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

Abstract

Background Several biomarkers for predicting intrauterine growth restriction (IUGR) have been proposed in recent years. However, the predictive performance of these biomarkers has not been systematically evaluated.Objective To determine the predictive accuracy of novel biomarkers for IUGR in women with singleton gestations.Search strategy Electronic databases, reference list checking and conference proceedings.Selection criteria Observational studies that evaluated the accuracy of novel biomarkers proposed for predicting IUGR.Data collection and analysis Data were extracted on characteristics, quality and predictive accuracy from each study to construct 2 9 2 tables. Summary receiver operating characteristic curves, sensitivities, specificities and likelihood ratios (LRs) were generated.Main results 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 IUGR was minimal (median pooled positive and negative LRs 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 IUGR 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.Conclusions None of the novel biomarkers evaluated in this review are sufficiently accurate to recommend their use as predictors of IUGR 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.

Molecular mechanisms of neoplasia

“…W regulacji procesu dojrzewania naczy-receptor activation triggers a cascade of signals that affect the interactions between vascular endothelial cells and the surrounding supporting cells, leading to the remodelling of immature blood vessels and stabilization of mature vessels. An increase in the angiopoietin production in neoplastic cells has also been demonstrated in colorectal cancer [25]. Kinase D1 is involved in regulating angiogenesis by influencing the VEGF pathway [26].…”

“…Aktywacja receptora Tie-2 uruchamia kaskadę sygnałów, wpływających na oddziaływania między komórkami śródbłonka naczyń i otaczającymi je komórkami podporowymi, co doprowadza do przebudowy niedojrzałych naczyń krwionośnych i stabilizacji naczyń dojrzałych. Wzrost produkcji angiopoetyn w komórkach nowotworowych wykazano także w raku jelita grubego [25]. Kinaza D1 bierze udział w regulowaniu angiogenezy poprzez wpływ na ścieżkę VEGF [26].…”

The Scandinavian Small-for-Gestational Age (SGA) pregnancy and birth cohort – A source to continual insight into fetal growth restriction and long term physical and neurodevelopmental health in mother and offspring

“…In 2013, Conde-Agudelo et al did a systematic review of predictive biomarkers for IUGR (75). They concluded that none have been found so far, and that biomarkers only may be useful in combination with anthropometric and other clinical data (75).…”

“…In 2013, Conde-Agudelo et al did a systematic review of predictive biomarkers for IUGR (75). They concluded that none have been found so far, and that biomarkers only may be useful in combination with anthropometric and other clinical data (75). In fact, this may be a reflection of the large number and variety of factors, i.e., fetal, placental/ uterine and maternal, that to some degree cause SGA and IUGR (1,2).…”

Angiogenic, neurotrophic, and inflammatory system SNPs moderate the association between birth weight and ADHD symptom severity

“…Prenatal ischemia-hypoxia is considered the primary pathway to lower birth weight, especially in well-nourished populations [Henriksen et al, 2002]. Placental insufficiency and fetal growth restriction are associated with altered angiogenic [Conde-Agudelo et al, 2013], dopaminergic [Vucetic et al, 2010], neurotrophic [MalamitsiPuchner et al, 2007], and inflammatory responses [Amarilyo et al, 2011], and numerous poor neurodevelopmental outcomes [Baschat, 2011]. Prenatal ischemia-hypoxia is a common element to multiple early risk factors for ADHD including maternal smoking [Bush et al, 2000] and maternal alcohol use during pregnancy [Bosco and Diaz, 2012] as well as ischemia-hypoxia related obstetric complications [Pineda et al, 2007;Rennie et al, 2007;Getahun et al, 2013].…”