TABLE 3.
Relationships between ferritin and BMI, as mediated by inflammation, among WRA (15–49 years) with normal weight to overweight or obesity by survey in the BRINDA project1
| CIC2 | Country, survey year | n | WRA mediation analyses, adjusted3 | |||||
|---|---|---|---|---|---|---|---|---|
| Total effect | Direct effect | Indirect effect | Mediated, % | Mediated by CRP, % | Mediated by AGP, % | |||
| Low | Afghanistan, 2013 | 571 | −2.1 (−4.3, 0.1) | −2.7 (−4.7, −0.8) | 0.6 (−0.02, 1.3) | NM | — | — |
| Burkina Faso, 2010 | 61 | −2.9 (−15.9, 10.1) | 5.1 (−6.1, 17.2) | −7.5 (−12.5, −3.2) | NM | — | — | |
| Cambodia, 2014 | 609 | 3.8 (2.0, 5.5) | 2.3 (0.4, 4.1) | 1.4 (0.2, 2.6) | 38% | 17% | 21% | |
| Côte d'Ivoire, 2007 | 706 | 0.5 (−1.1, 2.1) | −0.8 (−2.3, 0.7) | 1.3 (0.7, 1.8) | NM | — | — | |
| Laos, 2006 | 690 | 11.9 (8.3, 14.3) | 9.1 (5.5, 11.9) | 2.6 (1.2, 3.9) | 23%4 | 17% | 3% | |
| Malawi, 2016 | 594 | −0.5 (−2.5, 1.6) | −1.1 (−3.2, 0.1) | 0.6 (0.04, 1.2) | NM | — | — | |
| Low-middle | Cameroon, 2009 | 594 | 0.1 (−1.2, 1.4) | −0.6 (−1.9, 0.7) | 0.7 (0.4, 1.0) | NM | — | — |
| Georgia, 2009 | 1605 | 1.2 (0.6, 1.8) | 0.8 (0.2, 1.4) | 0.4 (0.1, 0.6) | 31% | 31% | — | |
| India, 2011 | 147 | 7.5 (0.07, 15.4) | 3.7 (−2.1, 9.4) | 3.6 (1.1, 6.2) | NM5 | — | — | |
| Nigeria, 2012 | 506 | −1.5 (−3.2, 0.3) | −1.5 (−3.2, 0.2) | 0.003 (−0.04, 0.5) | NM | — | — | |
| Pakistan, 2011 | 5004 | 1.0 (0.4, 1.7) | 0.8 (0.2, 1.5) | 0.2 (0.1, 0.3) | 21% | 9% | 11% | |
| Vietnam, 2010 | 1178 | 2.4 (−0.2, 4.9) | −0.5 (−3.2, 2.2) | 2.9 (2.0, 3.8) | NM | — | — | |
| Upper-middle | Azerbaijan, 2013 | 2528 | 3.5 (2.7, 4.3) | 1.4 (0.1, 2.3) | 2.1 (1.6, 2.6) | 60% | 45% | 15% |
| Colombia, 2010 | 8300 | 2.0 (1.4, 2.6) | 1.6 (1.0, 2.2) | 0.4 (0.2, 0.5) | 19% | 19% | — | |
| Mexico, 2006 | 2910 | 1.2 (0.1, 2.3) | 0.4 (−0.7, 1.5) | 0.9 (0.3, 1.5) | 71% | 71% | — | |
| Mexico, 2012 | 3540 | 2.7 (1.3, 4.1) | 0.8 (−1.0, 2.4) | 1.9 (1.2, 2.6) | 71% | 71% | — | |
| High | United Kingdom, 2014 | 862 | 1.9 (0.5, 3.3) | 1.3 (−1.0, 2.9) | 0.6 (−0.04, 1.2) | NM | — | — |
| United States, 2006 | 3024 | 1.3 (0.6, 2.0) | −0.03 (−1.0, 0.08) | 1.3 (1.0, 1.7) | 100% | 100% | — | |
Ferritin, CRP, and AGP variables were natural-log transformed for analysis due to nonnormal distributions. Mediation estimates were exponentiated, and results are presented as the percentage changes (95% CIs) in ferritin for every 1-unit change in BMI. Ferritin concentrations were measured in serum or plasma, as reported in the survey. All estimates account for the cluster survey design (cluster, strata) with survey weights applied. The inclusion criteria were having a BMI ≥ 18.5 kg/m2, not being pregnant, and having a negative malaria test result. AGP, alpha-1-acid glycoprotein; BRINDA, Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia; CIC, country income classification; CRP, C-reactive protein; NM, no mediation; WRA, women of reproductive age.
CIC was defined according to the World Bank definition for the year in which the survey was conducted (38).
Model for mediation analyses:
(1)
Here, all values were continuous and AGP was included as a mediator only in analyses for which it was available in the data set. Interpretation was as follows: total effect is the effect of BMI on ferritin; direct effect is the effect of BMI on ferritin, controlling for inflammation; and indirect effect is the effect of BMI on ferritin, as mediated by the effect of CRP or AGP. Mediation was considered present when both the total and indirect effects were significant (41). The covariates available for adjustment were age, education level (respondent or household head), household socioeconomic status, access to an improved water source, access to an improved toilet, and urban or rural residence. Covariates were included in the mediation model if they were associated with the outcome variable at a P value < 0.1 in bivariate models (Supplemental Table 6). Unadjusted mediation estimates are presented in Supplemental Table 11.
In the survey from Laos, 23% of the relationship between BMI and ferritin was mediated by inflammation, with 17% of the mediated effect through CRP, 3% of the mediated effect through AGP, and 3% of the mediated effect unexplained.
For the survey from India, the CI for the total effect appears significant; however, as the P value was 0.063, mediation was not considered to be present.