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. Author manuscript; available in PMC: 2024 Feb 15.
Published in final edited form as: Environ Res. 2022 Dec 16;219:115042. doi: 10.1016/j.envres.2022.115042

Per- and Polyfluoroalkyl Substances (PFAS) in Breast Milk and Infant Formula: A Global Issue

Judy S LaKind 1,2, Josh Naiman 3, Marc-Andre Verner 4,5, Laura Lévêque 4, Suzanne Fenton 6
PMCID: PMC9872587  NIHMSID: NIHMS1860719  PMID: 36529330

Abstract

Background:

Per- and polyfluoroalkyl substances (PFAS) are transferred from mother to infants through breastfeeding, a time when children may be particularly vulnerable to PFAS-mediated adverse health effects. Infants can also be exposed to PFAS from infant formula consumption. Our recent literature-based scoping of breast milk levels reported that four PFAS often exceeded the United States Agency for Toxic Substances and Disease Registry (ATSDR) children’s drinking water screening levels in both the general population and highly impacted communities in the U.S. and Canada. This work presents a comparison of global breast milk and infant formula PFAS measurements with the only reported health-based drinking water screening values specific to children.

Methods:

We focused on four PFAS for which ATSDR has developed children’s drinking water screening values: PFOA (perfluorooctanoic acid), PFOS (perfluorooctanesulfonic acid), PFHxS (perfluorohexanesulfonic acid), and PFNA (perfluorononanoic acid). Published literature on PFAS levels in breast milk and infant formula were identified via PubMed searches. Data were compared to children’s drinking water screening values.

Discussion:

Breast milk concentrations of PFOA and PFOS often exceed children’s drinking water screening values, regardless of geographic location. The limited information on infant formula suggests its use does not necessarily result in lower PFAS exposures, especially for formulas reconstituted with drinking water containing PFAS. Unfortunately, individuals generally cannot know whether their infant’s exposures exceed children’s drinking water screening values. Thus, it is essential that pregnant and lactating women, especially those having lived in PFAS-contaminated communities, and others have data required to make informed decisions on infant nutrition. An international monitoring effort and access to affordable testing is needed for breast milk, drinking water and infant formula to fully understand infant PFAS exposures. Currently, our understanding of demonstrable methods for reducing exposures to emerging PFAS is limited, making this research and the communications surrounding it even more important.

Keywords: drinking water, PFOS, PFOA, PFHxS, PFNA, human milk, children’s drinking water screening values

1. Introduction

The World Health Organization (WHO 2022a) recommends that infants be exclusively breastfed for the first 6 months of life. Mothers who are unable to or elect not to breastfeed typically feed their infant with formula, either liquid or reconstituted with drinking water. During this developmental period, nutrients critical for proper immunity, brain development and growth are provided to the infant. For example, human milk has macronutrients such as carbohydrates, proteins, lipids, and vitamins and bioactive compounds (e.g., growth factors, hormones, immunoglobulins, cytokines) (Garwolińska et al. 2018) and infant formula manufacturers have been exploring means to minimize differences between infant formula and breast milk (Hernell 2011). Therefore, it is important to know that these liquid nutrition sources are safe and will not adversely affect children’s development.

Per- and polyfluoroalkyl substances – or PFAS – are a family of man-made chemicals known to include thousands of different structures, and reported globally in personal care products, food contact surfaces, textiles, food products, and drinking water sources. These chemicals have been measured globally in the environment and in humans (Brase et al. 2021; Domingo and Nadal 2017). Parents have voiced concerns with regards to PFAS being transferred from mother to infant through breastfeeding, a time when children may be particularly vulnerable to PFAS-mediated adverse health effects (Banwell et al. 2021; Hurtes 2021). This transfer has been well substantiated in mother-child pairs, with children’s serum levels exceeding maternal levels by several fold after months of breastfeeding (Fromme et al. 2010). Our recent literature-based scoping of breast milk (also referred to as human milk) levels in both the general population and highly impacted communities in the United States (US) and Canada indicated that concentrations of four PFAS often exceeded US Agency for Toxic Substances and Disease Registry (ATSDR) children’s drinking water screening values (LaKind et al. 2022). At the time of that research, there was extremely limited data on PFAS in breast milk from the US and Canada, and so a modeling approach based on serum PFAS levels was also used to estimate breast milk PFAS levels.

Our approach presented in LaKind et al. (2022) - using the only reported health-based screening values for PFAS in drinking water specific to children (ATSDR 2018) and estimating general population breast milk levels - constituted an important step forward in evaluating the degree to which concern over infant PFAS exposure through breastfeeding is warranted. But because PFAS contamination is a global problem, the issue of early life exposures to PFAS exceeding children’s drinking water screening values cannot be assumed to only exist in the US/Canada. Also, breast milk PFAS concentrations are best interpreted compared to concentrations in the alternative nutrition sources during infancy (i.e., formula) to provide communities, parents and clinicians data to make informed decisions.

