Effects of Iron and Vitamin A Levels on Pregnant Women and Birth Outcomes: Complex Relationships Untangled Using a Birth Cohort Study in Uganda

Julieta Mezzano, Grace Namirembe, Lynne M Ausman, Elizabeth Marino-Costello, Robin Shrestha, Juergen Erhardt, Patrick Webb, Shibani Ghosh, Julieta Mezzano, Grace Namirembe, Lynne M Ausman, Elizabeth Marino-Costello, Robin Shrestha, Juergen Erhardt, Patrick Webb, Shibani Ghosh

Abstract

Introduction: Women and infants are among the most vulnerable groups for micronutrient deficiencies. Pregnancy micronutrient status can affect birth outcomes and subsequent infants' growth.

Methods: We determined the relationship between maternal iron and vitamin A status at delivery using several biomarkers (ferritin, soluble transferrin receptor [sTFR], body iron stores [BIS], hemoglobin and retinol binding protein [RBP]) and birth outcomes (body weight, Z-scores, head circumference, small-for-gestational-age and preterm birth) in rural Uganda. We investigated women who had serum results at the point of delivery and paired them to their infants at birth (n = 1244). We employed multivariable linear and logistic regression, adjusting for clustering at the subcounty level to determine the relationship between maternal micronutrients and birth outcomes.

Results: After adjusting for relevant factors, we found that maternal iron status (ferritin and BIS) and anemia (hemoglobin) were not significantly associated with the assessed birth outcomes. However, there was a significant association between serum sTFR and preterm births (AOR: 0.67; 95% CI 0.48-0.94). For Vitamin A, we observed a significant positive association between RBP and length-for-age (LAZ) at birth (β = 0.12, p < 0.030).

Discussion: These findings indicate that the relationship between maternal iron status and birth outcomes needs to be further investigated, because depending on the biomarker used the associations were either in favor of an adverse birth outcome or not significant. Additionally, they confirm that higher maternal RBP levels could be beneficial for birth outcomes.

Clinicaltrials: gov as NCT04233944.

Keywords: Birth outcomes; Iron; Pregnancy; Uganda; Vitamin A.

Conflict of interest statement

The authors declare that they have no competing interests. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Flowchart showing the subset of study participants from the UBC study. Multiple births were not excluded from the UBC study but were omitted from the analyses
Fig. 2
Fig. 2
Correlation between maternal RBP (µmol/L) and LAZ at birth, for women in rural Uganda
Fig. 3
Fig. 3
Flowchart of participants in the UBC Study

