Ebook Queenan’s management of high risk pregnancy: Part 1

Queenan’s Management of
High-Risk Pregnancy


Queenan’s
Management of
High-Risk
Pregnancy
An Evidence-Based Approach
EDI T ED BY

JOHN T. QUEENAN,

MD

Professor and Chairman Emeritus
Department of Obstetrics and Gynecology
Georgetown University School of Medicine
Washington, DC, USA

CATHERINE Y. SPONG,

MD

Bethesda, MD, USA

CHARLES J. LOCKWOOD,

MD

Anita O’Keeffe Young Professor and Chair
Department of Obstetrics, Gynecology and Reproductive Sciences
Yale University School of Medicine
New Haven, CT, USA

S IXT H E DI TI O N

A John Wiley & Sons, Ltd., Publication


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Library of Congress Cataloging-in-Publication Data
Queenan’s management of high-risk pregnancy : an evidence-based approach / edited by
John T. Queenan, Catherine Y. Spong, Charles J. Lockwood. – 6th ed.
p. ; cm.
Management of high-risk pregnancy
Rev. ed. of: Management of high-risk pregnancy / edited by John T. Queenan,

Catherine Y. Spong, Charles J. Lockwood. 5th. 2007.
Includes bibliographical references and index.
ISBN-13: 978-0-470-65576-4 (hard cover : alk. paper)
ISBN-10: 0-470-65576-3 (hard cover : alk. paper)
1. Pregnancy–Complications. I. Queenan, John T. II. Spong, Catherine Y.
III. Lockwood, Charles J. IV. Management of high-risk pregnancy. V. Title:
Management of high-risk pregnancy.
[DNLM: 1. Pregnancy Complications. 2. Evidence-Based Medicine. 3. Pregnancy,
High-Risk. WQ 240]
RG571.M24 2012
618.3–dc23
2011027303
A catalogue record for this book is available from the British Library.
Wiley also publishes its books in a variety of electronic formats. Some content that appears in
print may not be available in electronic books.
Set in 9.25/12pt Palatino by Toppan Best-set Premedia Limited, Hong Kong

1

2012


Contents

List of Contributors, vii
Foreword, xi

11 Interpreting Intrapartum Fetal Heart Tracings, 89
Michael Nageotte

Preface, xii
Acknowledgments, xii
List of Abbreviations, xiii
Part 1 Factors of High-Risk Pregnancy
1 Overview of High-Risk Pregnancy, 1
John T. Queenan, Catherine Y. Spong,
and Charles J. Lockwood

Part 4 Maternal Disease
12 Sickle Cell Anemia, 93
Scott Roberts
13 Anemia, 98
Alessandro Ghidini
14 Thrombocytopenia, 102
Robert M. Silver

2 Maternal Nutrition, 4
Edward R. Newton

15 Inherited and Acquired Thrombophilias, 108
Michael J. Paidas

3 Alcohol and Substance Abuse, 23
William F. Rayburn

16 Thromboembolic Disorders, 121
Christian M. Pettker and Charles J. Lockwood

4 Environmental Agents and Reproductive Risk, 32
Laura Goetzl

17 Cardiac Disease, 131
Stephanie R. Martin, Alexandria J. Hill,
and Michael R. Foley

Part 2 Genetics

18 Renal Disease, 151
David C. Jones

5 Genetic Screening for Mendelian Disorders, 41
Deborah A. Driscoll

19 Pregnancy in Transplant Patients, 160
James R. Scott

6 Screening for Congenital Heart Disease, 47
Lynn L. Simpson

20 Gestational Diabetes Mellitus, 168
Deborah L. Conway

7 First- and Second-Trimester Screening for Fetal
Aneuploidy and Neural Tube Defects, 55
Julia Unterscheider and Fergal D. Malone

21 Diabetes Mellitus, 174
George Saade

Part 3 Monitoring: Biochemical

and Biophysical

22 Hypothyroidism and Hyperthyroidism, 178
Brian Casey
23 Asthma, 183
Michael Schatz

8 Sonographic Dating and Standard Fetal Biometry, 63
Eliza Berkley and Alfred Abuhamad

24 Epilepsy, 193
Autumn M. Klein and Page B. Pennell

9 Fetal Lung Maturity, 75
Alessandro Ghidini and Sarah H. Poggi

25 Chronic Hypertension, 204
Heather A. Bankowski and Dinesh M. Shah

10 Antepartum Fetal Monitoring, 79
Brian L. Shaffer and Julian T. Parer

26 Systemic Lupus Erythematosus, 209
Christina S. Han and Edmund F. Funai

v


vi

Contents

27 Perinatal Infections, 218
Jeanne S. Sheffield

44 Management of Preterm Labor, 374
Vincenzo Berghella

28 Malaria, 231
Richard M.K. Adanu

45 Placenta Previa and Related Placental Disorders, 382
Yinka Oyelese

29 Group B Streptococcal Infection, 234
Ronald S. Gibbs
30 Hepatitis, 238
Patrick Duff
31 HIV Infection, 243
Howard L. Minkoff
32 Pregnancy in Women with Physical
Disabilities, 253
Caroline C. Signore

Part 5 Obstetric Complications
33 Recurrent Spontaneous Abortion, 260
Charles J. Lockwood
34 Cervical Insufficiency, 271
John Owen
35 Gestational Hypertension, Preeclampsia, and

Eclampsia, 280
Labib M. Ghulmiyyah and Baha M. Sibai
36 Postpartum Hemorrhage, 289
Michael A. Belfort
37 Emergency Care, 301
Garrett K. Lam and Michael R. Foley
38 Rh and Other Blood Group Alloimmunizations, 307
Kenneth J. Moise Jr
39 Multiple Gestations, 314
Karin E. Fuchs and Mary E. D’Alton
40 Polyhydramnios and Oligohydramnios, 327
Ron Beloosesky and Michael G. Ross
41 Prevention of Preterm Birth, 337
Paul J. Meis
42 Pathogenesis and Prediction of Preterm Delivery, 346
Catalin S. Buhimschi and Charles J. Lockwood
43 Preterm Premature Rupture of Membranes, 364
Brian M. Mercer

Part 6 Complications of Labor and Delivery
46 Prolonged Pregnancy, 391
Teresa Marino and Errol R. Norwitz
47 Induction of Labor, 399
Nicole M. Petrossi and Deborah A. Wing
48 Cesarean Delivery, 406
Michael W. Varner
49 Vaginal Birth After Cesarean Delivery, 414
Mark B. Landon
50 Breech Delivery, 424
Edward R. Yeomans and Larry C. Gilstrap

51 Operative Vaginal Delivery, 429
Edward R. Yeomans
52 Obstetric Analgesia and Anesthesia, 434
Gilbert J. Grant
53 Patient Safety, 439
Christian M. Pettker
54 Neonatal Encephalopathy and Cerebral Palsy, 445
Maged M. Costantine, Mary E. D’Alton,
and Gary D.V. Hankins

Part 7 Procedures
55 Genetic Amniocentesis and Chorionic Villus
Sampling, 453
Ronald J. Wapner
56 Fetal Surgery, 464
Robert H. Ball and Hanmin Lee

