Contents Foreword xv William F. Rayburn Preface xvii Judith U. Hibbard Pregestational Diabetes 143 Gabriella Pridjian The prevalence of preexisting diabetes in pregnancy is increasing largely because of an increase in type 2 diabetes. Outcomes of diabetic pregnan- cies for mother and newborn have improved greatly in recent decades from advances in understanding the disease process, improved educa- tion, and new treatment modalities delivered in a team approach. Nausea and vomiting from pregnancy and pregnancy-associated insulin resis- tance can make glycemic control a challenge. Care of women with preex- isting diabetes demands careful monitoring in the preconception, prenatal, and peripartum periods. Asthma in Pregnancy: Pathophysiology, Diagnosis and Management 159 Abbey J. Hardy-Fairbanks and Emily R. Baker Asthma is a common, potentially serious, even life-threatening, chronic medical condition seen amongst nearly all groups of patients, regardless of ethnicity and socioeconomic circumstances. This article addresses the group of pregnant women with symptomatic asthma as well as those whose asthma is asymptomatic as a result of good control. The incidence, the pathophysiologic changes of pregnancy, and the interplay between these changes and asthma are reviewed in this article. The classification of these patients and appropriate management strategies are discussed. Diagnosis and Management of Thyroid Disease in Pregnancy 173 Diana L. Fitzpatrick and Michelle A. Russell Thyroid disease is common, affecting 1% to 2% of pregnant women. Preg- nancy may modify the course of thyroid disease, and pregnancy outcomes can depend on optimal management of thyroid disorders. Consequently, obstetric providers must be familiar with thyroid physiology and manage- ment of thyroid diseases in pregnancy. Following a brief overview of phy- siology, this article provides an in-depth review of diagnosis and management of the spectrum of thyroid disease occurring in pregnancy. Recommendations for screening and treatment of hypo- and hyperthy- roidism are summarized. Specific attention is given to the limitations of current research and the status of ongoing work. Update on Medical Disorders in Pregnancy Management of Renal Disease in Pregnancy 195 Tiina Podymow, Phyllis August, and Ayub Akbari Although renal disease in pregnancy is uncommon, it poses considerable risk to maternal and fetal health. This article discusses renal physiology and assessment of renal function in pregnancy and the effect of pregnancy on renal disease in patients with diabetes, lupus, chronic glomerulonephri- tis, polycystic kidney disease, and chronic pyelonephritis. Renal diseases occasionally present for the first time in pregnancy, and diagnoses of glo- merulonephritis, acute tubular necrosis, hemolytic uremic syndrome, and acute fatty liver of pregnancy are described. Finally, therapy of end-stage renal disease in pregnancy, dialysis, and renal transplantation are reviewed. Pregnanc y in the RenalTransplant Recipient 211 Michelle A. Josephson and Dianne B. McKay March 10th, 1958, is the birthday of the first baby born to a kidney transplant recipient. The pregnancy went to term and the baby was delivered by cesar- ean section for fear that a vaginal birth could adversely affect the allograft kidney sitting in the iliac fossa. Undoubtedly, this pregnancy more than 50 years ago was considered high risk because of its pioneering nature. How- ever, given that the transplant recipient had received her kidney from her identical twin sister approximately 2 years before and was not taking any im- munosuppressive medications, the pregnancy was associated with far fewer risks than most pregnancies in transplant recipients of today. Not only are immunosuppressants now available that have potential adverse af- fects on the developing fetus but also many kidney transplant recipients have kidney function that is suboptimal. Although thousands of women with kidney transplants have successfully delivered healthy babies, many new issues must be considered during a transplant recipient’s pregnancy compared with 50 years ago. These issues are discussed in this article. Sickle Cell Disease in Pregnancy 223 Dennie T. Rogers and Robert Molokie The term sickle cell disease (SSD) encompasses several different sickle hemoglobinopathies. The ability to predict the clinical course of SSD dur- ing pregnancy is difficult. This article examines pregnancy-associated complications in SSD and the management of sickle cell disorders in preg- nant women. Outcomes have improved for pregnant women with SSD and nowadays the majority can achieve a successful live birth. However, preg- nancy is still associated with an increased incidence of morbidity and mor- tality. Optimal management during pregnancy should be directed at preventing pain crises, chronic organ damage, optimization of fetal health and minimizing early maternal mortality using a multidisciplinary team ap- proach and prompt, effective and safe relief of acute pain episodes. Abnormal Placentation, Angiogenic Factors, and the Pathogenesis of Preeclampsia 239 