(636) First Trimester Soluble fms-like Tyrosine Kinase 1 (sFlt-1) and Its Association with Adverse Neonatal Outcomes

Objective:
To evaluate the association between first-trimester angiogenic biomarkers, including of soluble fms-like tyrosine kinase-1 (sFlt-1), vascular endothelial growth factor (VEGF), placental growth factor (PIGF), and sFlt-1/PIGF ratio, and a composite of adverse neonatal outcomes (CANO).

Study Design:
This was retrospective case-control study of pregnancies enrolled in a first-trimester screening program for adverse neonatal outcomes and the redefinition of fetal growth restriction trial. We included singleton gestations at risk for fetal growth disorders between 26.0 and 36.6 weeks with available first-trimester measurements of sFlt-1, VEGF, and PlGF, and sFlt-1/PIGF ratio. Fetuses with chromosomal or congenital anomalies were excluded. We assessed the association of first-trimester sFlt-1, PlGF, and VEGF levels with a CANO using the area under the receiver operating characteristic curve (AUC). CANO included one or more of: neonatal intensive care unit admission, pH < 7.1, Apgar score < 7 at 5 minutes of life, seizures, respiratory distress syndrome, intraventricular hemorrhage grade III or IV, or neonatal death.  Optimal cutoff values were determined, and biomarker levels were compared between pregnancies with and without CANO for statistically significant predictors.

Results:
Among the 55 pregnancies analyzed, 15 neonates experienced CANO. First-trimester sFlt-1 levels were significantly associated with CANO (AUC: 0.70; 95% CI: 0.53–0.86; p = 0.018). In contrast, PlGF (AUC: 0.36; 95% CI: 0.21–0.52; p = 0.09) and VEGF (AUC: 0.51; 95% CI: 0.34–0.68; p = 0.93) were not significantly associated with the outcome (Figure 1). Pregnancies with CANO had significantly higher sFlt-1 levels compared to those without (Figure 2). An sFlt-1 threshold of 3588.29 pg/ml was identified as optimal cutoff for predicting CANO.

Conclusion:
In this cohort of pregnancies at risk for fetal growth disorders, first-trimester sFlt-1 was significantly associated with adverse neonatal outcomes. Larger, prospective studies in more diverse populations are warranted to validate these findings.