Index, 475

The color plate section can be found facing p. 192


List of Contributors

Alfred Abuhamad

MD

Chairman, Department of Obstetrics and Gynecology
Director, Maternal-Fetal Medicine

Mason C. Andrews Professor of Obstetrics and Gynecology
Professor of Radiology
Eastern Virginia Medical School
Norfolk, VA, USA

Richard M.K Adanu

MD, ChB, MPH, FWACS

Associate Professor of Obstetrics and Gynecology, Women’s
Reproductive Health
University of Ghana Medical School
Accra, Ghana

Eliza Berkley

Catalin S. Buhimschi

MD

Associate Clinical Professor
Department of Obstetrics, Gynecology and Reproductive
Sciences
University of California
San Francisco, CA, USA

Heather A. Bankowski
Clinical Instructor, Maternal-Fetal Medicine
University of Wisconsin Medical School
Madison, WI, USA

MD

Professor, Lead Doctor of Community Obstetrics
Department of Obstetrics and Gynecology
University of Texas Southwestern Medical Center
Dallas, TX, USA

Deborah L. Conway

MD

Assistant Professor
Department of Obstetrics and Gynecology
University of Texas School of Medicine
San Antonio, TX, USA

Maged M. Costantine
Michael A. Belfort

MBBCH, MD, PhD

Chairman and Professor
Department of Obstetrics and Gynecology
Baylor College of Medicine
Houston, TX, USA

Ron Beloosesky

MD

Department of Obstetrics, Gynecology and Public Health
UCLA School of Medicine and Public Health;
Harbor-UCLA Medical Center
Torrance, CA, USA
MD

Professor
Department of Obstetrics and Gynecology
Thomas Jefferson University
Philadelphia, PA, USA

MD

Department of Obstetrics and Gynecology
University of Texas Medical Branch
Galveston, TX, USA

Mary E. D’Alton

MD

Chair
Department of Obstetrics and Gynecology
Columbia University Medical Center;
Columbia Presbyterian Hospital
New York, NY, USA

Deborah A. Driscoll
Vincenzo Berghella

MD

Associate Professor
Department of Obstetrics, Gynecology and Reproductive
Sciences
Yale University School of Medicine
New Haven, CT, USA

Brian Casey
Robert H. Ball

MD

Associate Professor
Department of Obstetrics and Gynecology
Eastern Virginia Medical School
Norfolk, VA, USA

MD

Luigi Mastroianni Jr. Professor and Chair
Department of Obstetrics and Gynecology
Perelman School of Medicine at the University of Pennsylvania
Philadelphia, PA, USA

vii


viii

List of Contributors

Patrick Duff

Gilbert J. Grant

MD

Professor of Obstetrics and Gynecology and Residency Program
Director
University of Florida College of Medicine
Gainesville, FL, USA

MD

Associate Professor of Anesthesiology
New York University School of Medicine
New York, NY, USA

Christina S. Han
Michael R. Foley

MD

Clinical Professor
Department of Obstetrics and Gynecology
University of Arizona
Tuscon, AZ, USA

MD

Assistant Professor
Department of Obstetrics and Gynecology
The Ohio State University College of Medicine
Columbus, OH, USA

Gary D. V. Hankins
Karin E. Fuchs

MD

Assistant Clinical Professor
Department of Obstetrics and Gynecology
Columbia University Medical Center;
Columbia Presbyterian Hospital
New York, NY, USA

Edmund F. Funai

MD

Professor
Department of Obstetrics and Gynecology
The Ohio State University College of Medicine
Columbus, OH, USA

Alessandro Ghidini

MD

Professor of Obstetrics and Gynecology
Georgetown University Hospital
Washington, DC;
Perinatal Diagnostic Center
Inova Alexandria Hospital
Alexandria, VA, USA

Labib M. Ghulmiyyah
Department of Obstetrics and Gynecology
University of Cincinnati College of Medicine
Cincinnati, OH, USA

Ronald S. Gibbs

MD

Professor and Chairman
Department of Obstetrics and Gynecology
University of Colorado School of Medicine
Denver, CO, USA

Larry C. Gilstrap III

MD

Executive Director
American Board of Obstetrics and Gynecology
Dallas, TX, USA

Laura Goetzl

MD, MPH

Associate Professor
Department of Obstetrics and Gynecology
Medical University of South Carolina
Charleston, SC, USA

MD

Professor and Chairman
Department of Obstetrics and Gynecology
University of Texas Medical Branch
Galveston, TX, USA

Alexandria J. Hill

MD

Department of Obstetrics and Gynecology
University of Arizona
Tucson, AZ, USA

David C. Jones

MD

Associate Professor
Department of Obstetrics, Gynecology and Reproductive

Sciences
University of Vermont College of Medicine
Burlington, VT, USA

Autumn M. Klein

MD, PhD

Department of Neurology
Brigham and Women’s Hospital;
Harvard Medical School
Boston, MA, USA

Garrett K. Lam

MD

Clinical Associate Professor
Dept of Obstetrics and Gynecology
University of Tennessee-Chattanooga
Chattanooga, TN

Mark B. Landon

MD

Richard L. Meiling Professor and Chairman
Department of Obstetrics and Gynecology
Ohio State University
Columbus, OH, USA

Hanmin Lee

MD

Associate Professor
Department of Surgery
Director, Fetal Treatment Center
University of California
San Francisco, CA, USA

Fergal D. Malone

MD

Professor and Chairman
Department of Obstetrics and Gynaecology
Royal College of Surgeons in Ireland
Dublin, Ireland


List of Contributors
Teresa Marino

John Owen

MD

MD

Department of Obstetrics and Gynecology
Tufts Medical Center and
Tufts University School of Medicine
Boston, MA, USA

Bruce A. Harris Jr. Endowed Professor
Department of Obstetrics and Gynecology
University of Alabama at Birmingham
Birmingham, AL, USA

Stephanie R. Martin

Yinka Oyelese

DO

Associate Professor
Department of Obstetrics and Gynecology
Baylor College of Medicine
Houston, TX, USA

Paul J. Meis

MD

Assistant Professor of Obstetrics and Gynecology
Department of Obstetrics and Gynecology
Jersey Shore University Medical Center;
UMDNJ-Robert Wood Johnson Medical School
New Brunswick, NJ, USA

MD

Professor Emeritus of Obstetrics and Gynecology
Department of Obstetrics and Gynecology
Wake Forest University School of Medicine
Winston-Salem, NC, USA

Brian M. Mercer

BA, MD, FRCSC, FACOG

Director, Division of Maternal-Fetal Medicine
Metro Health Medical Center;
Professor, Reproductive Biology
Case Western Reserve University
Cleveland, OH, USA

Howard L. Minkoff

MD

Chairman, Department of Obstetrics and Gynecology
Maimonides Medical Center;
Distinguished Professor of Obstetrics and Gynecology
SUNY Downstate Medical Center
New York, NY, USA