Michelle Silasi, Bruce Cohen, S. Ananth Karumanchi, and Sarosh Rana Preeclampsia is a common complication of pregnancy with potentially devastating consequences to both the mother and the baby.It is the Contents x leading cause of maternal deaths in developing countries. In developed countries it is the major cause of iatrogenic premature delivery and con- tributes significantly to increasing health care cost associated with prema- turity. There is currently no known treatment for preeclampsia; ultimate treatment involves delivery of the placenta. Although there are several risk factors (such as multiple gestation or chronic hypertension), most pa- tients present with no obvious risk factors. The molecular pathogenesis of preeclampsia is just now being elucidated. It has been proposed that ab- normal placentation and an imbalance in angiogenic factors lead to the clinical findings and complications seen in preeclampsia. Preeclampsia is characterized by high levels of circulating antiangiogenic factors such as soluble fms-like tyrosine kinase-1 and soluble endoglin, which induce maternal endothelial dysfunction. These soluble factors are altered not only at the time of clinical disease but also several weeks before the onset of clinical signs and symptoms. Many methods of prediction and surveil- lance have been proposed to identify women who will develop preeclamp- sia, but studies have been inconclusive. With the recent discovery of the role of angiogenic factors in preeclampsia, novel methods of prediction and diagnosis are being developed to aid obstetricians and midwives in clinical practice. This article discusses the role of angiogenic factors in the pathogenesis, prediction, diagnosis, and possible treatment of preeclampsia. Update on Gestational Diabetes 255 Gabriella Pridjian and Tara D. Benjamin As the rate of obesity increases in adolescent and adult women in the United States, practitioners of obstetrics see higher rates of gestational di- abetes. Recent clinical studies suggest that women with gestational dia- betes have impaired pancreatic beta-cell function and reduced beta-cell adaptation resulting in insufficient insulin secretion to maintain normal gly- cemia. Despite recent evidence that even mild hyperglycemia is associ- ated with adverse pregnancy outcomes, controversies still exist in screening, management, and treatment of gestational diabetes. Initial studies regarding glyburide for treatment of gestational diabetes are prom- ising. Overall, only about half of the women with gestational diabetes are screened in the postpartum period, an ideal time for education and inter- vention, to decrease incidence of glucose intolerance and progression to type 2 diabetes. Cholestasis of Pregnancy 269 Bhuvan Pathak, Lili Sheibani, and Richard H. Lee Intrahepatic cholestasis (ICP) of pregnancy is a disease that is likely mul- tifactorial in etiology and has a prevalence that varies by geography and ethnicity. The diagnosis is made when patients have a combination of pru- ritus and abnormal liver-function tests. It is associated with a high risk for adverse perinatal outcome, including preterm birth, meconium passage, and fetal death. As of yet, the cause for fetal death is unknown. Because fetal deaths caused by ICP appear to occur predominantly after 37 weeks, it is suggested to offer delivery at approximately 37 weeks. Contents xi Ursodeoxycholic acid appears to be the most effective medication to im- prove maternal pruritus and liver-function tests; however, there is no med- ication to date that has been shown to reduce the risk for fetal death. Update on Peripartum Cardiomyopathy 283 Meredith O. Cruz, Joan Briller, and Judith U. Hibbard Although multiple mechanisms have been postulated, peripartum cardio- myopathy (PPCM) continues to be a cardiomyopathy of unknown cause. Multiple risk factors exist and the clinical presentation does not allow dif- ferentiation among potential causes. Although specific diagnostic criteria exist, PPCM remains a diagnosis of exclusion. Treatment modalities are dictated by the clinical state of the patient, and prognosis is dependent on recovery of function. Randomized controlled trials of novel therapies, such as bromocriptine, are needed to establish better treatment regimens to decrease morbidity and mortality. The creation of an international regis- try will be an important step to better define and treat PPCM. This article discusses the pathogenesis, risk factors, diagnosis, management, and prognosis of this condition. Pregnanc y After Bariatric Surgery 305 Michelle A. Kominiarek The incidence of obesity is increasing rapidly, and it affects a greater pro- portion of women than men. Unfortunately, obesity has a negative impact on women’s reproductive health, including increased adverse perinatal outcomes. Weight loss surgery, also known as bariatric surgery, is per- formed in many hospitals, and can allow for significant weight loss and im- provement in medical comorbidities such as diabetes and hypertension. A woman who becomes pregnant after bariatric surgery usually has an un- complicated pregnancy