Fanaroff and Martin’s Neonatal-Perinatal Medicine. Diseases of the Fetus and Infant [11 ed.] 9780323567114, 9996122883, 9996122948

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Fanaroff and Martin’s Neonatal-Perinatal Medicine

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Fanaroff and Martin’s Neonatal-Perinatal Medicine Diseases of the Fetus and Infant

11th Edition Richard J. Martin, MBBS, FRACP Professor, Pediatrics, Reproductive Biology, and Physiology and Biophysics Case Western Reserve University School of Medicine Drusinsky/Fanaroff Chair in Neonatology Rainbow Babies and Children’s Hospital Cleveland, Ohio

Avroy A. Fanaroff, MD, FRCPE, FRCPCH Emeritus Professor, Pediatrics and Reproductive Biology Case Western Reserve University School of Medicine Emeritus Eliza Henry Barnes Chair in Neonatology Rainbow Babies and Children’s Hospital Cleveland, Ohio

Michele C. Walsh, MD, MSE Professor, Pediatrics Case Western Reserve University School of Medicine William and Lois Briggs Chair in Neonatology Chief, Division of Neonatology Rainbow Babies and Children’s Hospital Cleveland, Ohio

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Elsevier 1600 John F. Kennedy Blvd. Ste 1800 Philadelphia, PA 19103-2899

FANAROFF AND MARTIN’S NEONATAL-PERINATAL MEDICINE, ELEVENTH EDITION Copyright © 2020 by Elsevier, Inc. All rights reserved.

ISBN: 978-0-323-56711-4 Volume 1 part number: 9996122883 Volume 2 part number: 9996122948

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To our spouses Patricia Martin and Roslyn Fanaroff to the Martin children and grandchildren Scott, Molly, William, and Adelaide Martin; Sonya Martin; and Peter, Mateo, and Soren Graif to the Fanaroff children and grandchildren Jonathan, Kristy, Mason, Cole, and Brooke Fanaroff; Jodi, Peter, Austin, and Morgan Tucker; and Amanda, Jason, Jackson, and Raya Hirsh to the Walsh children Sean and Tiffany Sukys and Ryan Sukys with love, admiration, and deep appreciation for their continued support and inspiration

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Contributors

Steven A. Abrams, MD Professor Pediatrics Dell Medical School at the University of Texas at Austin Austin, Texas Disorders of Calcium, Phosphorus, and Magnesium Metabolism in the Neonate Johan Ågren, MD, PhD Associate Professor Department of Women’s and Children’s Health Uppsala University Uppsala, Sweden Thermal Environment of the Intensive Care Nursery Sanjay Ahuja, MD, MSc Associate Professor Pediatrics Case Western Reserve University Rainbow Babies and Children’s Hospital Cleveland, Ohio Hematologic and Oncologic Problems in the Fetus and Neonate Mohammad A. Attar, MD Professor of Pediatrics Division of Neonatal-Perinatal Medicine C.S. Mott Children’s Hospital Michigan Medicine, University of Michigan Ann Arbor, Michigan Assisted Ventilation of the Neonate and Its Complications Jill E. Baley, MD Associate Medical Director, Transitional Care Unit Rainbow Babies and Children’s Hospital Professor of Pediatrics Case Western Reserve University School of Medicine Cleveland, Ohio Viral Infections in the Neonate Schedule for Immunization of Preterm Infants

A. Rebecca Ballard, MD Neonatologist Pediatrix Medical Group Woodlands, Texas Support for the Family Eduardo H. Bancalari, MD Professor Pediatrics University of Miami Miami, Florida Bronchopulmonary Dysplasia in the Neonate Nancy Bass, MD Associate Professor Pediatrics and Neurology Case Western Reserve University Rainbow Babies and Children’s Hospital Cleveland, Ohio Hypotonia and Neuromuscular Disease in the Neonate Sanmit K. Basu Director, Pediatric Cardiac CT-MR Imaging Assistant Professor of Pediatrics University of Chicago Medicine–Comer Children’s Hospital Chicago, Illinois Congenital Defects of the Cardiovascular System Cynthia F. Bearer, MD, PhD Mary Gray Cobey Professor of Neonatology Chief, Division of Neonatology Pediatrics University of Maryland School of Medicine Baltimore, Maryland Adverse Exposures to the Fetus and Neonate William E. Benitz, MD Professor of Neonatology Division of Neonatal and Developmental Medicine Stanford University School of Medicine Palo Alto, California Patent Ductus Arteriosus

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Contributors

John T. Benjamin, MD, MPH Assistant Professor of Pediatrics Division of Neonatology Vanderbilt University Medical Center Nashville, Tennessee Developmental Immunology Sheila C. Berlin, MD Associate Professor and Vice Chair Department of Radiology University Hospitals of Cleveland Cleveland, Ohio Diagnostic Imaging of the Neonate Shazia Bhombal, MD Clinical Assistant Professor of Pediatrics Division of Neonatal and Developmental Medicine Stanford University School of Medicine Palo Alto, California Patent Ductus Arteriosus Isaac Blickstein, MD Professor Department of Obstetrics and Gynecology Kaplan Medical Center Rehovot, Israel Pregnancy Complicated by Diabetes Mellitus Fetal Effects of Autoimmune Disease Obstetric Management of Multiple Gestation and Birth Post-Term Pregnancy Martin L. Bocks, MD Director of Pediatric Interventional Cardiology The Congenital Heart Collaborative Rainbow Babies and Children’s Hospital Cleveland, Ohio Neonatal Management of Congenital Heart Disease Brian A. Boe, MD Assistant Professor of Pediatrics The Heart Center Nationwide Children’s Hospital Columbus, Ohio Neonatal Management of Congenital Heart Disease Jennifer C. Burgis, BS, MD Clinical Associate Professor Pediatrics-Gastroenterology Stanford University Stanford, California Neonatal Jaundice and Liver Diseases

Bryan Cannon, MD, FAAP, FACC, FHRS Vice Chair for Education Department of Pediatrics Mayo Clinic Rochester, Minnesota Disorders of Cardiac Rhythm and Conduction in Newborns Waldemar A. Carlo, MD Edwin M. Dixon Professor of Pediatrics Pediatrics University of Alabama at Birmingham Birmingham, Alabama Perinatal and Neonatal Care in Developing Countries Assessment of Neonatal Pulmonary Function Gisela Chelimsky, MD Professor of Pediatrics Pediatrics-Gastroenterology Medical College of Wisconsin Milwaukee, Wisconsin Disorders of Digestion in the Neonate Alison Chu, MD Assistant Professor-in-Residence Pediatrics University of California Los Angeles Los Angeles, California Intrauterine Growth Restriction Janet Chuang, MD Assistant Professor Pediatric Endocrinology Cincinnati Children’s Hospital Medical Center Cincinnati, Ohio Thyroid Disorders in the Neonate Maged M. Costantine, MD Associate Professor, Maternal Fetal Medicine Department of Obstetrics and Gynecology The University of Texas Medical Branch Galveston, Texas Obstetric Management of Prematurity Moira A. Crowley, MD Associate Professor of Pediatrics Case Western Reserve University School of Medicine Cleveland, Ohio Neonatal Respiratory Disorders

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Contributors

Pe’er Dar, MD, FACOG, FACMG Professor, Obstetrics and Gynecology and Women’s Health Director, Division of Fetal Medicine and OBGYN Ultrasound Albert Einstein College of Medicine/Montefiore Medical Center Bronx, New York Perinatal Ultrasound Peter Davis, MBBS, MD Professor Neonatology The Royal Women’s Hospital Melbourne, Victoria, Australia Role of Positive Pressure Ventilation in Neonatal Resuscitation Linda S. de Vries, MD, PhD Neonatology Wilhelmina Children’s Hospital University Medical Center Utrecht Utrecht University Utrecht, Netherlands Intracranial Hemorrhage and Vascular Lesions in the Neonate Hypoxic–Ischemic Encephalopathy Katherine MacRae Dell, MD Professor of Pediatrics Case Western Reserve University School of Medicine Cleveland, Ohio Fluid, Electrolytes, and Acid-Base Homeostasis Eric J. Devaney, MD Department of Pediatrics Case Western Reserve University School of Medicine Division of Pediatric Cardiology Rainbow Babies and Children’s Hospital Cleveland, Ohio Cardiac Embryology Sherin U. Devaskar, MD Distinguished Professor of Pediatrics Pediatrics, Neonatology and Developmental Biology David Geffen School of Medicine at UCLA Los Angeles, California Intrauterine Growth Restriction Developmental Origins of Adult Health and Disease Disorders of Carbohydrate Metabolism in the Neonate

