NEONATOLOGY: MANAGEMENT, PROCEDURES, ON-CALL PROBLEMS, DISEASES, AND DRUGS - part 1 pdf

NEONATOLOGY: MANAGEMENT,
PROCEDURES, ON-CALL PROBLEMS,
DISEASES, AND DRUGS

5th Edition. (2004)




Tricia Lacy Gomella, MD
Part-Time Assistant Professor of Pediatrics The Johns Hopkins University School
of Medicine Baltimore, Maryland
Associate Editors M. Douglas Cunningham, MD Clinical Professor, Division of
Neonatology Department of Pediatrics College of Medicine University of
California, Irvine Vice President for Special Projects Pediatrix Medical Group
Orange, California

Fabien G. Eyal, MD
Professor of Pediatrics Chief and Louise Lenoir Locke Professor of Neonatology
Medical Director, Intensive Care Nurseries University of South Alabama Children's
and Women's Hospital Mobile, Alabama

Karin E. Zenk, PharmD,
FASHP Practice Consultant and Associate Clinical Professor of Pediatrics College
of Medicine University of California, Irvine, Irvine, California

Lange Medical Books/McGraw-Hill Medical Publishing Division
Copyright 2004 by The McGraw-Hill Companies
NEONATOLOGY: MANAGEMENT, PROCEDURES, ON-CALL PROBLEMS, DISEASES,
AND DRUGS - 5th Ed. (2004)

FRONT MATTER

TITLE PAGE

a LANGE clinical manual

Neonatology: Management, Procedures, On-Call Problems, Diseases, and Drugs - fifth edition

Editor

Tricia Lacy Gomella, MD
Part-Time Assistant Professor of Pediatrics
The Johns Hopkins University School of Medicine
Baltimore, Maryland

Associate Editors

M. Douglas Cunningham, MD
Clinical Professor, Division of Neonatology
Department of Pediatrics
College of Medicine
University of California, Irvine
Vice President for Special Projects
Pediatrix Medical Group
Orange, California

Fabien G. Eyal, MD
Professor of Pediatrics
Chief and Louise Lenoir Locke Professor of Neonatology
Medical Director, Intensive Care Nurseries
University of South Alabama Children's and Women's Hospital
Mobile, Alabama

Karin E. Zenk, PharmD, FASHP
Practice Consultant and Associate Clinical Professor of Pediatrics
College of Medicine
University of California, Irvine,
Irvine, California

Lange Medical Books/McGraw-Hill
Medical Publishing Division

New York Chicago San Francisco Lisbon London Madrid Mexico City Milan New Delhi San Juan
Seoul Singapore Sydney Toronto

COPYRIGHT

Neonatology: Management, Procedures, On-Call Problems, Diseases, and Drugs, fifth edition

Copyright  2004 by The McGraw-Hill Companies, Inc. All rights reserved. Printed in the United
States of America. Except as permitted under the United States Copyright Act of 1976, no part of this
publication may be reproduced or distributed in any form or by any means, or stored in a data base or
retrieval system, without the prior written permission of the publisher.

Previous editions copyright  1999, 1994, 1992, 1988 by Appleton & Lange

34567890 DOC/DOC 0987654

ISBN: 0-07-138918-0
ISSN: 0697-6295

Notice

Medicine is an ever-changing science. As new research and clinical experience broaden our
knowledge, changes in treatment and drug therapy are required. The authors and the publisher of this
work have checked with sources believed to be reliable in their efforts to provide information that is
complete and generally in accord with the standards accepted at the time of publication. However, in
view of the possibility of human error or changes in medical sciences, neither the authors nor the
publisher nor any other party who has been involved in the preparation or publication of this work
warrants that the information contained herein is in every respect accurate or complete, and they
disclaim all responsibility for any errors or omissions or for the results obtained from use of the
information contained in this work. Readers are encouraged to confirm the information contained
herein with other sources. For example and in particular, readers are advised to check the product
information sheet included in the package of each drug they plan to administer to be certain that the
information contained in this work is accurate and that changes have not been made in the
recommended dose or in the contraindications for administration. This recommendation is of
particular importance in connection with new or infrequently used drugs.

This book was set by PineTree Composition
The editors were Janet Foltin, Harriet Lebowitz, and Barbara Holton
The production supervisor was Richard Ruzycka
The cover designer was Mary Scudlarek
The index was prepared by Benjamin Tedoff
R. R. Donnelley, Inc. was the printer and binder.

This book is printed on acid-free paper.

INTERNATIONAL EDITION ISBN 0-07-121906-4
Copyright  2004. Exclusive rights by The McGraw-Hill Companies, Inc., for manufacture and
export. This book cannot be re-exported from the country to which it is consigned by McGraw-Hill.
The International Edition is not available in North America.

DEDICATION

To my twin sons, Leonard and Patrick, and singletons, Andrew and Michael

NOTICE

The authors and editors have made every effort to ensure timely and accurate guidelines in this
manual. However, it is impossible to list every clinical situation or institution-specific guidelines for
diagnosis and treatment. The authors and editors cannot be held responsible for any typographic or
other errors found in this manual. Trade names listed herein are the sole property of the manufacturer
and do not imply endorsement.

