Ultrasound and biochemical first trimester markers as predictive factors for intrauterine growth restriction: Systematic review

Background: Intrauterine growth restriction (IUGR) is important cause of perinatal morbidity and mortality. Early identification of pregnancies at risks enables timely interventions and improved outcomes. First trimester ultrasound and biochemical markers (pregnancy-associated plasma protein-A (PAPP-A)) and uterine artery Doppler indicators, show a potential as predictive tools for IUGR, but evidence is different. In this study we aimed to systematically review and evaluate the predictive value of ultrasound and biochemical markers in the first trimester to detect intrauterine growth restriction.

Methods: A literature search was conducted in major databases, which include PubMed and Scopus, for studies published between 2005 and 2024. Inclusion criteria comprised original research studies which evaluate first trimester markers (PAPP-A, Plage, β-chg., and uterine artery Doppler indicators) in relation to IUGR outcomes. Data were extracted on study design, population characteristics, predictive methods, and outcomes. 

Results: Eight studies met the inclusion criteria. All included studies examined PAPP-A levels, with the majority reporting lower levels in pregnancies complicated by IUGR. Several studies include uterine artery Doppler and PlGF as part of combined predictive models, which improved sensitivity. The detection rates for IUGR using integrated approaches are more than 70% in several studies. Variations in marker thresholds, definitions of IUGR, and study designs limited generalizability.

Conclusion: First trimester biochemical and ultrasound markers, mainly PAPP-A and uterine artery Doppler indicators, show potential in predicting IUGR. Integrative screening models in combination with maternal characteristics, serum biomarkers, and Doppler ultrasound produce higher predictive value.