Early-pregnancy HOMA-IR and a maternal-side low-flow placental hypoechoic-space phenotype in pregnancies with maternal obesity: a prospective cohort study

Early maternal insulin resistance may be associated with placental vascular change in pregnancies with maternal obesity, but its relationship with an operationally defined maternal-side low-flow placental hypoechoic-space phenotype is unclear. This prospective cohort included 299 women in the analysis with singleton pregnancies and pre-pregnancy BMI of at least 28 kg/m 2 during 2022–2024. HOMA-IR was measured at 11+0 to 13+6 weeks before standardized ultrasound at 20+0 to 23+6, 28+0 to 31+6, and 34+0 to 36+6 weeks. The primary analysis used separately fitted mixed-effects models for eligible-space visibility and maximum diameter among visible spaces.A prespecified model coding non-visualization as 0 mm was retained as a supportive exploratory summary. The cohort contributed 804 ultrasound assessments, and 93 women developed gestational diabetes mellitus. In the primary two-part analysis, higher ln(HOMA-IR) was associated with greater eligible-space visibility (conditional odds ratio, 2.08; 95% CI 1.42–3.05; p <0.001) and a larger maximum diameter among visible spaces (conditional beta, 0.86 mm; 95% CI 0.60–1.12; p <0.001). In the supportive exploratory zero-coded analysis, each 1-unit increase in ln(HOMA-IR) was associated with a 1.21-mm larger scan-level maximum diameter at 28 weeks (95% CI 0.87–1.55; p <0.001) and a 0.058 mm/week steeper gestational increase (95% CI 0.034–0.082; p <0.001). In a separate supportive tertile-based visualization model, the highest-tertile versus lowest-tertile contrast at 28 weeks was 1.29 mm (95% CI 0.88–1.70; p <0.001). In a secondary analysis, higher ln(HOMA-IR) was associated with gestational diabetes mellitus (adjusted odds ratio, 2.85; 95% CI 1.52–5.36; p =0.001; FDR q =0.005). Higher first-trimester HOMA-IR was associated with greater eligible-space visibility and a larger maximum diameter among visible spaces in the primary two-part analysis.The >1-mm tertile contrast arose only from a separate supportive, exploratory zero-coded analysis. Multicenter external validation is required to define a clinically validated threshold.