Does Provider Bias Affect Choice of a Facility for Family Planning Services by Women in Urban Senegal?

Few studies to date have determined the effect of provider bias based on age, parity, and marital status on women's method and facility choice. Using data from women using modern methods in six cities of Senegal and a facility survey that included a facility audit and provider interviews, we undertake conditional logit analyses to determine whether women's choice of a family planning facility is associated with provider bias at the facility, controlling for other facility characteristics (e.g., size, sector, and number of methods available). We find that women bypass facilities where there is greater provider bias to attain their current family planning method. Women also bypass facilities of lower quality. This is the first study to demonstrate the effects of provider bias on women's contraceptive seeking behaviors and suggests the importance of training providers to reduce age and parity bias that affect access to a full range of methods and facilities for all women.

Assessment of segmentation and targeted counseling on family planning quality of care and client satisfaction: a facility-based survey of clients in Niger.

BACKGROUND: Niger demonstrates high fertility and low contraceptive use that are typical in much of the West and Central African region. The government of Niger has committed to increasing modern contraceptive use as part of its health strategy. Designing and testing strategies to improve quality of care and satisfaction of family planning clients is important for addressing low contraceptive use in contexts like Niger. METHODS: This study uses recently collected client exit interview data from 2720 clients surveyed in the Dosso region of Niger to examine whether implementation of segmentation-based counseling leads to improved quality of services and client satisfaction. We compare three scenarios: a) facilities where segmentation counseling was implemented since 2017; b) facilities where segmentation counseling began in late 2019; and c) facilities without segmentation counseling. Bivariate and multivariate analyses are undertaken to determine if there are differences in quality of services and client satisfaction between the facility groups and between clients that were segmented and those who were not segmented in the first two scenarios. RESULTS: Results demonstrate that clients in facilities with segmentation generally received better quality services than clients in facilities without segmentation. Clients in facilities implementing segmentation longer reported higher quality services than the recent segmentation facilities. Clients who were segmented compared to those who were not segmented also reported better quality services. New clients reported higher quality services than returning clients and among new clients, those who were segmented also reported higher quality services. No differences were found in client satisfaction between facility scenarios or between segmented and non-segmented clients. CONCLUSIONS: These findings demonstrate that segmentation or another targeted counseling strategy could be useful to the government of Niger to improve the quality of services offered. As part of the scale up process, the government needs to consider strategies that ensure that all new clients are segmented and design an approach that is sustainable and does not risk failing should there be stock-out of segmentation sheets or loss of counseling cards. This type of targeted counseling could improve the quality of services offered and ideally lead to increased contraceptive use in Niger.

Intramuscular 17-hydroxyprogesterone caproate to prevent preterm birth among HIV-infected women in Zambia: study protocol of the IPOP randomized trial.

BACKGROUND: Each year, an estimated 15 million babies are born preterm, a global burden borne disproportionately by families in lower-income countries. Maternal HIV infection increases a woman's risk of delivering prematurely, and antiretroviral therapy (ART) may compound this risk. While prenatal progesterone prophylaxis prevents preterm birth among some high-risk women, it is unknown whether HIV-infected women could benefit from this therapy. We are studying the efficacy of progesterone supplementation to reduce the risk of preterm birth among pregnant women with HIV in Lusaka, Zambia. METHODS: The Improving Pregnancy Outcomes with Progesterone (IPOP) study is a Phase III double-masked, placebo-controlled, randomized trial of intramuscular 17-alpha hydroxprogesterone caproate (17P) to prevent preterm birth in HIV-infected women. A total of 800 women will be recruited prior to 24 weeks of gestation and randomly allocated to 17P or placebo administered by weekly intramuscular injection. The primary outcome will be a composite of live birth prior to 37 completed gestational weeks or stillbirth at any gestational age. Secondary outcomes will include very preterm birth (< 34 weeks), extreme preterm birth (< 28 weeks), small for gestational age (<10th centile), low birth weight (< 2500 g), and neonatal outcomes. In secondary analysis, we will assess whether specific HIV-related covariates, including the timing of maternal ART initiation relative to conception, is associated with progesterone's prophylactic efficacy, if any. DISCUSSION: We hypothesize that weekly prenatal 17P will reduce the risk of HIV-related preterm birth. An inexpensive intervention to prevent preterm birth among pregnant women with HIV could have substantial global public health impact. TRIAL REGISTRATION: NCT03297216 ; September 29, 2017.

