Features of placental morphology, fetal growth, and adverse cognitive outcomes in childhood 公开
Freedman, Alexa (Spring 2018)
Abstract
Background: The placenta plays a critical role in regulating healthy fetal development by mediating oxygen, nutrient, and waste transfer between the mother and the fetus. Poor placental development may result in suboptimal fetal growth due to failure of the placenta to meet the needs of the fetus. Neonates who experienced suboptimal fetal growth are at greater risk of perinatal morbidity and mortality, as well as cognitive delays in childhood. There may also be sex-specific differences in these associations due to potential differences in placental and fetal development.
Methods: We used data from four completed studies to investigate relationships between placental morphology (thickness, surface area, shape, and umbilical cord insertion), birthweight, and intelligence quotient (IQ). First, we examined the validity of using placental diameters to calculate surface area using 491 placentas that underwent a standardized examination. Next, we evaluated the associations between placental morphology and birthweight separately in 1,229 singletons and 208 sets of dichorionic twins. Finally, we assessed the relationships between placental morphology and IQ in 514 singletons at age five and 82 sets of twins at age seven.
Results: We found that diameter-based measures slightly under estimated placental surface area but were a good proxy for use in subsequent analyses. In investigating relationships between placental morphology and birthweight, we found that thickness and surface area were independently associated with birthweight among singletons and twins. Further, estimates of the associations diverged for same-sex male and same-sex female twin pairs, with stronger associations observed among same-sex male pairs. Finally, we found that features of placental morphology were not associated with IQ in childhood among singletons or twins. However, when we considered interaction between sex and placental morphology, estimates were stronger among both male singletons and same-sex male twin pairs as compared to female singletons and same-sex female twin pairs, respectively.
Conclusions: Our results suggest that features of placental morphology are associated with birthweight but not with IQ. Further, results from analyses in twins support sex-specific differences in these associations. Given the critical role of the placenta in regulating fetal growth, future studies should consider the role of the placenta in the developmental programming of long-term health outcomes. Promoting healthy pregnancy may be an important form of primary prevention for many adverse health outcomes.
Table of Contents
TABLE OF CONTENTS
List of Figures .............................................................................................................................. i
List of Tables .............................................................................................................................. iii
Chapter 1: Introduction and Literature Review .............................................................................. 1
Introduction ................................................................................................................................. 2
The placenta plays a critical role in regulating fetal growth and development ....................... 2
The placenta is the least understood organ .............................................................................. 7
Suboptimal fetal growth has short and long-term health consequences .................................. 9
Literature Review ...................................................................................................................... 14
Evaluating error in estimated placental surface area ............................................................. 14
Features of placental morphology and fetal growth .............................................................. 15
Features of placental morphology and cognitive outcomes .................................................. 24
Gaps in our knowledge .......................................................................................................... 26
Specific Aims ............................................................................................................................ 28
Chapter 2: Comparison of diameter-based and image-based measures of placental surface area
for use in epidemiologic studies ................................................................................................... 31
Authors ...................................................................................................................................... 32
Abstract ..................................................................................................................................... 33
Introduction ............................................................................................................................... 34
Methods ..................................................................................................................................... 35
Results ....................................................................................................................................... 37
Discussion ................................................................................................................................. 38
Figures and Tables .................................................................................................................... 41
Supplemental Material .............................................................................................................. 44
Acknowledgements ................................................................................................................... 46
Chapter 3: Associations between features of gross placental morphology and birthweight ........ 49
Authors ...................................................................................................................................... 50
Abstract ..................................................................................................................................... 51
Introduction ............................................................................................................................... 52
Methods ..................................................................................................................................... 53
Results ....................................................................................................................................... 57
Discussion ................................................................................................................................. 60
Figures and Tables .................................................................................................................... 65
Supplemental Material .............................................................................................................. 72
Acknowledgements ................................................................................................................... 80
Chapter 4: Associations between features of placental morphology and birthweight in
dichorionic twins ........................................................................................................................... 82
Authors ...................................................................................................................................... 83
Abstract ..................................................................................................................................... 84
Introduction ............................................................................................................................... 85
Methods ..................................................................................................................................... 86
Results ....................................................................................................................................... 90
Discussion ................................................................................................................................. 92
Figures and Tables .................................................................................................................... 96
Supplemental Material ............................................................................................................ 102
Acknowledgements ................................................................................................................. 107
Chapter 5: Associations between placental morphology and cognitive assessments in singletons
and dichorionic twins .................................................................................................................. 110
Authors .................................................................................................................................... 111
Abstract ................................................................................................................................... 112
Introduction ............................................................................................................................. 113
Methods ................................................................................................................................... 115
Results ..................................................................................................................................... 120
Discussion ............................................................................................................................... 122
Figures and Tables .................................................................................................................. 126
Supplemental Material ............................................................................................................ 132
Acknowledgements ................................................................................................................. 138
Chapter 6: Dissertation Conclusions and Implications ............................................................... 139
Tables ...................................................................................................................................... 148
References ................................................................................................................................... 149
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