Diagnostic Accuracy of an Integrated AI Tool to Estimate Gestational Age From Blind Ultrasound Sweeps.

Importance: Accurate assessment of gestational age (GA) is essential to good pregnancy care but often requires ultrasonography, which may not be available in low-resource settings. This study developed a deep learning artificial intelligence (AI) model to estimate GA from blind ultrasonography sweeps and incorporated it into the software of a low-cost, battery-powered device. Objective: To evaluate GA estimation accuracy of an AI-enabled ultrasonography tool when used by novice users with no prior training in sonography. Design, Setting, and Participants: This prospective diagnostic accuracy study enrolled 400 individuals with viable, single, nonanomalous, first-trimester pregnancies in Lusaka, Zambia, and Chapel Hill, North Carolina. Credentialed sonographers established the "ground truth" GA via transvaginal crown-rump length measurement. At random follow-up visits throughout gestation, including a primary evaluation window from 14 0/7 weeks' to 27 6/7 weeks' gestation, novice users obtained blind sweeps of the maternal abdomen using the AI-enabled device (index test) and credentialed sonographers performed fetal biometry with a high-specification machine (study standard). Main Outcomes and Measures: The primary outcome was the mean absolute error (MAE) of the index test and study standard, which was calculated by comparing each method's estimate to the previously established GA and considered equivalent if the difference fell within a prespecified margin of ±2 days. Results: In the primary evaluation window, the AI-enabled device met criteria for equivalence to the study standard, with an MAE (SE) of 3.2 (0.1) days vs 3.0 (0.1) days (difference, 0.2 days [95% CI, -0.1 to 0.5]). Additionally, the percentage of assessments within 7 days of the ground truth GA was comparable (90.7% for the index test vs 92.5% for the study standard). Performance was consistent in prespecified subgroups, including the Zambia and North Carolina cohorts and those with high body mass index. Conclusions and Relevance: Between 14 and 27 weeks' gestation, novice users with no prior training in ultrasonography estimated GA as accurately with the low-cost, point-of-care AI tool as credentialed sonographers performing standard biometry on high-specification machines. These findings have immediate implications for obstetrical care in low-resource settings, advancing the World Health Organization goal of ultrasonography estimation of GA for all pregnant people. Trial Registration: ClinicalTrials.gov Identifier: NCT05433519.

True and false positive HIV point of care test results in a prospective multinational study of at-risk African women: implications for large-scale repeat HIV testing in HIV prevention programs.

BACKGROUND: Accurate HIV point of care testing is the cornerstone of prevention and treatment efforts globally, though false (both negative and positive) results are expected to occur. SETTING: We assessed the spectrum of true and false positive HIV results in a large prospective study of HIV incidence in African women using three contraceptive methods tested longitudinally in Eswatini, Kenya, South Africa, and Zambia. METHODS: HIV serologic testing was conducted quarterly using two parallel rapid HIV tests. When one or both tests were positive, additional confirmatory testing was conducted, including HIV enzyme immunoassay (EIA) and ribonucleic acid (RNA). RESULTS: 7730 women contributed 48,234 visits: true positive results occurred at 412 visits (0.9%) and false positives at 96 visits (0.2%). Of 412 women with HIV seroconversion, 10 had discordant (i.e., one negative and one positive) rapid tests and 13 had undetectable HIV RNA levels. Of 62 women with false positive rapid HIV results, most had discordant rapid testing but six (9.7%) had dually-positive rapid results and four (6.5%) had false positive or indeterminate EIA results. The positive predictive value of dual positive rapid results was 98.3%. CONCLUSION: Although the majority of rapid test results were accurate, false positive results were expected and occurred in this population of initially HIV seronegative individuals tested repeatedly and prospectively. When HIV infection occurred, not all cases had textbook laboratory results. Our findings highlight the importance of confirmatory testing, particularly for individuals undergoing repeat testing and in settings where the point prevalence is expected to be low.

Clinic-based evaluation of point-of-care dual HIV/syphilis rapid diagnostic tests at primary healthcare antenatal facilities in South Africa and Zambia.

