Breastfeeding and brain development: the new data

So technically, I am on a blogging/twitter break, to allow me to focus on fieldwork and papers. However, yesterday was such an awesome day for human lactation research, I really had to check back in. Yesterday, MelissaBartick released an awesome piece showing the maternal health consequences and costs of not breastfeeding, following on earlier work looking at the economic side. And, Sean Deoni and colleagues reported differences in the white matter myelin content of specific brain areas between exclusively breastfed, formula fed, and infants receiving both during the first months of life. The paper was reported in Science News and I immediately pulled the actual paper. It started a journey of discovery, and the story is far more detailed – and interesting – than the Science News article reported. There are actually several papers of interest here, each building on the work of the other in addressing the common theme: are the brains of breastfed and formula fed infants different and if so, how permanent are these differences?

Figure 1: A reference map of the brain. Source: http://www.willamette.edu/~gorr/classes/cs449/brain.html

Prior research has demonstrated that breastfeeding infants have increased IQ and cognitive performance compared to formula fed infants; these differences are seen even in low resource populations, where maternal education and household income tend to be inversely associated with breastfeeding duration. It was speculated that certain fatty acids in human milk, specifically the very long chain essential fatty acids Docosahexaenoic acid (DHA) and Arachidonic acid (AA), may contribute to these differences. DHA and AA are preferentially used in neural myelin sheaths. They have excellent neural conductivity. Studies have found that DHA makes up about 20% of the fatty acids in the brain, although this varies by region (Xiao et al., 2005), and probably population as well, although we do not know for certain. However, we do not know if it is the DHA, if it is the cholesterol in milk, as Deoni (2013) also proposed, or hormones in milk (known or unknown) that may be contributing to these differences. So for the moment, we will leave DHA aside, and focus on the brain differences between breastfed and formula fed infants. 

There are a handful of useful papers here: today I will focus on three. These are Deoni et al. 2013 (Deoni, S.C.L., et al., Breastfeeding and early white matter development: A cross-sectional study, NeuroImage (2013),http://dx.doi.org/10.1016/j.neuroimage.2013.05.090), Kafouri et al., 2013 (International Journal of Epidemiology 2013;42:150–159; doi:10.1093/ije/dys172) and Khedr et al., 2004 (Acta Paediatrica 93:734-738).  Infant brains, by the way are amazing! Our fastest rates of brain growth are during gestation and the first two years of life. During this time, the brain consumes a huge amount of energy – and will reach about 80% of adult size by age two. Below is a map of the brain. I found it quite useful to keep track of what was going on where.

The most recent study, by Deoni et al., (2013) looks at white matter structure in the brains of 3 groups of 133 kids. Groups are defined by feeding status at 3 months of age: exclusively breastfed, formula fed, both. At the time of measurement, each group had a mean age of around 775 days – or just over 2 years of age. There were 85 kids in the EBF group, 38 in the combo group, and 51 in the exclusive formula feeding group. The children were scanned for 19-24 minutes using multicomponent relaxation magnetic resonance imaging (mcDESPOT, Figure 1) during natural sleep (no drugging!). McDESPOT allows for the estimation of the white matter content of neural tissue by measuring the amount of myelin associated water fraction. 

Figure 2:

: Graphic illustrating the principles behind mcDESPOT. Image is by Sean Deoni, the study author. 

Source: http://www.butler.org/CADASILSite/trials/imaging.htm

The major findings were that the breastfed infants had greater white matter growth in late maturing areas of the brain. This suggests that the absence of something in formula that is present in human milk may have delayed the brain growth in the mixed feed and formula feed kids. Key areas with increased VFm were the frontal brain, left temporal lobe, corpus callous, internal capsule, corticospinal tract, cerebellum, and left optic radiation. By comparison, infants receiving formula had increased white matter in the occipital lobe, right optic radiation, and right internal capsule.

Figure 3: How mcDESPOT looks in my mind. Source: http://www.wtfnews.org/general/kid-freaked-out-by-ronald-mcdonald/

Confused yet? Me too. I read this with a map of the brain and a lot of patience. Essentially, what Deoni et al., found was that the areas of the brain that are considering late maturing – and associated with higher order functions (such as performance on IQ tests, social and emotional functioning) had greater amount of white matter in infants exclusively breastfed to three months, and that these differences could be detected at age 2, along with high receptive language scores. There was also an association between breastfeeding duration and white matter content of specific brain regions. The right inferiorfrontal and corticospinal tract had a 30% increase in white matter compared to those same areas in formula fed infants, and longer breastfeeding durations (600 vs 200 days) were associated with greater white matter content of the Brodmann’s area.

The authors speculated that the greater amounts of white matter in the brains of breastfed infants might persist into later life. 