Because of the need for enhanced globally representative datasets to guide risk assessors and policy advisors, here we build on our previous work by comparing the children’s drinking water screening values to international data on PFAS in breast milk, infant formula, and drinking water (often used to reconstitute formula). The goals of this work were to: (i) examine the literature on PFAS in infant liquid nutrition; (ii) build on our past research on infant PFAS exposure via milk/formula consumption (LaKind et al. 2022) to extend it beyond the US and Canada; and (iii) bring attention to a potential research data gap regarding a critical aspect of infant environmental exposure.

2. Methods

We focused on those PFAS for which there are children’s drinking water screening values (ATSDR 2018): PFOA (perfluorooctanoic acid), PFOS (perfluorooctanesulfonic acid), PFHxS (perfluorohexanesulfonic acid), and PFNA (perfluorononanoic acid). To our knowledge, these are the only screening values available which used children-specific weights and drinking water intake (calculations based on an infant [age birth to one year old] weighing 7.8 kg and an intake rate of 1.113 liters per day), an important aspect, as infants have the highest drinking water intake to body weight ratio (US EPA 2022b). These child-protective health parameters are built into some recent drinking water health goals (US EPA 2022a, c), while older individual/adult parameters are being used in other cases (e.g., WHO default parameters for body weight (60 kg) (WHO 2022b), daily drinking-water intake (2 liters), and allocation factor (20%)).

2.1. Data Sources

We conducted a scoping review of the literature to identify existing publications and to evaluate the extent of the available data. As this was not a systematic review but rather a scoping review, we were looking to assess the extent of available studies and therefore did not conduct a formal assessment of the quality of the publications. However, two authors reviewed the data set from the included literature to ensure accuracy for figures and tables.

2.1.1. Measured breast milk concentrations

We searched for papers reporting PFAS concentrations in breast milk with PubMed using combinations of the following single search terms: “PFAS”, “PFC”, “PFOA”, “PFOS”, “PFHxS”, “PFNA”, (“and”) “breast milk” or “human milk” in addition to numerous country names (see Appendix A for search terms). Our first searches for information from the US and Canada were conducted in September 2021 and January 2022. Our follow-on searches for data from other countries and any newer data from the US and Canada were made on 19 July 2022. We included any primary or secondary English language publication with measured levels of any PFAS in breast milk. We also reviewed the bibliographies of retrieved papers to identify any paper not discovered with the electronic searches. If it was apparent that more than one publication included data from the same cohort, only one of the datasets was included for further assessment.

Publications were included if they contained mean, median or upper percentiles/maximum concentration values for at least one of the PFAS (PFOA, PFOS, PFHxS, or PFNA). For each publication with PFAS data, we extracted information – where available – on mean, median, and upper percentiles/maximum concentrations and detection frequencies for PFOA, PFOS, PFHxS, and PFNA.

2.1.2. Infant formula concentrations

We searched for papers reporting PFAS concentrations in infant formula with PubMed using the following single search terms: (PFAS OR PFOA OR PFNA OR PFHxS OR PFOS) AND (“infant formula” OR “baby formula”). The search was conducted on 2 June 2022. We included any English language publication with measured levels of any PFAS in infant formula. Bibliographies of retrieved papers were reviewed to identify any papers not discovered with the electronic searches.

Publications were included if they contained mean, median or upper percentiles/maximum concentration values for at least one of the PFAS (PFOA, PFOS, PFHxS, or PFNA). For infant formula, data from the publications were included if the paper described how the formulas were prepared, and then only if they were prepared as though for infant consumption. For each publication with PFAS data, we extracted information – where available – on mean, median, and upper percentiles/maximum concentrations and detection frequencies for PFOA, PFOS, PFHxS, and PFNA.

2.1.3. Comparison with children’s drinking water screening values

In seeking to evaluate whether exposure to a chemical may result in an adverse health outcome, we often compare exposures to a guidance value. These values are derived from toxicological or epidemiological research and are generally defined as concentrations that are not expected to result in adverse health effects. Guidance values are used as a basis for determining whether an exposure requires closer evaluation. Ideally, for this current exercise, we would use guidance values specifically developed for interpreting levels of PFAS in breast milk that would not be expected to cause adverse health effects in infants. However, these values do not yet exist. In the absence of child/infant-based guidance values for breast milk, we opted to use PFAS drinking water screening values developed by ATSDR (ATSDR 2018) to place international breast milk PFAS levels into context. The advantages of the ATSDR screening values are that: (i) they are based on child drinking water intake rates; and (ii) they assume 100% of the dose comes from water (as opposed to relative source contribution adjustments in most drinking water guidelines).

The process by which ATSDR developed child health-based screening values for four PFAS is shown in Figure 1 (ATSDR 2021). Of note, all points of departure used to derive screening values were based on rodent studies.

Figure 1.

Figure 1.

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Process for deriving Environmental Media Evaluation Guides (EMEGs), or “children’s drinking water screening values” (ATSDR 2021).

The screening values used here to place breast milk and infant formula PFAS levels into a health-based context are Environmental Media Evaluation Guides (EMEGs), referred to in this paper as “children’s drinking water screening values.” Exceeding a children’s drinking water screening value does not indicate that adverse health effects will occur. Exceedances do point to the need for further evaluation. The ATSDR children’s drinking water screening values are: PFOA - 21 ppt, PFOS - 14 ppt, PFHxS - 140 ppt, and PFNA - 21 ppt (or pg/mL).