BACKGROUND: Southern African countries have the largest global burden of HIV and syphilis, with a high prevalence among women of reproductive age. Although antenatal screening is standard of care, syphilis screening has generally lagged behind HIV screening. We aimed to evaluate the performance and operational characteristics of two commercial dual HIV/syphilis point-of-care tests (POCTs) for simultaneous maternal HIV/syphilis screening. METHODS: A clinic-based evaluation of dual HIV/syphilis POCTs (SD Bioline and Chembio) was conducted at five primary healthcare centres (PHCs) in South Africa and Zambia. POCT results using capillary fingerprick blood were compared to reference laboratory syphilis and HIV serological assays. RESULTS: Three thousand four hundred twelve consenting pregnant women aged ≥ 18 years were enrolled. The prevalence of treponemal antibody seropositivity and HIV infection ranged from 3.7 to 9.9% (n = 253) and 17.8 to 21.3% (n = 643), respectively. Pooled sensitivity for syphilis compared to the reference assay was 66.0% (95%CI 57.7-73.4) with SD Bioline and 67.9% (95%CI 58.2-76.3) with Chembio. Pooled specificity for syphilis was above 98% with both POCTs. The sensitivities of SD Bioline and Chembio assays were 78.0% (95%CI 68.6-85.7) and 81.0% (95%CI 71.9-88.2), respectively compared to an active syphilis case definition of treponemal test positive with a rapid plasma reagin titre of ≥ 8. The negative predictive values (NPVs) based on various prevalence estimates for syphilis with both assays ranged from 97 to 99%. The pooled sensitivity for HIV was 92.1% (95%CI 89.4-94.2) with SD Bioline; and 91.5% (95%CI 88.2-93.9) with Chembio. The pooled specificities for HIV were 97.2% (95%CI 94.8-98.5) with SD Bioline and 96.7% (95%CI 95.1-97.8) with Chembio. The NPV based on various prevalence estimates for HIV with both assays was approximately 98%. Most participating women (91%) preferred dual POCTs over two single POCTs for HIV and syphilis, and healthcare providers gave favourable feedback on the utility of both assays at PHC level. CONCLUSIONS: Based on the need to improve antenatal screening coverage for syphilis, dual HIV/syphilis POCTs could be effectively incorporated into antenatal testing algorithms to enhance efforts towards elimination of mother-to-child transmission of these infections.

High rates of placental inflammation among samples collected by the Multi-Omics for Mothers and Infants consortium.

BACKGROUND: The Multi-Omics for Mothers and Infants consortium aims to improve birth outcomes. Preterm birth is a major obstetrical complication globally and causes significant infant and childhood morbidity and mortality. OBJECTIVE: We analyzed placental samples (basal plate, placenta or chorionic villi, and the chorionic plate) collected by the 5 Multi-Omics for Mothers and Infants sites, namely The Alliance for Maternal and Newborn Health Improvement Bangladesh, The Alliance for Maternal and Newborn Health Improvement Pakistan, The Alliance for Maternal and Newborn Health Improvement Tanzania, The Global Alliance to Prevent Prematurity and Stillbirth Bangladesh, and The Global Alliance to Prevent Prematurity and Stillbirth Zambia. The goal was to analyze the morphology and gene expression of samples collected from preterm and uncomplicated term births. STUDY DESIGN: The teams provided biopsies from 166 singleton preterm (<37 weeks' gestation) and 175 term (≥37 weeks' gestation) deliveries. The samples were fixed in formalin and paraffin embedded. Tissue sections from these samples were stained with hematoxylin and eosin and subjected to morphologic analyses. Other placental biopsies (n=35 preterm, 21 term) were flash frozen, which enabled RNA purification for bulk transcriptomics. RESULTS: The morphologic analyses revealed a surprisingly high rate of inflammation that involved the basal plate, placenta or chorionic villi, and the chorionic plate. The rate of inflammation in chorionic villus samples, likely attributable to chronic villitis, ranged from 25% (Pakistan site) to 60% (Zambia site) of cases. Leukocyte infiltration in this location vs in the basal plate or chorionic plate correlated with preterm birth. Our transcriptomic analyses identified 267 genes that were differentially expressed between placentas from preterm vs those from term births (123 upregulated, 144 downregulated). Mapping the differentially expressed genes onto single-cell RNA sequencing data from human placentas suggested that all the component cell types, either singly or in subsets, contributed to the observed dysregulation. Consistent with the histopathologic findings, gene ontology analyses highlighted the presence of leukocyte infiltration or activation and inflammatory responses in both the fetal and maternal compartments. CONCLUSION: The relationship between placental inflammation and preterm birth is appreciated in developed countries. In this study, we showed that this link also exists in developing geographies. In addition, among the participating sites, we found geographic- and population-based differences in placental inflammation and preterm birth, suggesting the importance of local factors.

Acceptability of a Randomized Trial of Anti-depressant Medication or Interpersonal Therapy for Treatment of Perinatal Depression in Women with HIV.