Maternal Decision-Making and Uptake of Health Services for the Prevention of Mother-to-Child HIV Transmission: A Secondary Analysis.

Objectives We investigated whether a woman's role in household decision-making was associated with receipt of services to prevent mother-to-child HIV transmission (PMTCT). Methods We conducted a secondary analysis of the PEARL study, an evaluation of PMTCT effectiveness in Cameroon, Cote d'Ivoire, South Africa, and Zambia. Our exposure of interest was the women's role (active vs. not active) in decision-making about her healthcare, large household purchases, children's schooling, and children's healthcare (i.e., four domains). Our primary outcomes were self-reported engagement at three steps in PMTCT: maternal antiretroviral use, infant antiretroviral prophylaxis, and infant HIV testing. Associations found to be significant in univariable logistic regression were included in separate multivariable models. Results From 2008 to 2009, 613 HIV-infected women were surveyed and provided information about their decision-making roles. Of these, 272 (44.4%) women reported antiretroviral use; 281 (45.9%) reported infant antiretroviral prophylaxis; and 194 (31.7%) reported infant HIV testing. Women who reported an active role were more likely to utilize infant HIV testing services, across all four measured domains of decision-making (adjusted odds ratios [AORs] 2.00-2.89 all p < .05). However, associations between decision-making and antiretroviral use-for both mother and infant-were generally not significant. An exception was active decision-making in a woman's own healthcare and reported maternal antiretroviral use (AOR 1.69, p < 0.05). Conclusions for Practice Associations between decision-making and PMTCT engagement were inconsistent and may be related to specific characteristics of individual health-seeking behaviors. Interventions seeking to improve PMTCT uptake should consider the type of health-seeking behavior to better optimize health services.

Timing of Initiation of Antiretroviral Therapy and Risk of Preterm Birth in Studies of HIV-infected Pregnant Women: The Role of Selection Bias.

BACKGROUND: Women who initiate antiretroviral therapy (ART) during pregnancy are reported to have lower risk of preterm birth compared with those who enter pregnancy care already receiving ART. We hypothesize this association can be largely attributed to selection bias. METHODS: We simulated a cohort of 1000 preconceptional, HIV-infected women, where half were randomly allocated to receive immediate ART and half to delay ART until their presentation for pregnancy care. Gestational age at delivery was drawn from population data unrelated to randomization group (i.e., the true effect of delayed ART was null). Outcomes of interest were preterm birth (<37 weeks), very preterm birth (<32 weeks), and extreme preterm birth (<28 weeks). We analyzed outcomes in 2 ways: (1) a prospectively enrolled clinical trial, where all women were considered (the intent-to-treat (ITT) analysis); and (2) an observational study, where women who deliver before initiating ART were excluded (the naïve analysis). We explored the impact of later ART initiation and gestational age measurement error on our findings. RESULTS: Preconception ART initiation was not associated with preterm birth in ITT analyses. Risk ratios (RRs) for the effect of preconception ART initiation were RR = 1.10 (preterm), RR = 1.41 (very preterm), and RR = 5.01 (extreme preterm) in naïve analyses. Selection bias increased in the naïve analysis with advancing gestational age at ART initiation and with introduction of gestational age measurement error. CONCLUSIONS: Analyses of preterm birth that compare a preconception exposure to one that occurs in pregnancy are at risk of selection bias. See video abstract at, http://links.lww.com/EDE/B313.

Women's decision-making and uptake of services to prevent mother-to-child HIV transmission in Zambia.

