A Multicomponent Intervention to Improve Maternal Infection Outcomes

N Engl J Med. 2026 Apr 30;394(17):1685-1695. doi: 10.1056/NEJMoa2512698. Epub 2025 Nov 19.

Abstract

Background: Maternal infection and sepsis are major causes of maternal death and severe illness worldwide, particularly in low- and middle-income countries. Inconsistent implementation of evidence-based recommendations for infection prevention and management and delays in detection and treatment of maternal sepsis contribute to the number of preventable deaths.

Methods: We conducted a cluster-randomized trial to assess a multicomponent intervention, the Active Prevention and Treatment of Maternal Sepsis (APT-Sepsis) program. This program was designed to support health care providers in achieving three goals: adherence to World Health Organization (WHO) hand-hygiene standards; adoption of evidence-based practices for maternal infection prevention and management; and early detection of sepsis and use of the FAST-M (fluids, antibiotics, source control, transfer if required, and monitoring) treatment bundle. Usual care was provided in the control group, along with dissemination of guidelines. The primary outcome was a composite of infection-related maternal death, infection-related near-miss event (events in which women survived a life-threatening complication), or severe infection-related illness (deep surgical-site, deep perineal, or body-cavity infection) among women who were pregnant or had recently been pregnant.

Results: We randomly assigned 59 health facilities (where 431,394 women gave birth during the trial) in Malawi and Uganda to the intervention group (30 clusters) or the usual-care group (29 clusters). A primary-outcome event occurred in 1.4% of the patients in the intervention group and in 1.9% of those in the usual-care group (risk ratio, 0.68; 95% confidence interval, 0.55 to 0.83; P<0.001). This effect was generally consistent between countries and among facilities of difference sizes and was sustained over time.

Conclusions: Implementation of the APT-Sepsis program led to a significantly lower risk of a composite of infection-related maternal death, infection-related near-miss event, or severe infection-related illness than usual care. (Funded by the Joint Global Health Trials scheme and others; APT-Sepsis ISRCTN number, ISRCTN42347014.).

Publication types

  • Randomized Controlled Trial
  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Anti-Bacterial Agents / therapeutic use
  • Evidence-Based Medicine / methods
  • Evidence-Based Medicine / standards
  • Female
  • Fluid Therapy
  • Guideline Adherence
  • Hand Hygiene / standards
  • Health Plan Implementation* / standards
  • Health Plan Implementation* / statistics & numerical data
  • Humans
  • Infection Control* / methods
  • Infection Control* / standards
  • Malawi / epidemiology
  • Maternal Death / prevention & control
  • Maternal Health / standards
  • Maternal Health / statistics & numerical data
  • Maternal Mortality
  • Middle Aged
  • Near Miss, Healthcare / statistics & numerical data
  • Patient Care Bundles
  • Practice Guidelines as Topic
  • Pregnancy
  • Pregnancy Complications, Infectious* / diagnosis
  • Pregnancy Complications, Infectious* / mortality
  • Pregnancy Complications, Infectious* / prevention & control
  • Pregnancy Complications, Infectious* / therapy
  • Puerperal Infection* / diagnosis
  • Puerperal Infection* / mortality
  • Puerperal Infection* / prevention & control
  • Puerperal Infection* / therapy
  • Sepsis* / diagnosis
  • Sepsis* / mortality
  • Sepsis* / prevention & control
  • Sepsis* / therapy
  • Uganda / epidemiology
  • World Health Organization
  • Young Adult

Substances

  • Anti-Bacterial Agents

Associated data

  • ISRCTN/ISRCTN42347014