CONTENTS

Emergency Medications and Therapy for Neonates …(Inside front and back covers)

Contributors …xi

Preface …xix

Section I. Basic Management
1. Prenatal Testing …1
Prenatal Diagnosis 1 / Antepartum Tests of Fetal Well-Being 3 /
Intrapartum Tests of Fetal Well-Being 4 / Tests of Fetal Lung Maturity 6
2. Delivery Room Management …8
Obstetric Anesthesia and the Neonate 8 / Resuscitation of the Newborn 12
3. Assessment of Gestational Age …21
Classification 21 / Methods of Determining Postnatal Gestational Age 21
4. Newborn Physical Examination …29
5. Temperature Regulation …39
Hypothermia and Excessive Heat Loss 39 / Hyperthermia 43
6. Respiratory Management …44
General Physiologic Support 44 / Monitoring 44 / Ventilatory Support 51 /
Pharmacologic Respiratory Support and Surfactant 56 / Strategies for
Respiratory Management of Certain Newborn Diseases 60 / Overview of High-
Frequency Ventilation 61 / High-Frequency Ventilators, Techniques, and
Equipment 62 / Liquid Ventilation 66 / Glossary of Terms Used in Respiratory
Support 67
7. Fluids and Electrolytes …69
Fluid and Electrolyte Balance 69 / Fluid Therapy 70 / Fluid Calculations 73 /
Modifiers of Fluid and Electrolyte Requirements 75
8. Nutritional Management …77
Growth Assessment of the Neonate 77 / Nutritional Requirements in the
Neonate 77 / Principles of Infant Feeding 78 / Breast-feeding 90 / Total
Parenteral Nutrition 94 / Caloric Calculations 99

9. Neonatal Radiology …102
Common Radiologic Techniques 102 / Radiographic Examples 107 /
Radiographic Pearls 110
10. Management of the Extremely Low Birth Weight Infant During the First Week of Life …120
11. Extracorporeal Membrane Oxygenation (ECMO) …132
12. Infant Transport …136
13. Follow-up of High-Risk Infants …139
14. Studies for Neurologic Evaluation …144
Neuroimaging 144 / Electrographic Studies 146
15. Neonatal Bioethics …151

Section II. Procedures
16. Arterial Access …157
Arterial Puncture (Radial Artery Puncture) 157 / Percutaneous Arterial
Catheterization 158 / Umbilical Artery Catheterization 160
17. Bladder Aspiration (Suprapubic Urine Collection) …165
18. Bladder Catheterization …167
19. Chest Tube Placement …169
20. Endotracheal Intubation …172
21. Exchange Transfusion …175
22. Gastric Intubation …180
23. Heelstick (Capillary Blood Sampling) …182
24. Lumbar Puncture (Spinal Tap) …184
25. Paracentesis (Abdominal) …186
26. Pericardiocentesis …188
27. Venous Access …190
Percutaneous Venous Catheterization 190 / Percutaneous Central Venous
Catheterization 192 / Venipuncture (Phlebotomy) 197 / Umbilical Vein
Catheterization 197 / Intraosseous Infusion 201

Section III. On-Call Problems
28. Abnormal Blood Gas …203
29. Apnea and Bradycardia ("A's and B's") …208
30. Arrhythmia …212
31. Bloody Stool …219
32. Counseling Parents Before High-Risk Delivery …222
33. Cyanosis …226
34. Death of an Infant …230
35. Eye Discharge (Conjunctivitis) …233
36. Gastric Aspirate (Residuals) …237
37. Gastrointestinal Bleeding from the Upper Tract …241
38. Hyperbilirubinemia, Direct (Conjugated Hyperbilirubinemia) …244
39. Hyperbilirubinemia, Indirect (Unconjugated Hyperbilirubinemia) …247
40. Hyperglycemia …251
41. Hyperkalemia …254
42. Hypertension …257
43. Hypoglycemia …262
44. Hypokalemia …267
45. Hyponatremia …270
46. Hypotension and Shock …273
47. Is the Infant Ready for Discharge? …278
48. No Stool in 48 Hours …283
49. No Urine Output in 48 Hours …287
50. Pneumoperitoneum …289
51. Pneumothorax …292
52. Polycythemia …295
53. Poor Perfusion …298
54. Postdelivery Antibiotics …300
55. Pulmonary Hemorrhage …304
56. Sedation and Analgesia in a Neonate …306

57. Seizure Activity …310
58. Traumatic Delivery …314
59. Vasospasms …321

Section IV. Diseases and Disorders
60. Ambiguous Genitalia …324
61. Blood Abnormalities …332
ABO Incompatibility 332 / Anemia 334 / Polycythemia and Hyperviscosity 341 /
Rh Incompatibility 344 / Thrombocytopenia and Platelet Dysfunction 349
62. Cardiac Abnormalities …354
Congenital Heart Disease 354 / Patent Ductus Arteriosus 361 / Persistent
Pulmonary Hypertension of the Newborn 364
63. Common Multiple Congenital Anomaly Syndromes …373
64. Hyperbilirubinemia …381
Unconjugated (Indirect) Hyperbilirubinemia 381 / Conjugated (Direct)
Hyperbilirubinemia 388
65. Inborn Errors of Metabolism With Acute Neonatal Onset …396
66. Infant of a Diabetic Mother …418
67. Infant of a Drug-Abusing Mother …424
68. Infectious Diseases …434
Neonatal Sepsis 434 / Meningitis 440 / TORCH Infections 441 / Toxoplasmosis
442 / Rubella 444 / Cytomegalovirus (CMV) 445 / Herpes Simplex Virus 447 /
Viral Hepatitis 450 / Hepatitis A 450 / Hepatitis B 451 / Hepatitis C 453 /
Hepatitis D 453 / Hepatitis E 454 / Varicella-Zoster Infections 454 / Fetal
Varicella-Zoster Syndrome 454 / Congenital Varicella-Zoster Infection 455 /
Postnatal Varicella-Zoster Infection 456 / Syphilis 456 / Gonorrhea 458 /
Chlamydial Infection 460 / Human Immunodeficiency Virus (HIV) 461 /
Respiratory Syncytial Virus 464 / Lyme Disease 465 /Anthrax 466
69. Intrauterine Growth Retardation (Small for Gestational Age Infant) …469
70. Multiple Gestation …476

