Breastfeeding in the Age of Chemicals

It’s a catch-22 that would drive any new mother crazy.

Should she breastfeed, which is linked to many lasting health benefits for the newborn child, but take the risk of delivering toxic chemicals, such as dioxins and DDT, that are stored in her breast milk?

Or, should she use infant formula, which avoids the problem of breast milk contaminants but does not offer the same benefits to her newborn and may also contain toxic chemicals (because of lax food safety regulations or if contaminated water is used to reconstitute the formula, for example).

Last month, two papers (from the same group of collaborators) published in Environmental Health Perspectives attempted to address these issues by reviewing decades of relevant research. These papers are both quite extensive and represent impressive work by the authors – but it’s unlikely that non-scientists will wade through the details. So, I’ll do my best to help you out.

Breast milk vs. infant formula: What chemicals are in each?

The first paper starts by documenting all of the chemicals detected in either breast milk or infant formula, based on studies published between the years 2000-2014 (mostly in the United States). Below is a highly simplified table, with just the chemicals rather than other details (refer to the paper if you’re interested in more).

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Abbreviated list of chemicals detected in breast milk and infant formula in studies of women in the United States between 2000-2014. Adapted from Lehmann et al, 2018.
*No data from US studies, so information taken from international studies

 

What can we learn from these data, other than that it looks like complicated alphabet soup?

Well, toxic chemicals have been detected in both breast milk and infant formula, but there are some differences in the types of chemicals found in each. Breast milk is more likely to contain lipophilic (fat-loving/stored in fat) and long-lasting chemicals, such as dioxins and certain pesticides. By contrast, breast milk and formula both have some common short-lived chemicals, such as bisphenol-A (BPA) and parabens.

While the paper also provides information about the average and range of concentrations of chemicals in each medium (and how they compare to acceptable levels of exposure for infants), it’s hard to draw general conclusions because there are such limited data available. It is complicated, expensive and invasive to get samples of breast milk across wide segments of the population, and relatively few studies have looked at chemicals found in infant formula. We need more information before we can accurately understand the patterns of exposure across the population.

Nevertheless, the presence of all of these chemicals seems concerning. No one wants to deliver toxic milk to children during their early months of life, when they are more vulnerable because their organ systems and defense mechanisms are still developing.

But, what do the data indicate about the health consequences of these exposures?

Early dietary exposures and child health outcomes

That’s where the second paper comes in. Here, the same group of authors reviewed the literature on the association between chemicals in breast milk and adverse health outcomes in children. (Note: they had planned to ask the same question for infant formula, but there were not enough published studies). They looked at many chemicals (such as dioxins, PCBs, organochlorine pesticides, PBDEs) and many outcomes (including neurological development, growth & maturation, immune system, respiratory illness, infection, thyroid hormone levels).

Early studies in the field had indeed suggested cause for concern. For example, infants in Germany fed breast milk contaminated with high levels of PCBs were found to have neurodevelopmental deficits in early life. However, levels of PCBs in the general population have declined in recent years (because of worldwide bans), and subsequent studies in the same region found that these lower levels of PCBs were not associated with harmful neurodevelopmental effects.

Overall, when looking across various chemicals and health outcomes, the current literature is actually… inconclusive. Many studies reported no associations, and studies asking similar questions often reported conflicting results. Furthermore, studies that reported significant effects often evaluated health outcomes at only one or two periods in early life, and we don’t know if those changes really persist over time.

