Anemia and adverse outcomes in pregnancy: subgroup analysis of the CLIP cluster-randomized trial in India

Springer Science and Business Media LLC - Tập 22 - Trang 1-11 - 2022
Jeffrey N. Bone1,2, Mrutyunjaya Bellad3, Shivaprasad Goudar3, Ashalata Mallapur4, Umesh Charantimath3, Umesh Ramadurg4, Geetanjali Katageri4, Maria Lesperance5, Mai-Lei Woo Kinshella1, Raiya Suleman6, Marianne Vidler1, Sumedha Sharma1, Richard Derman7, Laura A. Magee8, Peter von Dadelszen8
1Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, Canada
2British Columbia Children’s Hospital Research Institute, Vancouver, Canada
3KLE Academy of Higher Education and Research’s J N Medical College, Belagavi, India
4S Nijalingappa Medical College and Hanagal Shree Kumareshwar Hospital and Research Center, Bagalkote, India
5Richmond Division of Family Practice, Vancouver Coastal Health, Vancouver, Canada
6Faculty of Medicine, University of British Columba, Vancouver, Canada
7Global Affairs, Thomas Jefferson University, Philadelphia, USA
8Department of Women and Children’s Health, School of Life Course Sciences, Faculty of Life Science and Medicine, Kings College London, London, UK

Tóm tắt

Iron-deficiency anemia is a known risk factor for several adverse perinatal outcomes, but data on its impact on specific maternal morbidities is less robust. Further, information on associations between anemia in early pregnancy and subsequent outcomes are understudied. The study population was derived from the Community Level Interventions for Pre-eclampsia (CLIP) trial in Karnataka State, India (NCT01911494). Included were women who were enrolled in either trial arm, delivered by trial end date, and had a baseline measure of hemoglobin (Hb). Anemia was classified by WHO standards into four groups: none (Hb ≥ 11 g/dL), mild (10.0 g/dL ≤ Hb < 11.0 g/dL), moderate (7.0 g/dL ≤ Hb < 10.0 g/dL) and severe (Hb < 7.0 g/dL). Targeted maximum likelihood estimation was used to estimate confounder-adjusted associations between anemia and a composite (and its components) of adverse maternal outcomes, including pregnancy hypertension. E-values were calculated to assess robustness to unmeasured confounding. Of 11,370 women included, 10,066 (88.5%) had anemia, that was mild (3690, 32.5%), moderate (6023, 53.0%), or severe (68, 0.6%). Almost all women (> 99%) reported taking iron supplements during pregnancy. Blood transfusions was more often administered to those with anemia that was mild (risk ratio [RR] 2.16, 95% confidence interval [CI] 1.31–3.56), moderate (RR 2.37, 95% CI 1.56–3.59), and severe (RR 5.70, 95% CI 3.00–10.85). No significant association was evident between anemia severity and haemorrhage (antepartum or postpartum) or sepsis, but there was a U-shaped association between anemia severity and pregnancy hypertension and pre-eclampsia specifically, with the lowest risk seen among those with mild or moderate anemia. In Karnataka State, India, current management strategies for mild-moderate anemia in early pregnancy are associated with similar rates of adverse maternal or perinatal outcomes, and a lower risk of pregnancy hypertension and preeclampsia, compared with no anemia in early pregnancy. Future research should focus on risk mitigation for women with severe anemia, and the potential effect of iron supplementation for women with normal Hb in early pregnancy.

