How much could anemia-related interventions reduce the HIV disparity in adverse birth outcomes?

Women and other people of childbearing potential living with HIV (WLHIV) have a higher risk of adverse birth outcomes than those without HIV (WWHIV). A higher risk of anemia in WLHIV could partially explain this disparity. Using a birth outcomes surveillance study in Botswana, we emulated target trials corresponding to currently available or feasible interventions on anemia. The first target trial evaluated two interventions: initiate multiple micronutrient supplementation (MMS), and MMS or iron and folic acid supplementation by 24 weeks gestation. The remaining target trials evaluated the interventions: eliminate anemia before pregnancy; and jointly eliminate anemia before pregnancy and initiate MMS. We estimated the observed disparity in adverse birth outcomes between WLHIV and WWHIV and compared the observed disparity measure (ODM) to the counterfactual disparity measure (CDM) under each intervention. Of 137,499 individuals (22% WLHIV), the observed risk of any adverse birth outcome was 26.0% in WWHIV and 34.5% in WLHIV (ODM, 8.5% [95% CI, 7.9-9.1%]). CDMs (95% CIs) ranged from 6.6% (4.8-8.4%) for the intervention to eliminate anemia and initiate MMS to 8.4% (7.7-9.1%) for the intervention to eliminate anemia only. Preventing anemia and expanding MMS may reduce HIV disparities in birth outcomes, but interventions with greater impact should be identified.

A Validated Algorithm to Identify Hepatic Decompensation in the Veterans Health Administration Electronic Health Record System.

PURPOSE: Accurate identification of hepatic decompensation is essential for pharmacoepidemiologic research among patients with chronic liver disease. METHODS: An algorithm using ≥ 1 inpatient or ≥ 2 outpatient International Classification of Diseases, 10th revision (ICD-10) codes for hepatic decompensation was developed in Veterans Health Administration data from October 2015 through July 2019. Medical records were reviewed by hepatologists to confirm cases. The positive predictive value (PPV) of the coding algorithm for confirmed hepatic decompensation was calculated. RESULTS: Hepatic decompensation was confirmed in 149/185 records meeting the algorithm (PPV 81%; 95% CI, 70%, 90%). The most common hepatic decompensation diagnosis was ascites. Only 56% of confirmed cases had an accompanying diagnosis code for cirrhosis. CONCLUSIONS: Our ICD-10-based coding algorithm identified hepatic decompensation with high PPV in Veterans Health Administration data.

Nirmatrelvir Plus Ritonavir for Early COVID-19 in a Large U.S. Health System : A Population-Based Cohort Study.

BACKGROUND: In the EPIC-HR (Evaluation of Protease Inhibition for Covid-19 in High-Risk Patients) trial, nirmatrelvir plus ritonavir led to an 89% reduction in hospitalization or death among unvaccinated outpatients with early COVID-19. The clinical impact of nirmatrelvir plus ritonavir among vaccinated populations is uncertain. OBJECTIVE: To assess whether nirmatrelvir plus ritonavir reduces risk for hospitalization or death among outpatients with early COVID-19 in the setting of prevalent SARS-CoV-2 immunity and immune-evasive SARS-CoV-2 lineages. DESIGN: Population-based cohort study analyzed to emulate a clinical trial using inverse probability-weighted models to account for anticipated bias in treatment. SETTING: A large health care system providing care for 1.5 million patients in Massachusetts and New Hampshire during the Omicron wave (1 January to 17 July 2022). PATIENTS: 44 551 nonhospitalized adults (90.3% with ≥3 vaccine doses) aged 50 years or older with COVID-19 and no contraindications for nirmatrelvir plus ritonavir. MEASUREMENTS: The primary outcome was a composite of hospitalization within 14 days or death within 28 days of a COVID-19 diagnosis. RESULTS: During the study period, 12 541 (28.1%) patients were prescribed nirmatrelvir plus ritonavir, and 32 010 (71.9%) were not. Patients prescribed nirmatrelvir plus ritonavir were more likely to be older, have more comorbidities, and be vaccinated. The composite outcome of hospitalization or death occurred in 69 (0.55%) patients who were prescribed nirmatrelvir plus ritonavir and 310 (0.97%) who were not (adjusted risk ratio, 0.56 [95% CI, 0.42 to 0.75]). Recipients of nirmatrelvir plus ritonavir had lower risk for hospitalization (adjusted risk ratio, 0.60 [CI, 0.44 to 0.81]) and death (adjusted risk ratio, 0.29 [CI, 0.12 to 0.71]). LIMITATION: Potential residual confounding due to differential access to COVID-19 vaccines, diagnostic tests, and treatment. CONCLUSION: The overall risk for hospitalization or death was already low (1%) after an outpatient diagnosis of COVID-19, but nirmatrelvir plus ritonavir reduced this risk further. PRIMARY FUNDING SOURCE: National Institutes of Health.

