13May 2018

CAN VITAMIN D SUPPLEMENTAL THERAPY IMPROVE PREGNANCY-ASSOCIATED ANEMIA AN INTERVENTIONAL PROSPECTIVE CLINICAL TRIAL.

  • Departments of Obstetrics & Gynecology, Faculty of Medicine, Benha University.
  • Departments of Clinical Pathology, Faculty of Medicine, Benha University.
Crossref Cited-by Linking logo
  • Abstract
  • Keywords
  • References
  • Cite This Article as
  • Corresponding Author

Objectives: To evaluate impact of vitamin D supplemental therapy (VD-ST) and iron ST (IST) on hemoglobin concentration (HC) in pregnant women. Patients & Methods: 187 women pregnant were clinically evaluated and gave blood samples at 1st trimester for estimation of HC and serum 25OH-VD, ferritin concentration (FC), hepcidin (HPC) and interleukin-6 (IL-6). Women were categorized according to the levels of estimated parameters into control and study groups A-D. Women of groups A and C received VD-ST alone, group B received IST alone and group D received both ST. At delivery, HC, extent of change and frequency of pregnancy- associated anemia (PAA) were determined. Results: At 1st trimester, 71.7% women were anemic and 38.5% had hypoferremia, 77% had VD deficiency (VDD) and 59.4% had both VDD and PAA. Serum HPC and IL-6 levels in anemic women especially those had VDD were significantly higher than control women. At delivery, 35% of control women developed PAA and mean HC was significantly lower than 1st trimester HC with a median deficit of 4.72 gm/dl (IQR: 2.8-6.4) among studied population. Frequency of anemic women in groups B-D was decreased at delivery by 21.7%, 30.8% and 30.6%, respectively. Statistical analyses defined high serum HPC and IL-6 levels at 1st trimester as specific early predictors for PAA development, but early institution of ST especially VD-ST is one of the best significant predictors for improved HC at time of delivery. Conclusion: VDD, hypoferremia, higher HPC and IL-6 levels constitute a vicious circle entrapping pregnant women and inducing iron deficiency anemia at delivery. Early institution of VD-ST and IST can burst this circle and induce improvement of HC up to normal range in about 30% of women presented by PAA. Thus, early estimation of HC and serum VD can be used as a guide for early institution of ST.

