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Acquisitions Editor: Matt Hauber Product Development Editor: Andrea Vosburgh Editorial Coordinator: Katherine Burland Marketing Manager: Michael McMahon Production Project Manager: Bridgett Dougherty Design Coordinator: Stephen Druding Manufacturing Coordinator: Margie Orzech Prepress Vendor: S4Carlisle Publishing Services Seventh edition Copyright © 2018 Wolters Kluwer. Copyright © 2013 Lippincott Williams & Wilkins, a Wolters Kluwer business. All rights reserved. This book is protected by copyright. No part of this book may be reproduced or transmitted in any form or by any means, including as photocopies or scanned-in or other electronic copies, or utilized by any information storage and retrieval system without written permission from the copyright owner, except for brief quotations embodied in critical articles and reviews. Materials appearing in this book prepared by individuals as part of their official duties as U.S. government employees are not covered by the abovementioned copyright. To request permission, please contact Wolters Kluwer at Two Commerce Square, 2001 Market Street, Philadelphia, PA 19103, via email at permissions@lww.com, or via our website at lww.com (products and services). 987654321 Printed in China (or the United States of America) Library of Congress Cataloging-in-Publication Data Names: Callahan, Tamara L., author. | Caughey, Aaron B., author. Title: Blueprints obstetrics & gynecology / Tamara L. Callahan, Aaron B. Caughey. Other titles: Blueprints obstetrics and gynecology | Obstetrics and gynecology | Blueprints. Description: Seventh edition. | Philadelphia : Wolters Kluwer Health, [2018] | Series: Blueprints | Includes bibliographical references and index. Identifiers: LCCN 2017016341 | e-ISBN 9781496349514 Subjects: | MESH: Pregnancy Complications | Genital Diseases, Female | Examination Questions Classification: LCC RG112 | NLM WQ 18.2 | DDC 618.0076—dc23 LC record available at https://lccn.loc.gov/2017016341 This work is provided “as is,” and the publisher disclaims any and all warranties, express or implied, including any warranties as to accuracy, comprehensiveness, or currency of the

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Contributing Editors Allison Allen, MD Fellow, Maternal-Fetal Medicine Department of Obstetrics and Gynecology Oregon Health & Science University Portland, Oregon Alison Barlow, WHNP Assistant Professor Department of Obstetrics and Gynecology Division of Midwifery and Advanced Practice Nursing Vanderbilt University Medical Center Nashville, Tennessee Howard Curlin, MD Assistant Professor Department of Obstetrics and Gynecology Division of Gynecologic Specialties Vanderbilt University Medical Center Nashville, Tennessee Jeff Davis, DO Assistant Professor Department of Obstetrics and Gynecology Division of General Obstetrics and Gynecology Vanderbilt University School of Medicine Nashville, Tennessee Jessica Heft, MD Fellow, Female Pelvic Medicine and Reproductive Surgery Department of Obstetrics and Gynecology Division of Female Pelvic Medicine and Reconstructive Surgery Vanderbilt University School of Medicine Nashville, Tennessee William J. Kellett, DO Associate Professor Department of Obstetrics and Gynecology

Division of General Obstetrics and Gynecology Vanderbilt University Medical Center Nashville, Tennessee Tamara Keown, MSN, WHNP-BC Assistant Professor Department of Obstetrics and Gynecology Division of Midwifery and Advanced Practice Nursing Vanderbilt University Medical Center Nashville, Tennessee Dineo Khabele, MD, FACOG, FACS Director, Division of Gynecologic Oncology The University of Kansas Cancer Center Professor, Obstetrics and Gynecology The University of Kansas School of Medicine Kansas City, Kansas Lucy Koroma, MSN, WHNP-BC Assistant Professor Department of Gynecology and Obstetrics Division of Minimally Invasive Gynecology Johns Hopkins University School of Medicine Baltimore, Maryland Erica E. Marsh, MD, MSCI Associate Professor and Chief Division Director Department of Obstetrics and Gynecology Division of Reproductive Endocrinology and Infertility University of Michigan Medical School Ann Arbor, Michigan Christina Megli, MD, PhD Fellow, Maternal-Fetal Medicine Department of Obstetrics and Gynecology University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Melinda New, MD Associate Professor and Vice Chair of Education Department of Obstetrics and Gynecology Division of Gynecologic Specialties Vanderbilt University Medical Center Nashville, Tennessee

Rachel Pilliod, MD Fellow, Maternal-Fetal Medicine Department of Obstetrics and Gynecology Oregon Health & Science University Portland, Oregon Jessica Pippen, MD Fellow, Maternal-Fetal Medicine Department of Obstetrics and Gynecology Ohio State University College of Medicine Columbus Ohio Erica Robinson, MD, FRCSC Assistant Professor Department of Obstetrics and Gynecology Division of Gynecology Wake Forest School of Medicine Winston-Salem, North Carolina Bethany Sabol, MD Fellow, Maternal-Fetal Medicine Department of Obstetrics and Gynecology Washington University St. Louis, Missouri Stacey Scheib, MD, FACOG Assistant Professor Director, Multidisciplinary Fibroid Center Department of Gynecology and Obstetrics Division of Minimally Invasive Gynecology Johns Hopkins University School of Medicine Baltimore, Maryland Katherine A. Smith, MD Fellow, Minimally Invasive Gynecologic Surgery Department of Obstetrics and Gynecology Mayo Clinic Jacksonville, Florida May Thomassee, MD Assistant Professor Department of Obstetrics and Gynecology Division of Gynecology University Hospitals and Clinics of Lafayette

Louisiana State University School of Medicine Lafayette, Louisiana Laurie Tompkins, WHNP Assistant Professor Department of Obstetrics and Gynecology Division of Midwifery and Advanced Practice Nursing Vanderbilt University Medical Center Nashville, Tennessee Ashley M. Van Wormer, MD Resident Department of Obstetrics and Gynecology Louisiana State University School of Medicine New Orleans, Louisiana Jessica L. Young, MD Assistant Professor Department of Obstetrics and Gynecology Division of General Obstetrics and Gynecology Vanderbilt University Medical Center Nashville, Tennessee

