Dissertations and Theses

Date of Degree

6-3-2021

Document Type

Dissertation

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Epidemiology and Biostatistics

Advisor(s)

Mary Schooling

Committee Members

Heidi Jonees

Jennifer Dowd

Marlene Camacho-Rivera

Subject Categories

Epidemiology | Maternal and Child Health | Public Health

Keywords

Genetics, low birth weight, fetal development, stress, perinatal epidemiology

Abstract

In the United States, low birth weight (LBW) is a leading cause of infant death overall, and the leading cause of death for Black infants. Understanding and preventing adverse birth outcomes is a major public health priority. Observationally, there is some evidence to support the hypothesis that maternal stress may be associated with LBW. To clarify the effect of maternal stress exposure on LBW, I conducted three separate-sample instrumental variable analyses with genetic instruments (Mendelian randomization) based on single nucleotide polymorphisms (SNP), from genome wide association studies, strongly (p-value < 5 × 10−6) and independently associated with neuroendocrine, vascular, and immune measures of maternal stress. These SNPs were applied to a large, extensively genotyped study of birth weight conducted by the Early Growth Genetics Consortium (EGGC), which contains mother's genetic effect on offspring birth weight, after adjusting for the correlated offspring's genotype (n =179,360). SNP-specific Wald estimates were meta-analyzed to obtain inverse variance weighted, weighted median, MR-Egger, and commix estimates. Based on these analyses, cortisol levels, systolic blood pressure, white blood cell count, and eosinophil count may cause LBW. More investigation is required into the role of stress in LBW, a leading cause of morbidity and mortality among infants, as a potential target of intervention.

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