Obstetrics

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[edit] Obstetrics

Urania Magriples

Joshua A. Copel

[edit] EPIDEMIOLOGY AND HIGH-RISK GROUPS

The physician delivering obstetric care has the unique opportunity to provide general medical treatment and screening to a large portion of the population that might not otherwise gain access to the health care system. There are over 7 million pregnancies in the United States yearly, with over 4.1 million live births (Fig. 41-1). Although rates of infant mortality and morbidity have been drastically reduced in this century, the United States still has one of the highest rates among industrialized countries, ranking twenty-first.

Figure 41-1 Mother and her youngest child, 1937. (From Collections of the Library of Congress.)

Certain demographic groups are at higher risk for poor outcomes. For example, the United States has one of the highest teenage pregnancy rates, with 1 million teenagers, or 5% to 8% of the teenage population, becoming pregnant each year. Teenagers are more likely to register late for prenatal care, be unmarried, and have less education, and they have more than twice the risk of low-birth-weight infants, neonatal mortality, and maternal mortality compared with older mothers. Racial differences persist in both maternal and infant morbidity and mortality. Currently, the infant mortality rate of African-Americans is higher than that of impoverished nations such as Cuba. As more women and children fall below the poverty line in the United States, a concerted effort is needed to expand access to prenatal care and thereby entry into the medical system.

[edit] PHYSIOLOGIC CHANGES OF PREGNANCY

The emerging concept that reproductive changes are a physiologic adaptation rather than a pathologic state has led internists and obstetricians to redefine their approach to the primary care of women. Although the physiologic changes during pregnancy are profound, most occur within a short period of time and are completely reversible. Those that are of primary interest to generalists are reviewed in Table 41-1.

Table 41-1 Physiologic Changes of Pregnancy by System

[edit] HISTORY AND PHYSICAL EXAMINATION

The presence of pregnancy must be considered in every woman of reproductive age. Common signs and symptoms of pregnancy include amenorrhea, breast fullness and tenderness, fatigue, nausea and/or vomiting, increased appetite, and increased abdominal girth. On physical examination, the cervix appears bluish, and on bimanual palpation it is soft and flexible. The uterus increases in size with advancing gestational age and fills the pelvis at around 12 weeks. It is palpated above the pubic bone after that point and reaches the umbilicus at 20 weeks. After 20 weeks, the fundal height correlates roughly with centimeters above the pubic bone.

[edit] LABORATORY STUDIES

Pregnancy can be rapidly ruled out using commonly available sensitive serum or urinary pregnancy tests. Human chorionic gonadotropin (hCG) is a specific marker for viable trophoblast tissue and is directly correlated with gestational age. Most urinary tests are enzyme-linked immunosorbent assays (ELISA), which use a color reaction produced by an enzyme that is linked to an antibody. They vary in sensitivity with the lower limits of the assays, ranging from 200 to 800 IU/ml. Urine tests are available that are positive by day 25 after the last menstrual period. Serum radioimmunoassays are sensitive and accurate if directed to the β-subunit of the hCG molecule. In early pregnancy, hCG concentrations double approximately every 2 days, and an inadequate rise should raise the question of either a nonviable gestation or an ectopic pregnancy.

[edit] DIFFERENTIAL DIAGNOSIS

Vaginal bleeding in the first trimester is not uncommon and occurs in about 25% of pregnancies. Implantation bleeding is common and consists of minimal bleeding around the time of the first missed menstrual period. Flow may vary from mere spotting to bleeding that is similar to a period, but is rarely heavier than a period. If bleeding is observed from a closed cervical os and there is a documented intrauterine pregnancy, the diagnosis of a threatened abortion can be made. The uterus is generally appropriate in size but may be tender to examination. Once the cervix is dilated or the bleeding is profuse, the diagnosis of an inevitable abortion is made. An incomplete abortion signifies that there is tissue still within the uterus. Incomplete abortions become more common after 6 weeks of gestation. In an anembryonic gestation, formerly referred to as a missed abortion, the pregnancy has partially resorbed but there is still viable trophoblast-secreting hCG.

