Seasonal Factors Are Associated with Activities of Enzymes Involved in High-Density Lipoprotein Metabolism among Pregnant Females in Ghana

Abstract

Background: Small-quantity lipid-based nutrient supplements (SQ-LNS) during pregnancy and postnatally were previously shown to improve high-density lipoprotein (HDL) cholesterol efflux capacity (CEC) and length in the children of supplemented mothers at 18 mo of age in the International Lipid-Based Nutrient Supplements (iLiNS) DYAD trial in Ghana. However, the effects of SQ-LNS on maternal HDL functionality during pregnancy are unknown.

Objective: The goal of this cross-sectional, secondary outcome analysis was to compare HDL function in mothers supplemented with SQ-LNS vs. iron and folic acid (IFA) during gestation.

Methods: HDL CEC and the activities of 3 HDL-associated enzymes were analyzed in archived plasma samples (N = 197) from a subsample of females at 36 weeks of gestation enrolled in the iLiNS-DYAD trial in Ghana. Correlations between HDL function and birth outcomes, inflammatory markers C-reactive protein (CRP) and alpha-1-acid glycoprotein (AGP), and the effects of season were explored to determine the influence of these factors on HDL function in this cohort of pregnant females.

Results: There were no statistically significant differences in HDL CEC, plasma lecithin-cholesterol acyltransferase (LCAT) activity, cholesteryl ester transfer protein (CETP) activity, or phospholipid transfer protein (PLTP) activity between mothers supplemented with SQ-LNS compared with IFA control, and no statistically significant relationships between maternal HDL function and childbirth outcomes. LCAT activity was negatively correlated with plasma AGP (R = -0.19, P = 0.007) and CRP (R = -0.28, P < 0.001), CETP and LCAT activity were higher during the dry season compared to the wet season, and PLTP activity was higher in the wet season compared to the dry season.

Conclusions: Mothers in Ghana supplemented with SQ-LNS compared with IFA during gestation did not have measurable differences in HDL functionality, and maternal HDL function was not associated with childbirth outcomes. However, seasonal factors and markers of inflammation were associated with HDL function, indicating that these factors had a stronger influence on HDL functionality than SQ-LNS supplementation during pregnancy.

Clinical trial registry number: The study was registered as NCT00970866. https://clinicaltrials.gov/study/NCT00970866.

Keywords: CETP activity; Ghana; HDL; LCAT activity; PLTP activity; SQ-LNS; cholesterol efflux capacity; pregnancy.

FIGURE 1

Study flow diagram. In this secondary outcome analysis, archived samples from a previously conducted study were utilized. A subset of participants were randomly selected from the original cohort as a representative sample set using the following criteria: the participant was randomly assigned to either SQ-LNS or IFA, enrolled between October 2010 and December 2011, adequate plasma volume (>500 μL), remained in the biorepository, and the sample was subjected to no more than 2 freeze-thaw cycles. IFA, iron and folic acid; SQ-LNS, small-quantity lipid-based nutrient supplements.

FIGURE 2

Spearman correlation analysis between HDL CEC, plasma enzyme activities, inflammation markers, and hemoglobin levels. AGP, alpha-1-acid glycoprotein; CEC, cholesterol efflux capacity; CETP, cholesteryl ester transfer protein; CRP, C-reactive protein; LCAT, lecithin-cholesterol acyltransferase; PLTP, phospholipid transfer protein.

FIGURE 3

Box and violin combination plots of plasma enzyme activities and HDL cholesterol efflux capacity (CEC) by season (Dry: November - April and Wet: May - October) at 36 weeks of gestation. Plasma (A) lecithin-cholesterol acyltransferase (LCAT) activity, (B) cholesteryl ester transfer protein (CETP) activity, (C) phospholipid transfer protein (PLTP) activity, and (D) HDL CEC. ∗∗P < 0.01, ∗∗∗P < 0.001, NS = not statistically significant.