Sunday, January 31, 2016

Wait, there's more: milk adiponectin and child growth varies!

It was a big day for the Biomarkers & Milk group. We had an important paper accepted at Annals of Human Biology. This paper is the second paper to come out of the Milk with Altitude Project (2013 edition), and I assure you, there will be more! 

This paper is important to me because it is further evidence for a hypothesis I have been working on. As I have written before, as an anthropologist, I tend to study non-western populations, and my research is primarily concentrated with two groups: Filipinos living in Cebu, Philippines, and ethnic Tibetans living in Nepal. Recently, working with an outstanding team of undergraduates, we published a paper looking at the hormone adiponectin in milk samples from 113 Filipino women.
So why are we excited about this? In the Cebu adiponectin article, we reported something new and different about milk adiponectin and child growth. Prior to our work, a phenomenal piece by Woo et al., (2012) had shown a significant, inverse association between milk adiponectin and infant weight for age z-score. Simply put: more adiponectin in milk, less growth in the child. BUT – and here’s the cool part – they found that the slower growing children had faster growth from 1-2 years of age.
Katie Hinde over at Mammals Suck suggested that this may be an adaptive strategy to allow mothers to mediate their energetic investment in offspring. By down regulating growth while it is directly dependent on her metabolism, mothers may be able to conceive sooner. The catch-up growth from 1-2 years then, makes complete sense – children are then growing when other community members can contribute to their energetic budgets.

And we think we’ve found the corollary – such trade-offs are environmentally sensitive. In a high resource (low pathogen?) environment such as that of the mothers Woo et al., studied, this is an excellent reproductive strategy, as it allows mothers to defer some of the costs of reproduction to others. However, in a low resource (high pathogen?) environment, the resources necessary to support later growth may be unavailable, and it may be a better reproductive strategy to promote early growth – when maternal metabolism can support it.

For the Cebu study, we had mean adiponectin levels of 7 ng/mL of milk, compared to 21 ng/mL for the US women Woo et al., studied. Child weight for age (centiles) also differed – the 50th percentile for our sample was equivalent to the 5th percentile for US infants. However, when we used a similar analytical technique as Woo et al., a really interesting picture emerged (Figure 1). Our data fit almost perfectly with that of Woo et al. In their model, there is a plateau for the association between milk adiponectin and child growth at lower levels of milk adiponectin (10-13 ng/mL) followed by a decline in weight for age as milk adiponectin increases. We found a positive association between milk adiponectin and infant weight for age at even lower levels of milk adiponectin (2 ng/mL to 8 ng/mL) – however there was a plateauing of the association from about 8-10 ng/mL, or the max of our range. The distribution of milk adiponectin in our sample barely overlapped with that of Woo et al.
Figure 1: Comparison of weight-for-age percentiles by milk adiponectin between the Woo et al., study and the Cebu study. C

When you put the two datasets together, instead of forming alternative models, they form a complementary model suggesting that the association between milk adiponectin and child weight for age z-score is not a linear association but rather a bell-shaped association, where at a very low levels (<7ng/mL) milk adiponectin is positively associated with growth, a flattening of the association at levels of 7-12 ng/mL (intermediate levels) and then an inverse association between milk adiponectin and growth at higher (>12 ng/mL) levels. And because milk adiponectin had not generally been studied in non-Western populations, such association was largely missed. This is why studying milk composition in a diversity of human populations and ecological zones is so important.

We’ve replicated this in our Tibetan study, but that’s a separate post because the relationships get even more interesting. Once the Tibetan study is out, I’ll continue the discussion started here with that piece. 

References cited
Anderson J, McKinley K, Onugha J, Duazo P, Chernoff M, Quinn EA. (2015) Lower levels of human milk adiponectin predict offspring weight for age: a study in a lean population of Filipinos. Matern Child Nutr. 2015 Oct 7. doi: 10.1111/mcn.12216. [Epub ahead of print]

Hinde K. (2012) Mother’ fat sends love letter to baby via the milk express., accessed Jan 26, 2016.

Martin LJ, Woo JG, Geraghty SR, Altaye M, Davidson BS, Banach W, Dolan LM, Ruiz-Palacios GM, Morrow AL. (2006) Adiponectin is present in human milk and is associated with maternal factors. Am J Clin Nutr. 2006 May;83(5):1106-11.

Woo JG, Guerrero ML, Guo F, Martin LJ, Davidson BS, Ortega H, Ruiz-Palacios GM, Morrow AL. (2012) Human milk adiponectin affects infant weight trajectory during the second year of life. J Pediatr Gastroenterol Nutr. 2012 Apr;54(4):532-9. doi: 10.1097/MPG.0b013e31823fde04.

Monday, January 25, 2016

Project video!

I actually have a post written . . . it will go up later this week.