Juliann M. Di Fiore, BSEE Research Engineer III Department of Pediatrics Case Western Reserve University Cleveland, Ohio Biomedical Engineering Aspects of Neonatal Cardiorespiratory Monitoring Assessment of Neonatal Pulmonary Function Michael Dingeldein, MD, FACS Assistant Professor of Surgery Division of General and Thoracic Pediatric Surgery Rainbow Babies and Children’s Hospital Case Western Reserve University Cleveland, Ohio Development of the Neonatal Gastrointestinal Tract Selected Gastrointestinal Anomalies in the Neonate Nancy C. Dobrolet, MD Director, Cardiac Stepdown Unit Cardiology Rainbow Babies and Children’s Hospital Cleveland, Ohio Congenital Defects of the Cardiovascular System Steven M. Donn, MD Professor of Pediatrics Division of Neonatal-Perinatal Medicine C.S. Mott Children’s Hospital Michigan Medicine, University of Michigan Ann Arbor, Michigan Assisted Ventilation of the Neonate and Its Complications Josephine M. Enciso, MD Associate Clinical Professor Pediatrics, Division of Neonatology and Developmental Biology David Geffen School of Medicine at UCLA Los Angeles, California Developmental Origins of Adult Health and Disease Frank Esper Staff Center for Pediatric Infectious Diseases Cleveland Clinic Children’s Hospital; Assistant Professor Department of Pediatrics Cleveland Clinic Lerner College of Medicine of Case Western Reserve University Cleveland, Ohio Postnatal Bacterial Infections

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Alison J. Falck, MD Pediatrics, Division of Neonatology University of Maryland School of Medicine Baltimore, Maryland Adverse Exposures to the Fetus and Neonate Mobolaji Famuyide, MD, MA Associate Professor Pediatrics/Newborn Medicine University of Mississippi Medical Center Jackson, Mississippi Social and Economic Contributors to Neonatal Outcome in the United States Jonathan M. Fanaroff, MD, JD Professor of Pediatrics Case Western Reserve University School of Medicine; Director, Rainbow Center for Pediatric Ethics Rainbow Babies & Children’s Hospital Cleveland, Ohio Medical Ethics in Neonatal Care Legal Issues in Neonatal-Perinatal Medicine Stephanie M. Ford, MD Department of Pediatrics Case Western Reserve University School of Medicine Divisions of Neonatology and Pediatric Cardiology Rainbow Babies and Children’s Hospital Cleveland, Ohio Cardiac Embryology Susan Hatters Friedman, MD The Phillip Resnick Professor of Psychiatry; Associate Professor of Pediatrics Case Western Reserve University School of Medicine Cleveland, Ohio; Associate Professor of Psychological Medicine University of Auckland Auckland, New Zealand Support for the Family Mark E. Galantowicz, MD Chief, Department of Cardiothoracic Surgery Co-Director, The Heart Center Nationwide Children’s Hospital Columbus, Ohio Neonatal Management of Congenital Heart Disease Meena Garg, MD Professor of Pediatrics Pediatrics, Neonatology and Developmental Biology David Geffen School of Medicine at UCLA Los Angeles, California Disorders of Carbohydrate Metabolism in the Neonate

Ciprian P. Gheorghe, MD, PhD Assistant Professor of Gynecology and Obstetrics and Basic Sciences Lawrence D. Longo MD Center for Perinatal Biology Loma Linda University School of Medicine Loma Linda, California Genetic Aspects of Perinatal Disease and Prenatal Diagnosis Allison Gilmore, MD Associate Professor Department of Pediatric Orthopaedic Surgery Rainbow Babies and Children’s Hospital Cleveland, Ohio Bone and Joint Infections in Neonates Jay P. Goldsmith, MD Clinical Professor Pediatrics Tulane University, New Orleans, Louisiana Overview and Initial Management of Delivery Room Resuscitation Blanca E. Gonzalez, MD Assistant Professor Pediatrics Infectious Diseases The Children’s Hospital Cleveland Clinic Foundation Cleveland, Ohio Viral Infections in the Neonate Jeffrey B. Gould, MD, MPH Robert L. Hess Professor of Pediatrics Stanford University School of Medicine and Lucile Packard Children’s Hospital Palo Alto, California Evaluating and Improving the Quality and Safety of Neonatal Intensive Care Pierre Gressens, MD, PhD Inserm-Paris Diderot University Paris, France Normal and Abnormal Brain Development White Matter Damage and Encephalopathy of Prematurity Floris Groenendaal, MD, PhD Doctor Department of Neonatology Wilhelmina Children’s Hospital University Medical Center Utrecht Utrecht University Utrecht, Netherlands Hypoxic–Ischemic Encephalopathy

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Contributors

Susan J. Gross, MD Professor Obstetrics & Gynecology and Women’s Health Albert Einstein College of Medicine Bronx, New York Genetic Aspects of Perinatal Disease and Prenatal Diagnosis Bhaskar Gurram, MBBS, MD Assistant Professor Department of Pediatrics Pediatric Gastroenterology, Hepatology, and Nutrition University of Texas Southwestern Medical Center Dallas, Texas Disorders of Digestion in the Neonate Iris Gutmark-Little, MD Associate Professor Pediatric Endocrinology Cincinnati Children’s Hospital Medical Center Cincinnati, Ohio Thyroid Disorders in the Neonate David N. Hackney Associate Professor Obstetrics and Gynecology University Hospitals Cleveland Medical Center Cleveland, Ohio Estimation of Fetal Well-Being Louis P. Halamek, MD, FAAP Professor, Division of Neonatal and Developmental Medicine Department of Pediatrics Stanford University Stanford, California Simulation and Debriefing in Neonatal-Perinatal Medicine Aaron Hamvas, MD Professor of Pediatrics Pediatrics/Neonatology Ann & Robert H. Lurie Children’s Hospital Northwestern University Feinberg School of Medicine Chicago, Illinois Respiratory Distress Syndrome in the Neonate Anne Hansen, MD, MPH Associate Professor of Pediatrics Medicine Harvard Medical School Boston, Massachusetts Physical Examination of the Newborn

Yenon Hazan, MD Head of Ultrasound Unit Obstetrics and Gynecology Ultrasound Unit Kaplan Medical Center Rehovot, Israel Pregnancy Complicated by Diabetes Mellitus Ann Hellström, MD, PhD Professor Pediatric Ophthalmology Neuroscience and Physiology Goteborg, Sweden Retinopathy of Prematurity Calanit Hershkovich-Shporen, MD Department of Neonatology Kaplan Medical Center Rehovot, Israel Fetal Effects of Autoimmune Disease Anna Maria Hibbs, MD, MSCE Associate Professor of Pediatrics Case Western Reserve University Vice Chair for Research; Eliza Henry Barnes Chair in Neonatology University Hospitals Rainbow Babies and Children’s Hospital Cleveland, Ohio Gastrointestinal Reflux and Motility in the Neonate Byron Hills, MD Resident Physician Neurosurgery University Hospitals Cleveland Medical Center Cleveland, Ohio Spinal Dysraphisms Susan R. Hintz, MD, MS Epi Professor of Pediatrics Division of Neonatal and Developmental Medicine Stanford University School of Medicine Palo Alto, California The Role of Neonatal Neuroimaging in Predicting Neurodevelopmental Outcomes of Preterm Neonates Shinjiro Hirose, MD Chief, Division of Pediatric General, Thoracic and Fetal Surgery, UC Davis Director, Pediatric Surgery, Shriners Hospitals for Children–Northern California Director, UC Davis Fetal Care and Treatment Center University of California–Davis Sacramento, California Surgical Treatment of the Fetus

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Contributors

Jeffrey D. Horbar, AB, MD Jerold F. Lucey Professor of Neonatal Medicine Pediatrics University of Vermont Burlington, Vermont Evaluating and Improving the Quality and Safety of Neonatal Intensive Care

Deepak Jain, MD Assistant Professor of Pediatrics Pediatrics/Division of Neonatology University of Miami Miller School of Medicine/Jackson Memorial Hospital Miami, Florida Bronchopulmonary Dysplasia in the Neonate

McCallum R. Hoyt, MD, MBA Director of Obstetric Anesthesiology Anesthesiology Institute Cleveland Clinic Foundation Cleveland, Ohio Anesthesia for Labor and Delivery

Lucky Jain, MD, MBA George W. Brumley Jr. Professor Chair, Department of Pediatrics Emory University; Chief Academic Officer Children’s Healthcare of Atlanta Atlanta, Georgia The Late Preterm Infant

Mark L. Hudak, MD Professor and Chairman Pediatrics University of Florida College of Medicine–Jacksonville Jacksonville, Florida Infants of Substance-Using Mothers Petra S. Hüppi, MD Professor Pediatrics University Children’s Hospital Geneva, Switzerland Normal and Abnormal Brain Development White Matter Damage and Encephalopathy of Prematurity

Arun Jeyabalan, MD, MS Associate Professor Obstetrics, Gynecology, and Reproductive Sciences University of Pittsburgh School of Medicine Pittsburgh, Pennsylvania Hypertensive Disorders of Pregnancy Alan H. Jobe, MD Professor of Pediatrics Pulmonary Biology, Neonatology Cincinnati Children’s Hospital Medical Center Cincinnati, Ohio Lung Development and Maturation

Terrie E. Inder, MBChB, MD Professor Pediatric Newborn Medicine Brigham and Women’s Hospital Boston, Massachusetts Seizures in Neonates

