Maternal Inflammation at Delivery Affects Assessment of Maternal Iron Status

Abstract

Pregnant adolescents (aged ≤ 18 y, n = 253) were followed from ≥ 12 wk of gestation to delivery to assess longitudinal changes in anemia and iron status and to explore associations between iron status indicators, hepcidin, and inflammatory markers. Hemoglobin, soluble transferrin receptor (sTfR), ferritin, serum iron, erythropoietin (EPO), hepcidin, C-reactive protein, interleukin-6 (IL-6), folate, and vitamin B-12 were measured, and total body iron (TBI) (milligrams per kilogram) was calculated using sTfR and ferritin values. Anemia prevalence increased from trimesters 1 and 2 (3-5%, <28 wk) to trimester 3 (25%, 33.2 ± 3.7 wk, P < 0.0001). The prevalence of iron deficiency (sTfR > 8.5 mg/L) doubled from pregnancy to delivery (7% to 14%, P = 0.04). Ferritin and hepcidin concentrations at delivery may have been elevated as a consequence of inflammation because IL-6 concentrations at delivery were 1.6-fold higher than those obtained at 26.1 ± 3.3 wk of gestation (P < 0.0001), and a positive association was found between IL-6 and both hepcidin and ferritin at delivery (P < 0.01). EPO was consistently correlated with hemoglobin (r = -0.36 and -0.43, P < 0.001), ferritin (r = -0.37 and -0.32, P < 0.0001), sTfR (r = 0.35 and 0.25, P < 0.001), TBI (r = -0.44 and -0.37, P < 0.0001), and serum iron (r = -0.22 and -0.16, P < 0.05) at mid-gestation and at delivery, respectively. EPO alone explained the largest proportion of variance in hemoglobin at 26.0 ± 3.3 wk of gestation (R(2) = 0.13, P = 0.0001, n = 113) and at delivery (R(2) = 0.19, P < 0.0001, n = 192). Pregnant adolescents are at high risk of anemia. EPO is a sensitive indicator of iron status across gestation, is not affected by systemic inflammation, and may better predict risk of anemia at term. The trial was registered at clinicaltrials.gov as NCT01019902.

Prevalence of anemia and associations between neonatal iron status, hepcidin, and maternal iron status among neonates born to pregnant adolescents

“…Volume 79 | Number 1 | January 2016 pregnant adolescents that gave birth to these newborns (19), and to that reported among pregnant women (27). An inverse correlation between neonatal Hb and storage iron has previously been reported in term newborns born to diabetic mothers (28) in support of the premise that iron is preferentially utilized for fetal red cell mass over storage iron but few normative data are available regarding these correlations in otherwise healthy term neonates.…”

“…Hepcidin concentrations were higher in newborns born to mothers with longer durations of labor. This is likely due to inflammation as maternal hepcidin was significantly elevated at delivery when compared to mid-gestation (19), and hepcidin was significantly associated with IL-6 in both the adolescent at delivery and in neonatal cord blood samples. This should be taken into account when considering use of either hepcidin or ferritin as an indicator of iron status in neonates and their mothers at delivery.…”

“…In contrast to the relationships observed at mid-gestation, no significant associations were observed between cord SF and maternal SF at delivery (P = 0.30) or between cord hepcidin and maternal hepcidin at delivery (P = 0.10). This may be explained by labor-induced inflammation as we have previously found that ferritin and hepcidin concentrations were affected by the increased maternal inflammation observed at delivery (19).…”

“…Maternal SF concentrations at delivery are affected by acute delivery-associated inflammatory events. In a previous publication of maternal data from this same study cohort (19), concentrations of SF, hepcidin, and IL-6 were significantly higher at delivery compared to values obtained at mid-gestation. Thus, inflammation may confound the utility of ferritin and hepcidin as iron status indicators at delivery.…”

“…Maternal dietary iron intake was assessed by 24-h dietary recall, and frequency of prenatal supplement use was self-reported via questionnaire. Details of the methodology used for each assay, maternal iron status, and maternal dietary iron intake have been previously reported (19). At present, there is no definitive cut-off that is indicative of suboptimal cord SF concentrations.…”