Pregnancy, Vol. 3: Just how tailor-made is breastmilk for baby?
By: Signpost Science
Tags: Nutrition, Evolutionary Biology, Science, Immune System, Breastfeeding

Let me start this particular blog by cutting off at the pass anyone who wants to fit it into the “Mommy Wars” battle over breastfeeding. Yes, this blog is about breastmilk and what a ridiculously awesome substance it is — but you know what? Formula is pretty incredible too. It helps feed untold number of babies when breastmilk can’t. There are no ‘legitimate vs illegitimate” reasons to choose formula over breastmilk; the decision you make as a caregiver to your child is the right one, period, the end. Are you feeding your baby? You’re nailing it.

BUT! That doesn’t mean we can’t take a minute to marvel over the substance that breastmilk! I might never eat kale, but I can still appreciate all the goodies that are in it; I can read about how amazing New Zealand is and still choose to visit Thailand (because it is also amazing); I can celebrate Friend A’s birthday without it meaning that Friend B’s birthday isn’t important. Forgive my stretched analogies, but all this boils down to this: breastmilk is biologically, scientifically fascinating. Formula is a marvel of modern nutritional science. We are going to spend this blog post ogling at the first, which does not in any way negate or diminish the second. This isn’t a shot fired in any war; it is a celebration of biology.

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On a Sunday afternoon recently, I was reading a book on early primate evolution in preparation for a research project I want to kick off after my maternity leave. The book (Fossil Primates, by Susan Cachel) starts off with a few chapters dedicated to basic evolutionary theory and ecology. My skimming slammed to a halt at one sentence on page 67: “Because male infants grow larger, the milk that mothers provide them has an energy content that is 25% greater than that provided to female infants.” Say what now??I know, generally, that breastmilk is dynamic and changes based on all sorts of astonishing feedback loops between mom and baby, but the idea of breastmilk tailoring to the biological sex of an infant was news. So: exactly how tailor-made is breastmilk to baby?Does breastmilk change based on your baby’s biological sex?

TL;DR: Milk is ridiculously and astonishingly tailored to your baby’s needs. As for shifting based on sex, the data is clear that it doesin many mammals, but the jury is still out for humans.

First thing’s first, the science is very clear on one thing: breastmilk is dynamic. The first milk that mom produces, called colostrum, is packed with goodies to boost the immune system (Hsu et al 2014), including proteins which specifically serve to boost baby’s developing immune system (as opposed to proteins that are strictly nutritional). These immunological proteins were higher in milk produced for preterm infants compared to infants born at full term, as well (Montagneet al 1999). Even for infants born full-term, the protein content of milk changes through time in both type and amount: milk produced immediately after birth is packed with whey proteins. Through time, the concentration of a second kind of protein, casein, increases, changing the amino acid content of the milk. Amino acids are the basic building blocks of bodily proteins — think about them like individual Legos of different shapes. You need different Legos (amino acids) to build different structures, and so the specific shapes and sizes needed varies through time as baby develops. At first, baby needs to build that immune system; mom produces Lego amino acids from the Immune System starter kit. As baby goes (rapidly) through different immunological stages in early life, needing different kinds of microbial protection, nutrients, and so on, mom produces different amino acids to build these different structures and passes them along in breastmilk.

So the type of protein changes based on what amino acids baby needs, but what about the total amount of protein through time? In a meta-analysis of 43 original studies, Lönnerdalet al (2017) demonstrate that total protein (regardless of form) decreases through time, plummeting in the first week or so of infancy. By the end of the first year, total protein content decreases by about 47% from colostrum. This shift is in close sync with changing protein requirements of babies at different developmental stages. But changes are even more fine-grained than that! The nutritional content of milk changes from the beginning of a breastfeeding session to the end and throughout the day. For example, fat content is higher in milk produced at the end of a feeding session (compared to the beginning) and in the afternoon and evening (compared to the morning and night) (see Chung et al 2014 for a good overview of these differences).

Breastmilk is also responsive to the immune system need of baby as an individual, not just based on their age and general stage of development. It contains a particularly high quantity of an antibody called IgA, a molecule that regulates immune function in the respiratory and digestive system of all humans no matter our age. On a very basic level, our immune system works by detecting antigens, foreign or toxin substances from the environment that aggravate the body, and producing specific antibodiesto combat and remove them. You can think of antigens as invader soldiers, and antibodies as the body’s defending army.

Mom produces specific IgA molecules, antibodies tailored to combat the antigens in the immediate environment, and passes them along to baby. This is adaptive under the assumption that mom and baby are in the same environment, and the IgA molecules that mom needs will be the same ones that baby needs, but perhaps doesn’t have an immune system developed enough to produce themselves.