Kenneth J. Moise Jr MD
Professor, Obstetrics and Gynecology

Department of Obstetrics, Gynecology and Reproductive
Sciences
University of Texas School of Medicine at Houston and the
Texas Fetal Center of Memorial Hermann Children’s Hospital
Houston, TX, USA

Michael Nageotte

MD

Department of Obstetrics and Gynecology
University of California
Irvine, CA, USA

Edward R. Newton

MD

Chair, Professor, Department of Obstetrics and Gynecology
East Carolina University
Brody School of Medicine
Greenville, NC, USA

Errol R. Norwitz

MD, PhD

Louis E. Phaneuf Professor and Chair
Department of Obstetrics and Gynecology
Tufts Medical Center and

Tufts University School of Medicine
Boston, MA, USA

Michael J. Paidas

MD

Associate Professor
Department of Obstetrics, Gynecology and Reproductive
Sciences
Yale University School of Medicine
New Haven, CT, USA

Julian T. Parer

MD, PhD

Professor
Department of Obstetrics, Gynecology and Reproductive
Sciences
University of California
San Fransisco, CA, USA

Page B. Pennell

MD

Director of Research
Division of Epilepsy, EEG and Sleep Neurology
Department of Neurology

Brigham and Women’s Hospital;
Harvard Medical School
Boston, MA, USA

Christian M. Pettker

MD

Assistant Professor
Department of Obstetrics, Gynecology and Reproductive
Sciences
Yale University School of Medicine
New Haven, CT, USA

Nicole M. Petrossi
Department of Obstetrics and Gynecology
University of California
Irvine, CA, USA

Sarah H. Poggi

MD

Associate Professor Obstetrics and Gynecology
Georgetown University Hospital
Washington, DC;
Perinatal Diagnostic Center
Inova Alexandria Hospital
Alexandria, VA, USA

William F. Rayburn

MD

Seligman Professor and Chair of Obstetrics and Gynecology
University of New Mexico Health Sciences Center
Albuquerque, NM, USA

ix


x

List of Contributors

Scott Roberts

Caroline C. Signore

MD

Professor and Lead Doctor in High Risk Obstetrics and
Gynecology
University of Texas Southwestern Medical Center
Dallas, TX, USA

Michael G. Ross

MD

Professor of Obstetrics, Gynecology and Public Health
UCLA School of Medicine and Public Health;
Chairman, Department of Obstetrics and Gynecology
Harbor-UCLA Medical Center
Torrance, CA, USA

George Saade

MD

Professor, Division Chief
Department of Obstetrics and Gynecology
University of Texas Medical Branch
Galveston, TX, USA

Michael Schatz

MD

Chief, Department of Allergy
Kaiser Permanente Medical Center
San Diego, CA, USA

James R. Scott

MD

Professor and Chair Emeritus
Department of Obstetrics and Gynecology
University of Utah

Salt Lake City, UT, USA

Brian L. Shaffer

MD

Department of Obstetrics, Gynecology and Reproductive
Sciences
University of California
San Francisco, CA, USA

Dinesh M. Shah

MD

Professor, Obstetrics and Gynecology
Director, Maternal-Fetal Medicine
University of Wisconsin Medical School
Madison, WI, USA

Jeanne S. Sheffield

MD

Associate Professor, Obstetrics and Gynecology
University of Texas Southwestern Medical Center
Dallas, TX, USA

Baha M. Sibai

MD

Professor of Clinical Obstetrics and Gynecology
Department of Obstetrics and Gynecology
University of Cincinnati College of Medicine
Cincinnati, OH, USA

MD, MPH

Medical Officer, Obstetrics and Gynecology
Eunice Kennedy Shriver National Institute of Child Health and
Human Development
National Institutes of Health
United States Department of Health and Human Services
Bethesda, MD, USA

Robert M. Silver

MD

Professor, Obstetrics and Gynecology
Division Chief, Maternal-Fetal Medicine
Medical Director, Labor and Delivery
Department of Obstetrics and Gynecology
University of Utah School of Medicine
Salt Lake City, UT, USA

Lynn L. Simpson

MD

Associate Professor of Clinical Obstetrics and Gynecology
Columbia University Medical Center
New York, NY, USA

Julia Unterscheider

MD

Clinical Lecturer and Research Registrar
Department of Obstetrics and Gynaecology
Royal College of Surgeons in Ireland
Dublin, Ireland

Michael W. Varner

MD

Professor Obstetrics and Gynecology
University of Utah Health Sciences Center
Salt Lake City, UT, USA

Ronald J. Wapner

MD

Director, Division of Maternal Fetal Medicine
Department of Obstetrics and Gynecology
Columbia University Medical Center
New York, NY, USA

Deborah A. Wing

MD

Professor and Director
Department of Obstetrics and Gynecology
University of California
Irvine, CA, USA

Edward R. Yeomans

MD

Professor, Chairman and Residency Program Director
Department of Obstetrics and Gynecology
Texas Tech University Health Sciences Center
Lubbock, TX, USA


Foreword

In 1980, the founding editor of Contemporary OB/GYN,
Dr. John Queenan, assembled 67 chapters by 73 authors
from the pages of Contemporary OB/GYN to create the first
edition of the textbook, Management of High-Risk Pregnancy.
This work became a classic. The fifth edition added
two eminent co-editors, Dr. Catherine Y. Spong and Dr.
Charles J. Lockwood, whose clinical and research experience further enhanced the publication’s national reputation. The addition of Dr. Charles Lockwood, then and
now the editor of Contemporary OB/GYN, cemented the

close relationship between the evolution of this textbook
and the journal. Credit for the success of this book most
deservedly goes to Dr. John Queenan, whose vision and
unique personal qualities make it difficult for most leaders
in the field to say no to him!
As in past editions, this book focuses on factors affecting pregnancy, genetics, and fetal monitoring. These sections are followed by a review of maternal diseases in
pregnancy, obstetric complications, intrapartum complications, a section on diagnostic and therapeutic procedures, perinatal asphyxia and neonatal considerations.
The sixth edition includes important new chapters on
maternal diseases – discussing iron deficiency anemia,
malaria and placenta accreta. These additional chapters
are timely and needed, as progress in maternal care in
recent decades has lagged behind advances in fetal and
neonatal care. In my opinion, we need to focus renewed
resources and attention on coordinating care for mothers
with complex medical and surgical complications, though
focus should never be removed from enhancing fetal and
neonatal care.
This edition also includes new chapters on induction of
labor, operative vaginal delivery and patient safety on
labor and delivery. These chapters are extremely valuable
as the climate towards patient safety has changed: labor

is more frequently induced in many hospitals; fewer
obstetricians are being trained to perform operative
vaginal deliveries; and the national attention on patient
safety has led to higher expectations for successful outcomes on labor floors. Finally, this edition includes a new
chapter on screening for congenital heart disease. As
screening protocols for Down syndrome and neural tube
defects have become standard, there is a need to focus on
better national programs to screen for the most common,

but perhaps the most difficult to diagnose condition, congenital heart disease.
The last 30 years have witnessed extraordinary
advances in prenatal screening and diagnosis. Prenatal
diagnosis of the majority of abnormalities is now possible. Severe Rh disease has been virtually eliminated and
fetal surgery has been demonstrated to improve outcomes for some fetuses diagnosed with neural tube
defects. The incidence of stillbirth and neonatal death has
declined significantly, due to a combination of better antenatal and invasive care in our neonatal units. These
advances have been beautifully and finely addressed in
previous editions of this text. The sixth edition upholds
the textbook’s place as a classic, outlining a practical
approach to management for physicians and trainees.
I offer my congratulations to the editors for their ability
to sustain excellence, and my humility for my small
contribution.
Mary E. D’Alton, M.D.
Willard C. Rappleye Professor of Obstetrics
and Gynecology
Chair, Department of Obstetrics and Gynecology
Director, Obstetric and Gynecologic Services
Columbia University College of Physicians & Surgeons
New York, NY, USA

xi


Preface

The sixth edition of Queenan’s Management of High-Risk
Pregnancy, like its predecessors, is directed to all health
professionals involved in the care of women with highrisk pregnancies. A series of articles appearing in