A glass half full…of challenges

In the end, the authors ended up with more questions than answers – and a long list of challenges that prevent us from understanding the effects of breast milk-related chemical exposures on children’s health. For example:

  • Chemicals in breast milk are often also present in the mother during pregnancy. How can we disentangle the effects of exposures during the prenatal period from exposures due only to breast milk in early postnatal life?
  • Many of these studies represent a classic case of “looking for your keys under the lamppost.” We can only study chemicals and outcomes that we choose to focus on, so we could be missing other important associations that exist.
  • On a related note, most studies focused on exposure to only one or a small group of chemicals, rather than the real-world scenario of the complex mixtures in breast milk.
  • There was little study replication (ie: more than one study looking at the same question). Generally, we feel more confident drawing conclusions based on a larger pool of studies.
  • The few studies that did ask the same questions often used different experimental designs. These distinctions also pose challenges for interpretation, since differences in how researchers measure exposures and outcomes could affect their results.
  • Most studies evaluated levels of chemicals in breast milk using one or two samples only. How accurate are these exposure assessments, given that levels in the milk may change over time?
  • Measuring chemicals in breast milk is just one aspect of exposure, but it doesn’t tell us how much the infant actually received. Mothers breastfeed for different amounts of time, which affects how much is delivered to the infant. These person-to-person differences within a study could make it challenging to see clear results in an analysis.

Filling in the gaps

Perhaps the only certain conclusion from these publications is that much work remains. Not only do we need more studies that document the levels of chemicals in breast milk and infant formula (as the first paper highlighted), but we also need more data on the links between these exposures and health outcomes – including targeted research to address the challenges and key gaps noted above.

Importantly, because breastfeeding is associated with many key health benefits (such as improved neurodevelopment and reduced risk of obesity, diabetes, infections, and more), any study that looks at the impact of chemical exposures in breast milk should also ask a similar question in a comparison group of formula-fed infants. It is likely that the positive effects of breast milk far outweigh any potential negative impacts from the chemicals in the milk, and that the infants would actually be worse off if they were fed formula that had the same level of chemicals (but did not receive the benefits of breast milk).

I’ll be the first to admit: it is scary to think about all of these chemicals in breast milk. But, all decisions have trade-offs, and here, when weighing the risks and benefits, the balance still seems to favor breastfeeding in most situations.

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A Decade into the “Vision,” Environmental Health gets a Progress Report

This year represents an important 10-year milestone for science and society.

No, I’m not referring to the 10th anniversary of the Apple iPhone, though that has undoubtedly changed all of our lives. Rather, 2017 marks ten years since the National Academy of Sciences (NAS) released its seminal report, Toxicity Testing in the 21st Century: A Vision and a Strategy.

In that report, the NAS laid out a vision for a new approach to toxicology that incorporates emerging cell-based testing techniques, rather than costly and time-intensive whole animal models, and utilizes early biological pathway perturbations as indications of adverse events, rather than relying on evaluations of end disease states. Tox21 and ToxCast, two federal programs focused on using alternative assays to predict adverse effects in humans, were initiated as first steps in this strategy. In the years since its release, the report has profoundly shaped the direction of environmental health sciences, particularly toxicology. (An analogous exposure sciences report, Exposure Science in the 21st Century: A Vision and a Strategy, was published in 2012.)

Now, one decade later, the NAS has reviewed progress on these efforts in its recently released report, Using 21st Century Science in Risk-Based Evaluations.

How are we doing, and what are next steps?

Overall, the committee supports efforts to use data from new tools, such as biological pathway evaluations, in risk assessment and decision-making. (Of course, limitations should be clearly communicated, and tools should be validated for their specific purposes.) Several case studies are described as examples of situations where emerging tools can be useful, such as quickly prioritizing chemicals of concern or evaluating risks from chemical mixtures at a contaminated site.

This report also documents advancements and challenges for each of the three interconnected fields of environmental health sciences: toxicology, exposure science, and epidemiology. I’ve summarized some of these key points in the chart below, and additional (digestible) information is available in the NAS report summary.

