Reference Intervals for Placental Biomarkers in Early Pregnancy

Abstract

Background: Placental dysfunction is important to recognize, and more evidence is needed on the dynamics of the placental biomarkers, soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF), in early pregnancy. This study aimed to establish reference intervals for placental biomarkers in early pregnancy.

Methods: This was a retrospective cohort study of pregnant women (n = 702) in the North Denmark Region, 2013, who had blood samples drawn in early pregnancy including measurements of sFlt-1 and PlGF (Kryptor Compact, Thermofisher Scientific). Reference intervals were established, and the association between sFlt-1 and PlGF and maternal characteristics (age, body mass index [BMI], country of birth, and smoking in pregnancy) was evaluated using linear regression analyses and reported as adjusted beta coefficient (aβ) with 95% confidence intervals (CIs).

Results: The placental biomarkers showed a dynamic trend with higher levels for increasing week of pregnancy; however, sFlt-1 reached a plateau around week 10 of pregnancy. Higher maternal age associated with higher sFlt-1 and PlGF (sFlt-1: aβ 1.02 [95% CI, 1.01-1.03], PlGF: aβ 1.02 [95% CI, 1.01-1.03]), and higher maternal BMI associated with lower sFlt-1 (aβ 0.97 [95% CI, 0.96-0.98]). Furthermore, the level of PlGF was higher among women born outside of Denmark (aβ 1.17 [95% CI, 1.03-1.34]) compared to women born in Denmark and among smokers (aβ 1.56 [95% CI, 1.38-1.78]) compared to nonsmokers.

Conclusions: In a large cohort of pregnant women in Denmark, levels of sFlt-1 and PlGF increased during early pregnancy and were influenced by a series of maternal characteristics.