Contemporary OB/GYN was the inspiration for the first
edition in 1980. The predominantly clinical articles provided a comprehensive perspective on diagnosis and
treatment of complicated problems in pregnancy. The
book contains clear, concise, practical material presented
in an evidence-based manner. Each chapter is followed by
an illustrative case report to help put the subject in
perspective.
The major challenge has been to select the subjects most
critical to providing good care, and then to invite the
outstanding authorities on the subjects to write the articles. This dynamic process requires adding new chapters
as the evidence dictates and eliminating others so that the
reader is presented with clinically useful contemporary
information. The addition of two editors for the fifth
edition enhanced our ability to bring our readers the critical information: Catherine Y. Spong, MD, is Chief of the
Pregnancy and Perinatology Branch at the National
Institute of Child Health and Human Development.
Charles J. Lockwood, MD, is Anita O’Keeffe Young
Professor of Obstetrics, Gynecology, and Reproductive

Services, Yale University School of Medicine. They are
outstanding experts in research and patient care.
We now present the sixth edition at a time when the
setting for health care is rapidly changing. We have
emphasized evidence-based information and clinical
practicality and included chapters on timely topics such
as safety, operative vaginal delivery, postpartum hemorrhage, and pregnancies in women with disabilities. In
response to concern for health professionals in developing countries we have added chapters including maternal
anemia, malaria, and HIV infection.
We are committed to bringing the reader the best possible clinical information. As a reader if you find an area
that needs correction or modification, or have comments

to improve this effort, please contact me at: JTQMD@aol.
com.
John T. Queenan, MD
Professor and Chairman Emeritus
of Obstetrics and Gynecology
Georgetown University School of Medicine
Washington, DC
Deputy Editor Obstetrics & Gynecology

Acknowledgments

We are fortunate to work in cooperation with a superb
editorial staff at Wiley Blackwell Publishing under the
direction of our publisher Martin Sugden who has generously shared his wisdom and guidance. Lucinda Yeates,
Rob Blundell, and Helen Harvey have also provided
guidance and editorial skills which are evident in this
edition.
We acknowledge with great appreciation and admiration the authors, experts all. Their contributions to this
book are in the best traditions of academic medicine, and
will be translated into a considerable decrease in morbidity and mortality for mothers and infants.

xii

We wish to thank our editorial assistant Michele Prince
who coordinated the assembly of the manuscripts in a
professional and efficient manner. Her editorial and managerial skills are in large part responsible for the success
of this book.
Use this book to improve the delivery of care for your
patients. Your dedication to women’s health has made it
a joy to prepare this resource.

John T. Queenan, MD
Catherine Y. Spong, MD
Charles J. Lockwood, MD


List of Abbreviations

17P
AAN
AAP
ABOG
ABP
AC
ACA
ACE
ACMG
ACOG
ACT
ACTH
adjOR
ADP
ADR
AED
AES
AF
AFE
AFI
AFP
AIUM
ALT

AMI
ANA
anti-β2GPI
anti-dsDNA
anti-RNP
anti-Sm
AOI
APA
APAS
APC
APE
APO
APTT
AQP
ARB
ART
AS

17α-hydroxyprogesterone caproate
American Academy of Neurology
American Academy of Pediatrics
American Board of Obstetrics and
Gynecology
American Board of Pediatrics
abdominal circumference
anticardiolipin antibody
angiotensin-converting enzyme
American College of Medical
Genetics
American College of Obstetricians and

Gynecologists
artemisin-based combination therapy
adrenocorticotropin
adjusted odds ratio
adenosine diphosphate
autonomic dysreflexia
antiepileptic drugs
American Epilepsy Society
amniotic fluid
amniotic fluid embolism
Amniotic Fluid Index
α-fetoprotein
American Institute of Ultrasound in
Medicine
alanine aminotransferase
acute myocardial infarction
antinuclear antibodies
anti-β2-glycoprotein-I
anti-double-stranded DNA
anti-ribonucleoprotein
anti-Smith
Adverse Outcome Index
antiphospholipid antibody
antiphospholipid antibody syndrome
activated protein C
acute pulmonary embolism
adverse pregnancy outcome
activated partial thromboplastin time
aquaporin
angiotensin receptor blocker

assisted reproductive technology
aortic stenosis

ASCUS
ASD
AST
AT
AV
BMI
BPA
BPD
BPP
BV
CBC
CBZ
CCB
CD
CDC
CDH
CHB
CHD
CI
CL
CMV
CNS
COX
CP
CPAM
CRH
CRL

CSE
CST
CT
CTPA
CVS
CXR
D&C
DAMP
dDAVP
DES
DHEAS
DIC
DM

atypical cells of undetermined
significance
atrial septal defect
aspartate aminotransferase
antithrombin
atrioventricular
Body Mass Index
bisphenol A
biparietal diameter
biophysical profile
bacterial vaginosis
complete blood count
carbamazepine
calcium channel blocker
cesarean delivery
Centers for Disease Control

congenital diaphragmatic hernia
congenital heart block
congenital heart diseases
confidence interval
cervical length
cytomegalovirus
central nervous system
cyclooxygenase
cerebral palsy
congenital pulmonary airway
malformation
corticotropin-releasing hormone
crown–rump length
combined spinal–epidural
contraction stress test
computed tomography
computed tomographic pulmonary
angiography
chorionic villus sampling
chest x-ray
dilation and curettage
damage-associated molecular pattern
molecules
deamino arginine vasopressin
diethylstilbestrol
dehydroepiandrosterone sulfate
disseminated intravascular coagulation
diabetes mellitus

xiii

xiv
DVT
ECG
ECM
ECMO
ECV
EDD
EF
EFM
EFW
EI
EIA
ELISA
eNO
EP
EPCR
ER-β
FAS
FDA
FDP
FEV1
fFN
FFP
FHT
FIGS
FiO2
FL
FLM

FMF
FMH
FSI
fT4
FVL
GBS
GCT
GDM
GFR
GP
GPL
GTCS
GTP
GTT
HAART
Hb
HBV
HBC
HC
hCG
Hct
HDFN
HELLP
HFUPR
HIE

List of Abbreviations
deep venous thrombosis
electrocardiogram
extracellular matrix