Measured breast milk and infant formula concentrations were compared to children’s drinking water screening values. Central tendency (e.g., mean, median) and upper ends of distributions (e.g., maxima, 95th percentile) of breast milk and formula concentrations were used. For central tendency values, we prioritized median values over means (i.e., the values used to compare across countries were medians unless only means were available).

3. Results

3.1. Measured breast milk PFAS concentrations

We identified 49 publications with measured breast milk PFAS concentrations. The number of breast milk samples within each study, the study country, and concentrations (median/mean and upper percentile/maximum where reported) of the four selected PFAS are given in Table 1. Most of the studies were conducted in European countries, with additional data derived from Asia, Africa, and North America.

Table 1.

Concentrations of PFOA, PFOS, PFHxS, and PFNA in breast milka. See comments in footnote on specific studies.

PFOA (pg/ml)
Screening value = 21 pg/ml		 PFOS (pg/ml)
Screening value = 14 pg/ml		 PFHxS (pg/ml)
Screening value = 140 pg/ml		 PFNA (pg/ml)
Screening value = 21 pg/ml
Reference; location, N (pooled) Mean Median Max** Freq Det (%) Mean Median Max** Freq Det (%) Mean Median Max** Freq Det(%) Mean Median Max** Freq Det(%)
Abafe et al. 2021; South Africa; 13 153 28 56 60
Abdallah et al. 2020; Ireland; (16) 130 100 350 100 38 20 120 62 <40 <40 87 31 26 14 100 69
Al-sheyab et al. 2015; Jordan; 79 143.64 82.5 1220 34.78 50 178
Antignac et al. 2013; France; 48 82 75 224 98 92 79 330 90 49 50 66 100 64 2
Barbarossa et al. 2013; Italy, primipara; 21 76 241 81 57 288 90
Barbarossa et al. 2013 Italy, multipara; 16 43 100 46 36 116 62
Bernsmann and Fürst 2008; Germany; 203 176 137 610 80 93 82 284 80
Beser et al. 2019b; Spain; 20 152 138 180 85 66 69 78 55 30 70 70 70 5
Cariou et al. 2015; France; 61 41 <LOQ 308 77 40 <LOQ 376 82 26 <LOQ 217 15 14 <LOQ <LOQ 0
Černá et al. 2020; Czech Republic; 59 230 100 162
Černá et al. 2020; Czech Republic; 183 159 96.7 158
Černá et al. 2020; Czech Republic; 164 159 99 212
Černá et al. 2020; Czech Republic; 232 160 100 169
Croes et al. 2012; Belgium; 84 80 70 [150] 100 130 100 [220] 100 20 [20] [20] 42.5
Fiedler and Sadia 2021; Africa; (14) 12.7 12.5 18.1 9.6 10.3 21.9 0 0 0
Fiedler and Sadia 2021; Asia; (13) 16.9 14.6 31.8 32 17.2 212 9.11 0 111
Fiedler and Sadia 2021; Europe, America, Oceania; (8) 28.6 31 37.4 22.3 17.8 51.4 3.24 0 17.4
Fiedler and Sadia 2021; (Latin America; (9) 14.3 15.9 19.0 12.5 11.8 40.5 0 0 0
Fiedler and Sadia 2021; Worldwide; (44) 17.2 15.8 37.4 19.1 13.2 212 3.28 0 111
Forns et al. 2015; Norway; 889 40 110
Fromme et al. 2010; Germany; 201 250 2 40 110 72 30 3
Fromme et al. 2022; Germany; 180 22 <25 326 29 17 <25 248 17 <LOQ <LOQ <LOQ 0 <LOQ <LOQ <LOQ 0
Fromme et al. 2022; Germany; 13 199 854 61 23 29 8
Fujii et al. 2012; China; 30 51.6 51 [103] 63.3 15.3 15 [27] 70
Fujii et al. 2012; Japan; 30 93.5 89 [173] 93.3 32.1 31 [62] 90
Fujii et al. 2012; South Korea; 30 64.5 62 [106] 80 14.7 15 [29] 66.7
