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      Anemia and Micronutrient Status during Pregnancy, and Their Associations with Obstetric and Infant Outcomes among HIV-Infected Ugandan Women Receiving Antiretroviral Therapy

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          ABSTRACT

          Background

          Women living with HIV (WLHIV) are at higher risk of micronutrient deficiencies and adverse health outcomes. There are limited data on the burden or sequelae of micronutrient deficiencies among pregnant WLHIV receiving antiretroviral therapy (ART).

          Objectives

          We aimed to examine anemia and vitamin B-12, folate, and vitamin D deficiencies, and their associations with obstetric and infant outcomes, among pregnant WLHIV initiating combination antiretroviral therapy (cART) in rural Uganda.

          Methods

          This was a prospective analysis among pregnant WLHIV (12–28 weeks of gestation) in PROMOTE-Pregnant Women and Infants (PIs), a randomized trial comparing the effects of protease inhibitor (PI)-based ART with those of a non-PI-based ART on placental malaria risk. We conducted a substudy on the burden of anemia [trimester 1/3: hemoglobin (Hb) <11.0 g/dL; trimester 2: Hb <10.5 g/dL; n = 367] and micronutrient deficiencies ( n = 127) in pregnant WLHIV and their associations with obstetric and infant outcomes. Hb was measured by cyanmethemoglobin, vitamin B-12 and folate were measured via electrochemiluminescence, and vitamin D was measured by ELISA. Linear and binomial regression were used to evaluate associations between micronutrient status during pregnancy and perinatal outcomes.

          Results

          26.8% women were anemic, 30.2% were vitamin B-12 insufficient (<221.0 pmol/L), 66.1% were folate insufficient (<13.5 nmol/L), and 65.4% were vitamin D insufficient (<30.0 ng/mL) at enrollment. Anemia during pregnancy was associated with a greater risk of small for gestational age (SGA) (RR: 1.88; 95% CI: 1.28, 2.77; P = 0.001); each 1-g/dL decrease in Hb was associated with greater risk of SGA (RR: 0.76; 95% CI: 0.65, 0.90; P = 0.001). Multivariate models showed that increased vitamin D concentrations predicted lower risk of infant wasting (WLZ < −2; RR: 0.94; 95% CI: 0.89, 0.99; P = 0.04). Multivariate models also indicated that maternal vitamin B-12 and folate concentrations at enrollment predicted maternal ( P < 0.001) and infant ( P = 0.02) concentrations postpartum.

          Conclusions

          Anemia and micronutrient deficiencies are associated with a variety of adverse obstetric and infant outcomes and are an important public health concern in perinatal WLHIV on cART and their children.

          This trial was registered at clinicaltrials.gov as NCT00993031.

          Abstract

          Anemia and micronutrient deficiencies were common among perinatal Ugandan women living with HIV and initiating combined antiretroviral therapy, as well as their infants. Lower hemoglobin, folate, vitamin D and vitamin B12 deficiencies were associated with a variety of adverse obstetric and infant outcomes. These data suggest micronutrient deficiencies likely remain an important public health concern for vulnerable populations, even in the era of combined antiretroviral therapy.

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          Most cited references58

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          Maternal anemia and risk of adverse birth and health outcomes in low- and middle-income countries: systematic review and meta-analysis.

          Anemia is a leading cause of maternal deaths and adverse pregnancy outcomes in developing countries.
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            Vitamin D: its role and uses in immunology.

            In recent years there has been an effort to understand possible noncalcemic roles of vitamin D, including its role in the immune system and, in particular, on T cell-medicated immunity. Vitamin D receptor is found in significant concentrations in the T lymphocyte and macrophage populations. However, its highest concentration is in the immature immune cells of the thymus and the mature CD-8 T lymphocytes. The significant role of vitamin D compounds as selective immunosuppressants is illustrated by their ability to either prevent or markedly suppress animal models of autoimmune disease. Results show that 1,25-dihydroxyvitamin D3 can either prevent or markedly suppress experimental autoimmune encephalomyelitis, rheumatoid arthritis, systemic lupus erythematosus, type I diabetes, and inflammatory bowel disease. In almost every case, the action of the vitamin D hormone requires that the animals be maintained on a normal or high calcium diet. Possible mechanisms of suppression of these autoimmune disorders by the vitamin D hormone have been presented. The vitamin D hormone stimulates transforming growth factor TGFbeta-1 and interleukin 4 (IL-4) production, which in turn may suppress inflammatory T cell activity. In support of this, the vitamin D hormone is unable to suppress a murine model of the human disease multiple sclerosis in IL-4-deficient mice. The results suggest an important role for vitamin D in autoimmune disorders and provide a fertile and interesting area of research that may yield important new therapies.
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              The World Health Organization Global Database on Child Growth and Malnutrition: methodology and applications.

