Prediction of neonatal complications based on quantitative proteome analysisin blood of pregnant women with fetal growth restriction

Objective: The objective of the study was to investigate relationship between early neonatal complications and plasma proteome composition in pregnant women diagnosed with fetal growth restriction.

Materials and methods: This pilot case-control study included 40 pairs of "pregnant woman – newborn baby". Four groups were formed: Group I and group II were the main groups, group III and group IV were the comparison groups. Group I was comprised of women with early fetal growth restriction (FGR) (<32 weeks) (n=10 pairs); group II was comprised of women with late FGR (≥32 weeks) (n=10 pairs). Group III and group IV consisted of pregnant women, who delivered before and after 32 weeks (n=10 pairs/n=10 pairs) (the comparison group). Confirmation of the diagnosis of fetal growth restriction, as well as definition of normal body weight in the group of women with preterm births (before and after 32 weeks), postnatal assessment of weight and growth indicators in newborns (n=40) was performed according to the INTERGROWTH-21st centile charts that reflected the international consensus reached by the members of Neonatal Group. Quantitative analysis of 125 plasma proteins was performed using BAK 125 plasma proteomics kit (MRM Proteomics Inc., Montreal, Canada) by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Based on the support vector machine used for classification, predictive models for possible development of asphyxia and intraventricular hemorrhage in newborns were created.

Results: Based on the results of quantitative proteomic analysis of maternal plasma proteins, two prognostic models were developed. Model 1 (AUC=0.96), including the proteins α-1-acid glycoprotein 1, α-1-antichimotrypsin, α-1-β-glycoprotein, α-2-macroglobulin, antithrombin III, apolypoprotein A-IV, apolypoprotein С–II, apolypoprotein С-IV, carboanhydrase 1, CD5 antigen like protein, ceruloplasmin, clasterin, complement C3, complement component C9, complement factor H, transcortin, fibrinogen α-chain, fibrinogen β-chain, fibronectin, fibulin-1, heparin cofactor II, kallistatin, keratin, type II cytoskeletal 2 epidermal, pregnancy zone protein, prothrombin, ferotransferrin, vitamin К-depended protein S, vitamin К-depended protein Z, vitronectin as variables, with 92% sensitivity and 76% specificity will enable to detect the risks for intraventricular hemorrhage in newborns. Model 2 (AUC=0.83), including the proteins α-1-antichimotrypsin, apolypoprotein С–III, apolypoprotein D, β-2-glycoprotein 1, complement C1q subcomponent subunit C, complement component C9, kininogen-1, plasma protease C1 inhibitor, pregnancy zone protein, AMBP protein, prothrombin, vitronectin as variables with 67% sensitivity and 100% specificity, will enable to predict birth asphyxia.

Conclusion: Using the plasma proteome of pregnant women to predict the development of birth asphyxia and intraventricular hemorrhage in newborns in early neonatal period will improve the quality of medical care, as well as reduce neonatal morbidity and mortality in the group of infants with intrauterine growth restriction (IUGR).