Emulating Target Trials to Avoid Immortal Time Bias - An Application to Antibiotic Initiation and Preterm Delivery.

BACKGROUND: Randomized trials in pregnancy are extremely challenging, and observational studies are often the only option to evaluate medication safety during pregnancy. However, such studies are often susceptible to immortal time bias if treatment initiation occurs after time zero of follow-up. We describe how emulating a sequence of target trials avoids immortal time bias and apply the approach to estimate the safety of antibiotic initiation between 24 and 37 weeks gestation on preterm delivery. METHODS: The Tsepamo Study captured birth outcomes at hospitals throughout Botswana from 2014 to 2021. We emulated 13 sequential target trials of antibiotic initiation versus no initiation among individuals presenting to care <24 weeks, one for each week from 24 to 37 weeks. For each trial, eligible individuals had not previously initiated antibiotics. We also conducted an analysis susceptible to immortal time bias by defining time zero as 24 weeks and exposure as antibiotic initiation between 24 and 37 weeks. We calculated adjusted risk ratios (RR) and 95% confidence intervals (CI) for preterm delivery. RESULTS: Of 111,403 eligible individuals, 17,009 (15.3%) initiated antibiotics between 24 and 37 weeks. In the sequence of target trials, RRs (95% CIs) ranged from 1.04 (0.90, 1.19) to 1.24 (1.11, 1.39) (pooled RR: 1.11 [1.06, 1.15]). In the analysis susceptible to immortal time bias, the RR was 0.90 (0.86, 0.94). CONCLUSIONS: Defining exposure as antibiotic initiation at any time during follow-up after time zero resulted in substantial immortal time bias, making antibiotics appear protective against preterm delivery. Conducting a sequence of target trials can avoid immortal time bias in pregnancy studies.

Does the Association Between Stimulant use and High Risk Sexual Behavior Vary by Injection Drug Use, Sexual Minority Status, or HIV Infection Status? A Meta-analysis.

There is strong evidence linking stimulant use, namely methamphetamine use, to sexual risk behavior among sexual minority men (SMM); we do not, however, have a good understanding of this relationship among other at-risk populations. In this study, we systematically reviewed associations between stimulant use (i.e., methamphetamine, crack cocaine, cocaine) and sexual risk behaviors among populations facing elevated risk of HIV transmission and acquisition (i.e., SMM, people who inject drugs (PWID), and people living with HIV/AIDS (PLWH)). Random-effects meta-analyses and sensitivity analyses that included crude and adjusted estimates separately were conducted to evaluate the impact of potential confounding variables. The results showed strong relationships between stimulant use and condomless sex, transactional sex, and multiple sexual partners. Results were broadly consistent when analyses were stratified by type of stimulant (methamphetamine, crack cocaine, and other stimulants) and risk group. Sensitivity analyses with confounding variables did not greatly impact results. The results indicate that stimulant use is associated with numerous sexual risk behaviors regardless of risk group, suggesting prevention efforts focused on reducing methamphetamine-related HIV risk should target a range of at-risk populations.

Cannabis use, pain interference, and prescription opioid receipt among persons with HIV: a target trial emulation study.

