Maternal and environmental influences on child health in a multi-country household air pollution intervention trial Restricted; Files Only
Sivalogan, Kasthuri (Fall 2024)
Abstract
The global prevalence of obesity has nearly tripled since 1975, and an estimated 144 million children under-5 experience stunted growth. The dual burden of malnutrition at the household level is predominately driven by the presence of an overweight/obese mother and stunted child under-4 in the majority of low- and middle-income countries globally. The overarching goal of this dissertation is to use complex data-driven analytical methods to critically examine key maternal and environmental determinants of child health and growth.
We used data from the Household Air Pollution Intervention Network, a multi-country randomized control trial to determine the effect of a randomized liquid petroleum gas stove and fuel intervention on adult and child health outcomes. First, we characterized human milk from 75 Guatemalan mothers at 6-months postpartum and explored associations between maternal body mass index and human milk. Maternal body mass index was associated with perturbations in energy-related metabolic pathways, and a number of significant pathways were identified in the fecal metabolome, indicating that the relationships between maternal weight, diet and infant diet need to be further explored. Next, we examined if longitudinal changes in length-for-age z-score among 2,802 infants 0-12 months differed by intervention assignment, country, child sex or timing of intervention delivery. Distributions did not differ by intervention assignment, but there was a difference according to child sex in the Guatemala trial site. And finally, we looked to identify latent patterns of household environmental characteristics and direct and indirect pathways through which these patterns are associated with length-for-age z-score among 2,231 households in Guatemala, India and Peru. We identified two distinct latent classes of households, which differed primarily by risk associated with exposure to sources of fecal contamination. Birth length-for-age z-score has the strongest direct effect on length-for-age z-score at 6-months and household environmental health characteristics were negatively associated with birth length-for-age z-score. The lack of a significant effect of the liquified petroleum gas intervention or solid fuel exposure on length-for-age z-score and differences in fecal contamination exposure risk, indicate that community-level transformative water, sanitation and hygiene efforts may be necessary to improve environmental conditions and reduce stunting risk in low- and middle-income countries.
The evidence presented in this dissertation reinforce the significance of maternal and environmental influences on child health and growth, especially in settings where child morbidity and mortality and stunted growth remain prevalent. Metabolomics and the use of nutritional biomarkers will continue to expand our knowledge of the consequences of an obesogenic environment on child growth and development. A system-level approach to WASH: incorporating water, air, sanitation and hygiene, is necessary to improve the household and environmental predictors of child health globally.
Table of Contents
Table of Contents
Chapter 1: Introduction 1
1.1 Specific Aims and Hypotheses 3
1.2 References 5
Chapter 2: Literature Review 7
2.1 Definitions 7
2.2 Human Milk 7
2.2.1 The public health benefits of breastfeeding 7
2.2. The composition of human milk 9
2.2.3 Maternal obesity and milk composition 11
2.3 Household Air Pollution 13
2.4 Infant Stunting 15
2.4.1 Stunting, an anthropometric measure of chronic undernutrition 15
2.4.2 Stunting in the first 1,000 days 15
2.5 Environmental health and infant stunting 17
2.5.1 The role of household air pollution exposure on infant stunting 18
2.5.2 The role of water, sanitation and hygiene on infant stunting 19
2.6 References 23
Chapter 3: Expanded Methodology 36
3.1 Specific Aims and Hypotheses 36
3.2 The Household Air Pollution Intervention Network Trial 37
3.3 The HERCULES Pilot Program 41
3.4 Metabolomics workflow for Chapter 4 42
3.5 Latent Class Growth Analysis for Chapter 6 46
3.6 Latent Class Analysis for Chapter 7 47
3.7 Measured Variable Path Analysis for Chapter 7 48
3.8 References 50
Chapter 4: Human Milk Composition Is Associated with Maternal Body Mass Index in a Cross-Sectional, Untargeted Metabolomics Analysis of Human Milk from Guatemalan Mothers 55
4.1 Abstract 56
4.2 Introduction 58
4.3 Methods 60
4.4 Results 66
4.5 Discussion 70
4.6 References 77
4.7 Tables and Figures 84
4.8 Supplemental Tables and Figures 90
Chapter 5: Comparison of Guatemalan maternal and infant microbiomes and association with infant developmental outcomes 94
5.1 Introduction 94
5.2 Methods 96
5.3 Discussion of Initial Results 100
5.4 References 102
Chapter 6: Provision of a liquefied petroleum gas cookstove and fuel during pregnancy and infancy and linear growth trajectories between birth and 12 months: evidence from the multi-center Household Air Pollution Intervention Network (HAPIN) trial 105
6.1 Abstract 106
6.2 Introduction 107
6.3 Methods 108
6.4 Results 113
6.5 Discussion 116
6.6 References 121
6.7 Tables and Figures 126
6.8 Supplemental Tables and Figures 133
Chapter 7: A pathway analysis of household environmental risk factors associated with length-for-age z-score in the first 1,000 days 141
7.1 Abstract 142
7.2 Introduction 144
7.3 Methods 146
7.4 Results 156
7.5 Discussion 157
7.6 References 164
7.7 Tables and Figures 173
7.8 Supplemental Tables and Figures 179
Chapter 8: Discussion and Conclusion 188
8.1 Key Findings 188
8.2 Strengths and Limitations 190
8.3 Clinical and Public Health Implications 193
8.4 Recommendations for Future Research 196
8.5 Conclusion 198
8.6 References 198
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