Objective: To determine whether first-trimester maternal serum Sonic Hedgehog (SHH) predicts subsequent preeclampsia and to compare its predictive performance with soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF). Materials and Methods: In a prospective cohort study, women with singleton pregnancies were enrolled at 8– 13 weeks’ gestation, clinical data were recorded, and fasting serum was collected. SHH, sFlt-1, and PlGF were quantified by ELISA in triplicate with coefficients of variation 34 weeks) preeclampsia. Results: Among 2532 enrolled pregnancies, 271 developed preeclampsia and 2261 remained normotensive. First-trimester SHH concentrations were significantly lower in pregnancies that later developed preeclampsia, with the greatest decrement in early-onset disease. Compared to the highest SHH tertile, adjusted odds of preeclampsia were higher in the middle (OR 2.64; 95% CI 1.334– 5.38) and lowest tertiles (OR 5.21; 95% CI 3.15– 8.42). SHH achieved an AUC of 0.86 (95% CI 0.62– 0.91), with 81.46% sensitivity and 76.58% specificity at 58.26 ng/mL; sFlt-1 and PlGF yielded AUCs of 0.71 and 0.62, respectively. Performance was strongest for early-onset preeclampsia with an AUC of 0.93 (95% CI 0.67– 0.97); sensitivity 87.73%; specificity 82.43% at 62.37 ng/mL, and modest for late-onset preeclampsia with an AUC of 0.75 (95% CI 0.54– 0.86); sensitivity 73.42%; specificity 68.24% at 55.78 ng/mL. Conclusion: Lower maternal serum SHH level in the first trimester is independently associated with later development of preeclampsia and provides clinically significant early prediction, particularly for early-onset disease. Incorporating SHH into first-trimester multiparametric screening alongside maternal factors and angiogenic markers may improve risk stratification and enable earlier prophylaxis and individualized antenatal surveillance. Keywords: Sonic Hedgehog protein, first-trimester, biomarker, preeclampsia, extravillous trophoblast
Deng et al. (Thu,) studied this question.