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To study the role of the TTR-RBP4-ROH complex components (transthyretin, serum retinol binding protein, retinol) and of angiogenic factors PlGF (placental growth factor) and sFlt-1 (soluble fms-like tyrosine kinase-1) in pregnancies complicated by small for gestational age infants (SGA). Case control study conducted on maternal serum collected between 11 + 0 to 13 + 6 weeks of gestation. TTR, RBP4, ROH, PlGF and sFlt-1 were measured in SGA patients (birth weight < 10%) who delivered at term (n = 37) and before 37 weeks of gestation (n = 17) and in a matched control group with uneventful pregnancies (n = 37). We found decreased RBP4 in SGA patients that delivered fetuses < 3% and in fetuses delivered after the 37 weeks of gestation compared to controls [1.50 (95% CI 1.40-1.75) vs 1.62 (95% CI 1.47-1.98), p < 0.05]. Further, we found lower PlGF and sFlt-1 concentrations in SGA that delivered before 37 weeks of gestation compared to controls (respectively, PIGF and sFlt-1: 39.7 pg/ml (95% CI 32.3-66.3) vs 62.9 pg/ml (95% CI 45.2-78.4) and 906 pg/ml (95% CI 727-1626) vs 1610 pg/ml (95% CI 1088-212), p < 0.05). First trimester maternal serum RBP4 and angiogenic factors PlGF and sFlt-1 can differently predict the timing of delivery of pregnancies complicated by SGA fetuses.
Background: The objective of the study was to investigate the relationship between first trimester maternal serum levels of the TTR-RBP4-ROH complex components and the later insurgence of an altered glucose metabolism during pregnancy.
Methods: Retrospective case control study including 96 patients between the 12th and 14th week of gestation, 32 that developed gestational diabetes mellitus (GDM), respectively, 21 non-insulin-treated (dGDM) and 11 insulin-treated (iGDM), 20 large for gestational age fetuses (LGA) without GDM and 44 patients with normal outcome as control. Serum concentrations of RBP4 and TTR were assessed by ELISA; serum concentration of ROH by reverse-phase high performance liquid chromatography (rpHPLC). The molecular heterogeneity of TTR and RBP4 was analyzed after immunoprecipitation by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS).
Results: iGDM patients were characterized by reduced TTR, RBP4 and ROH compared to controls (respectively, iGDM vs. controls, mean +/- SD: TTR 3.96 +/- 0.89 mu mol/L vs. 4.68 +/- 1.21 mu mol/L, RBP4 1.13 +/- 0.25 mu mol/L vs. 1.33 +/- 0.38 mu mol/L and ROH 1.33 +/- 0.17 mu mol/L vs. 1.62 +/- 0.29 mu mol/L, p < 0.05). TTR containing Gly10 in place of Cys10 was lower in the iGDM group (p < 0.05) compared to controls. In the final logistic regression model ROH significantly predicted the diagnosis of iGDM (OR 0.93, 95% CI 0.87-0.98, p < 0.05).
Conclusions: First trimester maternal serum ROH, RBP4 and TTR represent potential biomarkers associated with the development of iGDM.