Wednesday, September 25, 2013

The importance of thinking about human milk and infant needs

It is very interesting teaching a course on the importance of an evolutionary perspective on health, because as we often see in our in class examples or in news reports, this perspective is often lost in clinical research and in scientific publications. One big one has come to my attention this week, and is worth discussing in light of its limitations and general lack of evolutionary thinking. 

The paper, “Can we define an infant’s need from the composition of human milk?” by  Stam et al., (2013), was published this month in the American Journal of Clinical Nutrition. The authors immediately set up a straw man: milk should meet a baby’s needs, and thus, given the variation in human milk composition, this cannot possibly be true. As a follow-up, they go on to suggest that human milk therefore should not be used as the standard reference for infant formula, stating “The composition of infant formula is presently based on mean values for human milk. It might be better to base the composition on actual requirements of the newborn infant” (Stam: 526S). 

Let’s start with acknowledging that they do in fact have a point here. It would be optimal to feed an infant to their metabolic requirements, and not over- or under-feed. However, what this obscures is the considerable variation in infant metabolic requirements, as evidence by prior doubly labeled water studies (Butte et al., 1990, 1996; de Bruin et al., 1998).  It also assumes that the newborn period alone is sufficient to capture the energy requirements of an infant. It seems quite logical to think that a 7.5 pound newborn will have very different metabolic requirements than a 16 pound 6 month infant (Butte et al., 2000). For requirements to be used as a substitute reference value, you would have to have repeated measures on the same infant – and would likely need to do every infant to come up with an individualized nutritional recommendation. Measuring the total energy expenditure of an individual – including an infant – is quite costly, and requires very specific protocols. 
Figure 1: Seven pound, five ounce baby Jesus with your Baby Einstein tapes . . .

The second big issue here is the idea of means as somehow representative of an ideal of human milk, and that deviations from these means are problematic only if you assume uniformity is the goal. And on some levels, we like the idea of nutritional uniformity. That’s essentially what the nutritional information on a package is: the measure of how much fat, energy, protein, etc. is in the food item. And the printed information assumes uniformity per gram. 

Except the error of calculation for the nutritional information on food packaging is in the range of 8-20% (yup, the FDA allows for underestimates of up to 20%! (Urban et al., 2010)). So even products that we might think of as uniform, such as the Fig Newtons on my desk or formula in a bottle, are not uniform.  Means are just that – a value indicating that half the sample distribution falls above and half below that value. An individual with that mean may not even be present in the sample! So in basing reference values for infant formula nutritional composition off a hypothesized “mean milk” value, what is happening is that you are trying to balance over- and under- nutrition. Ideally, we’d use a product tailor made to individual infant needs. Like you for example . . . human milk. But for women who cannot breastfeed or for families where breastfeeding is not the best option, formula is necessary and its composition should be referenced to the natural first food an infant receives: human milk. Matching to TEE, unless collected on each infant at highly frequent intervals, is not going to be any better than matching to mean values derived from human milk. And we know from numerous studies that the composition of human milk changes over the course of lactation (Mitoulas et al., 2001). Perhaps you could make an argument that formula fed infants need more options: a sequence of formulas that are changed as the infant ages. Similar to toddler or follow-up milks, but more specific. 

Stam et al., also question the validity of measures of milk intake in breastfeeding studies. Yes, getting an accurate measure of infant milk intake is hard. Like the physics in the background of The Big Bang Theory hard. And the gold standard method – doubly labeled water is expensive. And if you’re seeing double (doubly labeled water that is) it is because the same method used to measure TEE is used to measure breast milk intake. In a TEE measure, the infant is given the doubly labeled water, in measuring human milk intake, the mother drinks the water. You then collect infant urine over a minimum of 3 days (12 is optimal). In an exclusively breastfed infant, TEE and milk energy intake should be fairly close – and the difference should be in energy allocated to fat deposition. Formula fed infants have higher TEEs compared to breastfeed infants (Butte et al., 1990).

