Poly- and perfluoroalkyl substances (PFASs) are synthetic fluorinated chemicals that have been used in a wide range of consumer products and industrial applications over six decades.¹ Because the remarkable strength of the fluorine–carbon covalent bond confers thermal and chemical stability, some PFASs are highly resistant to both chemical and biological degradation under normal environmental conditions.¹

The global occurrence of certain PFASs, persistence in the environment and bioaccumulation in biota have raised concerns about human exposures to PFASs,² and human biomonitoring has gained importance for exposure assessment of PFASs in the general population of several countries.³⁻⁹ While human exposure to PFASs is well recognized, pregnant women, infants, and young children are often poorly represented in general population biomonitoring surveys. Biomonitoring studies among subpopulations susceptible to the effects of potentially harmful environmental chemicals, such as PFASs, are of interest because exposures during these critical windows of susceptibility may impact health later in life.

Pregnant women worldwide are exposed to PFASs¹⁰⁻²⁴—even though data on pregnant women in the United States are limited^14,15,25—and several studies have identified previous pregnancies, breastfeeding duration, and diet as important determinants of exposure to PFASs among pregnant women.^{12,14,15,23,26} Of interest, PFASs can be transported across the placenta; several PFASs have been detected in cord serum.^{13,17,18,20,21,24,27−43} Furthermore, the transfer of PFASs across the placenta may differ depending on the compound. For example, available scientific evidence suggest that PFOA may pass through the placenta more easily than PFOS.^{17,20,21,24,28,30,32,34,35,39,41} Data on paired maternal and cord blood PFASs concentrations also exist for populations around the world, but not in the United States.^{13,17,18,20,21,24,28,30,32,34,35,37,39,41,43}

To improve our understanding of in utero exposure to PFASs among U.S. women, we quantified the concentrations of PFASs in maternal serum during pregnancy and at delivery, and in cord sera, and evaluated the trends of PFASs concentrations and their correlations during gestation in a cohort of Ohio women. We also determined the correlations of select PFASs for paired maternal–cord sera, and examined associations between maternal serum PFASs concentrations and demographic and lifestyle factors.

The frequency of detection and concentrations of 8 PFASs in maternal sera during pregnancy and delivery and in cord sera are shown in Table 1 for the 71 paired maternal/infant samples and in the Supporting Information, SI (Tables S1 and S2). The geometric means of concentration ratios for the 71 dyads are also shown in the SI (Table S3). We detected PFOS, PFOA, PFNA, and PFHxS in more than 90% of the paired samples, and Me-PFOSA-AcOH in about 90%. For the other analytes, we did not perform additional analyses because the frequency of detection was <30% at all of the time points examined (i.e., Et-PFOSA-AcOH, PFOSA) or the median was close to the LOD (i.e., PFDeA). The median concentrations in cord serum were lower than the corresponding paired maternal concentrations (Table 1).

We determined the Spearman rank correlations between the log₁₀ transformed maternal concentrations of Me-PFOSA-AcOH, PFHxS, PFOS, PFOA, and PFNA at 16 weeks and at delivery and their infants’ cord serum concentrations (Table 2). Correlations between the concentrations in maternal and infants’ samples collected at delivery (Spearman rank correlation coefficient (r) = 0.79–0.92) and between the maternal samples at 16 weeks gestation and the infants’ cord serum (r = 0.73–0.95) were high. The PFAS concentrations in maternal sera at 16 weeks gestation and at delivery were also highly correlated (r = 0.84–0.94).

We observed a statistically significant decrease in the unadjusted GM maternal serum concentrations of most PFASs from 16 weeks gestation to delivery (all paired t test P values <0.001) (Figure 1). Still, maternal concentrations of PFOS, PFOA, PFNA, and PFHxS at birth were significantly higher than cord concentrations (all paired t test P values <0.001), but were lower for Me-PFOSA-AcOH (P = 0.01). Specifically, the maternal geometric mean concentrations of PFOS, PFOA, PFNA, and PFHxS decreased 25–43%, depending on the compound, between 16 weeks gestation and delivery (SI Table S4). The percent change of geometric mean concentrations between maternal and cord sera during gestation and delivery for these five PFASs are shown in the SI (Table S4).

The Wilcoxon signed rank test showed the same pattern for the medians: maternal serum median concentrations of PFOS, PFOA, PFNA, and Me-PFOSA-AcOH decreased significantly from 16 weeks gestation to birth (all P values <0.001). Also, maternal median concentrations of PFOS, PFOA, PFNA, and PFHxS at delivery were significantly higher than the infants’ cord serum concentrations (P values <0.001). The maternal median concentrations of Me-PFOSA-AcOH were lower than in cord serum, but they did not reach statistical significance (P = 0.46). Because concentrations of Me-PFOSA-AcOH in the mothers’ serum at birth and their infants’ cord serum were close to the LOD, these data should be interpreted cautiously.