Guerranti et al. 2013; Italy; 49 160 7780 2 850 0 4280 41
Guzmàn et al. 2016; Spain; 67 54 26 211 60 41 40 70 6
Haug et al. 2011; Norway; 19 76 25 830 10 93 87 250 19
Iszatt et al. 2019; Norway; 230 57.6 50.77 182.55 97.2 126.7 116.73 370.63 100
Jin et al. 2020; China; 174 87 31 1102 100 25 1 202 50 <LOD 80 0.57 12 1 115 55
Jusko et al. 2016; Slovakia; 166 (PFOA), 176 (PFOS)* 33.5 160 100 33.5 650 100
Kadar et al. 2011; France; 30 57 102 100 74 171 100 <2.5 <2.5 0
Kang et al. 2016; South Korea; 264 72 98.5 50 98.5 <LOD 27.3
Kärrman et al. 2007; Sweden; 12* 492 8 201 166 470 100 85 70 172 100 17 20 17
Kärrman et al. 2010; Spain; 10 <LOQ 120 110 220 40 40 110 <LOQ
Kim et al. 2011; South Korea; 17 41 77 47 61 130 100 7.2 16 88 <8.8
Kubwabo et al. 2013; Canada; 13 250 520 85 <MDL <MDL <MDL
Lankova et al. 2013; Czech Republic; 50* 50 44 128 100 33 30 114 100 22 8 15 48
Lee et al. 2018; South Korea; 127 55.6 40.1 657 88 57.3 47.8 380 100 7.64 133 35 19.4 17.1 127 63
Lenters et al. 2019;* Norway; 1047 40 110 93 117.732 260.716 100
Liu et al. 2010; China; 1237 (24) 34.5 814 87.5 49 137 100 15 83 76 100
Liu et al. 2011; China; 50 181 121 1440 100 56 42 198 100 0 26 19 95 100
Llorca et al. 2010; Spain; 20 907 45 865 95
Lorenzo et al. 2016; Spain; 10 177 57.5 980 100 50 47 246 60 0 4 20 21 30
Macheka et al. 2022; South Africa; 50 260 210 1750 94 90 50 510 66 150 <LOQ 1180 46 70 50 320 64
Müller et al. 2019; Tanzania; 48 210 1130 90 500 1540 100 730 38 170 450 81
Nyberg et al. 2018; Sweden; 27 (pooled) 55 50 3.4 17
Pratt et al. 2013; Ireland; 109 (11) <LOD <LOD <LOD 0 <LOD <LOD <LOD 0 <LOD <LOD <LOD 0 <LOD <LOD <LOD 0
Rawn et al. 2022; Canada; 664* 41.3 34.1 284 99.5 10.9 7.2 167 62.5 8.69 6.1 396 61
Roosens et al. 2010; Belgium; 3–16 (22) 300 3500 2900 28200
Serrano et al. 2021; Spain; 82 7.17 251.8 84.1 <0.86 64.75 34.1 <0.66 45.45 24.4 2.59 136.5 70.7
So et al. 2006; China; 19 210 100 360 100 100 100 62 100
Sundström et al. 2011; Sweden; 1 (18)* 74 75 14
Tao et al. 2008a; Vietnam; 40 89.2 3 75.8 58.5 393 100 6.81 4.33 26.8 73 10.9 5
Tao et al. 2008a; Cambodia; 24 132 4 67.3 39.9 327 100 18.6 13 12.3 13
Tao et al. 2008a; India; 39 335 8 46.1 39.4 120 85 13.3 36 0
Tao et al. 2008a; Indonesia; 20 0 83.6 67.2 256 100 6.23 45 135 5
Tao et al. 2008; Japan; 24 77.7 67.3 170 92 232 196 523 100 7.55 6.45 18.2 92 23.9 13
Tao et al. 2008a; Malaysia; 13 90.4 23 121 111 350 100 6.45 6.68 13.3 85 14.9 8
Tao et al. 2008a; Philippines; 24 183 29 97.7 104 208 100 15.8 13.3 58.9 92 25 17
Tao et al. 2008b; USA; 45 43.8 36.1 161 89 131 106 617 96 14.5 12.1 63.8 51 7.26 6.97 18.4 64
Thomsen et al. 2010; Norway; 70* 16 50 190 90 28 110 360
van Beijsterveldt et al. 2022; Netherlands, Spain; 118–123* 43 99.2 35 95.2 <LOQ <LOQ <LOQ 0 <LOQ <LOQ <LOQ
Völkel et al. 2008; Germany; 70 77.4 <LOQ 460 158 128 639
Wilhelm et al. 2008; Germany; 183 160 66 90 54
Zheng et al. 2022; China; 60 148 356 78 85 341 90 33 111 67 31 126 33
Zheng et al. 2021; USA; 50 13.9 50.7 86 30.4 187 100 6.55 16.7 90 5.98 36.3 100
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*