Postpartum depression (PPD) affects nearly 20% of postpartum women in Sub-Saharan Africa (SSA), where HIV prevalence is high. Depression is associated with worse HIV outcomes in non-pregnant adults and mental health disorders may worsen HIV outcomes for postpartum women and their infants. PPD is effectively treated with psychosocial or pharmacologic interventions; however, few studies have evaluated the acceptability of treatment modalities in SSA. We analyzed interviews with 23 postpartum women with HIV to assess the acceptability of two depression treatments provided in the context of a randomized trial. Most participants expressed acceptability of treatment randomization and study visit procedures. Participants shared perceptions of high treatment efficacy of their assigned intervention. They reported ongoing HIV and mental health stigma in their communities and emphasized the importance of social support from clinic staff. Our findings suggest a full-scale trial of PPD treatment will be acceptable among women with HIV in Zambia.

Deep learning to estimate gestational age from fly-to cineloop videos: A novel approach to ultrasound quality control.

OBJECTIVE: Low-cost devices have made obstetric sonography possible in settings where it was previously unfeasible, but ensuring quality and consistency at scale remains a challenge. In the present study, we sought to create a tool to reduce substandard fetal biometry measurement while minimizing care disruption. METHODS: We developed a deep learning artificial intelligence (AI) model to estimate gestational age (GA) in the second and third trimester from fly-to cineloops-brief videos acquired during routine ultrasound biometry-and evaluated its performance in comparison to expert sonographer measurement. We then introduced random error into fetal biometry measurements and analyzed the ability of the AI model to flag grossly inaccurate measurements such as those that might be obtained by a novice. RESULTS: The mean absolute error (MAE) of our model (±standard error) was 3.87 ± 0.07 days, compared to 4.80 ± 0.10 days for expert biometry (difference -0.92 days; 95% CI: -1.10 to -0.76). Based on simulated novice biometry with average absolute error of 7.5%, our model reliably detected cases where novice biometry differed from expert biometry by 10 days or more, with an area under the receiver operating characteristics curve of 0.93 (95% CI: 0.92, 0.95), sensitivity of 81.0% (95% CI: 77.9, 83.8), and specificity of 89.9% (95% CI: 88.1, 91.5). These results held across a range of sensitivity analyses, including where the model was provided suboptimal truncated fly-to cineloops. CONCLUSIONS: Our AI model estimated GA more accurately than expert biometry. Because fly-to cineloop videos can be obtained without any change to sonographer workflow, the model represents a no-cost guardrail that could be incorporated into both low-cost and commercial ultrasound devices to prevent reporting of most gross GA estimation errors.

Comparison of Masimo Total Hemoglobin SpHb® continuous non-invasive hemoglobin monitoring device with laboratory complete blood count measurement using venous sample: Protocol for an observational substudy of the Pregnancy Risk and Infant Surveillance and Measurement Alliance Maternal and Newborn Health (PRISMA MNH) study.

Background: The Masimo Total Hemoglobin SpHb® is a continuous and non-invasive handheld device to measure hemoglobin levels. Previous research has found that SpHb is able to accurately detect hemoglobin levels in adult patients with a similar degree of bias and standard deviation to point-of-care invasive method measurements. Generally, limited clinical evidence, lack of validation of Masimo at higher than and lower than hemoglobin threshold values, and scientific consensus supporting the use of Masimo for accurate hemoglobin testing for the diagnosis of anemia during pregnancy calls for further research. Methods and analysis: The proposed prospective cohort will be nested within the ongoing Pregnancy Risk and Infant Surveillance and Measurement Alliance (PRISMA) Maternal and Newborn Health (MNH) study. Three study sites (located in Zambia, Kenya, and Pakistan) will participate and collect hemoglobin data at five time points (<20 weeks, 20 weeks, 28 weeks, 36 weeks' gestation, and six weeks postpartum). We will measure hemoglobin using a venous blood sample via hematology auto-analyzer complete blood count (gold standard) and the non-invasive device. The primary objective is to assess agreement between Masimo total hemoglobin and complete blood count and on a continuous scale using Intraclass Correlation Coefficient and Bland-Altman Analysis. The second objective is to assess agreement between the two measures on a binary scale using Positive Percentage Agreement and Negative Percentage Agreement, Cohen's Kappa, and McNemar Test. On an ordinal scale, agreement will be measured using Weighted Cohen's Kappa and Harrel's Concordance Index. Lastly, we will assess factors that might affect the accuracy of Masimo total hemoglobin using linear mixed models. Conclusions: The primary aim of this study is to assess the validity of the non-invasive Masimo device compared to the gold standard method of invasive hemoglobin measurements during pregnancy and postpartum periods for the diagnosis of anemia.