Maternal serum concentrations of PFOS, PFOA, PFNA, and PFHxS at 16 weeks gestation were lower in women younger than 25 years of age compared with older women, but only reached statistical significance for PFOS and PFHxS (Table 3). Non-Hispanic black women and women with the lowest household income had significantly lower concentrations of PFOS, PFOA, PFNA, and PFHxS than non-Hispanic white women and women in the most affluent households, respectively. Obese women had significantly lower PFOS and PFNA concentrations than other women; active smokers had significantly lower PFOS concentrations than nonsmokers or second-hand smokers; women with a high school education or below had significantly lower PFHxS concentrations than women having more than a high school education. Also, a history of previous breastfeeding was inversely and significantly associated with PFOS and PFOA serum concentrations, and nulliparous women had significantly higher concentrations of PFOS and PFOA than parous women (Table 3). Breastfeeding and parity were significantly associated with each other (χ² test P-value = <0.001), but parous women’s GM concentrations were essentially the same when we included parity and breastfeeding history together (data not shown) or separately (Table 3) in the model. For example, GM concentrations of PFOS were 13.19 μg/L (parity = 1) and 11.3 μg/L (parity >1) compared to 13.06 μg/L and 11.37 μg/L, respectively. Gestational age (preterm vs term) was not significantly associated with the concentrations of any of the PFASs examined. Cord serum concentrations varied similarly by demographic, perinatal, and lifestyle factors (SI Table S5) and will not be discussed further.

We found that serum concentrations of PFOS, PFOA, PFNA, and PFHxS among a group of U.S. pregnant women in 2003–2006 were within the concentration ranges of these compounds in the U.S. general population.⁵ These results suggest that PFAS exposure is ubiquitous in U.S. pregnant women. This information is important because, to date, published data on background exposure to PFASs among pregnant women in the United States are limited to 180 pregnant participants of the 2003–2008 National Health and Nutrition Examination Survey (NHANES).^14,25

Of interest, the PFOS median concentrations in these Cincinnati women recruited during early gestation in 2003–2006 (12.7 μg/L) are quite close to those reported for NHANES 2003–2004 pregnant participants (12.0 μg/L), while the PFOA median concentrations (4.8 μg/L) are about two times higher (2.6 μg/L).^14,25 These findings suggest similar exposure to PFOS but higher exposure to PFOA for this cohort of Cincinnati pregnant women compared to the U.S. general population. Consistent with our findings, previous investigations reported higher serum concentrations of PFOA, but not of other PFASs, in a group of 6–8 year-old Cincinnati girls recruited starting in the spring of 2004 from a school district in northern Kentucky^47,48 and in more than 65 000 residents of six water districts in two states near Parkersburg, West Virginia enrolled in 2005–2006.⁴⁹ The source of the exposure to PFOA in these populations was identified to be drinking water from the Ohio River that had been contaminated with PFOA.⁵⁰ Therefore, we speculate that the higher than background concentrations of PFOA in our study population may also be related to the consumption of PFOA contaminated drinking water as reported recently for Cincinnati girls recruited around the same time⁴⁸ as the HOME Study participants.

The observed PFAS concentration sequence PFOS ≫ PFOA > PFNA ∼ PFHxS in maternal and cord sera and the strong correlations between the PFAS serum concentrations between all of the maternal and infant samples are consistent with previous reports.^{13,17,18,20,21,24,28,30,32,34,35,37,39,41,43} The significantly higher maternal serum concentrations of these PFASs at 16 weeks than both the maternal and infant’s concentrations at birth suggest transplacental transfer of PFASs. Of interest, the ratio of concentrations between maternal and infant’s samples varied depending on the compound. For example, at delivery, the ratio between the median maternal and cord serum concentration was about 1 for PFOA but ∼2 for PFOS. These ratios, which are similar to those previously reported, indicate that there are differences in the transplacental transfer of these compounds.^{17,20,21,24,28,30,32,34,35,39,41}

Our results are consistent with other studies that examined PFAS concentrations in serial maternal blood samples collected during pregnancy, and compared maternal and infant’s concentrations at birth.^18,21 Glynn et al. reported a significant decline in mean serum concentrations between the first and third trimester of pregnancy for PFOS, PFOA, and PFNA among 19 primiparous Swedish women.¹⁸ Fromme et al. did not observe significant concentration differences of PFOS, PFOA, PFHxS, and PFNA between maternal samples collected at 34–37 weeks of pregnancy and at delivery from 27 German women,²¹ but the time interval between the two maternal samples was much shorter than the interval Glynn et al. examined. Consistent with our findings, both research groups reported lower concentrations of PFASs in the cord serum compared with maternal samples. Thus, our results, which show strong correlations between the concentrations of all five PFASs in the maternal sera early during pregnancy and at birth, are consistent with these two previous studies,^18,21 while also providing information for PFHxS and Me-PFOSA-AcOH, and with a larger sample size.