Contributing Editors from Previous Editions Marisa Adelman, MD Assistant Professor Department of Obstetrics and Gynecology Division of General Obstetrics and Gynecology University of Utah Salt Lake City, Utah Jeff Andrews, MD, FRCSC Executive Editor-in-Chief, Journal of Lower Genital Tract Disease Worldwide Medical Director of Women’s Health & Cancer BD Life Sciences BD Diagnostic Systems Sparks, Maryland Lisa Bayer, MD Assistant Professor, Family Planning Department of Obstetrics and Gynecology Oregon Health & Science University Portland, Oregon Stephanie Beall, MD, PhD Department of Obstetrics and Gynecology Division of Reproductive Endocrinology and Infertility Shady Grove Fertility Columbia, Maryland Daniel H. Biller, MD, MMHC Associate Professor Department of Obstetrics and Gynecology Division of Urogynecology and Female Pelvic Medicine Vanderbilt University Medical Center Nashville, Tennessee Lynne Black Research Coordinator Department of Obstetrics and Gynecology

Vanderbilt University Medical Center Nashville, Tennessee Nicole S. Carroll, MD Department of Obstetrics and Gynecology Wilmington Health Wilmington, North Carolina Annette Chen, MD Department of Obstetrics and Gynecology Division of Gynecologic Oncology Kaiser Permanente Oakland, California Yvonne W. Cheng, MD, PhD Director Maternal-Fetal Medicine California Pacific Medical Center San Francisco, California Bruce B. Feinberg, MD Assistant Professor Department of Obstetrics and Gynecology Division of Maternal-Fetal Medicine Columbia University Medical Center New York, New York Karen P. Gold, MD, MSCI Interim Chair and Residency Program Director Department of Obstetrics and Gynecology Division of Urogynecology-Female Pelvic Medicine and Reconstructive Surgery University of Oklahoma-Tulsa Tulsa, Oklahoma Linda J. Heffner, MD, PhD Professor Department of Obstetrics and Gynecology Division of Maternal-Fetal Medicine Boston University School of Medicine Boston, Massachusetts Celeste O. Hemingway, MD, MHPE Assistant Professor and Residency Director Department of Obstetrics and Gynecology

Division of General Obstetrics and Gynecology Vanderbilt University Medical Center Nashville, Tennessee Nariman Heshmati, MD Department of Obstetrics and Gynecology The Everett Clinic Everett, Washington Beth Colvin Huff, MSN, NP Editorial Board, Journal of Lower Genital Tract Disease Previous Board of Directors American Society for Colposcopy and Cervical Pathology Sarah E. Little, MD, MPH Assistant Professor Maternal-Fetal Medicine Department of Obstetrics and Gynecology Brigham and Women’s Hospital Boston, Massachusetts Sara Newmann, MD, MPH Associate Clinical Professor Department of Obstetrics, Gynecology and Reproductive Sciences University of California San Francisco San Francisco General Hospital San Francisco, California Erin Rebele, MD Assistant Professor Department of Obstetrics and Gynecology Division of General Obstetrics and Gynecology Vanderbilt University Medical Center Nashville, Tennessee Brian L. Shaffer, MD Director Department of Obstetrics and Gynecology Fetal Diagnosis & Treatment Center Associate Professor Oregon Health & Science University Portland, Oregon Christopher M. Sizemore, DO

Assistant Professor Department of Obstetrics and Gynecology Division of General Obstetrics and Gynecology Vanderbilt University Medical Center Nashville, Tennessee Merielle M. Stephens, MD Assistant Professor Department of Obstetrics and Gynecology Tufts University School of Medicine Boston, Massachusetts Susan H. Tran, MD Associate Professor, Maternal-Fetal Medicine Department of Obstetrics and Gynecology Oregon Health & Science University Portland, Oregon Jing Wang Chiang, MD Chief Division of Gynecologic Oncology Department of Obstetrics and Gynecology Santa Clara Valley Medical Center Santa Clara, California Keenan Yanit, MD Assistant Professor Department of Obstetrics and Gynecology Oregon Health & Science University Portland, Oregon Amanda Yunker, DO Associate Professor Department of Obstetrics and Gynecology Division of Minimally Invasive Gynecology Vanderbilt University Medical Center Nashville, Tennessee

Preface

n 1997, the first five books in the Blueprints series were published as board review for medical students, interns, and residents who wanted high-yield, accurate clinical content for USMLE Steps 2 and 3. Twenty years later, we are proud to report that the original books and the entire Blueprints brand of review materials have far exceeded our expectations. The feedback we have received from our readers has been tremendously helpful and pivotal in deciding what direction the seventh edition of the core books would take. To ensure that the seventh edition of the series continues to provide the content and approach that made the original Blueprints a success, we have expanded the text to include the most up-to-date topics and evidence-based research and therapies. Information is provided on the latest changes in the management of cervical dysplasia and cervical cancer screening, abnormal uterine bleeding, hypertension in pregnancy, cervical insufficiency, prenatal diagnosis, and preterm labor. The newest and future techniques in contraception and sterilization and menopausal hormone therapies are covered, as are contemporary treatment options for uterine fibroids and ovarian cysts. The succinct and telegraphic use of tables and figures was highly acclaimed by our readers, so we have redoubled our efforts to expand their usefulness by adding updated and improved artwork, including the section of color plates. In each case, we have tried to include only the most helpful and clear tables and figures to maximize the reader’s ability to understand and remember the material. We have likewise updated our bibliography to include evidence-based articles as well as references to classic articles and textbooks in both obstetrics and gynecology. These references are now provided in electronic format. It was also suggested that the review questions should reflect the current format of the boards. We are particularly proud to include new and revised board-format questions in this edition with full explanations of both correct and incorrect options provided in the answers. In particular, we have added a section of case-based clinical vignettes questions at the end of each

chapter to facilitate review of the topics and practice for the boards. That said, we have also learned from our readers that Blueprints is more than just board review for USMLE Steps 2 and 3. Students use the books during their clerkship rotations, sub-internships, and as a quick refresher while rotating on various services in early residency. Residents studying for USMLE Step 3 often use the books for reviewing areas outside their specialty. Students in physician assistant, nurse practitioner, and osteopath programs use Blueprints as a companion to review materials in their own areas of expertise. When we first wrote the book, we had just completed medical school and started residency training. Thus, we hope this new edition brings both that original viewpoint and our clinical experience garnered over the past 20 years. However, you choose to use Blueprints, we hope that you find the books in the series informative and valuable to your own continuing education. Tamara L. Callahan, MD, MPP, FACOGAaron B. Caughey, MD, MPP, MPH, PhD