Two strategies for partner notification and partner HIV self-testing reveal no evident predictors of male partner HIV testing in antenatal settings: A secondary analysis.

BACKGROUND: To meet global targets for the elimination of mother-to-child HIV transmission, tailored approaches to HIV testing strategies need prioritizing. Herein, we sought to identify individual-level factors associated with male partner HIV testing. METHODS: We conducted a secondary analysis of data from two parallel randomized trials of pregnant women living with HIV and those HIV-negative in Lusaka, Zambia. Across both trials, control groups received partner notification services only, while intervention groups received partner notification services plus HIV self-test kits for their partners. Associations between baseline factors and male partner testing were estimated using a probability difference. The outcome of interest was uptake of male partner HIV testing of any kind within 30 days of randomization. RESULTS: The parent study enrolled 326 participants. Among the 151 women in the control groups, no clear associations were noted between maternal or male partner characteristics and reported uptake of male partner HIV testing. There were positive trends favouring partner testing among women who completed primary school education, had larger households (>2 members), and whose partners were circumcised. Likewise, no clear predictors of male partner testing were identified among the 149 women in the intervention groups. However, negative trends favouring no testing were noted among older, multiparous women from larger households. CONCLUSION: No consistent predictors for male partner HIV testing across two compared strategies were observed. Our findings suggest that differentiated strategies for male partner HIV testing may not be necessary. Instead, consideration should be given to universal approaches when bringing such services to scale.

Multiomic signals associated with maternal epidemiological factors contributing to preterm birth in low- and middle-income countries.

Preterm birth (PTB) is the leading cause of death in children under five, yet comprehensive studies are hindered by its multiple complex etiologies. Epidemiological associations between PTB and maternal characteristics have been previously described. This work used multiomic profiling and multivariate modeling to investigate the biological signatures of these characteristics. Maternal covariates were collected during pregnancy from 13,841 pregnant women across five sites. Plasma samples from 231 participants were analyzed to generate proteomic, metabolomic, and lipidomic datasets. Machine learning models showed robust performance for the prediction of PTB (AUROC = 0.70), time-to-delivery (r = 0.65), maternal age (r = 0.59), gravidity (r = 0.56), and BMI (r = 0.81). Time-to-delivery biological correlates included fetal-associated proteins (e.g., ALPP, AFP, and PGF) and immune proteins (e.g., PD-L1, CCL28, and LIFR). Maternal age negatively correlated with collagen COL9A1, gravidity with endothelial NOS and inflammatory chemokine CXCL13, and BMI with leptin and structural protein FABP4. These results provide an integrated view of epidemiological factors associated with PTB and identify biological signatures of clinical covariates affecting this disease.

Diagnostic yield of urine lipoarabinomannan and sputum tuberculosis tests in people living with HIV: a systematic review and meta-analysis of individual participant data.

