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Contents

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Contributors

Richard M.K. Adanu MB ChB, FWACS, MPH

Senior Lecturer, Consultant Obstetrician & Gynecologist

University of Ghana Medical School

Accra, Ghana

Ray Bahado-Singh MD

Department of Obstetrics and Gynecology

Wayne State University and Hutzel Women’s Center

Detroit, MI, USA

Antonio Barbera MD

Assitant Professor, Obstetrics and Gynecology

Denver Health Medical Center

University of Colorado Denver School of Medicine

Denver, CO, USA

Vincenzo Berghella MD

Professor of Obstetrics and Gynecology

Director of Maternal-Fetal Medicine

Thomas Jefferson University

Philadelphia, PA, USA

Richard L. Berkowitz MD

Department of Obstetrics and Gynecology

Columbia University Medical Center

New York, NY, USA

Robert L. Brent MD, PhD, DSc (Hon.)

Distinguished Professor of Pediatrics, Radiology, and Pathology

Louis and Bess Stein Professor of Pediatrics

Thomas Jefferson University and

Alfred I. duPont Hospital for Children

Wilmington, DE, USA

Catalin S. Buhimschi MD

Director Perinatal Research

Yale University School of Medicine

New Haven, CT, USA

Brian M. Casey MD

Professor, University of Texas Southwestern Medical Center

Dallas, TX, USA

Patrick M. Catalano MD

Professor and Chair, Reproductive Biology

Case Western Reserve University

Metrohealth Medical Center

Cleveland, OH, USA

Nancy Chescheir MD

Clinical Professor, University of North Carolina

Department of Obstetrics & Gynecology

Chapel Hill, NC, USA

James F. Clapp MD

Emeritus Professor Reproductive Biology

Department of Reproductive Biology and the Schwartz Center for Metabolism and Nutrition

Case Western Reserve University at MetroHealth Medical Center

Cleveland, Ohio, USA

Joshua A. Copel MD

Professor of Obstetrics, Gynecology and Reproductive Sciences, and Professor of Pediatrics

Yale University School of Medicine

New Haven, CT, USA

F. Gary Cunningham MD

Professor, Department of Obstetrics and Gynecology

University of Texas Southwestern Medical Center

Dallas, TX, USA

Mary E. D’Alton MD

Chair, Department of Obstetrics and Gynecology

Columbia University College of Physicians and Surgeons

New York Presbyterian Hospital

New York, NY, USA

Mara J. Dinsmoor MD, MPH

Clinical Professor, Department of Obstetrics and Gynecology

Pritzker School of Medicine

University of Chicago, Chicago, IL and

North Shore University Health System

Evanston, IL, USA

Patrick Duff MD

Professor and Program Director, Department of Obstetrics and Gynecology

University of Florida College of Medicine

Gainesville, FL, USA

Gary S. Eglinton MD

Chairman, Department of Obstetrics and Gynecology, New York Hospital Queens;

Associate Professor of Obstetrics and Gynecology

Weill Medical College of Cornell University

Flushing, NY, USA

Mark I. Evans MD

Director, Comprehensive Genetics PLLC

Professor of Obstetrics and Gynecology

Mount Sinai School of Medicine

New York, NY, USA

Roger K. Freeman MD

Professor of Gynecology

University of California Irvine

Long Beach, CA, USA

Karin M. Fuchs MD

Department of Obstetrics and Gynecology

Columbia University College of Physicians and Surgeons

New York Presbyterian Hospital

New York, NY, USA

Steven G. Gabbe MD

Department of Obstetrics and Gynecology

The Ohio State University College of Medicine

Columbus, OH, USA

Sreedhar Gaddipati MD

Assistant Clinical Professor, Maternal Fetal Medicine, Department of Obstetrics and Gynecology

Columbia University Medical Center

New York, NY, USA

Henry L. Galan MD

Professor of Obstetrics & Gynecology

Chief of Maternal-Fetal Medicine

University of Colorado at Denver Health Sciences Center

Aurora, CO, USA

Stanley A. Gall MD

Professor of Obstetrics and Gynecology

University of Louisville

Louisville, KY, USA

Robert Gherman MD

Head, Division of Maternal Fetal Medicine

Prince George’s Hospital Center

Cheverly, MD, USA

Alessandro Ghidini MD

Director, Perinatal Diagnostic Center;