Nancy E. Judge, MD Associate Professor Obstetrics & Gynecology and Women’s Health Albert Einstein College of Medicine of Yeshiva University Bronx, New York Perinatal Ultrasound

Corey W. Iqbal, MD Director, Pediatric Surgery and Fetal Surgery Overland Park Regional Medical Center Overland Park, Kansas Surgical Treatment of the Fetus

Suhas G. Kallapur, MD Professor of Pediatrics Division of Neonatology David Geffen School of Medicine Los Angeles, California Lung Development and Maturation

Cyril Jacquot, MD, PhD Associate Medical Director, Blood Donor Center and Therapeutic Apheresis Department of Laboratory Medicine Children’s National Health System Assistant Professor of Pediatrics and Pathology George Washington University School of Medicine and Health Sciences Washington, DC Blood Component Therapy for the Neonate

Vishal Kapadia, MD, MSCS Assistant Professor of Pediatrics Division of Neonatal-Perinatal Medicine University of Texas Southwestern Medical Center Dallas, Texas Chest Compression, Medications, and Special Problems in Neonatal Resuscitation

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Contributors

Michael Kaplan, MB, ChB Emeritus Director Department of Neonatology Shaar Zedek Medical Center Faculty of Medicine of the Hebrew University Jerusalem, Israel Neonatal Jaundice and Liver Diseases David A. Kaufman, MD Professor Pediatrics University of Virginia School of Medicine Charlottesville, Virginia Fungal and Protozoal Infections of the Neonate Laura L. Konczal, BS, MS Assistant Professor of Genetics and Genome Sciences, and Pediatrics Case Western Reserve University Attending Physician Center for Human Genetics University Hospitals Cleveland Medical Center Cleveland, Ohio Inborn Errors of Metabolism Oleksandr Kudin, MD Richmond Commonwealth Neonatology Richmond, Virginia Neonatal Necrotizing Enterocolitis Megan Lagoski, MD Assistant Professor of Pediatrics Pediatrics/Neonatology Ann & Robert H. Lurie Children’s Hospital Northwestern University Feinberg School of Medicine Chicago, Illinois Respiratory Distress Syndrome in the Neonate Catherine Larson-Nath, MD Assistant Professor Pediatric Gastroenterology, Hepatology, and Nutrition University of Minnesota Minneapolis, Minnesota Disorders of Digestion in the Neonate Naomi T. Laventhal, MD, MA Associate Professor Department of Pediatrics and Communicable Diseases, Division of Neonatal-Perinatal Medicine University of Michigan Ann Arbor, Michigan Medical Ethics in Neonatal Care

Noam Lazebnik, MD Professor of OBGYN & Radiology, Associate Professor of Genetics Case Western Reserve University School of Medicine, Cleveland, Ohio Perinatal Ultrasound Hanmin Lee, MD Surgeon-In-Chief, UCSF Benioff Children’s Hospital Director, UCSF Fetal Treatment Center Division of Pediatric Surgery Department of Surgery University of California–San Francisco San Francisco, California Surgical Treatment of the Fetus Henry C. Lee, MD Associate Professor of Pediatrics Stanford University School of Medicine and Lucile Packard Children’s Hospital Palo Alto, California Evaluating and Improving the Quality and Safety of Neonatal Intensive Care Liisa Lehtonen, MD Professor in Pediatrics Pediatrics University of Turku Turku, Finland Optimization of the NICU Environment John Letterio, MD Professor of Pediatrics Pediatrics University Hospitals Rainbow Babies and Children’s Hospital Cleveland, Ohio Hematologic and Oncologic Problems in the Fetus and Neonate Tom Lissauer, MB, BChir, FRCPCH Hon Consultant Neonatologist Department of Paediatrics Imperial College Healthcare Trust London, United Kingdom Physical Examination of the Newborn Raymond W. Liu, MD Associate Professor, Pediatric Orthopaedics Victor M. Goldberg Endowed Chair in Orthopaedics Rainbow Babies and Children’s Hospital Cleveland, Ohio Musculoskeletal Disorders in Neonates

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Suzanne M. Lopez, MD Professor Pediatrics McGovern Medical School at The University of Texas Health Science Center at Houston Houston, Texas Practicing Evidence-Based Neonatal-Perinatal Medicine Naomi L. C. Luban, MD Vice Chair of Academic Affairs Medical Director of the Office for the Protection of Human Subjects Children’s National Health System Professor of Pediatrics and Pathology George Washington University School of Medicine and Health Sciences Washington, DC Blood Component Therapy for the Neonate Everett F. Magann, MD Maternal Fetal Medicine Division Director Obstetrics and Gynecology University of Arkansas for the Medical Sciences Little Rock, Arkansas Immune and Nonimmune Hydrops Fetalis Amniotic Fluid Volume Akhil Maheshwari, MD Josephine S. Sutland Professor of Newborn Medicine Director, Eudowood Division of Neonatology Vice-Chair (Integration), Department of Pediatrics Johns Hopkins University School of Medicine Baltimore, Maryland Developmental Immunology Henry H. Mangurten, MD Professor Pediatrics Rosalind Franklin University of Medicine and Science The Chicago Medical School North Chicago, Illinois Birth Injuries Paolo Manzoni, MD Professor of Pediatrics and Neonatology Degli Infermi Hospital Biella, Italy Fungal and Protozoal Infections of the Neonate Camilia R. Martin, MD, MS Associate Professor of Pediatrics Beth Israel Deaconess Medical Center Harvard Medical School Boston, Massachusetts Nutrient Requirements/Nutritional Support in Premature Neonate

Jacquelyn D. McClary, PharmD, BCPS Clinical Pharmacist Specialist Neonatal Intensive Care Unit Rainbow Babies and Children’s Hospital Cleveland, Ohio Principles of Drug Use in the Fetus and Neonate Principles of Drug Use During Lactation Therapeutic Agents Anna L. Mitchell, MD, PhD Associate Professor Genetics and Pediatrics Case Western Reserve University Cleveland, Ohio Congenital Anomalies Yunchuan Delores Mo, MD Associate Medical Director, Blood Bank and Therapeutic Apheresis Department of Laboratory Medicine Children’s National Health System Assistant Professor of Pediatrics and Pathology George Washington University School of Medicine and Health Sciences Washington, DC Blood Component Therapy for the Neonate Sandra Mooney, PhD Pediatrics, Division of Neonatology University of Maryland Baltimore, Maryland Adverse Exposures to the Fetus and Neonate Jarrett Moyer, MD, BA Resident Surgery University of California–San Francisco San Francisco, California Surgical Treatment of the Fetus Vivek Narendran, MD, MRCP (UK), MBA Professor of Pediatrics Perinatal Institute Cincinnati Children’s Hospital and Medical Center Cincinnati, Ohio The Skin of the Neonate Josef Neu, MD Professor Pediatrics University of Florida Gainesville, Florida Neonatal Necrotizing Enterocolitis

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Contributors

Mary L. Nock, MD Professor Department of Pediatrics Division of Neonatology Case Western Reserve University School of Medicine Rainbow Babies and Children’s Hospital Cleveland, Ohio Tables of Normal Values Shelley Ohliger, MD Assistant Professor Department of Anesthesiology Rainbow Babies and Children’s Hospital Cleveland, Ohio Anesthesia in the Neonate Arielle L. Olicker, MD Assistant Professor Department of Pediatrics Division of Neonatal-Perinatal Medicine Rainbow Babies and Children’s Hospital Cleveland, Ohio Tables of Normal Values Faruk H. Örge, MD, FAAO, FAAP William R. and Margaret E. Althans Professor and Director Center for Pediatric Ophthalmology and Adult Strabismus Department of Ophthalmology and Visual Sciences Cleveland, Ohio Examination and Common Problems in the Neonatal Eye Todd D. Otteson, MD, MPH Chief Division of Pediatric Otolaryngology University Hospitals/Rainbow Babies and Children’s Hospital Cleveland, Ohio Upper Airway Lesions in the Neonate Louise Owen, MBChB, MRCPCH, FRACP, MD Neonatologist Newborn Research Royal Women’s Hospital Melbourne, Victoria, Australia Role of Positive Pressure Ventilation in Neonatal Resuscitation Nehal A. Parikh, DO, MS Professor of Pediatrics Perinatal Institute/Pediatrics Cincinnati Children’s Hospital Medical Center Cincinnati, Ohio The Role of Neonatal Neuroimaging in Predicting Neurodevelopmental Outcomes of Preterm Neonates

