Prenatal perfluorooctanoic acid exposure is associated with early onset atopic dermatitis in 5-year-old children

doi:10.1016/j.chemosphere.2019.05.100

Chemosphere

Volume 231, September 2019, Pages 25-31

https://doi.org/10.1016/j.chemosphere.2019.05.100 Get rights and content

Highlights

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Prospective cohort study of 863 mother–infant pairs including AD children aged 0–5 years.
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Cord blood PFAS level was associated with significantly increased AD risk.
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Prenatal PFOA exposure is associated with earlier development of AD in children.

Abstract

Atopic dermatitis (AD) is the most common childhood skin disease and the first step of atopic march. Perfluoroalkyl substance (PFAS) exposure is associated with atopic diseases, including AD. However, whether PFAS exposure is related to earlier AD onset remains unclear. We aimed to investigate the association between prenatal PFAS exposure and earlier onset of AD in children in a 5-year follow-up study. From 2001 to 2005, 1264 mother-infant pairs were recruited from eight Taiwanese maternity hospitals. PFAS levels were analyzed from cord blood. Information on children's health status, including AD occurrence, was obtained via phone interviews at multiple time points. Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) concentrations were measured by ultra-high performance liquid chromatography/tandem mass spectrometry. Cox proportional hazards models assessed associations between prenatal PFAS exposure and early onset AD. Overall, 863 mother–infant pairs with complete measurements were recruited. The prevalence of physician-diagnosed AD before 5 years of age was 7.1%. PFOA and PFOS concentrations were grouped based on whether they were above the 75th percentile. PFOA exposure was positively associated with earlier onset of AD (Kaplan-Meier estimate, p = 0.014). In the Cox model, after adjusting for sex, family income, parental atopy, breast feeding, and maternal age at childbirth, significance was observed in children above the upper quartile (≥75th) of the PFOA group (hazard ratio: 1.89; 95% confidence interval, 1.10–3.16). Our findings suggested that children with higher prenatal PFOA exposure have a higher risk of earlier AD development. Minimizing early life PFAS exposure may help inhibit AD development.

Introduction

Atopic dermatitis (AD) is a common skin disorder in children, is one of the first manifestations of the atopic march, and is a risk factor for respiratory allergic diseases, such as asthma and allergic rhinitis(Somanunt et al., 2017). The prevalence of AD is increasing worldwide(Nutten, 2015). In Taiwan, the prevalence of physician-diagnosed AD among school-age children increased from 1.6% in 1995-96 to 2.8% in 2001, and among preschool-age children was 8.7% in 2008(Lee et al., 2005; Huang et al., 2018). Most AD symptoms appear early in life; about 50% of children with AD have symptoms before the age of 6 months and 85% of child patients develop symptoms in their first 5 years(Kay et al., 1994). The identification of risk factors of AD in early life may allow for potential prevention against AD development.

Perfluoroalkyl substances (PFASs) are widely used common synthetic chemicals in the environment(Fromme et al., 2009). In Taiwan, the concentration of PFASs in the downstream river of an industrial plant was 6930 ng/L for perfluorooctane sulfonate (PFOS) and 3298 ng/L for perfluorooctanoic acid (PFOA)(Lin et al., 2014). This concentration of PFOS exceeds the safe levels (43 ng/L) required for aquatic and avian life(Newsted et al., 2005). PFASs are composed of highly stable carbon-fluorine bonds with high chemical and thermal stability, durability, and strength(Buck et al., 2011). The health concerns for PFAS exposure are due to their persistence and bioaccumulation (Fernandez-Sanjuan et al., 2013).

The relationship between PFAS exposure and immune response/allergic disease has been reported previously. Decreased secretion of interferon-γ and interleukin (IL)-2 and increased secretion of IL-4, IL-10, and IgE antibody, the relevant immune response to atopic diseases, were found in PFOS exposed mice(Dong et al., 2011). In epidemiological studies, higher IgE concentrations were found in children with higher PFAS levels(Dong et al., 2013). Asthmatic children were also reported to have higher serum PFAS levels compared to children without(Dong et al., 2013). Furthermore, higher in utero PFOA exposure was associated with AD development in a 2-year follow-up birth cohort study(Chen et al., 2018).