Professor and Executive Director

Department of Obstetrics and Gynecology

INOVA Alexandria Hospital

Alexandria, VA, USA

Martin L. Gimovsky MD

Professor of Obstetrics and Gynecology

Mount Sinai School of Medicine, New York

Vice-Chair and Program Director

Department of Obstetrics and Gynecology

Newark Beth Israel Medical Center

Newark, NJ, USA

Gary D.V. Hankins MD

Jennie Sealy Smith Distinguished Professor

and Chairman, Department of Obstetrics & Gynecology

University of Texas Medical Branch at Galveston

Galveston, Texas, USA

Wendy F. Hansen MD

Director, Maternal Fetal Medicine

Associate Professor, Department of Obstetrics and Gynecology

University of Kentucky

Lexington, KY, USA

James W. Hanson MD

Director, Center for Developmental Biology and Perinatal Medicine

National Institute of Child Health and Human Development

Bethesda, MD, USA

Rosemary D. Higgins MD

Program Scientist for the Neonatal Research Network, Pregnancy and Perinatology Branch

Center for Developmental Biology and Perinatal Medicine

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Bethesda, MD, USA

Fred M. Howard MS, MD

Professor and Associate Chair;

Director of Gynecologic Specialties

University of Rochester School of Medicine and Dentistry

Rochester, NY, USA

Jeffrey R. Johnson MD

Assistant Professor, Dartmouth Hitchcock Medical Center

Manchester, NH, USA

Charles S. Kleinman MD

Professor of Pediatrics

Columbia University College of Physicians & Surgeons

New York, NY, USA

Neil K. Kochenour MD

Professor Emeritus, Department of Obstetrics & Gynecology

University of Utah

Salt Lake City

UT, USA

Mark B. Landon MD

Professor and Interim Chair, Department of Obstetrics and Gynecology

The Ohio State University College of Medicine

Columbus, OH, USA

Anna Locatelli MD

Assistant Professor, Department of Obstetrics & Gynecology

University of Milano-Bicocca

Italy

Charles J. Lockwood MD, MHCM

The Anita O’Keeffe Young Professor of Women’s Health and

Chair, Department of Obstetrics, Gynecology and Reproductive Sciences

Yale University School of Medicine

Chief of Obstetrics & Gynecology

Yale-New Haven Hospital

New Haven, CT, USA

George A. Macones MD, MSCE

Professor and Chairman, Department of Obstetrics & Gynecology

Washington University School of Medicine

St Louis, MO, USA

Maureen P. Malee PhD, MD

Medical Director, Maternal-Fetal Medicine

Bryan LGH Medical Center

Lincoln, NE, USA

Fergal D. Malone MD, FACOG, FRCPI, FRCOG

Professor and Chairman, Department of Obstetrics and Gynecology

Royal College of Surgeons in Ireland and

The Rotunda Hospital, Dublin, Ireland

Brian M. Mercer MD, FACOG, FRCSG

Professor Reproductive Biology

Case Western University

Director, Obstetrics and Maternal-Fetal Medicine

MetroHealth Medical Center

Cleveland, OH, USA

Howard Mikoff MD

Chair, Obstetrics and Gynecology, Maimonides Medical Center

Distinguished Professor State University of New York (SUNY)