  

 

Recent Advancements

Key Challenges

Toxicology

  • Incorporate metabolic capacity in in vitro assays
  • Understand applicability & limitations of in vitro assays
  • Improve biological coverage
  • Address human variability & diversity in response

Exposure Science

  • Coordination of exposure science data (ex: databases)
  • Integration of exposure data of multiple chemicals obtained through varied methods

Epidemiology

  • Improved data management & data sharing
  • Improved methods for estimation of exposures

I won’t go into detail on all of these points, but I do want to highlight some of the key challenges that the field of toxicology will need to continue to address in the coming years, such as:

  • Improving metabolic capacity of in vitro assays: Cell-based assays hold promise for predicting biological responses of whole animals, but it is critical to remember that these new tools rarely reflect human metabolic capacity. For example, if a chemical is activated or detoxified by an enzyme in our bodies, reductionist assays would not adequately reflect these changes – and thus their prediction would not be fully relevant to human health. We need continued work to incorporate metabolic capacity into such assays.
  • Improving biological coverage: An analogy that I’ve often heard in relation to the limitations of these new tools is that they are only “looking under the biological lamp post.” Essentially, we can only detect effects that the assays are designed to evaluate. So, we need further development of assays that capture the wide array of possible adverse outcomes. And we cannot assume that there is no hazard for endpoints that have not been evaluated.

New models of disease causation

Not only is the environmental health science ‘toolkit’ changing but also our understanding of disease causation. As discussed in the report, 21st century risk assessment must acknowledge that disease is “multifactorial” (multiple different exposures can contribute to a single disease) and “nonspecific” (a single exposure can lead to multiple different adverse outcomes). This advanced understanding of causality will pose challenges for interpreting data and making decisions about risk, and we will need to incorporate new practices and methods to address these complexities.

For example, we can no longer just investigate whether a certain exposure triggering a certain pathway causes disease in isolation, but also whether it may increase risk of disease when combined with other potential exposures. It gets even more complicated when we consider the fact that individuals may respond to the same exposures in different ways, based on their genetics or pre-existing medical conditions.

The Academy suggests borrowing a tool from epidemiology to aid in these efforts. The sufficient-component-cause model provides a framework for thinking about a collection of events or exposures that, together, could lead to an outcome.

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Sufficient-component-cause model. Three disease mechanisms (I, II, III), each with different component causes. Image from NAS Report, Using 21st Century Science to Improve Risk Related Evaluations

 

Briefly, each disease has multiple component causes that fit together to complete the causal pie. These components may be necessary (present in every disease pie) or sufficient (able to cause disease alone), and different combinations of component causes can produce the same disease. Using this model may promote a transition away from a focus on finding a single pathway of disease to a broadened evaluation of causation that better incorporates the complexities of reality. (I’ve blogged previously about the pitfalls of a tunnel-vision, single pathway approach in relation to cancer causation.)

Integration of information, and the importance of interdisciplinary training

As the fields of toxicology, exposure science, and epidemiology continue to contribute data towards this updated causal framework, a related challenge will be the integration of these diverse data streams for risk assessment and decision-making. How should we weigh different types of data in drawing conclusions about causation and risk? For example, what if the in vitro toxicology studies provide results that are different than the epidemiology studies?

The committee notes that we will need to rely on “expert judgment” in this process, at least in the short term until standardized methods are developed. And they discuss the need for more interaction between individuals from different disciplines, so that knowledge can be shared and applied towards making these difficult decisions.

One issue that was not discussed, however, is the importance of training the next generation of scientists to address these complex challenges. Given the inevitable need to integrate multiple sources of data, I believe it is critical that the students in these fields (like me!) receive crosscutting training as well as early practice with examples of these multi-faceted assessments. Some programs offer more opportunities in this area than others, but this should be a priority for all departments in the coming years. Otherwise, how can we be prepared to step up to the challenges of 21st century environmental health sciences?

Looking forward

Speaking of challenges, we certainly have our next decade of work cut out for us. It is amazing to think about how much progress we have made over the last ten years to develop new technologies, particularly in toxicology and exposure sciences. Now we must: refine and enhance these methods so they provide more accurate information about hazard and exposure; address the complexities of multifactorial disease causation and inter-individual susceptibility; and work across disciplines to make decisions that are better protective of public health and the environment.