Women's empowerment is associated with engagement in some areas of healthcare, but its role in prevention of mother-to-child HIV transmission (PMTCT) services has not been previously considered. In this secondary analysis, we investigated the association of women's decision-making and uptake of health services for PMTCT. Using data from population-based household surveys, we included women who reported delivery in the 2-year period prior to the survey and were HIV-infected. We measured a woman's self-reported role in decision-making in her own healthcare, making of large purchases, schooling of children, and healthcare for children. For each domain, respondents were categorized as having an "active" or "no active" role. We investigated associations between decision-making and specific steps along the PMTCT cascade: uptake of maternal antiretroviral drugs, uptake of infant HIV prophylaxis, and infant HIV testing. We calculated unadjusted and adjusted odds ratios via logistic regression. From March to December 2011, 344 HIV-infected mothers were surveyed and 276 completed the relevant survey questions. Of these, 190 (69%) took antiretroviral drugs during pregnancy; 175 (64%) of their HIV-exposed infants received antiretroviral prophylaxis; and 160 (58%) had their infant tested for HIV. There was no association between decision-making and maternal or infant antiretroviral drug use. We observed a significant association between decision-making and infant HIV testing in univariate analyses (OR 1.56-1.85; p < 0.05); however, odds ratios for the decision-making indicators were no longer statistically significant predictors of infant HIV testing in multivariate analyses. In conclusion, women who reported an active role in decision-making trended toward a higher likelihood of uptake of infant testing in the PMTCT cascade. Larger studies are needed to evaluate the impact of empowerment initiatives on the PMTCT service utilization overall and infant testing in particular.

The Role of Distance and Quality on Facility Selection for Maternal and Child Health Services in Urban Kenya.

Universal access to health care requires service availability and accessibility for those most in need of maternal and child health services. Women often bypass facilities closest to home due to poor quality. Few studies have directly linked individuals to facilities where they sought maternal and child health services and examined the role of distance and quality on this facility choice. Using endline data from a longitudinal survey from a sample of women in five cities in Kenya, we examine the role of distance and quality on facility selection for women using delivery, facility-based contraceptives, and child health services. A survey of public and private facilities offering reproductive health services was also conducted. Distances were measured between household cluster location and both the nearest facility and facility where women sought care. A quality index score representing facility infrastructure, staff, and supply characteristics was assigned to each facility. We use descriptive statistics to compare distance and quality between the nearest available facility and visited facility among women who bypassed the nearest facility. Facility distance and quality comparisons were also stratified by poverty status. Logistic regression models were used to measure associations between the quality and distance to the nearest facility and bypassing for each outcome. The majority of women bypassed the nearest facility regardless of service sought. Women bypassing for delivery traveled the furthest and had the fewest facility options near their residential cluster. Poor women bypassing for delivery traveled 4.5 km further than non-poor women. Among women who bypassed, two thirds seeking delivery and approximately 46% seeking facility-based contraception or child health services bypassed to a public hospital. Both poor and non-poor women bypassed to higher quality facilities. Our findings suggest that women in five cities in Kenya prefer public hospitals and are willing to travel further to obtain services at public hospitals, possibly related to free service availability. Over time, it will be important to examine service quality and availability in public sector facilities with reduced or eliminated user fees, and whether it lends itself to a continuum of care where women can visit one facility for multiple services reducing travel burden.

Impact of the Urban Reproductive Health Initiative on family planning uptake at facilities in Kenya, Nigeria, and Senegal.

BACKGROUND: The 2012 London Summit on Family Planning set ambitious goals to enable 120 million more women and adolescent girls to use modern contraceptives by 2020. The Urban Reproductive Health Initiative (URHI) was a Bill & Melinda Gates Foundation funded program designed to help contribute to these goals in urban areas in India, Kenya, Nigeria, and Senegal. URHI implemented a range of country-specific demand and supply side interventions, with supply interventions generally focused on improved service quality, provider training, outreach to patients, and commodity stock management. This study uses data collected by the Measurement, Learning & Evaluation (MLE) Project to examine the effectiveness of these supply-side interventions by considering URHI's influence on the number of family planning clients at health facilities over a four-year period in Kenya, Nigeria, and Senegal. METHODS: The analysis used facility audits and provider surveys. Principal-components analysis was used to create country-specific program exposure variables for health facilities. Fixed-effects regression was used to determine whether family planning uptake increased at facilities with higher exposure. Outcomes of interest were the number of new family planning acceptors and the total number of family planning clients per reproductive health care provider in the last year. RESULTS: Higher program component scores were associated with an increase in new family planning acceptors per provider in Kenya (ß = 18, 95% CI = 7-29), Nigeria (ß = 14, 95% CI = 8-20), and Senegal (ß = 7, 95% CI = 3-12). Higher scores were also associated with more family planning clients per provider in Kenya (ß = 31, 95% CI = 7-56) and Nigeria (ß = 26, 95% CI = 15-38), but not in Senegal. CONCLUSIONS: Supply-side interventions have increased the number of new family planning acceptors at facilities in urban Nigeria, Kenya, and Senegal and the overall number of clients in urban Nigeria and Kenya. While tailoring to the local environment, programs seeking to increase family planning use should include components to improve availability and quality of family planning services, which are part of a rights-based approach to family planning programming.

