“Actionable” Risk for Preterm Birth: Patterns and Prediction in California Singleton Births 2016-2020

Background

Preterm birth (PTB, <37 weeks of gestation) is the leading cause of child mortality in the United States (U.S.) and worldwide, and has substantial short- and long-term health consequences for mothers and infants. Each year, >350,000 infants in the U.S. are born preterm, and rates continue to rise in parallel with maternal risk factors such as hypertension, diabetes, anemia, asthma, and mental health conditions. Evidence-based interventions exist for many of these conditions and are associated with improved pregnancy outcomes, including low-dose aspirin for preeclampsia prevention in individuals with chronic hypertension or pregestational diabetes, inhalers for asthma, iron for anemia, and therapy or medication for mental health disorders, but fewer than half of eligible individuals receive them, reflecting persistent gaps in use. To address this, we developed the PTB Actionable Risk Index (PTB-ARIx), which leverages factors with known evidence-based interventions to identify individuals who are pregnant and are at increased risk for PTB. This study evaluates performance of the PTB-ARIx throughout pregnancy in terms of risk determination and characterization of actionable risk factors, including their combined contributions to PTB.

Methods and Findings

A retrospective cohort study was conducted using linked data for 1.9 million singleton live births in California in 2016-2020, divided into training and testing sets. Poisson regression estimated associations between 18 candidate risk factors for PTB with evidence-based interventions spanning clinical, behavioral, and social risks, including preeclampsia risk composites (≥1 high-risk or ≥2 moderate-risk factors based on U.S. Preventive Services Task Force (USPSTF) criteria), maternal conditions (e.g., gestational hypertension, asthma), substance use, and social adversity. Beta coefficients were combined to construct the PTB-ARIx, evaluated by per-unit associations with PTB and by area under the receiver operating characteristic curve (AUC) overall, by early (<32 weeks), late (32-36 weeks), spontaneous, and medically indicated PTB, and by PTB co-occurring with preeclampsia.

All risk factors were found to be associated with increased PTB risk. Having ≥1 high-risk or ≥2 moderate-risk factors for preeclampsia (based on composites) was most strongly related to PTB (relative risk (RR) 6.73, 95% confidence interval (CI) 6.57, 6.89). Each unit increase in PTB-ARIx was associated with >60% higher PTB risk (RRs 1.66–1.72) across training and testing samples, with consistent findings across PTB and race/ethnicity–insurance subgroups. Model performance was modest for late PTB (AUC ≈0.63), stronger for early PTB (0.69–0.72), and especially high for early PTB with preeclampsia (AUCs up to 0.97). Over 70% of individuals with PTB-ARIx scores ≥3.00 experienced PTB or another adverse outcome such as low birth weight (<2500 grams).

Conclusions

The PTB-ARIx is a well-performing metric for identifying individuals at increased risk for PTB and other adverse pregnancy outcomes. By centering on modifiable risks, the PTB-ARIx combines risk identification with opportunities for intervention. Demonstrating strong performance across subgroups, including for early PTB and PTB with preeclampsia, the PTB-ARIx provides a potential pathway to improve patient–provider communication and uptake of equitable, evidence-based care. Further validation, including integration with treatment data, is needed to confirm its potential to reduce PTB risk and rates.

Author Summary