71. Necrotizing Enterocolitis and Spontaneous Intestinal Perforation …482
72. Neurologic Diseases …488
Hydrocephalus 488 / Intraventricular Hemorrhage 491 / Neonatal
Seizures 496 / Neural Tube Defects 501
73. Perinatal Asphyxia …512
74. Pulmonary Diseases …524
Air Leak Syndromes 524 / Apnea and Periodic Breathing 530 / Bronchopulmonary
Dysplasia 534 / Hyaline Membrane Disease (Respiratory Distress
Syndrome) 539 / Meconium Aspiration 543 / Transient Tachypnea of the
Newborn 547
75. Renal Diseases …553
Acute Renal Failure 553 / Hematuria 556 / Urinary Tract Infection 556
76. Retinopathy of Prematurity …559
77. Disorders of Calcium and Magnesium Metabolism …563
Osteopenia of Prematurity 563 / Hypocalcemia 565 / Hypercalcemia 568 /
Hypomagnesemia 569 / Hypermagnesemia 570
78. Surgical Diseases of the Newborn …572
Alimentary Tract Obstruction 572 / Vascular Ring 572 / Esophageal
Atresia 572 / Duodenal Obstruction 573 / Proximal Intestinal Obstruction 574 /
Distal Intestinal Obstruction 574 / Imperforate Anus 575 / Causes of Respiratory
Distress 575 / Choanal Atresia 575 / Pierre Robin Syndrome 575 / Vascular
Ring 576 / Laryngotracheal Esophageal Cleft 576 / H-Type Tracheoesophageal
Fistula 576 / Intrinsic Abnormalities of the Airway 576 / Congenital Lobar
Emphysema 576 / Cystic Adenomatoid Malformation 577 / Congenital
Diaphragmatic Hernia 577 / Abdominal Masses 578 / Renal Masses 578 /
Ovarian Masses 579 / Hepatic Masses 579 / Gastrointestinal Masses 579 /
Retroperitoneal Tumors 579 / Neuroblastoma 579 / Wilms' Tumor (Nephroblastoma)
580 / Teratoma 580 / Abdominal Wall Defects 580 / Gastroschisis 580 /
Omphalocele 581/ Exstrophy of the Bladder 582 / Cloacal Exstrophy 582 /
Miscellaneous Surgical Conditions 583 / Necrotizing Enterocolitis 583 /

Hypospadias 583 / Inguinal Hernia and Hydrocele 583 / Umbilical Hernia 583 /
Undescended Testicles (Cryptorchidism) 584 / Posterior Urethral Valves 584
79. Thyroid Disorders …585
General Considerations 585 / Congenital Hypothyroidism 586 / Neonatal
Thyrotoxicosis 587 / Transient Disorders of Thyroid Function in the Newborn 588

Section V. Neonatal Pharmacology
80. Commonly Used Medications …590
81. Effects of Drugs and Substances on Lactation and Breast-feeding …644
82. Effects of Drugs and Substances Taken During Pregnancy …650

Appendices
A. Abbreviations Used in Neonatology …668
B. Apgar Scoring …669
C. Blood Pressure Determinations …670
D. Cerebrospinal Fluid Normal Values …670
E. Chartwork …670
Admission History 670 / Progress Notes 672 / Admission Orders 672 /
Discharge Summary 673
F. Growth Charts …675
G. Isolation Guidelines …680
H. Temperature Conversion Table …686
I. Weight Conversion Table …686

Index …687

CONTRIBUTORS

Marilee C. Allen, MD
Professor of Pediatrics, Associate Director of Neonatology

The Johns Hopkins University School of Medicine
Co-Director of NICU Clinic, Kennedy-Kreiger Institute
Baltimore, Maryland
Follow-up of High-Risk Infants; Counseling Parents Before High Risk Delivery

Gad Alpan, MD
Professor, Department of Pediatrics
New York Medical College
The Regional Neonatal Center
Westchester Medical Center
Valhalla, New York
Patent Ductus Arteriosus, Persistent Pulmonary Hypertension of the Newborn, Infant of a Drug
Abusing Mother

Hubert Ballard, MD
Fellow, Division of Neonatology
University of Kentucky Medical Center and Children's Hospital
Lexington, Kentucky
Apnea and Periodic Breathing

Fayez Bany-Mohammed, MD
Assistant Clinical Professor
Division of Neonatology
Department of Pediatrics, College of Medicine
University of California, Irvine
Irvine, California
Hyaline Membrane Disease

Daniel A. Beals, MD
Associate Professor

Division of Pediatric Surgery
University of Kentucky College of Medicine
Lexington, Kentucky
Neonatal Bioethics

Pasquale Casale, MD
Chief Resident, Department of Urology,
Thomas Jefferson University
Philadelphia, Pennsylvania
Renal Diseases

Carol M. Cottrill, MD
Pediatric Cardiologist
Professor Emeritus- University of Kentucky
Lexington, Kentucky
Central Baptist Hospital
Lexington, Kentucky
Arrhythmia; Congenital Heart Disease

M. Douglas Cunningham, MD
Clinical Professor, Division of Neonatology, Department of Pediatrics
College of Medicine, University of California, Irvine
Vice President for Special Projects, Pediatrix Medical Group, Inc.
Orange, California
Exchange Transfusion, Hydrocephalus, Intraventricular Hemorrhage

Nirmala S. Desai, MD
Professor of Pediatrics
Division of Neonatology
University of Kentucky Medical Center and Children's Hospital

Lexington, Kentucky
Intrauterine Growth Retardation (Small for Gestational Age Infant)
Nutritional Management, Management of the Extremely Low Birth Weight Infant During the First
Week of Life

Fabien G. Eyal, MD
Professor of Pediatrics, Division of Neonatology
Chief and Louis Lenoir Locke Professor of Neonatology
Medical Director, Intensive Care Nurseries
USA Children's and Women's Hospital
Mobile, Alabama
Temperature Regulation, Sedation and Analgesia in a Neonate, Anemia

T. Ernesto Figueroa, MD
Chief, Pediatric Urology
Alfred I. duPont Hospital for Children
Wilmington, Delaware
Associate Professor of Urology
Jefferson Medical College
Thomas Jefferson University
Philadelphia, Pennsylvania
Renal Diseases

Catherine A. Finnegan MS, CRNP
Neonatal Nurse Practitioner
Department of Neonatology
Johns Hopkins Bayview Medical Center
Baltimore, Maryland
Percutaneous Central Venous Catheterization

