Maternal diet, environmental contaminants, and growth and developmental outcomes in offspring Pubblico
Marks, Kristin J. (Fall 2020)
Abstract
Exposure to endocrine disrupting chemicals (EDCs) is ubiquitous. Diet, particularly food of animal origin, is considered the most important contributor to persistent EDC exposure. EDC exposure, especially during critical periods of development like the prenatal window, may interfere with the body’s endocrine system, which can affect growth and development. Most studies have examined one EDC at a time in relation to disease; however, humans are exposed to many EDCs. By studying mixtures, the human experience can be more closely replicated. This dissertation identified maternal dietary patterns that contributed to persistent EDC exposure (poly- and perfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), and organochlorine pesticides (OCPs)) and investigated the associations of prenatal exposure to persistent EDCs as mixtures with birth size, postnatal body size, and early menarche among girls. First, we identified maternal dietary patterns that are associated with persistent EDC exposure. More frequent consumption of cheese was associated with higher PFAS concentrations, more frequent consumption of white fish and rice with higher PCB concentrations, and more frequent poultry and white fish consumption with higher OCP concentrations. These patterns explained 8% to 20% of the total variance in EDC concentrations. Next, we investigated the association of prenatal exposure to persistent EDCs as a mixture with size at birth and postnatal body size. We found that PFAS, PCB, and OCP mixtures were inversely associated with lower birth weight. Further, we found inverse associations of a 31-chemical persistent EDC mixture with postnatal body size (weight-for-age z-scores) through 19 months driven by early postnatal body size. Lastly, we investigated the association of prenatal exposure to persistent EDCs as a mixture with early menarche (<11.5 vs. ≥11.5 years), and found no association. The results from this dissertation provide insight into maternal diet during pregnancy as a modifiable source of EDC exposure. Moreover, this dissertation estimates the overall effect of prenatal exposure to mixtures of persistent EDCs on growth and developmental outcomes, which gives a more complete estimate of the magnitude of the effects than under the single-chemical paradigm. Results from this work will inform public health strategies designed to improve maternal and child health.
Table of Contents
Chapter 1 Introduction and Overview 1
Background and Public Health Importance 1
Study Motivation 2
Study Population 3
Avon Longitudinal Study of Parents and Children (ALSPAC) 3
Norwegian Mother, Father, and Child Cohort Study (MoBa) 4
Study Aims 4
Chapter 2 Background and Literature Review 6
Heavy Metals 6
Methylmercury 6
Arsenic 7
Non-persistent EDCs 8
Bisphenol A 8
Phthalates 8
Phytoestrogens 9
Atrazines 9
Organophosphate pesticides 10
Persistent EDCs 10
Dioxins 10
Organochlorine pesticides 12
Polychlorinated biphenyls 12
Perfluoroalkyl substances 13
Flame Retardants 14
Perchlorate 15
Diet Scores/Patterns 21
Recommendations and Guidelines for Pregnant Women 27
Lifestyle 27
Vitamins and Minerals 28
Environmental Issues 29
Gaps in Recommendations 30
Prenatal Exposure to EDCs 31
Size at Birth 33
Perfluoroalkyl substances 33
Polychlorinated biphenyls 34
Organochlorine pesticides 35
Postnatal Body Size 37
Perfluoroalkyl substances 37
Polychlorinated biphenyls and organochlorine pesticides 38
Pubertal Development and Age at Menarche 40
Perfluoroalkyl substances 40
Polychlorinated biphenyls 41
Organochlorine pesticides 42
Assessing Health Effects of Environmental Chemical Mixtures 43
Challenges to Studying Chemical Mixtures 46
Measurement of environmental chemical exposure 47
Statistical challenges 48
Confounding due to correlated exposures 48
Differing degrees of measurement error among exposures 49
Identification of important mixtures 50
Lack of standard methods to evaluate environmental mixtures 50
Conclusion 51
Chapter 3 Maternal dietary patterns during pregnancy and exposure to persistent endocrine disrupting chemicals in two European birth cohorts 52
Introduction 53
Methods 55
Study populations 55
The Avon Longitudinal Study of Parents and Children (ALSPAC) 55
The Norwegian Mother, Father, and Child Cohort Study (MoBa) 55
Exposure assessment 56
Outcome assessment 58
Perfluoroalkyl substances 58
Organochlorine pesticides and polychlorinated biphenyls 59
Covariates 59
Statistical analyses 60
Results 61
Discussion 63
Acknowledgments 68
Chapter 4 Mixtures of prenatal concentrations of persistent endocrine disrupting chemicals and birth size in British girls 93
Introduction 94
Methods 96
Study population 96
Exposure assessment 97
Per- and polyfluoroalkyl substances 97
Organochlorine pesticides and polychlorinated biphenyls 97
Outcome assessment 98
Covariates 98
Statistical analyses 99
Results 101
Descriptive statistics 101
Single- and multi-chemical models 102
Weighted Quantile Sum Regression 102
Bayesian Kernel Machine Regression 103
Sensitivity analyses 103
Discussion 104
Chapter 5 Mixtures of prenatal concentrations of persistent endocrine disrupting chemicals and postnatal body size in British girls 132
Introduction 133
Methods 134
Study population 134
Exposure assessment 135
Per- and polyfluoroalkyl substances 136
Organochlorine pesticides and polychlorinated biphenyls 136
Outcome assessment 136
Covariates 137
Statistical analyses 137
Results 139
Descriptive statistics 139
Single- and multi-chemical models 140
Weight-for-age scores at 19 months 140
Weight-for-age scores at 0, 2, 9, and 19 months 140
Bayesian Kernel Machine Regression 141
All three classes combined and weight-for-age scores 141
All three classes combined and height- and BMI-for-age scores 142
Class-specific mixtures and weight-for-age scores 142
Sensitivity analyses 142
Discussion 143
Acknowledgments 147
Funding 147
Acknowledgments 147
Disclosures 147
Supplemental methods 175
Chapter 6 Prenatal exposure to mixtures of persistent endocrine disrupting chemicals and early menarche in a population-based cohort of British girls 179
Introduction 180
Methods 182
Study population 182
Exposure assessment 183
Poly- and perfluoroalkyl substances 183
Organochlorine pesticides and polychlorinated biphenyls 183
Outcome assessment 184
Covariates 184
Statistical analyses 184
Results 186
Descriptive statistics 186
Single- and multi-chemical models 187
Weighted Quantile Sum Regression 188
Bayesian Kernel Machine Regression 188
Sensitivity analyses 188
Discussion 189
Acknowledgments 192
Funding 192
Acknowledgments 193
Disclosures 193
Chapter 7 Summary of Findings and Future Research 215
Summary of Findings 215
Findings from Aim 1 215
Findings from Aim 2A 216
Findings from Aim 2B 217
Findings from Aim 3 217
Overall Findings 218
Strengths and Limitations 219
Strengths 219
Limitations in design 220
Limitations in ability to control for confounding 221
Limitations due to misclassification 223
Limitations in generalizability 224
Future Research 224
References 227
Funding 252
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