatologist practicing within 10 miles. CONCLUSION: Gaps in access and discordance between the availability of Level III or higher obstetric and neonatal care may affect delivery of risk appropriate care for high risk maternal fetal dyads. Further study is needed to understand the importance of these gaps and discordance on maternal and neonatal outcomes.