Retinol-Binding Protein 4 and Lipids Prospectively Measured During Early to Mid-Pregnancy in Relation to Preeclampsia and Preterm Birth Risk.
BACKGROUND
Maternal retinol-binding protein 4 (RBP4) and lipids may relate to preeclampsia and preterm birth risk but longitudinal data are lacking. This study examines these biomarkers longitudinally during pregnancy in relation to preeclampsia and preterm birth risk.


METHODS
Maternal serum samples from the Calcium for Preeclampsia Prevention (CPEP) trial were analyzed at baseline: average 15 gestational weeks; mid-pregnancy: average 27 weeks; and at >34 weeks. We measured RBP4, total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides and lipoprotein (a) (Lp(a)). Cross-sectional logistic regression analyses estimated the odds ratio (OR) and 95% confidence intervals (CI) for preterm preeclampsia (n = 63), term preeclampsia (n = 104), and preterm delivery (n = 160) associated with RBP4 and lipids at baseline and mid-pregnancy compared with controls (n = 136). Longitudinal trajectories across pregnancy were assessed using mixed linear models with fixed effects. Adjusted models included clinical and demographic factors.


RESULTS
RBP4 concentrations at baseline and mid-pregnancy were associated with a 4- to 8-fold increase in preterm preeclampsia risk but were not associated with term preeclampsia. RBP4 measured mid-pregnancy was also associated with preterm birth (OR = 6.67, 95% CI: 1.65, 26.84). Higher triglyceride concentrations in mid-pregnancy were associated with a 2- to 4-fold increased risk for both preeclampsia and preterm birth. Longitudinal models demonstrate that both preterm preeclampsia and preterm birth cases had elevated RBP4 throughout gestation.


CONCLUSIONS
Elevated RBP4 is detectable early in pregnancy and its strong relation with preterm preeclampsia merits further investigation and confirmation to evaluate its potential use as a predictor, particularly among high-risk women.
Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, USA.
Pauline
P
Mendola
Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, USA.
Akhgar
A
Ghassabian
Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, USA.
James L
JL
Mills
Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, USA.
Cuilin
C
Zhang
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA.
Michael Y
MY
Tsai
Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, USA.
Aiyi
A
Liu
Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, USA.
Edwina H
EH
Yeung
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D005260:Female; D005865:Gestational Age; D006801:Humans; D008055:Lipids / Q000097:blood*; D016015:Logistic Models; D008137:Longitudinal Studies; D016017:Odds Ratio; D011225:Pre-Eclampsia / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D011237:Predictive Value of Tests; D011247:Pregnancy; D047928:Premature Birth / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D011446:Prospective Studies; D054839:Retinol-Binding Proteins, Plasma / Q000378:metabolism*; D018570:Risk Assessment; D012307:Risk Factors; D015854:Up-Regulation; D055815:Young Adult
D015415:Biomarkers; D008055:Lipids; C101326:RBP4 protein, human; D054839:Retinol-Binding Proteins, Plasma
blood pressure; hypertension; lipids; preeclampsia; pregnancy; preterm birth; retinol-binding protein 4