Maureen M. Gilmore, MD
Assistant Professor of Pediatrics
Johns Hopkins University
Director of Neonatology and Medical Director of NICU
The Johns Hopkins Bayview Medical Center,
Baltimore, Maryland.
Death of an Infant; Hyperbilirubinemia, Direct (Conjugated Hyperbilirubinemia);
Hyperbilirubinemia, Indirect (Unconjugated Hyperbilirubinemia); Hyperglycemia; Hypoglycemia; Is
the Baby Ready for Discharge? No Stool in 48 Hours; No Urine Output in 48 Hours; Pulmonary
Hemorrhage; Traumatic Delivery

W. Christopher Golden, MD
Instructor, Department of Pediatrics
The Johns Hopkins University School of Medicine
Baltimore, Maryland
Eye Discharge (Conjunctivitis), Hypertension, Seizure Activity

Tricia Lacy Gomella, MD
Part-time Assistant Professor of Pediatrics
The Johns Hopkins University School of Medicine
Baltimore, Maryland
Assessment of Gestational Age, Newborn Physical Examination, Procedures, On Call Problems,
Transient Tachypnea of the Newborn

Janet E. Graeber, M. D.
Associate Professor of Pediatrics
Chief, Section of Neonatology
West Virginia University School of Medicine
Robert C. Byrd Health Science Center
Department of Pediatrics, Morgantown WV

Retinopathy of Prematurity

Deborah Grider, RN
Nurse Clinician, Neonatal Intensive Care Unit
University of Kentucky Medical Center and Children's Hospital
Lexington, Kentucky
Management of the Extremely Low Birth Weight Infant During the First Week of Life

George Gross, MD
Professor of Radiology
Director, Division of Pediatric Radiology
University of Maryland Medical System
Department of Diagnostic Radiology
Baltimore, Maryland
Neonatal Radiology

Wayne Hachey, DO, LTC, USA
Assistant Chief of Pediatrics
Chief, Newborn Medicine
Tripler Army Medical Center
Program Director, Neonatal-Perinatal Medicine
Tripler Army Medical Center/Kapiolani Medical Center
for Women and Children
Assistant Clinical Professor, Department of Pediatrics
John A. Burns Assistant Professor of Pediatrics
Trippler Army Medical Center
Uniformed Services
University of the Health Sciences
F. Edward Herbert School of Medicine
Trippler Army Medical Center

Honolulu, Hawaii
Meconium Aspiration

Bryan D. Hall, MD
Professor Emeritus
Division of Genetics and Dysmorphology
Department of Pediatrics
College of Medicine
University of Kentucky
Lexington, Kentucky
Common Multiple Congenital Anomaly Syndromes

Charles R. Hamm, Jr., MD
Associate Professor of Pediatrics, Division of Neonatology
University of South Alabama Children's and Women's Hospital
Mobile, Alabama
Respiratory Management

C. Kirby Heritage, MD
Pediatrix Medical Group
Miami Valley Hospital
Dayton, Ohio
Infant of a Diabetic Mother

H. Jane Huffnagle, DO
Associate Professor of Anesthesiology
Thomas Jefferson University
Philadelphia, Pennsylvania
Obstetric Anesthesia and the Neonate

Beverly Johnson, RN, BSN, CIC
Infection Control Practitioner, Kaiser Permanente Hospital
Fontana, California
Isolation Guidelines

William G. Keyes, MD, PhD
Medical Staff Vice-President
Children's Health Care of Atlanta
Atlanta, Georgia
Multiple Gestation

Janine Kruger, MD
Clinical Assistant Professor
Department of Obstetrics and Gynecology
University of Wisconsin
Madison, Wisconsin
Prenatal Testing

Christoph U. Lehmann, MD
Assistant Professor
Eudowood Neonatal Pulmonary Division and Division of Health Information Sciences
Department of Pediatrics
The Johns Hopkins University School of Medicine
Baltimore, Maryland
Studies for Neurologic Evaluation

Drew Litzenberger, MD
Co-Director, NICU
Mission and St. Joseph's Health System
Asheville, North Carolina

Infant Transport

Janet Murphy, MD
Associate Professor of Pediatrics
Division of Neonatology
Department of Pediatrics
University of Washington
Seattle, Washington
Resuscitation of the Newborn

Ronald Naglie, MD
Attending Neonatologist, Pediatrix Medical Group, Inc.
Medical Director, Neonatal Intensive Care Unit
Saddleback Memorial Medical Center
Laguna Hills, California
Infectious Diseases

Jeanne S. Nunez, MD
Attending Neonatologist
The Johns Hopkins University Bayview Medical Center
Clinical Associate, The Johns Hopkins University School of Medicine
Baltimore, Maryland
Abnormal Blood Gas, Apnea and Bradycardia, Bloody Stool, Cyanosis, Gastric Aspirate,
Gastrointestinal Bleeding from the Upper Tract, Hyperkalemia, Hypokalemia, Hyponatremia,
Hypotension and Shock, Pneumoperitoneum, Pneumothorax, Poor Perfusion, PostDelivery
Antibiotics, Vasospasms, Polycythemia

Ambadas Pathak, MD
Assistant Professor, Emeritus of Pediatrics
The Johns Hopkins University School of Medicine

Clinical Associate Professor of Pediatrics
University of Maryland School of Medicine
Baltimore, Maryland
Neonatal Seizures

Keith J. Peevy, JD, MD
Professor of Pediatrics
Division of Neonatology
USA Children's and Women's Hospital
Mobile, Alabama
Polycythemia and Hyperviscosity

Andrew R. Pulito, MD
Professor and Chief, Division of Pediatric Surgery
University of Kentucky College of Medicine
Lexington, Kentucky
Surgical Diseases of the Newborn

Rakesh Rao, MD
Fellow, Division of Neonatology
University of Kentucky Medical Center and Children's Hospital
Lexington, Kentucky
Nutritional Management

Tracey Robinson, RN
ECMO Coordinator
Neonatal Intensive Care Unit
University of Kentucky Medical Center and Children's Hospital
Lexington, Kentucky
Management of the Extremely Low Birth Weight Infant During the First Week of Life

Jack H. Sills, MD
Clinical Professor, Division of Neonatology
Department of Pediatrics, College of Medicine
University of California, Irvine
Irvine, California
Perinatal Asphyxia