Brooklyn, NY, USA

Kenneth J. Moise, Jr. MD

Professor of Obstetrics and Gynecology

& Professor of Surgery

Baylor College of Medicine

Houston, TX, USA

Thomas R. Moore MD

Department of Reproductive Medicine

University of California at San Diego

CA, USA

John C. Morrison MD

Professor of Obstetrics, Gynecology and Pediatrics

University of Mississippi Medical Center

Jackson, MS, USA

Michael P. Nageotte MD

Associate Chief Medical Officer, Memorial Care Center for Women

Miller Children’s Hospital, Long Beach, CA

Professor of Obstetrics and Gynecology

University of California

Irvine, CA, USA

Gayle Olson MD

Associate Professor, University of Texas Medical Branch, Galveston, TX, USA

John Owen MD, MSPH

Bruce A. Harris, Jr. Endowed Professor

Department of Obstetrics and Gynecology

University of Alabama at Birmingham

Birmingham, AL, USA

Yinka Oyelese MD

UMDNJ–Robert Wood Johnson Medical School

Jersey Shore University Medical Center

Neptune, NJ, USA

Marc R. Parrish MD

Department of Obstetrics, Gynecology and Pediatrics

University of Mississippi Medical Center

Department of Obstetrics and Gynecology

Jackson, MS, USA

Alan M. Peaceman MD

Professor and Chief, Division of Maternal-Fetal Medicine

Northwestern University Feinberg School of Medicine

Chicago, IL, USA

Lawrence D. Platt MD

Professor Obstetrics and Gynecology

David Geffen School of Medicine at UCLA

Director, Center for Fetal Medicine and Women’s Ultrasound

Los Angeles, CA, USA

Manuel Porto MD

Department of Obstetrics and Gynecology

University of California and Irvine Medical Center

CA, USA

Susan M. Ramin MD

Professor and Chair, Department of Obstetrics, Gynecology and Reproductive Sciences

The University of Texas Medical School at Houston, Houston, TX, USA

Robert Resnik MD

Professor Emeritus of Reproductive Medicine

UCSD School of Medicine

Solana Beach, CA, USA

Jean Rex MD

Instructor, Department of Pediatrics

Washington University School of Medicine

St. Louis, MO, USA

Adam A. Rosenberg MD

Professor of Pediatrics, University of Colorado Denver School of Medicine

and The Children’s Hospital

Aurora, CO, USA

Dwight J. Rouse MD

Attending Physician, Maternal-Fetal Medicine Division

Women & Infants Hospital of Rhode Island

Professor of Obstetrics and Gynecology

Warren Alpert School of Medicine at Brown University

Providence, RI, USA

George Saade MD

Professor, Department of Obstetrics and Gynecology

Chief of Obstetrics and Maternal-Fetal Medicine

Director, Perinatal Research Division

The University of Texas Medical Branch

Galveston, TX, USA

Michael Schatz MD, MS

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 Medical Center

Salt Lake City, UT, USA

Jeanne S. Sheffield MD

Director, Maternal-Fetal Medicine Fellowship

University of Texas Southwestern Medical Center

Dallas, TX, USA

Baha M. Sibai MD

Professor and Director of Clinical Perinatal Research

University of Cincinnati College of Medicine

Cincinnati, OH, USA

Robert M. Silver MD

Professor of Obstetrics & Gynecology

Chair of Maternal-Fetal Medicine

University of Utah Health Sciences Center

Salt Lake City, UT, USA

Lynn L. Simpson MD

Associate Professor of Obstetrics and Gynecology

Columbia University Medical Center

New York, NY, USA

Sindhu K. Srinivas MD

Department of Obstetrics & Gynecology

Washington University School of Medicine

St Louis, MO, USA

Jorge E. Tolosa MD MSCE

Associate Professor of Obstetrics and Gynecology

Oregon Health and Science University

Portland, OR, USA

Carl P. Weiner MD, MBA

K.E. Krantz Professor & Chair, Obstetrics and Gynecology

Professor, Molecular & Integrative Physiology

University of Kansas School of Medicine

Kansas City, KS, USA

George D. Wendel MD

Professor, Department of Obstetrics & Gynecology

University of Texas Southwestern Medical Center

Dallas TX, USA

Katharine D. Wenstrom MD

Professor, Obstetrics & Gynecology

Director, Divison of Maternal-Fetal Medicine

Women & Infants’ Hospital of Rhode Island

Brown Alpert Medical School

Providence, RI, USA

Erika Werner MD

Instructor, Yale University School of Medicine

Department of Obstetrics, Gynecology and Reproductive Sciences

New Haven, CT, USA

Marsha Wheeler MD

Department of Obstetrics & Gynecology

University of Colorado Health Sciences Center

Denver, CO, USA

Deborah A. Wing MD

Professor and Director, Division of Maternal-Fetal Medicine

Department of Obstetrics and Gynecology

University of California, Irvine, CA, USA

Jerome Yankowitz MD

University of Iowa Hospitals and Clinics

Department of Obstetrics and Gynecology

Division of Maternal-Fetal Medicine and Fetal Diagnosis and Treatment Unit

Iowa City, IA, USA

Preface

Today’s pressures of managed care, rapidly changing technology, and medically sophisticated patients who always expect good outcomes, make it essential to have correct information at hand. The nature and training of physicians instills the constant drive to do the right thing. Therefore, it is necessary to have appropriate, current, and practical information available as protocols to make good decisions. Why use protocols? Having a protocol or guideline organizes essential clinical material in a systematic, logical order and avoids omissions in patient care. It is to that end that we have created Protocols for High-Risk Pregnancies