  1. Cesareo R, Attanasio R, Caputo M, Castello R, Chiodini I, Falchetti A, Guglielmi R, Papini E, Santonati A, Scillitani A, Toscano V, Triggiani V, Vescini F, Zini M; AME and Italian AACE Chapter: Italian Association of Clinical Endocrinologists (AME) and Italian Chapter of the American Association of Clinical Endocrinologists (AACE) Position Statement: Clinical Management of Vitamin D Deficiency in Adults. Nutrients. 2018 Apr 27;10(5).
  2. Agudelo-Zapata Y, Maldonado-Acosta LM, Sandoval-Alzate HF, Poveda NE, Garc?s MF, Cort?s-V?squez JA, Linares-Vaca AF, Mancera-Rodr?guez CA, Perea-Ariza SA, Ram?rez-Iriarte KY, Castro-Saldarriaga CA, Arteaga-Diaz JM, Franco-Vega R, Angel-Muller E, Parada-Ba?os AJ, Caminos JE: Serum 25-hydroxyvitamin D levels throughout pregnancy: a longitudinal study in healthy and preeclamptic pregnant women. Endocr Connect. 2018 Apr 17. pii: EC-18-0055. doi: 10.1530/EC-18-0055. [Epub ahead of print]
  3. Ji?JL,?Muyayalo KP,?Zhang YH,?Hu XH,?Liao AH: Immunological function of?vitamin D?during human pregnancy. Am J Reprod Immunol.?2017; 78(2).
  4. Olmos-Ortiz A, Avila E, Durand-Carbajal M, D?az L: Regulation of calcitriol biosynthesis and activity: focus on gestational vitamin D deficiency and adverse pregnancy outcomes. Nutrients. 2015; 7(1):443-80.
  5. Tamblyn JA, Hewison M, Wagner CL, Bulmer JN, Kilby MD: Immunological role of vitamin D at the maternal-fetal interface. J Endocrinol. 2015; 224(3):R107-21.
  6. Karras SN, Wagner CL, Castracane VD: Understanding vitamin D metabolism in pregnancy: From physiology to pathophysiology and clinical outcomes. Metabolism. 2017 Oct 21. pii: S0026-0495(17)30275-5. doi: 10.1016/j.metabol.2017.10.001. [Epub ahead of print]
  7. Page CM, Patel A, Hibberd PL: Does smoke from biomass fuel contribute to anemia in pregnant women in Nagpur, India? A cross-sectional study. PLoS One. 2015; 10(5):e0127890.
  8. McArdle HJ, Gambling L, Kennedy C: Iron deficiency during pregnancy: the consequences for placental function and fetal outcome. Proc Nutr Soc. 2014; 73(1):9-15.
  9. Breymann C: Iron Deficiency Anemia in Pregnancy. Semin Hematol. 2015; 52(4):339-47.
  10. Ross AC: Impact of chronic and acute inflammation on extra- and intracellular iron homeostasis. Am J Clin Nutr. 2017;106(Suppl 6):1581S-1587S.
  11. Koenig MD, Tussing-Humphreys L, Day J, Cadwell B, Nemeth E: Hepcidin and iron homeostasis during pregnancy. Nutrients. 2014; 6(8):3062-83.
  12. Bacchetta J, Zaritsky JJ, Sea JL, Chun RF, Lisse TS, Zavala K, Nayak A, Wesseling-Perry K, Westerman M, Hollis BW, Salusky IB, Hewison M: Suppression of iron-regulatory hepcidin by vitamin D. J Am Soc Nephrol. 2014; 25(3): 564-72.
  13. Tabbah SM, Buhimschi CS, Rodewald-Millen K, Pierson CR, Bhandari V, Samuels P, Buhimschi IA: Hepcidin, an Iron Regulatory Hormone of Innate Immunity, is Differentially Expressed in Premature Fetuses with Early-Onset Neonatal Sepsis. Am J Perinatol. 2018 Feb 2. doi: 10.1055/s-0038-1626711. [Epub ahead of print]
  14. Ruchala P, Nemeth E: The pathophysiology and pharmacology of hepcidin. Trends Pharmacol Sci. 2014; 35(3):155-61.
  15. Li S, Liu Y, Wang Y, Qi P, Wang D: The role of serum hepcidin and ferroportin1 in placenta on iron transfer from mother to fetus. Zhonghua Xue Ye Xue Za Zhi. 2015; 36(4):307-11.