Hypospadias and maternal exposure to atrazine via drinking water in the National Birth Defects Prevention study.

BACKGROUND: Hypospadias is a relatively common birth defect affecting the male urinary tract. It has been suggested that exposure to endocrine disrupting chemicals might increase the risk of hypospadias by interrupting normal urethral development. METHODS: Using data from the National Birth Defects Prevention Study, a population-based case-control study, we considered the role of maternal exposure to atrazine, a widely used herbicide and potential endocrine disruptor, via drinking water in the etiology of 2nd and 3rd degree hypospadias. We used data on 343 hypospadias cases and 1,422 male controls in North Carolina, Arkansas, Iowa, and Texas from 1998-2005. Using catchment level stream and groundwater contaminant models from the US Geological Survey, we estimated atrazine concentrations in public water supplies and in private wells. We assigned case and control mothers to public water supplies based on geocoded maternal address during the critical window of exposure for hypospadias (i.e., gestational weeks 6-16). Using maternal questionnaire data about water consumption and drinking water, we estimated a surrogate for total maternal consumption of atrazine via drinking water. We then included additional maternal covariates, including age, race/ethnicity, parity, and plurality, in logistic regression analyses to consider an association between atrazine and hypospadias. RESULTS: When controlling for maternal characteristics, any association between hypospadias and daily maternal atrazine exposure during the critical window of genitourinary development was found to be weak or null (odds ratio for atrazine in drinking water = 1. 00, 95 % CI = 0.97 to 1.03 per 0.04 µg/day increase; odds ratio for maternal consumption = 1.02, 95 % CI = 0.99 to 1.05; per 0.05 µg/day increase). CONCLUSIONS: While the association that we observed was weak, our results suggest that additional research into a possible association between atrazine and hypospadias occurrence, using a more sensitive exposure metric, would be useful.

Geographic analysis of individual and environmental risk factors for hypospadias births.

BACKGROUND: Hypospadias is a relatively common birth defect affecting the male urinary tract. We explored the etiology of hypospadias by examining its spatial distribution in North Carolina and the spatial clustering of residuals from individual and environmental risk factors. METHODS: We used data collected by the North Carolina Birth Defects Monitoring Program from 2003 to 2005 to estimate local Moran's I statistics to identify geographic clustering of overall and severe hypospadias, using 995 overall cases and 16,013 controls. We conducted logistic regression and local Moran's I statistics on standardized residuals to consider the contribution of individual variables (maternal age, maternal race/ethnicity, maternal education, smoking, parity, and diabetes) and environmental variables (block group land cover) to this clustering. RESULTS: Local Moran's I statistics indicated significant clustering of overall and severe hypospadias in eastern central North Carolina. Spatial clustering of hypospadias persisted when controlling for individual factors, but diminished somewhat when controlling for environmental factors. In adjusted models, maternal residence in a block group with more than 5% crop cover was associated with overall hypospadias (odds ratio = 1.22; 95% confidence interval = 1.04-1.43); that is living in a block group with greater than 5% crop cover was associated with a 22% increase in the odds of having a baby with hypospadias. Land cover was not associated with severe hypospadias. CONCLUSION: This study illustrates the potential contribution of mapping in generating hypotheses about disease etiology. Results suggest that environmental factors including proximity to agriculture may play some role in the spatial distribution of hypospadias. Birth Defects Research (Part A) 100:887-894, 2014. © 2014 Wiley Periodicals, Inc.

Silk-Hyaluronic Acid for Vocal Fold Augmentation: Safety Profile and Long-Term Voice Outcomes.