extracorporeal membrane oxygenation
external cephalic version
estimated date of delivery
ejection fraction
electronic fetal monitoring
estimated fetal weight
erythema infectiosum
enzyme immunoassay
enzyme-linked immunosorbent assay
exhaled nitric oxide
erythropoietin
endothelial cell protein C receptor
estrogen receptor-β
fetal alcohol syndrome
Food and Drug Administration
fibrin degradation products
forced expiratory volume in 1 sec
fetal fibronectin
fresh frozen plasma
fetal heart rate tracing
fetal intervention guided by sonography
fraction of inspired oxygen
femur length/fetal loss
fetal lung maturity
frontomaxillary facial
fetomaternal hemorrhage
Foam Stability Index
free thyroxine
factor V Leiden
group B streptococci

glucose challenge test
gestational diabetes mellitus
glomerular filtration rate
glycoprotein
anticardiolipin antibody of IgG isotype
generalized tonic-clonic seizures
gestational thrombocytopenia
glucose tolerance testing/gestational
transient thyrotoxicosis
highly active antiretroviral therapy
hemoglobin
hepatitis B
hepatitis C
head circumference/homocysteine
human chorionic gonadotropin
hematocrit
hemolytic disease of the fetus and
newborn
hemolysis, elevated liver enzymes, and
low platelet count
hourly fetal urine production rate
hypoxic ischemic encephalopathy

HIT
HL
HLA
HPA
HPV
HSV
IAI

ICD
ICH
IFA
Ig
IGFBP
IL
IM
INR
IOM
IT
ITP
IU
IUD
IUFD
IUGR
IUT
IV
IVF
IVH
IVIG
IVT
KIR
LAC
LBC
LBW
LDA
LDH
LEEP
LFT
LGA

LMWH
LPS
LOS
LR
LRD
L:S
LTG
LUS
MCA
MCD
MCM
MCV
MFMU
MMC
MMP
MoM

hemorrhage, infection, toxemia
humeral length
human leukocyte antigen
human platelet antigen/
hypothalamic–pituitary–adrenal
human papillomavirus
herpes simplex virus
intraamniotic infection
implantable cardioverter-defibrillator
intracranial hemorrhage
immunofluorescent assay
immunoglobulin
insulin-like growth factor-binding

protein
interleukin
intramuscular/intramembranous
international normalized ratio
Institute of Medicine
intracranial translucency
idiopathic thrombocytopenic purpura
international unit
intrauterine device
intrauterine fetal death
intrauterine growth restriction
intrauterine transfusion
intravenous
in vitro fertilization
intraventricular hemorrhage
intravenous immunoglobulin
intravascular transfusion
killer cell immunoglobulin-like receptor
lupus anticoagulant
lamellar body count
low birthweight
low-dose aspirin
lactate dehydrogenase
loop electrosurgical excision procedure
liver function test
large for gestational age
low molecular weight heparin
lipopolysaccharide
length of stay
likelihood ratio

limb reduction defect
lecithin:sphingomyelin ratio
lamotrigine
lower uterine segment
middle cerebral artery
minimal change disease
major congenital malformation
mean corpuscular volume
Maternal-Fetal Medicine Unit
myelomeningocele
matrix metalloproteinase
multiples of the median


List of Abbreviations
MOMS
MPL
MPR
MR
MRI
MS
MSAFP
MSD
NAEPP
NAIT
NCHS
NEC
NICHD
NICU
NIH

NK
NLE
NNRTI
NOTSS
NRTI
NST
NT
NTD
NYHA
OGTT
OR
PAI
PAMG
PAMP
PaPP-A
PAR
PB
PC
PCA
PCB
PCEA
PCOS
PCR
PDA
PE
PEFR
PG
PGDH
PGM
PGS

PHT
PI
PICC
PKA

Management of Myelomeningocele
Study
anticardiolipin antibody of IgM isotype
multifetal pregnancy reduction
magnetic resonance/mass restricted
magnetic resonance imaging
multiple sclerosis
maternal serum α-fetoprotein
mean sac diameter
National Asthma Education and
Prevention Program
neonatal alloimmune thrombocytopenia
National Center for Health Statistics
necrotizing enterocolitis
National Institute of Child Health and
Human Development
neonatal intensive care unit
National Institutes of Health
natural killer
neonatal lupus erythematosus
nonnucleoside reverse transcriptase
inhibitor
nontechnical surgical skills
nucleoside analog reverse transcriptase
inhibitor

nonstress test
nuchal translucency
neural tube defects
New York Heart Association
oral glucose tolerance test
odds ratio
plasminogen activator inhibitor
placental α-microglobulin
pathogen-associated molecular pattern
pregnancy-associated plasma protein A
protease-activated receptor
phenobarbital
protein C
patient-controlled analgesia
polychlorinated biphenyl
patient-controlled epidural analgesia
polycystic ovarian syndrome
polymerase chain reaction
patent ductus arteriosus
pulmonary embolism
peak expiratory flow rate
phosphatidylglycerol/prostaglandin
15-hydroxy-prostaglandin
dehydrogenase
prothrombin G20210A gene mutation
preimplantation genetic screening
phenytoin
protease inhibitor
peripherally inserted central catheter
protein kinase A

PKC
PMC
PNV
PPCM
PPH
PPROM
PR
PRBC
PROM
PS
PT
PTB
PTD
PTH
PTL
PTSD
PTT
PTU
PZ
RA
RAGE
RBC
RCA
RDA
RDI
RDS
RE
RFA
Rh

RhIG
RIBA
RPF
RPR
RR
SAB
SAR
SB
SBE
SCD
SCI
SCT
S:D
SDP
SELDI-TOF
SERPIN
SGA
SLE
SMA
SNP
ST
SVT

protein kinase C
placenta-mediated complications
prenatal vitamins
peripartum cardiomyopathy
postpartum hemorrhage
preterm premature rupture of
membranes

progesterone receptor
packed red blood cell
premature rupture of membranes
protein S
prothrombin time
preterm birth
preterm delivery
parathyroid hormone
preterm labor
posttraumatic stress disorder
partial thromboplastin time
propylthiouracil
protein Z
rheumatoid arthritis
receptor for advanced glycation
end-products
red blood cell
root cause analysis
recommended dietary
allowance
recommended daily intake
respiratory distress syndrome
retinol equivalent
radiofrequency ablation
rhesus
rhesus immunoglobulin
recombinant immunoblot assay
renal plasma flow
rapid plasma reagin
relative risk

spontaneous abortion
surfactant:albumin ratio
spina bifida
systemic bacterial endocarditis
sickle cell disease
spinal cord injury
sacrococcygeal teratomas
systolic:diastolic
single deepest pocket
surface-enhanced laser desorption
ionization time-of-flight
serine protease inhibitor
small for gestational age
systemic lupus erythematosus
spinal muscular atrophy
single nucleotide polymorphism
selective termination
supraventricular tachycardia

xv


xvi
TAFI
TAT
TEC
TEE
TF
TFPI
TLR

TNF
TOGV
TOL
tPA
TRAP
TSH
TTTS
TVU
TWR
TXA2
UA
UDS
uE3

List of Abbreviations
thrombin-activatable fibrinolysis
inhibitor
thrombin–antithrombin
trauma, embolism, cardiac
transesophageal echocardiography
tissue factor
tissue factor pathway inhibitor
Toll-like receptor
tumor necrosis factor
transposition of the great vessels
trial of labor
tissue-type plasminogen activator
twin reversed arterial perfusion
thyroid-stimulating hormone
twin–twin transfusion syndrome

transvaginal ultrasound
tubular water reabsorption
thromboxane A2
umbilical artery
urinary drug screen
unconjugated estriol