Kimberly V. Parsons, MD Assistant Professor, Pediatrics Division of Neonatology Emory University and Children’s Healthcare of Atlanta Atlanta, Georgia The Late Preterm Infant Sandrine Passemard, MD Associate Professor Inserm-Paris Diderot University Paris, France Normal and Abnormal Brain Development Irina Pateva, MD Assistant Professor Pediatrics Case Western Reserve University Cleveland, Ohio Hematologic and Oncologic Problems in the Fetus and Neonate Mary Elaine Patrinos, MD Assistant Professor Pediatrics Case Western Reserve University School of Medicine Cleveland, Ohio Neonatal Apnea and the Foundation of Respiratory Control Allison H. Payne, MD, MS Assistant Professor Pediatrics/Neonatology Rainbow Babies and Children’s Hospital Case Western Reserve University Cleveland, Ohio Early Childhood Neurodevelopmental Outcomes of High-Risk Neonates Sharon Perlman, MD Prenatal Diagnostic Unit Department of Obstetrics and Gynecology Sheba Medical Center Ramat Gan, Israel; Sackler School of Medicine Tel Aviv University Tel Aviv, Israel Pregnancy Complicated by Diabetes Mellitus Agne Petrosiute, MD Assistant Professor Pediatrics Case Western Reserve University Cleveland, Ohio Hematologic and Oncologic Problems in the Fetus and Neonate

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Contributors

Christina M. Phelps, MD Assistant Professor Pediatric Cardiology Nationwide Children’s Hospital Columbus, Ohio Cardiovascular Problems of the Neonate Sarah Plummer, BA, MD Assistant Professor of Pediatrics Pediatrics Rainbow Babies and Children’s Hospital Cleveland, Ohio Prenatal Diagnosis of Congenital Heart Disease Brenda B. Poindexter, MD, MS Professor of Pediatrics Cincinnati Children’s Hospital, Perinatal Institute University of Cincinnati College of Medicine Cincinnati, Ohio Nutrient Requirements/Nutritional Support in Premature Neonate Richard Polin, BA, MD Director, Division of Neonatology Pediatrics Morgan Stanley Children’s Hospital New York, New York Perinatal Infections and Chorioamnionitis Preetha A. Prazad, MD Attending Neonatologist Advocate Children’s Hospital–Park Ridge Park Ridge, Illinois Birth Injuries Jochen Profit, MD, MPH Associate Professor of Pediatrics Division of Neonatology, Department of Pediatrics Stanford University School of Medicine and Lucile Packard Children’s Hospital, Palo Alto, California Evaluating and Improving the Quality and Safety of Neonatal Intensive Care Bhagya I. Puppala Assistant Professor of Pediatrics The Chicago Medical School Rosalind Franklin University of Medicine and Science Chicago, Illinois Birth Injuries Miriam N. Rajpal, MD Neonatologist Pediatrics Advocate Children’s Hospital, Park Ridge, Illinois Birth Injuries

Tonse N. K. Raju, MD, DCH, FAAP Chief Pregnancy and Perinatology Branch NICHD-National Institutes of Health Bethesda, MD Currently: Adjunct Professor of Pediatrics F. Edwards Hebert School of Medicine Uniformed Services School of Medicine Bethesda, Maryland Growth of Neonatal Perinatal Medicine—A Historical Perspective Tara M. Randis, MD, MS Assistant Professor Department of Pediatrics and Microbiology NYU School of Medicine New York, New York Perinatal Infections and Chorioamnionitis Raymond W. Redline, MD Professor Pathology and Reproductive Biology Case Western Reserve University School of Medicine Cleveland, Ohio Placental Pathology Orna Flidel Rimon, MD Director of Neonatology Neonatology Kaplan Medical Center Rehovot, Israel Post-Term Pregnancy Antonio Saad, MD Assistant Professor, Maternal Fetal Medicine Department of Obstetrics and Gynecology The University of Texas Medical Branch Galveston, Texas Obstetric Management of Prematurity George Saade, MD Professor Obstetrics-Gynecology and Cell Biology The University of Texas Medical Branch Galveston, Texas Obstetric Management of Prematurity Renate D. Savich, MD Professor Chief, Division of Neonatology and Newborn Medicine Pediatrics University of Mississippi Medical Center Jackson, Mississippi Social and Economic Contributors to Neonatal Outcome in the United States

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Contributors

Eric S. Shinwell, MD Professor of Neonatology Neonatology Ziv Medical Center Tzfat, Israel Pregnancy Complicated by Diabetes Mellitus Obstetric Management of Multiple Gestation and Birth

Jochen P. Son-Hing, MD, FRCSC Assistant Professor of Orthopaedics and Pediatrics Case Western Reserve University Rainbow Babies and Children’s Hospital Cleveland, Ohio Congenital Abnormalities of the Upper and Lower Extremities and Spine

Jill Shivapour, MD Assistant Professor of Pediatrics Department of Pediatrics, Division of Pediatric Cardiology Rainbow Babies and Children’s Hospital Cleveland, Ohio Cardiovascular Problems of the Neonate

Julia Catherine Sorbara, MD, FRCPC Pediatric Endocrinology Fellow Division of Endocrinology Department of Pediatrics The Hospital for Sick Children Toronto, Ontario, Canada Disorders of Sex Development

Eric Sibley, MD, PhD Associate Professor of Pediatrics (Gastroenterology) Assistant Dean for Academic Advising Stanford University School of Medicine Stanford, California Neonatal Jaundice and Liver Diseases

Tamar Springel, MD, MSHP Assistant Professor Pediatrics Virginia Commonwealth University Health System Richmond, Virginia The Kidney and Urinary Tract of the Neonate

Pamela M. Simmons, DO, MPH, BS Maternal Fetal Medicine Fellow Obstetrics and Gynecology University of Arkansas for Medical Sciences Little Rock, Arkansas Immune and Nonimmune Hydrops Fetalis Amniotic Fluid Volume

Robin H. Steinhorn, MD Senior Vice President Children’s National Health System; Professor of Pediatrics George Washington University Washington, DC Pulmonary Vascular Development

Lois E. H. Smith, MD, PhD Professor of Ophthalmology Department of Ophthalmology Harvard Medical School, Boston Children’s Hospital Boston, Massachusetts Retinopathy of Prematurity

David K. Stevenson, MD Harold K. Faber Professor of Pediatrics Division of Neonatal and Developmental Medicine Stanford University Stanford, California Neonatal Jaundice and Liver Diseases

Mickey Smith, MD, MBS Resident Physician Neurological Surgery University Hospitals Cleveland Medical Center Cleveland, Ohio Intracranial and Calvarial Disorders

Corey Stiver, MD Pediatric Cardiologist Cardiology Nationwide Children’s Hospital Columbus, Ohio Prenatal Diagnosis of Congenital Heart Disease

Christopher S. Snyder, MD, FAAP Key Bank-Meyer Family Chair of Pediatric Cardiology Pediatrics Case Western Reserve University Cleveland, Ohio Disorders of Cardiac Rhythm and Conduction in Newborns

Eileen K. Stork, MD Associate Professor Pediatrics Rainbow Babies and Children’s Hospital Cleveland, Ohio Therapy for Cardiorespiratory Failure in the Neonate

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Contributors

John E. Stork, MD Associate Professor Anesthesiology Rainbow Babies and Children’s Hospital Cleveland, Ohio Anesthesia in the Neonate

Andrea N. Trembath, MD, MPH Associate Professor of Pediatrics Division of Neonatal-Perinatal Medicine The University of North Carolina at Chapel Hill Chapel Hill, North Carolina Epidemiology for Neonatologists

James Strainic, MD Assistant Professor of Pediatrics Pediatrics Rainbow Babies and Children’s Hospital Cleveland, Ohio Prenatal Diagnosis of Congenital Heart Disease

Robert Turbow, MD, JD Neonatologist and Chief Patient Safety Officer Dignity Health of the Central Coast Marian Regional Medical Center Santa Maria, California Legal Issues in Neonatal-Perinatal Medicine

Ye Sun, MD, PhD Instructor of Ophthalmology Department of Ophthalmology Harvard Medical School, Boston Children’s Hospital Boston, Massachusetts Retinopathy of Prematurity

Jon E. Tyson, MD, MPH Professor Pediatrics UTHSC at Houston Medical School Houston, Texas Practicing Evidence-Based Neonatal-Perinatal Medicine

George H. Thompson, MD Professor and Chief, Pediatric Orthopaedics Rainbow Babies and Children’s Hospital Cleveland, Ohio Musculoskeletal Disorders in Neonates Bone and Joint Infections in Neonates Congenital Abnormalities of the Upper and Lower Extremities and Spine

Maximo Vento, MD, PhD Professor Division of Neonatology University & Polytechnic Hospital La Fe Valencia, Spain Oxygen Therapy in Neonatal Resuscitation

Frances Thomson-Salo, PhD Honorary Principal Fellow Department of Psychiatry University of Melbourne Melbourne, Australia Support for the Family Dov Tiosano, MD Professor Pediatric Endocrinology Rambam Medical Center Haifa, Israel Disorders of Calcium, Phosphorus, and Magnesium Metabolism in the Neonate Krystal Tomei, MD, MPH Assistant Professor Neurological Surgery Rainbow Babies and Children’s Hospital Cleveland, Ohio Intracranial and Calvarial Disorders Spinal Dysraphisms

