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A cohort study of haemoglobin and zinc protoporphyrin levels in term Zambian infants: effects of iron stores at birth, complementary food and placental malaria

Abstract

Objective:

To examine zinc-protoporphyrin (ZPP) and haemoglobin levels, and to determine predictors of iron deficiency anaemia (IDA) in Zambian infants.

Subjects and methods:

Ninety-one women and their normal birth weight (NBW) infants were followed bi-monthly during the first 6 months of life, and iron status, food intake, malaria parasitaemia and growth were monitored. At 4 months, the infants were divided into two groups, and the data were analysed according to whether or not they were exclusively breastfed.

Results:

Almost two-third of infants were born with low iron stores as defined by ZPP levels, and this proportion increased with age. Over 50% had developed IDA by 6 months. Exclusive breastfeeding at 4 months could be a protective factor for IDA (odds ratio (OR): 0.2; 95% confidence interval (CI): 0.0–1.1). Exclusively breastfed infants had higher haemoglobin values at 4 and 6 months (mean difference 0.6; 95% CI: 0.1–1.2 g/dl and mean difference 0.9; 95% CI: 0.2–1.7 g/dl, respectively), compared with infants with early complementary feeding. In univariate analysis, past or chronic placental malaria appeared to be a predictor of IDA at 4 and 6 months, but the significance was lost in multivariate analysis.

Conclusions:

Zambian NBW infants are born with low iron stores and have a high risk to develop IDA in the first 6 months of life. Continuation of exclusive breastfeeding after 4 months is associated with a reduction of anaemia. The effect of placental malaria infection on increased risk of infant IDA could not be proven.

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References

  • Arifeen S, Black RE, Antelman G, Baqui A, Caulfield L, Becker S (2001). Exclusive breastfeeding reduces acute respiratory infection and diarrhea deaths among infants in Dhaka slums. Pediatrics 108, E67.

    Article  CAS  Google Scholar 

  • Asobayire F, Adou P, Daviddson L, Cook JD, Hurrell R (2001). Prevalence of iron deficiency with and without concurrent anemia in population groups with high prevalences of malaria and other infections: a study in Cote d'Ivoire. Am J Clin Nutr 74, 776–782.

    Article  CAS  Google Scholar 

  • Brabin B (1992). Fetal anaemia in malarious areas: its causes and significance. Ann Trop Paediatr 12, 303–310.

    Article  CAS  Google Scholar 

  • Brabin BJ, Kalanda BF, Verhoeff FH, Chimsuku L, Broadhead RL (2004b). Risk factors for fetal anaemia in a malarious area of Malawi. Ann Trop Paediatr 24, 311–324.

    Article  CAS  Google Scholar 

  • Brabin BJ, Premji Z, Verhoeff F (2001). An analysis of anemia and child mortality. J Nutr 131, 636S–645S.

    Article  CAS  Google Scholar 

  • Brabin BJ, Prinsen-Geerligs P, Verhoeff F, Kazembe P (2003). Anaemia prevention for reduction of mortality in mothers and children. Trans R Soc Trop Med Hyg 97, 36–38.

    Article  Google Scholar 

  • Brabin BJ, Prinsen-Geerligs PD, Verhoeff FH, Fletcher KA, Chimsuku LH, Ngwira BM et al. (2004). Haematological profiles of the people of rural southern Malawi: an overview. Ann Trop Med Parasitol 98, 71–83.

    Article  CAS  Google Scholar 

  • Brabin BJ, Romagosa C, Abdelgalil S, Menendez C, Verhoeff FH, McGready R et al. (2004a). The sick placenta—the role of malaria. Placenta 25, 359–378.

    Article  CAS  Google Scholar 

  • Cornet M, Le Hesran JY, Fievet N, Cot M, Personne P, Gounoue R et al (1998). Prevalence of and risk factors for anemia in young children in southern Cameroon. Am J Trop Med Hyg 58, 606–611.

    Article  CAS  Google Scholar 

  • Crawley J (2004). Reducing the burden of anemia in infants and young children in malaria-endemic countries of Africa: from evidence to action. Am J Trop Med Hyg 71, 25–34.

    Article  Google Scholar 

  • Dallman PR (1988) In: R Tsang, B Nichols (eds) Nutrition During Infancy. Hanley and Belfus Inc: Philadelphia, PA. pp 217.

    Google Scholar 

  • Dewey KG, Cohen RJ, Brown KH (2004). Exclusive breast-feeding for 6 months, with iron supplementation, maintains adequate micronutrient status among term, low-birthweight, breast-fed infants in Honduras. J Nutr 134, 1091–1098.

