Evaluating the accuracy of International Classification of Disease Perinatal Mortality (ICD-PM) codes assigned on death certificates before and after expert panel review: a mixed methods observational study.

INTRODUCTION: The present study was conducted with the aim of evaluating the accuracy of International Classification of Disease Perinatal Mortality (ICD-PM) codes assigned on death certificates before and after an expert panel review. METHOD: The present study was a mixed methods observational study conducted at Umm al-Benin Hospital, the sole specialized obstetrics and gynecology center affiliated with Mashhad University of Medical Sciences. The study comprised three distinct stages: (1) Collecting primary ICD-PM codes assigned to perinatal death certificates, along with other relevant information, from October 2021 to March 2022; (2) Examining the circumstances of each perinatal death case and re-identifying the causes of death through a consensus process involving a panel of experts comprising pediatricians, obstetrics and gynecology specialists, and nursing and midwifery experts; presenting the new ICD-PM code; (3) Comparing the ICD-PM codes assigned to perinatal death certificates before and after the expert panel's evaluation. RESULT: During the study period, a total of seven specialized panels were conducted to examine perinatal deaths. Out of the 71 cases, 41 were carefully reviewed by experts. These cases included 32 stillbirths and nine neonatal deaths. The examination process followed specific inclusion and exclusion criteria. The findings revealed that there were no significant changes in the causes of neonatal deaths. However, it was notable that 80% of the previously unknown causes of stillbirths were successfully identified. Notably, the occurrence of stillbirths increased by 78% due to maternal causes and conditions. CONCLUSION: Convening panels of experts to discuss the causes of perinatal deaths can effectively reduce the percentage of unknown causes, as classified by ICD-PM. This approach also guarantees the availability of essential data for implementing effective interventions to decrease preventable perinatal deaths.

Qualineo Strategy Indicators Associated with Neonatal Death: A Cross-Sectional Study.

CONTEXT: The Qualineo Strategy is an effective measure for reducing neonatal mortality in regions with the highest death rates. In addition, it is a relevant Brazilian tool for strengthening teamwork and neonatal assistance. This study aims to analyze the predictors of neonatal death in the indicators of care provided by the Qualineo Strategy at a reference maternity hospital in Piauí, in the years 2021 to 2022. METHODS: This is a retrospective study of 1856 newborn records. Pearson's chi-squared test was used to assess the association between the variables; a predictive regression model was used to identify the variables that predict neonatal mortality. RESULTS: There was a significant association between all neonatal variables and the outcome of death (p < 0.05). The predictor variables for death in term newborns were the use of drugs by the mother and admission to the Neonatal Intensive Care Unit. For premature newborns, the predictor variables were, as follows: the use of cannula ventilation, an Apgar score in the 1st minute <7; and admission to the Neonatal Intensive Care Unit. CONCLUSIONS: The results will make it possible to visualize better strategies for the reality analyzed and reinforce the importance of prenatal care.

Implementation of maternal and perinatal death surveillance and response and related death review interventions in humanitarian settings: A scoping review.

Background: The global population impacted by humanitarian crises continues to break records each year, leaving strained and fractured health systems reliant upon humanitarian assistance in more than 60 countries. Yet little is known about implementation of maternal and perinatal death surveillance and response (MPDSR) within crisis-affected contexts. This scoping review aimed to synthesise evidence on the implementation of MPDSR and related death review interventions in humanitarian settings. Methods: We searched for peer-reviewed and grey literature in English and French published in 2016-22 that reported on MPDSR and related death review interventions within humanitarian settings. We screened and reviewed 1405 records, among which we identified 25 peer-reviewed articles and 11 reports. We then used content and thematic analysis to understand the adoption, appropriateness, fidelity, penetration, and sustainability of these interventions. Results: Across the 36 records, 33 unique programmes reported on 37 interventions within humanitarian contexts in 27 countries, representing 69% of the countries with a 2023 United Nations humanitarian appeal. Most identified programmes focussed on maternal death interventions; were in the pilot or early-mid implementation phases (1-5 years); and had limited integration within health systems. While we identified substantive documentation of MPDSR and related death review interventions, extensive gaps in evidence remain pertaining to the adoption, fidelity, penetration, and sustainability of these interventions. Across humanitarian contexts, implementation was influenced by severe resource limitations, variable leadership, pervasive blame culture, and mistrust within communities. Conclusions: Emergent MPDSR implementation dynamics show a complex interplay between humanitarian actors, communities, and health systems, worthy of in-depth investigation. Future mixed methods research evaluating the gamut of identified MPDSR programmes in humanitarian contexts will greatly bolster the evidence base. Investment in comparative health systems research to understand how best to adapt MPDSR and related death review interventions to humanitarian contexts is a crucial next step.

