A prospective observational multicenter cohort study of maternal serum sFlt-1 and PlGF concentration in prediction of adverse neonatal outcomes in small for gestational age newborns delivered ≥34 weeks of gestation.

INTRODUCTION

Small-for-gestational age (SGA) newborns are at increased risk of adverse neonatal outcomes and the risk is related to the etiology of growth restriction: highest in placental insufficiency, lowest in constitutional SGA. The aim of this study was to investigate if placental growth factor (PlGF), soluble fms-like tyrosine kinase-1(sFlt-1) or sFlt-1/PlGF ratio are efficient in prediction of adverse neonatal outcomes in SGA newborns delivered ≥34 weeks of gestation.

METHODS

A prospective observational multicenter cohort study was performed. Women in singleton gestation had serum PlGF, sFlt-1 and sFlt-1/PlGF ratio measured at the time of SGA diagnosis and included if they delivered ≥34 weeks. The primary outcome was adverse neonatal outcome, diagnosed in case of any of the following: Neonatal Intensive Care Unit hospitalization, mechanical ventilation, continuous positive airway pressure, sepsis, necrotizing enterocolitis, intraventricular hemorrhage grade III or IV and neonatal death before discharge. The Mann-Whitney test and the Fisher's exact test were used for the statistical analysis. Cutoff points for adverse outcome prediction were calculated based on ROC curves. Multivariate logistic regression analysis was performed to adjust for confounding factors.

RESULTS

A total of 102 women were included in the study. Serum PlGF concentration of 137 pg/mL had a sensitivity of 75% (95% CI 58.8 - 87.3), specificity of 56.45% (95% CI 43.3 - 69.0), positive likelihood ratio of 1.72 (95% CI 1.23 - 2.41) and negative likelihood ratio of 0.44 (95% CI 0.25 - 0.79) in prediction of adverse outcomes. Serum sFlt-1 level of 2018 pg/mL had a sensitivity of 82.05% (95% CI 66.5 - 92.5), specificity of 50% (95% CI 37.0 - 63.0), positive likelihood ratio of 1.64 (95% CI 1.23 - 2.19) and negative likelihood ratio of 0.36 (95% CI 0.18 - 0.73), while sFlt-1/PlGF ratio of 18.9 had a sensitivity of 79.92% (95% CI 60.7 - 88.9), specificity of 56.45% (95% CI 43.3 - 69.0), positive likelihood ratio of 1.77 (95% CI 1.27 - 2.46) and negative likelihood ratio of 0.41 (95% CI 0.22 - 0.75) in prediction of adverse outcomes. In logistic regression analysis only birth weight was an independent risk factors for adverse outcome.

CONCLUSION

In pregnancies with SGA, fetuses measurements of maternal serum sFlt-1 or PlGF provide poor prediction of adverse neonatal outcomes.