              For decades nutritional surveys have been conducted using various definitions, indicators and reference populations to classify child malnutrition. The World Health Organization (WHO) Global Database on Child Growth and Malnutrition was initiated in 1986 with the objective to collect, standardize, and disseminate child anthropometric data using a standard format. The database includes population-based surveys that fulfil a set of criteria. Data are checked for validity and consistency and raw data sets are analysed following a standard procedure to obtain comparable results. Prevalences of wasting, stunting, under- and overweight in preschool children are presented using z-scores based on the National Center for Health Statistics (NCHS)/WHO international reference population. New surveys are included on a continuous basis and updates are published bimonthly on the database's web site. To date, the database contains child anthropometric information derived from 846 surveys. With 412 national surveys from 138 countries and 434 sub-national surveys from 155 countries, the database covers 99% and 64% of the under 5 year olds in developing and developed countries, respectively. This wealth of information enables international comparison of nutritional data, helps identifying populations in need, evaluating nutritional and other public health interventions, monitoring trends in child growth, and raising political awareness of nutritional problems. The 15 years experience of the database can be regarded as a success story of international collaboration in standardizing child growth data. We recommend this model for monitoring other nutritional health conditions that as yet lack comparable data.
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                Author and article information

                Contributors
                Journal
                Curr Dev Nutr
                Curr Dev Nutr
                cdn
                Current Developments in Nutrition
                Oxford University Press
                2475-2991
                25 April 2020
                May 2020
                25 April 2020
                : 4
                : 5
                : nzaa075
                Affiliations
                [1 ] Division of Nutritional Sciences, Cornell University , Ithaca, NY, USA
                [2 ] Center for AIDS Prevention Studies, University of California San Francisco , San Francisco, CA, USA
                [3 ] Infectious Diseases Research Collaboration, Kampala, Uganda
                [4 ] Department of Medicine, University of California San Francisco , San Francisco, CA, USA
                [5 ] Department of Medicine, Makerere University , Kampala, Uganda
                [6 ] Division of Infectious Disease, Department of Pediatrics, UCSF Benioff Children's Hospital, University of California San Francisco , San Francisco, CA, USA
                [7 ] Department of Obstetrics and Gynecology, University of California San Francisco , San Francisco, CA, USA
                [8 ] Department of Anthropology and Global Health Studies, Northwestern University , Evanston, IL, USA
                [9 ] Institute for Policy Research, Northwestern University , Evanston, IL, USA
                Author notes
                Address correspondence to SLY (e-mail: sera.young@ 123456northwestern.edu )
                Author information
                http://orcid.org/0000-0001-9512-5559
                http://orcid.org/0000-0003-3788-0665
                http://orcid.org/0000-0002-1763-1218
                Article
                nzaa075
                10.1093/cdn/nzaa075
                7229869
                32440638
                49811d54-7fcf-4bc3-abbb-5f88e044474e
                Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@ 123456oup.com

                History
                : 06 December 2019
                : 18 March 2020
                : 09 April 2020
                Page count
                Pages: 12
                Funding
                Funded by: U.S. President’s Emergency Plan for AIDS Relief, DOI 10.13039/100009054;
                Funded by: National Institutes of Health, DOI 10.13039/100000002;
                Award ID: P01HD059454
                Award ID: K01MH098902
                Categories
                ORIGINAL RESEARCH
                Maternal and Pediatric Nutrition
                AcademicSubjects/MED00060

                anemia,vitamin d,vitamin b-12,folate,sub-saharan africa,pregnant,postpartum,micronutrient,aids

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