118 The Healthy Pregnancy
• The incidence of venous thromboembolism increases by a factor of 5 during pregnancy; pulmonary embolism is a leading cause of maternal mortality in the United States.
• Approximately 2% to 10% of gravid and nongravid patients have asymptomatic bacteriuria, which will eventually progress to acute pyelonephritis in as many as 40% of gravid patients.
• Acute pyelonephritis during pregnancy increases the risk for preterm labor; these patients should be admitted for intravenous antibiotic therapy.
• One third of patients will have improvement in their asthma symptoms during pregnancy, one third will remain the same, and one third will have worsening symptoms.
• As many as one third of patients with epilepsy will experience an increase in seizure activity during pregnancy.
• Treatment of human immunodeficiency virus infection during pregnancy with zidovudine can reduce the incidence of perinatal transmission from mother to infant by 70%.
Epidemiology
Each year, 4.1 million live births in the United States result from approximately 6.5 million pregnancies.1,2 These women routinely go to the emergency department (ED) for general medical complaints, as well as for pregnancy-specific issues. In addition, more patients with complex medical problems are becoming pregnant because of advances in fertility treatments. Pregnancy can be an emotionally stressful condition that requires special attention from caregivers. Because diagnostic and management strategies are altered in pregnancy, a thorough understanding of the physiologic changes that accompany pregnancy is mandatory (Box 118.1).
Pathophysiology
Gravidity refers to the total number of pregnancies conceived, including the current pregnancy. Parity characterizes the outcome of the pregnancy, and it is further subdivided into four categories described by the mnemonic TPAL (number of term infants, preterm infants, abortions, and living children; Box 118.2).
Box 118.2 Gestation and Parity Notation
Gestatation (G): Total number of pregnancies
Parity (P): Subdivided into four categories described by the mnemonic TPAL—number of term infants, preterm infants, abortions, and living children
Example: G4P3 describes a woman who has had four pregnancies and three deliveries; G4P3 (2-1-1-3), also written as G4P2113, describes a woman who has had two term deliveries, one preterm delivery, and one abortion (spontaneous or induced) and has three living children.
Presenting Signs and Symptoms
Emergency physicians (EPs) should consider the possibility of pregnancy in every female patient of childbearing age regardless of the chief complaint or symptoms. One study documented pregnancy in 7% of ED respondents who indicated that their last menstrual period was on time and normal and that there was “no chance” that they were pregnant.3 Early signs of pregnancy include missed menses, vaginal bleeding, nausea, vomiting, breast tenderness, urinary frequency, fatigue, near-syncope, and abdominal pain or bloating. Some patients may not have these symptoms or may ignore them and later go to the ED with an obviously enlarged uterus or in labor.
Respiratory System
The physiology of breathing in pregnancy is altered by both anatomic and hormonal changes. Anatomic changes include an increase in chest diameter and circumference, as well as a rise in the level of the diaphragm. The result is a reduction in total lung capacity by 5% and functional residual capacity by 20%. In contrast, vital capacity does not change.4 The respiratory rate also remains constant, but because of a progesterone-mediated increase in both tidal volume and minute ventilation, PaCO2 decreases to an average of 30 mm Hg. The sensation of dyspnea is increased during pregnancy.
Hematologic and Immunologic Systems
Blood volume increases during pregnancy by an average of 40% to 50% secondary to both plasma volume expansion and increased erythrocyte mass. Plasma volume increases approximately 50%, with a plateau reached at 30 weeks of gestation. Erythrocyte mass increases 20% to 30% over prepregnancy levels and peaks near term, with greater increases associated with iron supplementation. Asymmetric expansion of the plasma and erythrocyte mass results in a relative anemia, referred to as the physiologic anemia of pregnancy. Plasma expansion begins earlier than erythropoiesis but then stabilizes, with the nadir in hemoglobin concentration occurring between weeks 16 and 28.5 Hemoglobin levels normally do not drop below 10.5 g/dL during the nadir period and should measure 11 g/dL or higher during the remaining pregnancy.
