Dataset Information

Antenatal, intrapartum and infant azithromycin to prevent stillbirths and infant deaths: study protocol for SANTE, a 2×2 factorial randomised controlled trial in Mali.

ABSTRACT:

Introduction

In high mortality settings, prophylactic azithromycin has been shown to improve birth weight and gestational age at birth when administered antenatally, to reduce the incidence of neonatal infections when administered intrapartum, and to improve survival when administered in infancy. Questions remain regarding whether azithromycin can prevent stillbirths, and regarding the optimal strategy for the delivery of azithromycin to pregnant women and their infants.

Methods and analysis

Sauver avec l'Azithromycine en Traitant les Femmes Enceintes et les Enfants (SANTE) is a 2×2 factorial, individually randomised, placebo-controlled, double-masked trial in rural Mali. The primary aims are: (1A) to assess the efficacy of antenatal and intrapartum azithromycin on a composite outcome of stillbirths and infant mortality through 6-12 months and (1B) to assess the efficacy of azithromycin administered concurrently with the first and third doses of pentavalent vaccines (Penta-1/3) on infant mortality through 6-12 months. Pregnant participants (n=49 600) and their infants are randomised 1:1:1:1 to one of four treatment arms: (1) mother and infant receive azithromycin, (2) mother and infant receive placebo, (3) mother receives azithromycin and infant receives placebo or (4) mother receives placebo and infant receives azithromycin. Pregnant participants receive three single 2 g doses: two antepartum and one intrapartum. Infants receive a single 20 mg/kg dose at the Penta-1 and 3 visits. An additional cohort of 12 000 infants is recruited at the Penta-1 visit and randomised 1:1 to receive azithromycin or placebo at the same time points. The SANTE trial will inform guidelines and policies regarding the administration of antenatal and infant azithromycin using routine healthcare delivery platforms.

Ethics and dissemination

This trial was approved by the Institutional Review Board at the University of Maryland School of Medicine (Protocol #HP-00084242) and the Faculté de Médecine et d'Odonto-Stomatologie in Mali. The findings of this trial will be published in open access peer-reviewed journals.

Trial registration number

NCT03909737.

SUBMITTER: Driscoll AJ

PROVIDER: S-EPMC10471877 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Publications

Antenatal, intrapartum and infant azithromycin to prevent stillbirths and infant deaths: study protocol for SANTE, a 2×2 factorial randomised controlled trial in Mali.

Driscoll Amanda J AJ Haidara Fadima Cheick FC Tapia Milagritos D MD Deichsel Emily L EL Samake Ousmane S OS Bocoum Tiecoura T Bailey Jason A JA Fitzpatrick Meagan C MC Goldenberg Robert L RL Kodio Mamoudou M Moulton Lawrence H LH Nasrin Dilruba D Onwuchekwa Uma U Shaffer Allison M AM Sow Samba O SO Kotloff Karen L KL

BMJ open 20230830 8

<h4>Introduction</h4>In high mortality settings, prophylactic azithromycin has been shown to improve birth weight and gestational age at birth when administered antenatally, to reduce the incidence of neonatal infections when administered intrapartum, and to improve survival when administered in infancy. Questions remain regarding whether azithromycin can prevent stillbirths, and regarding the optimal strategy for the delivery of azithromycin to pregnant women and their infants.<h4>Methods and a ...[more]

PMID: 37648393

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Project description:BackgroundAn estimated >2 million babies stillborn around the world each year lack visibility. Low- and middle-income countries carry 84% of the burden yet have the least data. Most births are now in facilities, hence routine register-recording presents an opportunity to improve counting of stillbirths, but research is limited, particularly regarding accuracy. This paper evaluates register-recorded measurement of hospital stillbirths, classification accuracy, and barriers and enablers to routine recording.MethodsThe EN-BIRTH mixed-methods, observational study took place in five hospitals in Bangladesh, Nepal and Tanzania (2017-2018). Clinical observers collected time-stamped data on perinatal care and birth outcomes as gold standard. To assess accuracy of routine register-recorded stillbirth rates, we compared birth outcomes recorded in labour ward registers to observation data. We calculated absolute rate differences and individual-level validation metrics (sensitivity, specificity, percent agreement). We assessed misclassification of stillbirths with neonatal deaths. To examine stillbirth appearance (fresh/macerated) as a proxy for timing of death, we compared appearance to observed timing of intrauterine death based on heart rate at admission.Results23,072 births were observed including 550 stillbirths. Register-recorded completeness of birth outcomes was > 90%. The observed study stillbirth rate ranged from 3.8 (95%CI = 2.0,7.0) to 50.3 (95%CI = 43.6,58.0)/1000 total births and was under-estimated in routine registers by 1.1 to 7.3 /1000 total births (register: observed ratio 0.9-0.7). Specificity of register-recorded birth outcomes was > 99% and sensitivity varied between hospitals, ranging from 77.7-86.1%. Percent agreement between observer-assessed birth outcome and register-recorded birth outcome was very high across all hospitals and all modes of birth (> 98%). Fresh or macerated stillbirth appearance was a poor proxy for timing of stillbirth. While there were similar numbers of stillbirths misclassified as neonatal deaths (17/430) and neonatal deaths misclassified as stillbirths (21/36), neonatal deaths were proportionately more likely to be misclassified as stillbirths (58.3% vs 4.0%). Enablers to more accurate register-recording of birth outcome included supervision and data use.ConclusionsOur results show these routine registers accurately recorded stillbirths. Fresh/macerated appearance was a poor proxy for intrapartum stillbirths, hence more focus on measuring fetal heart rate is crucial to classification and importantly reduction in these preventable deaths.

