Novel biomarkers for predicting intrauterine growth restriction: a systematic review and meta‐analysis

<jats:sec><jats:title>Background</jats:title><jats:p>Several biomarkers for predicting intrauterine growth restriction (<jats:styled-content style="fixed-case">IUGR</jats:styled-content>) have been proposed in recent years. However, the predictive performance of these biomarkers has not been systematically evaluated.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>To determine the predictive accuracy of novel biomarkers for <jats:styled-content style="fixed-case">IUGR</jats:styled-content> in women with singleton gestations.</jats:p></jats:sec><jats:sec><jats:title>Search strategy</jats:title><jats:p>Electronic databases, reference list checking and conference proceedings.</jats:p></jats:sec><jats:sec><jats:title>Selection criteria</jats:title><jats:p>Observational studies that evaluated the accuracy of novel biomarkers proposed for predicting <jats:styled-content style="fixed-case">IUGR</jats:styled-content>.</jats:p></jats:sec><jats:sec><jats:title>Data collection and analysis</jats:title><jats:p>Data were extracted on characteristics, quality and predictive accuracy from each study to construct 2 × 2 tables. Summary receiver operating characteristic curves, sensitivities, specificities and likelihood ratios (<jats:styled-content style="fixed-case">LR</jats:styled-content>s) were generated.</jats:p></jats:sec><jats:sec><jats:title>Main results</jats:title><jats:p>A total of 53 studies, including 39 974 women and evaluating 37 novel biomarkers, fulfilled the inclusion criteria. Overall, the predictive accuracy of angiogenic factors for <jats:styled-content style="fixed-case">IUGR</jats:styled-content> was minimal (median pooled positive and negative <jats:styled-content style="fixed-case">LR</jats:styled-content>s of 1.7, range 1.0–19.8; and 0.8, range 0.0–1.0, respectively). Two small case–control studies reported high predictive values for placental growth factor and angiopoietin‐2 only when <jats:styled-content style="fixed-case">IUGR</jats:styled-content> was defined as birthweight centile with clinical or pathological evidence of fetal growth restriction. Biomarkers related to endothelial function/oxidative stress, placental protein/hormone, and others such as serum levels of vitamin D, urinary albumin : creatinine ratio, thyroid function tests and metabolomic profile had low predictive accuracy.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>None of the novel biomarkers evaluated in this review are sufficiently accurate to recommend their use as predictors of <jats:styled-content style="fixed-case">IUGR</jats:styled-content> in routine clinical practice. However, the use of biomarkers in combination with biophysical parameters and maternal characteristics could be more useful and merits further research.</jats:p></jats:sec>