Awad et al. (2020), Lankova et al. (2013; PFOS only), and Rawn et al. (2022; PFOS only): data not included here as PFCs are separated according to linear and branched compounds. Jusko et al. (2016) sampled colostrum. Kärrman et al. (2007) also reported older data from composite samples; not included here. Lenters et al. (2019): Values in “maximum” column are 95th percentile values. Nakata et al. (2007) and Nyberg et al. (2018): omitted due to insufficient information. Sundström et al. (2011): 2008 data only. Thomsen et al. (2010): The 70 samples were from 9 mothers. van Beijsterveldt et al. (2022): 124 and 133 human milk samples were collected at infant’s aged 1 and 3 months, respectively. Data shown are for one month postpartum.

**

Maximum values shown in brackets are 90th percentile values.

a

We reported the values as indicated in the studies, including zero values. Where concentration data were stratified (e.g., by year of sampling or geographic location), we presented the data as shown by the authors.

b

PFHxS in six of the samples were above the method detection limit but none were quantitated.

For North America (specifically the US and Canada), mean or median measured levels of PFOA and PFOS exceeded children’s drinking water screening values (Figures 2 and 3, Table 1 (Kubwabo et al. 2013; Rawn et al. 2022; Tao et al. 2008a; Zheng et al. 2021). Breast milk levels of measured PFHxS and PFNA were below the children’s drinking water screening values (Figures 4 and 5). It is recognized that results from the US are based on only a total of 95 samples from two states (LaKind et al. 2022). The database for Canada is 677 samples and includes many but not all of the provinces in Canada. To our knowledge, none of the sampling approaches in these studies focused on women in areas potentially highly contaminated by PFAS.

Figure 2.

Figure 2.

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International concentrations of PFOA in breast milk (white bars) and infant formula (gray bars), in comparison with the children’s drinking water screening value (dotted line). Bars represent the mean or median breast milk levels. Error bars represent maximum, 90th or 95th percentile concentrations. Missing bars indicate reported concentrations were below the limit of detection, or PFOA was not measured in the study. The X-axis is log-scale. N values are given in Tables 1 and 2. The ATSDR children’s drinking water screening value is 21 ppt (21 pg/mL) (ATSDR 2018).

Figure 3.

Figure 3.

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International concentrations of PFOS in breast milk (white bars) and infant formula (gray bars), in comparison with the children’s drinking water screening value (dotted line). Bars represent the mean or median breast milk levels. Error bars represent maximum, 90th or 95th percentile concentrations. Missing bars indicate reported concentrations were below the limit of detection, or PFOS was not measured in the study. The X-axis is log-scale. N values are given in Tables 1 and 2. The ATSDR children’s drinking water screening value is 14 ppt (14 pg/mL) (ATSDR 2018).

Figure 4.

Figure 4.

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International concentrations of PFHxS in breast milk (white bars) and infant formula (gray bars), in comparison with the children’s drinking water screening value (dotted line). Bars represent the mean or median breast milk levels. Error bars represent maximum, 90th or 95th percentile concentrations. Missing bars indicate reported concentrations were below the limit of detection, or PFHxS was not measured in the study. The X-axis is log-scale. N values are given in Tables 1 and 2. The ATSDR children’s drinking water screening value is 140 ppt (140 pg/mL) (ATSDR 2018).

Figure 5.

Figure 5.

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International concentrations of PFNA in breast milk (white bars) and infant formula (gray bars), in comparison with the children’s drinking water screening value (dotted line). Bars represent the mean or median breast milk levels. Error bars represent maximum, 90th or 95th percentile concentrations. Missing bars indicate reported concentrations were below the limit of detection, or PFNA was not measured in the study. The X-axis is log-scale. N values are given in Tables 1 and 2. The ATSDR children’s drinking water screening value is 21 ppt (21 pg/mL) (ATSDR 2018).

For the four studies conducted in Africa (Abafe et al. 2021; Fiedler and Sadia 2021; Macheko et al. 2022; Müller et al. 2019), all except Fiedler et al. (2021) reported mean or median levels exceeding the children’s drinking water screening values for three of the four PFAS (Figures 2–5, Table 1). Results from South Africa and Tanzania presented in these studies were based on between 13 and 50 samples. In addition, there was one pooled sample from several countries (Fiedler et al. 2021).

For Asia, the data were derived from a single pooled sample from each of Cambodia, Fiji, Kiribati, Marshall Islands, Mongolia, Niue (2 samples), Palau, Samoa, Solomon Islands, Thailand, Vanuatu, and Vietnam (Fiedler et al. 2021). There were also individual sample data from Japan (N = 24 and 30), South Korea (N = 17, 30, 127, 264), China (6 studies with N ranging from 19 to 174 single samples and one study with 24 pooled samples from 1,237 samples), Vietnam (N = 40), India (N = 39), Cambodia (N = 24), Indonesia (N = 20), Malaysia (N = 13), Jordan (N = 79), and the Philippines (N = 24) (Table 1). In these studies, most of the mean or median PFOA and PFOS values exceeded the children’s drinking water screening values. For PFHxS, the maximum reported values were below the corresponding screening value. For PFNA, two of the studies reported central tendency values above the screening value.

Finally, for Europe, PFAS breast milk data were available from Ireland, France, Italy, Germany, Spain, Czech Republic, Belgium, Norway, Slovakia, and Sweden (Table 1; see table for N values). Pooled samples used to assess levels in Europe overall were collected from Austria, Germany, Germany, Ireland, Sweden, Switzerland, Czech Republic, and Slovakia (Fiedler et al. 2021). With only a few exceptions, central tendency levels for PFOA and PFOS exceeded the children’s drinking water screening values. All central tendency PFHxS levels were below the screening value. The very few reports for PFNA showed mixed results.