Ectopic pregnancy should be suspected in any woman of reproductive age presenting with abdominal pain or vaginal bleeding. Because approximately 2% of pregnancies are ectopic, constant vigilance is necessary to make the diagnosis. Ectopic pregnancies are the most common cause of maternal mortality in the first half of pregnancy and account for up to 50 maternal deaths annually. The rates of ectopic pregnancy are two times higher for nonwhite females than white females; however, mortality rates are six times higher for African-American women, making ectopic pregnancy the single most common cause of all maternal deaths in this population. Risk factors for ectopic pregnancy include multiparity, pelvic inflammatory disease, tubal surgery, previous pelvic surgery, previous ectopic, and intrauterine device (IUD) use.

The most common presenting signs are abdominal and adnexal tenderness, which are present in nearly all patients. Vaginal bleeding is present in 90% of cases. A pelvic mass is palpable in over half of patients, and the uterus is usually not appropriately enlarged. Tachycardia, orthostasis, and shock may follow rupture. Levels of hCG over 2000 IU/ml without the presence of an intrauterine pregnancy by vaginal ultrasonography suggest an ectopic pregnancy. Ultrasonographic detection of a pelvic mass is not definitive in the diagnosis of an ectopic pregnancy, since a corpus luteum or other benign ovarian tumor may be present; therefore correlation with the quantitative hCG level is recommended. Medical intervention with methotrexate is a treatment option for early ectopic pregnancies.

[edit] MANAGEMENT

[edit] Prenatal Care

The physician taking care of women has the opportunity to have an impact not only on the lives of women, but on the lives of their children and future generations. Preconceptual care is essential in minimizing exposure to drugs and teratogens, maximizing nutritional status, and identifying medical conditions that may either affect pregnancy or be influenced by it. Primary care physicians play an important role in the care of women of reproductive age who are considering pregnancy.

In the United States, 200,000 birth defects and over a half million infant deaths, spontaneous abortions, stillbirths, and miscarriages occur each year from defective fetal development. It is estimated that 1% to 5% of congenital anomalies may be drug or chemical related. Factors that determine a drug's effect on the fetus include dosage, duration, and time of exposure, as well as drug metabolism, concurrent use of other drugs, genetic susceptibility, and placental transfer. There is a critical period of embryonic development from the third through the twelfth week when the embryo is undergoing organogenesis. Before this time, exposures tend either to cause abortion or to have no effect at all (known as the all-or-none phenomenon). Beyond the twelfth week, effects are generally limited to growth and neural development. Primary care physicians often care for women in the crucial weeks of fetal organogenesis and therefore need to be aware of the effects of drugs on fetal development. Examples of recognized teratogens and their associated malformations are listed in Table 41-2.

Table 41-2 Teratogenic and Fetopathic Therapies and Environmental Agents

Infectious agents also cause maldevelopment in the human (Table 41-3). The lethal or developmental effects are the result of mitotic inhibition, direct cytotoxicity, or necrosis. Inflammatory responses to infection can lead to metaplasia, scarring, or calcification, which further damages normal development.

Table 41-3 Infection-induced Fetopathy

Chronic maternal conditions also are associated with an increased risk of teratogenicity. For example diabetic mothers with hemoglobin A_1C levels greater than 7.5 have a twofold increased risk of congenital malformations, and the risk is greater with increasing levels. Levels of phenylalanine greater than 20 mg/dl in mothers with phenylketonuria are associated with a 90% incidence of congenital malformations, whereas levels less than 16 mg/dl are associated with a 20% incidence. Women with seizures have a twofold to threefold increased incidence of congenital anomalies regardless of whether they are on medications. Folate requirements increase in pregnancy and in women on antiepileptic medications. Therefore folate supplementation is recommended.

[edit] Nutrition.

Current recommendations for nutrition in pregnancy are based on the pregnant woman's pregravid weight. For women who are within the optimal weight range for their height, the recommended weight gain is 20 to 35 pounds, with 5 pounds gained in the first trimester and approximately 1 pound per week in the second and third trimesters. For women who are overweight (20% or more above ideal body weight) the total weight gain should be about 15 to 25 pounds, with 2 pounds gained in the first trimester and about two thirds of a pound gained per week in the second and third trimesters. For women who are underweight (10% or more below ideal body weight), the total weight gain should be 28 to 40 pounds, with 5 pounds gained in the first trimester and at least a pound a week gained in the second and third trimesters, depending on the pregravid weight.