Galdino Silva-Neto, MD
Assistant Professor of Clinical Pediatrics, Division of Neonatology
Department of Pediatrics, University of Miami
Miami, Florida
Attending Neonatologist, Pediatrix Medical Group, Inc.,
Broward General Medical Center
Fort Lauderdale, Florida
Fluids and Electrolytes, Rickets and Disorders of Calcium and Magnesium Metabolism

Lizette Sistoza, MD
Fellow, Division of Neonatology
University of Kentucky Medical Center and Children's Hospital,
Lexington, Kentucky
Air Leak Syndromes

Kendra Smith, MD
Assistant Professor
Division of Neonatology
Department of Pediatrics
University of Washington
Seattle, Washington
ECMO

Ganesh Srinivasan, MD
Fellow, Division of Neonatology, University of Kentucky
Medical Center and Children's Hospital
Lexington, Kentucky
Thyroid Disorders

Christiane Theda, MD
Assistant Professor, Department of Pediatrics,
The Johns Hopkins University School of Medicine,
Baltimore, Maryland
Neonatologist and Medical Geneticist
Johns Hopkins Hospital
Baltimore, Maryland
Frederick Memorial Hospital
Frederick, Maryland
Ambiguous Genitalia, Inborn Errors of Metabolism with Acute Neonatal Onset, Neural Tube Defects

Jorge E. Tolosa MD, MS
Assistant Professor, Obstetrics and Gynecology
Director, Division of Research in Reproductive Health
Department of Obstetrics and Gynecology
Thomas Jefferson University
Philadelphia, Pennsylvania
Prenatal Testing

Cherry C. Uy, MD
Assistant Clinical Professor, Division of Neonatology
Department of Pediatrics, College of Medicine
University of California, Irvine

Irvine, California
Hyperbilirubinemia

Feizal Waffarn, MD
Professor and Chairman
Department of Pediatrics and Chief, Division of Neonatology
College of Medicine, University of California, Irvine
Irvine, California
Necrotizing Enterocolitis

Richard Whitehurst, Jr., MD
Associate Professor of Pediatrics, Division of Neonatology
Assistant Professor of Pharmacology
USA Children's and Women's Hospital
Division of Neonatology
Mobile, Alabama
ABO Incompatibility, Rh Incompatibility

Jacki Williamson, RNC, CPNP, MSN
Clinical Nurse Specialist, Neonatal Services,
Kaiser Permanente Hospital
Fontana, California
Isolation Guidelines

Karin E. Zenk, PharmD, FASHP
Practice Consultant and Associate Clinical Professor of Pediatrics
College of Medicine
University of California, Irvine
Irvine, California
Commonly Used Medications, Effects of Drugs and Substance on Lactation and Breastfeeding,

Effects of Drugs and Substances Taken during Pregnancy, Emergency Medications and Therapy for
Neonates

Michael M. Zayek, MD
Associate Professor of Pediatrics, Division of Neonatology
USA Children's and Women's Hospital
Mobile, Alabama
Bronchopulmonary Dysplasia, Thrombocytopenia and Platelet Dysfunction

PREFACE

I am pleased to present the fifth edition of Neonatology. The manual continues to be widely accepted
both in the United States and internationally. It has been translated into many languages including
Russian, Spanish, Portuguese, and Polish, to name a few. This wide acceptance is only made possible
because of the contributions of our outstanding group of associate editors and contributors.

As the specialty of Neonatology continues to advance we have updated all chapters in the book.
Many concepts are well established and remain a cornerstone of the book. Our tradition of noting
areas of controversy in the field of neonatology continues. In order to maintain balance, contributors
and editors represent a cross section of neonatal practice in the United States.

I would like to thank all contributors to this and previous editions of the book, the editorial staff at
McGraw-Hill, and my family for their continued support of this project. In particular, Dr. George
Dover, Chairman of Pediatrics at Johns Hopkins is acknowledged for his academic support.

I welcome suggestions and comments about this manual. Letters should be addressed to:

Tricia Gomella, MD
c/o McGraw-Hill Medical Publishers
Two Penn Plaza, 12th Floor

New York, NY 10121-2298

Tricia Lacy Gomella, MD
August, 2003

Copyright © 2004 by The McGraw-Hill Companies, Inc. All rights reserved.
SECTION I. Basic Management

CHAPTER 1. Prenatal Testing

PRENATAL DIAGNOSIS

I. First-trimester screening. Maternal serum can be analyzed for certain biochemical markers that,
in combination with ultrasound measurement of the fetal nuchal translucency, can be used to
calculate a risk assessment for trisomies 18 and 21. In the first trimester, these serum markers are the
free β-human chorionic gonadotropin (hCG) and pregnancy-associated plasma protein A (PAPP-A).
It is an effective screening tool, with a detection rate of 87-92% for trisomy 21 and fewer false-
positive results than the traditional triple-screen test (alpha-fetoprotein [AFP], unconjugated estriol,
and hCG). First-trimester screening is performed between 10 and 13 weeks' gestation and requires
confirmation of a chromosomal abnormality by an invasive genetic test (usually chorionic villus
sampling [CVS]).

II. Second-trimester screening. Two common second-trimester tests are the maternal serum AFP
(MSAFP) and the triple-screen test. The MSAFP is a sensitive marker for open neural tube defects,
whereas the triple-screen test yields a risk assessment for open neural tube defects as well as
trisomies 18 and 21. These tests are usually performed between 15 and 20 weeks' gestation and
require an invasive test to confirm the diagnosis of a chromosomal abnormality (usually
amniocentesis). The usefulness of the triple-screen test is limited by its high number of false-positive
test results.

III. Ultrasound testing. Ultrasound examination is used in the following circumstances.

A. Calculation of gestational age. Measurement of the crown-rump length between 8 and 12
weeks' gestation allows for the most accurate assessment of gestational age, to within 5-7 days. After
the first trimester, a combination of biparietal diameter, head circumference, abdominal
circumference, and femur length is used to estimate gestational age and fetal weight. Measurements
in the second trimester are accurate to within approximately 2 weeks and in the third trimester to
within 3 weeks.

