Longitudinal evaluation of iron status during pregnancy: a prospective cohort study in a high-resource setting

Background: Iron deficiency affects a large proportion of pregnant women worldwide, with potentially serious consequences for perinatal and infant outcomes, but well-powered, comprehensive analyses of longitudinal iron status during pregnancy are scarce. Objectives: This study aimed to evaluate the longitudinal changes in iron biomarkers across pregnancy and prevalence of iron deficiency in primiparous women in a high-resource setting and propose early pregnancy iron status cutoffs that predict iron deficiency in the third trimester. Methods: In a prospective cohort of primiparous women with low-risk, singleton pregnancies in Ireland, iron [ferritin, soluble transferrin receptors (sTfR), total body iron (TBI)] and inflammatory markers (C-reactive protein, α-glycoprotein) were measured at 3 study visits: 15, 20, and 33 wk of gestation. Women with anemia (hemoglobin < 110g/L) at their first routine antenatal visit were excluded from this analysis. Results: Participants (N = 629) were Caucasian (98.2%) and born in Ireland (80.6%). The prevalence of iron deficiency (ferritin < 15 μg/L) increased throughout pregnancy, at 4.5%, 13.7% and 51.2% at 15, 20, and 33 wk of gestation, respectively. Using a ferritin threshold of <30 μg/L, rates of deficiency were 20.7%, 43.7%, and 83.8% across these time points, respectively. Application of sTfR of >4.4 mg/L generated similar prevalence data as ferritin of <15 μg/L at 7.2%, 12.6%, and 60.9%, respectively. Using TBI of <0 mg/kg, deficiency rates were lower than using ferritin or sTfR (P < 0.001). Using a cutpoint analysis method (area under the curve = 0.750), ferritin of <60 μg/L emerged as the ferritin threshold at 15 wk that predicted the presence of iron deficiency (ferritin < 15 μg/L) at 33 wk. Iron-containing supplements (mainly multivitamins) taken prepreganancy/early pregnancy was associated with reduced risk of deficiency throughout pregnancy, including the third trimester (odds ratio: 0.57; 95% confidence interval: 0.39, 0.82; P = 0.002). Conclusions: Pregnancy places a remarkable strain on maternal iron status even in a high-resource, generally iron-supplemented population. Women should be screened early in pregnancy for iron status, with a suggested target ferritin concentration of >60 μg/L. This trial was registered at clinicaltrials.gov as NCT01891240 (IMPROvED Study; ==https://www.clinicaltrials.gov/study/NCT01891240?cond=NCT01891240&rank=1).