Concomitant with expanded legalization, cannabis is increasingly used to treat chronic pain among persons with HIV (PWH), despite equivocal benefit in research limited by small sample sizes and short duration of follow-up. To address these limitations, among a sample of PWH with pain interference enrolled in the Veterans Aging Cohort Study, we performed a target trial emulation study to compare the impact of four cannabis use strategies on pain interference. Among those receiving long-term opioid therapy (LTOT), we also explored impact of these strategies on ≥ 25% LTOT dose reduction. Among the analytic sample (N = 1284), the majority were men with a mean age of 50. Approximately 31% used cannabis and 12% received LTOT at baseline. Adjusting for demographic and clinical factors, cannabis use in any of 4 longitudinal patterns was not associated with resolved pain interference over 12- to 24-month follow-up. Among 153 participants receiving LTOT at baseline, cannabis use at both baseline and follow-up was negatively associated with LTOT dose reduction compared to no use at both baseline and follow-up. These findings support other observational studies finding no association between cannabis use and improved chronic pain or LTOT reduction among PWH.

The associations of incarceration and depression with healthcare experiences and utilization among Black men who have sex with men in HPTN 061.

Associations of incarceration with healthcare access and utilization among Black sexual minority men (BSMM) and differences in association among those with and without pre-incarceration symptoms of depression were measured. Secondary analysis using survey data from the longitudinal cohort HIV Prevention Trials Network 061 study was conducted among 1553 BSMM from six major U.S. cities from 2009 to 2011. We used modified log-binomial regression with robust standard errors to estimate associations of incarceration (reported at 6 month follow-up) on next six-month healthcare utilization and access (reported at the 12 month follow-up). We tested the significance of baseline depressive symptoms by incarceration interaction and reported differences in associations when observed. Participants with a history of incarceration were more likely to have depressive symptoms at baseline compared to those without. Recent incarceration was associated with almost twice the risk of mistrust in healthcare providers and emergency room utilization. Among men reporting depressive symptoms, a history of incarceration was associated with almost tripled risk of reporting providers do not communicate understandably. Among those with depression, one in five reported a missed visit regardless of incarceration status.

High risk of adverse birth outcomes among adolescents living with HIV in Botswana compared to adult women living with HIV and adolescents without HIV.

BACKGROUND: Adolescent girls are three times more likely to be living with HIV than boys of the same age. Prior studies have found associations between adolescent pregnancies and increased maternal morbidity and infant mortality, but few studies have assessed the impact of HIV infection on maternal and infant outcomes in adolescents. METHODS: The Tsepamo Study abstracts maternal and infant data from obstetric records in government maternity wards in Botswana. We assessed maternal complications and adverse birth outcomes for all singleton pregnancies from August 2014 to August 2020 at eighteen Tsepamo sites among adolescents (defined as 10-19 years of age) and adults (defined as 20-35 years of age), by HIV status. Univariate and multivariate logistic regression using a complete case analysis method were used to evaluate differences in outcomes. RESULTS: This analysis included 142,258 singleton births, 21,133 (14.9%) to adolescents and 121,125 (85.1%) to adults. The proportion of adults living with HIV (N = 22,114, 22.5%) was higher than adolescents (N = 1593, 7.6%). The proportion of most adverse birth outcomes was higher in adolescents. Among adolescents, those with HIV had increased likelihoods of anemia (aOR = 1.89, 95%CI 1.66, 2.15) and cesarean sections (aOR = 1.49, 95%CI 1.3,1.72), and infants with preterm birth (aOR = 1.15, 95%CI 1.0, 1.32), very preterm birth (aOR = 1.35, 95%CI 1.0,1.8), small for gestational age (aOR = 1.37, 95%CI 1.20,1.58), and very small for gestational age (aOR = 1.46, 95%CI 1.20, 1.79). CONCLUSIONS: Adolescent pregnancy and adolescent HIV infection remain high in Botswana. Adolescents have higher risk of adverse maternal and infant birth outcomes than adults, with the worst outcomes among adolescents living with HIV. Linking HIV prevention and family planning strategies for this age group may help minimize the number of infants with poor birth outcomes among this already vulnerable population.