B. Anatomic survey. A large number of congenital anomalies can be diagnosed reliably by
ultrasonography, including anencephaly, hydrocephalus, congenital heart disease, gastroschisis,
omphalocele, spina bifida, renal anomalies, diaphragmatic hernia, cleft lip and palate, and skeletal
dysplasia. Identification of these anomalies before birth can help determine the safest type of delivery
and the support personnel needed. Ultrasonography can also aid in determining fetal gender.

C. Assessment of growth and fetal weight. Ultrasonography is useful to detect and monitor both
intrauterine growth restriction (IUGR) and fetal macrosomia. Estimation of fetal weight is also
important in counseling patients regarding expectations after delivering a premature infant.

D. Assessment of amniotic fluid volume

1. Oligohydramnios (decreased amniotic fluid). This is associated with a major anomaly in
15% of cases. Rupture of membranes is the most common cause of oligohydramnios. Other causes
include placental insufficiency, renal anomalies, bladder outlet obstruction, karyotypic abnormalities,
and severe cardiac disease. The kidneys and the bladder can be seen with ultrasonography at ~14
weeks' gestation.

2. Polyhydramnios (hydramnios) (excess of amniotic fluid). Polyhydramnios is associated
with major anomalies in 15% of cases. It is associated with gestational diabetes, anencephaly, neural
tube defects, bowel obstruction such as duodenal atresia, multiple gestation, nonimmune hydrops

fetalis, and exstrophy of the bladder.

E. Assessment of placental location and presence of retroplacental hemorrhage. This is useful
in suspected cases of placenta previa or abruptio placentae.

F. Diagnosis of multiple pregnancy and determination of chorionicity. The determination of
chorionicity is made by examination of the fetal membranes and is best done by 14 weeks' gestation.

G. Determination of pregnancy viability. This is important in the first trimester, when fetal heart
motion can be detected at 6-7 weeks' gestation. It is also important in the case of a suspected fetal
demise later in pregnancy.

H. Assessment of fetal well-being:

1. Biophysical profile. Ultrasonography is used to assess fetal movements and breathing
activity.

2. Doppler studies. Doppler ultrasonography of fetal vessels, particularly the umbilical artery, is
a useful adjunct in the management of high-risk pregnancies, especially those complicated by IUGR.
Changes in the vascular Doppler pattern (ie, absent or reversed end-diastolic flow in the umbilical
artery) signal a deterioration in placental function and possibly a worsening fetal condition. The use
of Doppler ultrasonography has been associated with a 38-50% decrease in perinatal mortality in
high-risk pregnancies; however, no benefit in using this technique to screen a low-risk population has
been proven.

I. Visual guidance for procedures such as amniocentesis, CVS, percutaneous umbilical blood
sampling (PUBS), and some fetal surgeries (eg, placement of bladder or chest shunts).

IV. Amniocentesis. Amniotic fluid can be analyzed for prenatal diagnosis of karyotypic
abnormalities, in fetuses diagnosed with congenital defects, to determine fetal lung maturity, to

monitor the degree of isoimmunization by measurement of the content of bilirubin in the fluid, and
for the diagnosis of chorioamnionitis. Testing for karyotypic and congenital abnormalities is usually
done at 16-20 weeks' gestation. A sample of amniotic fluid is removed under ultrasound guidance.
Fetal cells in the fluid can be grown in tissue culture for genetic study. With visual guidance from the
ultrasonogram, the pregnancy loss rate related to amniocentesis is usually quoted at between 0.3%
and 0.5%. Early amniocentesis (before 13 weeks) is associated with a higher rate of fetal loss. This is
indicated

• In women older than 35 years, because of the increased incidence of aneuploidy (ie, trisomies 13,
18, and 21).

• In those who have already had a child with a chromosomal abnormality.

• In those in whom X-linked disorders are suspected.

• To rule out inborn errors of metabolism.

V. Chorionic villus sampling. CVS is a technique for first-trimester genetic studies. Chorionic villi
are withdrawn either through a needle inserted through the abdomen and into the placenta or through
a catheter inserted through the vagina and cervix into the placenta. The cells obtained are identical to
those of the fetus and are grown and analyzed. CVS can be performed in the first trimester (usually
between 10 and 12 weeks' gestation). Results can be obtained more quickly than with other methods
via fluorescence in situ hybridization (FISH) rapid chromosome analysis, thus enabling the patient to
have a diagnosis before the end of the first trimester. Indications are the same as for amniocentesis.
Reported complications after CVS can include pregnancy loss and limb abnormalities; however, if
CVS is performed after 70 days' gestation, there is no increased incidence of limb reduction defects.
Pregnancy loss rates after CVS are usually quoted as ranging from 0.6-0.8% but are highly operator
dependent.

VI. Percutaneous umbilical blood sampling. Under ultrasound guidance, a needle is placed

transabdominally into the umbilical vein. Samples of fetal blood can be obtained for karyotype, viral
studies, fetal blood type, and hematocrit. This also provides a route for in utero transfusion. This
technique is most often used in cases of fetal hydrops.

ANTEPARTUM TESTS OF FETAL WELL-BEING

I. Nonstress test. The nonstress test (NST) is used to detect intact fetal brainstem function. Fetal well-
being is confirmed if the baseline heart rate is normal and there are periodic increases in the fetal
heart rate. These accelerations are often associated with fetal movement. The following guidelines
can be used, although there may be variations between institutions.

A. Reactive NST. In a 20-min monitoring period, there are at least two accelerations of the fetal
heart rate 15 beats/min above the baseline fetal heart rate; each acceleration lasts at least 15 s.

B. Nonreactive NST. Fetal heart rate does not meet the criteria just mentioned during a prolonged
period of monitoring (usually at least 1 h). Note: There are many causes of a nonreactive NST
besides fetal compromise, including a fetal sleep cycle, chronic maternal smoking, and exposure to
medications such as central nervous system depressants and propranolol. Because of this low
specificity, a nonreactive NST should be followed by more definitive testing such as a biophysical
profile or a contraction stress test.