This follows on Kafouri et al., (2013), who were also investigating the association between breastfeeding and brain development. However, Kafouri et al., are slightly later in time – specifically, they are looking at brain scans from 571 adolescents (12-18) and testing for differences in the cortical thickness of specific areas of the brain associated with cognitive function and performance on the Wescher Intelligence Scale Test. Key areas were identified from 23 prior studies and 30 analyses and were limited to 328 foci in 36 “IQ related regions” of the brain. All analyses were adjusted for potential confounders: education and income, and prenatal exposures such as maternal or second hand smoking, alcohol use, parity, birth weight, and infant sex. 

Figure 4: The process behind mapping cortisol thickness. Source: http://www.martinos.org/neurorecovery/technology.htm

Among adolescents, exclusive breastfeeding duration (EBF) had a positive association with cortical thickness in the superior and inferior parietal lobes. There were no differences by EBF duration in the front eye field, medial or ventrolateral prefrontal cortex, or occipital cortex. EBF duration was also associated with increased performance on the full IQ test. However, there was no association between cortical thickness in the superior and inferior parietal lobes and performance on the Wescher IQ test. Overall, the main finding was the increased cortical thickness in the parietal lobes with limited evidence for a dose dependent association between breastfeeding duration and cortical thickness. 

Our blast from the past is Khedr et al., 2004, specifically looking at neurological maturation between breastfeed and formula fed infants at age 1. In a sample of 53 infants, 30 breastfed and 23 formula fed, they reported shorter latencies in the breastfed infants compared to the formula fed infants on two parameters: visual and auditory, but not somatosensory. Essentially, the infants who were breastfed had more mature visual and auditory responses. This makes sense, as the somatosensory system is established prior to birth and postnatal feeding may have minimal influences. 

So what does it all mean? Well, it likely means that the absence of something in formula has long term influences on the neurological development of children, and that some of these differences persist at least into adulthood. And for a first few sentences into what this research will become, it is pretty cool stuff. For many years, researchers have argued about what in milk is associated with the decrease in risk of obesity and related metabolic conditions in breastfed infants. Now, we get to argue about what in milk is associated with the increased amount of white matter and cognitive thickness. And maybe it is DHA, but what we know about DHA is also pretty limited. Before we go jumping on the DHA bandwagon, the DHA content of American women’s milk is actually quite low (Figure 5) compared to the rest of the world. 

Figure 5: DHA in the milks of the world.

The DHA content of US women is actually quite low.  Take a supplement. We are also sad that our data for the Philippines is not on here. Source: http://www.dhababy.com/Infants/BreastisBest.aspx

We could all probably use more DHA in our diets, and maybe we should even recommend that reproductive aged women take a DHA supplement (fish oil) like we recommend folic acid. If it is DHA, that is an easy enough fix – the addition of DHA to infant formula a few years ago provides an opportunity to test the hypothesis that it is DHA by doing a similar set of analyses on breastfed, DHA fortified, and non-DHA fortified formula users. If two groups do not look like the others, you have some interesting results. DHA formula and breastfeeding grouping together? Hooray! It is DHA. The two formula groups lumping together – it is something else, or many, many something elses in the milk – or even the act of feeding. And of course, getting the milk would be awesome as well, because then you could look at the brain and the fatty acids and hormones in the milk (Maybe milk sugars are important? Maybe hormones?). And doing a longitudinal study, starting close to birth and following infants through a year or two. Oh yeah, and there are some gene polymorphisms (FADS) that appear to be involved in fatty acid content of milk and infant cognition as well (Steer et al., 2010).

In summary: there is some new evidence suggesting that breastfeeding is associated with improved growth in white matter in early life, and increased cortical thickness that persists at least until adolescents. However, how these factors change longitudinally is unknown, and what it is in milk that may be associated with normal brain maturation (because breastfeeding is the default feeding condition; infants evolved drinking human milk) is also unknown. But there is a lot of material here, and it will be very interesting to see where it goes next. 

References

Brion MJ, Lawlor DA, Matijasevich A, Horta B, Anselmi L, Araújo CL, Menezes AM, Victora CG, Smith GD. 2011. What are the causal effects of breastfeeding on IQ, obesity and blood pressure? Evidence from comparing high-income with middle-income cohorts. Int J Epidemiol. 2011 Jun;40(3):670-80. doi: 10.1093/ije/dyr020.

Deoni SC, Dean DC 3rd, Piryatinksy I, O'Muircheartaigh J, Waskiewicz N, Lehman K, Han M, Dirks H. 2013 Breastfeeding and Early White Matter Development: A Cross Sectional Study. Neuroimage. May 27. doi:pii: S1053-8119(13)00592-2. 10.1016/j.neuroimage.2013.05.090. [Epub ahead of print]

Kafouri S, Kramer M, Leonard G, Perron M, Pike B, Richer L, Toro R, Veillette S, Pausova Z, Paus T. 2013. Breastfeeding and brain structure in adolescence. Int J Epidemiol. 42(1):150-9. doi: 10.1093/ije/dys172. Epub 2012 Nov 21.

Khedr EM, Farghaly WM, Amry S, El-Din, Osman, AA. 2004. Neural maturation of breastfed and formula-fed infants. Acta Paediatrica. 93(6): 734-738.

