A 'Standard of Care PLUS' Model for Preterm Birth Prevention: Integrating Nutrient and Gene Variant Analysis with...

Background/Objectives: The rates of adverse maternal and neonatal outcomes-including preterm birth < 37 weeks' gestation (PTB), hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus (GDM), small for gestational age (SGA), and large for gestational age (LGA)-remain elevated in the United States. Preventive strategies beyond the current standard of care (SOC) may be needed, particularly in diverse and socioeconomically vulnerable populations. The study evaluated a targeted diet and lifestyle intervention incorporating selected nutrient and gene variant analysis with personalized trimester-based counseling and supplementation (Standard of Care Plus, PLUS). Methods: The prospective observational study compared outcomes among participants receiving PLUS in addition to SOC with regional SOC data. A Nevada PLUS cohort (n = 15), consisting of high-risk participants with 100% Medicaid coverage, received the intervention virtually. An Oregon PLUS cohort (n = 387), consisting of moderate-risk participants with approximately 50% Medicaid coverage, received PLUS through in-person group sessions. Outcomes were compared with regional SOC rates and between PLUS cohorts. Cochran-Mantel-Haenszel (CMH) analyses were performed to account for site-level differences in pooled analyses. Primary outcome was PTB < 37 weeks' gestation; secondary outcomes included HDP, GDM, SGA, and LGA. Results: The Nevada PLUS application was associated with lower adverse outcome rates compared with regional SOC; however, statistical significance was not observed, likely reflecting limited sample size. The Oregon PLUS cohort experienced statistically significant association with reductions across all five outcomes (all p < 0.001) compared to regional SOC. No statistically significant differences were observed between the Nevada (virtual) and Oregon (in-person) PLUS cohorts. In pooled analyses (n = 402), significant reductions compared with SOC were observed for PTB (RR = 0.23), HDP (RR = 0.11), GDM (RR = 0.06), SGA (RR = 0.25), and LGA (RR = 0.35) (all p < 0.001). Conclusions: The implementation of selected nutrient and gene variant analysis combined with targeted nutritional and lifestyle interventions, delivered in collaboration with standard obstetric care, was associated with reduced adverse maternal and neonatal outcomes. Interpretation of virtual delivery remains limited by small sample size.