But that’s not all! Mom also produces IgA molecules to combat antigens detected in baby’s saliva. That’s right: when a baby breastfeeds, it’s not a one-way path. Baby’s saliva, including antigens that baby might not be able to produce antibodies to protect itself against, enter into mom’s body. Mom, an expert in antigen production thanks to her immune system’s many years of living as a person in the world, produces antigens for baby, and passes them along in the next breastfeeding session. Personalized medicine at its most intimate!

Bottom line: breastmilk does not stay static through time. Morning milk is different than evening milk, the first milk of a feeding session is different than that at the end, milk produced when a baby is first born is different than that months or years later, and milk produced for baby during high pollen season will be different than that produced in the dead of winter.

But what about milk content changing based on biological sex? Studies of primates (macaques, specifically) show that, at infant age between 3 and 4 months, milk for maleinfants has higher overall energy content and higher fat content, while milk for female infants is higher in calcium (Hinde 2007, 2009; Hinde et al 2013). These patterns broadly hold true for other mammals tested (including bovines, wallabies, and kangaroos) (see Galanteet al 2018 for a good review of these studies). However, in humans, such patterns have been much harder to nail down. Conclusions range from there being no difference in milk macronutrients between male and female infants (Quinn 2013), to mothers of maleinfants producing more energy-rich milk (based on carbohydrate and lipid content, Powe et al 2010, Dafaallah et al 2018), to mothers of female infants producing more energy-rich milk (Hahn 2017), to variation in which sex received more energy-rich milk changing based on the socioeconomic status of the mother (Fujita2012). Looking at other nutrients produces mixed results as well: Dafaallah et al 2018 found male infants received breast milk with higher calcium and lipid content than females in Sudan, while Yahya et al 2009 found the opposite pattern with calcium looking at mothers in Iraq.

Frustrated yet? Me too! But let’s take a step back. We know that breastmilk in all mammals, humans included, is dynamic through time and based on the immunological needs of baby. In studies of other mammals, there is a clear pattern of increased fat and energy content in breastmilk with the infant is a male. In humans, this trend seems to fall apart (or at least is much harder to pin down). Why would this be?

There is a hypothesis within evolutionary biology called the Trivers-Willard Hypothesis that predicts what offspring parents will invest more energy in (Trivers and Willard 1973). Remember, this hypothesis is looking at the whole natural, biological world through the unemotional lens of natural selection. The driving motivation behind the natural selection of some traits over others is which of these traits helps morecopies of your genes get into the next generation. It helps me to think of individuals not as living, breathing, snuggling, loving individuals, but rather as a motley crew of different shaped vessels driven by genes and DNA for the sole and singular purpose of making more copies of them. Let’s keep our imaginations in this space, and turn back to Trivers-Willard.

Biological males contribute to reproduction — and duplicating those all-important genes — through the production of sperm. Lotsof sperm. Theoretically, the only thing that limits how many offspring a single male can produce are the number of eggs that he can get those sperm to unite with. Biological females, on the other hand, carry the energetic burden of gestation (growing the baby in the womb) and, for mammals, lactation (breastfeeding). Once a female is gestating one infant (or liter of infants), it doesn’t matter how much sperm she finds, she is limited in the number of offspring she can produce by sheer energetics.

So if I am a mother with a liter of offspring, some male and some female, which ones should I bet on being most likely to pass those genes along to their own offspring? It depends on if I am (and, by extension, if my offspring are) in ‘good’ or ‘poor’ biological condition. If I am in biological ‘good condition’ (high ranking in my social position, with lots of resources and good health), males are statistically more likely to produce more offspring than females simply because they are not limited by the time and energy demands of gestation and lactation. In social animals, if I am high-ranking then my sons likely will be as well, ensuring that they are able to secure lots of mates. Therefore, I should invest in my maleoffspring to increase my potential number of grand-offspring. However, if I am in biologicallypoor condition (low-ranking on the social hierarchy, resource stressed, or otherwise struggling to survive), then my sons may be blocked from any mates at all — I should invest in my female offspring in this case. We see evidence for this trend in many animals, including a classic study on European red deer in which mothers are more likely to have sons when they are in ‘good’ condition and daughters when they are in ‘poor’ condition.

OK, lift your imagination out of organisms-as-gene-vessels, and let’s return to actual human beings. Evidence for the Trivers-Willard hypothesis at play in human societies is mixed at best, but there are hints that it may influence breastmilk composition. For example, Fujita2012 looked at mothers in Kenya and found that mothers in higher socioeconomic classes produced higher-energy milk for malebabies, while mothers in lower socioeconomic classes produced milk with higher fat (energy) content for female babies. Of course this is only one study, but it is intriguing. Could variation in the health and economic conditions of mothers across studies account for the highly variable results in human studies?

Another angle is to remember that humans, across so many aspects of our evolution and biology, are insanely adaptable. Our ability to adapt and flex to myriad environments, cultural conditions, diets, environmental exposures, and more set us apart from just about every other animal on Earth. It is why we, singularly in the primate family, are able to live across all 7 continents, eat just about anything, and survive under nearly incalculably different microbial, environmental, and climatic conditions. Why shouldn’t our production of breastmilk be equally and impressively flexible? To me, this flexibility and adaptability is one of the most inspiring and invigorating things about being a self-aware human: there is almost never one right path, one right way, or one right answer to how to be a ‘good’ human. Our power is in our flexibility.

So where does that leave us? Personally, I’m left with a few key takeaways:

1. If you are able, breastmilk is a powerfully tailor-made food for your baby that will directly address the nutritional and immunological needs of your baby, right at each specific moment in their developmental time.

2. If you are formula-feeding your baby, selecting a developmentally appropriate formula for your baby’s age makes a difference, as their nutritional needs shift through the first year of life. The science behind formula has grown in leaps and bounds recently — everything baby needs is there! This also explains why non-human milk, like cow’s milk or goat’s milk, is not the first choice for human infants (although in case of certain allergies and other condition, is certainly essential and even life-saving in some cases).

3. Does the biological sex of your baby change the composition of your breastmilk? This specific feedback mechanism is less clear, but the muddled data bespeaks a greater truth about humanity: we are flexible, adaptable, and complicated. Future studies should strive to understand the underlying mechanism driving these feedback loops, which will both tell us more about how amazing breastmilk is and how to continue to improve formula to best serve every baby.

And, take a minute to stretch. Next time you’re in a tight spot, pause and remember: you are part of one of the most adaptable species this earth has ever seen. Whatever mountain sits in front of you, you’re got millions of years of evolution on your side. You got this.

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Sources:

Cachel, S. (2015). Fossil primates. Cambridge University Press.

Chung, M. Y. (2014). Factors affecting human milk composition. Pediatrics & Neonatology, 55(6), 421–422.

Dafaallah S, Amin M, Abbas T, Mohammed A, Kabbara E (2018) Biochemical Differences in Human Breast Milk Contents According to Infant’s Gender. J Mol Biol Biotech. Vol.3 №1:2

Fujita M., Roth E., Lo Y.-J., Hurst C., Vollner J., Kendell A. In poor families, mothers’ milk is richer for daughters than sons: A test of Trivers–Willard hypothesis in agropastoral settlements in Northern Kenya. Am. J. Phys. Anthropol. 2012;149:52–59. doi: 10.1002/ajpa.22092.

Galante, L., Milan, A., Reynolds, C., Cameron-Smith, D., Vickers, M., & Pundir, S. (2018). Sex-specific human milk composition: The role of infant sex in determining early life nutrition. Nutrients, 10(9), 1194.

Hahn W.-H., Song J.-H., Song S., Kang N. mi. Do gender and birth height of infant affect calorie of human milk? An association study between human milk macronutrient and various birth factors. J. Matern. Fetal Neonatal. Med. 2017;30:1608–1612. doi: 10.1080/14767058.2016.1219989.

Hinde K., Foster A.B., Landis L.M., Rendina D., Oftedal O.T., Power M.L. Daughter dearest: Sex-biased calcium in mother’s milk among rhesus macaques. Am. J. Phys. Anthropol. 2013;151:144–150. doi: 10.1002/ajpa.22229.

Hinde K. Richer milk for sons but more milk for daughters: Sex-biased investment during lactation varies with maternal life history in rhesus macaques. Am. J. Hum. Biol. 2009:512–519. doi: 10.1002/ajhb.20917.

Hinde K. First-time macaque mothers bias milk composition in favor of sons. Curr. Biol. 2007;17:958–959. doi: 10.1016/j.cub.2007.09.029.

Lönnerdal, B., Erdmann, P., Thakkar, S. K., Sauser, J., & Destaillats, F. (2017). Longitudinal evolution of true protein, amino acids and bioactive proteins in breast milk: a developmental perspective. The Journal of nutritional biochemistry, 41, 1–11.

Powe C.E., Knott C.D., Conklin-Brittain N. Infant sex predicts breast milk energy content. Am. J. Hum. Biol. Off. J. Hum. Biol. Assoc. 2010;22:50–54. doi: 10.1002/ajhb.20941.

Quinn E.A. No evidence for sex biases in milk macronutrients, energy, or breastfeeding frequency in a sample of filipino mothers. Am. J. Phys. Anthropol. 2013;152:209–216. doi: 10.1002/ajpa.22346.

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