Legislation strengthening Maternal and Perinatal Death Surveillance and Response systems.

Historically, countries have primarily relied on policy rather than legislation to implement Maternal and Perinatal Death Surveillance and Response systems (MPDSR). However, evidence shows significant disparities in how MPDSR is implemented among different countries. In this article, we argue for the importance of establishing MPDSR systems mandated by law and aligned with the country's constitutional provisions, regional and international human rights obligations, and public health commitments. We highlight how a "no blame" approach can be regulated to provide a balance between confidentiality of the system and access to justice and remedies.

[Call for attention to the prevention of perinatal death attributed to birth defect].

Birth defect and perinatal death are major public issues threatening the health of women and children in China. However, perinatal death attributed to birth defects has not yet received sufficient attention. To minimize the occurrence of perinatal death caused by birth defects, this review article deeply analyzed the current status of epidemiology, clinical, and basic research on perinatal death attributed to birth defects both domestically and internationally, and proposed to encourage the conduct of national research on perinatal causes. We should also pay attention to the application of the perinatal cause of death classification system, and focus on accurate diagnosis and the three-level prevention and control of perinatal death attributed to birth defect.

A hybrid approach to skill retention following neonatal resuscitation training: Assessing effectiveness.

 Perinatal death, a global health problem, can be prevented with simple resuscitation interventions that help the baby breathe immediately at birth. Latter-day Saint Charities (LDSC) and Safa Sunaulo Nepal (SSN) implemented a program to scale-up Helping Babies Breathe (HBB) training in Karnali Province, Nepal from January 2020-February 2021. The interventions were implemented using a hybrid approach with on-site mentoring in the pre/post COVID period combined with remote support and monitoring during the COVID period. This paper reports overall changes in newborn outcomes in relation to the unique implementation approach used. A prospective cohort design was used to compare outcomes of birth cohorts in 16 public health facilities in the first and last three months of program implementation. Results showed significant decreases in intrapartum stillbirths (23%), and neonatal deaths within (27%) and after (41.3%) 24 hours of life. The scale-up of HBB training resulted in 557 providers receiving training and mentoring support during the program period, half trained during the COVID period. Increased practice sessions, review meetings and debriefing meetings were reported during the COVID period compared to pre/post COVID period. The evaluation is suggestive of the potential of a hybrid approach for improved perinatal outcomes and scaling-up of newborn resuscitation trainings in health system facing disruptions.

Audit as a tool for improving obstetric care in low- and middle-income countries.

Maternal and/or perinatal death review or audits aim to improve the quality of health services and reduce deaths due to causes identified. A death review audit cycle identifies causes of deaths and possible modifiable factors, these can point to potential breaks in the continuity of health care and other health systems faults and challenges. It is an important function of audit cycles to develop, implement, monitor, and review action plans to improve the service. The WHO has produced two handbooks (Making Every Baby Count and Monitoring Emergency Obstetric Care) to guide maternal and perinatal death reviews. Health worker related factors accounts for two thirds of aspects that, if done differently may have prevented the adverse outcome. This emphasises the need for skilled health care workers at every delivery and for deliveries to take place in health facilities.