Protein, iron, and calcium requirements increase during pregnancy; however, the need for supplementation depends on the pregravid nutritional status. Women with short interpregnancy intervals, teenagers, grand multiparae, and patients of low socioeconomic status are at highest risk for nutritional deficiencies. Protein requirements increase in pregnancy from 50 to 90 gm/day. Iron needs average about 3.5 mg/day. Total iron demands during a singleton pregnancy average 1000 to 1100 mg and are higher for gestations with more than one fetus. Calcium requirements increase to 1200 mg/day, 50% higher than the nonpregnant recommendation. Folate requirements increase to 800 mg, and periconceptual folate supplementation decreases the incidence of neural tube defects.

[edit] Prenatal Visits.

The basic laboratory tests recommended for all pregnant women are listed in Box 41-1. Routine visits are scheduled monthly until 30 weeks, every 2 weeks until 36 weeks, and then weekly. At each visit, weight, blood pressure, urine screening for protein and glucose, and measurement of the fundal height and auscultation of the fetal heart are performed.

Genetic testing by amniocentesis or chorionic villus sampling (CVS) is routinely offered to women who will be 35 years old at the time of delivery because they are at increased risk for fetal aneuploidy. Thorough patient and family histories will reveal other risk factors for genetically transmissible diseases. A stillborn fetus has a 6% to 11% risk of having a chromosomal abnormality; therefore women with a history of stillborn births should be counseled. Couples with a history of three or more pregnancy losses or prolonged infertility have up to a 6% risk of a chromosomal abnormality. A previous child with a chromosomal abnormality or congenital malformation likewise puts the parents in a high-risk group with future pregnancies.

Ethnicity is also important, since certain groups carry a higher risk for genetic diseases. Whites have a 1 in 20 risk of carrying the recessive gene for cystic fibrosis. Individuals of Mediterranean descent have a 1 in 12 risk of being carriers of the β-thalassemia gene. (The mean corpuscular volume [MCV] is useful as a screening test for thalassemia trait.) Ashkenazi Jews, who have a 1 in 30 risk of carrying the gene for Tay-Sachs disease and a 1 in 40 risk of carrying the gene for Canavan's disease, should be offered testing for these carrier states. The carrier rate for sickle-cell disease is 1 in 12 in African-Americans. The chance of having an affected child when both parents are carriers of any of these autosomal recessive diseases is 25%, and prenatal testing should be offered.

Although the risk of Down syndrome (trisomy 21) is greatest in women aged 35 or over, the majority of affected infants are born to women younger than 35, since they represent a larger percentage of the childbearing population. Prenatal diagnosis on the basis of age alone detects only 20% to 30% of these infants; thus screening for maternal serum markers has been used to increase detection. Alpha-fetoprotein (AFP) is the major early fetal serum protein. It enters the amniotic fluid via fetal renal excretion, transudation through skin, and open lesions such as spina bifida and ventral wall defects. An elevated level is found with open neural tube and ventral wall defects, twin gestations, intrauterine fetal demise, as well as pregnancies at risk for growth retardation and fetal death. In contrast, a low level of maternal serum AFP (MSAFP) has been associated with an increased risk of trisomy 21 and other trisomies. MSAFP testing in women under the age of 35 will detect an additional 25% of pregnancies affected by Down syndrome, with a 5% false-positive rate. Recent studies have shown that maternal serum concentrations of hCG are at least two times higher than normal, and those of unconjugated estriol are 25% lower in the presence of fetal Down syndrome. The additional use of these markers improves the detection rate to 67%, with a 7.2% false-positive rate.

Ultrasound has been used as a screening tool in the detection of neural tube and ventral wall defects in women with elevated MSAFP, and in experienced hands has a very high sensitivity and specificity. Unfortunately, the detection rate of trisomies by ultrasound is variable, and therefore ultrasound is not expected to replace amniocentesis in women at high risk. Routine ultrasound in all obstetric patients is a controversial issue, but certainly if the couple desires information on prenatal diagnosis of congenital anomalies, then second trimester ultrasound at a tertiary center is advisable.

A fetal karyotype can be obtained by CVS or amniocentesis. An advantage of CVS is that it can be performed in the first trimester (10 to 12 weeks), with results obtained in less than a week. Thus pregnancy termination, if desired, is a less complicated procedure. CVS has a procedure-related miscarriage rate of 0.5% to 1%. Amniocentesis can be performed after 15 weeks' gestation with a procedure-related miscarriage rate of 0.5%. Amniocytes take 10 days to 2 weeks to grow in culture. Because of these delays, termination of pregnancy requires either a dilation and evacuation, a more complex procedure than in the first trimester, or induction of labor with prostaglandin.