Procoagulation factors are increased during pregnancy, whereas inhibitors of coagulation are reduced or unchanged. These changes in the coagulation cascade may serve to protect the mother against peripartum hemorrhage, but when combined with venous stasis and vessel wall injury, they predispose a patient to thromboembolic disease.6
Pregnancy has been described as a state of immunodeficiency but is more accurately described as a period of modified immune response.7 The peripheral white blood cell count is elevated during pregnancy; it ranges from 5110/mm3 to 12,200/mm3 during gestation and rises even higher during labor. Additionally, changes in both chemotaxis and adherence of neutrophils occur during pregnancy, as well as a shift by the immune system away from the cell-mediated immune response toward antibody-mediated immunity. This altered immune focus allows tolerance of the maternal immune system to paternal antigens but increases susceptibility to pathogens and variation in the activity of autoimmune diseases.8
Cardiovascular System
Cardiac output consistently and dramatically increases during pregnancy, with a 37% to 53% increase over prepregnancy values.9 This change is driven by increases in both heart rate and stroke volume. The heart rate increases 15 to 20 beats/min over pregravid rates, and stroke volume increases by 20% to 30%. In the later stages of pregnancy, decreased venous return as a result of compression of the inferior vena cava leads to decreased cardiac output. The highest levels of cardiac output occur in the right and left lateral positions; the lowest levels occur in the supine, sitting, and standing positions. Supine hypotension with symptoms such as dizziness, nausea, and syncope develop in a small number of pregnant patients (5% to 10%).6 Despite the increase in cardiac output, the pregnancy-associated reduction in systemic vascular resistance causes an overall reduction in maternal blood pressure. Blood pressure, like cardiac output, is dependent on position, highest when sitting and lowest in the lateral recumbent position.
Endocrine System
Enlargement of the breasts and nipples is normal, and discharge of colostrum from the nipples during the later stages of pregnancy is not uncommon. Despite histologic changes, women remain euthyroid during pregnancy, and the slight increase in thyroid size that does occur is not clinically detectable. A palpable increase in the thyroid during pregnancy is pathologic and must be further evaluated. The results of laboratory tests commonly used to evaluate thyroid function should be within normal limits. Significant hypothyroidism during pregnancy is associated with fetal neurologic defects such as mental retardation and lower IQ scores.10,11
Common Medical Diseases and Pregnancy
Diabetes
Diabetes occurs in approximately 3% to 5% of all gestations.12 Three types of diabetes affect pregnancy: type 1, type 2, and gestational diabetes. Gestational diabetes accounts for 90% of cases. Fetal risks during pregnancy in women with diabetes include congenital malformation, intrauterine growth retardation, macrosomia, fetal hypoglycemia, fetal respiratory distress syndrome, neonatal hypocalcemia, hyperbilirubinemia, polycythemia, intrauterine demise, and neonatal jaundice.13 These risks are greatest for women with type 1 diabetes, although type 2 and gestational diabetes are also associated with a significant increase in fetal mortality.
Urinary Tract Infections
The incidence of acute cystitis or acute pyelonephritis is approximately 1% during pregnancy. Asymptomatic bacteriuria is a related condition in which urine culture is positive in an asymptomatic patient. The incidence of asymptomatic bacteriuria is similar in both gravid and nongravid populations, with 2% to 10% of the population being affected.14,15 However, gravid patients have a much higher rate of progression to symptomatic infection, and as many as 40% of cases eventually progress to acute pyelonephritis. Chronic cystitis and chronic and acute pyelonephritis are associated with negative outcomes, and patients should receive antibiotic therapy. Patients with recurrent asymptomatic bacteriuria or urinary tract infection may require daily suppressive therapy or postcoital prophylaxis.
Asthma
Approximately 4% of pregnancies are complicated by asthma,16,17 roughly mirroring its incidence in women of childbearing age. The course of asthma during pregnancy is not uniformly predictable. One third of patients will have improvement in their symptoms during pregnancy, one third will experience stable disease, and another third will have worsening of their symptoms.18 Though somewhat controversial, patients with asthma have been reported to have increased rates of preeclampsia, cesarean delivery, and preterm rupture of membranes. Fetal risks include increased mortality, prematurity, intrauterine growth retardation, and low birth weight.
Seizure Disorders
Epilepsy is associated with an increased incidence of obstetric and fetal complications. However, more than 90% of pregnant women with epilepsy have a normal pregnancy with a good outcome.19 Seizure disorders affect approximately 1% of the general population and affect a similar percentage of gestations. As many as one third of women with epilepsy experience an increase in seizure activity during pregnancy. Patients with a higher pregravid incidence of seizures are at greater risk for increased seizure frequency during pregnancy. Increased seizure activity may result from decreased compliance with medical therapy, altered pharmacologic distribution, increased elimination of medications, or a combination of factors.
Red Flags
New seizure activity during pregnancy merits investigation; eclampsia must always be suspected in the third trimester.
Hemoglobin levels do not normally drop below 10.5 g/dL during pregnancy and should usually measure 11 g/dL. More significant anemia should be investigated.
Pregnancy is a state of modified immune response, and pregnant women have increased susceptibility to pathogens.