Beth A. Vogt, MD Associate Professor of Pediatrics The Ohio State University College of Medicine Nationwide Children’s Hospital Columbus, Ohio The Kidney and Urinary Tract of the Neonate Betty Vohr, MD Director of Neonatal Follow-up Neonatology Women and Infants Hospital Providence, Rhode Island Hearing Loss in the Newborn Infant Kelly C. Wade, MD, PhD, MSCE Assistant Professor Clinical Pediatrics University of Pennsylvania Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Pharmacokinetics in Neonatal Medicine

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Contributors

Jennifer A. Wambach, MD, MS Assistant Professor Pediatrics/Newborn Medicine St. Louis Children’s Hospital Washington University School of Medicine St. Louis, Missouri Respiratory Distress Syndrome in the Neonate

Deanne E. Wilson-Costello, MD Professor Pediatrics Rainbow Babies and Children’s Hospital Cleveland, Ohio Early Childhood Neurodevelopmental Outcomes of High-Risk Neonates

Tammy Wang, MD Ear, Nose, and Throat Institute University Hospitals Cleveland Medical Center/Rainbow Babies and Children’s Hospital Cleveland, Ohio Upper Airway Lesions in the Neonate

Ronald J. Wong, MD Senior Research Scientist Pediatrics Stanford University School of Medicine Stanford, California Neonatal Jaundice and Liver Diseases

Michiko Watanabe, PhD Professor Pediatrics Case Western Reserve University School of Medicine Cleveland, Ohio Cardiac Embryology

Myra Wyckoff, MD Professor of Pediatrics Pediatrics, Division of Neonatal-Perinatal Medicine UT Southwestern Medical Center Dallas, Texas Chest Compression, Medications, and Special Problems in Neonatal Resuscitation

Diane Katherine Wherrett, MD, FRCPC Professor Division of Endocrinology Department of Pediatrics Hospital for Sick Children Toronto, Ontario, Canada Disorders of Sex Development Robert White, MD Director, Regional Newborn Program Newborn ICU Beacon Children’s Hospital South Bend, Indiana Optimization of the NICU Environment

Arthur B. Zinn, MD, PhD Associate Professor of Genetics and Genome Sciences, and Pediatrics Case Western Reserve University Attending Physician Center for Human Genetics University Hospitals Cleveland Medical Center Cleveland, Ohio Inborn Errors of Metabolism

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xix

Preface

T

ogether with my colleague Avroy A. Fanaroff (and more recently, Michele C. Walsh), we have been privileged to transform the third edition (1983) of this text into its 11th edition over a span of 35 years. This has been a great honor and an enormous learning experience. Over this time, although neonatal survival rates may give reason to rejoice, the persistent respiratory and neurodevelopmental problems observed in former preterm infants remain cause for concern. Fortunately, we have made great strides in our ability to control nosocomial infections in preterm infants, and both target and achieve the intrauterine rate of growth through improved nutritional support. Meanwhile, the complex, ever-expanding genetic disorders and birth defects now loom as major problems in the neonatal intensive care unit and as leading causes of neonatal mortality. The field of Neonatal-Perinatal Medicine has transitioned from anecdotal medicine to evidence-based medicine. The problem is that evidence-based medicine predicts outcomes for groups but not individuals. The next frontier, individualized or personalized medicine, requires application of the human genome project to the individual patient. That frontier may be rapidly approaching with the acquisition and application of new knowledge and technology. Over the last decades, translation of bench research to bedside innovation has proceeded remarkably as has understanding of the underlying mechanisms of many complex disorders. Advances in genetics have provided insight into the etiology of many disorders, and many previously mysterious diseases can now be attributed to single gene defects or

mitochondrial disorders accompanied by cellular energy failure. We have attempted to address and incorporate these advances into the body of the text. For this 11th edition, we have added several new sections and multiple new authors, notably expanding our international contributors, hence providing a truly global perspective. Many sections have been completely reorganized, and a large number of chapters have been rewritten or updated. We remain exceedingly grateful to our accomplished authors who have responded enthusiastically and maintained our need for a rapid timeline in this electronic era. As with prior editions, the 11th edition is available both in print and as an e-book on the Expert Consult platform, in a fully searchable and portable format. This book would not exist without the remarkable clinical and intellectual environment that constitutes Rainbow Babies & Children’s Hospital in Cleveland. On a daily basis, we gain knowledge from our faculty colleagues and fellows, and wisdom from our nursing staff who are so committed to their young patients. Once again, we have been blessed with an in-house editor, Bonnie Siner, to whom we cannot adequately express our thanks. She is the glue behind the binding in the book, and she has worked tirelessly with Elsevier staff members to bring this project to fruition. Elsevier has, once again, provided the resources to accomplish this mammoth task. Richard J. Martin Avroy A. Fanaroff Michele C. Walsh

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1 

Growth of Neonatal Perinatal Medicine—A Historical Perspective TONSE N. K. RAJU

We trust we have been forgiven for coining the words, “neonatology” and “neonatologist.” We do not recall ever having seen them in print. The one designates the art and science of diagnosis and treatment of disorders of the newborn infant, the other the physician whose primary concern lies in the specialty. … We are not advocating now that a new subspecialty be lopped from pediatrics … yet such a subdivision … [has] as much merit as does pediatric hematology.

—A. J. Schaffer, 196075

T

he terms neonatology and neonatologist were not in general use until the mid-1960s. In the preface to the first edition of his monograph Diseases of the Newborn, Dr. Alexander Schaffer christened the new specialty and its practitioners, asking our “forgiveness” for doing so.75 An apology was not needed, because time has proven him to be immensely prophetic. In 1975, the first neonatal-perinatal medicine subspecialty examination was offered by the American Board of Pediatrics, and 355 were certified as the country’s first neonatologists. After the 2012 certifying examination, 5552 individuals have been certified by the Board as neonatologists, and several hundred more since then. This phenomenal growth has been matched by an increasing fund of knowledge. Today a cursory search using the subject heading “newborn” in the National Library of Medicine’s PubMed database yields nearly 60,000 citations.59 Thus at the beginning of the twenty-first century, neonatology stands tall and strong as a specialty, carving a unique niche, bridging obstetrics with pediatrics and intensive care with primary care. Although the formal naming of our specialty appears to be recent, its roots extend into the nineteenth century, when systematic and organized care for premature infants began in earnest. This chapter traces the origins and growth of modern perinatal and neonatal medicine, with a brief perspective on its promises and failures. The reader may consult scholarly monographs and review articles on specific topics for in-depth analyses.6,7,24,31,79,80

Perinatal Pioneers Many scientists played strategic roles in developing the basic concepts in neonatal-perinatal medicine that helped to formalize the scientific basis for neonatal clinical care. Their work and teachings inspired generations of further researchers advancing the field. For brevity’s sake, only a few are shown in Fig. 1.1. Medicinal chemistry (later called biochemistry) and classic physiology gained popularity and acceptance toward the end of the nineteenth century, inaugurating studies on biochemical and physiologic problems in the fetus and newborn. Some leading scientists in the early twentieth century, making fundamental contributions and training scores of scientists from around world, included Barcroft8,34 and his mentee Dawes in England (gas exchange and nutritional transfer across the placenta and oxygen carrying in fetal and adult hemoglobin); Ylppö in Finland (neonatal nutrition, jaundice, and thermoregulation); Lind in Sweden (circulatory physiology); Smith in Boston81(fetal and neonatal respiratory physiology); DeLee in Chicago26,27 (leading researcher on incubators and in high-risk obstetric topics, he also founded the first US “incubator station” at the Chicago Lying-in Hospital); Day in New York (temperature regulation, retinopathy of prematurity, and jaundice); and Gordon38 in Denver (nutrition). Although no formal curriculum existed, all these centers offered rigorous training in perinatal physiology and clinical medicine. Smith once said, “If you were interested in babies and liked Boston, I was the only wheel in town!”60 Table 1.1 highlights some milestones in perinatal medicine.

The High-Risk Fetus and Perinatal Obstetrics Because so many deaths occurred in early infancy in times past, many cultures adopted remarkably innovative methods to deal with such tragedies. According to a Jewish tradition, full, year-long mourning is not required for infants who die

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CHAPTER 1  Growth of Neonatal Perinatal Medicine—A Historical Perspective

Abstract

Keywords

Emerging from centuries of humble origins, the field of maternal and newborn care has matured into a robust medical specialty. This growth, however, has not been smooth. Along with spectacular advances in physiology, clinical sciences, and technological innovations over the decades, humbling setbacks have led to course corrections in our collective historic march. This chapter attempts to provide a historical perspective, highlighting important milestones, on the growth of neonatal perinatal medicine.