[edit] Medical Complications of Pregnancy

The primary care physician may intervene at two points in a high-risk pregnancy (Table 41-4). In the preconceptual patient, the physician has the opportunity to control disease and plan for its management during pregnancy. The primary care physician also may be involved in managing women who develop medical complications after conception. These patients are best cared for in close consultation with a perinatologist.

Table 41-4 Medical Complications of Pregnancy

[edit] Diabetes.

Previously diagnosed diabetes complicates 0.5% of pregnancies in the United States; gestational diabetes affects an additional 4% and is predominantly diet controlled.

The hormonal changes of pregnancy cause an increased insulin response to a glucose load in normal pregnant women and worsening of control in the diabetic pregnancy. Estrogen and progesterone induce pancreatic β-cell hyperplasia and increased insulin secretion, as well as increased glycogen storage, peripheral glucose utilization, and decreased hepatic glucose production. In the late second and third trimesters, human placental lactogen, prolactin, and cortisol combine to increase insulin resistance and decrease glucose tolerance and ensure adequate levels of glucose and amino acids for fetal growth. Because of these changes, patients with insulin-dependent diabetes will commonly have frequent episodes of hypoglycemia and ketonuria in the first trimester and are more prone to ketoacidosis in the second and third trimesters.

[edit] Gestational Diabetes.

Gestational diabetes is defined as the onset or recognition of glucose intolerance during pregnancy. This definition includes patients with preexisting diabetes that is first detected in pregnancy and those who develop glucose intolerance only in pregnancy. The latter group is not prone to hyperglycemia or ketosis in the first trimester and the associated increased incidence of congenital malformations.

All pregnant women should routinely be screened at 28 weeks of gestation with a 50 gm oral glucose tolerance test. Those with strong risk factors (e.g., obesity, a history of gestational diabetes, or an infant with a congenital anomaly, macrosomia, or fetal demise) should be screened earlier. Women who have an abnormal screening test (1 hour serum glucose greater than 145 mg/dl) undergo a 3-hour 100 gm glucose test. Criteria for diagnosing gestational diabetes vary. Many physicians follow the guidelines developed by the National Diabetes Data Group (NDDG) in which two elevated blood glucose values greater than 105, 190, 165, and 145 mg/dl for the fasting, 1-, 2-, and 3-hour tests, respectively, are considered abnormal. Although these criteria have been criticized as being too high, the current recommendations are that the NDDG data be used until an international consensus can be obtained.

The mainstay of therapy in gestational diabetes is diet. Current recommendations call for individualized caloric intake according to the patient's weight and a dietary composition containing 50% to 60% carbohydrate, 12% to 20% protein, and approximately 25% fat, with less than 10% as saturated fatty acids, up to 10% as polyunsaturated fatty acids, and the remainder of ingested fat derived from monosaturated forms. Glucose monitoring is accomplished with daily home blood glucose monitoring of fasting and 2-hour postprandial glucose assessment. The use of insulin is recommended for those with fasting glucose values consistently greater than 100 mg/dl, or 2-hour postprandial levels greater than 120 mg/dl. Oral hypoglycemics are not recommended for use in pregnancy, as the sulfonylureas are known to cross the placenta and stimulate the fetal pancreas to secrete insulin. (Hyperinsulinemia is one of the postulated mechanisms for adverse fetal outcomes such as macrosomia.) Oral hypoglycemics also cause prolonged neonatal hypoglycemia due to slower hepatic elimination of these drugs by the neonate.

Infants of gestational and overt diabetics are at an increased risk of perinatal complications, including hypoglycemia, hyperbilirubinemia, hypocalcemia, polycythemia, respiratory distress syndrome, macrosomia, and fetal trauma. Fetal demise due to poor control of gestational diabetics is rarely seen today since the implementation of glucose monitoring, diet, and antenatal testing.

Debate continues about the long-term maternal consequences of gestational diabetes. Women who have gestational diabetes are at increased risk for diabetes later in life. Longitudinal studies of women followed up to 20 years after the diagnosis of gestational diabetes report prevalence rates of diabetes requiring therapy as high as 21% and of diabetes not requiring therapy up to 54%. Individuals with persistent obesity are at highest risk for developing subsequent diabetes.