We found that maternal age was positively associated with PFAS concentrations during pregnancy. PFOS, PFOA, PFNA, and PFHxS concentrations were lower in women younger than 25 years of age compared with older women. In the early 2000s, 3M, the main manufacturer of PFOS worldwide, discontinued the production of PFOS precursors and related compounds (including PFHxS and PFOA) in the United States. This fact may explain why younger women had lower concentrations of these compounds than older women, who may have had experienced increased exposures when production of these PFASs peaked during the 1980s–1990s time period.⁵¹ NHANES data during 1999–2008 also suggest that PFOS, PFOA, PFHxS, and PFNA concentrations in females increased with age.⁵²

Non-Hispanic black women and women who reported the lowest household income had lower concentrations of PFOS, PFOA, PFNA, and PFHxS than non-Hispanic white women and women in the more affluent households, respectively. These results are in agreement with findings from the U.S. general population. Specifically, 1999–2008 NHANES data also suggest that non-Hispanic black females had lower concentrations of PFOA and PFHxS than non-Hispanic white females.⁵² Similarly, in an analysis of 2003–2008 NHANES data, PFOA and PFOS concentrations were higher in more affluent populations.⁵³ The reason for these differences is unknown, but may reflect differences related to lifestyle (e.g., use of PFASs-containing products), diet, physiology (e.g., elimination), or a combination of the above.⁵²

Active smokers had significantly lower PFOS concentrations than nonsmokers or second-hand smokers. Of interest, the associations between smoking and PFASs exposure are inconsistent among studies. In agreement with our findings, current Danish male smokers had lower PFOA and PFOS plasma concentrations than never smokers.⁵⁴ By contrast, smoking was positively associated with serum concentrations of PFNA and PFOA in 17–39 year old 2003–2008 NHANES female participants.¹⁴ In another study, smoking was not associated with concentrations of PFASs in French women’s breast milk.⁵⁵

Obese women had significantly lower PFOS and PFNA concentrations than other women. Like for smoking, there is no consistency in the literature about the potential associations between exposure to PFASs and BMI. Similar to our findings, plasma concentrations of PFOS and PFOA were inversely associated with BMI in Danish men.⁵⁴ However, in Korean adolescents and adults,^7,56 serum concentrations of several PFASs, including PFHxS, PFOS, PFOA, and PFNA, showed a positive association with BMI. Finally, others have reported no associations between plasma concentrations of PFASs (e.g., PFOS, PFOA, PFHxS, and PFNA) in a group of Vietnamese pregnant women⁵⁷ or middle-aged Norwegian women.⁵⁸ Interpreting these results is difficult because of the differences in study populations and inconsistent findings among studies.

Nulliparous women had significantly higher concentrations of PFOS and PFOA than parous women, in agreement with previous studies.^{12,26,28,40,59,60} We also observed a significant decrease in maternal concentrations of these compounds from 16 weeks gestation to delivery. Together, these findings suggest gestational transfer of PFASs to the fetus.^{17,20,28,30,32,34,40} However, we cannot rule out that physiologic changes occurring during pregnancy (e.g., increased maternal blood volume, fat and total body water; decreased plasma protein concentrations, especially albumin) may also be related to the observed decrease in maternal PFAS concentrations.^61,62

Finally, we observed that a history of previous breastfeeding was inversely associated with PFOS and PFOA serum concentrations, suggesting that breastfeeding may further decrease the mother’s body burden of these compounds and contribute to infants’ exposure to PFASs.^{14,21,35,37,43,55,63−72} Consistent with our findings, the duration of being breast-fed was also positively associated with serum PFOA concentrations among 6–8 year-old girls in Greater Cincinnati (N = 353) and the San Francisco Bay Area (N = 351).⁴⁸

Our study has several limitations. We lacked detailed information on some potentially important sources of PFAS exposure including paper/cardboard use, packaged food consumption, or use of fabric or carpet treatment products during pregnancy. Furthermore, we did not examine sources of dietary exposure as dietary variables collected in the larger HOME Study were designed to assess exposures to heavy metals, pesticides and other persistent pollutants rather than PFASs. Lastly, results from this study population may not be generalizable to the general population of U.S. pregnant women because our participants resided in an area in the United States where the nature of the exposure to at least some of the PFASs (i.e., PFOA) may have differed from the rest of the country. Nonetheless, our data support the hypothesis that PFASs transfer from the mother to her child, and suggests that nursing may decrease a woman’s body burden of PFASs. Our findings also show for the first time in a U.S. longitudinal birth cohort that exposure to PFASs among a population of pregnant women is a function of age, race, household income, parity, and previous history of breastfeeding. Future research should build on these results to examine the impact of prenatal and postnatal exposure to these persistent organic pollutants among the children in the HOME Study and other birth cohorts.