Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Minerals, trace elements, Vit. D and bone health

Contribution of iron status at birth to infant iron status at 9 months: data from a prospective maternal-infant birth cohort in China

Abstract

Background/Objectives

The contribution of iron status at birth to iron status in infancy is not known. We used a physiologic framework to evaluate how iron status at birth related to iron status at 9 months, taking iron needs and sources into account.

Subjects/Methods

In a longitudinal birth cohort in China, iron status measures in cord blood and venous blood in infancy (9 months) and clinical data were prospectively collected in 545 healthy term maternal–infant dyads. We used structural equation modeling (SEM) to create a 9-month iron composite and to assess direct and indirect contributions of multiple influences on 9-month iron status. Logistic regression was used to calculate odds ratios for iron deficiency (ID), iron deficiency anemia (IDA), and anemia.

Results

Approximately 15% (78/523) of infants were born with cord SF <75 µg/l, suggesting fetal-neonatal ID. At 9 months, 34.8% (186/535) and 19.6% (105/535) of infants had ID and IDA, respectively. The following factors were independently associated with poorer 9-month iron status: higher cord zinc protoporphyrin/heme (ZPP/H) (adjusted estimate −0.18, P < 0.001) and serum transferrin receptor (sTfR) (−0.11, P = 0.004), lower cord hemoglobin (Hb) (0.13, P = 0.004), lower birth weight (0.15, P < 0.001), male sex (0.10, P = 0.013), older age at testing (−0.26, P < 0.001), higher 9-month weight (−0.12, P = 0.006) and breastfeeding (0.38, P < 0.001). Breastfeeding at 9 months showed the strongest association, adjusting for all other factors. Compared to formula-fed infants, the odds of IDA were 19.1 (95% CI: 6.92, 52.49, P < 0.001) and 3.6 (95% CI: 1.04, 12.50, P = 0.043) times higher in breastfed and mixed-fed infants, respectively.

Conclusions

Indicators of iron status at birth, postnatal iron needs, and iron sources independently related to iron status at 9 months. Sex was an additional factor. Public health policies to identify and protect infants at increased risk of ID should be prioritized.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: Flow chart of participants.
Fig. 2: Structural equation model of iron status at 9 months in healthy term Chinese infants.

References

  1. 1.

    Georgieff MK. Long-term brain and behavioral consequences of early iron deficiency. Nutr Rev. 2011;69:S43–8.

    Article  Google Scholar 

  2. 2.

    World Health Organization. Guideline: Daily iron supplementation in infants and children. World Health Organization. 2016. Geneva.

  3. 3.

    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:e16–25.

    Article  Google Scholar 

  4. 4.

    Huo J, Sun J, Fang Z, Chang S, Zhao L, Fu P, et al. Effect of home-based complementary food fortification on prevalence of anemia among infants and young children aged 6 to 23 months in poor rural regions of China. Food Nutr Bull. 2015;36:405–14.

    Article  Google Scholar 

  5. 5.

    Gupta PM, Hamner HC, Suchdev PS, Flores-Ayala R, Mei Z. Iron status of toddlers, nonpregnant females, and pregnant females in the United States. Am J Clin Nutr. 2017;106(Suppl 6):1640S–6S. https://doi.org/10.3945/ajcn.117.155978.

  6. 6.

    Brotanek JM, Gosz J, Weitzman M, Flores G. Secular trends in the prevalence of iron deficiency among US toddlers, 1976-2002. Arch Pediatr Adolesc Med. 2008;162:374–81.

    Article  Google Scholar 

  7. 7.

    Baker RD, Greer FR. Committee on nutrition. diagnosis and prevention of iron deficiency and iron-deficiency anemia in infants and young children (0–3 years of age). Pediatrics. 2010;126:1040–50.

    Article  Google Scholar 

  8. 8.

    McDonagh MS, Blazina I, Dana T, Cantor A, Bougatsos C. Screening and routine supplementation for iron deficiency anemia: a systematic review. Pediatrics. 2015;135:723–33.

    Article  Google Scholar 

  9. 9.

    Lozoff B, Walter T, Kaciroti N. Iron deficiency in infancy: applying a physiologic framework for prediction. Am J Clin Nutr. 2006;84:1412–21.

    CAS  Article  Google Scholar 

  10. 10.

    Georgieff MK, Wewerka SW, Nelson CA, deRegnier RA. Iron status at 9 months of infants with low iron stores at birth. J Pediatr. 2002;141:405–9.

    CAS  Article  Google Scholar 

  11. 11.