3.2. Infant formula concentrations

We identified 9 publications with reports of PFAS concentrations in various types of infant formulas (Abafe et al. 2021; Fromme et al. 2010; Fujii et al. 2012; Lankova et al. 2013; Llorca et al. 2010; Lorenzo et al. 2016; Macheka et al. 2021; Tao et al. 2008b; van Beijsterveldt et al. 2022). Only four of these publications included data relevant for the current exercise; these are the studies that either used pre-prepared formulas in their analyses or specifically noted that powdered formula was reconstituted as per instructions for infant use (i.e., these latter samples were diluted to mirror concentrations relevant for infant exposures and concentrations were reported on a weight-per-volume basis) (Fromme et al. 2010; Fujii et al. 2012; Macheka et al. 2021; van Beijsterveldt et al. 2022). The remaining studies did not specify whether the PFAS concentrations in reconstituted samples were relevant to real-life infant exposure, reported levels of PFAS on a weight-per-weight basis, as indicated by reported concentration units of ng/kg, did not sufficiently specify how the samples were prepared for analyses, or did not present results in a manner that permitted inclusion of central tendency or maxima data (Abafe et al. 2021; Lankova et al. 2013; Llorca et al. 2010; Lorenzo et al. 2016; Tao et al. 2008); these studies are not discussed further here.

The numbers of samples, study country, type of formula, and concentrations (mean and maximum where reported) of the four PFAS that we focused on are shown in Table 2. The dry formulas were reconstituted with tap or bottled water, Milli-Q water, or de-ionized water. For the studies that measured PFAS in both breast milk and infant formula, the analytical limits of detection reported (method detection limit [MDL] for Fujii et al. [2012] or limit of quantitation [LOQ] for Fromme et al. [2010]) were the same for both breast milk and formula.

Table 2.

PFAS concentrations in infant formula

Reference; country, N PFOA PFOS PFHxS PFNA Formula type
Mean (pg/ml) Max (pg/mL) Freq Det (%) Mean (pg/ml) Max (pg/mL) Freq Det (%) Mean (pg/ml) Max (pg/mL) Freq Det (%) Mean (pg/ml) Max (pg/mL) Freq Det (%)
Fromme et al. 2010; Germany; 4 <LOQ <LOQ 0 <LOQ <LOQ 0 <LOQ <LOQ 0 ND ND ND Not specified; prepared with tap water
Fujii et al. 2012; Japan; 5 21.8 ± 11.8 35.8 60 ND ND ND ND ND ND 27.6 ± 37.2 92.0 80 Formulas with cow milk, cow milk-related products, edible oils; dissolved in Milli-Q water
Fujii et al. 2012; China; 4 21.8 ± 12.4 37.1 75 ND ND ND ND ND ND 22.4 ± 18.8 50.4 100 Formulas with cow milk, cow milk-related products, edible oils; dissolved in Milli-Q water
Macheka et al. 2021; South Africa; 9 (pooled from unspecified number of samples) 22 114 44 91 444 33 14 84 11 27 149 56 Not specified; prepared in de-ionized water
van Beijsterveldt et al. 2022; Netherlands; 6 <LOQ <LOQ 0 <LOQ <LOQ 0 <LOQ <LOQ 0 <LOQ <LOQ 0 Nutrilon, Hero, Kruidvat, Etos, Albert Heijn and Holle (biologic goat’s milk); with bottled water and tap water
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ND = no data

While PFAS measurement data for infant formula are extremely sparse, the results from the four available publications indicate that reported mean PFOA concentrations are slightly above the children’s drinking water screening values; maxima are above the screening values, in one case by a factor of approximately 5. Mean and maximum formula values for the one study with detectable PFOS levels (Macheka et al. 2021) were above the screening value by factors of approximately 6 and 31, respectively. PFHxS values were below the screening value in all four studies. The mean PFNA formula concentrations slightly exceeded the children’s drinking water screening value in two of the studies (Fujii et al. 2012; Macheka et al. 2021) while the maximum values in these studies were about 2 to 7 times greater than the children’s drinking water screening value (Figures 2–5 and Table 2).

3.3. Drinking water concentrations

A full description of infant PFAS exposures must consider drinking water PFAS levels, as reconstituted infant formulas will have PFAS levels generally reflective of the PFAS levels in both formula powder and local drinking water supplies, unless purified water is used in preparation (Chow et al. 2021). International data on PFAS in drinking water have been reviewed recently. Here we briefly describe PFAS concentration information from Kaboré et al. (2018) and Sims et al. (2022), who reviewed international PFAS levels in drinking water and groundwater/surface water, respectively.

Kaboré et al. (2018) measured PFAS in tap water samples (n=59) from Canada, the US, Japan, China, France, Norway, Chile, Burkina Faso, Ivory Coast, Guadeloupe (French West Indies), and China. PFOA and PFOS levels were generally below 5 ppt, less than the children’s drinking water screening values of 21 ppt and 14 ppt, respectively. Water concentrations of PFNA and PFHxS were all well below their respective screening values. While this is encouraging, these results are based on a total of 59 samples from 11 countries, and so cannot be considered representative of global or local levels of PFAS. In fact, extensive sampling of PFAS in drinking water in the US has revealed a wide variation in levels of PFAS (US EPA 2017).