Acknowledgments

would like to express my sincere and deep appreciation to my coauthor, Dr. Caughey, and to the OB/Gyn residents and faculties at Harvard and Vanderbilt who gave liberally of their time and expertise to make this book something of which we can all be proud. Without the extraordinary talent and commitment of these physicians and providers, this project would not have been possible. This accomplishment is also credited in no small part to an incredible core of family and friends who lovingly and selflessly allow me to follow my passion for education and women’s health. And to my children, Connor and Jaela, being your mother has been an indescribable honor and an immeasurable joy—a blessing which I try to earn each and every day. I would also like to acknowledge my mentors, Dr. William F. Crowley, Jr., Dr. Janet Hall, Dr. Linda J. Heffner, Dr. Nancy E. Oriol, Dr. Robert Barbieri, and Dr. Nancy Chescheir whose strength, insight, leadership, and drive are exemplary of what it means to be an active contributor to academic medicine and women’s health. Lastly, I’d like to thank the many medical students and residents who have shared their input and enthusiasm with us along this exciting journey. Their support has been paramount to the success of this project and to our quest to make this book the very best it can be. It has truly been a privilege to be a small part of their never-ending learning experience. Tamara L. Callahan, MD, MPP, FACOG

would like to acknowledge and extend my thanks to everyone involved in the seventh edition of our book, most importantly my coauthor, Dr. Callahan, as well as all of those who contributed to the first six editions, particularly Dr. Chen, Dr. Feinberg, and Dr. Heffner, and the staff at both Blackwell and LWW. I would also like to thank my colleagues and mentors for the supportive environment in which I work, in particular, the residents and faculty in the department of Obstetrics and Gynecology at OHSU as well as my mentors, Dr. Washington, Dr. Norton, Dr. Ames, Dr. Repke, Dr. Blatman, Dr. Macones, Dr. Robinson, and Dr. Norwitz. I would also like to acknowledge the suggestions and critiques from medical students around the

country and particularly those at Harvard, UCSF, and OHSU who keep pushing us to produce better editions of this work. I would also like to thank my parents, Bill and Carol, for their support for all these years. To my wife, Susan, thank you for your patience and support during all of my projects. To my children, Aidan, Ashby, Amelie, and, Atticus—you are my inspiration to work harder every day, but also to take the time to enjoy this journey we are on. I love you all so very much. Aaron B. Caughey, MD, MPP, MPH, PhD

Contents Contributing Editors Contributing Editors from Previous Editions Preface Acknowledgments Abbreviations

PART I: OBSTETRICS 1

Pregnancy and Prenatal Care

Early Pregnancy Complications

Prenatal Screening, Diagnosis, and Treatment

Normal Labor and Delivery

Antepartum Hemorrhage

Complications of Labor and Delivery

Fetal Complications of Pregnancy

Hypertension and Pregnancy

Diabetes During Pregnancy

10 Infectious Diseases in Pregnancy 11 Other Medical Complications of Pregnancy 12 Postpartum Care and Complications

PART II: GYNECOLOGY 13 Benign Disorders of the Lower Genital Tract 14 Benign Disorders of the Upper Genital Tract 15 Endometriosis and Adenomyosis 16 Infections of the Lower Female Reproductive Tract 17 Infections of the Upper Female Reproductive Tract and Systemic Infections 18 Pelvic Organ Prolapse 19 Urinary Incontinence 20 Puberty, the Menstrual Cycle, and Menopause 21 Amenorrhea 22 Abnormalities of the Menstrual Cycle 23 Hirsutism and Virilism 24 Contraception and Sterilization 25 Termination of Pregnancy 26 Infertility and Assisted Reproductive Technologies 27 Vulvar and Vaginal Neoplasia 28 Cervical Neoplasia and Cervical Cancer 29 Endometrial Cancer 30 Ovarian and Fallopian Tube Tumors 31 Gestational Trophoblastic Disease 32 Benign Breast Disease and Breast Cancer

Questions Answers Index

Abbreviations 3β-HSD 5-FU 17α-OHP ACTH AD ADH AED AFE AFI AFLP AFP AGC AIDS ALT AMA AMH APA AR ARDS ART ASC ASC-H ASC-US AST AV AZT β-hCG BID BP

3β-hydroxysteroid dehydrogenase 5-fluorouracil 17α-hydroxyprogesterone adrenocorticotropic hormone autosomal dominant antidiuretic hormone antiepileptic drug amniotic fluid embolus amniotic fluid index acute fatty liver of pregnancy α-fetoprotein atypical glandular cells acquired immunodeficiency syndrome alanine transaminase advanced maternal age anti-Mullerian hormone antiphospholipid antibody autosomal recessive adult respiratory distress syndrome assisted reproductive technology atypical squamous cells atypical squamous cells—cannot exclude high-grade squamous intraepithelial lesion atypical squamous cells of undetermined significance aspartate transaminase arteriovenous analogs—zidovudine β-human chorionic gonadotropin twice a day blood pressure

BPP BUN BV CAH CBC CCCT CF CHF CIN CKC CMV CNS CPD CRS CSF CT CVA CVAT CVD CVS CXR DA D&C D&E DCIS DES DEXA DHEA DHEAS DHT DIC DMPA DTRs DUB DVT ECG

biophysical profile blood urea nitrogen bacterial vaginosis congenital adrenal hyperplasia complete blood count clomiphene citrate challenge test cystic fibrosis congestive heart failure cervical intraepithelial neoplasia cold-knife conization (biopsy) cytomegalovirus central nervous system cephalopelvic disproportion congenital rubella syndrome cerebrospinal fluid computed tomography (CAT scan) cerebrovascular accident costovertebral angle tenderness collagen vascular disorders chorionic villus sampling chest X-ray developmental age dilation and curettage dilation and evacuation ductal carcinoma in situ diethylstilbestrol dual-energy X-ray absorptiometry dehydroepiandrosterone dehydroepiandrosterone sulfate dihydrotestosterone disseminated intravascular coagulation depot medroxyprogesterone acetate (Depo-Provera) deep tendon reflexes dysfunctional uterine bleeding deep venous thrombosis electrocardiogram

