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Investigating Placental Inflammation as a Mediator of Maternal Obesity and Risk of Preterm Birth

Layden, Alexander J (2022) Investigating Placental Inflammation as a Mediator of Maternal Obesity and Risk of Preterm Birth. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

Preterm birth (<37 weeks’ gestation) is the leading cause of infant mortality worldwide. Pre-pregnancy obesity is the most prevalent and potentially modifiable risk factor of preterm birth, which may partially be attributed to placental inflammation. However, evidence of a pro-inflammatory effect of obesity on the placenta in pregnancy has been conflicting due to limited tissue-level biomarkers of the placenta and bias attributed to study inclusion criteria. My dissertation uses a combination of placental histopathology and transcriptomic data to address these limitations and determine how pre-pregnancy obesity predisposes women to preterm birth through placental dysfunction.

My first manuscript leverages placental histopathology reports from a large, contemporary US birth cohort to evaluate if pre-pregnancy obesity increases the risk of acute and chronic placental inflammation in term pregnancies. Obesity was associated with a lower risk of acute placental inflammation, but a higher risk of chronic placental inflammation. After accounting for selection bias, obesity was still associated with risk of chronic but not acute placental inflammation. In my second manuscript, we performed a cluster analysis of placental features extracted from histopathology reports to classify early (<32 weeks’ gestation) and late (32 to <37 weeks’ gestation) preterm births into placental pathological phenotypes. We found that pre-pregnancy obesity may predispose women to preterm birth through placental vascular impairment and that obesity mainly affects placental health in more severe, early preterm births. In the third manuscript, we analyzed placental transcriptomic data from two pregnancy cohorts to elucidate inflammatory and non-inflammatory molecular pathways contributing to placental dysfunction in preterm births. Applying high-dimensional mediation analyses, we observed the interleukin 1 receptor-like 1 gene to be a mediator of a positive association between pre-pregnancy BMI and higher gestational age. Interleukin 1 receptor-like 1 is a known inhibitory gene of acute inflammatory pathways.

Contrary to our hypothesis, obesity may predispose women to preterm birth through mechanisms other than acute placental inflammation. We applied various analytic methods to identify preterm birth subtypes most susceptible to the adverse effects of obesity and have characterized nuanced relationships between obesity and placental inflammation to inform future preterm interventions.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Layden, Alexander Jajl117@pitt.eduajl1170000-0002-9601-9966
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairCatov, Janet Mjmcst43@pitt.edujmcst43
Committee MemberRoberts, James Mjroberts@mwri.magee.edu
Committee MemberAdibi, Jennifer Jadibij@pitt.eduadibij0000-0001-6562-8315
Committee MemberBertolet, Marniemhb12@pitt.edumhb120000-0002-5799-9033
Date: 10 May 2022
Date Type: Publication
Defense Date: 7 April 2022
Approval Date: 10 May 2022
Submission Date: 29 April 2022
Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages: 254
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Epidemiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: preterm birth, obesity, placenta, inflammation, bias, histopathology, mediation
Date Deposited: 10 May 2022 18:40
Last Modified: 10 May 2022 18:40
URI: http://d-scholarship.pitt.edu/id/eprint/42886

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