Pentaerythrityl tetranitrate improves the outcome of children born to mothers with compromised uterine perfusion-12-months follow-up and safety data of the double-blind randomized PETN trial.

BACKGROUND: This is a follow-up study to the pentaerythrityl tetranitrate randomized controlled multicenter trial that reports neonatal outcome data of newborns admitted to neonatal intensive care units and outcome data of the offspring at 12 months of age. OBJECTIVE: We present data on adverse events reported during the study to document the safety of pentaerythrityl tetranitrate treatment during pregnancy. To further evaluate the effects of pentaerythrityl tetranitrate on neonatal and long-term outcomes, we present follow up data from of 240 children at 12 months of age, including information on height, weight, head circumference, developmental milestones, and the presence of chronic disease and of 144 newborns admitted to the neonatal intensive care unit during the trial. STUDY DESIGN: The pentaerythrityl tetranitrate trial was a randomized, double-blind, placebo-controlled study designed to assess the efficacy and safety of the nitric oxide-donor pentaerythrityl tetranitrate in the prevention of fetal growth restriction and perinatal death in pregnancies complicated by abnormal placental perfusion. RESULTS: Results at 12 months demonstrated that significantly more children were age appropriately developed without impairments in the pentaerythrityl tetranitrate group (P=.018). In addition, the presence of chronic disease was lower in the pentaerythrityl tetranitrate group (P=.041). Outcome data of the 144 newborns admitted to the neonatal intensive care unit did not reveal differences between the treatment and placebo groups. There were no differences in the number or nature of reported adverse events between the study groups. CONCLUSION: The analysis shows that study children born in the pentaerythrityl tetranitrate cohort have a clear advantage compared with the placebo group at the age of 12 months, as evidenced by the increased incidence of normal development without the presence of chronic disease. Although safety has been proven, further follow-up studies are necessary to justify pentaerythrityl tetranitrate treatment during pregnancies complicated by impaired uterine perfusion.

A systematic review of standardised tools used in perinatal death review programmes.

INTRODUCTION: Reducing preventable perinatal deaths is the focus of perinatal death surveillance and response programmes. Standardised review tools can help identify modifiable factors in perinatal deaths. AIM: This systematic review aimed to identify, compare, and appraise perinatal mortality review tools (PMRTs) in upper-middle to high-income countries. METHODS: Four major scientific databases were searched for publications relating to perinatal death reviews. There were no restrictions on date, study, or publication type. Professional websites for each country were searched for relevant material. The Appraisal of Guidelines Research and Evaluation Health Systems (AGREE-HS) checklist was used for quality appraisal of each tool. A narrative synthesis was used to describe and compare tools. FINDINGS: Ten PMRTs were included. Five PMRTs were from high-income countries, four from upper-middle income countries and one was designed for use in a global context. The structure, content, and quality of each PMRT varied. Each tool collected information about the antepartum, intrapartum, and neonatal periods and a section to classify perinatal deaths using a standardised classification system. All tools reviewed the care provided. Five tools included recommendation development for changes to clinical care. Four tools mentioned parent involvement in the review process. For quality appraisal, one review tool scored "high quality", six scored "moderate quality" and two scored "poor quality". CONCLUSION: There is little standardisation when it comes to PMRTs. Guidance on structuring PMRTs in a standardised way is needed. Recommendation development from a review is important to highlight changes to care required to reduce preventable perinatal deaths.

Maternal interventions to decrease stillbirths and neonatal mortality in Tanzania: evidence from the 2017-18 cross-sectional Tanzania verbal and social autopsy study.