EDC

estimated date of confinement

EDD EFW EIF ELISA EMB EPT ERT ESR ET FAS FH FHR FIGO FIRS FISH FNA FSE FSH FTA-ABS FTP G GA GBS GDM GFR GH GI GLT GnRH GTD GTT GU GUSM HAART

estimated date of delivery estimated fetal weight echogenic intracardiac focus enzyme-linked immunosorbent assay endometrial biopsy estrogen and progesterone therapy estrogen replacement therapy erythrocyte sedimentation rate estrogen therapy fetal alcohol syndrome fetal heart fetal heart rate International Federation of Gynecology and Obstetrics fetal immune response syndrome fluorescent in situ hybridization fine-needle aspiration fetal scalp electrode follicle-stimulating hormone fluorescent treponemal antibody absorption failure to progress gravidity gestational age group B streptococcus gestational diabetes mellitus glomerular filtration rate gestational hypertension Gastrointestinal glucose loading test gonadotropin-releasing hormone gestational trophoblastic disease glucose tolerance test genitourinary genitourinary syndrome of menopause highly active antiretroviral therapy

Hb HbH

hemoglobin hemoglobin H disease

hCG hCS Hct HDL HELLP HIV hMG HNPCC HPL HPV HRT HSG HSIL HSV I&D ICSI Ig IM INR ITP IUD IUFD IUGR IUI IUP IUPC IUT IVC IVF IVP KB KOH KUB

human chorionic gonadotropin human chorionic somatomammotropin hematocrit high-density lipoprotein hemolysis, elevated liver enzymes, low platelets human immunodeficiency virus human menopausal gonadotropin hereditary nonpolyposis colorectal cancer syndrome human placental lactogen human papillomavirus hormone replacement therapy hysterosalpingogram high-grade squamous intraepithelial lesion herpes simplex virus incision and drainage intracytoplasmic sperm injection immunoglobulin intramuscular International Normalized Ratio idiopathic thrombocytopenic purpura intrauterine device intrauterine fetal demise or death intrauterine growth restricted intrauterine insemination intrauterine pregnancy intrauterine pressure catheter intrauterine transfusion inferior vena cava in vitro fertilization intravenous pyelogram Kleihauer–Betke potassium hydroxide kidneys/ureter/bladder (X-ray)

LBW LCHAD LCIS

low birth weight long-chain hydroxyacyl-CoA dehydrogenase lobular carcinoma in situ

LDH LDL LEEP LFT LGA LGV LH LIQ Lletz LMP LOQ LOT LSIL LTL MAO MESA MHA-TP MHT MI MIF MLK MRI MRKH MSAFP MTHFR NPV NSAID NST NT NTD OA OCP

lactate dehydrogenase low-density lipoprotein loop electrosurgical excision procedure liver function test large for gestational age lymphogranuloma venereum luteinizing hormone lower inner quadrant large loop excision of the transformation zone last menstrual period lower outer quadrant left occiput transverse low-grade squamous intraepithelial lesion laparoscopic tubal ligation monoamine oxidase microsurgical epididymal sperm aspiration microhemagglutination assay for antibodies to Treponema pallidum menopause hormone therapy myocardial infarction müllerian inhibiting factor myosin light-chain kinase magnetic resonance imaging Mayer–Rokitansky–Küster–Hauser (syndrome) maternal serum α-fetoprotein methyl tetrahydrofolate reductase negative predictive value nonsteroidal anti-inflammatory drug nonstress test nuchal translucency neural tube defect occiput anterior oral contraceptive pill

OCT OI OP

oxytocin challenge test ovulation induction occiput posterior

OT OTC P PALM-COEIN

occiput transverse over-the-counter parity Polyp, Adenomyosis, Leiomyoma, Malignancy and hyperplasia; Coagulopathy, Ovulatory dysfunction, Endometrial, Iatrogenic and Not yet classified polycystic ovarian syndrome polymerase chain reaction patent ductus arteriosus pulmonary embolus pelvic inflammatory disease premenstrual dysphoric disorder premature ovarian failure premenstrual syndrome per os (by mouth) products of conception primary ovarian insufficiency Pelvic Organ Prolapse Quantification system peripartum cardiomyopathy purified protein derivative preterm premature rupture of membranes postpartum sterilization positive predictive value premature rupture of membranes placental site trophoblastic tumor prothrombin time preterm labor partial thromboplastin time propylthiouracil percutaneous umbilical blood sampling each day four times a day

PCOS PCR PDA PE PID PMDD PMOF PMS PO POCs POI POP-Q PPCM PPD PPROM PPS PPV PROM PSTT PT PTL PTT PTU PUBS QD QID

RBC RDS ROM ROT RPR

red blood cell respiratory distress syndrome rupture of membranes right occiput transverse rapid plasma reagin

SAB SCC SERM SGA SHBG SIDS SIS SLE SNRIs SSRIs STD STI SVT TAC TAHBSO TENS TFTs TLC TNM TOA TOLAC TOV TPAL TRH TSE TSH TSI TSS TSST TTTS UAE

spontaneous abortion squamous cell carcinoma selective estrogen receptor modulator small for gestational age sex hormone binding globulin sudden infant death syndrome saline infusion sonogram systemic lupus erythematosus serotonin and norepinephrine reuptake inhibitors selective serotonin reuptake inhibitors sexually transmitted disease sexually transmitted infection superficial vein thrombophlebitis transabdominal cerclage total abdominal hysterectomy and bilateral salpingo-oophorectomy transcutaneous electrical nerve stimulation thyroid function tests (given in ch 26) total lung capacity tumor/node/metastasis tubo-ovarian abscess trial of labor after cesarean transposition of the vessels term, preterm, aborted, living thyrotropin-releasing hormone testicular sperm extraction(given in ch 26) thyroid-stimulating hormone thyroid-stimulating immunoglobulins toxic shock syndrome toxic shock syndrome toxin twin-to-twin transfusion syndrome uterine artery embolization

UG UIQ UOQ UPI

urogenital upper inner quadrant upper outer quadrant uteroplacental insufficiency

US UTI V/Q VAIN VBAC VD

ultrasound urinary tract infection ventilation/perfusion ratio vaginal intraepithelial neoplasia vaginal birth after cesarean volume of distribution

VDRL VIN VMS VSD VZIG VZV WBC

Venereal Disease Research Laboratory vulvar intraepithelial neoplasia vasomotor symptoms ventricular septal defect varicella zoster immune globulin varicella zoster virus white blood cell

PART I OBSTETRICS

Pregnancy and Prenatal Care

PREGNANCY Pregnancy is the state of having products of conception implanted normally or abnormally in the uterus or occasionally elsewhere. It is terminated by spontaneous or elective abortion or by delivery. Myriad physiologic changes occur in a pregnant woman, affecting every organ system.