  16. McDonagh M, 5BAuthor%5D&cauthor=true&cauthor_uid=26404445\"Cantor A1, 5BAuthor%5D&cauthor=true&cauthor_uid=26404445\"Bougatsos C1, 5BAuthor%5D&cauthor=true&cauthor_uid=26404445\"Dana T, Blazina I: Routine Iron Supplementation and Screening for Iron Deficiency Anemia in Pregnant Women: A Systematic Review to Update the U.S. Preventive Services Task Force Recommendation [Internet]. U.S. Preventive Services Task Force Evidence Syntheses, formerly Systematic Evidence Reviews. Rockville (MD): Agency for Healthcare Research and Quality (US); 2015 Mar. Report No.: 13-05187-EF-2.
  17. Domell?f M, Thorsdottir I, Thorstensen K: Health effects of different dietary iron intakes: a systematic literature review for the 5th Nordic Nutrition Recommendations. Food Nutr Res. 2013, 12; 57.
  18. Kinnunen TI, Luoto R, Helin A, Hemminki E: Supplemental iron intake and the risk of glucose intolerance in pregnancy: re-analysis of a randomised controlled trial in Finland. Matern Child Nutr. 2016; 12(1):74-84.
  19. Harvey NC, Holroyd C, Ntani G, Javaid K, Cooper P, Moon R, Cole Z, Tinati T, Godfrey K, Dennison E, Bishop NJ, Baird J, Cooper C: Vitamin D supplementation in pregnancy: a systematic review. Health Technol Assess. 2014; 18(45):1-190.
  20. P?rez-L?pez FR, Pasupuleti V, Mezones-Holguin E, Benites-Zapata VA, Thota P, Deshpande A, Hernandez AV: Effect of vitamin D supplementation during pregnancy on maternal and neonatal outcomes: a systematic review and meta-analysis of randomized controlled trials. Fertil Steril. 2015; 103(5):1278-88
  21. Stroud?ML,?Stilgoe S,?Stott VE,?Alhabian O,?Salman K: Vitamin D?- a review. Aust Fam Physician.?2008; 37(12):1002-5.
  22. Api O, Breyman C, ?etiner M, Demir C, Ecder T: Diagnosis and treatment of iron deficiency anemia during pregnancy and the postpartum period: Iron deficiency anemia working group consensus report. Turk J Obstet Gynecol. 2015; 12(3):173-181.
  23. Andersen L, Dinesen B, J?rgensen PN, Poulsen F, R?der ME: Enzyme immunoassay for intact human insulin in serum or plasma. Clinical Chemistry, 1993; 38: 578-82.
  24. Jacobs A, Warwood MJ: Ferritin in serum. Clinical and biochemical implications. N.Eng. J. Med., 1975; 292(18): 951-6.
  25. Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, Ganz T: Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science, 2004; 306(5704): 2090-3.
  26. Gaines-Das RE, Poole S: The international standard for interleukin-6?evaluation in an international collaborative study. J Immunol Methods. 1993; 160: 147?53.
  27. Grant CC,?Stewart AW,?Scragg R,?Milne T,?Rowden J,?Ekeroma A,?Wall C,?Mitchell EA,?Crengle S,?Trenholme A,?Crane J,?Camargo CA Jr: Vitamin D during pregnancy and infancy and infant serum 25-hydroxyvitamin D concentration. Pediatrics.?2014; 133(1):e143-53
  28. Abbas W, Adam I, Rayis DA, Hassan NG, Lutfi MF: Higher Rate of Iron Deficiency in Obese Pregnant Sudanese Women. Open Access Maced J Med Sci. 2017; 5(3):285-289.
  29. Milman N, Taylor CL, Merkel J, Brannon PM: Iron status in pregnant women and women of reproductive age in Europe. Am J Clin Nutr. 2017; 106(Suppl 6):1655S-1662S.
  30. Bah A, Pasricha SR, Jallow MW, Sise EA, Wegmuller R, Armitage AE, Drakesmith H, Moore SE, Prentice AM: Serum Hepcidin Concentrations Decline during Pregnancy and May Identify Iron Deficiency: Analysis of a Longitudinal Pregnancy Cohort in The Gambia. J Nutr. 2017; 147(6):1131-7.
  31. Ahmed F, Khan MR, Shaheen N, Ahmed KMU, Hasan A, Chowdhury IA, Chowdhury R: Anemia and iron deficiency in rural Bangladeshi pregnant women living in areas of high and low iron in groundwater. Nutrition. 2018; 51-52:46-52.