Apgar oxygen therapy cesarean birth retinopathy of prematurity premature baby side shows assisted ventilation neonatal resuscitation

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2.e1

CHAPTER 1  Growth of Neonatal Perinatal Medicine—A Historical Perspective

E

C

B

A

F

G

3

D

H

• Fig. 1.1  Pioneers in perinatal and neonatal physiology and medicine. A, Joseph Barcroft. B, Arvo Ylppö. C, John Lind. D, William Liley. E, Joseph DeLee. F, Richard Day. G, Clement Smith. H, Harry Gordon. (A, From Barcroft J. Research on Pre-natal Life. Vol 1. Oxford: Blackwell Scientific; 1977, courtesy of Blackwell Scientific; B-D and F-H, from Smith GF, Vidyasagar D, eds. Historical Review and Recent Advances in Neonatal and Perinatal Medicine: Neonatal Medicine. Vol 1. Evansville, IN: Ross Publication; 1984, pp ix [B], xix [C], xxii [D], xvi [F], xii [G], xiv [H], courtesy of Mead Johnson Nutritional; E, Courtesy of Mrs. Nancy DeLee Frank, Chicago.)

before 30 days of age.40 In some Asian ethnic groups, infantnaming ceremonies are held only after several months, until which time the infant is simply called “it.” In India, an odd or coarse-sounding name is given to the first surviving infant after the death of a previous sibling; this is aimed at deflecting evil spirits. In her book on the history of the Middle Ages, Tuchman notes that infants were seldom depicted in medieval artworks.89 When they were drawn (e.g., the infant Jesus), women in the pictures looked away from the infant, ostensibly conveying respect but perhaps because of fearful aloofness. Since antiquity, the care of pregnant women has been the purview of midwives, grandmothers, and experienced female elders in the community. Wet nurses helped when mothers were unavailable or unwilling to nurse their infants. Little or no assistance was needed for normal or uncomplicated labor and delivery. For complicated deliveries, male physicians had to be summoned, but they could do little because many of them lacked expertise or interest in treating women. Disasters during labor and delivery were common, rendering this phase in their lives the most dreaded for women.43 In the early 1900s unexpected intrapartum complications accounted for 50% to 70% of all maternal deaths in England and Wales.17,56 Because the immediate concern during most high-risk deliveries was to save the mother, sick

newborns were not given substantial attention; their death rates remained very high. Occasionally, happy outcomes of high-risk deliveries did occur. In one of the oldest works of art depicting labor and delivery (Fig. 1.2A), a bearded man and his assistant are standing behind a woman in labor, holding devices remarkably similar to the modern obstetric forceps. The midwife has delivered an evidently live infant. In Fig. 1.2B, three infants from a set of quadruplets, nicely swaddled, have been placed on the mother, as the unwrapped fourth infant is being handed to her for nursing. A divine figure in the background is blessing the newcomers. Cesarean sections were seldom performed on living women before the thirteenth century. Even subsequently, the procedure was performed only as a final act of desperation. Contrary to popular belief, Julius Caesar’s birth was not likely by cesarean section. Because Caesar’s mother was alive during his reign, historians believe that she probably delivered him vaginally. The term cesarean probably originated from lex caesarea, in turn from lex regia, the “royal law” prohibiting burial of corpses of pregnant women without removal of their fetuses.11,94 The procedure allowed for baptism (or a similar blessing) if the child was alive or burial otherwise. Infants surviving the ordeal of cesarean birth were assumed to possess special powers, as supposedly

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4 pa rt 1 The Field of Neonatal-Perinatal Medicine 4

TABLE Selected Milestones in Perinatal Medicine 1.1 

Category

Year(s)

Description

Antenatal aspects

1752 1915-1924 1923-1925 1928

Queen Charlotte’s Hospital, the world’s first maternity hospital, is founded in London.57 Campbell introduces outlines of regular prenatal visits, which become a standard. Estrogen and progesterone are discovered. First pregnancy test is described, in which women’s urine is shown to cause changes in mouse ovaries.

Fetal assessment

1543 1634 1819, 1821

Vesalius observes fetal breathing movements in pigs. Paré teaches that absence of movement suggests a dead fetus. Laënnec introduces the stethoscope in 1819, and his friend Kergaradec shows that fetal heart sounds can be heard using it. Forceps are recommended when there is “weakening of the fetal heart rate.” Einthoven publishes his work on the ECG. The first recording of fetal heart ECG is made. The term fetal distress is introduced. There are developments in the external tocodynamometer. Apgar describes her scoring system.3 Systematic studies are conducted on fetal heart rate monitoring. Dawes reports studies on breathing movement in fetal lambs. Fetal Doppler studies begin. Nelson and Ellenberg report that Apgar scores are poor predictors of neurologic outcome.

1866 1903 1906 1908 1948-1953 1953 1957-1963 1970 1980 1981 Labor and delivery

ca. 1000–500

Fetal physiology

1900-1950

BC

98-138 1500s 1610 1700s 1921 1953

In Ayurveda, the ancient Hindu medical system, physicians describe obstetric instruments. Soranus develops the birthing stool and other instruments. There are isolated reports of cesarean sections on living women. The first intentional cesarean section is documented. The Chamberlen forceps are kept as a family secret for three generations. Lower uterine segment cesarean section is reported. The modern vacuum extractor is introduced. Barcroft, Dawes, Lind, Liley, and others study physiologic principles of placental gas exchange and fetal circulation.

ECG, Electrocardiogram. See references 41, 43, 60-62, 70-72, 82, 83.

did Shakespeare’s Macduff—“not of a woman born,” but of a corpse, and able to slay Macbeth.54 Soranus of Ephesus (circa 38-138 AD) influenced obstetric practice for 1400 years. His Gynecology can be regarded as the first formal “textbook” of perinatal medicine. Initially extant, it was rediscovered in 1870 and translated into English for the first time in 1956.88 Soranus wrote superbly about podalic version, obstructed labor, multiple gestations, fetal malformations, and numerous other maternal and fetal disorders. In an age of belief in magic and the occult, he insisted that midwives should be educated and free from superstitions. He forbade wet nurses from drinking alcohol lest it render the infant “excessively sleepy.” His chapter, “How to Recognize the Newborn That Is Worth Rearing,” remains one of the earliest accounts on assessing viability of sick newborns—a topic of great concern even today.

Midwives and Perinatal Care Although occasionally caricatured (Fig. 1.3), midwives were responsible for delivering obstetric care for thousands of

years. Men disliked obstetrics, and women were too shy to let male physicians handle them. Good midwives were always in great demand, and many of them held important social and political positions in European courts.43,61,91 The emergence of man-midwives (Fig. 1.4) in England had a major effect on high-risk obstetric practice. Chamberlen the Elder (1575-1628) is usually credited for inventing the modern obstetric forceps.43,61,63 For 150 years, through three generations of Chamberlens, the instrument remained a trade secret. By then, others had developed similar devices, and patients began associating good obstetric outcomes with male physicians—a strategic factor in transforming midwifery to a male-dominated craft.43 The shift from women-midwifery to men-midwifery might also have been caused by changing social values and gender relationships in which women voluntarily began making choices about their bodies.91 Today’s increasing roles for female midwives and the higher proportion of women choosing specific birth practices (e.g., home versus hospital delivery, “underwater births,” cesarean delivery on request) offer interesting contrasts and perspectives to eighteenth century obstetrics.

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CHAPTER 1  Growth of Neonatal Perinatal Medicine—A Historical Perspective

A

B • Fig. 1.2

  High-risk deliveries. A, Marble relief of uncertain date depicting a high-risk delivery. The physician and his assistant in the background are holding devices similar to modern obstetric forceps. A midwife has just helped deliver a live infant while two people are looking through the window. B, Delivery of quadruplets. (From Graham H. Eternal Eve: The History of Gynecology and Obstetrics. New York: Doubleday; 1951, pp 68, 172.)

• Fig. 1.3

  On call. “A Midwife Going to a Labour,” caricature by Thomas Rowlandson, 1811. (Courtesy of The British Museum, London.)

• Fig. 1.4

  Man-midwife. (Courtesy of Clements C. Fry Print Collections, Harvey Cushing/John Hay Whitney Medical Library, Yale University, New Haven, CT.)

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5

6 pa rt 1 The Field of Neonatal-Perinatal Medicine 6

Neonatal Resuscitation: Tales of Heroism and Desperation Popular artworks and ancient medical writings provide accounts of miraculous revivals of apparently dead adults and children.66 These are tales of successes only, for the failures were buried and rarely reported. Attempts to “stimulate” and revive apparently dead newborns included beating, shaking, yelling, fumigating, dipping in ice-cold water, and dilating and blowing smoke into the rectum and other techniques.25,30,66,93 Oxygen administration through an orogastric tube to revive asphyxiated infants persisted well into the mid-1950s, when James and Apgar showed conclusively that the therapy was useless.1,52

Apgar and the Language of Asphyxia Few scientists in the twentieth century influenced the practice of neonatal resuscitation as profoundly as Apgar (1909-1974). A surgeon, she chose obstetric anesthesia for her career. Her simple scoring system inaugurated the modern era of assessing infants at birth on the basis of simple clinical examination.3 Right or wrong, the Apgar score became the language of asphyxia. It is often said that the first words heard by a newborn infant are “What’s the Apgar score?” Although “giving an Apgar” has become a ritual, its profound effect has been on formalizing the process of observing, assessing, and communicating the infant status at birth in a consistent and uniform manner. This process eventually led to the formal steps of resuscitation at birth using the score. Few people know that it was also Apgar who was the first to catheterize the umbilical artery in a newborn.16 A woman of enormous energy, talent, and compassion, Apgar was honored with her depiction on a 1994 US postage stamp (Fig. 1.5).