OBJECTIVES: Silk-hyaluronic acid (silk-HA) is a novel vocal fold augmentation material used in humans since July 2020. We aim to describe indications, voice outcomes, and longevity data for silk-HA injectable when used for vocal fold injection (VFI) augmentation in a large cohort of patients with longer-term follow-up than preliminary clinical studies. METHODS: Retrospective chart review of Silk-HA injections for glottic insufficiency (GI) and follow-up between July 2020 and November 2023. Subject demographics, diagnoses, volume of material injected, VHI-10 data, time from injection, need for reinjection, and complications were collected. Blinded perceptual voice analysis of randomly selected pre- and post-intervention voice samples for unilateral vocal fold paralysis patients was performed by three voice-specialized speech-language pathologists, and changes in VHI-10 determined at various time intervals up to 1year and beyond. RESULTS: A total of 160 silk-HA injection procedures were performed: 59% female, with a mean age of 66± 13 (range 21-90) years. Ninety-four subjects had unilateral paralysis (58.4%); the remainder had scar, atrophy, paresis, or a combination thereof. Mean volume of silk-HA injected was 0.24± 0.14 cc. Major complications were rare, most notable for laryngoscopic evidence of hemilaryngeal edema (n = 6, 3.8%), with a readmission rate to hospital of 1.3% (n = 2). There was a statistically significant decrease in paired ΔVHI-10 and CAPE-V ratings for each of the postoperative follow-up intervals. A total of 24 (27.2%) repeat medialization procedures were recommended following silk-HA injection for unilateral paralysis. CONCLUSIONS: This study demonstrates that silk-HA is a safe product for VFI augmentation, and effective injectable for the treatment of GI due to unilateral vocal fold paralysis. Based on the current data, it is reasonable to counsel patients that they should expect benefit for several months following the injection. If patients reach 1year from their injection with a stable and satisfactory outcome, the majority experience ongoing benefit without need for additional procedures, however, the final duration of clinical effect appears to be years, but it is yet to be determined.

Protective benefits of deep tube wells against childhood diarrhea in Matlab, Bangladesh.

OBJECTIVES: We investigated whether deep tube wells installed to provide arsenic-free groundwater in rural Bangladesh have the added benefit of reducing childhood diarrheal disease incidence. METHODS: We recorded cases of diarrhea in children younger than 5 years in 142 villages of Matlab, Bangladesh, during monthly community health surveys in 2005 and 2006. We surveyed the location and depth of 12,018 tube wells and integrated these data with diarrhea data and other data in a geographic information system. We fit a longitudinal logistic regression model to measure the relationship between childhood diarrhea and deep tube well use. We controlled for maternal education, family wealth, year, and distance to a deep tube well. RESULTS: Household clusters assumed to be using deep tube wells were 48.7% (95% confidence interval = 27.8%, 63.5%) less likely to have a case of childhood diarrhea than were other household clusters. CONCLUSIONS: Increased access to deep tube wells may provide dual benefits to vulnerable populations in Matlab, Bangladesh, by reducing the risk of childhood diarrheal disease and decreasing exposure to naturally occurring arsenic in groundwater.

Choice of a family planning outlet in urban areas: The role of distance and quality of services in Kenya and Uganda.

Introduction: Quality of care and physical access to health facilities affect facility choice for family planning (FP). These factors may disproportionately impact young contraceptive users. Understanding which components of service quality drive facility choice among contraceptive users of all ages can inform strategies to strengthen FP programming for all potential users of FP. Methods: This study uses data from Population Services International's Consumer's Market for Family Planning (CM4FP) project, to examine drivers of facility choice among female FP users. The data collected from female contraceptive users, the outlet where they obtained their contraceptive method, and the complete set of alternative outlets in select urban areas of Kenya and Uganda were used. We use a mixed logit model, with inverse probability weights to correct for selection into categories of nonuse and missing facility data. We consider results separately for youth (18-24) and women aged 25-49 in both countries. Results: We find that in both countries and across age groups, users were willing to travel further to public outlets and to outlets offering more methods. Other outlet attributes, including signage, pharmacy, stockouts, and provider training, were important to women in certain age groups or country. Discussion: These results shed light on what components of service quality drive outlet choice among young and older users and can inform strategies to strengthen FP programming for all potential users of FP in urban settings.

The more, the better: influence of family planning discussions during the maternal, newborn and child health continuum of care on postpartum contraceptive uptake and method type among young women in Ethiopia.