DIAGNOSIS In a patient who has regular menstrual cycles and is sexually active, a period delayed by more than a few days to a week is suggestive of pregnancy. Even at this early stage, patients may exhibit signs and symptoms of pregnancy. On physical examination, a variety of findings indicate pregnancy (Table 1-1). TABLE 1-1. Signs and Symptoms of Pregnancy Signs Bluish discoloration of vagina and cervix (Chadwick sign) Softening and cyanosis of the cervix at or after 4 wk (Goodell sign) Softening of the uterus after 6 wk (Ladin sign) Breast swelling and tenderness Development of the linea nigra from umbilicus to pubis Telangiectasias Palmar erythema Symptoms Amenorrhea Nausea and vomiting Breast pain Quickening—fetal movement

Many over-the-counter (OTC) urine pregnancy tests have a high sensitivity and will be positive around the time of the missed menstrual cycle. These urine tests and the hospital laboratory serum assays test for the β subunit of human chorionic gonadotropin (β-hCG). This hormone, produced by the placenta, will rise to a peak of 100,000 mIU/mL by 10 weeks of gestation, decrease throughout the second trimester, and then level off at approximately 20,000 to 30,000 mIU/mL in the third trimester. A viable pregnancy can be confirmed by ultrasound, which may show the gestational sac as early as 5 weeks on a transvaginal ultrasound or at a β-hCG of 1,500 to 2,000 mIU/mL. Fetal heart (FH) motion may be seen on transvaginal ultrasound as soon as 6 weeks or at a β-hCG of 5,000 to 6,000 mIU/mL.

TERMS AND DEFINITIONS From the time of fertilization until the pregnancy is 8 weeks along (10 weeks’ gestational age [GA]), the conceptus is called an embryo. After 8 weeks until the time of birth, it is designated a fetus. The term infant is used for the period between delivery and 1 year of age. Pregnancy is divided into trimesters. The first trimester lasts until 12 weeks but is also defined as up to 14 weeks’ GA, the second trimester lasts from 12 to 14 until 24 to 28 weeks’ GA, and the third trimester lasts from 24 to 28 weeks until delivery. An infant delivered prior to 23 to 24 weeks is considered to be previable, delivered between 24 and 37 weeks is considered preterm, and between 37 and 42 weeks is considered term. A pregnancy carried beyond 42 weeks is considered postterm. Gravidity (G) refers to the number of times a woman has been pregnant, and parity (P) refers to the number of pregnancies that led to a birth at or beyond 20 weeks’ GA or of an infant weighing more than 500 g. For example, a woman who has given birth to one set of twins would be a G1 P1, because a multiple gestation is considered to be just one pregnancy. A more specific designation of pregnancy outcomes divides parity into term and preterm deliveries and also adds the number of abortuses and the number of living children. This is known as the TPAL designation. Abortuses include all pregnancy losses prior to 20 weeks, both therapeutic and spontaneous, as well as ectopic pregnancies. For example, a woman who has given birth to one set of preterm twins, one term infant, and had two miscarriages would be

a G4 P1-1-2-3. The prefixes nulli-, primi-, and multi- are used with respect to gravidity and parity to refer to having 0, 1, or more than 1, respectively. For example, a woman who has been pregnant twice, one ectopic pregnancy and one fullterm birth, would be multigravid and primiparous. Unfortunately, this terminology often gets misused, with individuals referring to women with a first pregnancy as primiparous, rather than nulliparous. Obstetricians also use the term grand multip, which refers to a woman whose parity is greater than or equal to 5.

Dating of Pregnancy The GA of a fetus is the age in weeks and days measured from the last menstrual period (LMP). Developmental age (DA) or conceptional age or embryonic age is the number of weeks and days since fertilization. Because fertilization usually occurs about 14 days after the first day of the prior menstrual period, the GA is usually 2 weeks more than the DA. Classically, the Nagele rule for calculating the estimated date of confinement (EDC), or estimated date of delivery (EDD), is to subtract 3 months from the LMP and add 7 days. Thus, a pregnancy with an LMP of January 16, 2017, would have an EDC of October 23, 2017. Exact dating uses an EDC calculated as 280 days after a certain LMP. If the date of ovulation is known, as in assisted reproductive technology, the EDC can be calculated by adding 266 days. Pregnancy dating can be confirmed and should be consistent with the examination of the uterine size at the first prenatal appointment. With an uncertain LMP, ultrasound is often used to determine the EDC. Ultrasound has a level of uncertainty that increases during the pregnancy, but it is rarely off by more than 7% to 8% at any GA. A safe rule of thumb is that the ultrasound should not differ from LMP dating by more than 1 week in the first trimester, 2 weeks in the second trimester, and 3 weeks in the third trimester. The dating done with crown–rump length in the first half of the first trimester is probably even more accurate, to within 3 to 5 days. Other measures used to estimate GA include pregnancy landmarks such as auscultation of the FH at 20 weeks by nonelectronic fetoscopy or at 10 weeks by Doppler ultrasound, as well as maternal awareness of fetal movement or “quickening,” that usually occurs between 16 and 20 weeks.

Because ultrasound dating of pregnancy decreases in accuracy as the pregnancy progresses, determining and confirming pregnancy dating at the first interaction between a pregnant woman and the health care system is imperative. A woman who presents to the emergency department may not return for prenatal care, so dating should be confirmed at that visit. Pregnancy dating is particularly important because a number of decisions regarding care are based on accurate dating. One such decision is whether to resuscitate a newborn at the threshold of viability, which may be at 23 or 24 weeks of gestation, depending on the institution. Another is the induction of labor at 41 weeks of gestation. Approximately 5% to 15% of women may be oligo-ovulatory, meaning they ovulate beyond the usual 14th day of the cycle. Thus, their LMP dating may overdiagnose a prolonged (≥41 weeks’ gestation) or postterm pregnancy (≥42 weeks’ gestation). Luckily, early verification or correction of dating can correct such misdating.