Foundling Asylums and Infant Care In its early days, the Roman Empire experienced decreasing population growth. The emperors taxed bachelors and rewarded married couples to encourage procreation.82 In 315 ad, Emperor Constantine, hoping to curb infanticide and encourage the adoption of orphans, decreed that all “foundlings” would become slaves of those who adopted them. Similar humanitarian efforts by kings and the Council of the Roman Church led to the institutionalization of infant care by establishing foundling asylums for abandoned infants,82 also called “Hospitals for the Innocent”—the first children’s hospitals. Parents of unwanted infants “dropped off” their infants in a revolving receptacle at the door of such asylums, rang the doorbells, and disappeared into the night (Fig. 1.6). Sadly, such incidences occur even in modern times.73 Foundling asylums adopted pragmatic techniques for fundraising. In eighteenth century France, lotteries were held, and souvenirs were sold. In May 1749, Handel gave a concert to support London’s “Hospital for the Maintenance and Education of Exposed and Deserted Young Children.” The final item of the program was the playing of “The Foundling Hymn.”82

• Fig. 1.5  Virginia Apgar, US postage stamp. (Courtesy of the US Postal Service.)

Saving Infants to Man the Army During the French Revolution, France faced appalling rates of infant mortality. With rates greater than 50%, the Revolutionary Council in 1789 enacted a decree proclaiming that working-class parents “have a right to the nation’s succors at all times.”82 The post-revolutionary euphoria about equality and fraternity among men stimulated reforms, heralding an idealistic welfare state, leading to collecting and maintaining valid statistics about children. The world’s first national databases began in France in the late eighteenth century.82 Over the next century, France faced a population problem similar to that of ancient Rome—a negative population growth. The birth rate had declined, and infant mortality remained high. Fearing future shortages of troops, the military leaders, deeply engaged in battles with Prussia, were naturally alarmed. Commissions were set up to study the depopulation problem and develop remedial actions. A series of measures began to improve maternal and neonatal care.6,7,22,24,82,83 Young parents were encouraged to uphold their patriotism and bear more children to “man the future armies.” It is the irony of our times that such noble intentions as saving infants were motivated by brutal needs for enhancing military might.

An Ingenious Contrivance, the Couveuse, and Premature Baby Stations A popular story of the origin of modern incubator technology is that upon seeing the poultry section during a casual visit to the Paris Zoo in 1878, Tarnier (1828-1897), a

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CHAPTER 1  Growth of Neonatal Perinatal Medicine—A Historical Perspective

A

7

B • Fig. 1.6

  Foundling homes. A, Le Tour—revolving receptacle. Mother ringing a bell to notify those within that she is leaving her baby in the foundling home (watercolor by Herman Vogel, France, 1889). B, Remorce (“Remorse”)—parents after placing their infant in a foundling home (engraving and etching by Alberto Maso Gilli, France, 1875). (A and B, Courtesy of the Museum of the History of Medicine, Academy of Medicine, Toronto, Ontario, Canada; from Spaulding M, Welch P. Nurturing Yesterday’s Child: A Portrayal of the Drake Collection of Pediatric History. Philadelphia: Decker; 1991, p 110 [A] and p 119 [B].)

renowned obstetrician, conceived the idea of “incubators” similar to the “brooding hen” or couveuse.6,7,22,24 He asked an instrument maker, Martin, to construct similar equipment for infants. With a “thermo-syphon” method to heat the outside with an alcohol lamp, Martin devised a sufficiently ventilated, 1 m3 double-walled metal cage, spacious enough to hold two premature infants. The first couveuses were installed at the Paris Maternity Hospital in 1880. Tarnier’s efforts led to dramatic improvements in survival rates for preterm infants. Although a few others had developed incubators before Tarnier,7 it was he and his students, Budin (1846-1907) and Auvard (1855-1941), who are largely responsible for institutionalizing preterm infant care. They placed several incubators side by side, promoting the concept of caring for groups of sick preterm infants in geographically separate regions within their hospital.6,7,69,86 Budin and Auvard improved the original couveuse by replacing its walls with glass and using simpler methods for heating. Their efforts greatly influenced incubator technology during the first half of the twentieth century in Europe and the United States (Fig. 1.7 and Table 1.2). In 1884, Tarnier made another important contribution; he invented a small, flexible rubber tube for introduction through the mouth into the stomach of preterm infants. With this tube, he could drip milk directly into the stomach. This method of nutritional support he called “gavage feeding.” Gavage feeding plus keeping infants in relatively constant and warm temperatures had a dramatic impact on improving survival rates.15,21 Tarnier also recommended that

the legal definition of viability should be 180 days of gestation, which was opposed by contemporary obstetricians, who thought that the concept was “therapeutic nihilism.”7 Defining viability remains a highly emotional and contentious issue in contemporary neonatal-perinatal practice.

Incubators, Baby Shows, and Origins of Neonatal Intensive Care Units Almost two decades after its debut in France, incubator technology appeared in the United States, heralding organized newborn intensive care. As in France, it was an obstetrician who spearheaded the movement. In 1898, DeLee established the first “Premature Baby Incubator Station” at the Sara Morris Hospital in Chicago. During the early 1900s, as academic obstetricians and pediatricians were organizing specialized care for premature infants, an interesting, if bizarre, set of events led to the era of “premature baby shows,” which began in Europe and continued in the United States, lasting well into the 1940s.6,7,78 Couney, a Budin associate of doubtful medical credentials, wished to popularize the French technology abroad and show the value of “conserving” premature infants. (This account has been doubted.7) Couney obtained six incubators, probably from the French innovator Lion. Initially, Couney wanted to exhibit only the incubators as a technology of hope for saving infants. To add drama, however, he brought six preterm infants from Virchow’s maternity unit in Berlin and exhibited them inside the incubators at the

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8 pa rt 1 The Field of Neonatal-Perinatal Medicine 8

York City to organize annual incubator baby shows in Coney Island. The last infant show was held during the 1939 to 1940 season in Atlantic City.78 In 1914, Hess of Chicago started a Premature Infant Station at the Sarah Morris Children’s Hospital (of the Michael Reese Medical Center). With great attention to environmental control and aseptic practices and a regimental approach to feeding, Hess and his head nurse, Evelyn Lundeen (Fig. 1.8), achieved spectacular survival rates.47,68 Hess also developed an incubator built on the concept of a double-walled metallic “cage” with warm water circulating between the walls. He used electric current for heating and devised a system to administer free-flow oxygen (Fig. 1.9). Only a few Hess incubators are known to have survived to this day. Hess’s premature unit outlasted the DeLee Premature Station. In December 2008, the Michael Reese Medical Center closed, however, declaring bankruptcy. The story of development of incubators and their impact on pediatrics is a tale of the success of technology and that of the perils technology might beget (see later section on the relationship of improved incubator care and the retinopathy of prematurity [ROP] epidemic). In the heroic age of the mechanical revolution, the notion that machines could solve all human problems was all too appealing. The incubator stands as the most enduring symbol of the spectacular success of modern intensive care and (paradoxically) some of its failures.79,80

A

B

Sponge

Bed

Hot-Water Tank

C • Fig. 1.7 Early

Air Exit

Air Entrance Filling Funnel Bunsen Burner

Glass Cover

  incubators. A, Rotch incubator, circa 1893. B, Holt incubator. C, Schematics of the Holt incubator. (A, From Cone TE Jr. History of American Pediatrics. Boston: Little Brown; 1979, pp 57 and 58, courtesy of Little Brown; B and C, from Holt LE. The Diseases of Infants and Children. New York: Appleton; 1897, pp 12 and 13, courtesy of Appleton.)

1896 Berlin Exposition. He coined a catchy phrase for the show—kinderbrutanstalt or “child hatchery”—igniting the imagination of a public thirsty for sensational scientific breakthroughs. Couney’s Berlin exhibit was an astounding success. One such show was at Great Britain’s Victorian Era Exhibition in 1897. The show was praised by Lancet in an editorial that recommended that large “incubator stations” be established similar to fire stations, where parents could borrow incubators.36 This was the origin of the phrase “premature baby incubator stations,” which became part of the medical lexicon. In a later editorial, Lancet also criticized the “danger of making a public show of incubator for babies.”37 Couney sailed to the United States and, beginning in 1898, started premature infant exhibitions at many state fairs, traveling circuses, and science expositions, and finally settled in New

Supportive Care and Oxygen Therapy In a single-page note in 1891, Bonnaire referred to Tarnier’s use of oxygen in treating “debilitated” premature infants 2 years earlier14; this was the first published reference to the administration of supplemental oxygen in premature infants for a purpose other than resuscitation. The use of oxygen in premature infants did not become routine, however, until the 1920s. Initially, a mixture of oxygen and carbon dioxide—instead of oxygen alone—was employed to treat asphyxia-induced narcosis. It was argued that oxygen relieved hypoxia, whereas carbon dioxide stimulated the respiratory center.85 Oxygen alone was reserved for “pure asphyxia” (whatever that meant). The advent of mobile oxygen tanks and their easy availability in the mid-1940s enabled the use of oxygen for resuscitation.51,53,79 The success of incubator care brought new and unexpected challenges.68,69 Innovative methods had to be developed to feed the increasing number of premature infants who were surviving for longer periods than ever before. Their growth needed to be monitored, and illnesses related to prematurity, such as sepsis, apnea, anemia, jaundice, and respiratory distress, had to be studied and treated. Another completely unexpected peril from “improved” incubator technology was the epidemic of blindness from ROP (then called retrolental fibroplasia), documented in vivid detail elsewhere.79,80 The apparent culprit in cases of ROP was the “leakproof ” incubator that led to a great increase in the inspired oxygen concentrations (piped in free-flow manner),

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CHAPTER 1  Growth of Neonatal Perinatal Medicine—A Historical Perspective

TABLE Evolution of Incubators 1.2 

Year(s)

Developer/Product

Comments

1835, ca. 1850

von Ruehl (1769-1846)

A physician to Czarina Feodorovna, wife of Czar Paul I, von Ruehl develops the first known incubator for the Imperial Foundling Hospital in St. Petersburg. About 40 of these “warming tubs” are installed in the Moscow Foundling Hospital in 1850.

