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PRETERM BIRTH

CAUSES, CONSEQUENCES, AND PREVENTION

Committee on Understanding Premature Birth and Assuring Healthy Outcomes

Board on Health Sciences Policy

Richard E. Behrman and Adrienne Stith Butler, Editors

INSTITUTE OF MEDICINE OF THE ACADEMIES

THE NATIONAL ACADEMIES PRESS

Washington, D.C.
www.nap.edu



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Preterm Birth: Causes, Consequences, and Prevention PRETERM BIRTH CAUSES, CONSEQUENCES, AND PREVENTION Committee on Understanding Premature Birth and Assuring Healthy Outcomes Board on Health Sciences Policy Richard E. Behrman and Adrienne Stith Butler, Editors INSTITUTE OF MEDICINE OF THE ACADEMIES THE NATIONAL ACADEMIES PRESS Washington, D.C. www.nap.edu

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Preterm Birth: Causes, Consequences, and Prevention THE NATIONAL ACADEMIES PRESS 500 Fifth Street, N.W. Washington, DC 20001 NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance. This study was supported by Contract No. N01-OD-4-2139, Task Order No. 145 between the National Academy of Sciences and the National Institute for Child Health and Human Development, Centers for Disease Control and Prevention, Health Resources and Services Administration, Environmental Protection Agency, and NIH Office of Research on Women’s Health; and contracts with the March of Dimes, Burroughs Wellcome Fund, American College of Obstetricians and Gynecologists, American Society for Reproductive Medicine, and the Society for Maternal-Fetal Medicine. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the organizations or agencies that provided support for this project. Library of Congress Cataloging-in-Publication Data Preterm birth : causes, consequences, and prevention / Committee on Understanding Premature Birth and Assuring Healthy Outcomes, Board on Health Sciences Policy ; Richard E. Behrman, Adrienne Stith Butler, editors. p. ; cm. Includes bibliographical references and index. ISBN-13: 978-0-309-10159-2 (hardback) ISBN-10: 0-309-10159-X (hardback) 1. Labor, Premature. I. Behrman, Richard E., 1931- . II. Butler, Adrienne Stith. III. Institute of Medicine (U.S.). Committee on Understanding Premature Birth and Assuring Healthy Outcomes. [DNLM: 1. Premature Birth—diagnosis—United States. 2. Premature Birth—economics—United States. 3. Premature Birth—prevention & control—United States. 4. Public Policy—United States. WQ 330 P9413 2006] RG649.P744 2006 618.3′97—dc22 2006028538 Additional copies of this report are available from the National Academies Press, 500 Fifth Street, N.W., Lockbox 285, Washington, DC 20055; (800) 624-6242 or (202) 334-3313 (in the Washington metropolitan area); Internet, http://www.nap.edu. For more information about the Institute of Medicine, visit the IOM home page at: www.iom.edu. Copyright 2007 by the National Academy of Sciences. All rights reserved. Printed in the United States of America. The serpent has been a symbol of long life, healing, and knowledge among almost all cultures and religions since the beginning of recorded history. The serpent adopted as a logotype by the Institute of Medicine is a relief carving from ancient Greece, now held by the Staatliche Museen in Berlin.

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Preterm Birth: Causes, Consequences, and Prevention “Knowing is not enough; we must apply. Willing is not enough; we must do.” —Goethe INSTITUTE OF MEDICINE OF THE NATIONAL ACADEMIES Advising the Nation. Improving Health.

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Preterm Birth: Causes, Consequences, and Prevention THE NATIONAL ACADEMIES Advisers to the Nation on Science, Engineering, and Medicine The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Ralph J. Cicerone is president of the National Academy of Sciences. The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. Wm. A. Wulf is president of the National Academy of Engineering. The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Harvey V. Fineberg is president of the Institute of Medicine. The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy’s purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Ralph J. Cicerone and Dr. Wm. A. Wulf are chair and vice chair, respectively, of the National Research Council. www.national-academies.org

