Fever in Pregnancy
Authors: Dr. D. Maharaj
INTRODUCTION
Any acute or chronic infectious diseases may be contracted during the course of pregnancy, and conception may occur in women already subject to infection. The coexistence of pregnancy may aggravate the risk to maternal life of the more serious of these diseases. In pregnancy most infections are no more common, nor more serious than in non-pregnant women of similar age. Besides affecting the mother, some infections may be transmitted to the fetus in utero, during the intrapartum period or, postnatal, with potentially serious consequences. Infectious illnesses and fevers in the mother must be treated as any other serious illness. The effects on pregnancy depend on the extent of temperature elevation, its duration, and the stage of fetal development when it occurs. Mild exposures during the preimplantation period and more severe exposures during embryonic and fetal development often result in miscarriage, premature labor, growth restriction, and stillbirth.
Hyperthermia also causes a wide range of fetal structural and functional defects, with the central nervous system (CNS) being most at risk. While there is a greater incidence of neonatal morbidity and mortality with transmitted infections, not all maternal infections lead to transmission to the fetus, nor does transmission to the fetus lead to disease or sequelae. During the puerperium, parturient women are particularly susceptible to serious infections of the genital tract and childbed fever remains one of the most important causes of maternal death. This chapter will deal with fevers and infections during pregnancy, rather than the puerperium. While attempts have been made to list the more important causes of fever in pregnancy (Tables 1, 2, 3), the lists are by no means complete.
Infections in pregnancy may be viral, bacterial or protozoan, affecting both mother and fetus. The purpose of this document is to describe these infections, their modes of transmission, and their maternal and fetal effects, and to offer guidelines for counseling and management of these infections during pregnancy. Some of the infections cause fevers, while others may not; this chapter will concentrate on infections resulting in maternal pyrexia, and some other infections which may not result in maternal pyrexia, but have important implications for the pregnancy and the fetus (Table 1). A differential diagnosis of fever in pregnancy, including both infectious and non-infectious etiologies, may be found in Table 2.
Pathogenesis
Persistent elevation of body temperature above normal levels in an individual is defined as fever. The normal body temperature usually lies between 37.0 and 37.5◦C with diurnal variations. Disturbances of temperature regulationin disease can be explained by shifts in body water, inadequate hydration, and changes in metabolism. The pattern of febrile response may be intermittent (falling to normal each day), remittent (falling each day, but still remaining above the normal), sustained (without significant diurnal variation), or relapsing (alternating with periods of one to several days of normal temperatures). The underlying sequence of events seems to be the removal of endotoxins from the circulation by fixed phagocytes of the reticuloendothelial system, followed by margination of polymorphonuclear leukocytes along the margins of the vessels. These two types of cells undergo activation to release endogenous pyrogen in to the circulation. The pyrogen produced in response to toxic, immunological or infectious stimuli, is induced through the release of lymphocytic lymphokines arising in response to antigenic recognition, and acts on the hypothalamic thermoregulatory center, transmitting information to the vasomotor center, possibly through production of prostaglandin. The release of endogenous pyrogen by phagocytic cells appears to be the common factor in the pathogenesis of fever, irrespective of its cause (Table 2).
The immune status of an individual may be innate or acquired. Innate immunity is genetically or constitutionally determined, and is not a function of cells of the immune system or antibodies, but of physiological, biochemical or anatomical differences between species. The response of adults to antigen stimulation consists of production of IgM, followed by production of IgG. The pattern of response in the neonate is different; IgM is produced as a first response, and persists for several weeks before IgG is released. The fetus elaborates IgM in response to antigen exposure in utero, and it is the detection of the specific antibody in the IgM fraction of cord blood that is used for detection of congenital infections. The poor response of newborns to certain infections are not clearly understood, however, there is evidence that in addition to physiological dysglobinemia, the cellular response to infection varies, and the phagocytes are less active. Further, there is a lack of antigen-presenting macrophages. Immunity acquired either passively or actively, follows the transfer of immune antibody of the IgG class from mother to fetus by the transplacental route, and the ingestion of IgA antibody in colostrum. Artificially acquired passive immunity follows injection of immune products such as antitoxins, antisera, or immune globulin.
Somatic cell proliferation is adapted to, and proceeds optimally at the normal body temperature range of the species, and the deleterious effects of higher levels on meiotic and mitotic cell proliferation and survival are widely recognized. A hyperthermic episode during pregnancy can result in embryonic death, abortion, growth retardation, and defects of development. It has been proposed that defects following a maternal fever might be caused by metabolic changes in the mother due to the infection and fever, and not due to the associated elevation of temperature. The Collaborative Perinatal Study of the National Institute of the Neurological Diseases and Stroke found that children of mothers who experienced kidney-urinary tract infections (UTIs) with fever were nearly twice as likely to have neurological problems requiring institutional care as children whose mothers had the infection without fever. The association between maternal influenza, and fever, in the second trimester of pregnancy, and the later onset of schizophrenia in the offspring raises the possibility of hyperthermia being one of the initiating factors in this condition, and perhaps, a number of other neurological conditions of uncertain etiology such as cerebral palsy and autism. Inflammation (leukocytic invasion) of the chorioamnion (chorioamnionitis) and/or umbilical cord (funisitis) marks the maternal and fetal immune responses, respectively. While these histologic markers may result from numerous insults (hypoxic injury, trauma, meconium or allergens), by far the most common is the immune response to subclinical or clinical infection.