BACKGROUND: Reduction of Tanzania's neonatal mortality rate has lagged behind that for all under-fives, and perinatal mortality has remained stagnant over the past two decades. We conducted a national verbal and social autopsy (VASA) study to estimate the causes and social determinants of stillbirths and neonatal deaths with the aim of identifying relevant health care and social interventions. METHODS: A VASA interview was conducted of all stillbirths and neonatal deaths in the prior 5 years identified by the 2015-16 Tanzania Demographic and Health Survey. We evaluated associations of maternal complications with antepartum and intrapartum stillbirth and leading causes of neonatal death; conducted descriptive analyses of antenatal (ANC) and delivery care and mothers' careseeking for complications; and developed logistic regression models to examine factors associated with delivery place and mode. RESULTS: There were 204 stillbirths, with 185 able to be classified as antepartum (88 [47.5%]) or intrapartum (97 [52.5%]), and 228 neonatal deaths. Women with an intrapartum stillbirth were 6.5% (adjusted odds ratio (aOR) = 1.065, 95% confidence interval (CI) 1.002, 1.132) more likely to have a C-section for every additional hour before delivery after reaching the birth attendant. Antepartum hemorrhage (APH), maternal anemia, and premature rupture of membranes (PROM) were significantly positively associated with early neonatal mortality due to preterm delivery, intrapartum-related events and serious infection, respectively. While half to two-thirds of mothers made four or more ANC visits (ANC4+), a third or fewer received quality ANC (Q-ANC). Women with a complication were more likely to deliver at hospital only if they received Q-ANC (neonates: aOR = 4.5, 95% CI 1.6, 12.3) or ANC4+ (stillbirths: aOR = 11.8, 95% CI 3.6, 38.0). Nevertheless, urban residence was the strongest predictor of hospital delivery. CONCLUSIONS: While Q-ANC and ANC4 + boosted hospital delivery among women with a complication, attendance was low and the quality of care is critical. Quality improvement efforts in urban and rural areas should focus on early detection and management of APH, maternal anemia, PROM, and prolonged labor, and on newborn resuscitation.

Neonatal near-miss audits: a systematic review and a call to action.

BACKGROUND: Neonatal near-miss (NNM) can be considered as an end of a spectrum that includes stillbirths and neonatal deaths. Clinical audits of NNM might reduce perinatal adverse outcomes. The aim of this review is to evaluate the effectiveness of NNM audits for reducing perinatal mortality and morbidity and explore related contextual factors. METHODS: PubMed, Embase, Scopus, CINAHL, LILACS and SciELO were searched in February/2023. Randomized and observational studies of NNM clinical audits were included without restrictions on setting, publication date or language. PRIMARY OUTCOMES: perinatal mortality, morbidity and NNM. SECONDARY OUTCOMES: factors contributing to NNM and measures of quality of care. Study characteristics, methodological quality and outcome were extracted and assessed by two independent reviewers. Narrative synthesis was performed. RESULTS: Of 3081 titles and abstracts screened, 36 articles had full-text review. Two studies identified, rated, and classified contributing care factors and generated recommendations to improve the quality of care. No study reported the primary outcomes for the review (change in perinatal mortality, morbidity and NNM rates resulting from an audit process), thus precluding meta-analysis. Three studies were multidisciplinary NNM audits and were assessed for additional contextual factors. CONCLUSION: There was little data available to determine the effectiveness of clinical audits of NNM. While trials randomised at patient level to test our research question would be difficult or unethical for both NNM and perinatal death audits, other strategies such as large, well-designed before-and-after studies within services or comparisons between services could contribute evidence. This review supports a Call to Action for NNM audits. Adoption of formal audit methodology, standardised NNM definitions, evaluation of parent's engagement and measurement of the effectiveness of quality improvement cycles for improving outcomes are needed.

Antenatal Care Reduces Neonatal Mortality in Ethiopia: A Systematic Review and Meta-Analysis of Observational Studies.