[edit] Insulin-dependent Diabetes.

The leading cause of perinatal mortality in infants of mothers with insulin-dependent diabetes is congenital malformations. Major anomalies are two to three times more common and are correlated with an elevated hemoglobin A_1C (glycosylated hemoglobin). Malformations are most common in the central nervous system, cardiovascular, gastrointestinal, genitourinary, and skeletal systems. Preconceptual control is advocated to decrease the incidence of these malformations, as they occur in the first few weeks after conception, often before a patient presents for prenatal care. Because of these risks, a targeted ultrasound, maternal serum triple screen determination, and fetal echocardiogram are indicated.

Infants of diabetic mothers are at increased risk of developing diabetes later in life. Insulin-dependent diabetes is transmitted less frequently to the offspring of diabetic women than diabetic men. Offspring with two diabetic parents have the highest risk (30%) of developing diabetes. Type II diabetes is probably inherited as an autosomal dominant trait; thus 50% of offspring with one affected parent will inherit the tendency for the disease, although other factors, such as obesity and diet, influence penetrance.

Glucose control is accomplished by one to three daily injections of insulin and glucose monitoring to maintain fasting and two hour postprandial glucose levels less than 90 and 120 mg/dl, respectively. The addition of long-acting insulin at bedtime is often necessary to obtain euglycemia. The first trimester is characterized by episodes of hypoglycemia, whereas the second and third trimesters are characterized by increasing glucose and insulin resistance; therefore close monitoring is necessary. Poor control, frequent insulin reactions, and new onset diabetes require hospitalization for management and education.

Pregnancies complicated by diabetes are monitored closely by ultrasound for abnormalities in fetal growth and for polyhydramnios. All diabetic pregnancies have a higher incidence of preeclampsia, pyelonephritis, and worsening of hypertension and need to be monitored closely. Patients should be seen every 2 weeks until 30 weeks, then weekly. Pregnancies with good control are allowed to progress to term, whereas pregnancies with poor control, worsening hypertension, or fetal growth derangements are delivered before term after documentation of fetal lung maturity by amniocentesis.

In addition to a careful history and physical examination, all pregnant diabetic women should be screened for end-organ complications with a baseline ophthalmologic examination, 24-hour urine collection for creatinine and protein determinations, serum electrolytes, cholesterol, and electrocardiogram. Pregnant diabetic women with preexisting nephropathy, who have a creatinine level greater than 1.5 mg/dl, proteinuria greater than 3 gm in 24 hours in the first trimester, or poorly controlled hypertension have a poor prognosis in terms of pregnancy outcome. Renal function may remain stable after the pregnancy; however, in 20% to 40% of patients it declines. Pregnancy-induced hypertension occurs in 25% of diabetic pregnancies and is associated with worsening of renal function; therefore close monitoring is warranted. Proteinuria commonly increases along with the glomerular filtration rate (GFR), but returns to baseline after pregnancy in the majority of patients. Elevated blood pressure and a rapid decrease in creatinine clearance are the most common events leading to preterm delivery; therefore strict blood pressure control is necessary.

Most women with nephropathy have evidence of microvascular disease and atherosclerosis. The influence of pregnancy on diabetic retinopathy is not well understood. Initially, there was concern that pregnancy accelerated the process, particularly with rapid normalization of serum glucose; however, these changes may reflect the natural progression of disease and its identification in pregnancy. Close ophthalmologic follow-up is warranted. Maternal mortality rate may be as high as 67% in women with diabetes and ischemic heart disease; therefore pregnancy termination for maternal indications should be considered in these patients.

[edit] Hypertension.

Hypertension complicates 10% of pregnancies and causes significant fetal and maternal mortality and morbidity. Preeclampsia accounts for 70% of cases of hypertension in pregnancy, with chronic hypertension accounting for most of the remaining 30% of cases. The American College of Obstetrics and Gynecology defines hypertension in pregnancy as either a systolic pressure of 140 mm Hg or an increment of 30 mm Hg from the first prenatal value, or a diastolic pressure of 90 mm Hg or an increment of 15 mm Hg. The decrease in peripheral vascular resistance during pregnancy can make the diagnosis of hypertension difficult, since blood pressure normally drops in the first and second trimesters only to increase in the third trimester.

