자료유형  

 학위논문

Control Number  

0016933759

International Standard Book Number  

9798380263245

Dewey Decimal Classification Number  

610.73678

Main Entry-Personal Name  

Layden, Alexander James.

Publication, Distribution, etc. (Imprint  

[S.l.] : University of Pittsburgh., 2022

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2022

Physical Description  

1 online resource(255 p.)

General Note  

Source: Dissertations Abstracts International, Volume: 85-03, Section: B.

General Note  

Advisor: Bertolet, Marnie;Roberts, Janet M.

Dissertation Note  

Thesis (Ph.D.)--University of Pittsburgh, 2022.

Restrictions on Access Note  

This item must not be sold to any third party vendors.

Summary, Etc.  

요약Preterm 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 proinflammatory 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 prepregnancy 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.

Subject Added Entry-Topical Term  

Womens health.

Subject Added Entry-Topical Term  

Pregnancy complications.

Subject Added Entry-Topical Term  

Epidemiology.

Subject Added Entry-Topical Term  

Premature birth.

Subject Added Entry-Topical Term  

Obesity.

Subject Added Entry-Topical Term  

Obstetrics.

Subject Added Entry-Topical Term  

Public health.

Added Entry-Corporate Name  

University of Pittsburgh.

Host Item Entry  

Dissertations Abstracts International. 85-03B.

Host Item Entry  

Dissertation Abstract International

Electronic Location and Access  

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Control Number  

joongbu:641454