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A Murine Model of Fetal Exposure to Maternal Inflammation to Study the Effects of Acute Chorioamnionitis on Newborn Intestinal Development
Published on: June 24, 2020
In utero PFAS exposure, inflammation, and behavioral problems in childhood
Sarah Rocha1, Jessica L Buthmann1, Chase Antonacci1
1Stanford University, Department of Psychology, Building 420, 450 Jane Stanford Way, Stanford, CA, 94305, USA.
Insights
Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) is linked to childhood internalizing problems, particularly in early years. Inflammation may be a contributing factor, but further research is needed.
Area of Science:
- Environmental Health
- Developmental Psychology
- Toxicology
Background:
- Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) is a growing concern for child neurodevelopment.
- Longitudinal data on PFAS and childhood behavioral problems, including immunological links, are limited.
Purpose of the Study:
- To investigate the longitudinal associations between prenatal PFAS exposure and behavioral problems in children.
- To explore the potential mediating role of inflammation in these associations.
Main Methods:
- A birth-cohort study followed 264 mother-infant dyads from prenatal exposure to 10.5 years post-delivery.
- Umbilical cord blood was analyzed for 9 PFAS and 3 inflammatory markers.
- Child Behavior Checklist data were collected at multiple time points (ages 2, 3, 4, 7, and 10.5 years).
- Linear mixed-effects models and mediation analyses were employed.
Main Results:
- Higher cord blood concentrations of PFNA, PFDA, and PFUnDA were associated with increased internalizing problems at age 2.
- These associations weakened significantly as children aged, particularly for PFNA and PFDA.
- Elevated cord blood interleukin-6 (IL-6) levels mediated the link between PFNA exposure and internalizing problems.
Conclusions:
- In utero exposure to specific PFAS (PFNA, PFDA, PFUnDA) is associated with more severe internalizing problems in early childhood (ages 2-4).
- The observed associations tend to attenuate after age 7.
- Inflammation, specifically IL-6, may represent a key pathway through which PFAS impacts child development, warranting further investigation.
Background:
Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) has been posited to be harmful for neurodevelopment; however, researchers have not yet examined its influence on behavioral problems longitudinally across childhood or the immunological underpinnings of these links.
Methods:
This birth-cohort study followed 264 Singaporean mother-infant dyads from the prenatal period to 10.5 years post-delivery. Concentrations of 9 PFAS and 3 inflammatory markers were assayed from umbilical cord blood. Internalizing and externalizing problems were assessed using the Child Behavior Checklist when children were ages 2, 3, 4, 7, and 10.5 years. Linear mixed effect models estimated the associations of PFAS with children's internalizing and externalizing problems as children aged. For the PFAS that were significantly associated with children's behavioral problems, we tested whether levels of inflammatory cytokines statistically mediated the associations.
Results:
Higher cord blood concentrations of PFNA, PFDA and PFUnDA were associated with more severe internalizing problems at 2 years of age (PFNA: B = 1.65 [0.60, 2.71]; PFDA: B = 1.85 [0.81, 2.89]; PFUnDA: B = 1.26 [0.27, 2.25]). Two of these associations (PFNA, PFDA) weakened significantly as children aged (PFNA: B = -0.26 [-0.44, -0.08]; PFDA: B = -0.35 [-0.52, -0.17]). Higher levels of cord blood interleukin (IL)-6 mediated the association of PFNA with internalizing problems (B = 0.25 [0.01, 0.58]).
Conclusion:
Greater in utero exposure to three types of PFAS was related to more severe internalizing problems from two to four years of age, with associations attenuated after 7 years of age. Inflammation may be one pathway through which PFAS influence development, although replication is warranted.