Preeclampsia is classically described as the triad of edema, proteinuria, and hypertension. Unfortunately, edema is present in up to 80% of normotensive pregnancies and is not always present in eclampsia. Mild preeclampsia is diagnosed by a blood pressure reading of 140/90 taken on two occasions 6 hours apart in the presence of proteinuria. Severe preeclampsia is diagnosed when one of the following is present: (1) blood pressure ≥160 mm Hg systolic or ≥110 mm Hg diastolic on two occasions at least 6 hours apart with the patient at bed rest, (2) proteinuria ≥5 gm in a 24-hour urine collection or +3 on dipstick in at least two random clean catch samples 4 hours apart, (3) oliguria (urine output <30 cc/hour), (4) cerebral or visual disturbances, (5) epigastric pain, or (6) pulmonary edema or cyanosis. The appearance of preeclampsia in the first and second trimesters raises the suspicion of a molar pregnancy or maternal systemic lupus erythematosus.

Risk factors for preeclampsia include preexisting hypertension, renal disease, diabetes, multiple gestations, nulliparity, family history of preeclampsia, and a fetus with hydrops. Treatment of preeclampsia is delivery of the fetus and placenta. If the pregnancy is at or near term, delivery can be accomplished by cervical ripening and induction of labor. If the pregnancy is remote from term, then management depends on the severity of disease. Mild preeclampsia can be managed as an outpatient or inpatient, depending on patient reliability and compliance with bed rest and follow-up. Severe preeclampsia warrants admission and careful monitoring of maternal renal, hepatic, and hematologic parameters, as well as treatment of diastolic blood pressures ≥105 mm Hg. If fetal pulmonary maturity is documented, then delivery is warranted. If fetal pulmonary maturity is not present, conservative management can be considered if fetal well-being can be monitored. Steroids are given to accelerate lung maturation. These pregnancies are at high risk for intrauterine growth retardation (IUGR), fetal distress, and stillbirth; therefore close fetal monitoring and consultation with maternal-fetal medicine and neonatal teams are mandatory for conservative management of severe preeclampsia.

The reported incidence of HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) in preeclampsia ranges from 2% to 12%. A severe form of preeclampsia, it can be confused with other disorders associated with liver dysfunction or hemolytic anemia.

Eclampsia is defined as the development of seizures or coma in a patient with signs and symptoms of preeclampsia. The reported incidence is up to 0.5% of all deliveries. Only about 50% of cases occur antepartum.

Magnesium sulfate is widely used in the United States in preeclampsia to prevent and control seizures. The drug is administered by continuous intravenous infusion with a 6 gm load over 20 minutes followed by a maintenance rate of 2 gm/hour. Serum magnesium levels are followed, and the rate of the infusion is adjusted to maintain a level between 4.8 and 9.6 mg/dl. Magnesium is excreted by the kidneys; therefore close monitoring of urine output is necessary and dose adjustment is warranted in the face of persistent oliguria. In the therapeutic range, magnesium slows neuromuscular conduction. Suppression of deep tendon reflexes, respiration, and eventually coma and asystole are seen in overdoses. Overdose can be reversed with the administration of intravenous calcium gluconate. Magnesium sulfate therapy is continued for 24 hours postpartum or after an eclamptic episode. Other anticonvulsants have been used including phenobarbital, diphenylhydantoin and valium, but there are studies to support that magnesium sulfate is more effective at both prevention and recurrence of eclampsia.

Antihypertensive drug therapy in pregnancy is limited by concerns of teratogenicity and fetal side effects. Methyldopa has been used for many years with no adverse fetal side effects. Calcium channel blockers are now widely used in pregnancy for both the treatment of hypertension and preterm labor with minimal side effects. β-Blockers also have been used widely, and although initially they were thought to cause frequent fetal side effects, it is now established that side effects are due to maternal condition rather than drug effect. Angiotensin-converting enzyme inhibitors have been associated with oligohydramnios, IUGR, fetal renal failure, and intrauterine demise and are contraindicated in pregnancy. Diuretics are contraindicated for treatment of hypertension in pregnancy, as they decrease intravascular volume and therefore placental perfusion. Diuretics are used only in patients with congestive heart failure and pulmonary edema. Neither low-dose (80 mg) aspirin nor calcium supplementation has been shown to be effective in reducing the risk of preeclampsia or growth restriction in pregnancy and therefore are not indicated as treatment modalities.

