Early warning systems for identifying severe maternal outcomes: findings from the WHO global maternal sepsis study

Abstract

Background: Infections and sepsis are leading causes of morbidity and mortality in women during pregnancy and the post-pregnancy period. Using data from the 2017 WHO Global Maternal Sepsis Study, we explored the use of early warning systems (EWS) in women at risk of sepsis-related severe maternal outcomes.

Methods: On April 27, 2023, we searched the literature for EWS in clinical use or research in obstetric populations. We calculated the proportion of women for whom each existing EWS identified them as at risk for developing severe maternal outcomes by infection severity (complications and severe maternal outcomes). Sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratios, and J statistics were calculated to assess EWS performance. Machine learning was used to test the diagnostic potential of routine maternal sepsis markers.

Findings: 21 EWS were assessed in 2560 women from 46 countries with suspected or confirmed infections. The NICE Risk Stratification tool, Modified Shock Index, maternity Systemic Inflammatory Response Syndrome, and Early Maternal Infection Prompts scores had high sensitivity (88.1-97.5%) for identifying sepsis-related severe maternal outcomes. The quick Sequential Organ Failure Assessment (SOFA) in Pregnancy score and Obstetrically modified SOFA had high specificity (90.4-100%) for identifying women with sepsis-related severe maternal outcomes. Furthermore, combinations of sepsis markers had very low sensitivity and high specificity using machine learning.

Interpretation: No score demonstrated enough diagnostic accuracy to be used alone to identify sepsis. However, obstetric-and sepsis-specific EWS performed better for early identification of maternal sepsis than non-obstetric and non-sepsis-specific scoring systems. There are limitations to applying EWS to real-world data, mainly due to the incompleteness of medical data that hinders EWS effectiveness. There is a need to continue developing and testing criteria for early identification of maternal sepsis.

Funding: UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), WHO, Merck for Mothers, U.S. Agency for International Development, Wellcome Trust, and National Institute for Health and Care Research.

Keywords: Early identification; Early warning systems; Maternal sepsis; Sepsis; Severe maternal outcome.

Fig. 1

Early warning systems and composition of each score. Shadowed boxes mean that those variables are needed for the specific EWS. Shadowed boxes means that those variables are needed for the specific EWS. FAST-M: fluids, Antibiotics, Fluids, Antibiotics, source identification and control, transfer to an appropriate level of care, and ongoing monitoring of mother and neonate; FAST-M_RF: Fluids, Antibiotics, source identification and control, transfer to a proper level of care, and ongoing monitoring of mother and neonate red flags; IMEWS: Irish Maternity Early Warning System; MEOWS A-F: Modified early obstetric warning score; MEWT: Maternal Early Warning Trigger; NICE-RST-P: National Institute for Health and Care Excellence Risk Stratification Tool for pregnancy; NICE-RST-PP/PA: National Institute for Health and Care Excellence Risk Stratification Tool for postpartum or post-abortion; qSOFA: quick Sequential Organ Failure Assessment; SIRS: Systemic inflammatory response syndrome; SOS: Sepsis in Obstetrics Score; mSIRS: maternity systemic inflammatory response syndrome; OmqSOFA: Obstetrically modified quick Sequential Organ Failure Assessment; qSOFA-P: quick Sequential Organ Failure Assessment in Pregnancy; EMIP: Early Maternal Infection Prompt; SI: Shock Index; MSI: Modified Shock Index; mSIRS.

Fig. 2

Study flowchart of included women by infection severity. The dotted line indicates women included in this analysis. ¹290 women using a modified protocol in Western European countries (Belgium, Denmark, Italy, Spain, the Netherlands, and the United Kingdom) were excluded. ²Sources of infection were confirmed clinically, radiologically, or microbiologically. ³Maternal infections with complications were defined as women needing intensive care unit admission or invasive procedures to treat the source of infection or transfer. ⁴Infection-related severe maternal outcomes were defined as near miss or death. ⁵A proportion of women with infection-related severe maternal outcomes met at least one WHO near-miss criterium. ⁶Among the maternal deaths caused by an underlying infection, seven deaths were due to direct causes, five were due to abortion, and six were due to indirect causes. ⁷Among the maternal deaths with infection as a contributing cause were two deaths due to obstetric haemorrhage, one due to hypertensive disorder, one other direct cause, two due to indirect cause, and 2 with unknown cause.

Fig. 3

Receiver operating characteristic curve (ROC) Plot showing five zones of the zombie plot (ROC plot divided into zones) of early warning systems efficacy for identifying the development of sepsis-related severe maternal outcomes. The white and green zones form a slender, boomerang-shaped area of acceptable efficacy in the upper left corner. If the sensitivity and specificity values of an EWS (and their 95% confidence interval) lie within the boomerang-shaped area, then that EWS has acceptable diagnostic credibility. LR+: Positive likelihood ratio; LR-: Negative Likelihood ratio; EMIP: Early Maternal Infection Prompt; FAST-M: Fluids, Antibiotics, Fluids, Antibiotics, Source identification and control, Transfer to an appropriate level of care, and ongoing Monitoring of mother and neonate; FAST-M_RF: Fluids, Antibiotics, Source identification and control, Transfer to a proper level of care, and ongoing Monitoring of mother and neonate red flags; IMEWS: Irish Maternity Early Warning System; MEOWS A–F: Modified early obstetric warning score; MEWT: Maternal Early Warning Trigger; MSI: Modified Shock Index; mSIRS: maternity systemic inflammatory response syndrome; omqSOFA: Obstetrically modified quick Sequential Organ Failure Assessment; qSOFA: quick Sequential Organ Failure Assessment; SI: Shock Index; SIRS: Systemic inflammatory response syndrome; NICE-RST-P: National Institute for Health and Care Excellence Risk Stratification Tool for pregnancy; NICE-RST-PP/PA: National Institute for Health and Care Excellence Risk Stratification Tool for postpartum or post-abortion.