II. Biophysical profile. The biophysical profile (
Table 1-1) is another test used to assess fetal well-
being, often when the NST has been nonreactive. An NST is performed along with an ultrasound
examination to evaluate fetal breathing movements, gross body movements, tone, and amniotic fluid
volume. A score of 8-10 is considered normal, 4-6 indicates possible fetal compromise, and 0-2
predicts high perinatal mortality. This test has not been adequately assessed at early gestational ages.

III. Contraction stress test. The contraction stress test (CST) is used to assess a fetus at risk for
uteroplacental insufficiency. A monitor is placed on the mother's abdomen to continuously record the

fetal heart rate and uterine contractions. An adequate test consists of at least three contractions, each
lasting at least 40- 60 s, within a period of 10 min. If sufficient contractions do not occur
spontaneously, the mother is instructed to perform nipple stimulation or oxytocin is administered by
intravenous pump. If oxytocin is needed to produce contractions for the CST, it is called an oxytocin
challenge test (OCT). Normally, the fetal heart rate increases in response to a contraction, and no
decelerations occur during or after the contraction. If late decelerations occur during or after
contractions, uteroplacental insufficiency may be present. The CST is contraindicated in patients with
placenta previa, those who have had a previous cesarean section with a vertical incision, and those
with high-risk factors for preterm delivery (ie, premature rupture of membranes or incompetent
cervix). Test results are interpreted as follows:

A. Negative (normal) test. No late decelerations occur during adequate uterine contractions. The
baseline fetal heart rate is normal. This result is associated with a very low perinatal mortality rate in
the week after the test.

B. Positive (abnormal) test. Late decelerations occur with at least two of three contractions over a
10-min interval. This result can signify poor fetal outcome, and depending on gestational age,
delivery is usually recommended.

C. Equivocal (suspicious) test. A late deceleration occurs with one of three contractions over a 10-
min interval. Prolonged fetal monitoring is usually recommended.

INTRAPARTUM TESTS OF FETAL WELL-BEING

I. Fetal heart rate monitoring. Continuous fetal heart rate monitoring has been the standard clinical
practice since the 1970s. However, it has not been shown to improve perinatal mortality compared
with intermittent auscultation of the fetal heart rate. The only clear benefit to continuous fetal
monitoring in labor is a decrease in neonatal seizures. An abnormal fetal heart rate pattern is 50%
predictive of low Apgar scores. Fetal heart rate monitoring may be internal, with an electrode
attached to the fetal scalp, or external, with a monitor attached to the maternal abdomen. The baseline

heart rate, beat-to-beat variability, and long-term variability are measured.

A. Baseline fetal heart rate. The baseline fetal heart rate is the rate that is maintained apart from
periodic variations. The normal fetal heart rate is 110-160 beats/min. Fetal tachycardia is present at
160 beats/min or more. Causes of fetal tachycardia include maternal or fetal infection, fetal hypoxia,
thyrotoxicosis, and maternal use of drugs such as parasympathetic blockers or beta-mimetic agents.
Moderate fetal bradycardia is defined as a heart rate of 90-110 beats/min with normal variability.
Severe fetal bradycardia is a heart rate of <90 beats/min. Common causes of bradycardia include
hypoxia, complete heart block, and maternal use of drugs such as β-blockers.

B. Variability. Fetal heart rate variability has traditionally been broken down into categories of
short-term (beat-to-beat) and long-term variability, although for most practical purposes they are
assessed together. In the normal mature fetus, there are slight rapid fluctuations in the interval
between beats (beat-to-beat variability). This indicates a functioning sympathetic-parasympathetic
nervous system interaction. An amplitude range (baseline variability) >6 beats/min indicates normal
beat-to-beat variability and suggests the absence of fetal hypoxia. Absence of variability may be
caused by severe hypoxia, anencephaly, complete heart block, and maternal use of drugs such as
narcotics or magnesium sulfate. Long-term variability refers to fluctuations in the fetal heart rate over
longer periods of time (minutes rather than seconds).

C. Accelerations. Accelerations are often associated with fetal movement and are an indication of
fetal well-being.

D. Decelerations. There are three types of decelerations (Figure 1-1).

1. Early decelerations. Early decelerations (decelerations resulting from physiologic head
compression) occur secondary to vagal reflex tone, which follows minor, transient fetal hypoxic
episodes. These are benign and are not associated with fetal compromise.

2. Late decelerations. Two types of late decelerations exist.

a. Late decelerations with maintained beat-to-beat variability. These are seen in the
setting of normal fetal heart rate variability. They are associated with a sudden insult (eg, maternal
hypotension) that affects a normally oxygenated fetus and signifies uteroplacental insufficiency. The
normal variability of the fetal heart rate signifies that the fetus is physiologically compensated.

b. Late decelerations with decreased beat-to-beat variability. These are associated with
decreased or absent fetal heart rate variability. They may represent fetal hypoxia resulting from
uteroplacental insufficiency. Maneuvers such as maternal oxygen supplementation and maternal
positioning in the left lateral decubitus position may improve fetal oxygenation and placental
circulation and should be attempted.

3. Variable decelerations. These are most frequently associated with umbilical cord
compression. They are classified as severe when the fetal heart rate decreases to <60 beats/min, the
deceleration is longer than 60 s in duration, or the fetal heart rate is 60 beats/min below baseline. If
beat-to-beat variability is maintained, the fetus is compensated physiologically and oxygenated
normally.

II. Fetal scalp blood sampling. Fetal scalp blood sampling is used during labor to determine the
fetal acid-base status when the fetal heart rate tracing is non-reassuring or equivocal. This procedure
can be performed only after rupture of membranes. It is contraindicated in cases of possible blood
dyscrasias in the fetus and with maternal infections caused by herpesvirus or HIV. A blood sample is
obtained from the fetal presenting part (usually the scalp but sometimes the buttocks), and the fetal
blood pH is determined. A pH of ≥7.25 has been shown to correlate (with 92% accuracy) with a 2-
min Apgar score of ≥7. The protocol for interpreting fetal scalp blood pH varies among institutions.
Complications of this test are scalp infections (in <1% of infants) and soft tissue damage to the scalp.
An example of one such protocol is as follows.