BACKGROUND: Neonatal deaths remain a serious public health concern in Ethiopia; being one of the top five countries contributing to half of the neonatal deaths worldwide. Although antenatal care (ANC) is assumed as one of the viable options that contribute to neonatal survival, findings from original studies indicated disparities in the effect of ANC on neonatal mortality. Thus, this review aimed to determine the pooled effect of ANC on neonatal mortality in Ethiopia. METHODS: Databases such as PubMed, EMBASE, CINAHL, HINARI, and Cochrane Central Library were searched for articles using keywords. Selection of eligible articles and data extraction were conducted by an independent author. The risk of a bias assessment tool for non-randomized studies was used to assess the quality of the articles. Comprehensive meta-analysis version 2 software was used for meta-analysis. Heterogeneity and publication bias of included studies were assessed using I2 test statistic and Egger test, respectively. The random-effect model was employed; an outcome is reported using a risk ratio with a 95% confidence interval. RESULTS: Of 28 included studies, 20 showed receiving at least one ANC visit had a significant association with neonatal mortality. Accordingly, the estimated pooled risk ratio for neonatal mortality was 0.59 (95% CI 0.45, 0.77) among infants born to women who had at least one ANC visit compared to infants born to women who had no ANC visits. CONCLUSION: This finding indicated that neonatal mortality was decreased among infants born to women who had at least one ANC visit compared to infants born to women who had no ANC visit. Therefore, promoting and strengthening ANC service utilization during pregnancy would accelerate the reduction of neonatal mortality in Ethiopia.

In some studies, providing ANC services reduces the risk of neonatal mortality, in others, the ANC visits did not significantly decrease neonatal mortality in Ethiopia, which represents a dismal picture of neonatal mortality (NM) in sub-Saharan Africa (SSA) region. Therefore, evidence emanated from comprehensive searches of review performed with several studies represented from various regions of the country which determine the effect of ANC on NM is essential to reinforce strategies that could help for newborn survival and wellbeing of neonates in Ethiopia. Hence, this study aimed to systematically examine the effect of ANC on NM by combining a wide range of reviews, to provide concrete evidence for policymakers.

Planned delivery or expectant management for late preterm pre-eclampsia in low-income and middle-income countries (CRADLE-4): a multicentre, open-label, randomised controlled trial.

BACKGROUND: Pre-eclampsia is a leading cause of maternal and perinatal mortality. Evidence regarding interventions in a low-income or middle-income setting is scarce. We aimed to evaluate whether planned delivery between 34+ 0 and 36+ 6 weeks' gestation can reduce maternal mortality and morbidity without increasing perinatal complications in India and Zambia. METHODS: In this parallel-group, multicentre, open-label, randomised controlled trial, we compared planned delivery versus expectant management in women with pre-eclampsia from 34+ 0 to 36+ 6 weeks' gestation. Participants were recruited from nine hospitals and referral facilities in India and Zambia and randomly assigned to planned delivery or expectant management in a 1:1 ratio by a secure web-based randomisation facility hosted by MedSciNet. Randomisation was stratified by centre and minimised by parity, single-fetus pregnancy or multi-fetal pregnancy, and gestational age. The primary maternal outcome was a composite of maternal mortality or morbidity with a superiority hypothesis. The primary perinatal outcome was a composite of one or more of: stillbirth, neonatal death, or neonatal unit admission of more than 48 h with a non-inferiority hypothesis (margin of 10% difference). Analyses were by intention to treat, with an additional per-protocol analysis for the perinatal outcome. The trial was prospectively registered with ISRCTN, 10672137. The trial is closed to recruitment and all follow-up has been completed. FINDINGS: Between Dec 19, 2019, and March 31, 2022, 565 women were enrolled. 284 women (282 women and 301 babies analysed) were allocated to planned delivery and 281 women (280 women and 300 babies analysed) were allocated to expectant management. The incidence of the primary maternal outcome was not significantly different in the planned delivery group (154 [55%]) compared with the expectant management group (168 [60%]; adjusted risk ratio [RR] 0·91, 95% CI 0·79 to 1·05). The incidence of the primary perinatal outcome by intention to treat was non-inferior in the planned delivery group (58 [19%]) compared with the expectant management group (67 [22%]; adjusted risk difference -3·39%, 90% CI -8·67 to 1·90; non-inferiority p<0·0001). The results from the per-protocol analysis were similar. There was a significant reduction in severe maternal hypertension (adjusted RR 0·83, 95% CI 0·70 to 0·99) and stillbirth (0·25, 0·07 to 0·87) associated with planned delivery. There were 12 serious adverse events in the planned delivery group and 21 in the expectant management group. INTERPRETATION: Clinicians can safely offer planned delivery to women with late preterm pre-eclampsia, in a low-income or middle-income country. Planned delivery reduces stillbirth, with no increase in neonatal unit admissions or neonatal morbidity and reduces the risk of severe maternal hypertension. Planned delivery from 34 weeks' gestation should therefore be considered as an intervention to reduce pre-eclampsia associated mortality and morbidity in these settings. FUNDING: UK Medical Research Council and Indian Department of Biotechnology.

