Mass spectrometric profiling of cord blood serum proteomes to distinguish infants with intrauterine growth restriction from those who are small for gestational age and from control individuals

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Abstract

Intrauterine growth restriction (IUGR) is a multifactorial condition in that the fetus does not reach its genetically given growth potential. Besides its contribution to perinatal mortality, it is a risk factor for cardiovascular and metabolic diseases later in life. The diagnosis is based on antenatal sonography, which allows differentiating between IUGR and fetuses that are small by constitution (small for gestational age [SGA]). Yet, neither a clinical nor a biochemical tool is available to confirm reliably the diagnosis of IUGR postnatally. Recently, we identified umbilical cord blood proteins of the apolipoprotein family by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry with differential signal intensities between the IUGR group and a control group. We hypothesized that identified molecules have the potential to generate a proteome profile specific for IUGR. A total of 114 serum samples (42 from the IUGR group, 12 from the SGA group, and 60 from the control group) of the umbilical vein (99 samples) and umbilical artery (15 samples) were analyzed. Sample quality was estimated by determining the abundance of hemoglobin (hemolysis) and CXC-motif chemokines CXCL4 and CXCL7 (platelet activation). Samples passing the quality criteria were forwarded to multiplex apolipoprotein profiling. Assay performance was tested with the sample sets, resulting in a sensitivity of 0.91 and a specificity of 0.85 in the test set with venous blood samples. Arterial cord blood samples followed the trend (sensitivity, 0.67; specificity, 0.85). SGA samples grouped together with the control samples. We conclude that the proteome profiling signature is confirmatory to clinical surveillance with the potential to identify neonates with IUGR postnatally in low-birth weight babies born at uncertain gestational age when antenatal sonography data have not been recorded.

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