BACKGROUND: Sputum is the most widely used sample to diagnose active tuberculosis, but many people living with HIV are unable to produce sputum. Urine, in contrast, is readily available. We hypothesised that sample availability influences the diagnostic yield of various tuberculosis tests. METHODS: In this systematic review and meta-analysis of individual participant data, we compared the diagnostic yield of point-of-care urine-based lipoarabinomannan tests with that of sputum-based nucleic acid amplification tests (NAATs) and sputum smear microscopy (SSM). We used microbiologically confirmed tuberculosis based on positive culture or NAAT from any body site as the denominator and accounted for sample provision. We searched PubMed, Web of Science, Embase, African Journals Online, and clinicaltrials.gov from database inception to Feb 24, 2022 for randomised controlled trials, cross-sectional studies, and cohort studies that assessed urine lipoarabinomannan point-of-care tests and sputum NAATs for active tuberculosis detection in participants irrespective of tuberculosis symptoms, HIV status, CD4 cell count, or study setting. We excluded studies in which recruitment was not consecutive, systematic, or random; provision of sputum or urine was an inclusion criterion; less than 30 participants were diagnosed with tuberculosis; early research assays without clearly defined cutoffs were tested; and humans were not studied. We extracted study-level data, and authors of eligible studies were invited to contribute deidentified individual participant data. The main outcomes were the tuberculosis diagnostic yields of urine lipoarabinomannan tests, sputum NAATs, and SSM. Diagnostic yields were predicted using Bayesian random-effects and mixed-effects meta-analyses. This study is registered with PROSPERO, CRD42021230337. FINDINGS: We identified 844 records, from which 20 datasets and 10 202 participants (4561 [45%] male participants and 5641 [55%] female participants) were included in the meta-analysis. All studies assessed sputum Xpert (MTB/RIF or Ultra, Cepheid, Sunnyvale, CA, USA) and urine Alere Determine TB LAM (AlereLAM, Abbott, Chicago, IL, USA) in people living with HIV aged 15 years or older. Nearly all (9957 [98%] of 10 202) participants provided urine, and 82% (8360 of 10 202) provided sputum within 2 days. In studies that enrolled unselected inpatients irrespective of tuberculosis symptoms, only 54% (1084 of 1993) of participants provided sputum, whereas 99% (1966 of 1993) provided urine. Diagnostic yield was 41% (95% credible interval [CrI] 15-66) for AlereLAM, 61% (95% Crl 25-88) for Xpert, and 32% (95% Crl 10-55) for SSM. Heterogeneity existed across studies in the diagnostic yield, influenced by CD4 cell count, tuberculosis symptoms, and clinical setting. In predefined subgroup analyses, all tests had higher yields in symptomatic participants, and AlereLAM yield was higher in those with low CD4 counts and inpatients. AlereLAM and Xpert yields were similar among inpatients in studies enrolling unselected participants who were not assessed for tuberculosis symptoms (51% vs 47%). AlereLAM and Xpert together had a yield of 71% in unselected inpatients, supporting the implementation of combined testing strategies. INTERPRETATION: AlereLAM, with its rapid turnaround time and simplicity, should be prioritised to inform tuberculosis therapy among inpatients who are HIV-positive, regardless of symptoms or CD4 cell count. The yield of sputum-based tuberculosis tests is undermined by people living with HIV who cannot produce sputum, whereas nearly all participants are able to provide urine. The strengths of this meta-analysis are its large size, the carefully harmonised denominator, and the use of Bayesian random-effects and mixed-effects models to predict yields; however, data were geographically restricted, clinically diagnosed tuberculosis was not considered in the denominator, and little information exists on strategies for obtaining sputum samples. FUNDING: FIND, the Global Alliance for Diagnostics.

Perspectives on sexual and reproductive health self-care among women, healthcare providers, and other key informants: a mixed-methods study in South Africa and Zambia.

BACKGROUND: "Self-care" for sexual and reproductive health (SRH) includes contraceptive methods and other supplies that people can use with or without the support of a healthcare provider. Self-administered tests, self-injection of injectable contraception, or self-removal of intrauterine devices (IUDs) can increase people's access to and autonomy over their own SRH. Objectives of this study were to assess women's current interest in and use of SRH self-care and explore key informants' (KI) opinions of self-care, especially during the COVID-19 pandemic. METHODS: Data for this study came from female participants in the longitudinal Contraceptive Use Beyond ECHO (CUBE) study, and KIs, including healthcare providers, in South Africa and Zambia between September 2020 and June 2021. For this analysis, we used data from a participant phone survey (n = 537), and from in-depth interviews (IDIs) completed with a sub-sample of women (n = 39) and KIs (n = 36). Survey data were analyzed with descriptive statistics, and IDI data were analyzed using applied thematic analysis. RESULTS: Female survey participants in South Africa were more interested in learning about emergency contraceptive pills, subcutaneous injectable contraception, and CycleBeads, while Zambian participants wanted more information and access to condoms. However, in IDIs in both countries, women described minimal experience with self-care beyond condom use. In the Zambian KI IDIs, COVID-19 led to increased self-care counseling on subcutaneous injectable contraception and HIV self-testing. KIs who do not counsel on self-care were concerned that women may harm themselves or blame the provider for difficulties. Two KIs thought that women could possibly self-remove IUDs, but most expressed concerns. Reported barriers to self-care included COVID movement restrictions, transport costs, lack of accessible pharmacies, women's low awareness, and possible stigma. CONCLUSIONS: Women surveyed reported interest in learning more about SRH self-care methods and resources, but in IDIs did not report extensive previous use besides condoms. KIs described some concerns about women's ability to use self-care methods. Counseling on and provision of self-care methods and supplies may have increased during the COVID-19 pandemic, but ensuring that self-care is more than just a temporary measure in health systems has the potential to increase access to SRH care and support women's autonomy and healthcare needs.

