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      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

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          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.

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          Maternal or infant antiretroviral drugs to reduce HIV-1 transmission.

          We evaluated the efficacy of a maternal triple-drug antiretroviral regimen or infant nevirapine prophylaxis for 28 weeks during breast-feeding to reduce postnatal transmission of human immunodeficiency virus type 1 (HIV-1) in Malawi. We randomly assigned 2369 HIV-1-positive, breast-feeding mothers with a CD4+ lymphocyte count of at least 250 cells per cubic millimeter and their infants to receive a maternal antiretroviral regimen, infant nevirapine, or no extended postnatal antiretroviral regimen (control group). All mothers and infants received perinatal prophylaxis with single-dose nevirapine and 1 week of zidovudine plus lamivudine. We used the Kaplan-Meier method to estimate the cumulative risk of HIV-1 transmission or death by 28 weeks among infants who were HIV-1-negative 2 weeks after birth. Rates were compared with the use of the log-rank test. Among mother-infant pairs, 5.0% of infants were HIV-1-positive at 2 weeks of life. The estimated risk of HIV-1 transmission between 2 and 28 weeks was higher in the control group (5.7%) than in either the maternal-regimen group (2.9%, P=0.009) or the infant-regimen group (1.7%, P<0.001). The estimated risk of infant HIV-1 infection or death between 2 and 28 weeks was 7.0% in the control group, 4.1% in the maternal-regimen group (P=0.02), and 2.6% in the infant-regimen group (P<0.001). The proportion of women with neutropenia was higher among those receiving the antiretroviral regimen (6.2%) than among those in either the nevirapine group (2.6%) or the control group (2.3%). Among infants receiving nevirapine, 1.9% had a hypersensitivity reaction. The use of either a maternal antiretroviral regimen or infant nevirapine for 28 weeks was effective in reducing HIV-1 transmission during breast-feeding. (ClinicalTrials.gov number, NCT00164736.) 2010 Massachusetts Medical Society
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            Lipid-based nutrient supplement increases the birth size of infants of primiparous women in Ghana.

            The International Lipid-Based Nutrient Supplements Project developed a small-quantity (20 g/d) lipid-based nutrient supplement (LNS) for pregnant and lactating women.
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              Vitamin B-12 supplementation during pregnancy and early lactation increases maternal, breast milk, and infant measures of vitamin B-12 status.

              Pregnant women in resource-poor areas are at risk of multiple micronutrient deficiencies, and indicators of low vitamin B-12 status have been associated with adverse pregnancy outcomes, including anemia, low birth weight, and intrauterine growth retardation. To evaluate whether daily oral vitamin B-12 supplementation during pregnancy increases maternal and infant measures of vitamin B-12 status, we performed a randomized, placebo-controlled clinical trial. Pregnant women <14 wk of gestation in Bangalore, India, were randomly assigned to receive daily oral supplementation with vitamin B-12 (50 μg) or placebo through 6 wk postpartum. All women were administered iron and folic acid supplements throughout pregnancy. One hundred eighty-three women were randomly assigned to receive vitamin B-12 and 183 to receive placebo. Compared with placebo recipients, vitamin B-12-supplemented women had significantly higher plasma vitamin B-12 concentrations at both the second (median vitamin B-12 concentration: 216 vs. 111 pmol/L, P < 0.001) and third (median: 184 vs. 105 pmol/L, P < 0.001) trimesters. At 6 wk postpartum, median breast milk vitamin B-12 concentration was 136 pmol/L in vitamin B-12-supplemented women vs. 87 pmol/L in the placebo group (P < 0.0005). Among vitamin B-12-supplemented women, the incidence of delivering an infant with intrauterine growth retardation was 33 of 131 (25%) vs. 43 of 125 (34%) in those administered placebo (P = 0.11). In a subset of infants tested at 6 wk of age, median plasma vitamin B-12 concentration was 199 pmol/L in those born to supplemented women vs. 139 pmol/L in the placebo group (P = 0.01). Infant plasma methylmalonic acid and homocysteine concentrations were significantly lower in the vitamin B-12 group as well. Oral supplementation of urban Indian women with vitamin B-12 throughout pregnancy and early lactation significantly increases vitamin B-12 status of mothers and infants. It is important to determine whether there are correlations between these findings and neurologic and metabolic functions. This trial was registered at clinicaltrials.gov as NCT00641862.
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                Author and article information

                Contributors
                daniela.hampel@ars.usda.gov
                Journal
                Matern Child Nutr
                Matern Child Nutr
                10.1111/(ISSN)1740-8709
                MCN
                Maternal & Child Nutrition
                John Wiley and Sons Inc. (Hoboken )
                1740-8695
                1740-8709
                29 August 2017
                April 2018
                : 14
                : 2 ( doiID: 10.1111/mcn.2018.14.issue-2 )
                : e12503
                Affiliations
                [ 1 ] USDA, ARS Western Human Nutrition Research Center Davis California USA
                [ 2 ] Department of Nutrition University of California Davis California USA
                [ 3 ] Gillings School of Global Public Health University of North Carolina Chapel Hill North Carolina USA
                [ 4 ] Centers for Disease Control and Prevention Atlanta Georgia USA
                [ 5 ] UNC Project Lilongwe Malawi
                [ 6 ] School of Public Health University of Witwatersrand Johannesburg South Africa
                [ 7 ] School of Medicine University of North Carolina Chapel Hill North Carolina USA
                Author notes
                [*] [* ] Correspondence

                Daniela Hampel, UC Davis Department of Nutrition and USDA, ARS Western Human Nutrition Research Center, 430 W. Health Sciences Drive, University of California, Davis, CA 95616, USA.

                Email: daniela.hampel@ 123456ars.usda.gov

                Author information
                http://orcid.org/0000-0003-0288-7680
                http://orcid.org/0000-0003-0200-3355
                Article
                MCN12503 MCN-02-17-OA-2476.R1
                10.1111/mcn.12503
                5832511
                28851037
                9115b88c-df44-4dce-9cb5-b62aa069432d
                © 2017 The Authors. Maternal and Child Nutrition Published by John Wiley & Sons, Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 13 February 2017
                : 27 June 2017
                : 12 July 2017
                Page count
                Figures: 4, Tables: 4, Pages: 14, Words: 7090
                Funding
                Funded by: Bill and Melinda Gates Foundation
                Award ID: OPP1061055
                Award ID: OPP53107
                Funded by: Intramural USDA‐ARS Project
                Award ID: 5306‐51000‐003‐00D
                Funded by: NIH Fogarty AIDS International Training and Research Program
                Award ID: DHHS/NIH/FIC 2‐D43 Tw01039‐06
                Award ID: R24 Tw007988
                Funded by: Carolina Population Center
                Award ID: P2C HD050924
                Funded by: National Institute of Allergy and Infectious Diseases, the University of North Carolina Center for AIDS Research
                Award ID: P30‐AI50410
                Funded by: Centers for Disease Control and Prevention
                Award ID: SIP 13‐01 U48‐CCU409660‐09
                Award ID: SIP 22‐09 U48‐DP001944‐01
                Award ID: SIP 26‐04 U48‐DP000059‐01
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                mcn12503
                April 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.3.4 mode:remove_FC converted:16.04.2018

                copper,haemoglobin status,hiv,human milk,iron,zinc
                copper, haemoglobin status, hiv, human milk, iron, zinc

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