References

    1. Alwan NA, Cade JE, McArdle HJ, Greenwood DC, Hayes HE, Simpson NAB. Maternal iron status in early pregnancy and birth outcomes: Insights from the baby’s vascular health and iron in pregnancy study. British Journal of Nutrition. 2015;113(12):1985–1992. doi: 10.1017/S0007114515001166.
    1. Baingana RK, Enyaru JK, Tjalsma H, Swinkels DW, Davidsson L. The aetiology of anaemia during pregnancy: A study to evaluate the contribution of iron deficiency and common infections in pregnant Ugandan women. Public Health Nutrition. 2015;18(8):1423–1435. doi: 10.1017/s1368980014001888.
    1. CDC. (2019). Micronutrients Facts. Retrieved August 8, 2019, from
    1. Christian P, Klemm R, Shamim AA, Ali H, Rashid M, Shaikh S, Wu L, Mehra S, Labrique A, Katz J, West KP., Jr Effects of vitamin A and beta-carotene supplementation on birth size and length of gestation in rural Bangladesh: A cluster-randomized trial. American Journal of Clinical Nutrition. 2013;97(1):188–194. doi: 10.3945/ajcn.112.042275.
    1. Coates J, Rogers BL, Blau A, Lauer J, Roba A. Filling a dietary data gap? Validation of the adult male equivalent method of estimating individual nutrient intakes from household-level data in Ethiopia and Bangladesh. Food Policy. 2017;72:27–42. doi: 10.1016/j.foodpol.2017.08.010.
    1. Col Madendag I, Eraslan Sahin M, Madendag Y, Sahin E, Demir MB, Acmaz B, Acmaz G, Muderris II. The effect of iron deficiency anemia early in the third trimester on small for gestational age and birth weight: A retrospective cohort study on iron deficiency anemia and fetal weight. BioMed Research International. 2019;2019:7613868–7613868. doi: 10.1155/2019/7613868.
    1. Cook JD, Flowers CH, Skikne BS. The quantitative assessment of body iron. Blood. 2003;101(9):3359–3364. doi: 10.1182/blood-2002-10-3071.
    1. Dewey KG, Oaks BM. U-shaped curve for risk associated with maternal hemoglobin, iron status, or iron supplementation. American Journal of Clinical Nutrition. 2017;106(Suppl 6):1694s–1702s. doi: 10.3945/ajcn.117.156075.
    1. Engle-Stone R, Haskell MJ, Ndjebayi AO, Nankap M, Erhardt JG, Gimou MM, Brown KH. Plasma retinol-binding protein predicts plasma retinol concentration in both infected and uninfected Cameroonian women and children. Journal of Nutrition. 2011;141(12):2233–2241. doi: 10.3945/jn.111.145805.
    1. Erhardt JG, Estes JE, Pfeiffer CM, Biesalski HK, Craft NE. Combined measurement of ferritin, soluble transferrin receptor, retinol binding protein, and C-reactive protein by an inexpensive, sensitive, and simple sandwich enzyme-linked immunosorbent assay technique. Journal of Nutrition. 2004;134(11):3127–3132. doi: 10.1093/jn/134.11.3127.
    1. Fisher AL, Nemeth E. Iron homeostasis during pregnancy. American Journal of Clinical Nutrition. 2017;106(Suppl 6):1567S–1574S. doi: 10.3945/ajcn.117.155812.
    1. Fowkes FJI, Moore KA, HerbertOpi D, Simpson JA, Langham F, Stanisic DI, Ura A, King CL, Siba PM, Mueller I, Rogerson SJ, Beeson JG. Iron deficiency during pregnancy is associated with a reduced risk of adverse birth outcomes in a malaria-endemic area in a longitudinal cohort study. BMC Medicine. 2018;16(1):156. doi: 10.1186/s12916-018-1146-z.
    1. Gernand AD, Schulze KJ, Stewart CP, West KP, Jr, Christian P. Micronutrient deficiencies in pregnancy worldwide: Health effects and prevention. Nature Reviews. Endocrinology. 2016;12(5):274–289. doi: 10.1038/nrendo.2016.37.
    1. Howson, C., Kinney, M., & Lawn, J. (2012). March of Dimes, PMNCH, Save the children, WHO. Born too soon: the global action report on preterm birth. Geneva: World Health Organization.
    1. Hsu W-Y, Wu C-H, Hsieh C, Lo H-C, Lin J-S, Kao M-D. Low body weight gain, low white blood cell count and high serum ferritin as markers of poor nutrition and increased risk for preterm delivery. Asia Pacific Journal of Clinical Nutrition. 2013;22:90–99. doi: 10.6133/apjcn.2013.22.1.05.
    1. Kiwanuka T, Ononge S, Kiondo P, Namusoke F. Adherence to iron supplements among women receiving antenatal care at Mulago national referral hospital, Uganda-cross-sectional study. BMC Research Notes. 2017;10:510. doi: 10.1186/s13104-017-2834-z.
    1. Larson LM, Guo J, Williams AM, Young MF, Ismaily S, Addo OY, Thurnham D, Tanumihardjo SA, Suchdev PS, Northrop-Clewes CA. Approaches to assess vitamin A status in settings of inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project. Nutrients. 2018 doi: 10.3390/nu10081100.
    1. Lynch S, Pfeiffer CM, Georgieff MK, Brittenham G, Fairweather-Tait S, Hurrell RF, McArdle HJ, Raiten DJ. Biomarkers of Nutrition for Development (BOND)-iron review. The Journal of Nutrition. 2018;148(suppl1):1001s–1067s. doi: 10.1093/jn/nxx036.
    1. Madzorera I, Ghosh S, Wang M, Fawzi W, Isanaka S, Hertzmark E, Namirembe G, Bashaasha B, Agaba E, Turyashemererwa F, Webb P, Duggan C. Prenatal dietary diversity may influence underweight in infants in a Ugandan birth-cohort. Maternal & Child Nutrition. 2021;17(3):e13127. doi: 10.1111/mcn.13127.