Background: This study examines the association between family planning (FP) discussions with health professionals during contact points on the maternal, newborn and child health continuum of care and timing of modern contraceptive uptake and method type in the one-year following childbirth in six regions of Ethiopia among adolescent girls and young women (AGYW). Methods: This paper uses panel data of women aged 15-24 who were interviewed during pregnancy and the postpartum period between 2019-2021 as part of the PMA Ethiopia survey (n=652).  Results: Despite the majority of pregnant and postpartum AGYW attending antenatal care (ANC), giving birth in a health facility, and attending vaccination visits, one-third or less of those who received the service reported discussion of FP at any of these visits. When considering the cumulative effect of discussions of FP at ANC, pre-discharge after childbirth, postnatal care and vaccination visits, we found that discussion of FP at a greater number of visits resulted in increased uptake of modern contraception by one-year postpartum. A greater number of FP discussions was associated with higher long-acting reversible contraceptive use relative to non-use and relative to short-acting method use. Conclusions: Despite high attendance, there are missed opportunities to discuss FP when AGYW access care.

Preliminary Results on the Safety and Efficacy of Silk-Hyaluronic Acid for Treatment of Glottic Insufficiency.

OBJECTIVES: Silk-Hyaluronic Acid (Silk-HA) is a novel vocal fold augmentation material that has been used in humans since July 2020. There is a paucity of published data on Silk-HA and its longevity remains a question. This study aimed to evaluate a single surgeon's initial experience performing Silk-HA injection laryngoplasty for the treatment of glottic insufficiency. METHODS: Retrospective chart review of Silk-HA injections between July 2020 and December 2021. Subject demographics, diagnoses, volume of material injected, VHI-10 data, and complications were collected. A blinded perceptual voice analysis of voice samples was performed by two voice-specialized speech-language pathologists (SLP) for a subset of unilateral vocal fold paralysis patients before and 3-months following silk-HA injection. Univariate assessment of the change in VHI-10 and perceptual voice analyses at 3-month follow up was determined. RESULTS: 58 patients (43.1% female) underwent Silk-HA injection with a mean age of 64 (range 21-88). 38 subjects had unilateral paralysis (65.6%), and the remaining had scar, atrophy, paresis or a combination thereof. 49 injections were unilateral (84.5%). Mean volume of silk injected was 0.26 mL. Complications were rare, most notable though for 2 admissions for dyspnea and laryngoscopic evidence of hemi-laryngeal edema (3.4%). Mean change in CAPE-V overall severity rating was -32.9 (P<0.0001), and VHI-10 was -14.6 ± 10 (P=0.0013). 14 patients underwent a repeat silk-HA injection for ongoing glottic insufficiency (loss of augmentation vs under-augmentation). CONCLUSIONS: Preliminary results for Silk-HA show potential for ongoing improvement of glottic insufficiency at 3 months from date of augmentation. Clinician and patient perception of voice outcomes showed overall improvement at three months, though longevity remains to be determined. While overall well tolerated and without serious complications in 96% of the cohort, patients should be counseled on the potential for airway edema and symptomatic dyspnea requiring steroid management and observation.

Diarrheal disease risk in rural Bangladesh decreases as tubewell density increases: a zero-inflated and geographically weighted analysis.

BACKGROUND: This study investigates the impact of tubewell user density on cholera and shigellosis events in Matlab, Bangladesh between 2002 and 2004. Household-level demographic, health, and water infrastructure data were incorporated into a local geographic information systems (GIS) database. Geographically-weighted regression (GWR) models were constructed to identify spatial variation of relationships across the study area. Zero-inflated negative binomial regression models were run to simultaneously measure the likelihood of increased magnitude of disease events and the likelihood of zero cholera or shigellosis events. The aim of this study was to examine the effect of tubewell density on both the occurrence of diarrheal disease and the magnitude of diarrheal disease incidence. RESULTS: In Matlab, households with greater tubewell density were more likely to report zero cholera or shigellosis events. Results for both cholera and shigellosis GWR models suggest that tubewell density effects are spatially stationary and the use of non-spatial statistical methods is appropriate. CONCLUSIONS: Increasing the amount of drinking water available to households through increased density of tubewells contributed to lower reports of cholera and shigellosis events in rural Bangladesh. Our findings demonstrate the importance of tubewell installation and access to groundwater in reducing diarrheal disease events in the developing world.

Vaginal progesterone to prevent preterm delivery among HIV-infected pregnant women in Zambia: A feasibility study.