Saturday, January 2, 2016

2016 Happenings at Biomarkers&Milk

I have not been very reliable about posting to this blog. Part of that was that 2015 was an unbelievably busy year for me, and I had very little time for the blog. Another part of the issue was me - I was uncertain as to whether or not this was still a priority for me. In 2015, I received a large grant from the National Science Foundation for a 3 year birth cohort study in Nubri, Nepal. This project is HUGE and has been very time consuming. I have backed off on the blog simply to have more time for this project.

So what is the future of Biomarkers&Milk? I’m staying. I’m committing to 12 posts in 2016 – one a month – plus additional topical posts. 

Growing up with altitude: field report

Figure 1: Checking in mothers, collecting informed consent at a measurement session.
Last month, I arrived back in the United States after a month long field season in the Himalayas. As it is mid-semester, my trip was designed to maximize field time and minimize missed classroom time. I missed six classes, generous covered by my colleagues from within and outside of the university. We spent just over 3 weeks in the field, and one week in Kathmandu. I arrived Friday evening and we left Sunday afternoon for Nubri; we returned to Kathmandu on Monday and left Friday for the United States. In the interim, we had an amazingly successful project – in 3 weeks, we measured from than 500 children living in the Nubri Valley in 11 major villages and 5 smaller villages both on and off the tourist routes. Upon returning to Kathmandu, we made arrangements with the two largest boarding schools to come and measure children from Nubri who were currently in Kathmandu for schooling. We measured another 270 children in Kathmandu over a 4 day period, bringing our total to just under 800. Based on our demographic data and population census data from the Nepali government, we captured more than 80% of Nubri children, with all but about 35 children living in the Nubri valley measured. We had 1 refusal, and missed the rest of the children because of comings and goings to and from the boarding schools within the villages – they would be in their home village when we measured the boarding school and then in the boarding school when we reached the home village. We also measured almost all women of reproductive age in the villages.

Figure 2: A village in Nubri.
What can I say about the growth project? It was exhausting, and we collected an unbelievable amount of data in just a few weeks. I just started entering data, and it will be a long, but steady process to get everything worked out. We saw unbelievable patterns of migration, and many of the biological and social processes going on will require considerable investigation and thought before we are able – and willing – to better share the research. The growth project was generously sponsored by an early career development grant from the American Association of Physical Anthropologists.

Figure 3: My three AMAZING field assistants and I. This photo was taken by our camp manager.
The primary reason we were in Nubri however, was to start a longitudinal birth cohort. Thanks to a substantial grant by the National Science Foundation, we have funds to start the first ever high altitude birth cohort study. Over the next 18 months, all children born in 11 study villages will be recruited into the birth cohort. We had intended on recruiting from 9 study villages; my field assistants who will be living in Nubri for the next several years, insisted that we add in three extra villages and remove one village from the study. I think they had great justifications for this, and we have modified recruitment accordingly. We also happened to have great luck with births, and were around for six births, which meant I was able to get birth weights almost immediately. Another 20 women were 5-9 months pregnant and agreed to be in the study – meaning we are starting the birth cohort off with 26 mothers – about a quarter of our targeted sample size. Infants in the birth cohort will be measured at birth by community midwives and each month thereafter until 1 year of age by the 3 field assistants living in the Nubri Valley. We’ll collect milk, basic anthropometrics on mothers and infants, health histories, feeding histories, caregiving and breastfeeding practices, and some really cool body composition data. It is a huge, exhaustive project but has incredible potential to transform what we know about infancy and early childhood in high altitude adapted – and high altitude living – populations.

Sunday, September 20, 2015

Burgers on breasts – what is really going on here?

Recently, a series of advertisements came into the public consequence. These images depict women breastfeeding, with one breast painted to look like a hamburger, doughnut, or can of soda. The message is “Your child is what you eat”, suggesting that the mother’s diet is directly related to the construction of the baby – that is, eat a burger, build a baby from burgers.

Before we get into a discussion of the factual accuracy of the statement, it is worth taking a moment to think about the ads themselves. The ads were most likely produced by the advertising company PAIM, and the logo depicted is that of the SPRS – the Pediatric Society of Rio Grande (Brazil). SPRS is sponsored by Nestle, and there is some evidence that PAIM also holds the Nestle ad campaign for Brazil. But here’s my big question: why are the ads in English? The national language of Brazil is Portuguese, and as of 2011, the best guess for English fluency among educated Brazilians was 8-11% (Glickhouse, 2012). Your milk what you eat should be “Seu leite é o que você come” (if Google translate is accurate). 

Although the images contain the logo for SPRS and a link to the website, the ads are not on the SPRS website. The SPRS website is also in Portuguese. Moreover, the food images just don’t quite match up to typical Brazilian cuisine – burgers commonly have eggs or corn for example, and doughnuts with holes in the middle are not that common in Brazil. So – just who were those ads designed for?
Leaving aside this very big question, the ads have generated considerable international attention and debate. Many mothers have expressed concern about the message: your baby is what you eat. But is it true? Well, the best answer is “somewhat – but not really”, at least as a far as breast milk is concerned.

