Prenatal Iron

Arija et al. (2019), in a prospective cohort study in Spain, found that children born to mothers who had taken prenatal iron supplements (14-30 mg/day) scored better on tasks designed to evaluate working memory and executive functioning at age 7 than those whose mothers had not taken prenatal iron.  Nguyen et al. (2021), in a randomized controlled trial (RCT) in Vietnam, found that 6-7 year old children whose mothers had taken 60 mg of iron once a week prior to pregnancy scored better on a working memory scale than those whose mothers did not receive the preconception iron supplements.  In this study, all the mothers were given 60 mg of iron per day during pregnancy.  They also looked at a multi-micronutrient supplement, and both the iron group and the control received folic acid. 

 

These two studies both looked at outcomes seven years after the exposure, so both had the benefits of a longitudinal design.  Both are able to show temporality, which is an important component of causality, in that the exposure to iron supplementation they are investigating occurred seven years before they measured the outcomes.  The cohort study (Arija et al., did not have the randomization, blinding, and control group contributing to internal validity that the RCT (Nguyen et al., 2021) had, although the cohort study did analyze the participants in three groups according to tertiles of maternal iron intake.  I appreciate that the RCT gave iron to the control group once they became pregnant. 

 

The cohort study cited the full study of which they were a part (Guxens et al., 2012), which reported 2150 participants in the groups that the cohort study was looking at.   The follow up included 2032 participants, so only 5% were lost to follow up, but the report does not discuss the characteristics of those lost, which could have been a source of bias affecting the results.  The RCT had a total of 1599 participants, 9% of whom were lost to follow up, but the authors note that the groups who remained were similar to those lost, and there were not proportionately more lost from one group to another, implying this attrition was not a considerable source of bias.   Both studies were able to adjust for many potentially confounding factors that could have influenced the appearance of the associations they were looking for, even including Mediterranean diet adherence and organochlorine exposure for the cohort study and maternal mental health, child dietary diversity, and home social/emotional/cognitive support for the RCT.  A few sources of potential selection bias were identified in the cohort study, such as less educated women being more likely to decline to participate (Guxens et al., 2012), and these were also adjusted for as confounders.  Sources of potential selection bias in the RCT included exclusion from the study of women who were already taking iron and folic acid or multi micronutrient supplements (Nguyen et al., 2012).  The cohort study was a multicenter study covering several different geographic areas, and the population of the cohort study was more similar in ethnicity, culture, and socioeconomic status to the population I work with than the RCT population, making the results more generalizable.  The RCT was in a region with high rates of malnutrition including caloric deficiencies (Nguyen et al., 2012).

 

When I took the Evidence Based Nutrition class, I had noted that women of childbearing age were more likely to be deficient in iron because of menstrual blood loss.  In my future clinical practice, I would monitor labs and adjust the dosage of iron supplementation recommended as needed.  I began monitoring my own iron levels and taking a supplement prior to my own pregnancy, so I know this is an easy intervention.  These two studies both support this practice and increase my confidence in recommending iron supplements to women of childbearing age, whether they are pregnant or not, after reviewing their labs and confirming indications of deficiency. 

 

References:

 

Arija, V., Hernández-Martínez, C., Tous, M., Canals, J., Guxens, M., Fernández-Barrés, S., Ibarluzea, J., Babarro, I., Soler-Blasco, R., Llop, S., Vioque, J., Sunyer, J., & Julvez, J. (2019). Association of Iron Status and Intake During Pregnancy with Neuropsychological Outcomes in Children Aged 7 Years: The Prospective Birth Cohort Infancia y Medio Ambiente (INMA) Study. Nutrients, 11(12). 

 

Guxens, M., Ballester, F., Espada, M., Fernández, M. F., Grimalt, J. O., Ibarluzea, J., Olea, N., Rebagliato, M., Tardón, A., Torrent, M., Vioque, J., Vrijheid, M., & Sunyer, J. (2012). Cohort Profile: the INMA–INfancia y Medio Ambiente–(Environment and Childhood) Project. International Journal of Epidemiology, 41(4), 930–940. 

 

Nguyen, P. H., Lowe, A. E., Martorell, R., Nguyen, H., Pham, H., Nguyen, S., Harding, K. B., Neufeld, L. M., Reinhart, G. A., & Ramakrishnan, U. (2012). Rationale, design, methodology and sample characteristics for the Vietnam pre-conceptual micronutrient supplementation trial (PRECONCEPT): a randomized controlled study. BMC Public Health, 12, 898. 

 

Nguyen, P. H., Young, M. F., Tran, L. M., Khuong, L. Q., Duong, T. H., Nguyen, H. C., Truong, T. V., DiGirolamo, A. M., Martorell, R., & Ramakrishnan, U. (2021). Preconception micronutrient supplementation positively affects child intellectual functioning at 6 y of age: A randomized controlled trial in Vietnam. The American Journal of Clinical Nutrition, 113(5), 1199–1208.