Date of Award

12-2023

Degree Type

Thesis

Degree Name

MS in Epidemiology & Biostatistics

First Advisor

Dr. Fyezah Jehan

Second Advisor

Dr. Waqasuddin Khan

Third Advisor

Mr. Syed Iqbal Azam

Department

Community Health Sciences

Abstract

Introduction: The rising popularity of smokeless tobacco use during pregnancy is a global concern. With many people consuming it worldwide, its prevalence is particularly significant in South Asia and Southeast Asia. In Pakistan, the prevalence of smokeless tobacco use among pregnant women has surged from 1.9% in 2013 to 7.7% in 2020. Expectant mothers who use smokeless tobacco face an increased risk of complications, including intrauterine growth restriction and small for gestational age (SGA) births. SGA births are associated with significant health and economic implications, particularly in low- and middleincome countries. Studies consistently show that smokeless tobacco use during pregnancy increases the risk of SGA births, with a dose-response relationship. Placental transcriptomics can provide insights into SGA births and the effects of smokeless tobacco. This research aims to bridge the knowledge gap regarding the impact of maternal smokeless tobacco use during pregnancy and contribute to healthcare, policy, and public health initiatives. It seeks to shed light on the prevalence of smokeless tobacco use in peri-urban areas and identify differentially expressed genes in SGA infants compared to AGA infants, offering insights into the genetic basis of this condition.
Objectives: This study investigated the association of maternal smokeless tobacco consumption and small for gestational age births in peri-urban areas of Karachi, Pakistan. It also studied differential expression of genes in placenta among mothers delivering SGA and AGA.
Methods: This was a secondary analysis of epidemiologic data of AMANHI biobank cohort in Pakistan and transcriptomic data of all five sites of MOMI consortium. It utilized an 1:3 unmatched nested case-control design. Data of pregnant women aged 15-49 years who delivered singleton live births was extracted from extensive questionnaire filled during the cohort development and its follow-up and placental read count file after RNA-sequencing was obtained from consortium authorities for further analysis. Multiple logistic regression was used for multivariable analysis and adjusted odds ratio with their 95% confidence intervals were reported.
Results: The study included mostly mothers under the age of 35, with around 11% being teenagers. More than half of them had no formal education, belonged to lower wealth quintile and nearly all were homemakers. Smokeless tobacco use was reported by about 35% of mothers in both groups. Most of the participants were Urdu-speaking. participants mothers being the largest group in both SGA (42%) and AGA (32.53%) groups. 29% of SGA, while 14% of AGA mothers were first-time mothers. More than 80% of deliveries were normal vaginal deliveries across the groups. Both groups had a similar distribution of baby gender, with a slight increase in male infants in the SGA group. Multivariable analysis did not show significant association with SGA delivery but other variables explained the outcome. First-time mothers had 1.64 times higher odds of SGA births compared to AGA infants (95% CI: 1.14 - 2.38), and underweight mothers had 1.43 times higher odds of SGA deliveries (95% CI: 1.04 - 1.96). In transcriptomic analysis via DESeq2 analysis, 262 genes exhibited differential expression, with 104 downregulated and 158 upregulated in SGA cases (p < 0.05, log2 fold change >1). Functional analysis of these top genes revealed 130 upregulated and 39 downregulated biological pathways, potentially contributing to the observed differences between SGA and AGA cases. Leptin and Cytochrome P450 1A2 were identified to be the most repeated genes.
Conclusion: While this study did not establish statistical significance, the perilous nature of smokeless tobacco use during pregnancy necessitates continued vigilance. Special attention is warranted for first-time mothers, particularly those of a very young or advanced age, to ensure favorable outcomes. Moreover, the exploration of gene expression profiles holds promise for shedding light on the underlying pathways associated with diverse health outcomes, motivating further in-depth research in this crucial area.

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1

Last Page

92

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