1857

Denucé (1824-1889)

The first published account of introducing an incubator is a 400-word report by Denucé. This is a “double-walled” cradle.

1880-1883

Tarnier (1828-1897)

Tarnier incubator is developed by Martin and installed in 1880 at the Port-Royal Maternité.

1884

Credé (1819-1892)

Credé reports the results of 647 infants treated over 20 years using an incubator similar to that of Denucé.

1887

Bartlett

Bartlett reads a paper on a “warming crib” based on Tarnier’s concept but uses a “thermo-syphon.”

1893

Budin (1846-1907)

Budin popularizes the Tarnier incubator and establishes the world’s first “special care unit for premature infants” at Maternité and Clinique Tarnier in Paris.

1893

Rotch (1849-1914)

The first American incubator with a built-in scale, wheels, and fresh-air delivery system is developed; the equipment is very expensive and elaborate.

1897

Holt incubator

A simplified version of the Rotch incubator is developed. In this double-walled wooden box, hot water circulates between the walls.

1897-1920s

Brown, Lyons, DeLee, Allin

Many modifications are made to the early American and European incubators by physicians. These are called baby-tents, baby boxes, warming beds, and other names.

1922

Hess

Hess introduces his famous incubator with an electric heating system. For transportation, he develops special boxes that can be plugged into the cigarette lighters in Chicago’s taxi cabs.

1930-1950s

Large-scale commercial incubators

There is worldwide distribution of Air-Shields and other commercial ventilators.

1970-1980

Modern incubators

Transport incubators with built-in ventilators and monitoring equipment are developed—mobile intensive care units.

See references 6, 7, 21-24, 77-80 for primary citations.

• Fig. 1.8

  Hess and Lundeen medallions at the Michael Reese Hospital, Chicago. (Photo courtesy of Tonse N. K. Raju.)

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9

10 pa rt 1 10

The Field of Neonatal-Perinatal Medicine

• Fig. 1.10  The Man-Can, circa 1873 to 1875. A handheld, negativepressure ventilatory device for which a patent was applied in 1876.19,20 (From DeBono E. Eureka! How and When the Greatest Inventions Were Made: An Illustrated History of Inventions from the Wheel to the Computer. New York: Holt, Rinehart & Winston; 1974, p 159.)

• Fig. 1.9

  A Hess incubator on display at the Spertus Museum in Chicago. (From the International Museum of Surgical Sciences, Chicago.)

coupled with the belief that oxygen was innocuous and that if a little bit could save lives, a lot could save even more lives. Because more and more sick and small preterm infants began to survive with incubator care, providing ventilatory assistance became an urgent necessity.

Ventilatory Care: “Extended Resuscitation” The first mechanical instrument used for intermittent positive pressure ventilation in newborns was the aerophore pulmonaire, a simple device developed by the French obstetrician Gairal.65,66 It was a rubber bulb attached to a J-shaped tube. By placing the bent end of the tube into the infant’s upper airway, one could pump air into the lungs. Holt recommended its use for resuscitation in his influential 1897 book.48 Before starting mechanical ventilation, one needed to cannulate the airway, a task nearly impossible without a laryngoscope and an endotracheal tube. Blundell (1790-1878), a Scottish obstetrician, was the first to use a mechanical device for tracheal intubation in living newborns.13,32 Introducing two fingers of his left hand over the infant’s tongue, he would feel the epiglottis and then guide a silver pipe into the trachea with his right hand. His tracheal pipe had a blunt distal end and two side holes. By blowing air into the tube about 30 times a minute until the heartbeat began, Blundell saved hundreds of infants with birth asphyxia and infants with laryngeal diphtheria. His method of tracheal intubation is practiced in many countries today.90 In the

late nineteenth century, a wide array of instruments evolved to provide longer periods of augmented or extended ventilation for infants who had been resuscitated in the labor room. Most of the early instruments were designed for use in adults, however, and were used later in newborns and infants, particularly to treat paralytic polio and laryngeal diphtheria.39,45,81,85 The iron lung (or “man-can”) was one of the earliest mechanical ventilatory devices (Fig. 1.10), and a US patent was issued for it in 1876.19,20,42 In other ventilatory equipment, varying methods for rhythmic inflation and deflation of the lungs were used for prolonged ventilation. Among those, the Fell-O’Dwyer apparatus used a unique footoperated bellows system connected to an implement similar to the aerophore bulb.25,65,66 Between 1930 and 1950, there were sporadic but important reports of prolonged assisted ventilation provided to newborns.12,62,84,85 Beginning in the late 1950s and through the 1960s, more neonatal intensive care units (NICUs) began providing ventilatory assistance regularly (Table 1.3). Ventilatory care did not become predictably successful, however, until the early 1970s, when continuous positive pressure was incorporated into ventilatory devices.44,58,62,84

Supportive Care: Intravenous Fluid and Blood Transfusions When it comes to intravenous therapy, our legacy is one of bloodletting, not of transfusing. Blundell (of intubation fame) also made a major contribution to transfusion science. Believing that “only human blood should be employed for humans,” he developed instruments, syringes, and funnels for this purpose. In 1818, Blundell carried out the first direct transfusion from a healthy donor into a recipient; 5 of his first 10 patients survived. Human-to-human transfusions gradually became accepted, but physicians in the nineteenth century were puzzled about unexpected disasters among blood transfusion recipients. It took 15 years after Landsteiner’s discovery of blood groups in 1901 for the general acceptance

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CHAPTER 1  Growth of Neonatal Perinatal Medicine—A Historical Perspective

11

TABLE Ventilatory Care, Respiratory Disorders, and Intensive Care 1.3 

Approximate Time Span

Category Resuscitation and oxygen

From antiquity to early 1970s 1878 1900-1930s

Procedures and Techniques

1950 to late 1960s 1950-1960s

Mouth-to-mouth breathing (although it fell from favor in the late eighteenth century because many influential physicians declared it a “vulgar method” of revival) Tarnier uses oxygen in debilitated premature infants. Schultz, Sylvester, and Laborde methods of resuscitation involve various forms of swinging infants (Schultz), traction of the tongue (Sylvester), and compression of the chest (Laborde). Oxygen administration to the oral cavity through a rubber catheter Tight-fitting tracheal tube and direct tracheal oxygen administration Byrd-Dew method: immersion in warm water, with alternate flexing and extending of the pelvis to help the “lungs open” Dilation of the rectum Inhalation of oxygen and 7% CO2 mixture (for morphine-induced narcosis) Positive-pressure air-lock (Bloxsom method) Concept that “air in the digestive tract is good for survival” is promoted— administration of oxygen to the stomach Hyperbaric oxygen in Vickers pressure chamber Mouth-to-mouth or mouth-to-endotracheal tube breathing

Assisted ventilation

1930s-1980s 1930-1950 1960s 1971 1973 1970-1980s

Bell develops a negative-pressure jacket Negative-pressure ventilators and iron lungs, used rarely in infants Positive-pressure respirators used for prolonged ventilatory support Continuous positive airway pressure introduced for use in newborns Intermittent mandatory ventilator High-frequency ventilators; continuous monitoring of pulmonary function

Surfactant

1903 1940-1950s 1955–1956 1959

Hochheim reports “hyaline membranes” noted in the lungs of infants with RDS Clinical descriptions and pathology studied Pattle discovers surfactant in pulmonary edema foam and lung extracts. Avery and Mead show absence of surfactant in infants with hyaline membrane disease.4 Gluck introduces lecithin/sphingomyelin ratio. Liggins suggests that antenatal steroids help mature the pulmonary surfactant system. First effective clinical trial of postnatal surfactant therapy (bovine, Fujiwara) Commercial surfactants become available. Widespread antenatal steroid use leads to declines in rates for RDS and improves survival rates for infants with birth weight