Bimodal ultrasound assessment of cerebral hemodynamics in preterm infants stratified by maternal immunotherapy: implications for early prediction of intraventricular hemorrhage.

OBJECTIVE: To evaluate the clinical value of bedside bimodal ultrasound in assessing early cerebral circulation in preterm infants from structural and functional perspectives, and to examine whether maternal recurrent spontaneous abortion (RSA), maternal active immunotherapy status, and ultrasound-derived markers were associated with neonatal cerebral hemodynamic trajectories and clinically significant intraventricular hemorrhage (IVH).

METHODS: In this single-center prospective cohort study, 120 preterm infants born to mothers with RSA were enrolled and stratified by maternal active immunotherapy status. Bedside bimodal ultrasound, including transcranial Doppler (TCD) and optic nerve sheath diameter (ONSD) measurement, was performed on postnatal days 1, 3, 5, and 7. The coefficient of variation of the middle cerebral artery pulsatility index (PI-CV) was calculated. Generalized estimating equations (GEE) were used for longitudinal analyses, and multivariable logistic regression was used to evaluate associations with clinically significant IVH (Papile grade ≥II). Because the dataset was a limited tabular cohort, no random training/validation/test split and no class-balancing procedure were used; internal validation was performed using bootstrap resampling. Model performance was assessed using discrimination, calibration, clinical-utility, and likelihood-based model-quality metrics.

RESULTS: PI-CV and ONSD decreased during the first postnatal week in both groups. GEE analysis using an AR(1) working correlation structure showed significant time effects and group × time interactions for PI-CV and ONSD (all P < 0.001), with a faster decline in the active immunotherapy group. ONSDmax and PI-CV at 24 h remained associated with clinically significant IVH after clinical adjustment. The bimodal model had an AUC of 0.759 (95% CI, 0.674-0.844), the clinical-ultrasound model had an AUC of 0.799 (95% CI, 0.721-0.877), and the expanded explanatory model had an AUC of 0.817 (95% CI, 0.743-0.892). For the expanded model, the likelihood-ratio chi-square was 40.915, AIC was 139.301, BIC was 161.601, McFadden pseudo-R2 was 0.249, and the apparent Brier score was 0.174. Bootstrap internal validation using 1,000 resamples yielded optimism-corrected AUC/Brier scores of 0.762/0.190 for the clinical-ultrasound model and 0.774/0.203 for the expanded explanatory model. These results support exploratory risk stratification rather than definitive clinical deployment.

CONCLUSION: Bedside bimodal ultrasound is a feasible noninvasive approach for dynamic assessment of early cerebral hemodynamics in preterm infants. The combination of ONSDmax and PI-CV may improve exploratory early IVH risk stratification. Maternal immunotherapy status was associated with distinct longitudinal cerebral hemodynamic and ONSD trajectories, reflected by faster modeled declines in PI-CV and ONSD during the first postnatal week. However, given the observational design and associational regression models, these findings do not establish a direct protective effect of maternal immunotherapy on IVH risk. External validation and longer-term outcome studies are required before clinical implementation.