Migraine
Migraine symptoms are reduced or resolved in 60% to 80% of women during pregnancy.20 Acceptable pharmacologic agents to treat symptoms include acetaminophen, narcotics, and antiemetics such as prochlorperazine, promethazine, and metoclopramide. Caffeine is sometimes effective and may be used in moderation. Propranolol is generally considered safe for migraine prophylaxis but may carry a risk for intrauterine growth retardation.
Thromboembolic Disease
Thromboembolic disease is a major source of maternal morbidity and mortality during pregnancy. The incidence of venous thromboembolism increases by a factor of 5 during pregnancy, and pulmonary embolism is a leading cause of maternal mortality in the United States.21 Factors believed to contribute to the increased incidence of venous thromboembolism include alteration of normal clotting factor levels, increased stasis, and vessel damage. These factors may be aggravated by advanced maternal age and inherited or acquired thrombophilias.
Hypertension
Pregnant women with elevated blood pressure may have preexisting hypertension, gestational hypertension, preeclampsia, or eclampsia.22
No consensus regarding initiation of antihypertensive therapy during pregnancy has currently been established. Most authorities prescribe treatment for patients with a blood pressure of 160/105 or higher; others argue that a lower threshold of 150/100 should be the criteria for treatment. In one review of pregnant patients experiencing stroke secondary to preeclampsia, systolic blood pressures recorded before the event were 159 to 198 mm Hg, and diastolic blood pressures were 81 to 113 mm Hg23; arterial hemorrhage was the cause of stroke in 93% of patients who underwent intracranial imaging. Of note, evidence is not sufficient to recommend bed rest as an effective or practical treatment of hypertension during pregnancy.24
Medication Use During Pregnancy
The U.S. Food and Drug Administration classifies medications into five categories according to potential fetal risk based on animal and human studies (Table 118.1).25 Medications commonly used in the ED and generally considered safe are listed in Box 118.3; often-used medications considered unsafe for use during pregnancy are listed in Table 118.2.
PREGNANCY CATEGORY | DESCRIPTION |
---|---|
A | Adequate well-controlled studies in pregnant women have not shown an increased risk for fetal abnormalities. |
B | Animal studies have revealed no evidence of harm to the fetus; however, there are no adequate and well-controlled studies in pregnant women.orAnimal studies have shown an adverse effect, but adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus. |
C | Animal studies have shown an adverse effect, and there are no adequate well-controlled studies in pregnant women.orNo animal studies have been conducted, and no adequate well-controlled studies have been performed in pregnant women. |
D | Adequate well-controlled or observational studies in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy may outweigh the potential risks. |
X | Adequate well-controlled or observational studies in animals or pregnant women have demonstrated positive evidence of fetal abnormalities. Use of the product is contraindicated in women who are or may become pregnant. |
FDA, Food and Drug Administration.
Modified from Meadows M. Pregnancy and the drug dilemma. FDA Consum 2001;35:16-20. Available at http://www.fda.gov/fdac/features/2001/301_preg.html.
Box 118.3 Medications Considered Safe During Pregnancy
* Avoid chronic use of opiates during pregnancy. Also use caution when giving opiates near the time of delivery because of the risk for respiratory and central nervous system depression.
† Do not give the estolate salt of erythromycin because of the risk for maternal hepatic toxicity.
‡ Use caution when giving benzodiazepines near the time of delivery because of the risk for respiratory depression. Early studies showed teratogenicity, which was unconfirmed in later studies; however, the drug is still class D and should be used with caution in the first trimester.
Table 118.2 Common Emergency Department Pharmaceutical Agents Contraindicated in Pregnancy
AGENT | CONTRAINDICATION |
---|---|
Analgesics | |
Aspirin | Premature closure of the ductus arteriosus, increased incidence of hemorrhage |
NSAIDs (ibuprofen, indomethacin, naproxen) | Oligohydramnios, pulmonary hypertension, constriction of the ductus arteriosus |
Antimicrobials | |
Tetracyclines | Discolored teeth, inhibition of bone growth |
Fluoroquinolones | Arthropathy in immature animals |
Aminoglycosides | Ototoxicity, nephrotoxicity |
Anticoagulants | |
Warfarin | Nasal bone hypoplasia, bone stippling, ophthalmologic abnormalities, mental retardation |
Antiepileptics | |
Phenytoin | Fetal hydantoin syndrome (ossification abnormalities, cleft lip and palate, impaired growth, cardiac abnormalities) |
Carbamazepine, valproic acid | Dysmorphic syndrome, similar to fetal hydantoin syndrome |
Antihypertensives | |
ACE inhibitors | Renal malformation, oligohydramnios, craniofacial malformations, lung malformations |
Angiotensin II receptor blockers | Linked to malformations similar to those from ACE inhibitors |
Other | |
Isotretinoin | Craniofacial, cardiac, thymic, and CNS malformations |
ACE, Angiotensin-converting enzyme; CNS, central nervous system; NSAIDs, nonsteroidal antiinflammatory drugs.
