A Population-based Cohort Study:the Associations Between Maternal Plasma Protein Levels During Pregnancy And Gestational Diabetes And Birth Outcomes

Objective:To access the influence of maternal protein levels during pregnancy on gestational diabetes(GDM)and birth outcomes in Wuhan,China.Methods:A total of 4,265 pairs of mothers and their babies extracted from Tongji Maternal and Child Health Cohort(TMCHC)were included in this prospective cohort study.We measured mtaternal plasma transthyretin(TTR),total protein(TP),albumin(Alb)and globulin(Gb)levels in the regular liver and renal function test.GDM was diagnosed based on a 75-g oral glucose tolerance test(OGTT)at 24-28 gestational weeks.We collected the the birth weight(BW)and birth height(BH)and so on at term.1,914 mothers who had their liver and renal function test measured at 13-20 gestational weeks were selected to analyze the associations between quartiles of maternal protein and GDM with logistic regression.To eliminate the effects of interindividual protein status differences on TTR levels,we used the ratios TTR/TP,TTR/Alb and TTR/Gb to assess maternal plasma TTR.Further analysis explored the relationship of plasma TTR to fasting(FBG)and 1-h and 2-h post-load blood glucose(1-h and 2-h PBG)in three pregnancy BMI(pre-BMI)subgroups.Multivariate linear regression analyze the relationship of maternal protein to BW,BH in 4,265 pair of mothers and babies,and logistic regression was used to analyze the associations between quartiles of maternal protein with the risk of small for gestational age(SGA)and large for gestational age(LGA).Results:There were no difference of maternal TP,Alb,Gb and TTR/Gb between GDM and non-GDM group.But the TTR/TP and TTR/Alb were significantly higher in GDM group when compared with non-GDM group.After adjustment for relevant covariates,quartile 4 vs.quartile 1 TTR/TP(odds ratio[OR]1.94,95%CI 1.06,3.71)and TTR/Alb(OR 2.25,95%CI 1.21,4.19)correlated significantly with GDM.Furthermore,plasma TTR/TP and TTR/Alb correlated positively with PBG but not FBG.In normal pre-BMI mothers,each additional of 1 mg/g TTR/TP initiated a 0.19g/L increase of 1-h PBG and 0.18 increase of 2-h PBG:and each additional of 1 mg/g TTR/Alb initiated a 0.l0g/L increase of 2-h PBG.In low pre-BMI persons.each additional of 1 mg/g TTR/Alb(but not TTR/TP)induced a 0.18g/L increase of 2-h PBG.For high pre-BMI women,neither TTR/TP nor TTR/Alb were associatied with glucose levels.In male babies,there were threshold effects between BW,BH and maternal TP and Alb levels,and their BW and BH decreased with the maternal TP from 68-75g/L,and/or decreased with the maternal Alb from 37g/L;In female babies.their BW and BH decreased with maternal TP and Alb levels all the time.In male babies,after adjustment for relevant covariates,quartile 4 vs.quartile 1TP(OR 2.84,95%CI 1.25,6.45)and(OR 0.63,95%CI0.41,0.96)correlated significantly with SGA and LGA;Q2(OR 2.63,95%CI 1.12,6.16).Q3(OR 2.66,95%CI 1.12.6.30)and Q4(OR 2.78.95%Cl 1.18.6.59)vs.QIGb were all positively associatied with SGA,but Q4 vs Q1 TTR/TP(OR 0.32,95%CI 0.12,0.84)and TTR/Gb(OR 0.42,95%CI 0.20.0.85)were both negatively associatied with SGA.Conclusions:Maternal plasma TTR is the risk factors of GDM.And TTR upregulated PBG other then FBG.In male babies,there were threshold effects between BW.BH and maternal TP and Alb levels.Their BW and BH decreased with the maternal TP from 68-75g/L.and decreased with the maternal Alb from 37g/L;In female babies,their BW and BH decreased with maternal TP and Alb levels all the time.TP correlated positively with risk of SGA but correlated negatively with risk of LGA in male babies;Gb were positively associatied with the risk of SGA,but TTR/TP and TTR/Gb were both negatively associatied with the risk of SGA in male babies.