Making Breathing Easier: Does Surfactant Reduce the Association of Neonatal Respiratory Distress Syndrome with Maternal Hypertension? Open Access

Abstract

CONTEXT: There is conflicting information regarding the association between maternal hypertension (mHTN, any diagnosis of hypertension while pregnant) and neonatal respiratory distress syndrome (RDS). Additionally, few studies have investigated mHTN and surfactant administration, which is a common treatment of neonatal RDS.

OBJECTIVE: To assess the direct effects of mHTN on neonatal RDS, and to see what total effect remains after consideration of surfactant administration (indirect effect).

DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort was comprised of U.S. birth certificate information from 2005-2009. Eligibility included live, singleton hospital births from 24-36 completed weeks' gestation, with exclusion of births including antenatal steroids and meconium staining (n=1,049,473). Directed acyclic graphs were constructed to incorporate information from literature review and expert opinion and select risk factors. Associative models for direct and indirect effects were constructed via multivariable logistic regression and using chunk method followed by backwards elimination.

MAIN OUTCOME MEASURES: Adjusted OR (aOR) of mHTN with and without adjustment for surfactant administration, percent difference in aORs between direct effect (mHTN on RDS) and indirect effect (mHTN on RDS via surfactant administration), and prevalence of neonatal RDS (given proxy of ventilation over 6 hours).

RESULTS: There is a significant association with mHTN and neonatal RDS by all gestational age categories, (aOR 1.77 for all eligible births, 1.47-1.81 after stratification by gestational age, P<0.0001). The association with mHTN and RDS continues after adjustment for surfactant administration (aOR 1.69 for all eligible births, 1.42-1.70 after stratification by gestational age, P<0.0001).

CONCLUSION: Given the extensive literature affirming the ability of exogenous surfactant to diminish the morbidity associated with neonatal RDS, this analysis suggests that healthcare providers are not appropriately targeting neonates in need of surfactant in cases of mHTN.

Table of Contents

TABLE OF CONTENTS

Distribution Agreement i
Approval Sheet ii
Abstract Cover Page iii
Abstract v
Cover Page vi
Table of Contents viii
List of Abbreviations xii

CHAPTER 1: Background 1

Maternal Hypertension 1

Methods of Classification
Relationship to Gestational Age and Birth Weight

Surfactant 2

Synergism with Antenatal Steroids
Timing of Administration

Respiratory Distress Syndrome 3
Other Considerations 4

Antenatal Steroids
Meconium Aspiration Syndrome
Maternal Race and Ethnicity
Limitations of Birth Certificates

CHAPTER II: Making Breathing Easier: Does Surfactant Reduce the Association of Neonatal Respiratory Distress Syndrome with Maternal Hypertension? 8

Introduction 8
Methods 11 Results 13
Discussion 18
Tables for Chapter II 21

Table II.I: Descriptive Analysis of Eligible Births, by frequency (%)
Table II.2: Descriptive Analysis for Eligible Births, by frequency (%) for Extremes of Age (Extremely Preterm Births vs. Late Preterm Births)
Table II.3 Potential Confounders between Maternal Hypertension and Neonatal Respiratory Distress Syndrome (All eligible births)

Table II.3A Potential Confounders between Maternal Hypertension and Neonatal Respiratory Distress Syndrome (Extremely preterm births)
Table II.3B Potential Confounders between Maternal Hypertension and Neonatal Respiratory Distress Syndrome (Very preterm births)
Table II.3C Potential Confounders between Maternal Hypertension and Neonatal Respiratory Distress Syndrome (Preterm births)
Table II.3D Potential Confounders between Maternal Hypertension and Neonatal Respiratory Distress Syndrome (Late preterm births)

Table II.4 Interactions between Risk factors and Surfactant
Table II.5: Variables used in Model Construction, by gestational age
Table II.6 Final Models, by gestational age
Table II.7: Comparing Associations from final models, by gestational age
Table II.8: Comparing Odds of Neonatal Respiratory Distress Syndrome by Surfactant Status, by gestational age

Figures for Chapter II 29

Figure II.1: Directed Acyclic Graph for Primary and Secondary Analysis
Figure II.2: Directed Acyclic Graph for Primary and Secondary Analysis, with all Considered Variables
Figure II.3: Directed Acyclic Graph for Primary and Secondary Analysis, with Final Variables
Legend for Figures II.1-II.3
Figure II.4 Considered Variables and Potential Causes for Elimination

CHAPTER III: Making Breathing Easier: A Birth Certificate Analysis Examining Maternal Hypertension and Neonatal Respiratory Distress Syndrome

Introduction 31
Methods 33
Results 35 Discussion 39
Tables for Chapter III 41

Table III.I: Descriptive Analysis of Eligible Births, by frequency (%)
Table III.2: Descriptive Analysis for Eligible Births, by frequency (%) for Extremes of Age (Extremely Preterm Births vs. Late Preterm Births)
Table III.3 Potential Confounders between Maternal Hypertension and Neonatal Respiratory Distress Syndrome (All eligible births)

Table III.3A Potential Confounders between Maternal Hypertension and Neonatal Respiratory Distress Syndrome (Extremely preterm births)
Table III.3B Potential Confounders between Maternal Hypertension and Neonatal Respiratory Distress Syndrome (Very preterm births)
Table III.3C Potential Confounders between Maternal Hypertension and Neonatal Respiratory Distress Syndrome (Preterm births)
Table III.3D Potential Confounders between Maternal Hypertension and Neonatal Respiratory Distress Syndrome (Late preterm births)

Table III.4 Interactions between Risk factors and Maternal Hypertension
Table III.5: Variables used in Model Construction, by gestational age
Table III.6 Final Models, by gestational age

Figures for Chapter III 47

Figure III.1: Directed Acyclic Graph
Figure III.2: Directed Acyclic Graph, with all Considered Variables
Figure III.3: Directed Acyclic Graph, with Final Variables
Legend for Figures III.1- III.3
Figure III.4 Considered Variables and Potential Causes for Elimination

CHAPTER IV: Public Health Implications and Possible Future Directions 49

Public Health Implications 49

Direct Effect of Maternal Hypertension on Neonatal Respiratory Distress Syndrome
Indirect Effect with Exogenous Surfactant Administration
Other Considerations

Possible Future Directions 50
References 52
Appendix 56

Variables

About this Master's Thesis

Rights statement

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School	Rollins School of Public Health
Department	Epidemiology
Degree	MPH
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Public Health Health Sciences, Epidemiology
Keyword	Hypertension in pregnancy Neonatal Respiratory Distress Syndrome
Committee Chair / Thesis Advisor	Hogue, Carol J, Emory University
Committee Members	Raskind-Hood, Cheryl, Emory University
Partnering Agencies	Emory University schools, faculty or affiliated programs CDC

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