BACKGROUND: "Self-care" refers to healthcare that does not have to be given by a provider, but that people can use themselves. In sexual and reproductive health (SRH), this includes medicines or supplies like pills and injections that people can use to prevent or test for pregnancy or sexually transmitted infections. This study wanted to better understand women's interest in and use of SRH self-care and explore key informants' opinions of self-care, especially during the COVID-19 pandemic. METHODS: We surveyed 537 women in KwaZulu-Natal province, South Africa and Lusaka, Zambia in 2020­2021. We also conducted interviews with 39 women and 36 key informants, including healthcare providers, government officials, and community advocates. RESULTS: Women surveyed in South Africa were more interested than those in Zambia in learning more about self-care contraception, especially daily pills, emergency pills, and injections they could give themselves. In interviews, some key informants said that they do not tell women about self-care because they worried that women could hurt themselves or blame the provider if they experienced problems. COVID movement restrictions, transport costs, and inaccessible pharmacies were all barriers that key informants mentioned to accessing tests, tools, or contraceptive methods that women could give or use themselves. CONCLUSIONS: Women surveyed were interested in learning more about self-care and those interviewed reported minimal previous use of self-care methods besides condoms. Providers also have some concerns about women's ability to use self-care methods. Counseling on and providing self-care methods and supplies may have increased during COVID-19, but increasing access to self-care could help more women take care of their own sexual and reproductive healthcare.

Strategies to increase couples HIV testing and counselling in sub-Saharan Africa: a systematic review.

INTRODUCTION: Couple HIV testing and counselling (CHTC) is associated with measurable benefits for HIV prevention and treatment. However, the uptake remains limited in much of sub-Saharan Africa, despite an expanded range of strategies designed to promote access. METHODS: Following PRIMSA guidelines, we conducted a systematic review to characterize CHTC uptake strategies. Five databases were searched. Full-text articles were included if they were: conducted in sub-Saharan Africa during the study period (1980-2019), targeted heterosexual couples, reported at least one strategy to promote CHTC and provided a quantifiable measure of CHTC uptake. After the initial and full-text screening, key features of the studies were abstracted and synthesized. RESULTS: Of the 6188 unique records found in our search, 365 underwent full-text review with 29 distinct studies included and synthesized. Most studies recruited couples through antenatal care (n = 11) or community venues (n = 8) and used provider-based HIV testing (n = 25). The primary demand creation strategies included home-based CHTC (n = 7); integration of CHTC into clinical settings (n = 4); distribution of HIV self-testing kits (n = 4); verbal or written invitations (n = 4); community recruiters (n = 3); partner tracing (n = 2); relationship counselling (n = 2); financial incentives (n = 1); group education with CHTC coupons (n = 1); and HIV testing at other community venues (n = 1). CHTC uptake ranged from negligible to nearly universal. DISCUSSION: We thematically categorized a diverse range of strategies with varying levels of intensity and resources used across sub-Saharan Africa to promote CHTC. Offering CHTC within couples' homes was the most common approach, followed by the integration of CHTC into clinical settings. Due to heterogeneity in study characteristics, we were unable to compare the effectiveness across studies, but several trends were observed, including the high prevalence of CHTC promotion strategies in antenatal settings and the promising effects of home-based CHTC, distribution of HIV self-tests and integration of CHTC into routine health services. Since 2019, an updated literature search found that combining partner notification and secondary distribution of HIV self-test kits may be an additionally effective CHTC strategy. CONCLUSIONS: There are many effective, feasible and scalable approaches to promote CHTC that should be considered by national programmes according to local needs, cultural context and available resources.

Contraceptive Continuation and Experiences Obtaining Implant and IUD Removal Among Women Randomized to Use Injectable Contraception, Levonorgestrel Implant, and Copper IUD in South Africa and Zambia.

Few longitudinal studies have measured contraceptive continuation past one year in sub-Saharan Africa. We surveyed 674 women who had been randomized to receive the three-month intramuscular contraceptive injectable (DMPA-IM), levonorgestrel (LNG) implant, or copper intrauterine device (IUD) during the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial in South Africa and Zambia and were subsequently followed for two additional years to explore method continuation, reasons for discontinuation, and access to implant and IUD removal services. We also conducted in-depth qualitative interviews with 39 participants. We estimated cumulative discontinuation probabilities using Kaplan-Meier estimates and assessed factors associated with discontinuation using Cox-proportional hazards models. The LNG implant continuation rate over the maximum 44-month study period was 60 percent, while rates for the copper IUD and DMPA-IM were 52 percent and 44 percent, respectively. Reasons for method discontinuation included side effects, particularly menstrual changes, and method stock-outs. Most implant and IUD users who sought removal were able to access services; however, room for improvement exists. In this cohort originally randomized to receive a contraceptive method and attend regular study visits, implants and IUDs continued to be highly acceptable over an additional two years, but facilities should continue to ensure that insertions and removals are available as requested.