but requires special attention to some complica- tions that can occur after these procedures. This article reviews the perinatal outcomes and provides recommendations for care regarding the unique issues that arise during a pregnancy after bariatric surgery. Selected Viral Infections in Pregnancy 321 Britta Panda, Alexander Panda, and Laura E. Riley This article reviews the impact of seasonal influenza on pregnancy with par- ticular emphasis on the 2009 novel H1N1 pandemic. Antiviral therapy for in- fluenza, as well as recommendations and safety data on vaccination are discussed. In addition, the impact of hepatitis A, B, and C in pregnancy is addressed with a focus on prevention and treatment strategies for hepatitis B and C. Thromboprophylaxis in Pregnancy: Who and How? 333 Sarah M. Davis and D. Ware Branch Venous thrombosis and embolism (VTE) is one of the most common, seri- ous complications associated with pregnancy, and now ranks as a leading Contents xii cause of maternal morbidity and mortality in developed countries. Informa- tion regarding the association of VTE with acquired and heritable thrombo- philias has greatly expanded in the last 20 years, adding a new layer of complexity to decisions about thromboprophylaxis. The objective of this review is to detail which patients are at clinically important increased risk for VTE, are candidates for thrombophilia screening, and warrant thrombo- prophylaxis. Recommended management regimens for use in specific patient subgroups are also provided. Ethical Issues in Obstetrics 345 Laura M. DiGiovanni Obstetricians must become comfortable addressing the ethical issues involved in clinical obstetrics and therefore must have an understanding of the key elements of clinical medical ethics. Balancing the principles of medical ethics can guide clinicians toward solutions to ethical dilemmas encountered in the care of pregnant women. The purpose of this article is to review the ethical foundations of clinical practice, recognize the eth- ical issues obstetricians face every day in caring for patients, and facilitate decision making. This article discusses the relevant ethical principles, identifies unique features of obstetrical ethics, examines ethical principles as they apply to pregnant patient and her fetus, and thereby, provides a conceptual framework for considering ethical issues and facilitating de- cision making in clinical obstetrics. Index 359 Contents xiii Foreword William F. Rayburn, MD, MBA Consulting Editor This issue of Obstetrics and Gynecology Clinics of North America, with Dr Judith Hibbard as Guest Editor, provides a timely update on topics pertaining to medical disorders in pregnancy. It is important that obstetricians have working knowledge of medical diseases common to women of childbearing age. It is difficult, however, to quantify accurately the broad range of medical illnesses that complicate pregnancy. Estimates have been derived from conditions warranting hospitalization. One study reported an overall antenatal hospitalization rate of 10 per 100 deliveries in their managed-care population of more than 46,000 pregnant women. About one third of those admissions were for nonobstetric conditions, such as renal, gastrointestinal, pulmonary, and infectious diseases. The care for some of these women warrants a team effort between obstetricians and specialists in either maternal-fetal medicine or internal medicine. It is essential to be familiar with pregnancy-induced physiologic changes. Even during normal pregnancy, virtually every organ system undergoes anatomic and func- tional changes that can alter criteria for diagnosis and treatment of medical complica- tions. Without such knowledge, it is nearly impossible to understand how a disease process can threaten a woman and her fetus. On review of these articles, several fundamental principles apply to the rational approach for managing and prescribing drugs during pregnancy. (1) A woman should not be penalized for being pregnant. (2) What management plan would be recommen- ded if she were nonpregnant? (3) What justifications are there to change such therapy because of pregnancy? (4) Individualization of care is especially important during pregnancy. (5) The healthiest mother is likely to deliver the healthiest fetus. Practice guidelines offered here result from a formal synthesis of evidence, devel- oped according to a rigorous research and review process. The authors’ contributions offer a better understanding of evidence-based medicine, particularly as they relate to the development of guidelines. As evidence-based medicine continues to be inte- grated into clinical practice, an understanding of its basic elements is critical in trans- lating the peer-reviewed literature into appropriate management of these medical Obstet Gynecol Clin N Am 37 (2010) xv–xvi doi:10.1016/j.ogc.2010.03.002 obgyn.theclinics.com 0889-8545/10/$ – see front matter ª 2010 Elsevier Inc. All rights reserved. Update on Medical Disorders in Pregnancy conditions. The emphasis on evidence-based medicine has taken on even more importance with the accessibility