The effects of a lipid-based nutrient supplement and antiretroviral therapy in a randomized controlled trial on iron, copper, and zinc in milk from HIV-infected Malawian mothers and associations with maternal and infant biomarkers

Abstract

We evaluated effects of antiretroviral (ARV) therapy and lipid-based nutrient supplements (LNSs) on iron, copper, and zinc in milk of exclusively breastfeeding HIV-infected Malawian mothers and their correlations with maternal and infant biomarkers. Human milk and blood at 2, 6, and 24 weeks post-partum and blood during pregnancy (≤30 weeks gestation) were collected from 535 mothers/infant-pairs in the Breastfeeding, Antiretrovirals, and Nutrition study. The participants received ARV, LNS, ARV and LNS, or no intervention from 0 to 28 weeks post-partum. ARVs negatively affected copper and zinc milk concentrations, but only at 2 weeks, whereas LNS had no effect. Among all treatment groups, approximately 80-90% of copper and zinc and <50% of iron concentrations met the current adequate intake for infants at 2 weeks and only 1-19% at 24 weeks. Pregnancy haemoglobin was negatively correlated with milk iron at 2 and 6 weeks (r = -.18, p < .02 for both). The associations of the milk minerals with each other were the strongest correlations observed (r = .11-.47, p < .05 for all); none were found with infant biomarkers. At 2 weeks, moderately anaemic women produced milk higher in iron when ferritin was higher or TfR lower. At 6 weeks, higher maternal α-1-acid glycoprotein and C-reactive protein were associated with higher milk minerals in mildly anaemic women. Infant TfR was lower when milk mineral concentrations were higher at 6 weeks and when mothers were moderately anaemic during pregnancy. ARV affects copper and zinc milk concentrations in early lactation, and maternal haemoglobin during pregnancy and lactation could influence the association between milk minerals and maternal and infant iron status and biomarkers of inflammation.

Keywords: HIV; copper; haemoglobin status; human milk; iron; zinc.

Figure 1

Relative median decrease (%) in human milk iron, copper, and zinc over time compared to AI (values pooled from all treatment groups at each time point of sample collection: (a) FTP2 subgroup (2–24 weeks; n = 366); (b) FTP6 subgroup (6–24 weeks; n = 169). AI = adequate intake; FTP = first time point

Figure 2

Significant correlations between milk minerals and maternal biomarkers at 2, 6, and 24 weeks. Pearson's correlation coefficients (Spearman correlations coefficient for the characteristics) are shown and level of significance as: *p < .05; **p < .01; ***p < .001. Preg = pregnancy (during screening); Hb = haemoglobin; BM = breast milk; Fe = iron; Cu = copper; Zn = zinc; Mat = maternal; AGP = α‐1‐acid glycoprotein; CRP = C‐reactive protein; BMI = body mass index

Figure 3

Associations of human milk iron, copper, and zinc with maternal biomarkers stratified by maternal haemoglobin status during pregnancy and lactation (coefficients and SEs obtained from regression procedure displayed as bar graphs with error bars). p values for comparisons of moderately or mildly anaemic to non‐anaemic group, and comparison of moderately to mildly anaemic group, using linear regression analysis. Anaemia, state of anaemia—moderately, mildly, or non‐anaemic—based on maternal haemoglobin status at indicated week post‐partum (World Health Organization, 2003). Anaemia_Preg, state of anaemia during pregnancy (moderately, mildly, or non‐anaemic based on maternal Hb during pregnancy, World Health Organization, 2003). BM = breast milk; CRP = C‐reactive protein; AGP = α‐1‐acid glycoprotein; TfR = soluble transferrin receptors; n = number of samples (moderately anaemic/mildly anaemic/non‐anaemic): 2 weeks anaemia: 41/49/276; 2 weeks anaemia_Preg: 91/106/169; 6 weeks anaemia: 13/25/131; 6 weeks anaemia_Preg: 35/53/81; 24 weeks anaemia: 16/45/476; 24 weeks anaemia_Preg: 126/160/251; separate models were used for each time point and first time point and anaemia status

Figure 4

Associations of human milk iron, copper, and zinc with infant biomarkers stratified by maternal haemoglobin status during pregnancy and lactation (coefficients and SEs obtained from regression procedure displayed as bar graphs with error bars). p values for comparisons of moderately or mildly anaemic to non‐anaemic group, and comparison of moderately to mildly anaemic group, using linear regression analysis. Anaemia, state of anaemia—moderately, mildly, or non‐anaemic—based on maternal haemoglobin status at indicated week post‐partum (World Health Organization, 2003). Anaemia_Preg, state of anaemia during pregnancy (moderately, mildly, or non‐anaemic based on maternal Hb during pregnancy, World Health Organization, 2003). BM = breast milk; CRP = C‐reactive protein; AGP = α‐1‐acid glycoprotein; TfR = soluble transferrin receptors; n = number of samples (moderately anaemic/mildly anaemic/non‐anaemic): 2 weeks anaemia: 41/49/276; 2 weeks anaemia_Preg: 91/106/169; 6 weeks anaemia: 13/25/131; 6 weeks anaemia_Preg: 35/53/81; 24 weeks anaemia: 16/45/476; 24 weeks anaemia_Preg: 126/160/251; separate models were used for each time point and FTP and anaemia status