Evidence map›Paper›PMID 36964604›Full record

ArticleClinical epigenetics2023

Mediation effects of DNA methylation and hydroxymethylation on birth outcomes after prenatal per- and polyfluoroalkyl substances (PFAS) exposure in the Michigan mother-infant Pairs cohort.

Rebekah L Petroff, Raymond G Cavalcante, Elizabeth S Langen, Dana C Dolinoy, Vasantha Padmanabhan, Jaclyn M Goodrich

Open access · goldFull text read
In one paragraph

Article in Clinical epigenetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 1 pooled it
4.9field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.

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  13. Epigenetic Consequences of In Utero PFAS Exposure: Implications for Development and Long-Term Health.International journal of environmental research and public health · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Rebekah L PetroffDepartment of Environmental Health Sciences, School of Public Health, University of Michigan, 1415 Washington Heights, Ann Arbor, MI, 48109, USA.
Raymond G CavalcanteEpigenomics Core, Biomedical Research Core Facilities, University of Michigan Medical School, Ann Arbor, MI, USA.
Elizabeth S LangenDepartment of Obstetrics and Gynecology, University of Michigan Medical School, Ann Arbor, MI, USA.
Dana C Dolinoy *Department of Environmental Health Sciences, School of Public Health, University of Michigan, 1415 Washington Heights, Ann Arbor, MI, 48109, USA.
Vasantha Padmanabhan *Department of Environmental Health Sciences, School of Public Health, University of Michigan, 1415 Washington Heights, Ann Arbor, MI, 48109, USA.
Jaclyn M Goodrich *Department of Environmental Health Sciences, School of Public Health, University of Michigan, 1415 Washington Heights, Ann Arbor, MI, 48109, USA. gaydojac@umich.edu.
University of Michigan–Ann Arbor · US

Funding

Statistical Services and Methods Development ResourceU2CES026555 · NIEHS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI GENNINGS, CHRIS · 2015 to 2025
$26.4M
Strategic Vision & Impact on Environmental HealthP30ES017885 · NIEHS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Dana Dolinoy · 2011 to 2026
$21.3M
Pilot and Feasibility (P and F) ProgramP30DK089503 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Kanakadurga Singer · 2010 to 2026
$20.3M
Prenatal Exposures and Child Health Outcomes: A Statewide StudyUG3OD023285 · OD · MICHIGAN STATE UNIVERSITY · PI BARONE, CHARLES JAMES, ELLIOTT, MICHAEL R. · 2016 to 2024
$12.9M
ENVIRONMENTAL TOXICOLOGY PRE/POST DOCTORAL RES.TRAININGT32ES007062 · NIEHS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Justin Adam Colacino · 1985 to 2026
$10.5M
Untargeted Analysis ResourceU2CES026553 · NIEHS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MEEKER, JOHN D. · 2015 to 2015
$9.5M
Environmental Epigenomics and Precision Environmental HealthR35ES031686 · NIEHS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Dana Dolinoy · 2020 to 2026
$6.1M
Project 3: Developmental Exposures and Diet: Epigenetics of Metabolic SyndromeP01ES022844 · NIEHS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PADMANABHAN, VASANTHA, PETERSON, KAREN EILEEN · 2013 to 2018
$3.9M
Endocrine Disruptors and Fetal DevelopmentR01ES017005 · NIEHS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PADMANABHAN, VASANTHA · 2009 to 2010
$998k
NIDDK NIH HHS P30 DK089503NIEHS NIH HHS P01 ES022844NIEHS NIH HHS P30 ES017885NIEHS NIH HHS R01 ES017005NIEHS NIH HHS R35 ES031686NIEHS NIH HHS T32 ES007062NIEHS NIH HHS U2C ES026553NIEHS NIH HHS U2C ES026555NIH HHS UG3 OD023285
6 · The paper itself

Abstract

backgroundPer- and polyfluoroalkyl substances (PFAS) are chemicals that are resistant to degradation and ubiquitous in our environments. PFAS may impact the developing epigenome, but current human evidence is limited to assessments of total DNA methylation. We assessed associations between first trimester PFAS exposures with newborn DNA methylation, including 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC). DNA methylation mediation of associations between PFAS and birth outcomes were explored in the Michigan Mother Infant Pairs cohort. Nine PFAS were measured in maternal first trimester blood. Seven were highly detected and included for analysis: PFHxS, PFOA, PFOS, PFNA, PFDA, PFUnDA, and MeFOSAA. Bisulfite-converted cord blood DNA (n = 141) and oxidative-bisulfite-converted cord blood (n = 70) were assayed on Illumina MethylationEPIC BeadChips to measure total DNA methylation (5-mC + 5-hmC) and 5-mC/5-hmC. Correcting for multiple comparisons, beta regressions were used to assess associations between levels of PFAS and total methylation, 5-mC, or 5-hmC. Nonlinear mediation analyses were used to assess the epigenetic meditation effect between PFAS and birth outcomes.

resultsPFAS was significantly associated with total methylation (q < 0.05: PFHxS-12 sites; PFOS-19 sites; PFOA-2 sites; PFNA-3 sites; PFDA-4 sites). In 72 female infants and 69 male infants, there were sex-specific associations between five PFAS and DNA methylation. 5-mC and 5-hmC were each significantly associated with thousands of sites for PFHxS, PFOS, PFNA, PFDA, PFUnDA, and MeFOSAA (q < 0.05). Clusters of 5-mC and 5-hmC sites were significant mediators between PFNA and PFUnDA and decreased gestational age (q < 0.05).

conclusionsThis study demonstrates the mediation role of specific types of DNA methylation on the relationship between PFAS exposure and birth outcomes. These results suggest that 5-mC and 5-hmC may be more sensitive to the developmental impacts of PFAS than total DNA methylation.

Indexed as

Environmental PollutantsFluorocarbonsDNA MethylationFatty AcidsFemaleHumansInfantInfant, NewbornMaleMichiganMothersPregnancySulfitesEnvironmental PollutantsFatty AcidsFluorocarbonshydrogen sulfiteperfluoroundecanoic acidSulfitesChildren’s healthDevelopmental origins of health and diseaseDNA methylationEpigenomicsHydroxymethylationPer- and polyfluoroalkyl substancesPrenatal exposuresPreterm birth

Identifiers

PMID36964604
PMCPMC10037903
OpenAlexW4360854462

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.