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Prenatal Phthalate Exposure and Infant Anogenital Distance: infant size adjustment, evaluating phthalate mixture effects, and exposure patterns

Xun, Xiaoshuang (2023) Prenatal Phthalate Exposure and Infant Anogenital Distance: infant size adjustment, evaluating phthalate mixture effects, and exposure patterns. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Anogenital distance (AGD) is the distance from anus to genitalia. AGD at birth reflects androgen disruption during the fetal period. Phthalates, a group of endocrine-disrupting chemicals that are widely used in plastics, can alter AGD at birth in rodents, and possibly in humans. Prenatal higher phthalate exposure caused shorter AGD in animal studies and this association has also been reported in several epidemiological studies. However, the results are not consistent, which could be due to several reasons.
First, most studies adjust for infant size in the model or standardize AGD by infant size. Infant size is highly correlated with AGD and may operate as an intermediate variable in the association between phthalates and AGD. The standard approach of controlling for it in statistical models has not been evaluated analytically or quantitatively. Unmeasured confounders of the mediator-outcome association will create bias when estimating the exposure effect on outcome. Using simulated data, we quantified the bias using the effect decomposition method. We concluded that the direct effect of an exposure is a valid estimate only if the unmeasured confounder of the mediator-outcome association is weak or null.
Second, as humans are exposed to multiple phthalates simultaneously, the current approach to assessing risk for individual phthalates may be insufficient. We estimated the mixture effect of phthalates using Bayesian kernel machine regression and found a decreasing trend for the effects of phthalate mixture on AGD in male infants and an increasing trend for female infants. Important contributors to the mixture effect were identified.
Third, the longitudinal effects of phthalates over time in pregnancy have not been reported previously. We used group-based trajectory models to identify phthalate exposure patterns during pregnancy. We also explored maternal predictors of specific trajectories and the effect of different trajectories on AGD. Inverse associations were observed between high exposure levels of phthalates and AGD. The first trimester was a critical effect period for di-(2-ethyl-hexyl) phthalate metabolites. This work advances our understanding of phthalate effects on fetal reproductive system development, and future efforts to reduce levels of specific phthalates to protect the fetus and the child.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Xun, Xiaoshuangxix49@pitt.eduxix49
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairAdibi, Jennifer Jadibij@pitt.eduadibij
Committee MemberHaggerty, Catherine LHaggertyC@edc.pitt.eduHaggertyC
Committee MemberTang, LuLUTANG@pitt.eduLUTANG
Committee MemberQin, Xuxuqin@pitt.eduxuqin
Date: 3 January 2023
Date Type: Publication
Defense Date: 25 October 2022
Approval Date: 3 January 2023
Submission Date: 15 December 2022
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 166
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Epidemiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Phthalates, anogenital distance, mixture, trajectory analysis, adjustment, normalization
Date Deposited: 03 Jan 2023 17:00
Last Modified: 03 Jan 2023 17:00

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