Comparison of circulating maternal placenta growth factor levels and sonographic evaluation of patients with abnormal first trimester screening analytes

Abstract

Objective: To evaluate the role of mid-trimester placental growth factor (PlGF) in patients with abnormal circulating levels of first-trimester biomarkers.Methods: Retrospective cohort study including singleton pregnancies complicated by abnormal first-trimester biomarkers (2017-2020). Pregnancies complicated with chromosomal/structural anomalies were excluded. All patients had ultrasound imaging including uterine artery Doppler combined with measurement of maternal circulating PlGF. Sonographic findings, maternal and perinatal outcomes, and placental histopathology were compared between pregnancies with normal and low (<10th percentile for gestational age) PlGF levels. The diagnostic accuracy of PlGF for the prediction of specific placental-mediated complications was compared with the uterine artery Doppler assessment and additional sonographic findings.Results: Seventy-one pregnancies were assessed, of which 35 (49.3%) had low PlGF levels. Maternal sociodemographic characteristics, nulliparity, and aspirin consumption were comparable. In comparison with patients with normal PlGF levels, individuals with low PlGF levels had a higher rate of fetal growth restriction (EFW <3rd centile; 42.9% vs. 8.3%, p = 0.001), preterm-preeclampsia (22.9% vs. 0%, p = 0.002), preterm delivery <34 weeks (54.3% vs. 8.3%, p < 0.001) and maternal vascular malperfusion placental pathology (72.7% vs. 21.7%, p < 0.001) following delivery. Adjusting for uterine artery Doppler and fetal biometry status, midtrimester low PlGF remained significantly associated with these placentalmediated complications. The predictive capacity of PlGF outperformed ultrasound imaging with only minimal diagnostic improvement when ultrasound information was combined with PlGF status. Conclusion:In pregnancies with unexplained abnormal first-trimester biomarkers, mid-trimester PlGF outperformed a comprehensive ultrasound assessment in the identification of a subset of patients destined to develop placental dysfunction. This blood test may be an alternative initial approach in this context, especially where access to specialist care is more geographically challenging.

Prediction of preterm birth in growth‐restricted and appropriate‐for‐gestational‐age infants using maternal PlGF and the sFlt‐1/PlGF ratio—A prospective study

“…PlGF levels significantly affected time to PTB. Median survival time when PlGF was <100 ng/L was reduced to 26 days (95% CI [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] for the entire FGR cohort, 26 days (95% CI 15-32) for early FGR, 38 (95% CI 8-72) for late FGR and 40 days (95% CI 15-55) for the AGA group. Multivariable Cox proportional hazard models revealed that women with PlGF <100 ng/L were more than 21 times more likely to have a PTB compared with those with PlGF ≥100 ng/L (HR 21.47, 95% CI 7.91-58.26) in the FGR cohort and nearly four times the AGA cohort (HR 3.85, 95% CI 1.68-8.81) (Table 2).…”

“…Similarly, the sFlt-1/PlGF ratio significantly affected time to PTB. Median survival time for women with an abnormal sFlt-1/PlGF ratio was reduced to 28 days (95% CI 15-39) in the overall FGR group, 26 days (95% CI for in the early FGR, 62 (95% CI 10-106) in the late FGR and 29 days (95% CI [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] in the AGA cohorts. Multivariable Cox proportional hazard models revealed that women with a raised sFlt-1/PlGF ratio were nearly seven times as likely to have a PTB (HR 6.91, 95% CI 3.43-13.92) in the FGR cohort and almost six times as likely in the AGA cohort (HR 5.65, 95% CI 2.35-13.61) (Table 2).…”

“…17,18 Placental dysfunction is associated with an imbalance in circulating placentally derived angiogenic and antiangiogenic factors. 14,19,20 Low levels of placental growth factor (PlGF), high levels of soluble fms-like tyrosine kinase 1 (sFlt-1) and an elevated sFlt-1/PlGF ratio are strongly associated with placental dysfunction [21][22][23] and show promise for screening, diagnosis and management of these high-risk pregnancies. [24][25][26][27][28] However, the optimal predictive thresholds for these biomarkers for PTB in women with FGR remain unknown.…”

Placental growth factor and fetoplacental Doppler indices in combination predict preterm birth reliably in pregnancies complicated by fetal growth restriction

“…Placental dysfunction is associated with an imbalance in placentally derived pro-and anti-angiogenic factors. Low levels of placental growth factor (PlGF), a strongly proangiogenic hormone, and elevated levels of its antiangiogenic counterpart, soluble fms-like tyrosine kinase-1 (sFlt-1) 17,18 , as well as an increased sFlt-1/PlGF ratio are seen in women with pre-eclampsia and FGR, and are reflective of placental dysfunction 17,[19][20][21][22] . Although there is some evidence that maternal PlGF levels and the sFlt-1/PlGF ratio may be helpful in predicting timing of delivery and rate of disease progression in pregnancies complicated by FGR [23][24][25][26][27] , there are limited data regarding their association with, or potential for, prediction of PTB beyond their utility in screening 28,29 and diagnosis 30,31 of adverse outcome 24,32,33 in women with pre-eclampsia or FGR.…”