PMID- 35333099
OWN - NLM
STAT- MEDLINE
DCOM- 20220506
LR  - 20220506
IS  - 1552-9924 (Electronic)
IS  - 0091-6765 (Print)
IS  - 0091-6765 (Linking)
VI  - 130
IP  - 3
DP  - 2022 Mar
TI  - Biomarkers of Exposure to Phthalate Mixtures and Adverse Birth Outcomes in a 
      Puerto Rico Birth Cohort.
PG  - 37009
LID - 10.1289/EHP8990 [doi]
LID - 037009
AB  - BACKGROUND: Humans are exposed to complex mixtures of phthalate chemicals from a 
      range of consumer products. Previous studies have reported significant 
      associations between individual phthalate metabolites and pregnancy outcomes, but 
      mixtures research is limited. OBJECTIVES: We used the Puerto Rico Testsite for 
      Exploring Contamination Threats longitudinal pregnancy cohort to investigate 
      associations between phthalate metabolite mixtures and pregnancy outcomes. 
      METHODS: Women (n = 462 carrying females, n = 540 carrying males) provided up to 
      three urine samples throughout gestation (median 18, 22, and 26 wk), which were 
      analyzed for 13 phthalate metabolites. Pregnancy outcomes including preterm birth 
      (PTB), spontaneous PTB, small and large for gestational age (SGA, LGA), birth 
      weight z-score, and gestational age at delivery were abstracted from medical 
      records. Environmental risk scores (ERS) were calculated as a weighted linear 
      combination of the phthalates from ridge regression and adaptive elastic net, 
      which are variable selection methods to handle correlated predictors. Birth 
      outcomes were regressed on continuous ERS. We assessed gestational average and 
      visit-specific ERS and stratified all analyses by fetal sex. Finally, we used 
      Bayesian kernel machine regression (BKMR) to explore nonlinear associations and 
      interactions between metabolites. RESULTS: Differences in metabolite weights from 
      ridge and elastic net were apparent between birth outcomes and between fetal 
      sexes. An interquartile range increase in gestational average phthalate ERS was 
      associated with increased odds of PTB [male odds ratio (OR) = 1.56; 95% 
      confidence interval (CI): 1.08, 2.27; female OR = 1.91; 95% CI: 1.23, 2.98], 
      spontaneous PTB (male OR = 2.32; 95% CI: 1.46, 3.68; female OR = 2.00; 95% CI: 
      1.04, 3.82), and reduced gestational age at birth (male beta =  - 0.39 wk, 95% CI: 
      - 0.62, - 0.15; female beta =  - 0.29 wk, 95% CI: - 0.52, - 0.05). Analyses by study 
      visit suggested that exposure at   approximately  22 wk (range 20-24 wk) was driving those 
      associations. Bivariate plots from BKMR analysis revealed some nonlinear 
      associations and metabolite interactions that were different between fetal sexes. 
      DISCUSSION: These results suggest that exposure to phthalate mixtures was 
      associated with increased risk of early delivery and highlight the need to study 
      mixtures by fetal sex. We also identified various metabolites displaying 
      nonlinear relationships with measures of birth weight. 
      https://doi.org/10.1289/EHP8990.
FAU - Cathey, Amber L
AU  - Cathey AL
AD  - Department of Environmental Health Sciences, University of Michigan School of 
      Public Health, Ann Arbor, Michigan, USA.
FAU - Watkins, Deborah J
AU  - Watkins DJ
AD  - Department of Environmental Health Sciences, University of Michigan School of 
      Public Health, Ann Arbor, Michigan, USA.
FAU - Rosario, Zaira Y
AU  - Rosario ZY
AD  - Graduate School of Public Health, University of Puerto Rico, San Juan, Puerto 
      Rico, USA.
FAU - Velez, Carmen
AU  - Velez C
AD  - Graduate School of Public Health, University of Puerto Rico, San Juan, Puerto 
      Rico, USA.
FAU - Mukherjee, Bhramar
AU  - Mukherjee B
AD  - Department of Biostatistics, University of Michigan School of Public Health, Ann 
      Arbor, Michigan, USA.
FAU - Alshawabkeh, Akram N
AU  - Alshawabkeh AN
AD  - College of Engineering, Northeastern University, Boston, Massachusetts, USA.
FAU - Cordero, Jose F
AU  - Cordero JF
AD  - College of Public Health, University of Georgia, Athens, Georgia, USA.
FAU - Meeker, John D
AU  - Meeker JD
AUID- ORCID: 0000-0001-8357-5085
AD  - Department of Environmental Health Sciences, University of Michigan School of 
      Public Health, Ann Arbor, Michigan, USA.
LA  - eng
GR  - P30 ES017885/ES/NIEHS NIH HHS/United States
GR  - P42 ES017198/ES/NIEHS NIH HHS/United States
GR  - UH3 OD023251/OD/NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20220325
PL  - United States
TA  - Environ Health Perspect
JT  - Environmental health perspectives
JID - 0330411
RN  - 0 (Biomarkers)
RN  - 0 (Environmental Pollutants)
RN  - 0 (Phthalic Acids)
RN  - 6O7F7IX66E (phthalic acid)
SB  - IM
MH  - Bayes Theorem
MH  - Biomarkers
MH  - Birth Cohort
MH  - Birth Weight
MH  - *Environmental Pollutants/urine
MH  - Female
MH  - Humans
MH  - Infant, Newborn
MH  - Male
MH  - *Phthalic Acids/urine
MH  - Pregnancy
MH  - *Premature Birth/chemically induced/epidemiology
MH  - Puerto Rico/epidemiology
PMC - PMC8953418
EDAT- 2022/03/26 06:00
MHDA- 2022/05/07 06:00
PMCR- 2022/03/25
CRDT- 2022/03/25 12:10
PHST- 2022/03/25 12:10 [entrez]
PHST- 2022/03/26 06:00 [pubmed]
PHST- 2022/05/07 06:00 [medline]
PHST- 2022/03/25 00:00 [pmc-release]
AID - EHP8990 [pii]
AID - 10.1289/EHP8990 [doi]
PST - ppublish
SO  - Environ Health Perspect. 2022 Mar;130(3):37009. doi: 10.1289/EHP8990. Epub 2022 
      Mar 25.