    1. McCauley ME, van den Broek N, Dou L, Othman M. Vitamin A supplementation during pregnancy for maternal and newborn outcomes. Cochrane Database of Systematic Reviews. 2015 doi: 10.1002/14651858.CD008666.pub3.
    1. Namaste SM, Aaron GJ, Varadhan R, Peerson JM, Suchdev PS. Methodologic approach for the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project. American Journal of Clinical Nutrition. 2017;106(Suppl 1):333s–347s. doi: 10.3945/ajcn.116.142273.
    1. Radhika MS, Bhaskaram P, Balakrishna N, Ramalakshmi BA, Devi S, Kumar BS. Effects of vitamin A deficiency during pregnancy on maternal and child health. BJOG: an International Journal of Obstetrics and Gynaecology. 2002;109(6):689–693. doi: 10.1111/j.1471-0528.2002.01010.x.
    1. Rahman MM, Abe SK, Rahman MS, Kanda M, Narita S, Bilano V, Ota E, Gilmour S, Shibuya K. Maternal anemia and risk of adverse birth and health outcomes in low- and middle-income countries: Systematic review and meta-analysis. The American Journal of Clinical Nutrition. 2016;103(2):495–504. doi: 10.3945/ajcn.115.107896.
    1. Samimi M, Asemi Z, Taghizadeh M, Azarbad Z, Rahimi-Foroushani A, Sarahroodi S. Concentrations of serum zinc, hemoglobin and ferritin among pregnant women and their effects on birth outcomes in Kashan, Iran. Oman Medical Journal. 2012;27(1):40–45. doi: 10.5001/omj.2012.08.
    1. Sapin V, Alexandre MC, Chaïb S, Bournazeau JA, Sauvant P, Borel P, Jacquetin B, Grolier P, Lémery D, Dastugue B, Azaïs-Braesco V. Effect of vitamin A status at the end of term pregnancy on the saturation of retinol binding protein with retinol. American Journal of Clinical Nutrition. 2000;71(2):537–543. doi: 10.1093/ajcn/71.2.537.
    1. Smith ER, Shankar AH, Wu LS, Aboud S, Adu-Afarwuah S, Ali H, Agustina R, Arifeen S, Ashorn P, Bhutta ZA, Christian P, Devakumar D, Dewey KG, Friis H, Gomo E, Gupta P, Kaestel P, Kolsteren P, Lanou H, Maleta K, Mamadoultaibou A, Msamanga G, Osrin D, Persson LA, Ramakrishnan U, Rivera JA, Rizvi A, Sachdev HPS, Urassa W, West KP, Jr, Zagre N, Zeng L, Zhu Z, Fawzi WW, Sudfeld CR. Modifiers of the effect of maternal multiple micronutrient supplementation on stillbirth, birth outcomes, and infant mortality: A meta-analysis of individual patient data from 17 randomised trials in low-income and middle-income countries. The Lancet Global Health. 2017;5(11):e1090–e1100. doi: 10.1016/s2214-109x(17)30371-6.
    1. Srour MA, Aqel SS, Srour KM, Younis KR, Samarah F. Prevalence of anemia and iron deficiency among palestinian pregnant women and its association with pregnancy outcome. Anemia. 2018 doi: 10.1155/2018/9135625.
    1. Tanumihardjo SA, Russell RM, Stephensen CB, Gannon BM, Craft NE, Haskell MJ, Lietz G, Schulze K, Raiten DJ. Biomarkers of Nutrition for Development (BOND)-Vitamin A review. Journal of Nutrition. 2016;146(9):1816s–1848s. doi: 10.3945/jn.115.229708.
    1. Thorne-Lyman AL, Fawzi WW. Vitamin A and carotenoids during pregnancy and maternal, neonatal and infant health outcomes: A systematic review and meta-analysis. Paediatric and Perinatal Epidemiology. 2012;26(Suppl 1):36–54. doi: 10.1111/j.1365-3016.2012.01284.x.
    1. USAID. (2015). Collaborating, learning and adapting: Experiences from first four years of the USAID community connector project (January 2012–June 2015).
    1. WHO . Guideline: Vitamin A supplementation in infants and children 6–59 months of age. World Health Organization; 2011.
    1. WHO. (2011b). Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity Retrieved October 12, 2018, from
    1. WHO. (2011c). Serum retinol concentrations for determining the prevalence of vitamin A deficiency in populations. Retrieved November 17, 2019, from
    1. Wiseman EM, Bar-El Dadon S, Reifen R. The vicious cycle of vitamin a deficiency: A review. Critical Reviews in Food Science and Nutrition. 2017;57(17):3703–3714. doi: 10.1080/10408398.2016.1160362.
    1. Yang J, Cheng Y, Pei L, Jiang Y, Lei F, Zeng L, Wang Q, Li Q, Kang Y, Shen Y, Dang S, Yan H. Maternal iron intake during pregnancy and birth outcomes: A cross-sectional study in Northwest China. British Journal of Nutrition. 2017;117(6):862–871. doi: 10.1017/s0007114517000691.
    1. Yuan X, Hu H, Zhang M, Long W, Liu J, Jiang J, Yu B. Iron deficiency in late pregnancy and its associations with birth outcomes in Chinese pregnant women: A retrospective cohort study. Nutrition & Metabolism. 2019;16:30–30. doi: 10.1186/s12986-019-0360-9.
    1. Zhang Y, Li Z, Li H, Jin L, Zhang Y, Zhang L, Liu J, Ye R, Liu J, Ren A. Maternal haemoglobin concentration and risk of preterm birth in a Chinese population. Journal of Obstetrics and Gynaecology. 2018;38(1):32–37. doi: 10.1080/01443615.2017.1325454.
    1. Zhang Y, Wray AE, Ross AC. Perinatal exposure to vitamin A differentially regulates chondrocyte growth and the expression of aggrecan and matrix metalloprotein genes in the femur of neonatal rats. Journal of Nutrition. 2012;142(4):649–654. doi: 10.3945/jn.111.152660.

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren