On Operation Stork Speed
A History and contextualization of infant formula
This week we had a new announcement from HHS that the FDA will be launching “Operation Stork Speed”, an effort to take a look at infant formula in the USA. There’s a lot in here that sounds good (although scant on details) that calls for updating the nutrient composition of formula, better regulations around heavy metals, improving transparency and potentially funding better research.
At a high-level, this is much needed - we are coming off the backs of a massive infant formula shortage following the shutdown of a plant in Michigan that revealed the detrimental impacts of the extreme market consolidation in the industry. Parents are regularly met with (often-misleading) headlines about levels of heavy metals in foods for infants/children - we just had one this week about metals in infant formula despite the levels being below both USA and EU safety standards. Parents and clinicians also have to navigate an infant formula market that is replete with (rarely supported) claims made by manufacturers about their product having the optimal composition for infant health and development. Add to this mix all of the health influencers saying that infant formula is feeding your baby poison because of the toxic GMOs, seed oils, and sugar, and you’ve got the recipe for a nightmare situation where parents/caregivers are afraid to feed their kids. There is an obvious need for the government to try to improve trust and ensure a marketplace that the most basic infant formula products provide what is likely to be best for infants health & development - the only people benefiting from the distrust and fear are folks with something to sell.
Whether the current administration is up to the task of addressing the infant formula landscape remains to be seen, and the details in Operation Stork Speed are a bit scant (to be frank: I’m not confident given the current cuts at FDA but we’ll see if there’s a reversal). I figured it would be worthwhile to write a primer post that orients folks to some of the interesting history on the development of infant formula and how we landed where we are today. From there, I’ll also comment on some considerations for how we actualize having the safest and most quality infant formulas, and address sensational claims around toxic ingredients. The history also provides a nice reference point for how risky infant formula practices have been, how far we’ve come, and how relatively privileged we are to be debating about some of the topics that dominate today’s conversations.
Before we dive in, I want to note up front that breastfeeding is considered the gold-standard for infant feeding and there’s a whole lot the administration could do to promote and facilitate this but that’s beyond the scope of this post. There are innumerable reasons why a mother/caregiver may choose not to or be unable to breastfeed or feed human milk and we should prioritize supporting feeding autonomy and optimizing outcomes regardless of the feeding approach (‘fed is best’).
History
The best way to feed infants who cannot be fed breastmilk exclusively has long plagued humanity. Wet nursing might be the first thing that someone thinks of when considering alternatives to direct mother-to-infant breastfeeding and wet nursing is indeed seen throughout history and across cultures; however, it was often only available to the afluent in societies and/or was stigmatized in some cultures. Thus, infants who were unable to be breastfeed (many reasons from milk supply issues to high rates of maternal mortality, etc) had to be fed alternatives. Histories of infant feeding practices detail all sorts of unsafe modalities (even feeding beverages that contain alcohol!) that will make you long for the modern convos about the relative safety of GMO seed oils.
When looking for breast milk alternatives, it is probably unsurprising to most readers that many cultures turned to animal’s milk (the animal source depended upon the culture but references include everything from goats to camels to pigs and cows). I want to be very clear that, from a modern scientific perspective, we now know that unprocessed/unmodified animal’s milk is unsafe for infant feeding - the higher protein and mineral content (sodium, phosphorus) can cause GI bleeding, stress the underdeveloped infant kidney, and cause electrolyte abnormalities. Animal milk also typically provides inadequate amounts of a number of essential nutrients, including iron, vitamin D, vitamin C, folate and essential fatty acids. Raw animal milks are also at risk of being contaminated with pathogens and infants have relatively underdeveloped immune systems. These issues with animal milk feeding can result in serious sequelae including impaired growth and bone mineralization, lasting neural and behavioral impacts and death from metabolic and infectious etiologies. I stress this issue because we’ve reached the abjectly dangerous point in the online discourse where infant formulas are portrayed as so hyperbolically toxic that it is not uncommon to find recommendations to feed animal’s milks, often raw (goat is the most commonly recommended despite documented case studies of its harm to infants).
Our modern understanding of the risks of animals milk for infants benefits from knowledge of chemistry, physiology and human nutrient requirements. However, if you try to place yourself back in time, particularly back to the 18th-19th centuries when there was significant interest in alternative infant feeding strategies, identifying whether animal milk was suitable for infants was challenging. Milk could be life-saving if the alternative was abject starvation; it could also be a source of pathogens (pasteurization was not common until the early 1900s), harm vulnerable infants due to its native compositional issues noted above, be a source of contaminants (e.g. nitrates, plant toxins in milk), and be processed in ways that are harmful (heat-treatment destroys vitamin C and infantile scurvy was a big issue during the 19th century). Any observer could reasonably conclude animal milks were both the perfect food or harmful and you can indeed find accounts of either perspective. The harms perceived from milk nevertheless led to efforts to find alternatives.
The 19th century saw important advances in our basic understanding of the macronutrient composition of foods generally, including human and cow’s milk, that laid the foundation for efforts to modify animal milks to be suitable for infants (note: the concept of essential micronutrients were not established for the most part at this time). The first chemical composition of cow and human milk was published in 1838 by Johan Franz Simon, with much work followed by Arthur Meigs into the 1900s, that ultimately concluded human milk was higher in carbohydrate (lactose) and lower in protein than cow’s milk, with some observations that the protein was more resistant to acid hydrolysis. These findings led to efforts by a number of scientists and physicians to modify the carbohydrate and protein composition of milk through mechanisms like the addition of water and starch to milk and treatment of milk with rennet (proteolytic enzymes from cow stomach that digested the milk protein to make it easier on the infant digestive tract). While relatively unsophisticated, this notion of modifying cow’s milk to more closely match the composition of human milk underlies much of the philosophy still present today as we try to make infant formula’s match as close to breast milk as possible.
The most famous effort to modify cow’s milk was undertaken in the mid 19th century by the organic chemist and one of the pioneers in nutrition science, Justus von Liebig. Liebig had a daughter who struggled to breastfeed and he sought to create an ‘artificial’ human milk replacement - his formulation was relatively crude by modern standards, relying on 1 part wheat flour and 10 parts skimmed cow’s milk with the addition of potassium bicarbonate. Liebig’s big innovation was the inclusion of malt, flour made from grains that had started to germinate and had higher levels of amylase, capable of breaking down the starch into glucose that can be absorbed by infants (adults produce their own amylase but the infant salivary gland and pancreas produce low to no amylase in the first months of life and thus struggle to break down starch to utilize its glucose for energy). Liebig put the recipe out into the public domain and controversy erupted following reports of infants dying after being fed the formula. The Science History Institute has a good article/podcast covering this controversy. Liebig patented his formulation and spurred a huge industry a number of competitors by the end of the 19th century, essentially marking the beginning of the commercialization of infant feeding. Physicians got involved heavily in infant feeding in this era as well, with a precise method for modifying milk with water, cream and sugar popularized by Rotch.
The general knowledge about human milk composition led to the basis of the modern formula emerging in 1915 - the formula was “Synthetic Milk Adapted”, developed by Gerstenberger, and contained nonfat cow milk, added lactose, oleo oils and vegetable oils. This was commercialized as “SMA” in 1919 with the addition of cod liver oil (a known remedy to prevent vitD deficiency/rickets at the time). Gerstenberger published his results of using SMA for 3 years in a number of cases of infants failing to thrive that showed a relative resumption of normal growth upon feeding. Other notable players in the formula industry space emerged at this time, including Nestle and Mead Johnson. Bosworth & Bowditch, prolific researchers in infant formula mineral and fatty acid composition, produced research that ultimately led to a formula that would be renamed ‘Similac” (the basis of the modern Similac brand owned by Abbott).
Despite early development, formulas didn’t become a huge market until the 1960s, predominantly due to the use of cheap and shelf-stable evaporated milks. Milk evaporation without added sugar emerged in the late 1800s but wasn’t initially used for infant feeding due to concerns about inducing infantile scurvy. However, in the 1920s, it became more customary to supplement the diet of infants with fruit and vegetable juices, providing an alternative source of vitamin C and facilitating the use of canned evaporated milks. Evaporated milks had the added bonus of the heat-treatment both killing pathogenic microorganisms as well as denaturing proteins and improving digestibility. In early trials, evaporated milks supported growth similar to breastfed infants, leading to physicians recommending their use widely.
By the mid-20th century, both evaporated milk-based home formulations as well as SMA-like commercial formulations were available but there was little in the way of legislation to standardize the nutrient composition of formula. Unsurprisingly, problems emerged; these included the high renal solute load of formulas (determined by the protein and electrolyte content of formulas —> increasing the risk of dehydration and electrolyte imbalances that can cause severe harm/death), low bioavailable iron content (increasing the risk of anemia that can influence the risk of cognitive and motor developmental issues, as well as infections), low vitamin C content (increasing the risk of scurvy, still relatively prevalent at the time), and low intakes of essential fatty acids. Incidences of fat (vits K, D) and water soluble (folate) vitamin inadequacies were also reported at the time. Isolated incidences of infant nutritional inadequacies can be found throughout the literature but it was ultimately 2 major incidences that catalyzed regulation of the industry.
Modern Regulation Emerges
Up until the 1970s, the only regulations around infant formula came from the 1938 Food and Drug Act that labeled infant formula a ‘food for special dietary purposes’. In 1941, the FDA required food for infants must list energy, protein, fat, carbohydrate, fiber, calcium, phosphorus, iron , vits A, B1, C and D on the label and established minimum levels in formula for the latter 5. Other than this, the FDA had little regulatory authority (note: special formulas for infants with metabolic defects, like PKU, were regulated initially as drugs until reclassified in 1972). Things started to change when a number of infants developed vitamin B6 deficiency following a change in the heating method for liquid SMA that decreased its vitamin B6 content. The FDA proposed a revision in 1966, expanding the list of formula minimums to 7 vitamins and four minerals; however, the regulation was ultimately stayed due to requests for public hearings and objections to FDA oversight. The FDA ultimately asked the Committee on Nutrition of the American Academy of Pediatrics to put forth recommended levels of nutrients in formula, which it published in 1967, and these were used in 1971 regulations from the FDA to set minimums for protein, fat, linoleic acid (essential n-6 fatty acid), and 17 vitamins and minerals.
Another nutrient deficiency crisis ultimately led to the landmark Infant Formula Act of 1980. In 1978, reformulation of soy-protein based formulas by Syntex Laboratories resulted in chloride deficiency and severe hypochloremic hypokalemic metabolic alkalosis (Bartter-like syndrome) in at least 130 infants (symptoms included failure to thrive, diarrhea and blood in the urine). The event led to public outcry and a Congressional investigation that highlighted the need for better regulation of the industry and put the FDA in the hotseat. The events also highlighted the FDA’s limited authority (it could only recall the formulas due to its labeling authority because the formula claimed more chloride than it had, not because the formula was abjectly dangerous) and resulted in the development and passing of the Infant Formula Act of 1980 (the IFA was also amended some in 1986). This act gave FDA much broader regulatory authority to not only establish & update the composition of formulas and regulate labeling but also to regulate the quality control of its manufacturing and recall formulas.
The Infant Formula Act is still what regulates the composition of infant formulas to this day. It defines essential nutrient minimums in infant formula for 29 components as well as maximums for 10 - you can find the full listing of values in the Code of Federal Regulations 21, Part 107, Infant Formula. The majority of these values were established in the 1980s, with a recent 2016 update setting mins and maxes for selenium.
If you’re a follower of infant formulas - be it its controversies around ingredients like seed oils and corn syrup, or common additives linked to health claims - you may be a little surprised by the limited components listed here and the lack of a broader regulatory framework for the ingredient sources of these nutrients. Formula manufacturers are allowed to choose which ingredients ultimately provide these essential nutrients, and can add additional ingredients through the Generally Recognized as Safe (GRAS) system. GRAS also regulates other additives some might be concerned about, such as emulsifiers or stabilizers (e.g. lecithin, carrageenan). The GRAS system started to be heavily utilized in the 90s as there was skepticism about the incomplete nature of formula relative to human milk, particularly its non-essential nutrient bioactive components. Infant formula manufacturers sought to add ingredients to better match formula composition to human milk, a fair scientific and medical goal but undoubtedly one driven by marketing and trying to appeal to a consumer who had continuously heard ‘breast is best’ for the past couple decades. In the 1990-2000s, we saw the addition of nucleotides (thought to be immunomodulatory) and long chain omega 3 fatty acids like docosahexaenoic acid (DHA; thought to be important for neural and visual development) to infants formula. In the couple decades since, we’ve seen numerous other ingredients like human milk oligosaccharides, lutein, probiotics, and various hydrolyzed protein sources be added to infant formulas and heavily marketed to consumers. This relatively free-for-all marketing-informed approach to infant formula composition isn’t great, to say the least, and is part of why I’m open to the new attention being placed on infant formula. The situation presents with both challenges and opportunities for the future.
Challenges & Opportunities 1:
As it relates to ‘essential’ nutrients, the federal regulations are pretty solid - we don’t see huge outbreaks of nutrient deficiencies like in the past. Individual nutrient experts may certainly quibble with the levels for general infant formula, and I think many experts would be open to tighter federal regulation of infant formula composition for special groups like preterm infants, where there’s been a growing interest in meeting their unique nutrient needs. There’s a lot of innovation here that the FDA could consider in its updated regulation but it would ultimately expand its regulatory mandate, requiring significantly more staffing and resources.
Preventing deficiency and maintaining essential nutrient status is not the beast everyone cares about though. Most of the hype/concern around infant formula modifications relate to ‘optimization’ of developmental processes or prevention of disease/symptoms. These include ‘optimizing’ neurocognitive and visual development, immune function, gut microbiota and GI health, and long-term obesity & cardiometabolic disease risk. Tweaking ingredients and the levels of essential nutrients as well as adding minimums for non-essential bioactive compounds to improve these outcomes is a both a valid goal and extremely challenging because the effects are not dichotomous (life/death, disease/not disease) but are continous and likely to be subtle (e.g. slight improvements in IQ; modestly lower risk of obesity) - things you will only pick up with well-designed/controlled studies and withsensitive measurement instruments. This brings up to challenge & opportunity 2.
Challenges & Opportunities 2:
What type of evidence do you use to update infant formula composition? There is something of a split in the thinking here:
There are those who say, just match infant formula composition to breast milk composition. If it’s in breast milk, add it to formula at a similar level - you don’t need a randomized controlled trial to show its health benefits.
For others, they want rigorous evidence that the addition of an ingredient is both safe and leads to desired health outcomes. This can be done in a number of ways, from randomized controlled trials comparing formulas of different composition to cohorts that compare different formula-fed infants relative to breastfed cohorts. Ultimately, this approach requires NIH and industry to be funding a whole massive amount more research than is currently done.
The ‘just match breast milk’ approach might sound like the easier and obvious route but is way more challenging than it sounds. We’ve long known that matching the complex biological matrix of breast milk is difficult - for example, the form of iron (lactoferrin) in breast milk is much more bioavailable than common fortificants, and require adding more iron (ferrous sulfate) to achieve the same iron status. Trying to match breast milk can also be problematic because breastmilk is also not homogeneous - the amount of compounds like long chain omega 3 PUFAs (DHA) are heavily dependent on the diet, and you can’t just assume the mean/median value in the population is ideal. Nutrients like DHA’s effects are also dependent upon their complex interplay with other nutrients - this has been an area of concern for the oft-venerated European formula composition, because the European Food Safety Authority chose to require levels for DHA but not for the long chain omega 6 arachidonic acid (ARA), that has dynamic physiological interactions with DHA and is found in breastmilk. There is limited evidence on this but the available data demonstrates potential harms of DHA alone without ARA, and a better minimicking of neurocognitive development similar to breastfeeding when formulas provide both preformed DHA & ARA. The list of bioactives are seemingly never ending (human milk oligosaccharides, other prebiotics and probiotics, milk fat globule membranes, etc) and present with their own nuances that make simple task of ‘matching’ breastmilk challenging.
These complexities, as well as the dearth of data, highlight the need to seriously invest in clinical trials that test how infant formulas that vary in the concentration of their components improve a whole host of health and developmental outcomes. Long-term observational cohorts and valid preclinical models will also be needed. This will require a huge boost to fund, not just for grant money to undertake the studies but training for a workforce big enough to assess all of the relevant outcomes (e.g. cognitive assessment is very technical and few researchers are trained in this) and the infrastructure that can handle such large trials involving vulnerable research subjects like infants. The National Academies laid out a roadmap of a number ofconsiderations for research (and the regulatory infrastructure) to address novel ingredients back in 2004 but we’ve largely not implemented most of their recommendations.
Efforts to review the evidence, update levels of all the major compounds to be added, and identify critical research gaps will take time, be expensive, and require significant federal-industry-academic coordination to a level we’ve not seen in history. Whether the current administration is up to looking at the current landscape and coordinating this isn’t really clear #DOGE.
Challenges & Opportunities 3:
The history of FDA relying on AAP early on to bear the brunt of the scientific decision making process on what the composition of infant formula should look like makes me wonder a lot about who will assess the current ingredient landscape, undertake systematic reviews of the data, and ultimately decide on what ingredients and at what levels they will be in. Compared to the 1960s and 1970s when AAP was involved, we have more players in the recommendation space - these includes the National Academies that set DRIs for infancy, the DGAs (under USDA) that now consider infant feeding recommendations within their purview, and internal FDA teams with more relevant toxicological expertise as well food additives & novel food ingredients that aren’t classical nutrients. Ideally this will be an opportunity for HHS to improve the efficiency of our current scientific enterprises and streamline the workflow within the USA and possibly even with other countries - EFSA, other professional organizations (ESPGHAN), and the WHO Codex Alimentarius also provide standards for infant formula. It makes sense for individual countries to make their own considerations based on relevant contextual factors for countries (e.g. supply chains; maternal diets; rates of exclusive formula feeding ,etc) but there’s no doubt global redundancy in processes that could be much more efficient (feels daft to say given that America isn’t playing very nice right now on the world stage but worth mentioning). Whichever scientific entity/approach is chosen, it’ll need funding for initial systematic reviews and follow up scoping reviews to continually update the process. It might be helpful if FDA institutes some user fees to the infant formula industry similar to the way it does for Pharma to resource this large endeavor.
Challenges & Opportunities 4:
We’ve publicly seen a lot of public concern about the specific ingredients used in infant formulas, and Secretary Kennedy even called out the use of corn syrup and ‘seed’ oils in infant formulas. The specific ingredients used to meet nutrient requirements is an area where the current FDA regulation of infant formulas are pretty limited and some more specific guidance could be useful. However, the wellness narratives are going to make things complicated. For example, ‘seed oils’ are only in infant formula to provide the essential fatty acids and meet the FDA requirement to have a minimum level of linoleic acid. You’ll often see other vegetable oils like coconut or palm kernel oil that provide lauric acid, to match breastmilk’s uniquely high levels of this fatty acid. The narrative around seed oils being a concern in infant formula isn’t driven by some concerning data in infants (we have very little) but rather an extrapolation of the general influencer claims that seed oils are ‘pro-inflammatory’ and cause chronic disease in adulthood (claims that are not supported by any dietary guidance or systematic reviews of the literature). These claims around seed oils in infant formula are not saying that the levels of too high and need to be reduced but rather take a ‘good’/’bad’ approach to ingredients and want them out of formula. If this is something to be considered, we need a new, non-seed oil source of essential fatty acids to add to infant formula (no idea what this would be..) - regardless of whatever it is, it will have to add linoleic acid, the seed oil ‘boogeyman’, and thus create a circular issue. MAHA may be leveraging the seed oil wellness anxiety to garner enthusiasm for this review of infant formula but its not clear that how it will tackle the issue to satisfy seed oil mania while seriously engaging with the data to ensure infant formulas provide optimal fatty intake and identify key research.
The corn syrup solids issue is another one where there is a grain of truth that needs to be addressed but the broader issue has spun out of control. As you can see in screenshots above, several folks in and out of MAHA are conflating corn syrup solids with Coca Cola, which uses high fructose corn syrup (HFCS). Corn syrup is derived from corn starch, that is treated with enzymes to break down the starch - starch is just long chains of glucose so when you break it down you get glucose. You have to do another step, adding an isomerase enzyme, to convert that corn-derived glucose syrup to a fructose-rich syrup, which is how HFCS is made. Anybody who looks at corn syrup on an infant formula label and conflates it with HFCS in Coca-Cola is shouting loudly that they don’t understand the basics of food chemistry. No one is recommended to feed infants tons of fructose because they’re actually pretty poor at absorbing it. So to be clear, infant formula is not just coca cola with micronutrients and protein. There is a real problem here though. Most infant formulas provide carbohydrate in the form of lactose to match breast milk (either from the milk used as its main ingredient or as pure added lactose); however, there’s been an explosion of gentle and lactose-free formulas that use corn syrup solids as a lactose-free carbohydrate source. The market size outpaces the actual clinical need, and it seems that the marketing around these products is being served up as a solution to an infant that parents perceive is crying too much/colicky/some other behavioral issues. The FDA will need to navigate both the real need to have lactose-free formulas that are accessible to consumers but also reign in their excessive marketing. There is some observational evidence that presents some cause for concern that the use of lactose-free formulas are associated with a small increased risk of obesity in children. This isn’t enough to shift policy to say they’re overtly dangerous but enough to say that infants who don’t need to be consuming these should probably be consuming formulas that most closely resemble human milk (I.e. use lactose).
Other Challenges:
There’s a whole bunch more practical issues that will have to be considered by HHS to implement Operation Stork Speed. I’ve focused mainly on nutrients and future research so far but Operation Stork Speed also wants to look at things like heavy metals and contaminants. This will again require systematic reviews of the literature and an assessment and strengthening of available surveillance mechanisms to identify whether exposure risk thresholds need to be modified from current standards, what ingredients/sources contribute the most exposure, and a detailed, continual market analysis of the globalized supply chain to identify points of intervention to reduce sources of key contaminants.
I’d be remiss to not point out that the Operation Stork Speed doesn’t have a strong emphasis on microbiological controls in infant formula, yet we just made it through a massive formula shortages due to Cronobacter contamination. FDA released a long-term national strategy to improve the resiliency of the formula supply following this debacle. On the point of both microbiological as well as environmental contaminants the FDA prior to this administration (and before cuts to its staffing) had been doing great work with its Closer to Zero Initiative to improve the infant food supply. I hope that HHS is consulting with past FDA CSFAN folks like Susan Mayne to learn from their expertise.
Other Readings:
This post aims to provide the basics of where we’ve been in infant formula so you can follow where we’re going and understand the complexities at hand. There are other resources that i’d highly recommend.
If you’re not following Steve Abrams, MD , on social media, I’d highly recommend it - he had some relevant threads here, here and here. Steve has a great perspective perspective in Advances in Nutrition looking at some nutrients where there may be enough data to consider updating regulations.
The 2004 NASEM report lays out a number of considerations for building a robust regulatory and scientific framework for regulating novel ingredients in Infant Formula that remains relevant to this day. NASEM also has a relevant 2024 report on infant formula that’s a sort of post-mortem on the 2022 infant formula shortages. Lastly, NASEM has a forthcoming report from a large study its doing looking at protein quality in infant formula and ways to assess this.
ESPGHAN has global standards for the composition of infant formula that are a bit more expansive than the FDA’s and provide an alternative framework, in addition to the 2014 EFSA standards.
If you want more on the history of infant feeding, I recommend here, here, here, here , here, here and here.