Project description:IntroductionInfants born to women living with HIV initiating combination antiretroviral therapy (cART) late in pregnancy are at high risk of intrapartum infection. Mother/infant perinatal antiretroviral intensification may substantially reduce this risk.MethodsIn this single-arm Bayesian trial, pregnant women with HIV receiving standard of care antiretroviral prophylaxis in Thailand (maternal antenatal lopinavir-based cART; nonbreastfed infants 4 weeks' postnatal zidovudine) were offered "antiretroviral intensification" (labor single-dose nevirapine plus infant zidovudine-lamivudine-nevirapine for 2 weeks followed by zidovudine-lamivudine for 2 weeks) if their antenatal cART was initiated ≤8 weeks before delivery. A negative birth HIV-DNA polymerase chain reaction (PCR) followed by a confirmed positive PCR defined intrapartum transmission. Before study initiation, we modeled intrapartum transmission probabilities using data from 3738 mother/infant pairs enrolled in our previous trials in Thailand using a logistic model, with perinatal maternal/infant antiretroviral regimen and predicted viral load at delivery as main covariates. Using the characteristics of the women enrolled who received intensification, prior intrapartum transmission probabilities (credibility intervals) with/without intensification were estimated. After including the transmission data observed in the current study, the corresponding Bayesian posterior transmission probability was derived.ResultsNo intrapartum transmission of HIV was observed among the 88 mother/infant pairs receiving intensification. The estimated intrapartum transmission probability was 2·2% (95% credibility interval 0·5-6·1) without intensification versus 0·3% (0·0-1·6) with intensification. The probability of superiority of intensification over standard of care was 94·4%. Antiretroviral intensification appeared safe.ConclusionMother/infant antiretroviral intensification was effective in preventing intrapartum transmission of HIV in pregnant women receiving ≤8 weeks antepartum cART.

Project description:BackgroundThe safety and efficacy of adding antiretroviral drugs to standard zidovudine prophylaxis in infants of mothers with human immunodeficiency virus (HIV) infection who did not receive antenatal antiretroviral therapy (ART) because of late identification are unclear. We evaluated three ART regimens in such infants.MethodsWithin 48 hours after their birth, we randomly assigned formula-fed infants born to women with a peripartum diagnosis of HIV type 1 (HIV-1) infection to one of three regimens: zidovudine for 6 weeks (zidovudine-alone group), zidovudine for 6 weeks plus three doses of nevirapine during the first 8 days of life (two-drug group), or zidovudine for 6 weeks plus nelfinavir and lamivudine for 2 weeks (three-drug group). The primary outcome was HIV-1 infection at 3 months in infants uninfected at birth.ResultsA total of 1684 infants were enrolled in the Americas and South Africa (566 in the zidovudine-alone group, 562 in the two-drug group, and 556 in the three-drug group). The overall rate of in utero transmission of HIV-1 on the basis of Kaplan-Meier estimates was 5.7% (93 infants), with no significant differences among the groups. Intrapartum transmission occurred in 24 infants in the zidovudine-alone group (4.8%; 95% confidence interval [CI], 3.2 to 7.1), as compared with 11 infants in the two-drug group (2.2%; 95% CI, 1.2 to 3.9; P=0.046) and 12 in the three-drug group (2.4%; 95% CI, 1.4 to 4.3; P=0.046). The overall transmission rate was 8.5% (140 infants), with an increased rate in the zidovudine-alone group (P=0.03 for the comparisons with the two- and three-drug groups). On multivariate analysis, zidovudine monotherapy, a higher maternal viral load, and maternal use of illegal substances were significantly associated with transmission. The rate of neutropenia was significantly increased in the three-drug group (P<0.001 for both comparisons with the other groups).ConclusionsIn neonates whose mothers did not receive ART during pregnancy, prophylaxis with a two- or three-drug ART regimen is superior to zidovudine alone for the prevention of intrapartum HIV transmission; the two-drug regimen has less toxicity than the three-drug regimen. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development [NICHD] and others; ClinicalTrials.gov number, NCT00099359.).