PHYSIOLOGY OF PREGNANCY Cardiovascular During pregnancy, cardiac output increases by 30% to 50%. Most increases occur during the first trimester, with the maximum being reached between 20 and 24 weeks’ gestation and maintained until delivery. The increase in cardiac output is first due to an increase in stroke volume and is then maintained by an increase in heart rate as the stroke volume decreases to near prepregnancy levels by the end of the third trimester. Systemic vascular resistance decreases during pregnancy, resulting in a fall in arterial blood pressure. This decrease is most likely due to elevated progesterone, leading to smooth muscle relaxation. There is a decrease in systolic blood pressure of 5 to 10 mm Hg and in diastolic blood pressure of 10 to 15 mm Hg that reaches a nadir at week 24. Between 24 weeks’ gestation and term, the blood pressure slowly returns to prepregnancy levels but should never exceed them.

Pulmonary There is an increase of 30% to 40% in tidal volume (TV) during pregnancy (Fig. 1-1) despite the fact that the total lung capacity (TLC) is decreased by

5% because of the elevation of the diaphragm. This increase in VT decreases the expiratory reserve volume by about 20%. The increase in VT with a constant respiratory rate leads to an increase in minute ventilation of 30% to 40%, which in turn leads to an increase in alveolar (PAO2) and arterial (PaO2) PO2 levels and a decrease in PACO2 and PaCO2 levels.

FIGURE 1-1. Lung volumes in nonpregnant and pregnant women. PaCO2 decreases to approximately 30 mm Hg by 20 weeks’ gestation from 40 mm Hg during prepregnancy. This change leads to an increased CO2 gradient between mother and fetus and is likely caused by elevated progesterone levels that either increase the respiratory system’s responsiveness to CO2 or act as a primary stimulant. This gradient facilitates oxygen delivery to the fetus and carbon dioxide removal from the fetus. Dyspnea of pregnancy occurs in 60% to 70% of patients. This is possibly secondary to decreased PaCO2 levels, increased VT, or decreased TLC.

Gastrointestinal Nausea and vomiting occur in more than 70% of pregnancies. This has been termed morning sickness even though it can occur anytime throughout the

day. These symptoms have been attributed to the elevation in estrogen, progesterone, and hCG. They may also be due to hypoglycemia and can be treated with frequent snacking. The nausea and vomiting typically resolve by 14 to 16 weeks’ gestation. Hyperemesis gravidarum refers to a severe form of morning sickness associated with weight loss (≥5% of prepregnancy weight) and ketosis. During pregnancy, the stomach has prolonged gastric emptying times, and the gastroesophageal sphincter has decreased tone. Together, these changes lead to reflux and possibly combine with decreased esophageal tone to cause ptyalism, or spitting, during pregnancy. The large bowel also has decreased motility, which leads to increased water absorption and constipation.

Renal The kidneys increase in size and the ureters dilate during pregnancy, which may lead to increased rates of pyelonephritis. The glomerular filtration rate (GFR) increases by 50% early in pregnancy and is maintained until delivery. As a result of increased GFR, blood urea nitrogen and creatinine decrease by about 25%. An increase in the renin–angiotensin system leads to increased levels of aldosterone, which results in increased sodium resorption. However, plasma levels of sodium do not increase because of the simultaneous increase in GFR.

Hematology Although the plasma volume increases by 50% in pregnancy, the RBC volume increases by only 20% to 30%, which leads to a decrease in the hematocrit or dilutional anemia. The WBC count increases during pregnancy to a mean of 10.5 million/mL with a range of 6 to 16 million. During labor, stress may cause the WBC count to rise to over 20 million/mL. There is a slight decrease in the concentration of platelets, probably secondary to increased plasma volume and an increase in peripheral destruction. Although in 7% to 8% of patients, the platelet count may be between 100 and 150 million/mL, a drop in the platelet count below 100 million/mL over a short time is not normal and should be investigated promptly. Pregnancy is considered to be a hypercoagulable state with an increase in the number of thromboembolic events. There are elevations in the levels of fibrinogen and factors VII–X. However, the actual clotting and bleeding

times do not change. The increased rate of thromboembolic events in pregnancy may also be secondary to the other elements of Virchow triad, that is, an increase in venous stasis and vessel endothelial damage.

Endocrine Pregnancy is a hyperestrogenic state. The increased estrogen is produced primarily by the placenta, with the ovaries contributing to a lesser degree. Unlike estrogen production in the ovaries, where estrogen precursors are produced in ovarian theca cells and transferred to the ovarian granulosa cells, estrogen in the placenta is derived from circulating plasma-borne precursors produced by the maternal adrenal glands. Fetal well-being has been correlated with maternal serum estrogen levels, with low estrogen levels being associated with conditions such as fetal death and anencephaly. The hormone hCG is composed of two dissimilar α and β subunits. The α subunit of hCG is identical to the α subunits of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and thyroid-stimulating hormone (TSH), whereas the β subunits differ. The levels of hCG double approximately every 48 hours during early pregnancy, reaching a peak at approximately 10 to 12 weeks, and thereafter declining to reach a steady state after week 15. The placenta produces hCG, which acts to maintain the corpus luteum in early pregnancy. The corpus luteum produces progesterone, which maintains the endometrium. Eventually, the placenta takes over progesterone production, and the corpus luteum degrades into the corpus albicans. Progesterone levels increase over the course of pregnancy. Progesterone causes relaxation of smooth muscle, which has multiple effects on the gastrointestinal, cardiovascular, and genitourinary systems. Human placental lactogen (hPL) is produced in the placenta and is important for ensuring a constant nutrient supply to the fetus. hPL, also known as human chorionic somatomammotropin (hCS), induces lipolysis with a concomitant increase in circulating free fatty acids. hPL also acts as an insulin antagonist, along with various other placental hormones, thereby having a diabetogenic effect. This leads to increased levels of insulin and protein synthesis. The levels of prolactin are markedly increased during pregnancy. These levels decrease after delivery but later increase in response to suckling. There are two major changes in thyroid hormones during pregnancy. First, estrogen stimulates thyroid binding globulin, leading to an elevation in total

T3 and T4, but free T3 and T4 remain relatively constant. Second, hCG has a weak stimulating effect on the thyroid, likely because its α subgroup is similar to TSH. This leads to a slight increase in T3 and T4 and a slight decrease in TSH early in pregnancy. Overall, however, pregnancy is considered a euthyroid state.