UFH
uPA
UPD
UTI
VAS
VBAC
VDRL
VOC
VPA
V/Q
VSD
VTE
VUS
vWF
VZV
WB
WHO
WWE
ZDV
ZPI

unfractionated heparin
urokinase-type plasminogen activator

uniparental disomy
urinary tract infection
vibroacoustic stimulation
vaginal birth after cesarean
Venereal Disease Research Laboratory
vasoocclusion
valproic acid
ventilation/perfusion
ventricular septal defect
venous thromboembolism
venous ultrasonography
von Willebrand factor
varicella zoster virus
Western blot
World Health Organization
women with epilepsy
zidovudine
protein Z-related protease inhibitor


(A)

(C)

(B)

(D)

Plate 6.1 (A) Two-dimensional image of the aortic arch demonstrating head and neck vessels. The aortic arch has a candy cane shape.
(B) Same image with color Doppler demonstrating forward flow through the aortic arch (blue). (C) Two-dimensional image of the ductal

arch which has the shape of a hockey stick. (D) Color flow mapping of the ductal arch showing normal antegrade flow (blue).


(A)

(B)

(C)

Plate 6.2 (A) Color Doppler demonstrating forward flow from the atria to the ventricles across the atrioventricular valves (red). The
atrioventricular valves are open and the interventricular septum appears to be intact. (B) Long-axis view of the left ventricular outflow
tract demonstrating normal antegrade flow across the aortic valve (blue). (C) Color flow mapping showing forward flow in the right
ventricular outflow tract (blue). Note that the main pulmonary artery crosses over the ascending aorta as it exits the right ventricle.

(A)

(B)

Plate 6.3 (A) Four-chamber view suspicious for an apical muscular ventricular septal defect (VSD) based on an echogenic spot on the
interventricular septum (arrow). (B) Muscular VSD confirmed on color Doppler which demonstrated right-to-left flow during systole
(blue; arrow).


Plate 7.1 Septated cystic hygroma at 11 weeks’ gestation:
midsagittal view demonstrating increased NT space extending
along the entire length of the fetus. The ductus venosus shows
positive a-wave. Chorionic villus sampling revealed normal male
karyotype. The pregnancy proceeded to full term with the
delivery of a healthy infant.

Plate 7.2 Ductus venosus flow velocity waveform with reversed
a-wave. The Doppler gate is placed in the ductus venosus
between the umbilical venous sinus and the inferior vena cava.
Subsequent CVS confirmed a fetus affected by trisomy 21.


(A)

(B)
Plate 19.1 (A) Frontal view of the newborn presenting ptosis of
the left eyelid, upper cleft lip, hypertelorism, and micrognathia.
(B) Lateral view of the newborn with microtia with the absence
of the external auditory duct. Reproduced from Perez-Aytes et al
[18] with permission from Wiley-Blackwell.


Chapter 1
Overview of High-Risk Pregnancy
John T. Queenan1, Catherine Y. Spong2 and Charles J. Lockwood3
1

Department of Obstetrics and Gynecology, Georgetown University School Medicine, Washington, DC, USA
Bethesda, MD, USA
3
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT,
USA
2

With the changing demographics of the United States
population, including increasing maternal age and weight

during pregnancy, higher rates of pregnancies conceived
by artificial reproductive technologies and increasing
numbers of cesarean deliveries, complicated pregnancies
have risen. Although most pregnancies are low risk with
favorable outcomes, high-risk pregnancies – the subject
of this book – may have potentially serious occurrences.
We classify any pregnancy in which there is a maternal
or fetal factor that may adversely affect the outcome as
high risk. In these cases, the likelihood of a positive
outcome is significantly reduced. In order to improve the
outcome of a high-risk pregnancy, we must identify risk
factors and attempt to mitigate problems in pregnancy
and labor.
Many conditions lend themselves to identification and
intervention before or early in the perinatal period. When
diagnosed through an appropriate work-up before pregnancy, conditions such as rhesus (Rh) immunization, diabetes, and epilepsy can be managed to minimize the risks
of mortality and morbidity to both mother and baby. It is
not possible, however, to predict other conditions, such
as multiple pregnancies, preeclampsia, and premature
rupture of membranes prior to pregnancy. To detect and
manage these challenging situations, the obstetrician
must maintain constant vigilance once pregnancy is
established.
Although much progress has been made since the
1950s, there is still much to accomplish. Fifty years ago,
the delivering physician and the nursing staff were
responsible for newborn care. The incidence of perinatal
mortality and morbidity was high. Pediatricians and
pediatric nurses began appearing in the newborn nursery
in the 1950s, taking responsibility for the infant at the

moment of birth. This decade of neonatal awareness
ushered in advances that greatly improved neonatal
outcome.

Many scientific breakthroughs directed toward evaluation of fetal health and disease occurred in the 1960s,
which is considered the decade of fetal medicine. Early in
that decade, the identification of patients with the risk
factor of Rh immunization led to the prototype for the
high-risk pregnancy clinic. Rh-negative patients were
screened for antibodies, and if none were detected, these
women were managed as normal or “low-risk” cases.
Those who developed antibodies were enrolled in a highrisk pregnancy clinic, where they could be carefully followed by specialists with expertise in Rh immunization.
With the advent of scientific advances such as amniotic
fluid bilirubin analysis, intrauterine transfusion, and,
finally, Rh immune prophylaxis, these often perilous
high-risk pregnancies generally became success stories.
A note of caution is in order. The creation of special Rh
clinics for Rh-immunized mothers in the early 1960s was
a logical strategy since the Rh-immunized mother with
an Rh-positive fetus had a 50% chance of losing her baby
either in utero or in the nursery. With increasing technologic and scientific advances physicians achieved markedly better outcomes. We are sensitive to the use of the
term “high-risk pregnancy” and believe it should be
avoided in patient counseling as it can cause unnecessary
anxiety for the parents.
During the 1970s, the decade of perinatal medicine,
pediatricians and obstetricians combined forces to continue improving perinatal survival. Some of the most significant perinatal advances are listed in Box 1.1. Also
included are the approximate dates of these milestones
and (where appropriate) the names of investigators who
are associated with the advances.
Among the advances in perinatal medicine that

occurred during the 1980s were the development of comprehensive evaluation of fetal condition with the biophysical profile, the introduction of cordocentesis for diagnosis
and therapy, the development of neonatal surfactant

Queenan’s Management of High-Risk Pregnancy: An Evidence-Based Approach, Sixth Edition. Edited by John T. Queenan, Catherine Y. Spong,
Charles J. Lockwood.
© 2012 John Wiley & Sons, Ltd. Published 2012 by John Wiley & Sons, Ltd.