Modest reduction in adverse birth outcomes following the COVID-19 lockdown.

BACKGROUND: Widespread lockdowns imposed during the coronavirus disease 2019 crisis may impact birth outcomes. OBJECTIVE: This study aimed to evaluate the association between the COVID-19 lockdown and the risk of adverse birth outcomes in Botswana. STUDY DESIGN: In response to the coronavirus disease 2019 crisis, Botswana enforced a lockdown that restricted movement within the country. We used data from an ongoing nationwide birth outcomes surveillance study to evaluate adverse outcomes (stillbirth, preterm birth, small-for-gestational-age fetuses, and neonatal death) and severe adverse outcomes (stillbirth, very preterm birth, very-small-for-gestational-age fetuses, and neonatal death) recorded prelockdown (January 1, 2020-April 2, 2020), during lockdown (April 3, 2020-May 7, 2020), and postlockdown (May 8, 2020-July 20, 2020). Using difference-in-differences analyses, we compared the net change in each outcome from the prelockdown to lockdown periods in 2020 relative to the same 2 periods in 2017-2019 with the net change in each outcome from the prelockdown to postlockdown periods in 2020 relative to the same 2 periods in 2017-2019. RESULTS: In this study, 68,448 women delivered a singleton infant in 2017-2020 between January 1 and July 20 and were included in our analysis (mean [interquartile range] age of mothers, 26 [22-32] years). Across the included calendar years and periods, the risk of any adverse outcome ranged from 27.92% to 31.70%, and the risk of any severe adverse outcome ranged from 8.40% to 11.38%. The lockdown period was associated with a 0.81 percentage point reduction (95% confidence interval, -2.95% to 1.30%) in the risk of any adverse outcome (3% relative reduction) and a 0.02 percentage point reduction (95% confidence interval, -0.79% to 0.75%) in the risk of any severe adverse outcome (0% relative reduction). The postlockdown period was associated with a 1.72 percentage point reduction (95% confidence, -3.42% to 0.02%) in the risk of any adverse outcome (5% relative reduction) and a 1.62 percentage point reduction (95% confidence interval, -2.69% to -0.55%) in the risk of any severe adverse outcome (14% relative reduction). Reductions in adverse outcomes were largest among women with human immunodeficiency virus and among women delivering at urban delivery sites, driven primarily by reductions in preterm birth and small-for-gestational-age fetuses. CONCLUSION: Adverse birth outcomes decreased from the prelockdown to postlockdown periods in 2020, relative to the change during the same periods in 2017-2019. Our findings may provide insights into associations between mobility and birth outcomes in Botswana and other low- and middle-income countries.

Estimating optimal dynamic treatment strategies under resource constraints using dynamic marginal structural models.

Methods for estimating optimal treatment strategies typically assume unlimited access to resources. However, when a health system has resource constraints, such as limited funds, access to medication, or monitoring capabilities, medical decisions must account for competition between individuals in resource usage. The problem of incorporating resource constraints into optimal treatment strategies has been solved for point exposures (1), that is, treatment strategies entailing a decision at just one time point. However, attempts to directly generalize the point exposure solution to dynamic time-varying treatment strategies run into complications. We sidestep these complications by targeting the optimal strategy within a clinically defined subclass. Our approach is to employ dynamic marginal structural models to estimate (counterfactual) resource usage under the class of candidate treatment strategies and solve a constrained optimization problem to choose the optimal strategy for which expected resource usage is within acceptable limits. We apply this method to determine the optimal dynamic monitoring strategy for people living with HIV when resource limits on monitoring exist using observational data from the HIV-CAUSAL Collaboration.

Integrating Screening and Treatment of Unhealthy Alcohol Use and Depression with Screening and Treatment of Anxiety, Pain, and Other Substance Use Among People with HIV and Other High-Risk Persons.