Is long-acting reversible contraceptive method use associated with HIV testing frequency in KwaZulu-Natal, South Africa and Lusaka, Zambia? Findings from the CUBE study.

Objectives: To assess differences in HIV testing at 6-months intervals over 24 months among intramuscular depot medroxyprogesterone acetate (DMPA-IM) injectable, levonorgestrel implant, or copper intrauterine devices (IUD) users in KwaZulu-Natal, South Africa, and Lusaka, Zambia. Testing at recommended intervals has not been previously assessed in long-acting reversible contraceptive (LARC) users (implant and IUD users) compared to those using effective but shorter-acting methods (such as DMPA-IM) in sub-Saharan Africa. Study design: As part of the longitudinal contraceptive use beyond ECHO (CUBE) study, we measured HIV testing over 24 months. Participants were considered continuous users of DMPA-IM, levonorgestrel implant, or copper IUD if they used the same method across all months of their study participation, or not continuous users of their baseline CUBE method if they switched or discontinued their method. We used multivariable logistic regression models with generalized estimating equations and robust standard errors, stratified by country, to assess differences in HIV testing. Results: Among the 498 participants, HIV testing rates were higher in Zambia for all methods compared to South Africa. In bivariate analyses, continuous implant or IUD users (the LARC users) were significantly less likely to report having received HIV testing at the 6-months and 24-months surveys, compared to continuous DMPA-IM users. In adjusted longitudinal models, continuous IUD users (adjusted odds ratio: 0.42, 95% CI: 0.24, 0.74), continuous implant users (adjusted odds ratio: 0.23, 95% CI: 0.12, 0.42) in South Africa had significantly lower odds of HIV testing compared to continuous DMPA-IM users. There were no significant differences in Zambia in the adjusted models. Conclusion: LARC use may reduce opportunities for HIV testing and users should be counseled on regular HIV testing and the option of HIV self-testing. Implications: Due to infrequent clinical contacts which may lead to lower rates of HIV testing at recommended intervals, LARC users should be provided opportunities to test for HIV at home or when seeking other health services.

Different effects for different questions: An illustration using short cervix and the risk of preterm birth.

OBJECTIVE: To illustrate the difference between exposure effects and population attributable effects. METHODS: We examined the effect of mid-pregnancy short cervical length (<25 mm) on preterm birth using data from a prospective cohort of pregnant women in Lusaka, Zambia. Preterm birth was live birth or stillbirth before 37 weeks of pregnancy. For estimation, we used multivariable regression and parametric g-computation. RESULTS: Among 1409 women included in the analysis, short cervix was rare (2.4%); 13.6% of births were preterm. Exposure effect estimates were large (marginal risk ratio 2.86, 95% confidence interval [CI] 1.80-4.54), indicating that the preterm birth risk was substantially higher among women with a short cervix compared with women without a short cervix. However, the population attributable effect estimates were close to the null (risk ratio 1.06, 95% CI 1.02-1.10), indicating that an intervention to counteract the impact of short cervix on preterm birth would have minimal effect on the population risk of preterm birth. CONCLUSION: Although authors often refer to "the" effect, there are actually different types of effects, as we have illustrated here. In planning research, it is important to consider which effect to estimate to ensure that the estimate aligns with the research objective.

Maternal mid-upper arm circumference to predict small for gestational age: Findings in a Zambian cohort.

OBJECTIVE: To compare the performance of mid upper arm circumference (MUAC) and body mass index (BMI) for prediction of small for gestational age (SGA) in Zambia. METHODS: This is a secondary analysis of an ongoing clinical cohort that included women with a single gestation and MUAC measured before 24 weeks of pregnancy. We assessed relationships between maternal MUAC and birth weight centile using regression. The performance of MUAC and BMI to predict SGA was compared using receiver operating characteristic curves and the effect of maternal HIV was investigated in sub-group analyses. RESULTS: Of 1117 participants, 847 (75%) were HIV-negative (HIV-) and 270 (24%) were HIV-positive (HIV+). Seventy-four (7%) delivered severe SGA infants (<3rd centile), of whom 56 (76%) were HIV- and 18 (24%) were HIV+ (odds ratio [OR] 1.01, 95% confidence interval [CI] 0.58-1.75). MUAC was associated with higher birth weight centile (+1.2 centile points, 95% CI 0.7-1.6; P < 0.001); this relationship was stronger among HIV+ women (+1.7 centile points, 95% CI 0.8-2.6; P < 0.001) than HIV- women (+0.9 centile points, 95% CI 0.4-1.4; P = 0.001). The discriminatory power was similar, albeit poor (area under the curve [AUC] < 0.7), between MUAC and BMI for the prediction of SGA. In stratified analysis, MUAC and BMI showed excellent discrimination predicting severe SGA among HIV+ (AUC 0.83 and 0.81, respectively) but not among HIV- women (AUC 0.64 and 0.63, respectively). CONCLUSION: Maternal HIV infection increased the discrimination of both early pregnancy MUAC and BMI for prediction of severe SGA in Zambia. CLINICAL TRIAL NUMBER: ClinicalTrials.gov (NCT02738892).