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Preterm Birth: Causes, Consequences, and Prevention COMMITTEE ON UNDERSTANDING PREMATURE BIRTH AND ASSURING HEALTHY OUTCOMES RICHARD E. BEHRMAN (Chair), Executive Chair, Pediatric Education Steering Committee, Federation of Pediatric Organizations, Inc., Menlo Park, CA ELI Y. ADASHI, Dean of Medicine and Biological Sciences, Brown University, Providence, RI MARILEE C. ALLEN, Professor of Pediatrics, The John Hopkins Hospital, Baltimore, MD RITA LOCH CARUSO, Professor, Environmental Health Sciences, Associate Research Scientist, School of Public Health, University of Michigan, Ann Arbor JENNIFER CULHANE, Associate Professor, Department of Obstetrics & Gynecology, Drexel University College of Medicine, Philadelphia, PA CHRISTINE DUNKEL SCHETTER, Professor, Department of Psychology, Health and Social Psychology, University of California, Los Angeles MICHEAL G. GRAVETT, Professor and Vice-Chairman, Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle JAY D. IAMS, Professor and Vice-Chairman, Department of Obstetrics and Gynecology, Ohio State University College of Medicine, Columbus MICHAEL C. LU, Assistant Professor, Department of Community Health Sciences, School of Public Health, Deparment of Obstetrics and Gynecology, School of Medicine, University of California, Los Angeles MARIE C. MCCORMICK, Professor, Department of Society, Human Development and Health, School of Public Health, Harvard University, Boston, MA LAURA E. RILEY, Director, Labor and Delivery, Director, Infectious Disease, Massachusetts General Hospital, Boston JEANNETTE A. ROGOWSKI, University Professor, Department of Health Systems and Policy, School of Public Health, University of Medicine and Dentistry of New Jersey, New Brunswick SAROJ SAIGAL, Professor of Pediatrics, Director, Neonatal Follow-up Program, Senior Scientist, CIHR, McMaster University, Hamilton, Ontario, Canada DAVID A. SAVITZ, Professor, Department of Community and Preventive Medicine, Mount Sinai School of Medicine, New York HYAGRIV N. SIMHAN, Assistant Professor, Divisions of Maternal-Fetal Medicine and Reproductive Infectious Diseases and Immunology, University of Pittsburgh, Magee-Women’s Hospital, Pittsburgh, PA

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Preterm Birth: Causes, Consequences, and Prevention NORMAN J. WAITZMAN, Associate Professor, Deparment of Economics, University of Utah, Salt Lake City XIAOBIN WANG, Director and Mary Ann and J. Milburn Smith Research Professor, Children’s Memorial Hospital and Children’s Memorial Research Center, Chicago, IL Health Sciences Policy Board Liaison GAIL H. CASSELL, Vice President, Scientific Affairs, Distinguished Lilly Research Scholar for Infectious Diseases, Eli Lilly and Company, Indianapolis, IN IOM Project Staff ADRIENNE STITH BUTLER, Study Director EILEEN J. SANTA, Research Associate THELMA L. COX, Senior Program Assistant Copy Editor MICHAEL HAYES

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Preterm Birth: Causes, Consequences, and Prevention BOARD ON HEALTH SCIENCES POLICY FRED H. GAGE (Chair), The Salk Institute for Biological Studies, La Jolla, CA GAIL H. CASSELL, Eli Lilly and Company, Indianapolis, IN JAMES F. CHILDRESS, University of Virginia, Charlottesville ELLEN WRIGHT CLAYTON, Vanderbilt University Medical School, Nashville, TN DAVID R. COX, Perlegen Sciences, Mountain View, CA LYNN R. GOLDMAN, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD BERNARD D. GOLDSTEIN, University of Pittsburgh, Pittsburgh, PA MARTHA N. HILL, Johns Hopkins University School of Nursing, Baltimore, MD ALAN LESHNER, American Association for the Advancement of Science, Washington, DC DANIEL MASYS, Vanderbilt University Medical Center, Nashville, TN JONATHAN D. MORENO, University of Virginia, Charlottesville E. ALBERT REECE, University of Arkansas, Little Rock MYRL WEINBERG, National Health Council, Washington, DC MICHAEL J. WELCH, Washington University School of Medicine, St. Louis, MO OWEN N. WITTE, University of California, Los Angeles MARY WOOLLEY, Research!America, Alexandria, VA IOM Staff ANDREW M. POPE, Director AMY HAAS, Board Assistant DAVID CODREA, Financial Associate