While not specifically focused on drinking water, Sims et al. (2022) summarized PFAS data for surface and groundwater from 371 publications published since 2001 from Asia, Europe, North America, and Oceania (N = 77,541 and 16,246 for surface water and groundwater samples, respectively). For PFOA, the 75th percentile concentrations for surface water and groundwater data were 31 ppt and 224 ppt, as compared to the children’s drinking water screening value of 21 ppt. Overall, total PFAS concentrations above limits of detection were observed to span orders of magnitude, from low pg/L to low mg/L levels.

4. Discussion

The results from our earlier paper on measured and modeled levels of PFAS in breast milk in the US and Canada – and confirmed by more recent Canadian data (Rawn et al. 2022) – indicate that breast milk PFAS levels often exceed children’s drinking water screening values and that this issue warrants immediate attention (LaKind et al. 2022). The results from this current effort make it clear that this issue is a global one. The available data suggest that it is not uncommon for PFOS and PFOA breast milk levels from around the world to exceed the respective children’s drinking water screening values.

Whether feeding infants with formula may result in lower PFAS exposures is unclear and of course should not be the only recourse for parents. First, breastfeeding confers well-documented health advantages to the infant and mother (AAP 2022; WHO 2022). Second, it cannot be assumed that levels in formula are lower compared to breast milk or that formula is PFAS-free. For example, Fujii et al. (2012) observed that total perfluorinated carboxylic acid concentrations in infant formulas were higher than in breast milk in samples from China. Third, infant formula may be reconstituted with water that contains PFAS, and for most people the PFAS levels in their drinking water will be unknown. Also, to the best of our knowledge, there are currently no food safety regulations regarding PFAS in powdered or reconstituted baby formula. Because of the very small number of studies reporting data in infant formula, this is an important research data gap. Industries producing infant formula could take the lead in assuring their products (powdered or liquid) do not contain PFAS or other organic pollutants.

Based on the collected published data, regardless of the type of infant nutrition, infant PFAS exposure is certainly likely. Most often, parents will not know whether their infant’s exposures exceed children’s drinking water screening values. On-going global discussions regarding banning or regulating PFAS could have a significant impact on reduction of children’s exposures (ECHA 2022; US EPA 2022a). However, exposure to replacement PFAS levels may increase, which would impact the PFAS mixture composition in breast milk. It is possible that children’s drinking water screening value exceedances will become commonplace as new or more stringent health-protective values are announced by risk assessment agencies. For example, in their most recent assessments, the US EPA (2022c) moved toward using epidemiological data instead of animal studies to derive drinking water health advisory values as well as using the drinking water intake rate for children aged 0 to 5 years in their assessment; the new values are substantially lower than the previous health advisories.

An international sampling and analysis effort is needed for breast milk, drinking water, and infant formula to fully understand infant PFAS exposures. These data can be linked to either epidemiological studies or risk assessment processes to better understand short- and long-term health implications. In addition, affordable or free testing of drinking water or blood levels of PFAS should be available to individuals wishing to have this information for themselves or their family. These data would allow affected communities, health care providers, regulators, and other stakeholders to facilitate decision-making and establish strategies to reduce exposures. This recommendation is in accordance with that of the National Academies of Sciences, Engineering and Medicine (NASEM 2022) Committee on the Guidance on PFAS Testing and Health Outcomes, and based on the principles of proportionality, autonomy, and justice: “Clinicians should offer PFAS testing to patients likely to have a history of elevated exposure. In all discussions of PFAS testing, clinicians should describe the potential benefits and harms of the testing and the potential clinical consequences (such as additional follow-up), related social implications, and limitations of the testing so patient and clinician can make a shared, informed decision.

The main strength of this study is the use of children’s drinking water screening values for placing infant PFAS exposures via breast milk and infant formula into context. While these values were developed in the US, they were derived using data from rodent studies deemed strong and unbiased; thus, they are considered applicable regardless of geographic location. These values, while based on drinking water consumption, can serve as screening values for breastfeeding and formula-fed infants because they were derived using exposure factors specific for young children and assume no other sources of exposure (100% allocation factor), similar to infants who exclusively consume breast milk, liquid formula or formula reconstituted with drinking water. Further, the intake rates used to develop these values (143 mL/kg-d) are similar to upper percentile intakes for exclusively breastfed infants (220 mL/kg-d in young infants to 130 mL/kg-d in older exclusively breastfed infants) (US EPA 2011). Goeden et al. (2019) used a similar approach to assess the risk of early-life exposure to PFAS, namely through the development and use of a pharmacokinetic model incorporating chemical-specific properties and exposure parameters for early life stages (0–5 yr of age). In line with this approach, the US EPA used pharmacokinetic modeling to reconstruct early-life PFAS exposures through placental and lactational transfer for the interim drinking water health advisories on PFOA and PFOS (US EPA 2022c).

Some limitations to this research exist. First, we note that we utilized PubMed as the search engine for this research. It is possible that additional publications may have been identified with additional search engines. This would not, however, change the result that international data are showing exceedances of PFAS screening levels in both breast milk and infant formula. Second, there is a lack of population-based representative data for any country for breast milk. For most countries, very small databases are available. One exception is Canada, for which several hundred data points from several provinces have recently been reported (Rawn et al. 2022). Even for this study, it is not possible to say that the reported levels represent the country as a whole, as several provinces remain without data. In addition, it does not appear that women from locations with confirmed or suspected PFAS contamination were specifically included in the study.