We review and synthesize results from a series of analyses estimating the benefit of screening for unhealthy alcohol use, depression, and tobacco to detect individuals at heightened risk for co-occurring anxiety, pain, depression, unhealthy alcohol use, and other substance use among people with HIV and HIV-uninfected individuals in the Veterans Aging Cohort Study. We also examine the potential impact of reducing unhealthy alcohol use and depressive symptoms on the incidence of co-occurring conditions. We found that screening for alcohol and depression may help identify co-occurring symptoms of anxiety, depression, and pain interference, treating unhealthy alcohol use may improve co-occurring pain interference and substance use, and improving depressive symptoms may improve co-occurring anxiety, pain interference, and smoking. We propose that an integrated approach to screening and treatment for unhealthy alcohol use, depression, anxiety, pain, and other substance use may facilitate diagnostic assessment and treatment of these conditions, improving morbidity and mortality.

Assessing knowledge, attitudes, and practices towards causal directed acyclic graphs: a qualitative research project.

Causal graphs provide a key tool for optimizing the validity of causal effect estimates. Although a large literature exists on the mathematical theory underlying the use of causal graphs, less literature exists to aid applied researchers in understanding how best to develop and use causal graphs in their research projects. We sought to understand why researchers do or do not regularly use DAGs by surveying practicing epidemiologists and medical researchers on their knowledge, level of interest, attitudes, and practices towards the use of causal graphs in applied epidemiology and health research. We used Twitter and the Society for Epidemiologic Research to disseminate the survey. Overall, a majority of participants reported being comfortable with using causal graphs and reported using them 'sometimes', 'often', or 'always' in their research. Having received training appeared to improve comprehension of the assumptions displayed in causal graphs. Many of the respondents who did not use causal graphs reported lack of knowledge as a barrier to using DAGs in their research. Causal graphs are of interest to epidemiologists and medical researchers, but there are several barriers to their uptake. Additional training and clearer guidance are needed. In addition, methodological developments regarding visualization of effect measure modification and interaction on causal graphs is needed.

Perceived Stress, Sexually Transmitted Infection, and Pelvic Inflammatory Disease: Examination of Differences in Associations Among Black and White Women.

INTRODUCTION: Perceived stress is linked to poor sexual and reproductive health, but its relationship with sexually transmitted infections (STIs) is less clear. The elevated burden of stress and STI among Black women suggests a need to examine racial differences in the associations on additive and multiplicative scales. METHODS: Using data from Black and White female participants from wave IV of the National Longitudinal Study of Adolescent to Adult Health (n = 4744), we examined the association of high stress (scores ≥6 on the Perceived Stress Scale-4) with self-reported past-year chlamydia diagnosis, combined curable STI, and lifetime pelvic inflammatory disease using modified Poisson regression with robust variance to estimate prevalence ratios and prevalence differences. Models included a race-stress product-interaction term and adjusted for sociodemographic variables, prior trauma and stressors, and mental health factors. RESULTS: In unadjusted analyses, stress was associated with STI among Black and White women. Adjusted associations were attenuated among White women; among Black women, stress remained associated with chlamydia (adjusted prevalence ratio, 2.22; 95% confidence interval, 1.30-3.79) and curable STI (adjusted prevalence ratio, 1.59; 95% confidence interval, 1.05-2.40), corresponding to approximately 5 excess cases of each. Among White women, poverty and personality traits were the strongest confounders; among Black women, poverty, trauma, and neurotic personality traits were the strongest confounders for chlamydia, although no factors seemed to confound the association with curable STI. CONCLUSIONS: Stress is independently linked to STI, particularly among Black women. Additional research with longitudinal data is needed to understand the role of stress on STI and address a significant health disparity.

Does Reducing Drinking in Patients with Unhealthy Alcohol Use Improve Pain Interference, Use of Other Substances, and Psychiatric Symptoms?