of information being easier for both obstetricians and their patients. This issue provides a fresh perspective to the treatment of commonly seen, chronic medical illnesses during pregnancy. It is our desire that this timely review activates attention to issues about such conditions in pregnancy. It is hoped that the practical information provided herein by this distinguished group of clinicians aids in the eval- uation and treatment of medical complications to optimize favorable outcomes for both mother and fetus. William F. Rayburn, MD, MBA Department of Obstetrics and Gynecology University of New Mexico School of Medicine MSC 10 5580, 1 University of New Mexico Albuquerque, NM 871310001, USA E-mail address: wrayburn@salud.unm.edu Foreword xvi Preface Judith U. Hibbard, MD Guest Editor I am delighted to have the opportunity to edit this important issue of Obstetrics and Gynecology Clinics of North America on the topic of Medical Complications in Preg- nancy. The broad field of medicine changes rapidly, with constantly occurring new breakthroughs, approaches, and recommendations. The area of medical disorders in pregnancy encompasses a broad range of diseases; a woman may have a long-term chronic disorder that can have major implications for undertaking a pregnancy. Yet, other medical conditions are unique to pregnancy but also influence gestational outcomes. Although the obstetrician has to be knowledgeable in regard to the normal physiologic changes occurring with gestation, understanding the interplay of medical conditions with these changes on not only 1 but 2 patients, mother and fetus, can be a daunting task. I have invited a group of outstanding physicians to author articles that are timely and clinically useful to the practicing obstetrician. Several manuscripts in this issue focus on commonly occurring illnesses but bring fresh perspective to our understanding of these disease causes, management schemes, and newer medical therapies. Other complications included are much less frequently addressed in a clear, concise article in which the obstetrician can find dependable advice for clinically managing patients. Frequently the obstetrician must make difficult management decisions that involve their 2 patients, which may lead to conflicting strategies. The issue begins with articles on several chronic illnesses that many obstetri- cians encounter on a daily basis. A timely review of pregestational diabetes in preg- nancy and a clinical approach to asthma in gestation begin the series. Thyroid disease in pregnancy is revisited, providing insight into issues of screening. A clin- ical framework for understanding renal disease in pregnancy is presented, whereas an approach to pregnant women with renal transplant, becoming more common, is provided. Sickle disease in pregnancy, seen frequently in urban centers across the country, is examined and clinical guidance offered. Several diseases unique to pregnancy present challenges for the obstetrician. A timely update on preeclampsia, clarifying the role that angiogenic factors play in the genesis and prediction of this Obstet Gynecol Clin N Am 37 (2010) xvii–xviii doi:10.1016/j.ogc.2010.02.016 obgyn.theclinics.com 0889-8545/10/$ – see front matter ª 2010 Elsevier Inc. All rights reserved. Update on Medical Disorders in Pregnancy disease, is included. Insight is provided into newer treatment modalities in gesta- tional diabetes, particularly oral hypoglycemic agents. Cholestasis in pregnancy is reviewed, and its medical impact as well as a management scheme is described. Newer therapies and clinical trials are described in the article on peripartum cardio- myopathy. As the incidence of obesity continues to increase, so does the number of pregnant women who have undergone previous bypass surgery; a practical approach to these gravidas is suggested. An update on the unique impact of H1N1 virus on pregnancy is reviewed. A clear, logical framework for thrombophilia screening and thromboprophylaxis in pregnancy is included. In the final article, there is an exploration of some of the ethical issues that affect mother and fetus maligned by medical diseases during gestation. The opportunity to edit this issue of Obstetrics and Gynecology Clinics of North America has not only been a challenge but also an enjoyable learning experience for me. I hope you will find these articles to be as enlightening as I have found them. Judith U. Hibbard, MD Division of Maternal Fetal Medicine Department of Obstetrics and Gynecology University of Illinois at Chicago 840 South Wood Street, M/C 808 Chicago, IL 60612, USA E-mail address: jhibbar@uic.edu Preface xviii Pregestational Diabetes Gabriella Pridjian, MD The number of pregnant women with preexisting diabetes is increasing, mainly from an increase in type 2 1,2 but also an increase in type 1 diabetes. 