Figure 2: Sheldon attempts to measure infant milk intake and decides to go back to physics. Image: Big Bang Theory, by way of

And here’s the final thing. Babies have agency. I work with breastfeeding infants primarily, so my exposure is largely limited to them. And in collecting milk samples, we need the infant to nurse. And as any mother can tell you – you really can’t force a baby to nurse. Maybe a newborn. But for most infants, you cannot force a baby to nurse – successful transfer of milk requires anatomical coordination between the infant and the mother. And infants can stop when they get full, or not eat if not hungry – or eat for longer or nurse more frequently if hungry. There is a large body of literature supporting the role of self-regulation in infant intake, and in particular the likely importance of this self-regulation for the development of appetite control and satiety. These factors have been suggested to play a role in the protective effects of breastfeeding on later risk of obesity and related metabolic disorders. 

Finally, and this is something that I think anthropology really brings to the study of human milk in particular and lactation in general, is an appreciation for the fact that human milk has evolved. There have been distinctive selective pressures on human milk – well on all milk (Milligan and Hinde, 2011). This likely includes meeting the TEE of an infant, with some energy left over for storage as fat. If you don’t meet the TEE needs of the infant, the infant is not going to do well – chronic malnutrition is associated with growth faltering, wasting, reduced immune function leading to increased risk of infection, and if prolonged – death. 

And providing too much energy is wasteful – in models of fitness, we often talk about reproductive fitness, and the allocation of energy between competing functions such as reproduction and maintenance. In reproduction, energy needs to be balanced between current and future reproduction. Investing too much energy in a single reproduction – by making milk that is far in excess of infant nutritional needs would be wasteful and may have long term consequences on reproductive fitness. Ergo, there should be relative balance between the TEE of the infant and the energy intake from the milk.  Some aspects of milk will not be always be perfectly matched to infant needs – especially those aspects that may vary based on maternal diet or activity, such as DHA and Vitamin D. For example, milk from mothers in the United States is low in DHA compared to habitually fish eating populations. Many lactating mothers take DHA supplements, and the recent move to fortify formula with DHA reflects knowledge on the importance of DHA for infant development. Too often, we are thinking about human milk nutritional composition as homogeneous, and balking uneasily at the variation found within and between populations in composition. But this variation in composition is actually incredibly important – and only problematic if we think that all infants have a uniform nutritional need and the variation in human milk around some fictional mean is starving some infants and overfeeding others. No; variation in infant TEE is perfectly normal, variation in milk composition is perfectly normal, and infants are not passive consumers of milk but active participants in getting their needs met.*

*Obviously, mothers can limit and control access to the breast, but infants can often compensate by altering intake during suckling. 

Agostoni C.  2005. Ghrelin, leptin and the neurometabolic axis of breastfed and formula-fed infants. Acta Paediatr. 94(5):523-5.

Butte NF, Wong WW, Hopkinson JM, Heinz CJ, Mehta NR, Smith EO. 2000. Energy requirements derived from total energy expenditure and energy deposition during the first 2 y of life. Am J Clin Nutr. 72(6):1558-69.

Butte NF, Wong WW, Ferlic L, Smith EO, Klein PD, Garza C. 1990. Energy expenditure and deposition of breast-fed and formula-fed infants during early infancy. Pediatr Res. 28(6):631-40.

Butte NF. 1996. Energy requirements of infants. Eur J Clin Nutr. 50 Suppl 1:S24-36.

de Bruin NC, Degenhart HJ, Gàl S, Westerterp KR, Stijnen T, Visser HK. 1998. Energy utilization and growth in breast-fed and formula-fed infants measured prospectively during the first year of life. Am J Clin Nutr. 67(5):885-96.

Hinde K, Milligan LA. 2011. Primate milk: proximate mechanisms and ultimate perspectives. Evol Anthropol. 20(1):9-23. doi: 10.1002/evan.20289.

Mitoulas LR, Kent JC, Cox DB, Owens RA, Sherriff JL, Hartmann PE. 2002. Variation in fat, lactose and protein in human milk over 24 h and throughout the first year of lactation. Br J Nutr. 88(1):29-37.

Stam J, Sauer PJ, Boehm G. 2013. Can we define an infant's need from the composition of human milk? Am J Clin Nutr. 98(2):521S-8S. doi: 10.3945/ajcn.112.044370.

Urban LE, Dallal GE, Robinson, LM, Ausman, LM, Saltzman E, Roberts SB. 2010. The accuracy of stated energy contents of reduced-energy, commercially prepared foods. J Am Diet Assoc. 110(1):116-123.