Regarding infant formula PFAS levels, there is a general dearth of information. At present, in any geographic location, it is not possible to state with any certainty that infant formula will have lower PFAS levels compared to breast milk. The same is true for drinking water used to reconstitute infant formula; PFAS levels in sources used for drinking water are known to vary widely (US EPA 2017; Sims et al. 2022), even within a relatively constrained geographic area. There are no robust databases sufficient for drawing general conclusions regarding exposure to PFAS from infant formula. Further, industries making these products outside of Europe are not currently required to assess PFAS levels in their products.

Regarding infant exposure to PFAS in water, the key points are that: (i) PFAS are frequently detected globally in drinking water and water sources that ultimately may be used for reconstituting formula; (ii) PFAS levels vary over orders of magnitude depending on location and water type; (iii) for many parts of the world, available data, especially for drinking water, are limited; and (iv) in some instances, individual PFAS levels may be above their respective children’s drinking water screening values. Therefore, without geographically diverse, location-specific data, it is not possible for an individual using drinking water to reconstitute infant formula to be confident that the resulting product’s PFAS levels will be below respective screening values.

In terms of understanding infant health and safety from any source of infant nutrition, we note that this assessment only included four “legacy” PFAS out of the thousands in existence (NASEM 2022; Carlson et al 2022). Conclusions drawn from this literature review will need to be updated once children’s drinking water screening values are developed for more PFAS, and breast milk, infant formula and drinking water databases are developed for a greater number of PFAS over many more locations. Global data demonstrates that emerging PFAS (including <8-carbon carboxylates and sulfonates and ether-substituted structures) are being measured in women seeking reproductive assistance, pregnant women and/or their infants (Derakhshan et al. 2022; Hong et al. 2022; Li et al. 2021; Varshavsky et al. 2021). We were not able to take these PFAS into consideration because many of these compounds are considered data poor, and there may not yet be sufficient information with which to develop children’s drinking water screening values. However, these global data demonstrate a critical need to act at the community level to protect women of reproductive age from PFAS exposures, as current levels in breast milk and some infant formulas and drinking water can exceed the children’s drinking water screening values.

The idea that a society is judged by how it treats its most vulnerable members has been ascribed to various leaders, including US President Harry Truman. Certainly, infants are a vulnerable part of every society, and it is time for societies around the world to dedicate resources to ensuring that the breast milk and infant formula are as healthy as possible. The scant amount of information on infant formula PFAS content in the literature was surprising, as this is typically the only source of infant nutrition when breastfeeding is not sufficient/conducted. The literature assessment conducted here on international breast milk and infant formula concentrations points to the immediate need for data on PFAS in sources of infant nutrition, including formula and water sources used to reconstitute formula. Further, international prospective epidemiology studies of infants’ lactational exposure to PFAS and health status should be initiated now, in particular in communities living near contaminated sites.

International communities will be exposed to persistent PFAS for decades to come, and health agencies, physicians, lactation consultants, and parents should have the information needed to be fully confident that breast milk remains “…the ideal food for infants” (WHO 2022). In the meantime, we remind the reader that the results shown here are based on a screening approach and that exceedance of screening values does not indicate that adverse health effects will occur. Further, exceedances should not be interpreted as a reason to wean early or to not breastfeed. Rather, the results point to the immediate need for data and research on PFAS levels in sources of infant nutrition, initiation of prospective health studies, and regulatory actions to prevent these exposures in the first place. At present, our understanding of demonstrable methods for reducing exposures to PFAS is limited (NASEM 2022), making research on exposure and health even more important. As noted by LaKind et al. (2022), “…it is well known that infancy is a susceptible life stage and minimizing environmental chemical exposures to infants has been - and should be - a priority.”

Supplementary Material

1

Acknowledgements:

We thank the people who participated in the biomonitoring PFAS analysis studies cited herein. This work would not be possible without you. Marc-André Verner is the recipient of a Research Scholar J2 Award from the Fonds de recherche du Québec – Santé (FRQS), and a Discovery Grant from the Natural Sciences and Engineering Research Council of Canada (NSERC) (RGPIN-2016-06101). Dr. Fenton is supported by NIEHS ES103375-01.

Funding:

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Footnotes

Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Conflicts of interest: All authors declare that they have no actual or potential competing financial interests. The views expressed here are those of the authors and do not necessarily represent the views or policies of the NIEHS.

CRediT: JSL: Conceptualization, Data curation, Visualization, Writing, original draft, Writing, review & editing, Supervision. M-A Verner: Conceptualization, Visualization, Writing, review & editing, Supervision. SF: Conceptualization, Visualization, Writing, review & editing. LL: Data curation and quality assurance. JN: Data curation and quality assurance.

Declaration of interests

Judy S. LaKind reports a relationship with National Academies of Sciences Engineering and Medicine that includes: consulting or advisory. Marc-Andre Verner served as a member on a National Academies of Sciences, Engineering and Medicine committee on PFAS, and reviewed documents related to PFAS for multiple agencies.

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