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Preterm Birth: Causes, Consequences, and Prevention Reviewers This report has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise, in accordance with procedures approved by the NRC’s Report Review Committee. The purpose of this independent review is to provide candid and critical comments that will assist the institution in making its published report as sound as possible and to ensure that the report meets institutional standards for objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We wish to thank the following individuals for their review of this report: GLEN AYLWARD, Southern Illinois University School of Medicine PAULA A. BRAVEMAN, University of California, San Francisco School of Medicine CHRISTOS COUTIFARIS, University of Pennsylvania Medical Center JANET CURRIE, Columbia University M. SEAN ESPLIN, University of Utah Health Sciences Center NEIL FINER, University of California, San Diego THOMAS J. GARITE, Professor Emeritus, University of California, Irvine LAURA GLYNN, University of California, Irvine JOHN GODDEERIS, Michigan State University MAUREEN HACK, Case Western Reserve University HOWARD HU, Harvard School of Public Health

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Preterm Birth: Causes, Consequences, and Prevention KATHY S. KATZ, Georgetown University Hospital CHARLES LOCKWOOD, Yale University School of Medicine JEROME F. STRAUSS, Virginia Commonwealth University School of Medicine MICHELLE A. WILLIAMS, University of Washington School of Public Health and Community Medicine Although the reviewers listed above have provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations nor did they see the final draft of the report before its release. The review of this report was overseen by NANCY E. ADLER. Appointed by the National Research Council, she was responsible for making certain that an independent examination of this report was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content of this report rests entirely with the authoring committee and the institution.

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Preterm Birth: Causes, Consequences, and Prevention Preface Preterm birth and its consequences constitute a major health problem in the United States and worldwide. However, there has been relatively little attention from the public and research community despite the significant impact preterm birth and prematurity have on infant mortality and subsequent disabilities of many survivors, and on societal and economic costs to the nation. This health problem is associated with multiple complex and poorly understood, but interrelated, biologic, psychologic, and social factors that appear to be expressed in the common pathway of preterm birth. Low socioeconomic status alone does not explain the increase in preterm births among African Americans compared to the white non-Hispanic population. Prenatal care is currently primarily directed at identifying and managing preeclampsia; maternal infections, diabetes, and other major illnesses; birth defects; and intrauterine fetal growth failure. As our knowledge and understanding of preterm birth increase, prenatal care will provide a health infrastructure for women from which it is possible to prevent, diagnose, and treat preterm births. The nature of this health problem and the charge to the committee required a comprehensive assessment as well as an in depth analysis resulting in a large-volume report. The Committee suggests that readers first review the executive summary for essential ideas and recommendations, then turn to the abstracts of each chapter before reading each of the individual chapters. Richard E. Behrman, M.D. Chair Committee on Understanding Premature Birth and Assuring Healthy Outcomes

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Preterm Birth: Causes, Consequences, and Prevention Acknowledgments Several individuals and organizations made important contributions to the study committee’s process and to this report. The committee wishes to thank these individuals, but recognizes that attempts to identify all and acknowledge their contributions would require more space than is available in this brief section. To begin, the committee would like to thank the sponsors of this report. Funds for the committee’s work were provided by the National Institute for Child Health and Human Development, the Centers for Disease Control and Prevention, the Health Resources and Services Administration, March of Dimes, Burroughs Wellcome Fund, American College of Obstetricians and Gynecologists, Environmental Protection Agency, National Institutes of Health Office of Research on Women’s Health, American Society for Reproductive Medicine, and the Society for Maternal-Fetal Medicine. The committee thanks Capt. Donald Mattison, Scott Grosse, and Samuel Posner, who served as project officers and who were instrumental in the initiation of this activity. The committee thanks Ann Koontz, Marina Weiss, Nancy Green, Lisa Potetz, Enriqueta Bond, Nancy Sung, Ralph Hale, Nicole Owens, Lanelle Bembenek Wiggins, Vivian Pinn, Loretta Finnegan, Robert Rebar, and Richard Depp for their support and guidance on the committee’s task. Special recognition is also given to Eli Adashi and Gloria Sarto for the fundamental roles they played in the initiation of this activity. The committee found the perspectives of many individuals and organizations to be valuable in understanding the causes and consequences of preterm birth. The committee thanks the numerous individuals and organizations who generously provided information and assistance during delib