1


2

Part 1 Factors of High-Risk Pregnancy

Box 1.1 Milestones in perinatology
Before 1950s
Neonatal care by obstetricians and nurses
1950s: decade of neonatal awareness
Pediatricians entered the nursery
1950
Allen and Diamond
1953
du Vigneaud
1954
Patz
1955
Mann
1956
Tjio and Levan
1956

Bevis

1958
1958
1959

Donald
Hon
Burns, Hodgman,
and Cass

Exchange transfusions
Oxytocin synthesis
Limitation of O2 to prevent toxicity
Neonatal hypothermia
Demonstration of 46 human
chromosomes
Amniocentesis for bilirubin in Rh
immunization
Obstetric use of ultrasound
Electronic fetal heart rate evaluation
Gray baby syndrome

1960s: decade of fetal medicine
Prototype
1960
1962
1963
1964

1965
1965
1966
1967
1967
1967
1968
1968
1968
1968

of the high-risk pregnancy clinic
Eisen and Hellman
Lumbar epidural anesthesia
Saling
Fetal scalp blood sampling
Liley
First intrauterine transfusion for
Rh immunization
Wallgren
Neonatal blood pressure
Steele and Breg
Culture of amniotic fluid cells
Mizrahi, Blanc, and
Necrotizing enterocolitis
Silverman
Parkman and Myer
Rubella immunization
Neonatal blood gases
Neonatal transport

Jacobsen
Diagnosis of cytogenetic disorders
in utero
Dudrick
Hyperalimentation
Nadler
Diagnosis of inborn errors of
metabolism in utero
Stern
NICU effectiveness
Freda et al
Rh prophylaxis

1972
1973
1973
1973
1975
1976
1977
1977
1978
1978
1979

ABOG
Sadovsky

Maternal-Fetal Medicine Boards
Fetal movement

Real-time ultrasound
Hobbins and Rodeck Clinical fetoscopy
ABP
Neonatology Boards
Schifrin
Nonstress test
March of Dimes
Towards Improving the Outcome of
Pregnancy I
Kaback
Heterozygote identification (Tay–Sachs
disease)
Bowman
Antepartum Rh prophylaxis
Steptoe and Edwards* In vitro fertilization
Boehm
Maternal transport

1980s: decade of progress
Technologic progress
1980
Bartlett
1980
Manning and Platt
1981
Fujiwara, Morley, and Jobe
1982
Harrison and Golbus
Bang, Brock and Toll
1983

1985
1986
1986
1986

Kazy, Ward, and Brambati
Daffos, Hobbins
NICHD
Michaels et al

ECMO
Biophysical profile
Neonatal surfactant therapy
Vesicoamniotic shunt for fetal
hydronephrosis
First fetal transfusion under
ultrasound guidance
Chorionic villus sampling
Cordocentesis
DNA analysis
MFMU network established
Cervical ultrasound and
preterm delivery

1990s: decade of managed care
Managed care alters practice patterns
1991
Lockwood et al
Fetal fibronectin and preterm delivery
1993

March of Dimes
Towards Improving the Outcome of
Pregnancy II
Fetal therapy
Preimplantation genetics
Stem cell research
1994
NIH Consensus
Antenatal corticosteroids
Conference

1970s: decade of perinatal medicine
Refinement of NICU
Regionalization of high-risk perinatal care
1971 Gluck
L:S ratio and respiratory distress
syndrome
1972 Brock and Sutcliffe
α-Fetoprotein and neural tube defects
Liggins and Howie
Betamethasone for induction of fetal
lung maturity
1972
1972
1972
1972
1972

Quilligan
Dawes

Ray and Freeman

Neonatal temperature control with
radiant heat
Fetal heart rate monitoring
Fetal breathing movements
Oxytocin challenge test

2000s: decade of evidence-based perinatology
2000
2002
2003
2006
2008
2009

Mari
CDC
MFMU
MFMU
Merck
MFMU
MFMU

Middle cerebral artery monitoring for Rh disease
Group B streptococcus guidelines
Antibiotics for PPROM
Progesterone to prevent recurrent prematurity
Immunization against human papillomavirus
Magnesium for prevention of cerebral palsy

Gestational diabetes trial

2010s: current decade
2010
2011

NIH
MOMS

Consensus conference on VBAC
Fetal surgery improves outcome for
myelomeningocele

ABOG, American Board of Obstetrics and Gynecology; ABP, American Board of Pediatrics; CDC, Centers for Disease Control; ECMO, extracorporeal
membrane oxygenation; L:S, lecithin:sphingomyelin ratio; MFMU, Maternal-Fetal Medicine Units; MOMS, Management of Myelomeningocele Study:
NICU, neonatal intensive care unit; NICHD, National Institute of Child Health and Human Development; NIH, National Institutes of Health; PPROM,
preterm premature rupture of membranes; VBAC, vaginal birth after cesarean.
*Recipient of the 2010 Nobel Prize in Medicine.


Chapter 1 Overview of High-Risk Pregnancy
therapy, antenatal steroids and major advances in genetics and assisted reproduction. These technologic advances
foreshadowed the “high-tech” developments of the 1990s.
Clearly, the specialty has come to realize that “high tech”
must be accompanied by “high touch” to ensure the emotional and developmental well-being of the baby and the
parents. This decade was one of adjusting to the challenges of managed care under the control of “for profit”
insurance companies.
The new millennium brought the decade of evidencebased perinatology. Clinicians became aware of the value
of systematic reviews of the Cochrane Database. Major
perinatal research projects by the Maternal-Fetal Medicine

Units network of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development
answered many clinical questions.
The future will bring better methods of determining
fetal jeopardy and health. Continuous readout of fetal

3

conditions will be possible during labor in high-risk pregnancies. Look for the new advances to be made in immunology and genetics. Immunization against group B
streptococcus and eventually human immunodeficiency
virus will become available. Preimplantation genetics will
continue to provide new ways to prevent disease. Alas,
prematurity and preeclampsia with their many multiple
etiologies may be the last to be conquered.
New technology will increase the demand for trained
workers in the healthcare industry. The perinatal professional team will expand to emphasize the importance of social workers, nutritionists, child development
specialists, and psychologists. New developments will
create special ethical issues. Finally, education and
enlightened attitudes toward reproductive awareness
and family planning will help to prevent unwanted
pregnancies.