Musculoskeletal and Dermatologic The obvious change in the center of gravity during pregnancy can lead to a shift in posture and lower back strain, which worsens throughout pregnancy, particularly during the third trimester. Numerous changes occur in the skin, including spider angiomata and palmar erythema secondary to increased estrogen levels, and hyperpigmentation of the nipples, umbilicus, abdominal midline (the linea nigra), perineum, and face (melasma or chloasma) secondary to increased levels of the melanocyte-stimulating hormones and the steroid hormones. Pregnancy is also associated with carpal tunnel syndrome, which results from compression of the median nerve. The incidence in pregnancy varies greatly, and symptoms are usually self-limited.

Nutrition Nutritional requirements increase during pregnancy and breastfeeding. An average woman requires 2,000 to 2,500 kcal/day. The caloric requirement is increased by 300 kcal/day during pregnancy and by 500 kcal/day when breastfeeding. Thus, pregnancy is not the caloric equivalent of eating for two; more accurately, it is approximately eating for 1.15. Most patients should gain between 20 and 30 lb during pregnancy. Overweight women are advised to gain less, between 15 and 25 lb; underweight women are advised to gain more, 28 to 40 lb. Unfortunately, a large proportion of women gain more than the recommended amount, which contributes to a number of complications in pregnancy plus postpartum weight retention and downstream obesity. It is the responsibility of each prenatal care provider to review diet and exercise during pregnancy. In addition to the increased caloric requirements, there are increased nutritional requirements for protein, iron, folate, calcium, and other vitamins and minerals. The protein requirement increases from 60 to 70 or 75 g/day. Recommended calcium intake is 1.5 g/day. Many patients develop iron deficiency anemia because of the increased demand on hematopoiesis both

by the mother and by the fetus. Folate requirements increase from 0.4 to 0.8 mg/day and are important in preventing neural tube defects. All patients are advised to take prenatal vitamins during pregnancy. These are designed to compensate for the increased nutritional demands of pregnancy. Furthermore, any patient whose hematocrit falls during pregnancy is advised to increase iron intake with oral supplementation (Table 1-2). TABLE 1-2. Recommended Daily Dietary Allowances for Nonpregnant, Pregnant, and Lactating Women Nonpregnant Women by Age 11–14 y 15– 19– 23– 51+ y 18 y 22 y 50 y 2,400 2,100 2,100 2,000 1,800 44 48 46 46 46 800 800 800 800 800

Energy (kcal) Protein (g) Fat-soluble vitamins Vitamin A 4,000 activity (RE) (IU) Vitamin D (IU) 400 Vitamin E 12 activity (IU) Water-soluble vitamins Ascorbic acid 45 (mg) Folacin (mg) 400 Niacin (mg) 16 Riboflavin (mg) 1.3 Thiamin (mg) 1.2 Vitamin B6 1.6 (mg) Vitamin B12 3 (mg) Minerals Calcium (mg) Iodine (mg) Iron (mg)

1,200 115 18

Pregnant Women +300 +30 1,000

Lactating Women +500 +20 1,200

4,000

5,000

6,000

400 12

– 12

400 15

400 14 1.4 1.1 2

400 13 1.2 1 2

400 12 1.1 1 2

800 +2 +0.3 +0.3 2.5

600 +4 +0.5 +0.3 2.5

1,200 115 18

800 100 18

800 80 10

1,200 125 +18

1,200 150 18

Magnesium (mg) Phosphorus (mg) Zinc (mg)

300

450

1,200

800

1,200

IU, international unit. (From Gabbe SG, Niebyl JR, Simpsen JL. Obstetrics: Normal and Problem Pregnancies, 4th ed. New York, NY: Churchill Livingstone; 2002:196.)

PRENATAL CARE Prenatal visits are designed to screen for various complications of pregnancy and to educate the patient. They include a series of outpatient office visits that involve routine physical examinations and various screening tests that occur at different points in the prenatal care. Important issues of prenatal care include initial patient evaluation, routine patient evaluation, safety and housing, nutrition and food security, disease states during the pregnancy, and preparing for the delivery.

INITIAL VISIT This is often the longest of the prenatal visits because it involves obtaining a complete history and performing a physical examination as well as a battery of initial laboratory tests. It should occur early in the first trimester, between 6 and 10 weeks, although occasionally patients will not present for their initial prenatal visit until later in their pregnancy. At this visit, diet, exercise, and weight gain goals should also be discussed.

History The patient’s history includes the present pregnancy, the LMP, and symptoms during the pregnancy. After this, an obstetric history of prior pregnancies, including date, outcome (e.g., spontaneous abortion [SAB], therapeutic abortion, ectopic pregnancy, and term delivery), mode of delivery, length of time in labor and second stage, birth weight, and any complications, should be obtained. Finally, a complete medical, surgical, family, and social history should be obtained.

Physical Examination A complete physical examination is performed, paying particular attention to the patient’s prior medical and surgical history. The pelvic examination includes a Pap smear according to standard cervical cancer screening guidelines and cultures for gonorrhea and chlamydia. On bimanual examination, the size of the uterus should be consistent with the GA from the LMP. If a woman is unsure of her LMP or if size and dates are not consistent, one should obtain an ultrasound for dating. Accurate dating is crucial for all subsequent obstetric evaluations and interventions.

