Antenatal micronutrient supplementation and third trimester cortisol and erythropoietin concentrations

Abstract

Antenatal iron and multiple micronutrient supplementation has been shown in randomized trials to improve birthweight, although mechanisms are unknown. We examined late pregnancy serum erythropoietin (EPO) and cortisol concentrations in relation to maternal micronutrient supplementation and iron status indicators (haemoglobin, serum ferritin, soluble transferrin receptor) in 737 rural Nepalese women to explore evidence of stress or anaemia-associated hypoxia. A double-masked randomized control trial was conducted from December 1998 to April 2001 in Sarlahi, Nepal, in which women received vitamin A alone (as control), or with folic acid (FA), FA + iron, FA + iron + zinc and a multiple micronutrient supplement. In a substudy, we collected maternal blood in the first and third trimester for biochemical assessments. Generalized estimating equations linear regression analysis was used to examine treatment group differences. EPO was ∼ 14-17 mIU mL(-1) lower (P < 0.0001) in late pregnancy in groups receiving iron vs. the control group, with no difference in the FA-only group. Cortisol was 1.3 μg dL(-1) lower (P = 0.04) only in the micronutrient supplement group compared with the control group. EPO was most strongly associated with iron status indicators in groups that did not receive iron, and in the non-iron groups cortisol was positively correlated with EPO (r = 0.15, P < 0.01) and soluble transferrin receptor (sTfR, r = 0.19, P < 0.001). In adjusted analyses, third trimester EPO was associated with a reduction in low birthweight, whereas cortisol was negatively associated with length of gestation and higher risk of preterm birth. Iron and multiple micronutrient supplementation may enhance birth outcomes by reducing mediators of maternal stress and impaired erythropoiesis.

Keywords: Nepal; cortisol; erythropoietin; micronutrients; pregnancy.

Figure 1

Study design and number of substudy pregnant women by treatment group and final sample contributing to the erythropoietin and cortisol data and analysis. FA, folic acid; FAFe, folic acid and iron; FAFeZn, folic acid, iron and zinc; MM, multiple micronutrients; TM, trimester.

Figure 2

Differences (95% confidence interval) in log erythropoietin (EPO) and cortisol concentrations in the intervention groups relative to the control. Differences estimated using generalized estimating equations linear regression models.

Figure 3

Correlation matrices showing correlation coefficients and P‐values for log erythropoietin (EPO), cortisol and iron status indicators among pregnant women in the intervention groups not containing iron.

Figure 4

Correlation matrices showing correlation coefficients and P‐values for log erythropoietin (EPO), cortisol and iron status indicators among pregnant women in the intervention groups containing iron.