Evaluating all pregnancies for risk factors is an effective way of identifying patients who need additional care. Some patients have factors present from the outset of pregnancy such as diabetes or history of prematurity that place them at increased risk. Others start with a normal pregnancy but subsequently develop risk factors such as pre-eclampsia or premature rupture of the membranes. This may develop quickly and therefore, it is important to have a protocol for management. Of course, care must be taken to be sure that the term “high risk” does not cause alarm or anxiety for your patient.

Since the 4th edition was published, advances in medical knowledge and technology have dictated changes in management. Thus, in this 5th edition all original protocols have been updated. New ones have been added to cover such advances as nuances in Doppler and sonography, as well as changes in the approach to prematurity, diabetes, hypertension, prophylactic immunizations, among others. We have also included protocols in areas of critical importance to the developing world, such as malaria, tuberculosis, and chronic anemia. For each protocol we have invited the physicians whom we believe to be the outstanding authorities on the topics. They start with a brief introduction and pathophysiology and write the protocols as if they were working up their patient and following her through the various stages of management. We require that each protocol is evidence-based to the extent that is possible. In areas where no evidence exists we have asked the experts to make recommendations. There is some intentional overlap in protocols, as medicine is an art as well as a science. All protocols represent the individual thoughts and opinions of these experts.

We realize that the future will bring new medical advances and that new editions of Protocols will need to be published in a timely fashion, thus we welcome your comments for future incorporation. We thank Martin Sugden, Lewis O’Sullivan, and the excellent editorial and production staff at Wiley-Blackwell for their professional skills.

This edition, as with the others, was created to be practical, cost effective and clearly presented: a format that is easy to carry with you on rounds and consultations. We have designed this book to help you in your practice. Make it you own!

John T. Queenan

John C. Hobbins

Catherine Y. Spong

PART 1

Hazards to Pregnancy

PART 2

Antenatal Testing

PART 3

Special Procedures

PART 4

Maternal Disease

PART 5

Obstetric Problems

PART 6

Labor and Delivery

PART 7

Clinical Reference Tables

PROTOCOL 1

Developmental Toxicology and Teratology

James W. Hanson

Center for Developmental Biology and Perinatal Medicine, National Institute of Child Health and Human Development, Bethesda, MD, USA

Exposures to potentially hazardous agents during pregnancy are common. Such agents include drugs (both therapeutic agents and abused substances), environmental chemicals, infectious agents, physical agents (radiation, heat and mechanical factors) and maternal health conditions. Many of these exposures are not readily avoidable, as pregnancy is often not planned or recognized for an extended period after conception, or because there is a continuing need for maternal treatment for health conditions (e.g. epilepsy, infection, asthma, chronic cardiovascular disorders). Exposure to various agents in the home or workplace, or as a consequence of maternal lifestyles and self-medication, is almost universal, and pre-conception planning only rarely provides an opportunity to identify exposures of concern. As a consequence, questions about the significance of such an exposure, whether stated or not, are often a source of concern to pregnant women or their care provider.

Not all developmental toxicants need result in permanent adverse outcomes for the fetus or newborn. Some agents may have at least partially reversible or transient effects if recognized early, such as fetal growth restriction from tobacco smoking. It is important to recognize that structural birth defects resulting from exposure to human teratogens are not the only manifestations of exposure to developmental toxicants. Fetal or postnatal growth disorders, functional developmental disorders including cognitive and behavioral deficits, abnormalities of placental function putting the fetus at increased risk, and death (embryonic, fetal, perinatal or postnatal) are all among potential manifestations of exposures. Furthermore, some adverse outcomes may not become apparent until many years later (e.g. reproductive consequences and cancer from exposure to diethylstilbestrol).

Pathogenetic factors in evaluation of risk from exposure to teratogens and other developmental toxicants

When evaluating the likely significance of exposure to potentially hazardous agents, it is essential to consider the following issues in the context of the known or likely pathogenetic mechanisms for adverse fetal outcomes.