Tài liệu tham khảo

McLean E, Cogswell M, Egli I, Wojdyla D, de Benoist B. Worldwide prevalence of anaemia, WHO Vitamin and Mineral Nutrition Information System, 1993–2005. Public Health Nutr. 2009;12(4):444–54. Lee AI, Okam MM. Anemia in Pregnancy. Hematol Oncol Clin North Am. 2011;25(2):241–59. Balarajan Y, Ramakrishnan U, Özaltin E, Shankar AH, Subramanian SV. Anaemia in low-income and middle-income countries. The Lancet. 2011;378(9809):2123–35. Stevens GA, Finucane MM, De-Regil LM, Paciorek CJ, Flaxman SR, Branca F, et al. Global, regional, and national trends in haemoglobin concentration and prevalence of total and severe anaemia in children and pregnant and non-pregnant women for 1995–2011: a systematic analysis of population-representative data. Lancet Glob Health. 2013;1(1):e16-25. Kalaivani K, Ramachandran P. Time trends in prevalence of anaemia in pregnancy. Indian J Med Res. 2018;147(3):268. Rahman MM, Abe SK, Rahman MS, Kanda M, Narita S, Bilano V, et al. Maternal anemia and risk of adverse birth and health outcomes in low- and middle-income countries: systematic review and meta-analysis1,2. Am J Clin Nutr. 2016;103(2):495–504. Rahmati S, Delpishe A, Azami M, Hafezi Ahmadi MR, Sayehmiri K. Maternal Anemia during pregnancy and infant low birth weight: A systematic review and Meta-analysis. Int J Reprod Biomed. 2017;15(3):125–34. Figueiredo ACMG, Gomes-Filho IS, Silva RB, Pereira PPS, Mata FAFD, Lyrio AO, et al. Maternal Anemia and Low Birth Weight: A Systematic Review and Meta-Analysis. Nutrients. 2018 May 12;10(5). Jessani S, Saleem S, Hoffman MK, Goudar SS, Derman RJ, Moore JL, et al. Association of haemoglobin levels in the first trimester and at 26–30 weeks with fetal and neonatal outcomes: a secondary analysis of the Global Network for Women’s and Children’s Health’s ASPIRIN Trial. BJOG Int J Obstet Gynaecol [Internet]. [cited 2021 May 20];n/a(n/a). Available from: https://obgyn.onlinelibrary.wiley.com/doi/abs/https://doi.org/10.1111/1471-0528.16676 Daru J, Zamora J, Fernández-Félix BM, Vogel J, Oladapo OT, Morisaki N, et al. Risk of maternal mortality in women with severe anaemia during pregnancy and post partum: a multilevel analysis. Lancet Glob Health. 2018;6(5):e548–54. Say L, Chou D, Gemmill A, Tunçalp Ö, Moller A-B, Daniels J, et al. Global causes of maternal death: a WHO systematic analysis. Lancet Glob Health. 2014;2(6):e323-333. Severe Maternal Sepsis in the UK, 2011–2012: A National Case-Control Study [Internet]. [cited 2021 Apr 12]. Available from: https://journals.plos.org/plosmedicine/article?id=https://doi.org/10.1371/journal.pmed.1001672 Rukuni R, Bhattacharya S, Murphy MF, Roberts D, Stanworth SJ, Knight M. Maternal and neonatal outcomes of antenatal anemia in a Scottish population: a retrospective cohort study. Acta Obstet Gynecol Scand. 2016;95(5):555–64. Kassa GM, Muche AA, Berhe AK, Fekadu GA. Prevalence and determinants of anemia among pregnant women in Ethiopia; a systematic review and meta-analysis. BMC Hematol [Internet]. 2017 Oct 17 [cited 2021 Apr 8];17. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5646153/ Ali SA, Tikmani SS, Saleem S, Patel AB, Hibberd PL, Goudar SS, et al. Hemoglobin concentrations and adverse birth outcomes in South Asian pregnant women: findings from a prospective Maternal and Neonatal Health Registry. Reprod Health. 2020;17(Suppl 2):154. Rath WH. Postpartum hemorrhage–update on problems of definitions and diagnosis. Acta Obstet Gynecol Scand. 2011;90(5):421–8. Imdad A, Bhutta ZA. Routine iron/folate supplementation during pregnancy: effect on maternal anaemia and birth outcomes. Paediatr Perinat Epidemiol. 2012;26(Suppl 1):168–77. Peña-Rosas JP, De-Regil LM, Garcia-Casal MN, Dowswell T. Daily oral iron supplementation during pregnancy. Cochrane Database Syst Rev. 2015;7:CD004736. Zhao G, Xu G, Zhou M, Jiang Y, Richards B, Clark KM, et al. Prenatal Iron Supplementation Reduces Maternal Anemia, Iron Deficiency, and Iron Deficiency Anemia in a Randomized Clinical Trial in Rural China, but Iron Deficiency Remains Widespread in Mothers and Neonates123. J Nutr. 2015;145(8):1916–23. Bellad MB, Goudar SS, Mallapur AA, Sharma S, Bone J, Charantimath US, et al. Community level interventions for pre-eclampsia (CLIP) in India: A cluster randomised controlled trial. Pregnancy Hypertens. 2020;1(21):166–75. Goudar SS, Stolka KB, Koso-Thomas M, Honnungar NV, Mastiholi SC, Ramadurg UY, et al. Data quality monitoring and performance metrics of a prospective, population-based observational study of maternal and newborn health in low resource settings. Reprod Health. 