    Strauss MB. Anemia of infancy from maternal iron deficiency in pregnancy. J Clin Invest. 1933;12:345–53.

    CAS  Article  Google Scholar 

  12. 12.

    de Pee S, Bloem MW, Sari M, Kiess L, Yip R. The high prevalence of low hemoglobin concentration among Indonesian infants aged 3-5 months is related to maternal anemia. J Nutr. 2002;132:2215–21.

    Article  Google Scholar 

  13. 13.

    Colomer J, Colomer C, Gutierrez D, Jubert A, Nolasco A, Donat J, et al. Anaemia during pregnancy as a risk factor for infant iron deficiency: report from the Valencia Infant Anaemia Cohort (VIAC) study. Paediatr Perinat Epidemiol. 1990;4:196–204.

    CAS  Article  Google Scholar 

  14. 14.

    Miller MF, Stoltzfus RJ, Mbuya NV, Malaba LC, Iliff PJ, Humphrey JH, et al. 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. 2003;133:3461–8.

    CAS  Article  Google Scholar 

  15. 15.

    Hay G, Refsum H, Whitelaw A, Melbye EL, Haug E, Borch-Iohnsen B. Predictors of serum ferritin and serum soluble transferrin receptor in newborns and their associations with iron status during the first 2 y of life. Am J Clin Nutr. 2007;86:64–73.

    CAS  Article  Google Scholar 

  16. 16.

    Clark KM, Li M, Shao J, Liang F, Zhang Y, Chai J, et al. Breastfeeding, mixed or formula feeding at 9 months and the prevalence of iron deficiency and iron deficiency anemia in two cohorts of infants in China. J Pediatr. 2017;181:56–61.

    CAS  Article  Google Scholar 

  17. 17.

    Chen CM, Mu SC, Shih CK, Chen YL, Tsai LY, Kuo YT, et al. Iron status of infants in the first year of life in Northern Taiwan. Nutrient. 2020;12:139–51. https://doi.org/10.3390/nu12010139

    CAS  Article  Google Scholar 

  18. 18.

    Armony-Sivan R, Zhu B, Clark KM, Ji C, Kaciroti N, Shao J et al. Iron deficiency(ID) at both birth and 9 months predicts right frontal EEG asymmetry in infancy. Dev Psychobiol. 2016;58:462–70.

  19. 19.

    Lorenz L, Peter A, Poets CF, Franz AR. A review of cord blood concentrations of iron status parameters to define reference ranges for preterm infants. Neonatology. 2013;104:194–202.

    Article  Google Scholar 

  20. 20.

    Shao J, Lou J, Rao R, Georgieff MK, Kaciroti N, Felt BT, et al. Maternal serum ferritin concentration is positively associated with newborn iron stores in women with low ferritin status in late pregnancy. J Nutr. 2012;142:2004–9.

    CAS  Article  Google Scholar 

  21. 21.

    Tamura T, Goldenberg RL, Hou J, Johnston KE, Cliver SP, Ramey SL, et al. Cord serum ferritin concentrations and mental and psychomotor development of children at five years of age. J Pediatr. 2002;140:165–70.

    CAS  Article  Google Scholar 

  22. 22.

    Amin SB, Orlando M, Eddins A, MacDonald M, Monczynski C, Wang H. In utero iron status and auditory neural maturation in premature infants as evaluated by auditory brainstem response. J Pediatr. 2010;156:377–81.

    CAS  Article  Google Scholar 

  23. 23.

    Amin SB, Orlando M, Wang H. Latent iron deficiency in utero is associated with abnormal auditory neural myelination in >= 35 weeks gestational age infants. J Pediatr. 2013;163:1267–71.

    CAS  Article  Google Scholar 

  24. 24.

    Armony-Sivan R, Eidelman AI, Lanir A, Sredni D, Yehuda S. Iron status and neurobehavioral development of premature infants. J Perinatol. 2004;24:757–62.

    CAS  Article  Google Scholar 

  25. 25.

    World Health Organization. Worldwide Prevalence of Anaemia 1993-2005: WHO Global Database on Anaemia. 2008; Geneva, Switzerland: WHO Press.

  26. 26.

    Centers for Disease Control. Healthy People - 2000 National Health Promotion and Disease Prevention Objectives Final Review. 2001. Hyattsville, MD, Department of Health and Human Services.

  27. 27.

    Centers for Disease Control and Prevention. Recommendations to prevent and control iron deficiency in the United States. MMWR. 1998;47:1–29.

    Google Scholar 

  28. 28.