BACKGROUND: We aimed to investigate the impact of reducing drinking in patients with unhealthy alcohol use on improvement of chronic pain interference, substance use, and psychiatric symptoms. METHODS: We analyzed longitudinal data from 2003 to 2015 in the Veterans Aging Cohort Study, a prospective, multisite observational study of US veterans, by emulating a hypothetical randomized trial (a target trial). Alcohol use was assessed using the Alcohol Use Disorders Identification Test (AUDIT) questionnaire, and outcome conditions were assessed via validated survey items. Individuals were followed from the first time their AUDIT score was ≥ 8 (baseline), a threshold consistent with unhealthy alcohol use. We compared individuals who reduced drinking (AUDIT < 8) at the next follow-up visit with individuals who did not (AUDIT ≥ 8). We fit separate logistic regression models to estimate odds ratios for improvement of each condition 2 years postbaseline among individuals who had that condition at baseline: moderate or severe pain interference symptoms, tobacco smoking, cannabis use, cocaine use, depressive symptoms, and anxiety symptoms. Inverse probability weighting was used to account for potential selection bias and confounding. RESULTS: Adjusted 2-year odds ratios (95% confidence intervals) for associations between reducing drinking and improvement or resolution of each condition were as follows: 1.49 (0.91, 2.42) for pain interference symptoms, 1.57 (0.93, 2.63) for tobacco smoking, 1.65 (0.92, 2.95) for cannabis use, 1.83 (1.03, 3.27) for cocaine use, 1.11 (0.64, 1.92) for depressive symptoms, and 1.33 (0.80, 2.22) for anxiety symptoms. CONCLUSIONS: We found some evidence for improvement of pain interference symptoms and substance use after reducing drinking among US veterans with unhealthy alcohol use, but confidence intervals were wide.

Methodological Challenges When Studying Distance to Care as an Exposure in Health Research.

Distance to care is a common exposure and proposed instrumental variable in health research, but it is vulnerable to violations of fundamental identifiability conditions for causal inference. We used data collected from the Botswana Birth Outcomes Surveillance study between 2014 and 2016 to outline 4 challenges and potential biases when using distance to care as an exposure and as a proposed instrument: selection bias, unmeasured confounding, lack of sufficiently well-defined interventions, and measurement error. We describe how these issues can arise, and we propose sensitivity analyses for estimating the degree of bias.

Emulating a trial of joint dynamic strategies: An application to monitoring and treatment of HIV-positive individuals.

Decisions about when to start or switch a therapy often depend on the frequency with which individuals are monitored or tested. For example, the optimal time to switch antiretroviral therapy depends on the frequency with which HIV-positive individuals have HIV RNA measured. This paper describes an approach to use observational data for the comparison of joint monitoring and treatment strategies and applies the method to a clinically relevant question in HIV research: when can monitoring frequency be decreased and when should individuals switch from a first-line treatment regimen to a new regimen? We outline the target trial that would compare the dynamic strategies of interest and then describe how to emulate it using data from HIV-positive individuals included in the HIV-CAUSAL Collaboration and the Centers for AIDS Research Network of Integrated Clinical Systems. When, as in our example, few individuals follow the dynamic strategies of interest over long periods of follow-up, we describe how to leverage an additional assumption: no direct effect of monitoring on the outcome of interest. We compare our results with and without the "no direct effect" assumption. We found little differences on survival and AIDS-free survival between strategies where monitoring frequency was decreased at a CD4 threshold of 350 cells/µl compared with 500 cells/µl and where treatment was switched at an HIV-RNA threshold of 1000 copies/ml compared with 200 copies/ml. The "no direct effect" assumption resulted in efficiency improvements for the risk difference estimates ranging from an 7- to 53-fold increase in the effective sample size.

Does smoking cessation reduce other substance use, psychiatric symptoms, and pain symptoms? Results from an emulated hypothetical randomized trial of US veterans.