There are several ways in which maternal infection might lead to inflammation within the fetal tissue and the loss of vulnerable cell populations. Bacterial products could cross to the fetal circulation, bind specific cell-membrane receptors, such as CD-14 and toll-like receptors, on inflammatory cells within the systemic circulation initiating a cascade of intracellular events. They activate transcription factors such as nuclear factor κ-B and production of proinflammatory cytokines. These proinflammatory cytokines, such as granulocyte colony-stimulating factor, tumor necrosis factor-α, interleukin-1β, C-reactive protein and interferon γ, have a variety of effects. These include a direct toxic effect on neurones and vulnerable oligodendrocyte precursor populations, gliosis with release of nitric oxide and mitochondrial dysfunction, as well as microglial activation in the brain. Animal studies describe the direct correlation between increasing temperature and susceptibility to a variety of neurotoxic factors. Hypothermia can be neuroprotective after hypoxia–ischemia in neonatal animals, while hyperthermia increases brain injury after ischemia in adult rats. Maternal pyrexia, resulting from both microbial infection as well as non-infective causes such as epidural anaesthesia, could therefore augment the deleterious effects of hypoxia on the fetal brain, possibly by increasing the cerebral metabolic rate and demand for oxygen. Systemic fetal hypotension, endothelial injury and leukocyte aggregation may all contribute to local tissue ischemia, especially in vulnerable areas. Many of these mechanisms could lead directly to cell death. They may also have an indirect neurotoxic effect by sensitizing the brain and lowering the threshold at which hypoxia triggers apoptosis.
Modes of transmission of infective agents include transplacental transfer via the umbilical blood flow or by direct spread to the amniotic fluid, ascending transmission from the cervix and uterus to the amniotic fluid, intrapartum exposure to maternal vaginal secretions and blood, or by postpartum exposure to maternal respiratory secretions or breast milk.
CLINICAL CONDITIONS AND MANIFESTATIONS
In general, perinatal infections have more severe fetal consequences when they occur early in gestation, because first-trimester infections may disrupt organogenesis. Second- and third-trimester infections can cause neurologic impairment or growth disturbances. In utero infection may be associated with certain ultrasound findings, such as intrauterine growth restriction, echogenic bowel, intracranial or intrahepatic calcifications, hydrocephalus, microcephaly, isolated ascites, pericardial or pleural effusions, or nonimmune hydrops, although congenital infections may be asymptomatic, and difficult to detect on ultrasound.
Intra-Amniotic Infection
Intraamniotic infection is a term used to describe a clinically diagnosed infection of the contents of the uterus. It is found most often after rupture of the membranes. Fever is less specific and uterine tenderness less sensitive in patients with epidural anesthesia. Possibly because of a vascular or thermoregulatory effect, pyrexia is more likely to develop in patients with epidural anesthesia. Intrauterine infection is often chronic, and it is usually asymptomatic until labor begins or the membranes rupture. Even during labor, most women who are later demonstrated (by histologic findings or culture) to have chorioamnionitis have no symptoms other than preterm labor — no fever, abdominal pain, or peripheral-blood leukocytosis, and there is usually no fetal tachycardia. Therefore, identifying women with intrauterine infections is a major challenge. Most women with a clinically apparent intraamniotic infection typically have histological evidence of chorioamnionitis, but not all placentas with this finding come from women with intraamniotic infection. Although histological inflammation of the chorion and amnion is found in 20% of term, and 60% of preterm pregnancies, the clinical diagnosis of intraamniotic infection is made in only 0.5% to 10.5% of pregnancies. Another term, microbial invasion of the amniotic fluid, describes a preclinical phase of amniotic fluid infection. The distinction between histological chorioamnionitis and intraamniotic infection is important because the histological diagnosis cannot be made while the patient is pregnant, and to diagnose microbial invasion of the amniotic fluid requires amniocentesis.
The greatest risk for intraamniotic infection occurs after rupture of the membranes. Although hematogenous spread is possible, pathogenic organisms more easily reach the amniotic cavity once this barrier is breached. Bacterial access to the amniotic cavity by itself is not sufficient to produce an infectious process. The size of the inoculum, the pathogenicity of the organisms, and the susceptibility of the hosts, both mother and fetus, affect the risk of intraamniotic infection. Factors that increase the exposure of the amniotic cavity to pathogenic bacteria from the vagina such as duration of ruptured membranes, transcervical instrumentation, vaginal examinations, and cerclage placement seem to increase the risk of intraamniotic infection. Intraamniotic infection has been described in some patients with intact membranes who undergo procedures such as amniocentesis and percutaneous umbilical blood sampling, however, these are rare. Certain microorganisms, such as group B streptococcus, Listeria monocytogenes, fusobacterium, and group A streptococcus, are implicated more frequently in intraamniotic infection. Other organisms that have been reported in association with intraamniotic infection include Ureaplasma urealyticum, Candida sp, and Haemophilus influenzae; the most common high virulence isolates are Bacteroides species, group B streptococcus, and Escherichia coli.
