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Contents
Foreword xv
William F. Rayburn
Preface xvii
Judith U. Hibbard
Pregestational Diabetes 143
Gabriella Pridjian
The prevalence of preexisting diabetes inpregnancy 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 inPregnancy 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 onMedicalDisordersin Pregnancy
Management of Renal Disease inPregnancy 195
Tiina Podymow, Phyllis August, and Ayub Akbari
Although renal disease inpregnancy is uncommon, it poses considerable
risk to maternal and fetal health. This article discusses renal physiology
and assessment of renal function inpregnancy 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 inPregnancy 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 disordersin 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 inmedical 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 inPregnancy 321
Britta Panda, Alexander Panda, and Laura E. Riley
This article reviews the impact of seasonal influenza onpregnancy 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 inpregnancy 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 updateon 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 Disordersin 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 medicaldisorders 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 inpregnancy is revisited, providing insight into issues of screening. A clin-
ical framework for understanding renal disease inpregnancy 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 updateon 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 Disordersin Pregnancy
disease, is included. Insight is provided into newer treatment modalities in gesta-
tional diabetes, particularly oral hypoglycemic agents. Cholestasis inpregnancy 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 updateon the unique impact of
H1N1 virus onpregnancy is reviewed. A clear, logical framework for thrombophilia
screening and thromboprophylaxis inpregnancy 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 inpregnancy 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 inpregnancy 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