A. pH ≥7.20. Fetus is not acidotic; no intervention required.

B. pH 7.10-7.19. Fetus is preacidotic. Repeat sampling in 15-20 min.

C. pH <7.10. Fetus may be acidotic. Delivery is indicated.

III. Scalp stimulation/vibroacoustic stimulation. An acceleration in fetal heart rate in response to
either manual stimulation of the fetal presenting part or vibroacoustic stimulation through the
maternal abdomen has been associated with a fetal pH of >7.20. These tests are often used in labor to
determine fetal well-being in lieu of a scalp blood sampling; however, a lack of fetal response to
stimulation is not predictive of acidemia.

IV. Fetal pulse oximetry. This promising new technique is designed as an adjunct to nonreassuring
fetal heart rate tracings in order to reduce the number of unnecessary interventions. A normal fetal
oxygen saturation as measured by pulse oximetry (SpO
2
) is 30-70%. A pulse oximetry reading of at
least 30% has good correlation with a fetal pH of at least 7.20. Long-term studies are still needed to
evaluate this technique.

FIGURE 1-1. Examples of fetal heart rate monitoring. FHR, Fetal heart rate (beats
per minute); UC, uterine contraction (mm Hg); HC, head compression; UPI,
uteroplacental insufficiency; CC, cord compression. (Modified and reproduced,
from McCrann JR, Schifrin BS: Fetal monitoring in high-risk pregnancy. Clin
Perinatol 1974;1:149 with permission from Elsevier Science.)

TESTS OF FETAL LUNG MATURITY

I. Lecithin-sphingomyelin (L-S) ratio. Lecithin, a saturated phosphatidylcholine (the condensation
product of a phosphatidic acid and choline), can be measured specifically in amniotic fluid and is a
principal active component of surfactant. It is manufactured by type II alveolar cells. Sphingomyelin
is a phospholipid found predominantly in body tissues other than the lungs. The L-S ratio compares

levels of lecithin, which increase in late gestation, with levels of sphingomyelin, which remain
constant. The L-S ratio is usually 1:1 by 31-32 weeks' gestation and 2:1 by 35 weeks' gestation. The
following are guidelines to L-S ratios.

• L-S ≥ 2:1: Lungs are mature (98% accuracy). Only 2% of these infants will experience
respiratory distress syndrome (RDS).

• L-S = 1.5-1.9:1: 50% of infants will experience RDS.

• L-S <1.5:1: 73% of infants will experience RDS.

Some disorders are associated with delayed lung maturation, and higher than normal L-S ratios may
be needed before fetal lung maturity is ensured. The two most common disorders are diabetes
mellitus (an L-S ratio of 3:1 is usually accepted as indicating maturity) and Rh isoimmunization
associated with hydrops fetalis. Acceleration of fetal lung maturity is seen in sickle cell disease,
maternal narcotic addiction, prolonged rupture of membranes, chronic maternal hypertension,
intrauterine growth restriction, and placental infarction. Differences may also occur in various racial
groups.

II. Phosphatidylglycerol. Phosphatidylglycerol appears in amniotic fluid at ~35 weeks, and levels
increase at 37-40 weeks. This substance is a useful marker for lung maturation late in pregnancy. It is
reported as either present or absent.


FIGURE 1-1. Examples of fetal heart rate monitoring. FHR, Fetal heart rate (beats per minute); UC,
uterine contraction (mm Hg); HC, head compression; UPI, uteroplacental insufficiency; CC, cord
compression. (Modified and reproduced, from McCrann JR, Schifrin BS: Fetal monitoring in high-
risk pregnancy. Clin Perinatol 1974;1:149 with permission from Elsevier Science.)

III. TDx fetal lung maturity (TDx FLM). This test (Abbott Laboratories, North Chicago, IL)

measures the relative concentrations of surfactant and albumin (milligrams of surfactant per gram of
albumin) in amniotic fluid and gives a result that helps assess fetal lung maturity. TDx FLM has
several advantages over L-S ratio: (1) Less technical expertise is required; (2) this test can be
performed more easily; and (3) results are obtained more quickly. Results are interpreted in the
following ways.

• 30-70 mg/g: The infant is at risk for immature lungs. Other conditions may weigh more heavily
on the decision to deliver early.

• >70 mg/g: The likelihood of RDS is small.

REFERENCES

Boehm FH: Intrapartum fetal heart rate monitoring.
Obstet Gynecol Clin North Am 1999;26:623.

Dildy GA: Fetal pulse oximetry: current issues.
J Perinat Med 2001;29:5.

Krantz DA et al: First-trimester Down syndrome screening using dried blood chemistry and nuchal
translucency.
Obstet Gynecol 2000;96:207.

Manning FA et al: Fetal biophysical profile scoring: a prospective study in 1184 high-risk patients.
Am J Obstet Gynecol 1981;140:289.

Porter TF et al: Vibroacoustic and scalp stimulation.
Obstet Gynecol Clin North Am 1999;26:657.

Russell JC et al: Multicenter evaluation of TDx test for assessing fetal lung maturity.

Clin Chem
1989;35:1005.

Wilson RD: Amniocentesis and chorionic villus sampling.
Curr Opin Obstet Gynecol 2000;12:81.

TABLE 1-1. BIOPHYSICAL PROFILE SCORING SYSTEM USED
TO ASSESS FETAL WELL-BEING
Variable Normal (2) Abnormal (0)
Fetal breathing One episode >30 s in 30 min None or episode <30 s
in 30 min
Body movement Three or more movements in
30 min
Two or less
movements in 30 min
Fetal tone One episode or active limb
or trunk extension with
flexion
No movement
Nonstress test Reactive Nonreactive
Amniotic fluid One pocket of amniotic fluid
1 cm or more
No fluid pockets or
pocket <1 cm
Based on guidelines from Manning FA et al: Fetal biophysical profile
scoring: a prospective study in 1184 high-risk patients. Am J Obstet
Gynecol 1981;140:289. Reprinted with permission from Elsevier Science