Chapter 2
Maternal Nutrition
Edward R. Newton
Department of Obstetrics and Gynecology, East Carolina University, Brody School of Medicine, Greenville, NC, USA

The medical profession and the lay public associate
maternal nutrition with fetal development and subsequent pregnancy outcome. Classic studies from Holland

and Leningrad during World War II [1] suggest that when
maternal caloric intake fell acutely to below 800 kcal/day,
birthweights were reduced 535 g in Leningrad and 250 g
in Holland, the difference perhaps related to the better
nutritional status of the Dutch women prior to the famine
and the shorter duration of their famine. Exposure to
famine conditions during the second half of pregnancy
had the greatest adverse effect on birthweight and placental weight and to a lesser extent, birth length, head circumference, and maternal postpartum weight [2–5].
While these studies are used as prima facie evidence of
a link between maternal nutrition and fetal development,
a more discerning examination reveals many confounding variables that are common to the investigation of
maternal nutrition and fetal development. While the
onset of rationing was distinct and the birthweight and
other anthropomorphic measurements were recorded
reliably, other confounders were not identified. For
example, menstrual data were notoriously unreliable, and
the problem of poor determination of gestational dates
was exacerbated by the disruption and stress of war.
In 2011, many of the most vulnerable mothers have
little or no prenatal care (10–30%), often with unreliable
menstrual data (15–35%). In Holland and Leningrad, the
stress of war may have been associated with both preterm
delivery and reduced birthweight. In a modern context,
the urban war produces a similar stress through lack of
social supports, domestic violence, and drugs. The content
of the individual’s diet in wartime Europe or the diet of
underprivileged women in the United States in 2011
remains largely speculation; perhaps it is not the total
number of kilocalories or protein content but an issue of
overall quality that leads to decreased birthweights. In

2011, as in 1944–5, the link between maternal nutrition
and pregnancy outcome relies on a relatively weak proxy

for a woman’s nutritional status: Body Mass Index (BMI).
A prospective, longitudinal study that follows a sufficiently large cohort of women from preconception
through each trimester and into the puerperium (with
and without breastfeeding), measures the quality and
quantity of women’s diet, and correlates the diet with
maternal and fetal and neonatal outcomes has not yet
been performed.
The purpose of this chapter is to review the associations
between maternal nutrition and perinatal outcome. It
briefly summarizes the basic concepts of fetal growth, the
multiple predictors of fetal growth, the use of maternal
weight gain as a measure of maternal nutrition, adverse
pregnancy outcomes as they relate to extremes in maternal weight gain, and the importance or controversy
related to specific components of the diet (i.e. iron,
calcium, sodium, and prenatal vitamins).

Fetal growth
Linear growth of the fetus is continuous, whereas the
velocity of growth varies. Multiple researchers have
studied linear fetal growth by examining birthweights or
estimated fetal weights as determined by ultrasound, and
found it to be nearly a straight line until approximately
35 weeks when the fetus grows 200–225 g/wk (Fig. 2.1).
Thereafter, the curve falls such that by 40 weeks, the
weight gain is 135 g/wk [6].
Twin pregnancies have a proportionately lower rate of
growth, reaching a maximum at 34–35 weeks (monochorionic placentation, 140–160 g/wk; dichorionic placentation, 180–200 g/wk) [7]. Thereafter, the growth rate slows

to 25–30 g/wk in both types of placentation. In 20–30% of
term twin pregnancies, one or the other twin, or both, will
have a birthweight less than the 10th percentile based on
singleton growth charts. There is controversy as to
whether singleton or separate twin charts should be the

Queenan’s Management of High-Risk Pregnancy: An Evidence-Based Approach, Sixth Edition. Edited by John T. Queenan, Catherine Y. Spong,
Charles J. Lockwood.
© 2012 John Wiley & Sons, Ltd. Published 2012 by John Wiley & Sons, Ltd.

4


Chapter 2 Maternal Nutrition
225

Fetal weight gain (g/week)

200

175

150

125
100

75
Singleton
50

25

29

Twins

33

37

41

Weeks gestation
Figure 2.1 Fetal weight gain in grams among singleton and twin
pregnancies.

4000

Fetal/Birthweight (g)

3500
3000
2500
2000
1500
1000
500
25

Ultrasound EFW (g)

29

33

Birthweight (g)
37

41

Weeks gestation
Figure 2.2 Fetal growth curves by method of estimation:
ultrasound or birthweight. EFW, mean estimated fetal weight.

comparison resource in an individual pregnancy. Given
the rapidly increasing incidence of twin and triplet pregnancies through assisted reproductive technologies, there
is a need to resolve this controversy.
Fetal growth curves are based on two sources for fetal
weight: birthweight [8] and estimated fetal weight based
on ultrasound findings (Fig. 2.2). Birthweight sources
encompass the pathophysiology that led to the preterm
birth. Twenty to 25% of preterm births occur as the result
of medical intervention in the setting of maternal pathology such as preeclampsia. In these cases, the effects of
maternal nutrition (BMI) are muted significantly. Fetal
growth curves derived by ultrasonographic estimation of

5

fetal weight reflect a more physiologic environment.
Unfortunately, the comparison of coincidental estimated
fetal weight and birthweight reveals a relatively large

error; 20% of estimated fetal weights will differ from the
actual weight by one standard deviation or more, 400–
600 g at term.
The velocity of fetal growth is more instructive regarding the mechanisms of fetal growth restriction [9]. Length
peaks earlier than weight, as the fetus stores fat and
hepatic glycogen (increasing abdominal circumference) in
the third trimester. When an insult occurs early, such as
with alcohol exposure, severe starvation, smoking, perinatal infection (cytomegalovirus infection or toxoplasmosis), chromosomal or developmental disorders, or chronic
vasculopathies (diabetes, autoimmune disease, chronic
hypertension), the result is a symmetrically growthrestricted fetus with similarly reduced growth of its
length, head circumference, and abdominal circumference. This pattern is often referred to as dysgenic growth
restriction and these infants often have persistent handicaps (mental retardation, infectious retinopathy, i.e. toxoplasmosis infection) [10].
When the insult occurs after the peak in the velocity of
length growth, the result is a disproportionately reduced
body-length ratio (ponderal index), with a larger head
circumference relative to abdominal circumference. This
pattern is often referred to as nutritional growth restriction
and usually is the result of developing vasculopathy (placental thrombosis/infarcts, preeclampsia) or a reduction
of the absorptive capacity of the placenta (postdate pregnancy). The obstetrician uses the ultrasonographically
defined ratio of head circumference to abdominal circumference as it compares to established nomograms. The
pediatrician uses the ponderal index (birthweight [kg]/
height [cm3]) in a similar fashion. Abnormality is defined
statistically (i.e. two standard deviations from the mean)
rather than as it relates to adverse clinical outcomes.
While the risk of adverse outcomes may be considerably
higher, most small for gestational age babies (less than the
10th percentile) who are delivered at term have few significant problems. Likewise, the vast majority of term
infants whose size is more than the 90th percentile at birth
have few perinatal challenges.
Fetal growth requires the transfer of nutriments as

building blocks and the transfer of enough oxygen to fuel
the machinery to build the fetus. Maternal nutritional and
cardiac physiology is changed through placental hormones (i.e. human placental lactogen) to accommodate
the fetal-placental needs. The central role of the placenta
in the production of pregnancy hormones, the transfer of
nutriments, and fetal respiration is demonstrated by the
fact that 20% of the oxygen supplied to the fetus is
diverted to the metabolic activities of the placenta and
placental oxygen consumption at term is about 25%
higher than the amount consumed by the fetus as a whole.