Blood‐based biomarkers in the maternal circulation associated with fetal growth restriction

Abstract

Fetal growth restriction (FGR) is associated with threefold to fourfold increased risk of stillbirth. Identifying FGR, through its commonly used surrogate-the small-forgestational-age (SGA, estimated fetal weight and/or abdominal circumference <10th centile) fetus-and instituting fetal surveillance and timely delivery decrease stillbirth risk. Methods available to clinicians for antenatal identification of SGA fetuses have surprisingly poor sensitivity. About 80% of cases remain undetected.Measuring the symphysis-fundal height detects only 20% of SGA fetuses, and even universal third trimester ultrasound detects, at best, 57% of those born SGA. There is an urgent need to find better ways to identify this at-risk cohort. This review summarises efforts to identify molecular biomarkers (proteins, metabolites, or ribonucleic acids) that could be used to better predict FGR. Most studies examining potential biomarkers to date have utilised case-control study designs without proceeding to validation in independent cohorts. To develop a robust test for FGR, large prospective studies are required with a priori validation plans and cohorts. Given that current clinical care detects 20% of SGA fetuses, even a screening test with ≥60% sensitivity at 90% specificity could be clinically useful, if developed. This may be an achievable aspiration. If discovered, such a test may decrease stillbirth.

Development of standard definitions and grading for Maternal and Fetal Adverse Event Terminology

“…71 As analysis of fetal circulating DNA, RNA and proteins in the maternal blood advances, it is possible that fetal laboratory-based AEs will be developed to further assess fetal well-being. 72,73 The goal of a standardised AE severity scale is to reduce subjectivity in severity assessments and thus reduce interobserver variability. We are currently planning prospective validation studies of agreement among observers in different countries for the generic and specific severity criteria for maternal and fetal AEs.…”

Consecutive measurements show association of IGF-1 with fetal growth in type 1 diabetic pregnancy

“…SGA fetuses are at three to four times higher risk for stillbirth than appropriate weight fetuses, which signifies that early prediction of SGA and intrauterine growth restriction is crucial in prevention 2,3 . For this reason, researchers are trying to find possible Copyright 2021 KEI Journals.…”

“…http://journals.ke-i.org/index.php/mra biomarkers with a strong predictive value. Pregnancy-associated plasma protein-A (PAPP-A) and human placental growth factor (hPGH) were linked to SGA but showed little clinical value when evaluated alone 2 . Insulinlike growth factor-1 (IGF-1) was proposed as a possible marker for several pregnancy outcomes, including preeclampsia and SGA.…”

Neonatal Adverse Outcomes of Induction and Expectant Management in Fetal Growth Restriction: A Systematic Review and Meta-Analysis

“…Recently, the cerebral–placental ratio (CPR) and cerebral–placental–uterine ratio (CPUR) were identified as novel predictors, and at a 90% specificity, a low CPUR had sensitivities of 50% for birthweight <10th centile ( 8 ). Additionally, maternal serum biomarkers are novel approaches to screening the suspected FGR (PIGF, sFlt-1), but the specific effectiveness needs more studies for verification ( 7 , 9 ). A study showed that 82% of stillbirths with FGR were not detected in the prenatal period ( 9 ) so accurate identification is important.…”

“…Additionally, maternal serum biomarkers are novel approaches to screening the suspected FGR (PIGF, sFlt-1), but the specific effectiveness needs more studies for verification ( 7 , 9 ). A study showed that 82% of stillbirths with FGR were not detected in the prenatal period ( 9 ) so accurate identification is important. Ultrasonic Doppler is the main means of monitoring.…”