Angiogenic and inflammatory biomarkers in midpregnancy and small-for-gestational-age outcomes in Tanzania

Abstract

Objective: We sought to investigate the relationship between a panel of angiogenic and inflammatory biomarkers measured in midpregnancy and small-for-gestational-age (SGA) outcomes in sub-Saharan Africa.

Study design: Concentrations of 18 angiogenic and inflammatory biomarkers were determined in 432 pregnant women in Dar es Salaam, Tanzania, who participated in a trial examining the effect of multivitamins on pregnancy outcomes. Infants falling below the 10th percentile of birthweight for gestational age relative to the applied growth standards were considered SGA. Multivariate binomial regression models with the log link function were used to determine the relative risk of SGA associated with increasing quartiles of each biomarker. Restricted cubic splines were used to test for nonlinearity of these associations.

Results: A total of 60 participants (13.9%) gave birth to SGA infants. Compared to those in the first quartile, the risk of SGA was reduced among those in the fourth quartiles of vascular endothelial growth factor-A (adjusted risk ratio [RR], 0.38; 95% confidence interval [CI], 0.19-0.74), placental growth factor (adjusted RR, 0.28; 95% CI, 0.12-0.61), soluble fms-like tyrosine kinase-1 (adjusted RR, 0.48; 95% CI, 0.23-1.01), monocyte chemoattractant protein-1 (adjusted RR, 0.48; 95% CI, 0.25-0.92), and leptin (adjusted RR, 0.46; 95% CI, 0.22-0.96).

Conclusion: Our findings provide evidence of altered angiogenic and inflammatory mediators, at midpregnancy, in women who went on to deliver SGA infants.

Keywords: angiogenesis; inflammation; small for gestational age.

Figure 1. Median levels of selected biomarkers according to gestational age at sample collection

a) VEGF-A, B) PGF, C) sFlt-1, D) MCP-1/CCL2, E) Leptin, F) sICAM-1

Figure 2. Non-linear relation (p=0.001) between mid-pregnancy VEGF levels and (pg/ml) and SGA

Adjusted for literacy (yes/no), marital status (yes/no), gestational age at study entry (<20, 20-25, 25-30 weeks), and district of recruitment (Ilala/Temeke/Kinondoni). Because VEGF levels were non-normally distributed, only those between the 5^th and 95^th percentile are displayed. The solid line shows the estimated odds ratio for mortality for each increasing pg/ml of VEGF compared to the reference value of 0.03. The horizontal line represents the null OR of 1.0. Dashed lines signify the upper and lower bounds of the 95% CI for the OR.

Figure 3. Non-linear relation (p=0.008) between mid-pregnancy PGF levels and (pg/ml) and SGA

Adjusted for literacy (yes/no), marital status (yes/no), gestational age at study entry (<20, 20-25, 25-30 weeks), and district of recruitment (Ilala/Temeke/Kinondoni). Because VEGF levels were non-normally distributed, only those between the 5^th and 95^th percentile are displayed. The solid line shows the estimated odds ratio for mortality for each increasing pg/ml of VEGF compared to the reference value of 74.07. The horizontal line represents the null OR of 1.0. Dashed lines signify the upper and lower bounds of the 95% CI for the OR.