Cervical Pessary for Prevention of Preterm Birth in Individuals With a Short Cervix: The TOPS Randomized Clinical Trial.

Importance: A short cervix as assessed by transvaginal ultrasound is an established risk factor for preterm birth. Study findings for a cervical pessary to prevent preterm delivery in singleton pregnancies with transvaginal ultrasound evidence of a short cervix have been conflicting. Objective: To determine if cervical pessary placement decreases the risk of preterm birth or fetal death prior to 37 weeks among individuals with a short cervix. Design, Setting, and Participants: We performed a multicenter, randomized, unmasked trial comparing a cervical pessary vs usual care from February 2017 through November 5, 2021, at 12 centers in the US. Study participants were nonlaboring individuals with a singleton pregnancy and a transvaginal ultrasound cervical length of 20 mm or less at gestations of 16 weeks 0 days through 23 weeks 6 days. Individuals with a prior spontaneous preterm birth were excluded. Interventions: Participants were randomized 1:1 to receive either a cervical pessary placed by a trained clinician (n = 280) or usual care (n = 264). Use of vaginal progesterone was at the discretion of treating clinicians. Main Outcome and Measures: The primary outcome was delivery or fetal death prior to 37 weeks. Results: A total of 544 participants (64%) of a planned sample size of 850 were enrolled in the study (mean age, 29.5 years [SD, 6 years]). Following the third interim analysis, study recruitment was stopped due to concern for fetal or neonatal/infant death as well as for futility. Baseline characteristics were balanced between participants randomized to pessary and those randomized to usual care; 98.9% received vaginal progesterone. In an as-randomized analysis, the primary outcome occurred in 127 participants (45.5%) randomized to pessary and 127 (45.6%) randomized to usual care (relative risk, 1.00; 95% CI, 0.83-1.20). Fetal or neonatal/infant death occurred in 13.3% of those randomized to receive a pessary and in 6.8% of those randomized to receive usual care (relative risk, 1.94; 95% CI, 1.13-3.32). Conclusions and Relevance: Cervical pessary in nonlaboring individuals with a singleton gestation and with a cervical length of 20 mm or less did not decrease the risk of preterm birth and was associated with a higher rate of fetal or neonatal/infant mortality. Trial Registration: ClinicalTrials.gov Identifier: NCT02901626.

A qualitative evaluation and conceptual framework on the use of the Birth weight and Age-at-death Boxes for Intervention and Evaluation System (BABIES) matrix for perinatal health in Uganda.

