Prenatal Exposure to Perfluoroalkyl Substances and the Risk of Congenital Cerebral Palsy in Children

Zeyan Liew; Beate Ritz; Eva Cecilie Bonefeld-Jørgensen; Tine Brink Henriksen; Ellen Aagaard Nohr; Bodil Hammer Bech; Chunyuan Fei; Rossana Bossi; Ondine S. von Ehrenstein; Elani Streja; Peter Uldall; Jørn Olsen


Am J Epidemiol. 2014;180(6):574-581. 

In This Article

Abstract and Introduction


Perfluoroalkyl substances (PFASs) are persistent pollutants and endocrine disruptors that may affect fetal brain development. We investigated whether prenatal exposure to PFASs increases the risk of congenital cerebral palsy (CP). The source population for this study includes 83,389 liveborn singletons and mothers enrolled in the Danish National Birth Cohort during 1996–2002. We identified 156 CP cases by linking the cohort to the Danish National Cerebral Palsy Register, and we randomly selected 550 controls using a case-cohort design. We measured 16 PFASs in maternal plasma collected in early or midpregnancy, and 6 PFASs were quantifiable in more than 90% of the samples. We found a higher risk of CP in boys with higher maternal PFAS levels; per 1-unit (natural-log ng/mL) increase, the risk ratios were 1.7 (95% confidence interval: 1.0, 2.8) for perfluorooctane sulfonate and 2.1 (95% confidence interval: 1.2, 3.6) for perfluorooctanoic acid. We also observed a dose-response pattern of CP risk in boys per quartile of maternal level of perfluorooctane sulfonate and perfluorooctanoic acid (P for trend < 0.01). PFASs were associated with both unilateral and bilateral spastic CP subphenotypes. No association between PFASs and CP was found in girls. Prenatal exposures to PFASs may increase the risk of CP in boys, but the finding is novel and replication is needed.


Congenital cerebral palsy (CP) is a group of permanent and nonprogressive movement and posture disorders attributed to early brain lesions.[1] CP affects approximately 2–3 per 1,000 births,[2,3] with an incidence as high as 100 cases per 1,000 births among extremely preterm births.[4] More than half of the children affected by CP are unable to walk without assistive devices or have comorbidities such as mental retardation and vision impairment.[5] Fewer than 10% of cases experienced birth asphyxia or trauma,[3] and the etiology of the majority of CP cases remains unexplained.[6]

Perfluoroalkyl substances (PFASs) are a group of synthetic chemicals used extensively in food packaging, nonstick pan coatings, fire-fighting foams, paper and textile coatings, and personal care products. PFASs have surfactant properties and are extremely persistent in the environment.[7] Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) were the 2 most frequently used PFASs in Denmark during the study period, with biological half-lives of 4–5 years.[8] After a drop in manufacturing emission in 2002, PFOS levels in humans were reported to decrease in some countries; however, exposure to substitute PFASs, such as perfluorobutane sulfonate and perfluorononanoic acid, has subsequently increased.[9]

Although the low level of PFASs found in the adult population may cause no harm, concerns about the potential health consequences of PFAS exposure in fetal life have been raised. PFASs can cross the placental barrier,[10] affect neuronal cell development,[11] change motor function, and lead to delayed learning in animals.[12,13] In addition, PFASs have endocrine disruptive properties[14] and can interfere with thyroid hormone function,[15–18] which, during fetal development, may cause mental retardation and neurological deficits.[19]

Thus, we hypothesized that prenatal PFAS exposure affects fetal brain development and increases the risk of CP. Within the framework of the Danish National Birth Cohort (DNBC), we measured PFAS concentrations in maternal plasma collected prenatally to examine the association with children's risk of developing CP.