Treatment of hypertension has significant maternal benefit, but there has been no proven fetal benefit in prolonging gestation, increasing birthweight, or reducing the risk of placental abruption or preeclampsia.

[edit] Thyroid Disease.

Several physiologic changes occur in the thyroid gland during pregnancy to maintain a euthyroid state. The thyroid increases iodine uptake and production of thyroid hormone in response to a decline in plasma iodine concentration that results from an increase in GFR and iodine clearance. Estrogen stimulates production of thyroid-binding globulin (TBG), and because 85% of circulating thyroid hormone is bound to TBG, levels of thyroxine (T₄) and triiodothyronine (T₃) increase. The T₃ uptake (T₃U), which is inversely related to thyroid hormone-binding capacity in serum, is reduced due to elevated TBG concentrations. Levels of free thyroid hormone (free thyroxine index) are in the normal range. Thyroid-stimulating hormone (TSH) levels are slightly suppressed in the first trimester and subsequently normalize; therefore they are an accurate marker for hypothyroidism.

[edit] Hypothyroidism.

Although hypothyroidism is common in reproductive-aged women, untreated hypothyroidism is not commonly seen in pregnancy, probably because of the inability of hypothyroid patients to ovulate.

Untreated hypothyroidism during pregnancy is associated with an increased incidence of spontaneous abortion, IUGR, stillbirth, and congenital anomalies, as well as preeclampsia and abruption. Autoimmune thyroiditis usually improves during pregnancy and relapses postpartum. Antimicrosomal and antithyroglobulin antibodies, if present, are rarely associated with any fetal side effects.

Treatment of hypothyroidism is with oral l-thyroxine at a starting dose of 125 to 150 mg, with follow-up determinations of serum TSH and T₄ levels every 3 weeks. If TSH levels remain elevated, the dose of l-thyroxine is increased by 50-mg increments. The increase in TBG may necessitate higher doses than in the nonpregnant state.

[edit] Hyperthyroidism.

Hyperthyroidism occurs in about 2 of every 1000 pregnancies. Graves' disease or autoimmune thyrotoxicosis is the most common cause. Subclinical hyperthyroidism may be difficult to distinguish in early pregnancy, as an increase in heart rate, heat intolerance, skin warmth, nausea, and poor weight gain are common symptoms in the first trimester. Tachycardia, thyromegaly, exophthalmos, and failure to gain weight with normal or increased caloric intake are not normal and can be helpful clues. Thyrotoxicosis can be associated with severe vomiting and may be the cause of hyperemesis gravidarum, or result from molar gestations and choriocarcinoma. In the latter two conditions, elevated hCG levels, which stimulate thyroid hormone, and the thyroid dysfunction are completely reversible with uterine evacuation.

Hyperthyroidism is diagnosed by elevated free T₄ level and values of TSH below 0.1 mU/ml. Occasionally, the free T₄ is normal and the T₃ is elevated. Determination of the presence of autoantibodies (thyroid-stimulating immunoglobulins or long-acting thyroid stimulator) is necessary because they are IgG and can cross the placenta. Fetal or neonatal hyperthyroidism secondary to transfer of maternal antibodies complicates approximately 1% of pregnancies in women with a history of Graves' disease or Hashimoto's thyroiditis. In women who have undergone thyroid ablation, the presence of antibodies still must be determined.

In pregnancy, treatment of hyperthyroidism is most commonly medical. The thiourea derivatives propylthiouracil (PTU), methimazole, and carbamazole are all used. PTU is the most commonly used medication and is not associated with fetal abnormalities. The objective is to maintain the mother in the high normal range to avoid fetal hypothyroidism. Initially, thyroid function tests are followed every 2 weeks, but when a stable dosage is obtained, they can be followed monthly. If a drug reaction occurs, therapy is changed to methimazole (Tapazole). Methimazole is associated with reversible aplasia cutis in the fetus and therefore is kept as the second-line drug. Although both drugs are secreted in breast milk, less PTU is secreted because it is more protein-bound. Thyroidectomy is reserved for women who cannot adhere to medical therapy or who have toxic side effects to it. Radioactive iodine is contraindicated in pregnancy, since iodine is concentrated in the fetal thyroid after 10 weeks and can result in fetal goiter.

Maternal complications of hyperthyroidism in pregnancy include hyperemesis, poor weight gain, preterm labor, thyroid storm, and high-output cardiac failure. Fetal complications include fetal tachydysrhythmias, high output cardiac failure, hydrops, IUGR, and goiter.