Dose and duration of exposure

Timing

Pathogenetic mechanism(s)

Host susceptibility

Exposures to human teratogens and developmental toxicants commonly are manifest across a wide spectrum of effects. At the severe end, a clinically recognizable pattern of effects (a ‘syndrome’) may be identified. However, variability of manifestations within the scope of specific adverse outcomes comprising a syndrome is the rule. Among the population of exposed and affected infants, less severe and less pervasive manifestations are often more frequent. Thus infants exposed to alcohol prenatally may have outcomes ranging from mild effects on cognition and behavior from smaller amounts consumed on a few occasions, to the full-blown fetal alcohol syndrome.

presents a list of agents, including therapeutic agents, for which substantial human data is available establishing a risk for humans.

Important human teratogens

Agent Dose Susceptible period
Medications
Acitretin Usual therapeutic 1st trimester
Aminopterin Usual therapeutic 1st trimester
Amodarone Usual therapeutic 12 weeks–term
Androgens (including danazol) Usual therapeutic Unknown
Angiotensin II receptor inhibitors (candesartan, eprosartan, irbesartan, losartan, olmesartan, tasosartan, telmisartan, valsartan) Usual therapeutic 2nd and 3rd trimesters
Angiotensin-converting enzyme inhibitors (benazepril, captopril, cilazapril, enalapril, enalaprilat, fosinopril, lisinopril, moexipril, perindopril, quinapril, ramipril, trandolapril) Usual therapeutic 2nd and 3rd trimesters
Carbamazepine Usual therapeutic 1st trimester
Clonazepam Usual therapeutic 1st trimester
Coumarin anticoagulants Usual therapeutic 1st trimester
Cyclophosphamide Usual therapeutic 1st trimester
Diethylstilbestrol 1.5–150 mg/d 1st and 2nd trimesters
Ethosuximide Usual therapeutic 1st trimester
Etretinate Usual therapeutic 1st trimester
Fluconazole Chronic, parenteral, 400–800 mg/d 1st trimester
Indomethacin Usual therapeutic 2nd and 3rd trimesters
Isotretinoin Usual therapeutic (oral) 1st trimester
Lithium Usual therapeutic 1st trimester
Methimazole Usual therapeutic 1st trimester (malformations) 12 weeks–term (hypothyroidism, goitre)
Methotrexate ≥12.5 mg/wk 1st trimester
Methylene blue Intra-amniotic injection 2nd trimester
Misoprostol Usual therapeutic 1st and 2nd trimesters
Penicillamine Usual therapeutic Unknown
Phenobarbital Usual therapeutic 1st trimester
Phenytoin Usual therapeutic 1st trimester
Primidone Usual therapeutic 1st trimester
Quinine ≥2g/d Entire pregnancy
Tetracyclines (chlortetracycline, demeclocycline, doxycycline, methacycline, minocycline, oxytetracycline, tetracycline) Usual therapeutic 1st trimester
Thalidomide Usual therapeutic 41–54 days
Trimethadione, paramethadione Usual therapeutic 1st trimester
Trimethoprim Usual therapeutic 1st trimester
Valproic acid Usual therapeutic 1st trimester
Agents of abuse
Alcohol Abuse Unknown
Cigarette smoking Risks greater with heavy smoking Entire pregnancy
Cocaine Abuse Entire pregnancy
Toluene Abuse (inhalation) Unknown
Environmental exposures
Methyl mercury Associated with maternal methylmercury concentration ≥0.1 μg/mL Unknown
PCBs Toxic exposure Unknown
Infections
Varicella Primary infection (much smaller risk with recurrent infection) Entire pregnancy (but higher in 2nd trimester)
Parvovirus B19 Primary infection Entire pregnancy (but higher in 2nd trimester)
Cytomegalovirus Primary infection (much smaller risk with recurrent infection) Entire pregnancy (but much higher in first half)
Syphilis 2nd and 3rd trimester
HIV 3rd trimester, especially during labor
LMCV Unknown
Toxoplasmosis Primary infection Entire pregnancy
Rubella Primary infection (rarely secondary infection) 1st and 2nd trimester (but much higher in 1st trimester)
Maternal illnesses and conditions
Maternal diabetes mellitus 1st trimester
Maternal autoantibodies (Rh, SLE, platelet) 2nd and 3rd trimester
Maternal endocrinopathies Unknown
Maternal phenylketonuria Untreated Unknown
Maternal obesity Risk greater with severe obesity than with mild obesity 1st trimester
Physical agents
Chorionic villus sampling <10 weeks
Early amniocentesis <14 weeks
Ionizing radiation >10–20 cGy Entire pregnancy (but highest in 1st trimester)
Radioactive iodine Therapeutic 12 weeks–term

The list continues to grow as new research reveals more details about the magnitude and nature of risks associated with many of these and other newly recognized agents. Thus it is important to check the current literature before counseling an exposed family. A variety of information resources, ranging from Internet-based computerized databases and commercially available information resources, to standard reference resources for further reading are listed in .