Steer CD, Davey Smith G, Emmett PM, Hibbeln JR, Golding J. 2010. FADS2 polymorphisms modify the effect of breastfeeding on child IQ. PLoS One. 2010 Jul 13;5(7):e11570. doi: 10.1371/journal.pone.0011570.

Xiao Y, Huang Y, Chen ZY. 2005. Distribution, depletion and recovery of docosahexaenoic acid are region-specific in rat brain. Br J Nutr 94(4):544-50.

Some thoughts on weaning: Shakira and the Neaderthal

Greetings, and welcome to my inaugural blog post. EA is still in Nepal – in Kathmandu, last I heard – and I’m settling in and trying to find my blogging voice. As EA said, I’m a cultural anthropologist, which in my case means not only keeping up with the scientific journal articles about breastfeeding but also looking at  the ways breastfeeding is talked about in popular media. I had been contemplating writing about weaning even before checking the news today, but reading about Shakira's desire to breastfeed her son "until he goes to college" clinched it. Yes, I'm pretty sure she was joking, but she wouldn't be the first celebrity to breastfeed past a year or two. Mayim Bialik (Big Bang Theory) nursed her second son until he weaned this February at age four, a fact she wrote about publicly and triumphantly.

But before this blog deteriorates entirely into a synopsis of Us Magazine articles (probably not what EA intended), I'll note that the original inspiration for a blog entry on weaning was this article from Nature by Austin et al. (2013), about using barium-to-calcium ratios in tooth enamel to determine when nursing infants began to eat supplemental foods and when they stopped breastfeeding altogether. Although the bulk of the research was based on the teeth of humans and macaques with known weaning ages, perhaps the most interesting piece was an analysis of the tooth of a young Middle Paleolithic Neanderthal. According to the barium distribution, the infant began eating supplemental foods at seven months and weaned entirely at fourteen months. This is younger than most researchers would have suspected, based on what we know about weaning ages in non-industrial societies. Of course with an n of one one can't really draw general conclusions - it's possible the infant's mother became ill or died - but it's an intriguing finding nonetheless.

So, how long should a child be breastfed? How long is too long - college? four? - and how long is not long enough? The American Academy of Pediatrics last year reaffirmed its declaration that breastfeeding should continue for a minimum of one year and "as long as mutually desired by mother and baby", although only about 25% of babies in the U.S. meet this goal. Katherine Dettwyler's classic 1995 piece A Time to Wean: The Hominid Blueprint for the Natural Age of Weaning in Modern Human Populations (summarized on her website) suggested that if weaning was not influenced by culture, humans would wean somewhere between age 2.5 and 7. But of course, weaning in humans is influenced by culture, as is breastfeeding itself (the concept of breastfeeding as both a biological and a social and cultural practice is summarized well in the first few pages of this 2012 article by Fouts et al.). Last year's Time magazine cover showing a women breastfeeding her 3 year old son ignited a storm of controversy and a slew of negative comments calling the practice everything from attention-seeking and tacky to abusive (examples in this article and in these comments). Dowling and Brown (2013) echo this finding in their recent study of  British mothers who breastfeed longer-term (which they define as more than six months). These women report accusations that they were hurting their children or enjoyed pain, and felt that many saw their breastfeeding as bizarre or comical - even though many were actually breastfeeding for a shorter time than suggested by medical authorities.

Finally, another recent study found that sixty percent of U.S. women surveyed weaned their children before they wanted to (Odom et al. 2013). I found it significant that many of the problems associated with early termination - cracked nipples, perceived poor weight gain and insufficient milk, pain during breastfeeding - could potentially have been managed by a competent lactation consultant. Perhaps, in western countries with clean water and access to artificial baby milks (infant formula), the focus should shift from telling women "too long" or "not long enough" to understanding how women determine the optimal length of time for breastfeeding and giving them the tools they need to breastfeed "as long as mutually desired by mother and baby", whether that's 14 months or four years. Not college, though. I'm betting Shakira changes her mind by then.

References

Austin C, Smith T, Bradman A, Hinde K, Joannes-Boyau R, Bishop D, Hare D, Doble P, Eskenazi B, Arora M.(2013) Barium distributions in teeth reveal early-life dietary transitions in primates. Nature doi:10.1038/nature12169

Dettwyler, K (1995). A time to wean: the hominid blueprint for the natural age of weaning in modern human populations. Breastfeeding: Biocultural Perspectives. Hawthorne, NY: Aldine de Gruyter, 39-73.

Dowling, S, Brown, A. (2013). An Exploration of the experiences of mothers who breastfeed long-term: What are the issues and why does it matter? Breastfeeding Medicine 8(1):45-52.

Fouts H, Hewlett B, and Lamb M. (2012) A biocultural approach to breastfeeding interactions
in Central Africa. American Anthropologist 114(1):123-136.

Odom, E. C., Li, R., Scanlon, K. S., Perrine, C. G., & Grummer-Strawn, L. (2013). Reasons for earlier than desired cessation of breastfeeding. Pediatrics,131(3), e726-e732.