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5080529 
Journal Article 
Exposure to perfluoroalkyl substances during fetal life and pubertal development in boys and girls from the Danish National Birth Cohort 
Ernst, A; Brix, N; Lauridsen, LLB; Olsen, J; Parner, ET; Liew, Z; Olsen, LH; Ramlau-Hansen, CH 
2019 
Yes 
Environmental Health Perspectives
ISSN: 0091-6765
EISSN: 1552-9924 
127 
17004 
English 
BACKGROUND: It remains unsettled whether prenatal exposure to perfluoroalkyl substances (PFASs) affects human reproductive health through potential endocrine disruption.

OBJECTIVES: We aimed to explore the associations between prenatal exposure to several PFASs and various aspects of pubertal development in boys and girls.

METHODS: We studied two samples ([Formula: see text] and 445) from the Puberty Cohort, nested within the Danish National Birth Cohort (DNBC), measuring PFAS in maternal plasma from early gestation. Data on pubertal development were collected biannually from the age of 11 y until full maturation, using web-based questionnaires. Outcomes were age at menarche, voice break, first ejaculation, and Tanner stages 2 to 5 for pubic hair, breast, genital development, and a combined puberty indicator. A regression model for censored data was used to estimate mean difference (months) in age at achieving the pubertal outcomes across tertiles of PFAS concentrations and with a doubling of PFAS concentrations (continuous). For perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS), a meta-analysis was used to provide a weighted average of the point estimates from samples 1 and 2.

RESULTS: Overall, prenatal exposure to PFOS, perfluorohexane sulfonate (PFHxS), perfluoroheptane sulfonate (PFHpS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PDFA) (girls) and PFHxS and PFHpS (boys) was associated with lower mean age at puberty marker onset. PFDA and PFNA exposure was associated with higher mean age at onset of puberty in boys. Nonmonotonic associations in girls (PFOS, PFHpS, PFDA) and boys (PFDA, PFNA) were observed, showing larger mean age differences for the combined puberty indicator in the middle tertile [girls: PFOS: [Formula: see text] mo, 95% confidence interval (CI): [Formula: see text], [Formula: see text]; PFHpS: [Formula: see text] mo, 95% CI: [Formula: see text], 1.85; PFDA: [Formula: see text] mo, 95% CI: [Formula: see text], 1.83; and boys: PFNA: 4.45 mo, 95% CI: [Formula: see text], 10.21; PFDA: 4.59 mo, 95% CI: [Formula: see text], 10.11] than in the highest tertile with the lowest as reference.

CONCLUSIONS: Our population-based cohort study suggests sex-specific associations of altered pubertal development with prenatal exposure to PFASs. These findings are novel, and replication is needed. 
Reproduction; Womens health; Hormones; Regression models; Reproductive health; Menarche; Questionnaires; Girls; Age; Pregnancy; Acids; Exposure; Reproductive systems; Endocrine disruptors; Perfluorodecanoic acid; Perfluoro compounds; Statistical analysis; Fetuses; Puberty; Gestation; Perfluoroalkyls; Perfluorooctanoic acid; Health care; Confidence intervals; Studies; Ejaculation; Perfluorooctanesulfonic acid; Disruption; Public health; Regression analysis; Children & youth; Population studies; Systematic review; Age differences; Perfluorohexane; Prenatal experience; Consumption 
PFAS
• Additional PFAS (formerly XAgency)
     Literature Search November 2019
          Other Sources
               Reference list review of included studies
               TEDX
     Screened Studies
          Excluded
               Exclude (TIAB)
• Expanded PFAS SEM (formerly PFAS 430)
     Litsearch: September 2019
          Web of Science
          Other Sources
               PFAS TOX Database
     Screened Studies
          Excluded
               Exclude (TIAB)
     Perfluorooctane
• PFAS 150
     Literature Search Update December 2020
          PubMed
          WOS
     Literature Search August 2019
          PubMed
          Web of Science
          Other sources
               Reference list review of included studies
               PFAS TOX Database
     Screened Studies
          Included
               Include (TIAB)
               Include (Full Text)
     Ammonium perfluorooctanoate
     Perfluorodecanoic acid
     Perfluoroheptanesulfonic acid
     Perfluorohexanesulfonic acid
     Perfluorononanoic acid
     Perfluorooctane
     Perfluorooctanesulfonic acid
     Perfluorooctanoic acid
• PFDA
     Literature Search Update 5/2019
          PubMed
     Literature Search Update 4/2021
          WoS
     Scopus: April 2021
     June 2022 Pelch Database
     Literature Searches (through April 2023 update and post-public comment/peer review)a    
          Other
               Published PFAS SEMs
          Title & Abstract Screening
               Tagged as Supplemental
                    Full Text Screening
                         Studies Meeting PECO
                              Human health effects studies
• PFHxS
     Database searches
          Pubmed
          WOS
          Scopus
          Pelch PFAS SEM
     Inclusion
          TiAb
          Full Text
               Human Study
• PFNA
     Literature Search
          Pubmed
          WOS
     PFNA May 2019 Update
          Pubmed
          Web of Science
     LitSearch: May 2019 - May 2020
          WoS
     Title and Abstract Screening
          Full Text Screening
               Studies Meeting PECO
                    Human health effects studies
     June 2022 Pelch Database
• PFOA (335-67-1) and PFOS (1763-23-1)
     Literature Search Update (2013-2019)
          PubMed
          WOS
• PFOA and PFOS OW MCLG Approaches
     Cited in White Papers