Antenatal vaginal progesterone (VP) reduces the risk of preterm birth (PTB) in women with shortened cervical length, and we hypothesize that it may also prevent PTB in women with HIV as their primary risk factor. We conducted a pilot feasibility study in Lusaka, Zambia to investigate uptake, adherence, and retention in preparation for a future efficacy trial. This was a double-masked, placebo-controlled, randomized trial of 200mg daily self-administered VP suppository or placebo. Pregnant women with HIV who were initiating or continuing antiretroviral therapy were eligible for participation. Potential participants underwent ultrasound to assess eligibility; we excluded those ≥24 gestational weeks, with non-viable, multiple gestation, or extrauterine pregnancies, with short cervix (<2.0cm), or with prior spontaneous PTB. Participants initiated study product between 20-24 weeks of gestation and continued to 37 weeks (or delivery, if sooner). The primary outcome was adherence (proportion achieving ≥80% study product use), assessed by dye stain assay of returned single-use vaginal applicators. Secondary outcomes with pre-defined feasibility targets were: uptake (≥50% eligible participants enrolled) and retention (≥90% ascertainment of delivery outcomes). We also evaluated preliminary efficacy by comparing the risk of spontaneous PTB <37 weeks between groups. From July 2017 to June 2018, 208 HIV-infected pregnant women were eligible for screening and 140 (uptake = 67%) were randomly allocated to VP (n = 70) or placebo (n = 70). Mean adherence was 94% (SD±9.4); 91% (n = 125/137) achieved overall adherence ≥80%. Delivery outcomes were ascertained from 134 (96%) participants. Spontaneous PTB occurred in 10 participants (15%) receiving placebo and 8 (12%) receiving progesterone (RR 0.82; 95%CI:0.34-1.97). Spontaneous PTB < 34 weeks occurred in 6 (9%) receiving placebo and 4 (6%) receiving progesterone (RR 0.67; 95%CI:0.20-2.67). In contrast to findings from vaginal microbicide studies in HIV-uninfected, non-pregnant women, our trial participants were highly adherent to daily self-administered vaginal progesterone. The study's a priori criteria for uptake, adherence, and retention were met, indicating that a phase III efficacy trial would be feasible.

Multiomics Characterization of Preterm Birth in Low- and Middle-Income Countries.

Importance: Worldwide, preterm birth (PTB) is the single largest cause of deaths in the perinatal and neonatal period and is associated with increased morbidity in young children. The cause of PTB is multifactorial, and the development of generalizable biological models may enable early detection and guide therapeutic studies. Objective: To investigate the ability of transcriptomics and proteomics profiling of plasma and metabolomics analysis of urine to identify early biological measurements associated with PTB. Design, Setting, and Participants: This diagnostic/prognostic study analyzed plasma and urine samples collected from May 2014 to June 2017 from pregnant women in 5 biorepository cohorts in low- and middle-income countries (LMICs; ie, Matlab, Bangladesh; Lusaka, Zambia; Sylhet, Bangladesh; Karachi, Pakistan; and Pemba, Tanzania). These cohorts were established to study maternal and fetal outcomes and were supported by the Alliance for Maternal and Newborn Health Improvement and the Global Alliance to Prevent Prematurity and Stillbirth biorepositories. Data were analyzed from December 2018 to July 2019. Exposures: Blood and urine specimens that were collected early during pregnancy (median sampling time of 13.6 weeks of gestation, according to ultrasonography) were processed, stored, and shipped to the laboratories under uniform protocols. Plasma samples were assayed for targeted measurement of proteins and untargeted cell-free ribonucleic acid profiling; urine samples were assayed for metabolites. Main Outcomes and Measures: The PTB phenotype was defined as the delivery of a live infant before completing 37 weeks of gestation. Results: Of the 81 pregnant women included in this study, 39 had PTBs (48.1%) and 42 had term pregnancies (51.9%) (mean [SD] age of 24.8 [5.3] years). Univariate analysis demonstrated functional biological differences across the 5 cohorts. A cohort-adjusted machine learning algorithm was applied to each biological data set, and then a higher-level machine learning modeling combined the results into a final integrative model. The integrated model was more accurate, with an area under the receiver operating characteristic curve (AUROC) of 0.83 (95% CI, 0.72-0.91) compared with the models derived for each independent biological modality (transcriptomics AUROC, 0.73 [95% CI, 0.61-0.83]; metabolomics AUROC, 0.59 [95% CI, 0.47-0.72]; and proteomics AUROC, 0.75 [95% CI, 0.64-0.85]). Primary features associated with PTB included an inflammatory module as well as a metabolomic module measured in urine associated with the glutamine and glutamate metabolism and valine, leucine, and isoleucine biosynthesis pathways. Conclusions and Relevance: This study found that, in LMICs and high PTB settings, major biological adaptations during term pregnancy follow a generalizable model and the predictive accuracy for PTB was augmented by combining various omics data sets, suggesting that PTB is a condition that manifests within multiple biological systems. These data sets, with machine learning partnerships, may be a key step in developing valuable predictive tests and intervention candidates for preventing PTB.