[edit] Cardiac Disease.

The physiologic changes of pregnancy, delivery, and the puerperium cause significant alteration in the maternal cardiovascular system. Increase in the myocardial workload is related to increased blood volume, metabolic demands, cardiac output, and heart rate. Increases in blood pressure and anemia also can affect cardiac output. Patients with well-compensated heart disease may thus have heart failure for the first time during pregnancy. The goal of medical management is to optimize maternal hemodynamics by changing preload, afterload, and contractility once symptomatology is present. Diuretics are reserved for pulmonary edema or right-sided heart failure. Digoxin is used to control atrial fibrillation. Afterload reduction may be beneficial in improving cardiac output.

Labor and delivery are a crucial time, with increased hemodynamic load associated with contractions, pain, anesthesia, possible surgery, blood loss, and intravenous therapy. Therefore complete hemodynamic monitoring optimizes fluid management and pharmacologic manipulation of cardiac output. In labor, epidural anesthesia is recommended to relieve pain and to avoid Valsalva maneuvers. Use of the lateral position is important, since it minimizes hypotension and increases preload and cardiac output. Cesarean delivery is undertaken for obstetric indications, as vaginal delivery avoids the stress and blood loss of surgery. Instrumental delivery by low forceps or vacuum extraction is recommended to avoid Valsalva's maneuvers. Postpartum, intensive monitoring in the first 48 hours is necessary, since this is the period of highest risk for fluid shifts secondary to autotransfusion with placental delivery and uterine involution.

Classification of maternal mortality for various types of cardiac disease is useful in counseling patients. Mitral stenosis with atrial fibrillation or New York Heart Association classes III and IV aortic stenosis, uncorrected tetralogy of Fallot, previous myocardial infarction, and Marfan syndrome with a normal aorta are associated with a maternal mortality rate of 5% to 15%. Pulmonary hypertension, aortic coarctation, and Marfan syndrome with aortic root dilation greater than 4 cm carry a 25% to 50% maternal mortality rate and can be considered a contraindication to pregnancy.

Peripartum cardiomyopathy is characterized by the development of cardiac failure in the third trimester or within 5 months of delivery for which no other cause can be determined. The incidence of peripartum cardiomyopathy is 1 in 3000 to 4000 pregnancies. In the United States, it is more frequent among older, multiparous African-American women, twins, and patients with preeclampsia. It has a tendency to recur with subsequent pregnancies. Some investigators have implicated inadequate nutrition, viral agents, preeclampsia, or immunologic factors in its pathogenesis. Another theory suggests that viral myocarditis may be the primary inciting factor. The prognosis for dilated cardiomyopathy is poor, with progressive deterioration once symptoms occur. The mortality rate for peripartum cardiomyopathy in the United States ranges from 25% to 50%. There may be a subset of patients in whom the heart size returns to normal who have a significantly better prognosis. This group also may include patients who had stable cardiac disease before conception.

[edit] ADDITIONAL READINGS

• GG Briggs, RK Freeman, SJ Yaffe: Drugs in pregnancy and lactation: a reference guide to fetal and neonatal risk ed 5. Baltimore: Williams & Wilkins; 1998:
• GN Burrow, TP Duffy: Medical complications during pregnancy ed 5. Philadelphia: WB Saunders; 1999:
• RK Creasy R Resnik Maternal-fetal medicine: principles and practice. ed 4. Philadelphia: WB Saunders; 1999:
• AT Geronimus, J Bound: Black/white differences in women's reproductive-related health status: evidence from vital statistics. Demography 1990; 27:457.
• N Gleicher Principles and practice of medical therapy in pregnancy. ed 3. Connecticut: Appleton & Lange; 1998:
• A Milunsky Genetic disorders and the fetus. Baltimore: Johns Hopkins University; 1992:
• DA Nyberget al.: Transvaginal sonography. St Louis: Mosby; 1992:
• EA Reece DR Coustan Diabetes mellitus in pregnancy: principles and practice. ed 2. New York: Churchill Livingstone; 1995:
• EA Reeceet al.: Medicine of the mother and fetus. ed 2. Philadelphia: Lippincott-Raven; 1999:
• ME Wegman: Annual summary of vital statistics—1991. Pediatrics 1992; 90:835.