Umbilical Cord Serum Ferritin Concentration is Inversely Associated with Umbilical Cord Hemoglobin in Neonates Born to Adolescents Carrying Singletons and Women Carrying Multiples

Abstract

Background: It has been proposed that the fetus prioritizes iron for hemoglobin production over delivery to tissues. However, few studies have evaluated the interrelations between hemoglobin and multiple iron status biomarkers in umbilical cord blood. A full understanding is needed of how these parameters influence each other within cord blood to fully interpret iron and hematologic status at birth.

Objectives: We evaluated the determinants of neonatal hemoglobin and assessed the interrelations between hemoglobin, serum iron status indicators, and serum iron regulatory hormones in healthy neonates.

Methods: This was an observational study that assessed umbilical cord hemoglobin (Hb), serum ferritin (SF), erythropoietin (EPO), soluble transferrin receptor (sTfR), serum iron, hepcidin, vitamin B-12, folate, IL-6, and CRP measured in 234 neonates born to adolescents or to women carrying multiples. Correlations between these indicators were evaluated and mediation models consistent with the observed significant determinants of cord Hb concentrations were developed.

Results: A highly significant inverse association was found between cord SF and Hb concentrations that was not attributable to neonatal or maternal inflammation (as measured by IL-6 and CRP). The inverse association was present in the combined cohort, as well as in the adolescent and multiples cohorts independently. Mediation analyses found that EPO and hepcidin had significant indirect effects on cord Hb, associations that are explicable by mediation through SF and sTfR.

Conclusion: In contrast to observations made in older infants, a highly significant inverse association between Hb and SF, as well positive associations between Hb and both sTfR and EPO, were observed in umbilical cord blood from neonates born to adolescents or women carrying multiples. These findings, combined with review of the published literature, indicate a need for analysis of the relations between multiple parameters to assess iron and hematologic status at birth. These clinical trials were registered at clinicaltrials.gov as NCT01582802 (https://ichgcp.net/clinical-trials-registry/NCT01582802) and NCT01019902 (https://ichgcp.net/clinical-trials-registry/NCT01019902).

Keywords: anemia; erythropoietin; hepcidin; iron; multiple births; neonates; transferrin receptor.

© 2019 American Society for Nutrition.

Figures

FIGURE 1

Participant flowchart for the pregnant women in the multiples or adolescent cohorts. Participants were recruited to Strong Memorial Hospital or Highland Hospital and included in the study according to umbilical cord iron status indicator measurements.

FIGURE 2

Literature search on hemoglobin and serum ferritin in umbilical cord blood. Flowchart of all identified articles from both PUBMED and Web of Science and those included when both serum ferritin and hemoglobin were measured in umbilical cord blood.

FIGURE 3

Inverse association between umbilical cord hemoglobin and serum ferritin in neonates born to adolescents or women carrying multiples. (A) Neonates in the multiples cohort. (B) Neonates in the adolescent cohort. (C) All neonates as a combined cohort.

FIGURE 4

Direct effects of umbilical cord serum iron status indicators and serum iron regulatory hormones on hemoglobin status in neonates born to adolescents or women carrying multiples. A mediation model was developed to evaluate the direct and indirect effects of these iron status indicators and regulatory hormones on hemoglobin status in 234 neonates. Each indicator was standardized and the model is controlled for birth weight. *(P < 0.05) and **(P < 0.001). Direct pathways are shown with a solid line. Indirect pathways are shown in Table 6.