The complex interaction between breastfeeding and IQ: another piece in the puzzle

Tozzi et al. report on the effect of duration of breastfeeding on neuropsychological outcome of children aged 10 to 12 years. The study is well performed and comprises a large sample of 1403 children and is one of the few that examines the long-term consequences of breastfeeding. They report that longer duration of exclusive breastfeeding has a positive influence on certain verbal subtests. The effects were, albeit statistically significant, only small and therefore have a limited clinical significance. The study by Tozzi et al. is the most recent publication in the large body of literature examining the effects of breastfeeding on intellectual outcome. The idea that breastfeeding could positively influence intellectual outcome was first raised by Hoefer and Hardy in 1929. Thereafter, a series of papers have been published on term and preterm populations. A metaanalysis by Anderson et al. summarizing 20 published papers showed that after adjustment for covariates, cognitive function increased by 3.1 IQ points. This difference persisted across ages and was stronger for children born with a low birthweight. This is in contrast to a recent study by Der et al. examining 5475 children from the 1979 US National Longitudinal Survey of Youth. They demonstrated that after controlling for a large set of confounders including maternal IQ, the effect of breastfeeding on intellectual outcome was non-significant. What is the assumed mechanism by which breastfeeding is thought to lead to improved cognitive function? Long-chain polyunsaturated fatty acids (LCPUFAs) are important substrates for brain development. LCPUFAs are present in human milk, but not in cow’s milk or most infant formulas. In addition, preterm infants are particularly in need of LCPUFAs as they lack the maternal transplacental supply. Interestingly, effects of LCPUFAs supplementation to infant formulas have not been conclusive whereas a maternal diet supplementation with very-long-chain n-3 polyunsaturated fatty acids (cod liver oil) during pregnancy and lactation was associated with a beneficial effect on the child’s cognitive function after controlling for confounding factors. More light has been shed onto the complexity of the association between breastfeeding and intellectual outcome by the important study of Caspi et al. who demonstrated that there is an interaction in the association between breastfeeding and intellectual outcome: an effect was only seen in children in whom a polymorphism in the FADS2 gene was detected. FADS2 plays a critical role in the synthesis of LCPUFAs. Further, the expression of FADS2 is enhanced if dietary fatty acids are available in higher concentrations. This new line of research points to the growing evidence that gene-environment interaction may play an important role in determining the variability of outcome. One has to keep in mind that intellectual abilities and their development over time do not only depend on one factor (e.g. breastfeeding), but on a large set of other determinants. Among those are maternal factors (IQ, smoking, age, education), sociodemographic and environmental factors (home environment, stimulation, emotional support), and non-modifiable factors (sex, gestational age). These factors combined probably have a stronger effect on long-term intellectual outcome than breastfeeding in the first few months of life. The small effect of breastfeeding on early adolescent outcome in the population by Tozzi et al. supports the notion of a stronger environmental effect on long-term outcome than early breastfeeding duration. In summary, breastfeeding may have an effect on intellectual abilities, but this effect is modulated by genetic variations in fatty acid metabolism. Further, many other factors, sociodemographic in particular are more important in determining long-term intellectual outcome. Future research should focus on children at risk for low supply of LCPUFAs (such as preterm infants) and focus on tailoring supplementation based on variations of genes involved in the pathway of fatty acid metabolism. In addition, other candidate genes should be examined regarding their role in the association between breastfeeding and brain development.