Maternal diet, environmental contaminants, and growth and developmental outcomes in offspring Open Access

Marks, Kristin J. (Fall 2020)

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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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