Chronically Low Iron in Infancy Reveals Lower Intelligence

ANN ARBOR, Mich., Nov. 7 -- Chronic iron deficiency in infancy may lead to long-term cognitive deficits, particularly in poor families, according to a study of Costa Rican children.

Although chronically iron-deficient children in both middle-class and poor families suffered from consistent cognitive deficits, as seen in a longitudinal study through age 19, the children in poor families fared worse, found Betsy Lozoff, M.D., of the University of Michigan, in Ann Arbor, and colleagues.

Chronically iron-deficient babies born into the middle class consistently had 8% to 9% lower intelligence scores through age 19 compared with their healthy peers, the investigators reported in the November issue of Archives of Pediatrics & Adolescent Medicine.

For low-economic-status children with iron deficiency, the gap actually widened over time to 25% to 28% lower cognitive scores, which is "likely to be functionally significant regarding educational attainment and career choices in adulthood," wrote Dr. Lozoff, and colleagues.

"In an economically stressed family environment, there might not be the resources or capacity to help children compensate," the authors wrote, which results in a "worse outcome among individuals who experience both an early biological insult or stressor and more disadvantaged background."

The 185 urban Costa Rican children included in the longitudinal observation study were followed from the time they were one or two years old to age 19 with serum measures of iron status and a battery of cognitive tests about every five years.

Chronic iron deficiency was defined as having a serum ferritin concentration less than12 ng/mL and either a free erythrocyte protoporphyrin level of at least 100 ?g/dL red blood cells or transferrin saturation less than 10%. It was present in 20 of 87 middle-class children and 33 of 98 less well-off children despite iron treatment sufficient to correct anemia. None were born preterm or with low birth weight or had acute or chronic health problems.

For the middle-socioeconomic status participants, differences in scores between groups did not change significantly over time. The researchers reported:

• Average initial cognitive scores were 101.2 iron deficient versus 109.3 control (difference ?8.15, 95% confidence interval ?10.1 to ?6.2, effect size 0.54 SD), and
• At the 19 year follow-up scores were 98.2 iron deficient versus 107.6 control (difference ?9, 95% CI for the difference ?11.0 to ?7.0).

For low-socioeconomic status participants, the difference between groups increased over time. The findings were:

• Baseline scores were 93.1 iron deficient versus 102.8 control (difference ?9.7, 95% CI ?12.8 to ?6.6, effect size 0.67 SD),
• The difference in the rate of change was ?1.8 between groups from infancy to age 5 (95% CI ?2.6 to ?1.1),
• From age 5 to 19, the difference in the rate of change was ?0.6 (95% CI ?0.8 to ?0.3), and
• At the 19 year follow-up, cognitive scores were 70.4 iron deficient versus 95.3 control (95% CI for difference 20.6 to 29.4, effect size 1.67 SD).

The researchers said this pattern of increasing decrement compared to their peers could be explained by "the cumulative and transactional nature of cognitive development" as acquiring new skills requires mastery of skills at an earlier developmental stage.

"If direct and indirect effects of early iron deficiency on the brain disrupted or delayed basic developmental processes, there could be a snowball effect," Dr. Lozoff and colleagues wrote.

Since good iron status in infancy seemed to have a protective effect in low-income families, "it seems reasonable to prevent iron deficiency in infancy and treat it before it becomes chronic or severe," they added.

The iron deficient group overall was more likely to be male (75% versus 48% with good iron status, P=0.005) and weigh less at birth (mean 3.1 kg versus 3.3 kg, P=0.02). All analyses adjusted for these factors.

Anemia from iron deficiency affects an estimated 20% to 25% of infants worldwide, and iron deficiency without anemia is likely more widespread. Infants in families with low income status, who are ethnic minorities or immigrants in industrialized countries are at increased risk.

The researchers said the study was limited by a relatively small sample size and the lack of measures to assess specific central nervous system effects of early iron deficiency as well as duration of iron deficiency. Consequently, this longitudinal analysis cannot provide evidence of specific CNS effects of early iron deficiency.

They also pointed out that "socioeconomic status may exert its effects in different ways in various societies and cultures. Thus, the relationships observed in this Costa Rican sample may not generalize to other parts of the world."

The study was sponsored by the National Institutes of Health.