Project description:ObjectiveTo identify current and emerging self-care interventions to improve maternity healthcare.DesignScoping review.Data sourcesMEDLINE, Embase, EmCare, PsycINFO, Cochrane CENTRAL/CDSR, CINAHL Plus (last searched on 17 October 2021).Eligibility criteriaEvidence syntheses, interventional or observational studies describing any tool, resource or strategy to facilitate self-care in women preparing to get pregnant, currently pregnant, giving birth or post partum.Data extraction/synthesisScreening and data collection were conducted independently by two reviewers. Self-care interventions were identified based on predefined criteria and inductively organised into 11 categories. Characteristics of study design, interventions, participants and outcomes were recorded.ResultsWe identified eligible 580 studies. Many included studies evaluated interventions in high-income countries (45%) and during antenatal care (76%). Self-care categories featuring highest numbers of studies were diet and nutrition (26% of all studies), physical activity (24%), psychosocial strategies (18%) and other lifestyle adjustments (17%). Few studies featured self-care interventions for sexual health and postpartum family planning (2%), self-management of medication (3%) and self-testing/sampling (3%). Several venues to introduce self-care were described: health facilities (44%), community venues (14%), digital platforms (18%), partner/peer support (7%) or over-the-counter products (13%). Involvement of health and community workers were described in 38% and 8% of studies, who supported self-care interventions by providing therapeutics for home use, training or counselling. The most common categories of outcomes evaluated were neonatal outcomes (eg, birth weight) (31%), maternal mental health (26%) and labour outcomes (eg, duration of labour) (22%).ConclusionSelf-care interventions in maternal care are diverse in their applications, implementation characteristics and intended outcomes. Many self-care interventions were implemented with support from the health system at initial stages of use and uptake. Some promising self-care interventions require further primary research, though several are matured and up-to-date evidence syntheses are needed. Research on self-care in the preconception period is lacking.

Project description:BackgroundWorldwide, an estimated 5.1 million stillbirths and neonatal deaths occur annually, 98% in low- and middle-income countries. Limited coverage of civil and vital registration systems necessitates reliance on women's retrospective reporting in household surveys for data on these deaths. The predominant platform, Demographic and Health Surveys (DHS), has evolved over the last 35 years and differs by country, yet no previous study has described these differences and the effects of these changes on stillbirth and neonatal death measurement.MethodsWe undertook a review of DHS model questionnaires, protocols and methodological reports from DHS-I to DHS-VII, focusing on the collection of information on stillbirth and neonatal deaths describing differences in approaches, questionnaires and geographic reach up to December 9, 2019. We analysed the resultant data, applied previously used data quality criteria including ratios of stillbirth rate (SBR) to neonatal mortality rate (NMR) and early NMR (ENMR) to NMR, comparing by country, over time and by DHS module.ResultsDHS has conducted >320 surveys in 90 countries since 1984. Two types of maternity history have been used: full birth history (FBH) and full pregnancy history (FPH). A FBH collecting information only on live births has been included in all model questionnaires to date, with data on stillbirths collected through a reproductive calendar (DHS II-VI) or using additional questions on non-live births (DHS-VII). FPH collecting information on all pregnancies including live births, miscarriages, abortions and stillbirths has been used in 17 countries. We found no evidence of variation in stillbirth data quality assessed by SBR:NMR over time for FBH surveys with reproductive calendar, some variation for surveys with FBH in DHS-VII and most variation among the surveys conducted with a FPH. ENMR:NMR ratio increased over time, which may reflect changes in data quality or real epidemiological change.ConclusionDHS remains the major data source for pregnancy outcomes worldwide. Although the DHS model questionnaire has evolved over the last three and half decades, more robust evidence is required concerning optimal methods to obtain accurate data on stillbirths and neonatal deaths through household surveys and also to develop and test standardised data quality criteria.

Dataset Information

Antenatal, intrapartum and infant azithromycin to prevent stillbirths and infant deaths: study protocol for SANTE, a 2×2 factorial randomised controlled trial in Mali.

Introduction

Methods and analysis

Ethics and dissemination

Trial registration number

Publications

Antenatal, intrapartum and infant azithromycin to prevent stillbirths and infant deaths: study protocol for SANTE, a 2×2 factorial randomised controlled trial in Mali.

Similar Datasets

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