Impact of the COVID-19 pandemic on women's contraceptive use: a mixed-methods study in South Africa and Zambia.

Background: The COVID-19 pandemic affected global access to health services, including contraception. We sought to explore effects of the pandemic on family planning (FP) service provision and use in South Africa and Zambia, including on implant and intrauterine device (IUD) users' desire and ability to obtain removal. Methods: Between August 2020 and April 2021, we conducted surveys with 537 women participating in an ongoing longitudinal contraceptive continuation study. We also carried out in-depth interviews with 39 of the survey participants and 36 key informants involved in FP provision. We conducted descriptive analysis of survey responses and thematic analysis of interviews. Results: Contraceptive use changed minimally in this sample with the emergence of COVID-19. Fewer than half of women (n=220) reported attempting to access FP since the start of the pandemic, the vast majority of whom were using short-acting methods. Among those who sought services, 95% obtained their preferred method. The proportion of women not using a method before and after pandemic start did not change in Zambia (31%); in South Africa, the proportion increased from 8% to 10%. Less than 7% of implant or IUD users in either country reported wanting removal. Among those who sought removal (n=22), 91% (n=10) in Zambia and 55% (n=6) in South Africa successfully obtained removal. In qualitative interviews, women with challenges accessing FP services mentioned long queues, deprioritization of contraceptive services, lack of transportation, stock-outs, and fear of contracting COVID-19 at a facility. Key informants reported stock-outs, especially of injectables, and staff shortages as barriers. Conclusions: We did not find a substantial impact of COVID-19 on contraceptive access among this sample; however, providers and others involved in service provision identified risks to continuity of care. As the COVID-19 pandemic wanes, it continues to be important to monitor people's ability to access their preferred contraceptive methods.

Effect of weekly 17-hydroxyprogesterone caproate on small for gestational age among pregnant women with HIV in Zambia.

The IPOP trial demonstrated a reduced risk of severe small for gestational age among infants born to women with HIV who received weekly intramuscular 17 alpha-hydroxyprogesterone caproate. This secondary analysis examined the 17P treatment effect in subgroups of maternal BMI, parity, timing of antiretroviral therapy (ART) initiation, and ART regimen. We found that 17P was more effective among nulliparous women, women who started ART before pregnancy, and those taking protease inhibitors.

A mobile-optimized artificial intelligence system for gestational age and fetal malpresentation assessment.

Background: Fetal ultrasound is an important component of antenatal care, but shortage of adequately trained healthcare workers has limited its adoption in low-to-middle-income countries. This study investigated the use of artificial intelligence for fetal ultrasound in under-resourced settings. Methods: Blind sweep ultrasounds, consisting of six freehand ultrasound sweeps, were collected by sonographers in the USA and Zambia, and novice operators in Zambia. We developed artificial intelligence (AI) models that used blind sweeps to predict gestational age (GA) and fetal malpresentation. AI GA estimates and standard fetal biometry estimates were compared to a previously established ground truth, and evaluated for difference in absolute error. Fetal malpresentation (non-cephalic vs cephalic) was compared to sonographer assessment. On-device AI model run-times were benchmarked on Android mobile phones. Results: Here we show that GA estimation accuracy of the AI model is non-inferior to standard fetal biometry estimates (error difference -1.4 ± 4.5 days, 95% CI -1.8, -0.9, n = 406). Non-inferiority is maintained when blind sweeps are acquired by novice operators performing only two of six sweep motion types. Fetal malpresentation AUC-ROC is 0.977 (95% CI, 0.949, 1.00, n = 613), sonographers and novices have similar AUC-ROC. Software run-times on mobile phones for both diagnostic models are less than 3 s after completion of a sweep. Conclusions: The gestational age model is non-inferior to the clinical standard and the fetal malpresentation model has high AUC-ROCs across operators and devices. Our AI models are able to run on-device, without internet connectivity, and provide feedback scores to assist in upleveling the capabilities of lightly trained ultrasound operators in low resource settings.