    Article  CAS  Google Scholar 

  • Dewey KG, Cohen RJ, Brown KH, Rivera LL (1999). Age of introduction of complementary foods and growth of term, low-birth-weight, breast-fed infants: a randomized intervention study in Honduras. Am J Clin Nutr 69, 679–686.

    Article  CAS  Google Scholar 

  • Domellof M, Dewey KG, Lonnerdal B, Cohen RJ, Hernell O (2002). The diagnostic criteria for iron deficiency in infants should be reevaluated. J Nutr 132, 3680–3686.

    Article  CAS  Google Scholar 

  • Dorea J (2000). Iron and copper in human milk. Nutrition 16, 209–220.

    Article  CAS  Google Scholar 

  • Fuchs R, Ellinger I (2004). Endocytic and transcytotic processes in villous syncytiotrophoblast: role in nutrient transport to the human fetus. Traffic 5, 725–738.

    Article  CAS  Google Scholar 

  • Grantham-McGregor S, Ani C (2001). A review of studies on the effect of iron deficiency on cognitive development in children. J Nutr 131, 649S–666S.

    Article  CAS  Google Scholar 

  • Griffin IJ, Abrams SA (2001). Iron and breastfeeding. Pediatr Clin N Am 48, 401–413.

    Article  CAS  Google Scholar 

  • Hinchliffe R (1999). Reference values. In: J Lilleyman, I Hahn, V Blanchette (eds). Pediatric Hematology, 2nd edn.Churchill Livingstone: London.

    Google Scholar 

  • INACG (1985). Measurements of Iron Status. International Life Sciences Institute: Washington, DC.

  • Ismail MR, Ordi J, Menendez C, Ventura PJ, Aponte JJ, Kahigwa E et al (2000). Placental pathology in malaria: a histological, immunohistochemical, and quantitative study. Hum Pathol 31, 85–93.

    Article  CAS  Google Scholar 

  • Jones G, Steketee RW, Black RE, Bhutta ZA, Morris SS (2003). How many child deaths can we prevent this year? Lancet 362, 65–71.

    Article  Google Scholar 

  • Juul S, Zerzan J, Strandjord T, Woodrum D (2003). Zinc protoporphyrin/heme as an indicator of iron status in NICU patients. J Pediatr 142, 273–278.

    Article  CAS  Google Scholar 

  • Kalanda BF, Verhoeff FH, Brabin BJ (2006). Breast and complementary feeding practices in relation to morbidity and growth in Malawian infants. Eur J Clin Nutr 60, 401–407.

    Article  CAS  Google Scholar 

  • Kitua AY, Smith TA, Alonso PL, Urassa H, Masanja H, Kimario J et al (1997). The role of low level Plasmodium falciparum parasitaemia in anaemia among infants living in an area of intense and perennial transmission. Trop Med Int Health 2, 325–333.

    Article  CAS  Google Scholar 

  • Kling P (2006). The zinc protoporphyrin/heme ration in premature infants: has it found its place? J Pediatr 148, 8–10.

    Article  Google Scholar 

  • Kramer M, Kakuma R (2002). Optimal duration of exclusive breastfeeding. Cochrane Database Syst Rev 1, (Art. No. CD003517. DOI 10.1002/14651858.CD003517).

  • le Cessie S, Verhoeff FH, Mengistie G, Kazembe P, Broadhead R, Brabin BJ et al. (2002). Changes in haemoglobin levels in infants in Malawi: effect of low birth weight and fetal anaemia. Arch Dis Child Fetal Neonatal Ed 86, F182–F187.

    Article  CAS  Google Scholar 

  • Letsky EA (1991). The haematological system. In: FE Hytten, G Chamberlain (eds). Clinical Physiology in Obstetrics. Blackwell Science: Oxford, pp 2–75.

    Google Scholar 

  • Lott D, Zimmerman M, Labbe RF, Kling P, Widness J (2006). Erythrocyte zinc protoporphyrin ratios are elevated with prematurity and with fetal hypoxia. Pediatrics 116, 414–422.

    Article  Google Scholar 

  • Michaelsen KF, Milman N, Samuelson G (1995). A longitudinal study of iron status in healthy Danish infants: effects of early iron status, growth velocity and dietary factors. Acta Paediatr 84, 1035–1044.

    Article  CAS  Google Scholar 

  • Miettinen OS (1983). The need for randomization in the study of intended effects. Stat Med 2, 267–271.

    Article  CAS  Google Scholar 

  • Miller MF, Stoltzfus RJ, Mbuya NV, Malaba LC, Iliff PJ, Humphrey JH et al (2003). Total body iron in HIV-positive and HIV-negative Zimbabwean newborns strongly predicts anemia throughout infancy and is predicted by maternal hemoglobin concentration. J Nutr 133, 3461–3468.