  32. Michalski ES, Nguyen PH, Gonzalez-Casanova I, Nguyen SV, Martorell R, Tangpricha V, Ramakrishnan U: Serum 25-hydroxyvitamin D but not dietary vitamin D intake is associated with hemoglobin in women of reproductive age in rural northern Vietnam. J Clin Transl Endocrinol. 2017; 8:41-8.
  33. Yuan Y, Cai Z, Dai Y, Hong Q, Wang X, Zhu L, Xu P, You L, Wang X, Ji C, Wen J, Guo X: Association of Maternal Serum 25-Hydroxyvitamin D Concentrations with Risk of Gestational Anemia. Cell Physiol Biochem. 2017; 43(4):1526-32.
  34. Al-Ajlan A, Al-Musharaf S, Fouda MA, Krishnaswamy S, Wani K, Aljohani NJ, Al-Serehi A, Sheshah E, Alshingetti NM, Turkistani IZ, Afrah Alharbi A, Alraqebah BA, Ali AM, Al-Saeed G, Al-Daghri NM: Lower vitamin D levels in Saudi pregnant women are associated with higher risk of developing GDM. BMC Pregnancy Childbirth. 2018; 18(1):86.
  35. Krieger JP, Cabaset S, Canonica C, Christoffel L, Richard A, Schr?der T, von Wattenwyl BL, Rohrmann S, L?tscher KQ: Prevalence and determinants of vitamin D deficiency in the third trimester of pregnancy: a multicentre study in Switzerland. Br J Nutr. 2018 Feb; 119(3):299-309.
  36. Wheeler BJ, Taylor BJ, de Lange M, Harper MJ, Jones S, Mekhail A, Houghton LA: A Longitudinal Study of 25-Hydroxy Vitamin D and Parathyroid Hormone Status throughout Pregnancy and Exclusive Lactation in New Zealand Mothers and Their Infants at 45? S. Nutrients. 2018 Jan 13;10(1).
  37. Akoh CC, Pressman EK, Cooper E, Queenan RA, Pillittere J, O\'Brien KO: Low Vitamin D is Associated With Infections and Proinflammatory Cytokines During Pregnancy. Reprod Sci. 2018; 25(3):414-423.
  38. Cutone A, Rosa L, Lepanto MS, Scotti MJ, Berlutti F, Bonaccorsi di Patti MC, Musci G, Valenti P: Lactoferrin Efficiently Counteracts the Inflammation-Induced Changes of the Iron Homeostasis System in Macrophages. Front Immunol. 2017; 8:705.
  39. Rosa L, Cutone A, Lepanto MS, Paesano R, Valenti P: Lactoferrin: A Natural Glycoprotein Involved in Iron and Inflammatory Homeostasis. Int J Mol Sci. 2017;18(9).
  40. Zittermann A, Jungvogel A, Prokop S, Kuhn J, Dreier J, Fuchs U, et al. Vitamin D deficiency is an independent predictor of anemia in end-stage heart failure.?Clin Res Cardiol.?2011;100:781?8.
  41. Ernst JB, Becker T, Kuhn J, Gummert JF, Zittermann A. Independent association of circulating Vitamin D metabolites with anemia risk in patients scheduled for cardiac surgery.?PLoS One.?2015;10: e0124751.
  42. Smith EM, Tangpricha V: Vitamin D and anemia: insights into an emerging association. Curr Opin Endocrinol Diabetes Obes. 2015; 22(6):432-8.
  43. Sharma S, Jain R, Dabla PK: The role of 25-hydroxy Vitamin D deficiency in iron deficient children of North India.?Indian J Clin Biochem.?2015; 30:313?7.
  44. Thomas CE, Guillet R, Queenan RA, Cooper EM, Kent TR, Pressman EK, Vermeylen FM, Roberson MS, O\'Brien KO: Vitamin D status is inversely associated with anemia and serum erythropoietin during pregnancy. Am J Clin Nutr. 2015; 102(5):1088-95.
  45. Azizi-Soleiman F, Vafa M, Abiri B, Safavi M: Effect of iron on vitamin D metabolism: A Systemic Review. Int J Prev Med., 2016; 7: 126.

[Ayman A. Shedid MD and Amira MN Abdelrahman MD. (2018); CAN VITAMIN D SUPPLEMENTAL THERAPY IMPROVE PREGNANCY-ASSOCIATED ANEMIA AN INTERVENTIONAL PROSPECTIVE CLINICAL TRIAL. Int. J. of Adv. Res. 6 (May). 140-149] (ISSN 2320-5407). www.journalijar.com

Ayman A. Shedid
Departments of Obstetrics & Gynecology, Faculty of Medicine, Benha University, Benha, Egypt.

DOI:

Article DOI: 10.21474/IJAR01/7017      
DOI URL: http://dx.doi.org/10.21474/IJAR01/7017

Download Full Paper

Download PDF No. of Downloads: 11 | No. of Views: 60