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BLOG: January 2009

DHA in brain development study - why not boys?

It is no news that essential fatty acids are needed to maintain health. One of them, Docosahexaenoic acid (much better known as DHA), is particularly popular, as there is solid evidence that it boosts protection from cardiovascular disease. It is also no news that - shame on us - we still don't know much of what exactly DHA, and other essential fatty acids, are used for by the body.

A recent Australian study moves us another small step deeper into that uncharted territory.

 The study (Neurodevelopmental Outcomes of Preterm Infants Fed High-Dose Docosahexaenoic Acid, Makrides, Gibson et al., JAMA, 01/14/2009) investigated the effect of supplementing DHA to preterm infants on their mental development. In all, 657 babies born after less than 33 weeks of pregnancy have been given either standard (about 0.3% of total fats) or high DHA supplementation (about 1% of total fats) for the remainder of the average 40-week term.

Their neurological development was then evaluated at 18 months with Bayley Mental Development Index (MDI), which scores baby's memory function, problem solving ability, early number concepts, alertness, curiosity, ability to do simple tasks for a reward, and language proficiency.

After six years, the study arrived at somewhat intriguing conclusion: supplementation didn't significantly help preterm boys, but did help girls. Girls on high supplemental DHA had overall MDI score 99.1, compared to 94.4 score for girls on standard DHA. High-DHA group had the incidence of mildly and significantly delayed mental development of 9.9% and 1.4%, respectively, compared to 25%% and 9.7% in the standard-DHA group.

Boys scored nearly the same in both groups: 91.4 high-and 91.9 standard-DHA. High-DHA seemed to be somewhat beneficial for underweight babies (<1.25kg), with the incidence of mildly delayed mental development about cut in half (16% vs. 32.6% for high- and standard-DHA groups, respectively).

So, at the same time, the initial hypothesis - that preterm babies have elevated need for DHA, being born significantly before the end of the last trimester of gestation, during which DHA supply to their brains peaks - has been both, proved and refuted by study results.

Sure, we all know that girls and boys are different: on average, girls have smaller brain, but it is more complex and develops faster (which is reflected by study's MDI figures). It could be that boys didn't have as much use of the additional DHA simply because their brain develops at somewhat slower rate. Still, it is to expect at least some measurable positive effect, not zero.

The very structure of the brain - as well as functioning - is also different for the two genders. Girls have better language related functions, including reading, as well as social integration, while boys get better at abstract thinking and spatial coordination. Girls are (latter in life) affected only 1/4 as often by attention deficit disorder as boys, and so on.

But we are talking here about a substance needed for the

very basic body structures and functions.

It is not likely that boys simply burned most of the extra DHA for energy, due to their faster metabolism, as the authors hypothesize. If anyone, they should give more respect to human body: it is much smarter than to burn - for the lousy 9 calories from about 1g of extra DHA daily - what is needed for vital cellular functions. Rather, they should turn to the possible study shortcomings, making its final results less reliable.

And we don't have to look far to find them. Authors themselves state that study results were "robust" enough to be interpreted as positive - even if only for girls significantly - despite wide variations in what we can generalize as the degree of physical derangement of baby participants (the authors address it more specifically as substantial differences in gestation period - 23 to 33 weeks - nutritional stressors, organ immaturity and illnesses).

In other words, it was a random, uncontrolled factor in the study; isn't it possible that this was influencing how babies were doing, independently of DHA supplementation?

Of course it's possible. In fact, this is exactly what another study (Morris et al., Journal of Pathology 2002) implies. The study followed 96 high-risk and 137 low-risk pre-term infants, as well as 136 full-term infants at 6, 18, 30, 42 and 54 months of age (high- and low-risk levels were determined according to the degree of present medical complications). It concluded that the two most important predictors of neurological development, measured by TCR (motor tone, coordination and reflex) score, were the

level of medical complications and gender,

which were more consistent predictors than the third main factor, gestational age.

While the TCR is narrower in scope than MDI in assessing neurological function, there is clear correlation between the two. It is not to expect that the medical risk level is the major factor for the former, and insignificant for the latter. Thus, if the incidence of medical complications among babies in all four primary groups of the Australian study (DHA supplemented girls and boys, and standard-intake girls and boys groups) wasn't at least roughly similar, it would very likely induce bias in study results.

Another possibly influential factor that this study indicates stems, again, from the difference in the rate of brain development between girls and boys. Morris et al. established that the initial differences in the level of neurological development tend to lessen going from 6 to 18 months of age, as infants that were behind developed at a faster rate in this period. However, as more refined movements were developing, the difference in the level of neurological development widened again.

In other words, girls in the Australian study could have shown more of a difference in their neurological development in part due to being at a more advanced level than boys. This could have been neutralized by testing girls and boys not at the same age, but at a similar level of their average development; such balancing of all relevant factors should be a part of study design.

But that is still only wishful thinking. A crucial factor routinely neglected in 99% of medical studies - with no justifiable reason - is nutritional status of the participants. It depends not only on their nutritional intake, but just as much on individual metabolism processing that intake. If one single nutrient, DHA, according to the researchers, may have the power to significantly affect brain development,

how about all the rest of them?

Factors that should be controlled in this type of study also include socioeconomic status, parents education, both general and health and nutrition-related, genetic inheritance, familial environment, as well as the always present chemical environment. High exposure to plasticizers (phthalates), for instance, can interfere with fatty acid metabolism, resulting in low DHA at the cellular level.

Sure, a study controlling all relevant factors would be both, more complex and more expensive. Funding constraints are often to blame for compromises in this respect. But as long as we settle with compromised medical studies, we'll keep getting these unreliable, confusing, often contradicting results.

As for the DHA, it is no news that it plays important role in development, as it does latter in life. But so does host of other nutrients. It is only logical that preterm babies have increased need for DHA, but it certainly includes other nutrients as well. If we are to single out the greatest value of this Australian study, it is in turning our focus to what really matters for health.

And it ain't drugs...