Diagnostic Evaluation The panel of tests in the first trimester includes a complete blood count, primarily for hematocrit, blood type, antibody screen, rapid plasma reagin (RPR) or Venereal Disease Research Laboratory (VDRL) screening for syphilis, rubella antibody screen, hepatitis B surface antigen, urinalysis, and urine culture. If a patient has no history of chickenpox, a titer for varicella zoster virus (VZV) antibodies is sent. A purified protein derivative (PPD) is usually placed during the first or second trimester to screen for tuberculosis in high-risk patients. A urine pregnancy test should be sent if the patient is not entirely certain she is pregnant. If there has been any bleeding or cramping, a serum β-hCG level should be obtained. Although there is some debate over the use of routine toxoplasma titers, they are often ordered as well. All patients are counseled about HIV, and testing should be offered routinely (Table 1-3). In addition, first-trimester screening tests for aneuploidy with nuchal translucency (NT) by ultrasound and serum markers are increasingly being obtained in most women via referral to a prenatal diagnosis unit. In addition to this battery of tests, there are a variety of other screens offered to high-risk patients (Table 1-4). TABLE 1-3. Routine Tests in Prenatal Care Initial Visit and First Trimester Hematocrit Blood type and screen RPR/VDRL

Second Trimester

Third Trimester

MSAFP/triple or quad screen Obstetric ultrasound Amniocentesis for women

Hematocrit RPR/VDRL GLT

interested in prenatal diagnosis Rubella antibody screen

Group B streptococcal culture

Hepatitis B surface antigen Gonorrhea culture Chlamydia culture PPD Pap smear Urinalysis and culture VZV titer in patients with no history of exposure HIV offered Early screening for aneuploidy (NT plus serum markers) GLT, glucose loading test; MSAFP, maternal serum alpha fetoprotein; NT, nuchal translucency; PPD, purified protein derivative; RPR, rapid plasma regain; VZV, varicella zoster virus.

TABLE 1-4. Initial Screens in Specific High-Risk Groups High-Risk Group African American, Southeast Asian Family history of genetic disorder (e.g., hemophilia, sickle cell disease, fragile X syndrome), maternal age 35 or older at time of EDC Prior gestational diabetes, family history of diabetes, Hispanic, Native American, Southeast Asian, obese Pregestational diabetes, unsure dates, recurrent miscarriages Hypertension, renal disease, pregestational diabetic, prior preeclampsia, renal transplant, Systemic Lupus Erythematosus

Specific Test Sickle cell prep for African Americans; Hgb electrophoresis for both Prenatal genetics referral

Early GLT

Dating sonogram at first visit Blood Urea Nitrogen, Cr, uric acid, and 24-h urine collection for protein and creatinine clearance (to establish a baseline)

Pregestational diabetes, prior cardiac disease, hypertension Pregestational diabetes Graves disease All thyroid disease PPD+ SLE

ECG Hgb A1C, ophthalmology for eye examination Thyroid-stimulating immunoglobulins (can cause fetal disease) TSH, possibly free T4 Chest X-ray after 16 wk’s gestation AntiRho, antiLa antibodies (can cause fetal complete heart block)

EDC, estimated date of confinement; GLT, glucose loading test; PPD, purified protein derivative TSH, thyroid-stimulating hormone.

ROUTINE PRENATAL VISITS Blood pressure, weight, urine dipstick, measurement of the uterus, and auscultation of the FH are performed and assessed on each follow-up prenatal care visit. Maternal blood pressure decreases during the first and second trimesters and slowly returns to baseline during the third trimester; elevation may be a sign of preeclampsia. Maternal weight is followed serially throughout the pregnancy as a proxy for adequate nutrition. Also, large weight gains toward the end of pregnancy can be a sign of fluid retention and preeclampsia. Measurement of the uterine fundal height in centimeters corresponds roughly to the weeks of gestation. If the fundal height is progressively decreasing or is 3 cm less than GA, an ultrasound is done to more accurately assess fetal growth. After 10 to 14 weeks, Doppler ultrasound is used to auscultate the fetal heart rate (FHR). Urine is routinely dipped for protein, glucose, blood, and leukocyte esterase. The presence of protein may be indicative of preeclampsia, glucose of diabetes, and leukocyte esterase of urinary tract infection (UTI). Pregnant women are at an increased risk for complicated UTIs such as pyelonephritis, given increased urinary stasis from mechanical compression of the ureters and progesterone-mediated smooth muscle relaxation. At each visit, the patient is asked about symptoms that indicate complications of pregnancy. These symptoms include vaginal bleeding, vaginal discharge or leaking of fluid, and urinary symptoms. In addition, after 20 weeks, patients are asked about contractions and fetal movement. Vaginal

bleeding is a sign of possible miscarriage or ectopic pregnancy in the first trimester and of placental abruption or previa as the pregnancy advances. Vaginal discharge may be a sign of infection or cervical change, whereas leaking fluid can indicate ruptured fetal membranes. While irregular (Braxton Hicks) contractions are common throughout the third trimester, regular contractions occurring more frequently than five or six per hour may be a sign of preterm labor and should be assessed. Changes in or the absence of fetal movement should be evaluated by auscultation of the FH in the previable fetus and with further testing such as a nonstress test (NST) or biophysical profile (BPP) in the viable fetus.

First-Trimester Visits During the first trimester, patients—particularly nulliparous women—need to be familiarized with pregnancy. The symptoms of pregnancy and what will occur at each prenatal visit should be reviewed. At the second prenatal visit, all of the initial laboratory test results should be reviewed with the patient. Those with poor weight gain or decreased caloric intake secondary to nausea and vomiting may be referred to a nutritionist. Patients treated for infections noted at the initial prenatal visit should be cultured for test of cure. Additionally, early screening for aneuploidy, either combined screening with an ultrasound for NT and serum levels of pregnancy-associated plasma protein A and free β-hCG, or with a blood test to assess the relative quantity of fetal DNA (cell-free DNA) for chromosomes 13, 18, and 21, is offered between 11 and 13 weeks of gestation to all women. Of note, the tradeoffs between combined first trimester screening and the new cfDNA screening are evolving and controversial.

Second-Trimester Visits During the second trimester, much of the screening for genetic and congenital abnormalities is done. This allows a patient to obtain an elective termination if there are abnormalities. Screening for maternal serum alpha fetoprotein (MSAFP) is usually performed between 15 and 18 weeks. An elevation in MSAFP is correlated with an increased risk of neural tube defects, and a decrease is seen in some aneuploidies, including Down syndrome. The sensitivity of aneuploidy screening is augmented using β-hCG and estriol along with MSAFP, called the triple screen. The addition of inhibin A to this