Although PFAS exposure is associated with atopic diseases, the effect of PFAS exposure on earlier AD onset remains unclear. This study aimed to investigate the association between prenatal PFAS exposure and earlier onset of AD in children in a 5-year follow-up study.

Section snippets

Study population

Pregnant women who had prenatal examinations at our eight cooperated maternity hospitals or medical centers were invited. They are from seven administration areas in Taiwan, including Taipei County, Yulin County, Jiayi City, Tainan County, Tainan City, Kaohsiung City, and Taitung City. Neonates born after July 2001 were consecutively recruited until July 2005(Wen et al., 2011). Pregnant women provided written informed consent and were required to complete a structured questionnaire in their

Results

A total of 863 out of 1264 mother-infant pairs who had at least one follow-up at 3, 6, 12, 18, 24 and 60 months were recruited in this study. Among excluded pairs, there was one pair with the outcome of infant death, one pair for infant adoption, 13 pairs exhibiting multiple births, 32 pairs without cord plasma PFAS concentrations, 91 pairs suspected of cord blood contamination via maternal blood, and 264 pairs lost during follow-up (Fig. 1).

The prevalence of AD was 7.1% (n = 61) in the

Discussions

The results of the present study indicate that in-utero PFOA exposure is associated with AD development in children younger than 5 years. Children with a cord plasma PFOA concentration >1.96 ng/mL developed AD earlier than those with lower PFOA exposure. However, no significant association was found between in-utero PFOS exposure and AD. To our knowledge, this is the first study to investigate the effects of PFAS exposure on the age of AD development.

AD is a common skin disease in children and

Conclusions

In utero PFOA exposure was associated with childhood AD. Children with higher prenatal PFOA exposure exhibited an earlier occurrence of AD than those with lower exposure. AD is considered a major risk factor for the progression of respiratory allergic disease in later life, and knowing these risk factors for early onset AD is helpful for applying appropriate environmental preventive measures. Minimal PFAS exposure during pregnancy may be helpful towards protecting against allergic disease

Declarations and interest

All authors have no financial conflicts of interests to declare.

Acknowledgements

The authors thank all the pairs of mothers and their children who participated in this follow-up study. The authors thank the collaborating hospitals' medical personnel who helped with biological sample collection. The authors also thank the interviewers who supported the data collection and phone interview. This study was supported by the Ministry of Science and Technology, Taiwan [grant No. NSC101-2621-M-002-002-, MOST106-3114-B-400-002 -, MOST 107-2321-B-400-010 -].

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Major immune-related sequelae from PFAS exposures on infant and child health outcomes documented in recent literature include:
• Strong indication of immunosuppression, with diminished childhood antibody response to vaccination, particularly with PFOA, PFOS and PFHxS exposures.
• Some indication of increased risks of childhood infectious diseases/infections, particularly from PFOS exposures.
• Limited indication of an effect of PFAS exposure on allergic reactions/allergen specific IgE antibodies.
• Limited indication of an effect of PFAS exposure on atopic dermatitis (AD).
• Limited indication of an effect of PFAS exposure on asthma and lung function.
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Prenatal perfluorooctanoic acid exposure is associated with early onset atopic dermatitis in 5-year-old children

Highlights

Abstract

Introduction

Section snippets

Study population

Results

Discussions

Conclusions

Declarations and interest

Acknowledgements

Int. J. Hyg Environ. Health

Environ. Res.

J. Am. Acad. Dermatol.

Environ. Int.

Toxicol. Lett.

Environ. Res.

Perfluoroalkyl and polyfluoroalkyl substances in the environment: terminology, classification, and origins

Integr. Environ. Assess. Manag.

Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances and childhood atopic dermatitis: a prospective birth cohort study

Environ. Health

Immunotoxicity of perfluorinated compounds: recent developments

Toxicol. Pathol.

Sub-chronic effect of perfluorooctanesulfonate (PFOS) on the balance of type 1 and type 2 cytokine in adult C57BL6 mice

Arch. Toxicol.