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Background: Guidelines to treat iron deficiency recommend daily provision of oral iron, but this may decrease fractional iron absorption and increase side effects. Our objective was to compare consecutive-day versus alternate-day iron supplementation. Methods: In a double-masked, randomized, placebo-controlled trial, young Swiss women (n = 150; serum ferritin ≤30 µg/L) were assigned to: daily 100 mg iron for 90 d, followed by daily placebo for another 90 d (consecutive-day group) or the same daily dose of iron and placebo on alternate days for 180 d (alternate-day group). The study period was 24/11/2021-10/8/2022. Co-primary outcomes, at equal total iron doses, were serum ferritin and gastrointestinal side effects; secondary outcomes were iron deficiency and serum hepcidin. Compliance and side effects were recorded daily using a mobile application. Data were analysed using mixed models and longitudinal prevalence ratios (LPR). The trial was registered at ClinicalTrials.gov (NCT05105438). Findings: 75 women were assigned to each group and included in the intention-to-treat analysis. Capsule adherence and side effect reporting was >97% in both groups. At equal total iron doses, comparing consecutive-day and alternate-day groups, median serum ferritin was 43.8 µg/L (31.7-58.2) versus 44.8 µg/L (33.8-53.6) (P = 0.98), the LPR for gastrointestinal side effects on days of iron intake was 1.56 (95% CI: 1.38, 1.77; P < 0.0001), and median serum hepcidin was 3.0 nM (IQR 2.0-5.0) versus 1.9 nM (1.4-2.9) (P < 0.0001). Iron deficiency prevalence after 3 months was 5.5% versus 4.3% (P = 0.74) and after 6 months was 11.4% and 3.0% (P = 0.049). Interpretation: At equal total iron doses, compared to consecutive day dosing of iron, alternate day dosing did not result in higher serum ferritin but reduced iron deficiency at 6 months and triggered fewer gastrointestinal side effects. Funding: Swiss National Science Foundation, Bern, Switzerland.
RESUMO
BACKGROUND: The habitual/usual iodine intake and the prevalence of iodine inadequacy may be estimated from spot urinary iodine concentrations in cross-sectional studies by collecting a repeat spot urine in a subgroup of the study population and accounting for within-person variability in iodine intake. However, guidance on the required overall sample size (N) and the replicate rate (n) is lacking. OBJECTIVES: To determine the sample size (N) and replicate rate (n) needed to estimate the prevalence of iodine inadequacy in cross-sectional studies. METHODS: We used data from local observational studies conducted in women 17-49 y old in Switzerland (N = 308), South Africa (N = 154), and Tanzania (N = 190). All participants collected 2 spot urine samples. We calculated the iodine intake using urinary iodine concentrations and accounted for urine volume using urinary creatinine concentration. For each study population, we estimated the habitual iodine intake distribution and determined the prevalence of iodine intake below the average requirement using the Statistical Program to Assess habitual Dietary Exposure (SPADE). We used the obtained model parameters in power analyzes and estimated the prevalence of iodine inadequacy for different sample sizes (N = 400, 600, and 900) and replicate rates (n = 50, 100, 200, 400, 600, and 900). RESULTS: The estimated prevalence (95% CI) of inadequate iodine intake was 21% (15, 28%), 5.1% (1.3, 8.7%), and 8.2% (3.4, 13%) for Swiss, South African, and Tanzanian women, respectively. An N of 400 women, with a repeated measure (n) in 100 women, achieved a satisfactory precision of the prevalence estimate in all study populations. Increasing the replicate rate (n) improved the precision more effectively than increasing the N of the study. CONCLUSIONS: The sample size for cross-sectional studies aiming to assess the prevalence of inadequate iodine intake depend on the expected prevalence, the overall variance in intake, and the study design. However, an N of 400 participants with a repeated measure of 25% may be used as guidance when planning observational studies applying simple random sampling. This trial was registered at clinicaltrials.gov as NCT03731312.