    Saarinen UM, Siimes MA. Serum ferritin in assessment of iron nutrition in healthy infants. Acta Pediatr. 1978;67:745–51.

    CAS  Article  Google Scholar 

  29. 29.

    Soldin OP, Miller M, Soldin SJ. Pediatric reference ranges for zinc protoporphyrin. Clin Biochem. 2003;36:21–25.

    CAS  Article  Google Scholar 

  30. 30.

    Cook JD, Flowers CH, Skikne BS. The quantitative assessment of body iron. Blood. 2003;101:3359–64.

    CAS  Article  Google Scholar 

  31. 31.

    Flowers CH, Skikne BS, Covell AM, Cook JD. The clinical measurement of serum transferrin receptor. J Lab Clin Med. 1989;114:368–77.

    CAS  PubMed  Google Scholar 

  32. 32.

    Pfeiffer CM, Cook JD, Mei Z, Cogswell ME, Looker AC, Lacher DA. Evaluation of an automated soluble transferrin receptor (sTfR) assay on the Roche Hitachi analyzer and its comparison to two ELISA assays. Clin Chim Acta. 2007;382:112–6.

    CAS  Article  Google Scholar 

  33. 33.

    World Health Organization. Child growth standards. WHO Anthro (version 3.2.2, January 2011) and macros [Internet]. Available from: http://www.who.int/childgrowth/software/en/. 2011. Geneva, World Health Organization.

  34. 34.

    Domellof M, Lonnerdal B, Dewey KG, Cohen RJ, Rivera LL, Hernell O. Sex differences in iron status during infancy. Pediatrics. 2002;110:545–52.

    Article  Google Scholar 

  35. 35.

    Labbé RF, Vreman HJ, Stevenson DK. Zinc protoporphyrin: a metabolite with a mission. Clin Chem. 1999;45:2060–72.

    Article  Google Scholar 

  36. 36.

    McLimore HM, Phillips AK, Blohowiak SE, Pham DQ, Coe CL, Fischer B, et al. Impact of multiple risk factors on newborn iron status. J Pediatr Hematol Oncol. 2013;35:473–7.

    CAS  Article  Google Scholar 

  37. 37.

    Rettmer RL, Carlson TH, Maurice L, Origenes ML, Jack RM, Labbe´ RF. Zinc protoporphyrin/Heme Ratio diagnosis preanemic iron deficiency. Pediatrics.1999;104:e37 https://doi.org/10.1542/peds.104.3.e37.

    CAS  Article  PubMed  Google Scholar 

  38. 38.

    Yu KH. Effectiveness of zinc protoporphyrin/heme ratio for screening iron deficiency in preschool-aged children. Nutr. Res Pract. 2011;5:40–45. https://doi.org/10.4162/nrp.2011.5.1.40

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Hennig G, Homann C, Teksan I, Hasbargen U, Hasmuller S, Holdt LM, et al. Non-invasive detection of iron deficiency by fluorescence measurement of erythrocyte zinc protoporphyrin in the lip. Nat Commun. 2016;17:10776 https://doi.org/10.1038/ncomms10776.

    Article  Google Scholar 

Download references

Acknowledgements

We acknowledge Drs. Sean Lynch and Bo Lonnerdalfor their service on the Independent Data Monitoring Committee, which had oversight of the small randomized clinical trial component. We also thank Dr. Yaping Shi and her colleagues for their assistance with participant enrollment and cord blood collection, Liqin Chen for the iron status assays, and Julie Sturza for data analysis.

Funding

This work was supported by grants from the National Institutes of Health (HD039386, B. Lozoff, Principal Investigator) and the China National Sciences Foundation (81273085, J. Shao, Principal Investigator). Iron supplements and placebo were donated by Lee’s Pharmaceutical Holdings Limited (Hong Kong). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.

Author information

Affiliations

Authors

Contributions

JS was a co-investigator in the Brain and Behavior in Early Iron Deficiency study and principal investigator (PI) in the grant from NSFC; BL was the overall PI of the study; BL and JS were responsible for designing and conducting the research, writing and interpreting results; NK conducted methodology and formal analysis; BR conducted data extraction and analysis; BZ was responsible for investigation and data collection. KMC contributed to writing, review and editing. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Jie Shao.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict ofinterest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Shao, J., Richards, B., Kaciroti, N. et al. Contribution of iron status at birth to infant iron status at 9 months: data from a prospective maternal-infant birth cohort in China. Eur J Clin Nutr 75, 364–372 (2021). https://doi.org/10.1038/s41430-020-00705-4

Download citation

Search

Quick links