Antimicrobial Agents
All antibiotics have been shown to cross the placenta and enter the fetal circulation to some degree.26,27 Penicillin and its derivative compounds, including nafcillin, dicloxacillin, amoxicillin, and ampicillin, have been used extensively in pregnant patients without any ill effects on fetal development being reported. Newer derivatives, such as piperacillin and ticarcillin, have not been used as extensively but are believed to be safe in pregnancy. Cephalosporins are prescribed routinely, although there is less experience with the use of cephalosporins than with penicillin and ticarcillin.
Metronidazole has not been shown to be a human teratogen. However, its use is somewhat controversial because of potential mutagenesis and carcinogenicity. Trimethoprim-sulfamethoxazole has two contraindications, one related to each of its constituents—trimethoprim should be avoided during the first trimester because it is a folate antagonist and its use may lead to an increased incidence of neural tube defects; use of sulfamethoxazole is discouraged near term because of competitive binding of albumin with bilirubin, which leads to concern for an increased risk for kernicterus. Although this concern exists for all sulfonamides, no cases of kernicterus resulting from prenatal use have been reported.27
Tetracyclines are contraindicated during pregnancy as a result of calcium binding, which causes staining of deciduous teeth, poor development of tooth enamel, and inhibition of skeletal growth in the fetus. Fluoroquinolones have not been shown to increase the rate of fetal malformation in humans but are contraindicated because of the development of arthropathy in immature animals exposed to quinolones.28,29
Antiepileptic Drugs
Management of epilepsy during pregnancy is difficult and requires a multidisciplinary approach. The risk for maternal death during pregnancy can be up to 10 times higher than that for patients without epilepsy.30 In addition, rates of intrauterine fetal demise and malformation are also increased.31 Many commonly available anticonvulsive medications are known or suspected teratogens, which can make management decisions difficult for both caregivers and patients.
Phenytoin, carbamazepine, valproate, and lamotrigine are associated with an increased incidence of congenital abnormalities. A recent review of data from 25 epilepsy centers recorded the following rates of serious adverse outcomes: valproate, 20.3%; phenytoin, 10.7%; carbamazepine, 8.2%; and lamotrigine, 1.0%.32 Newer antiepileptic drugs, including levetiracetam, felbamate, gabapentin, oxcarbazepine, tiagabine, and topiramate, seem to be safe for use in pregnancy, although fewer data are available for these agents.33
Antihypertensive Medications
Several agents for the treatment of hypertension during pregnancy have favorable safety profiles. Commonly used medications include α-methyldopa and hydralazine. Hydralazine has been used extensively in pregnancy and is available in both intravenous and oral formulations.34–36 Beta-blockers are believed to be safe in pregnancy, although some association with lower placental and fetal weight has been reported with atenolol.37 Labetalol is the preferred agent because it does not carry this risk. The combined alpha- and beta-blocking characteristics of labetalol may act to preserve uteroplacental blood flow.
Immunizations
Indications for vaccines composed of toxoid or inactivated virus are similar to those for nongravid females. In general, the protection gained by vaccination during pregnancy usually outweighs the risks.38 Live virus or attenuated vaccines (measles, mumps, poliomyelitis, rubella, yellow fever, and varicella) may cause infection or malformation (or both) in the fetus and are therefore contraindicated. Patients planning to became pregnant should ideally have their vaccines updated several months before conceiving.
Influenza is indicated for all women who will be pregnant during the flu season (October to March) and for all women at high risk for pulmonary complications.39 Tetanus–diphtheria toxoid vaccine should be administered as usual for tetanus-prone wounds.
ACOG educational bulletin. Antimicrobial therapy for obstetric patients. Number 245, March 1998 (replaces no. 117, June 1988). American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet. 1998;6:299-–308.
Barton JR. Hypertension in pregnancy. Ann Emerg Med. 2008;51(2 Suppl):S16–S17.
Hodder R, Lougheed MD, Rowe BH, et al. Management of acute asthma in adults in the emergency department: nonventilatory management. CMAJ. 2010;182(2):E55–E67.
Stead LG. Seizures in pregnancy/eclampsia. Emerg Med Clin North Am. 2011;29:109–116.
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