Information resources: computerized databases

Database Contact
REPROTOX (202) 687-5137
TERIS (206) 543-2465

For the clinician whose practice only rarely encounters these questions, or for those who encounter a question for which current data is limited or difficult to access, consultation with a specialist may be an appropriate option. Many states or academic centers have established Teratogen Information Services to help meet this need. presents a current listing of these resources.

Teratogen information services in North America

For information regarding the Teratology Information Service in your area, contact the Organization of Teratology Information Services (OTIS) at: (866) 626-6847 or .

Service Telephone number
Alabama Birth Defects Surveillance (800) 423-8324 or (334) 460-7691
Arizona Teratogen Information Program (888) 285-3410 or (520) 626-3410 (in Tucson)
Arkansas Teratogen Information Service (800) 358-7229 or (501) 296-1700
CTIS Pregnancy Risk Information (800) 532-3749 (CA only)
IMAGE: Info-Medicaments en Allaitement et Grossesse, Province of Quebec, Canada (514) 345-2333
Motherisk Program, Ontario, Canada (416) 813-6780
Connecticut Pregnancy Exposure Information Service (800) 325-5391 (CT only) or (860) 679-8850
Reproductive Toxicology Center, District of Columbia, MD (301) 620-8690 or (301) 657-5984
Illinois Teratogen Information Service (800) 252-4847 (IL only) or (312) 981-4354
Indiana Teratogen Information Service (317) 274-1071
Massachusetts Teratogen Information Service (MaTIS) (800) 322-5014 (MA only) or (781) 466-8474
Genetics & Teratology Unit, Pediatric Service, Massachusetts General Hospital (617) 726-1742
Missouri Teratogen Information Service (MOTIS) (800) 645-6164 or (573) 884-1345
Nebraska Teratogen Project (402) 559-5071
Pregnancy Healthline, Southern New Jersey Perinatal Cooperative (888) 722-2903 (NJ) or (856) 665-6000
Pregnancy Risk Network (800) 724-2454 (then press 1) (NY only) or (716) 882-6791 (then press 1)
PEDECS, Rochester, NY (716) 275-3638
NCTIS Pregnancy Exposure Riskline 1-800-532-6302 (NC)
North Dakota Teratogen Information Service (701) 777-4277
Texas Teratogen Information Service (800) 733-4727 or (940) 565-3892
Pregnancy RiskLine, Salt Lake City, UT (801) 328-2229 or (800) 822-2229
Pregnancy Risk Information Service 800-531-9800 (VT only) and 800-932-4609
CARE Northwest, Seattle, WA (888) 616-8484
West Virginia University Hospitals (304) 293-1572
Wisconsin Teratogen Information Service (800) 442-6692
Workplace Hazards to Reproductive Health, Madison, WI (608) 266-2074

Suggested readings

Bennett PN. Drugs and Human Lactation. Amsterdam: Elsevier, 1988.

Briggs GG, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation, 6th edn. Baltimore: Williams & Wilkins, 2001.

Friedman JM, Hanson JW. Protocol 39. Clinical teratology. In: Rimoin DL, Connnor JM, Pyeritz R, Korf, B (eds) Emory & Rimoin’s Principles and Practice of Medical Genetics, 4th edn. London: Churchill Livingstone, 2002.

Paul M: Occupational and Environmental Reproductive Hazards. Baltimore: Williams & Wilkins, 1993.

Schardein JL. Chemically Induced Birth Defects. 3rd edn. New York: Marcel Dekker, 2001.

Scialli AR. A Clinical Guide to Reproductive and Developmental Toxicology. Boca Raton: CRC Press, 1992.

Shepard TH. Catalog of Teratogenic Agents, 10th edn. Baltimore: Johns Hopkins, 2001.