Breast milk is produced by the mothers’ body (for review, see my prior post here). Generally, the proteins and sugars in the milk are largely independent of what the mother eats. This reflects the synthesis of protein and sugar by specialized cells, called lactocytes, in the breast. Synthesis occurs from glucose, amino acids, and similar. Very few dietary or lifestyle factors appears to influence milk protein, especially milk proteins that are not immunoproteins. 

Total milk fat, at least for humans, is largely independent of the mother’s diet (Villalpando and Del Prado, 1999). However, the fatty acid composition of the milk fat is strongly correlated with the maternal diet.

Probably the best known example is that of DHA. Most pre- and post-natal vitamins contain fish oils or DHA. DHA is a long chain, polyunsaturated fatty acid that cannot be produced by the mother’s body and must be derived from her diet. Ergo, milk DHA is very sensitive to the mother’s diet – more dietary DHA, more DHA in milk. Figure 1 shows an example from our work in the Philippines (Quinn et al., 2012), where we found a dose association between meals of a local fish (bodboron) and milk DHA. If you haven’t heard of bodboron, don’t be surprised – in the US, it is commonly fed to salmon rather than consumed. Working with mothers in Denmark, Lauritzen et al., (2002) also showed a positive association between fish consumption (in this case salmon) and milk DHA. Fish oil consumption has long been recognized as a source of milk DHA (Harris et al., 1984). It is also understood that fatty acids – especially long chain fatty acids like DHA – accumulate in body fat where they can be utilized later. 
Figure 1: Fish consumption and milk DHA content in a sample of Filipino mothers living in Cebu, Philippines (Quinn et al., 2012).

What if a mother is consuming a diet that is very low in fat? There is no substantial evidence that her total milk fat will be lower (Villalpando and Del Prado 1999). This is another one of those instances where mothers’ bodies are amazing – her body will produce certain fatty acids from glucose derived from the carbohydrates in her diet. Humans cannot produce long chain fatty acids like DHA – but the breast and liver can produce medium chain fatty acids – fatty acids with less than 14-16 carbons (Figure 2).  These medium chain fatty acids are routinely incorporated into milk fat, and, when dietary and existing fat stores are insufficient to meet demand, the mother’s body will produce more medium chain fatty acids to maintain milk fat (Rudolph et al., 2007). Thus, total fat is maintained, even if fatty acid composition is altered.

Figure 2: Comparison of two fatty acids - TOP: lauric acid, which has a carbon chain length of 12 and can be produced by the mammary gland and liver, and BOTTOM: DHA, which cannot be produced by the body.

Another concern would be man-made food products, like trans-fatty acids or artificial sweetners (up next!). These have been found in human milk; and there is general concern about the levels of trans-fatty acids in human milk. Product labeling has resulted in lower dietary intakes and a reduction in milk trans-fatty acids in Canadian mothers (Ratnayake et al., 2014); a recent analysis of some 2327 food products in Brazil found that more than half contained trans-fatty acids. The worst offenders were cookies, so if this was really an ad about trans-fatty acids, a cookie would be the appropriate image.

What does it come back to? These advertisements are making the same fictional point we have discussed here before with medical devices. You are a threat to your baby. Your body can’t be trusted. You can’t be trusted to eat right for your baby and thank heavens there is formula so you can’t harm your baby with your hamburgers.  These ads are deliberate, and the target audience is very much open for debate.

Glickhouse R. (2012) Lost in Translation. Christian Science Monitor.

Lauritzen L, Jørgensen MH, Hansen HS, Michaelsen KF. (2002) Fluctuations in human milk long-chain PUFA levels in relation to dietary fish intake. Lipids 37(3):237-44.

Quinn EA, Kuzawa CW. (2012) A dose-response relationship between fish consumption and human milk DHA content among Filipino women in Cebu City, Philippines. Acta Paediatr 101(10):e439-45. 

Ratnayake WN, Swist E, Zoka R, Gagnon C, Lillycrop W, Pantazapoulos P. (2014) Mandatory trans fat labeling regulations and nationwide product reformulations to reduce trans fatty acid content in foods contributed to lowered concentrations of trans fat in Canadian women's breast milk samples collected in 2009-2011. Am J Clin Nutr 100(4):1036-40.

Rudolph MC, Neville MC, Anderson SM. (2007) Lipid synthesis in lactation: diet and the fatty acid switch. J Mammary Gland Biol Neoplasia 12(4):269-81.

Villalpando S, del Prado M. (1999) Interrelation among dietary energy and fat intakes, maternal body fatness, and milk total lipid in humans. J Mammary Gland Biol Neoplasia 4(3):285-95.