3,4 Therefore, the knowl- edge and management of this medical condition in pregnancy has become even more important. The epidemics of obesity and the low level of physical activity, and possibly the exposure to diabetes in utero, 5,6 are major contributors to the increase in type 2 diabetes in adults and in childhood and adolescence. Reasons for the increase in type 1 diabetes are somewhat unclear but may be related to harmful environmental conditions. CLASSIFICATION Diabetes in pregnancy has been traditionally grouped according to the pioneering work of Priscilla White, 7 who classified diabetes according to onset, duration, and complications to predict perinatal outcome (Table 1). An important distinction in clas- sification is the existence of micro or macrovascular complications of diabetes. If no vascular complications exist, then placental growth and development are most often not impeded and the risk for intrauterine growth restriction (IUGR) is smaller. However, with vascular complications such as those noted in the lower half of Table 1, the risk for IUGR increases with increasing severity. 8 Although the White’s classification is still valuable, the more recent diabetes classi- fication from the Expert Committee on the Diagnosis and Classification of Diabetes, 9 summarized in Table 2, may be more useful in patient management because it alerts clinicians to the type of diabetes, which may have somewhat different treatment strat- egies. Overall, type 1 diabetes accounts for approximately 5% to 10% of all diabetes outside of pregnancy, and type 2 diabetes for 90% to 95%. METABOLISM IN PREGNANCY Pregnancy itself is a diabetogenic state that exacerbates preexisting diabetes. Metab- olism changes dramatically during pregnancy. Both basal and postprandial glucose Division of Maternal-Fetal Medicine, Department of Obstetrics & Gynecology, SL11, Tulane University Medical School, 1430 Tulane Avenue, New Orleans, LA 70112, USA E-mail address: Pridjian@Tulane.edu KEYWORDS  Diabetes type 1  Diabetes type 2  Pregnancy Obstet Gynecol Clin N Am 37 (2010) 143–158 doi:10.1016/j.ogc.2010.02.014 obgyn.theclinics.com 0889-8545/10/$ – see front matter ª 2010 Elsevier Inc. All rights reserved. [...]... analog, was approved by the FDA in 2000 for use as basal insulin Insulin glargine has a glycine substitution in the a-chain at position 21 and two arginines attached to the b-chain terminal at position 30 Glargine has been shown to provide a peakless, sustained 24-hour level of insulin with once-a-day administration at bedtime or in the morning; in certain individuals glargine administered every 12 hours... degree of control is best accomplished with an intravenous insulin infusion during labor Women should be instructed to not take their basal or long-acting insulin when in labor or the day of labor induction, and to begin an 153 154 Pridjian Table 5 Intrapartum intravenous insulin infusion Capillary Blood Glucose (mg/dL) Insulin Infusion Rate (U/ha) Intravenous Fluids (125 mL/h) 60 mg/dL AM insulin At minimum, women with prepregnancy diabetes require three to four injections per day or the continuous insulin pump for optimal glucose control during pregnancy Traditional types of insulin used for treatment of diabetes in pregnancy have been regular human and neutral protamine Hagedorn (NPH) (Table 4) Although these types of insulin have been widely used, their insulin profiles... Despite a decrease in fasting glucose in pregnancy, basal hepatic glucose production increases and hepatic insulin sensitivity decreases The first and second phases of insulin secretion increase, and insulin sensitivity decreases In women who are pregnant and obese, hepatic insulin sensitivity further decreases11 and approaches the degree observed in type 2 diabetes Insulin resistance in pregnancy is likely... Consumption of the slow digesting waxy maize starch leads to blunted plasma glucose and insulin response but does not influence energy expenditure or appetite in humans Nutr Res 2009;29:387; with permission.) Fig 2 Plasma insulin levels corresponding to glucose levels in Fig 1 Insulin secretion closely mimics glucose levels; foods with low glycemic index will result in a more blunted insulin response... divided in three parts depending upon carbohydrate intake and administered 15 minutes before each meal The dinner dose may need to be decreased to accommodate the morning NPH peak Glargine and aspart or lispro can be administered in four injections per day Approximately 50% to 60% of the total daily insulin requirement is administered at bedtime as glargine, and the remaining insulin is divided into three... combined metabolic effects of hormones in the maternal circulation, specifically human placental lactogen, progesterone, prolactin, and cortisol and various cytokines The increase in insulin resistance generally parallels placental mass and the increase in placental hormones Table 2 Diabetes classification Findings Phenotype Type 1 Immune-mediated, genetic predisposition Insulinopenic Ketoacidosis Begins . diabetes. 16,17 Glargine, a long-acting insulin analog, was approved by the FDA in 2000 for use as basal insulin. Insulin glargine has a glycine substitution in the a-chain. Basal insulin is approximately 50% to 60% of the total daily insulin requirement; the remaining insulin would then be divided into injections of short-acting Pregestational