BACKGROUND: Perinatal mortality (newborn deaths in the first week of life and stillbirths) continues to be a significant global health threat, particularly in resource-constrained settings. Low-tech, innovative solutions that close the quality-of-care gap may contribute to progress toward the Sustainable Development Goals for health by 2030. From 2012 to 2018, the Saving Mothers, Giving Life Initiative (SMGL) implemented the Birth weight and Age-at-Death Boxes for Intervention and Evaluation System (BABIES) matrix in Western Uganda. The BABIES matrix provides a simple, standardized way to track perinatal health outcomes to inform evidence-based quality improvement strategies. METHODS: In November 2017, a facility-based qualitative evaluation was conducted using in-depth interviews with 29 health workers in 16 health facilities implementing BABIES in Uganda. Data were analyzed using directed content analysis across five domains: 1) perceived ease of use, 2) how the matrix was used, 3) changes in behavior or standard operating procedures after introduction, 4) perceived value of the matrix, and 5) program sustainability. RESULTS: Values in the matrix were easy to calculate, but training was required to ensure correct data placement and interpretation. Displaying the matrix on a highly visible board in the maternity ward fostered a sense of accountability for health outcomes. BABIES matrix reports were compiled, reviewed, and responded to monthly by interprofessional teams, prompting collaboration across units to fill data gaps and support perinatal death reviews. Respondents reported improved staff communication and performance appraisal, community engagement, and ability to track and link clinical outcomes with actions. Midwives felt empowered to participate in the problem-solving process. Respondents were motivated to continue using BABIES, although sustainability concerns were raised due to funding and staff shortages. CONCLUSIONS: District-level health systems can use data compiled from the BABIES matrix to inform policy and guide implementation of community-centered health practices to improve perinatal heath. Future work may consider using the Conceptual Framework on Use of the BABIES Matrix for Perinatal Health as a model to operationalize concepts and test the impact of the tool over time.

Azithromycin to Prevent Sepsis or Death in Women Planning a Vaginal Birth.

BACKGROUND: The use of azithromycin reduces maternal infection in women during unplanned cesarean delivery, but its effect on those with planned vaginal delivery is unknown. Data are needed on whether an intrapartum oral dose of azithromycin would reduce maternal and offspring sepsis or death. METHODS: In this multicountry, placebo-controlled, randomized trial, we assigned women who were in labor at 28 weeks' gestation or more and who were planning a vaginal delivery to receive a single 2-g oral dose of azithromycin or placebo. The two primary outcomes were a composite of maternal sepsis or death and a composite of stillbirth or neonatal death or sepsis. During an interim analysis, the data and safety monitoring committee recommended stopping the trial for maternal benefit. RESULTS: A total of 29,278 women underwent randomization. The incidence of maternal sepsis or death was lower in the azithromycin group than in the placebo group (1.6% vs. 2.4%), with a relative risk of 0.67 (95% confidence interval [CI], 0.56 to 0.79; P<0.001), but the incidence of stillbirth or neonatal death or sepsis was similar (10.5% vs. 10.3%), with a relative risk of 1.02 (95% CI, 0.95 to 1.09; P = 0.56). The difference in the maternal primary outcome appeared to be driven mainly by the incidence of sepsis (1.5% in the azithromycin group and 2.3% in the placebo group), with a relative risk of 0.65 (95% CI, 0.55 to 0.77); the incidence of death from any cause was 0.1% in the two groups (relative risk, 1.23; 95% CI, 0.51 to 2.97). Neonatal sepsis occurred in 9.8% and 9.6% of the infants, respectively (relative risk, 1.03; 95% CI, 0.96 to 1.10). The incidence of stillbirth was 0.4% in the two groups (relative risk, 1.06; 95% CI, 0.74 to 1.53); neonatal death within 4 weeks after birth occurred in 1.5% in both groups (relative risk, 1.03; 95% CI, 0.86 to 1.24). Azithromycin was not associated with a higher incidence in adverse events. CONCLUSIONS: Among women planning a vaginal delivery, a single oral dose of azithromycin resulted in a significantly lower risk of maternal sepsis or death than placebo but had little effect on newborn sepsis or death. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; A-PLUS ClinicalTrials.gov number, NCT03871491.).