2015;12(2):S2. Payne BA, Hutcheon JA, Ansermino JM, Hall DR, Bhutta ZA, Bhutta SZ, et al. A risk prediction model for the assessment and triage of women with hypertensive disorders of pregnancy in low-resourced settings: the miniPIERS (Pre-eclampsia Integrated Estimate of RiSk) multi-country prospective cohort study. PLoS Med. 2014;11(1): e1001589. Nathan HL, de Greeff A, Hezelgrave NL, Chappell LC, Shennan AH. An accurate semiautomated oscillometric blood pressure device for use in pregnancy (including pre-eclampsia) in a low-income and middle-income country population: the Microlife 3AS1-2. Blood Press Monit. 2015;20(1):52–5. Magee LA, Sharma S, Nathan HL, Adetoro OO, Bellad MB, Goudar S, et al. The incidence of pregnancy hypertension in India, Pakistan, Mozambique, and Nigeria: A prospective population-level analysis. PLOS Med. 2019;16(4): e1002783. Greenland S, Pearce N. Statistical Foundations for Model-Based Adjustments. Annu Rev Public Health. 2015;36(1):89–108. Laan MJ van der, Rose S. Targeted Learning: Causal Inference for Observational and Experimental Data. Springer Science & Business Media; 2011. 678 p. Benkeser D, Carone M, Laan MJVD, Gilbert PB. Doubly robust nonparametric inference on the average treatment effect. Biometrika. 2017;104(4):863–80. Schnitzer ME, van der Laan MJ, Moodie EEM, Platt RW. EFFECT OF BREASTFEEDING ON GASTROINTESTINAL INFECTION IN INFANTS: A TARGETED MAXIMUM LIKELIHOOD APPROACH FOR CLUSTERED LONGITUDINAL DATA. Ann Appl Stat. 2014;8(2):703–25. VanderWeele TJ, Ding P. Sensitivity Analysis in Observational Research: Introducing the E-Value. Ann Intern Med. 2017;167(4):268–74. R Core Team (2020). R: A language and environment for statistical computing. R Foundation for Statistical Computing [Internet]. Vienna, Austria.; Available from: URL https://www.R-project.org/ Wasserstein RL, Lazar NA. The ASA Statement on p-Values: Context, Process, and Purpose. Am Stat. 2016;70(2):129–33. District-wise Key Indicators of NFHS-4 for Karnataka [Internet]. Open Government Data (OGD) Platform India. 2017 [cited 2021 Apr 8]. Available from: https://data.gov.in/resources/district-wise-key-indicators-nfhs-4-karnataka Patel A, Prakash AA, Das PK, Gupta S, Pusdekar YV, Hibberd PL. Maternal anemia and underweight as determinants of pregnancy outcomes: cohort study in eastern rural Maharashtra, India. BMJ Open. 2018;8(8): e021623. Finkelstein JL, Kurpad AV, Bose B, Thomas T, Srinivasan K, Duggan C. Anaemia and iron deficiency in pregnancy and adverse perinatal outcomes in Southern India. Eur J Clin Nutr. 2020;74(1):112–25. Allen LH. Anemia and iron deficiency: effects on pregnancy outcome. Am J Clin Nutr. 2000;71(5):1280S-1284S. Nair M, Churchill D, Robinson S, Nelson-Piercy C, Stanworth SJ, Knight M. Association between maternal haemoglobin and stillbirth: a cohort study among a multi-ethnic population in England. Br J Haematol. 2017;179(5):829–37. Jung J, Rahman MM, Rahman MS, Swe KT, Islam MR, Rahman MO, et al. Effects of hemoglobin levels during pregnancy on adverse maternal and infant outcomes: a systematic review and meta-analysis. Ann N Y Acad Sci. 2019;1450(1):69–82. Ali AA, Rayis DA, Abdallah TM, Elbashir MI, Adam I. Severe anaemia is associated with a higher risk for preeclampsia and poor perinatal outcomes in Kassala hospital, eastern Sudan. BMC Res Notes. 2011;26(4):311. Dewey KG, Oaks BM. U-shaped curve for risk associated with maternal hemoglobin, iron status, or iron supplementation. Am J Clin Nutr. 2017;106(Suppl 6):1694S-1702S. Bakacak M, Avci F, Ercan O, Köstü B, Serin S, Kiran G, et al. The effect of maternal hemoglobin concentration on fetal birth weight according to trimesters. J Matern-Fetal Neonatal Med Off J Eur Assoc Perinat Med Fed Asia Ocean Perinat Soc Int Soc Perinat Obstet. 2015;28(17):2106–10. Agarwal KN, Agarwal DK, Sharma A, Sharma K, Prasad K, Kalita MC, et al. Prevalence of anaemia in pregnant & lactating women in India. Indian J Med Res. 2006;124(2):173–84. Ahamed F, Yadav K, Kant S, Saxena R, Bairwa M, Pandav CS. Effect of directly observed oral iron supplementation during pregnancy on iron status in a rural population in Haryana: A randomized controlled trial. Indian J Public Health. 2018;62(4):287–93. Sajith M, Nimbargi V, Shah S, Tekawade S, Agiwale J, Pawar A. Correlations of adherence to iron supplements and prevalence of anemia in antenatal women. Int J Reprod Contracept Obstet Gynecol. 2016;5(10):3448–52.