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Preterm Birth: Causes, Consequences, and Prevention erations. Appendix A of this report contains the names of those who participated in the committee’s meetings by providing important information at its open workshops. The committee also gratefully acknowledges the contributions of the many individuals who assisted the committee in its work, either by providing data and research support or by assisting in the preparation of draft material. The committee would like to thank Brent James and Intermountain Healthcare (IHC) for data used to generate the cost estimates provided in the chapter, “Societal Costs of Preterm Birth.” In particular, Pascal Briot, Russell Staheli, and Erick Henry performed much of the data generation used for the medical care estimates. C. Jason Wang of the RAND Corporation served as an appointed consultant and assisted the committee in preparation of the chapter, “Public Policies Affected by Preterm Birth.” James Perrin of Massachusetts General Hospital, and Wendy Chavkin and Blair Johnson of Columbia University’s Mailman School of Public Health also served as appointed consultants and provided information on policies related to preterm birth. Stavros Petrou of the University of Oxford, an appointed consultant, provided information and assistance on the economic consequences of preterm birth. Ciaran Phibbs of Stanford University; Wanda Barfield of the Massachusetts Department of Public Health; Charles Mercier of the University of Vermont; Joyce Martin of the Centers for Disease Control and Prevention; Mona Rowe of the National Institutes of Health; Ralph Hale, Albert Strunk, Bernice Rose, Nonda Wilson, Donna Kovacheva of the American College of Obstetricians and Gynecologists; Mario Merialdi of the World Health Organization; and Vipul Mankad of the University of Kentucky provided information, reports, and data. The committee thanks each of these individuals. Finally, the committee would also like to thank the authors whose paper contributions added to the evidence base that the committee examined. These include John A.F. Zupancic, Harvard Medical School; Gerri R. Baer and Robert M. Nelson, The Children’s Hospital of Philadelphia and the University of Pennsylvania School of Medicine; and Greg R. Alexander, University of South Florida.

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Preterm Birth: Causes, Consequences, and Prevention Contents     Summary   1 1   Introduction   31 Section I Measurement   53 2   Measurement of Fetal and Infant Maturity   55 Section I   Recommendations   84 Section II Causes of Preterm Birth   87 3   Behavioral and Psychosocial Contributors to Preterm Birth   89 4   Sociodemographic and Community Factors Contributing to Preterm Birth   124 5   Medical and Pregnancy Conditions Associated with Preterm Birth   148 6   Biological Pathways Leading to Preterm Birth   169 7   Role of Gene-Environment Interactions in Preterm Birth   207 8   The Role of Environmental Toxicants in Preterm Birth   229 Section II   Recommendations   255 Section III Diagnosis and Treatment of Preterm Labor   259 9   Diagnosis and Treatment of Conditions Leading to Spontaneous Preterm Birth   261 Section III   Recommendations   308

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Preterm Birth: Causes, Consequences, and Prevention Section IV Consequences of Preterm Birth   311 10   Mortality and Acute Complications in Preterm Infants   313 11   Neurodevelopmental, Health, and Family Outcomes for Infants Born Preterm   346 12   Societal Costs of Preterm Birth   398 Section IV   Recommendations   430 Section V Research and Policy   433 13   Barriers to Clinical Research on Preterm Birth and Outcomes for Preterm Infants   435 14   Public Policies Affected by Preterm Birth   455     Section V Recommendations   473 15   A Research Agenda to Investigate Preterm Birth   477     REFERENCES   493 APPENDIXES     A   Data Sources and Methods   591 B   Prematurity at Birth: Determinants, Consequences, and Geographic Variation   604 C   A Review of Ethical Issues Involved in Premature Birth   644 D   A Systematic Review of Costs Associated with Preterm Birth   688 E   Selected Programs Funding Preterm Birth Research   725 F   Committee and Staff Biographies   732 INDEX   741

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Preterm Birth: Causes, Consequences, and Prevention PRETERM BIRTH

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