Levels of Maternal Serum Angiogenic Factors in Third-Trimester Normal Pregnancies: Reference Ranges, Influence of Maternal and Pregnancy Factors and Fetoplacental Doppler Indices

Abstract

Aim: To establish normal ranges of maternal placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and sFlt-1/PlGF ratio at 32-41 weeks' gestation and to evaluate the influence of maternal characteristics, and of fetoplacental Doppler. Material and Methods: Serum levels of PlGF, sFlt-1 and sFlt-1/PlGF ratio were measured in 300 noncomplicated pregnancies (30 at each gestational week between 32 and 41). Quantile regression analysis was used to derive gestational age (GA)-adjusted normal ranges, and to account for characteristics that might influence serum levels. The relationship with Doppler indices was tested, including umbilical artery pulsatility index and middle cerebral artery pulsatility index. Results: PlGF decreased with GA from 32 weeks, while sFlt-1 and sFlt-1/PlGF ratio increased steadily. None of the factors evaluated showed any significant influence on the levels of angiogenic factors. PlGF multiple of the median significantly correlated with mean uterine artery Doppler (R -0.17; p = 0.029). Conclusions: In normal pregnancies during the third trimester, serum PlGF decreases, sFlt-1 increases and sFlt-1/PlGF ratio increases with GA. Angiogenic factor levels needed no adjustment for factors such as smoking, body mass index, blood pressure or parity.

Angiogenic factors vs Doppler surveillance in the prediction of adverse outcome among late‐pregnancy small‐for‐ gestational‐age fetuses

“…Receiver–operating characteristics (ROC) curves of Doppler, angiogenic/antiangiogenic factors and a combination of both for the prediction of pre‐eclampsia and adverse perinatal outcome were constructed using logistic regression analysis. As in previous work by our group, only gestational age was found to influence PlGF and sFlt‐1 values, with no other confounders considered in the model. The resulting areas under the ROC curves (AUC) were compared by pairwise analysis.…”

“…Maternal serum levels of sFlt‐1 and PlGF were expressed as multiples of the median (MoM) for gestational age. Normal references for median values were calculated from a control group using reciprocal‐linear regression in R.…”

sFlt‐1/PlGF ratio and timing of delivery in early‐onset fetal growth restriction with antegrade umbilical artery flow

“…Second, the widely used sFlt‐1/PlGF ratio cut‐off of 85 has been inferred from that described for pre‐eclampsia 11,12 since there are no specific thresholds for FGR. Third, although we observed higher values of the sFlt‐1/PlGF ratio in Hispanic women, in correlation with their higher risk for pre‐eclampsia 29 , we did not make adjustments since the impact of confounding factors such as ethnicity, BMI or parity on the ratio is insufficient to require correction 30 . Finally, the sample size was underpowered for further subgroup analyses of clinical interest such as cases diagnosed before viability, those with concurrent hypertensive disorders or those with normal fetal Doppler.…”

Use of Placental Growth Factor and Uterine Artery Doppler Pulsatility Index in Pregnancies Involving Intrauterine Fetal Growth Restriction or Preeclampsia to Predict Perinatal Outcomes

“…Z-scores were calculated from reference tables for the Spanish population [30]. The clinicians were blinded to PlGF determination and to UA Doppler information during the study.…”