    Article  CAS  Google Scholar 

  • Nduati R, John G, Mbori-Ngacha D, Richardson B, Overbaugh J, Mwatha A et al (2000). Effect of breastfeeding and formula feeding on transmission of HIV-1. A randomised clinical trial. JAMA 283, 1167–1174.

    Article  CAS  Google Scholar 

  • Oski FA (1993). Iron deficiency in infancy and childhood. N Engl J Med 329, 190–193.

    Article  CAS  Google Scholar 

  • Picciano M (2001). Nutrient composition of human milk. Pediatr Clin N Am 48, 53–67.

    Article  CAS  Google Scholar 

  • Redd SC, Wirima JJ, Steketee RW (1994). Risk factors for anemia in young children in rural Malawi. Am J Trop Med Hyg 51, 170–174.

    Article  Google Scholar 

  • Rettmer R, Carlson T, Origenes M, Jack R, Labbe R (1999). Zinc protoporphyrin/heme ratio for diagnosis of preanemic iron deficiency. Pediatrics 104, e37.

    Article  CAS  Google Scholar 

  • Saarinen UM, Siimes MA (1978). Developmental changes in red blood cell counts and indices of infants after exclusion of iron deficiency by laboratory criteria and continuous iron supplementation. J Pediatr 92, 412–416.

    Article  CAS  Google Scholar 

  • Schellenberg D, Schellenberg JR, Mushi A, Savigny D, Mgalula L, Mbuya C et al (2003). The silent burden of anaemia in Tanzanian children: a community-based study. Bull World Health Organ 81, 581–590.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Serjeant GR, Grandison Y, Mason K, Serjeant B, Sewell A, Vaidya S (1980). Haematological indices in normal negro children: a Jamaican cohort from birth to five years. Clin Lab Haematol 2, 169–178.

    Article  CAS  Google Scholar 

  • Soldin O, Miller M, Soldin S (2003). Pediatric reference ranges for zinc protoporphyrin. Clin Biochem 36, 21–25.

    Article  CAS  Google Scholar 

  • Srai S, Bomford A, McArdle H (2002). Iron transport across cell membranes: molecular understanding of duodenal and placental iron uptake. Best Pract Res Clin Haematol 15, 243–259.

    Article  CAS  Google Scholar 

  • Stoltzfus RJ, Chwaya HM, Montresor A, Albonico M, Savioli L, Tielsch JM (2000). Malaria, hookworms and recent fever are related to anemia and iron status indicators in 0- to 5-y old Zanzibari children and these relationships change with age. J Nutr 130, 1724–1733.

    Article  CAS  Google Scholar 

  • van Eijk AM, Ayisi JG, Ter Kuile FO, Misore AO, Otieno JA, Kolczak MS et al (2002). Malaria and human immunodeficiency virus infection as risk factors for anemia in infants in Kisumu, western Kenya. Am J Trop Med Hyg 67, 44–53.

    Article  Google Scholar 

  • van Rheenen PF, de Moor LTT, Eschbach S, de Grooth H, Brabin BJ (2007). Delayed cord clamping and haemoglobin levels in infancy: a randomised controlled trial in term babies. Trop Med Int Health 12, 603–616.

    Article  Google Scholar 

  • Verhoeff FH, Milligan P, Brabin BJ, Mlanga S, Nakoma V (1997). Gestational age assessment by nurses in a developing country using the Ballard method, external criteria only. Ann Trop Paediatr 17, 333–342.

    Article  CAS  Google Scholar 

  • WHO (2001). Iron Deficiency Anaemia. Assessment, prevention and control. A guide for programme managers, WHO/NHD/01.3. World Health Organization: Geneva.

Download references

Acknowledgements

We thank the management board of Mpongwe Mission Hospital for their hospitality; and maternity and laboratory staff for their assistance. This study received financial support from the Amsterdam–Liverpool Programme for research in Tropical Child Health and from the Bemmel Support Group.

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Correspondence to P F van Rheenen.

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Guarantor: PF van Rheenen.

Contributors: PFvR and BJB were responsible for the study idea and design. Both contributed to the analysis and interpretation of the data and to the writing of the paper. LTTdM and SE collected the data.

Competing interests

None declared.

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van Rheenen, P., de Moor, L., Eschbach, S. et al. A cohort study of haemoglobin and zinc protoporphyrin levels in term Zambian infants: effects of iron stores at birth, complementary food and placental malaria. Eur J Clin Nutr 62, 1379–1387 (2008). https://doi.org/10.1038/sj.ejcn.1602862

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