BACKGROUND: Quitting smoking may lead to improvement in substance use, psychiatric symptoms, and pain, especially among high-risk populations who are more likely to experience comorbid conditions. However, causal inferences regarding smoking cessation and its subsequent benefits have been limited. METHODS: We emulated a hypothetical open-label randomized control trial of smoking cessation using longitudinal observational data of HIV-positive and HIV-negative US veterans from 2003-2015 in the Veterans Aging Cohort Study. We followed individuals from the first time they self-reported current cigarette smoking (baseline). We categorized participants as quitters or non-quitters at the first follow-up visit (approximately 1 year after baseline). Using inverse probability weighting to adjust for confounding and selection bias, we estimated odds ratios for improvement of co-occurring conditions (unhealthy alcohol use, cannabis use, illicit opioid use, cocaine use, depressive symptoms, anxiety symptoms, and pain symptoms) at second follow-up (approximately 2 years after baseline) for those who quit smoking compared to those who did not, among individuals who had the condition at baseline. RESULTS: Of 4,165 eligible individuals (i.e., current smokers at baseline), 419 reported no current smoking and 2,330 reported current smoking at the first follow-up. Adjusted odds ratios (95% confidence intervals) for associations between quitting smoking and improvement of each condition at second follow-up were: 2.10 (1.01, 4.35) for unhealthy alcohol use, 1.75 (1.00, 3.06) for cannabis use, 1.10 (0.58, 2.08) for illicit opioid use, and 2.25 (1.20, 4.24) for cocaine use, 0.78 (0.44, 1.38) for depressive symptoms, 0.93 (0.58, 1.49) for anxiety symptoms, and 1.31 (0.84, 2.06) for pain symptoms. CONCLUSIONS: While a causal interpretation of our findings may not be warranted, we found evidence for decreased substance use among veterans who quit cigarette smoking but none for the resolution of psychiatric conditions or pain symptoms. Findings suggest the need for additional resources combined with smoking cessation to reduce psychiatric and pain symptoms for high-risk populations.

No impact of COVID-19 at delivery on maternal mortality or infant adverse birth outcomes in Botswana during the Omicron era.

SARS-CoV-2 infection during pregnancy was associated with maternal mortality and adverse birth outcomes in the pre-Omicron era, including a stillbirth rate of 5.6% in Botswana. We re-evaluated these outcomes in the Tsepamo Study during the Omicron era. We assessed maternal mortality and adverse birth outcomes for all singleton pregnancies from mid-November 2021 (the start of the Omicron era) to mid-August 2022 at nine Tsepamo sites, among individuals with documented SARS-CoV-2 screening PCR or antigen tests and known HIV status. Of 9,705 women routinely screened for SARS-CoV-2 infection at delivery (64% of deliveries at these sites), 373 (3.8%) tested positive. Women with HIV were as likely to test positive for SARS-CoV-2 (77/1833, 4.2%) as women without HIV (293/6981, 4.2%) (p = 1.0). There were 5 recorded maternal deaths (0.03%), one occurring in a woman with a positive SARS-CoV-2 test result. In contrast, maternal mortality was 3.7% and 0.1% in those with and without SARS-CoV-2, respectively, during the pre-Omicron era. In the Omicron era, there were no differences among infants exposed or unexposed to SARS-CoV-2 in overall adverse birth outcomes (28.1% vs 29.6%; aRR 1.0, 95%CI 0.8-1.1), severe adverse birth outcomes (11.9 vs 10.6%; aRR 1.1, 95%CI 0.8-1.5), preterm delivery (15.1% vs 14.9%; aRR 1.0, 95%CI 0.8-1.3), or stillbirth (1.9% vs 2.3%; aRR 0.8, 95%CI 0.4-1.7). Adverse outcomes among those exposed to both HIV and SARS-CoV-2 were similar to those exposed to HIV alone (31.2% vs. 33.1%; aRR 0.9, 95%CI 0.6-1.3; p = 0.5). Maternal mortality was far lower in Botswana during the Omicron era than in the pre-Omicron era, and adverse birth outcomes were no longer significantly impacted by exposure to SARS-CoV-2 either overall or with HIV co-exposure. Increased population immunity to SARS-CoV-2, less stress on the hospital systems in the Omicron era, and possible differences in viral pathogenicity may combine to explain these findings.