HIV serostatus, viral load, and midtrimester cervical length in a Zambian prenatal cohort.

OBJECTIVE: To evaluate whether maternal HIV serostatus and plasma viral load (VL) are associated with midtrimester cervical length (CL). METHODS: The Zambian Preterm Birth Prevention Study (ZAPPS) is an ongoing prospective cohort that began enrolling in Lusaka in August 2015. Pregnant women undergo ultrasound to determine gestational age and return for CL measurement at 16-28 weeks. We evaluated crude and adjusted associations between dichotomous indicators and short cervix (≤2.5 cm) via logistic regression, and between VL and CL as a continuous variable via linear regression. RESULTS: This analysis includes 1171 women enrolled between August 2015 and September 2017. Of 294 (25.1%) HIV-positive women, 275 (93.5%) had viral load performed close to CL measurement; of these, 148 (53.8%) had undetectable virus. Median CL was 3.6 cm (IQR 3.5-4.0) and was similar in HIV-infected (3.7 cm, IQR 3.5-4.0) versus uninfected (3.6 cm, IQR 3.5-4.0) participants (P=0.273). The odds of short CL were similar by HIV serostatus (OR 0.64; P=0.298) and detectable VL among those infected (OR 2.37, P=0.323). We observed no association between log VL and CL via linear regression (-0.12 cm; P=0.732). CONCLUSION: We found no evidence of association between HIV infection and short CL.

Adverse birth outcomes and their clinical phenotypes in an urban Zambian cohort.

Background: Few cohort studies of pregnancy in sub-Saharan Africa use rigorous gestational age dating and clinical phenotyping. As a result, incidence and risk factors of adverse birth outcomes are inadequately characterized. Methods: The Zambian Preterm Birth Prevention Study (ZAPPS) is a prospective observational cohort established to investigate adverse birth outcomes at a referral hospital in urban Lusaka. This report describes ZAPPS phase I, enrolled August 2015 to September 2017. Women were followed through pregnancy and 42 days postpartum. At delivery, study staff assessed neonatal vital status, birthweight, and sex, and assigned a delivery phenotype. Primary outcomes were: (1) preterm birth (PTB; delivery <37 weeks), (2) small-for-gestational-age (SGA; <10 th percentile weight-for-age at birth), and (3) stillbirth (SB; delivery of an infant without signs of life). Results: ZAPPS phase I enrolled 1450 women with median age 27 years (IQR 23-32). Most participants (68%) were multiparous, of whom 41% reported a prior PTB and 14% reported a prior stillbirth. Twins were present in 3% of pregnancies, 3% of women had short cervix (<25mm), 24% of women were HIV seropositive, and 5% were syphilis seropositive. Of 1216 (84%) retained at delivery, 15% were preterm, 18% small-for-gestational-age, and 4% stillborn. PTB risk was higher with prior PTB (aRR 1.88; 95%CI 1.32-2.68), short cervix (aRR 2.62; 95%CI 1.68-4.09), twins (aRR 5.22; 95%CI 3.67-7.43), and antenatal hypertension (aRR 2.04; 95%CI 1.43-2.91). SGA risk was higher with twins (aRR 2.75; 95%CI 1.81-4.18) and antenatal hypertension (aRR 1.62; 95%CI 1.16-2.26). SB risk was higher with short cervix (aRR 6.42; 95%CI 2.56-16.1). Conclusio ns: This study confirms high rates of PTB, SGA, and SB among pregnant women in Lusaka, Zambia. Accurate gestational age dating and careful ascertainment of delivery data are critical to understanding the scope of adverse birth outcomes in low-resource settings.