Antibiotics, when given to patients with preterm premature rupture of membranes, may decrease the frequency of intraamniotic infection and prolong the interval between rupture of membranes and delivery. The accurate and timely diagnosis of intraamniotic infection is important so that those affected women may be treated without delay. Unfortunately, early diagnosis is difficult because clinical signs and symptoms of intraamniotic infection occur late and are neither sensitive nor specific. To avoid a delay in diagnosis, a high index of suspicion should be maintained. Patients with fever, and maternal or fetal tachycardia, especially in the presence of ruptured membranes, are likely to have intraamniotic infection.
Sexually Transmitted Infections
The Centers for Disease Control and Prevention (CDC) recommends screening for some sexually transmitted infections (STIs) at the first prenatal visit, then again in the third trimester for mothers at high risk. Though sexually transmitted infections usually do not cause fevers in pregnancy, they may predispose to co-infections, and have implications for the fetus and neonate. Many sexually transmitted infections have been linked with increased risks of premature delivery and low birth weight, and associated morbidity and mortality. Because of these risks, the Centers for Disease Control and Prevention (CDC) has recommended screening for some sexually transmitted infections at the first prenatal visit, then again in the third trimester for mothers at high risk. Other screening tests that are recommended for all pregnant women include those for Chlamydia trachomatis, and women at risk should be tested for Neisseria gonorrhea. Women younger than 25 years and those who are at risk of Chlamydia (e.g., those who have multiple sex partners) should be rescreened in the third trimester. Women who continue to be at risk of gonorrhea should also be rescreened in the third trimester. When infection is detected, the physician must inform the mother, ensure adequate and safe treatment, and advise partner notification and treatment. Physicians should counsel the patient to use condoms and avoid sexual contact until her partner has been treated.
HIV
HIV and Pregnancy chapter in HIV Clinical Manual
Chlamydia
C. trachomatis is the most common sexually transmitted bacterial pathogen in the United States, and as many as 5% to 15 % of pregnant women are infected. Increasing numbers of Chlamydia infections have made it the most widespread sexually transmitted infections in the United Staes. In 1996 there were 492,631 reported diagnoses, corresponding to a rate of 190.6 per 100,000 population. However, by 2005 the annual total had increased by 98% to 976,445 and the rate per 100,000 had risen to 332.5.
Mother-to-child transmission of C. trachomatis can occur at the time of birth and may result in ophthalmia neonatorum or pneumonitis in the newborn, or postpartum endometritis in the mother. Some reports have linked chlamydia to low birth weight and preterm birth.
Gonorrhea
Although the 2005 rate of 115.6 diagnoses per 100 000 population is one of the lowest ever recorded, gonorrhea remains the second most commonly reported sexually transmitted infections in the United States. The rate is still much higher than the "Healthy People 2010" target of 19 cases per 100 000 population. N. gonorrhea can be transmitted to the newborn from the mother's genital tract at the time of birth and can cause ophthalmia neonatorum, systemic neonatal infection, maternal endometritis, or pelvic infection. The risk of transmission from an infected mother to her infant is between 30% and 47%.
Human Papillomavirus
Human papillomavirus (HPV) infection is extremely common and often resolves spontaneously. Because genital warts can proliferate and become friable during pregnancy, many specialists recommend their removal. Podofilox, imiquimod, and podophyllin are not recommended during pregnancy. Trichloroacetic acid 80% - 90% applied by a health care professional weekly has been used safely in pregnancy. The advent of a prophylactic quadrivalent vaccine may reduce the incidence of genital warts in future.
Syphilis
Treponema pallidum, the cause of syphilis, is highly transmissible, even in the absence of any specific symptoms or clinical findings. Maternal syphilis has been associated with complications such as hydramnios, spontaneous abortion, and preterm delivery. Fetal complications such as congenital syphilis, fetal hydrops, prematurity, fetal distress, and stillbirth also occur.
Vaginal Infections
Trichomonas vaginalis, a sexually transmitted vaginal infection, has been associated with preterm delivery and low birth weight. Trichomonas infection can have unpleasant symptoms such as itching, profuse discharge, vaginal irritation, and odor. It also causes a chronic inflammatory condition and may facilitate HIV transmission.
Bacterial vaginosis is not a sexually transmitted infection, but it is more common in sexually active women. Although many studies have shown an association between bacterial vaginosis and preterm birth, premature rupture of membranes, and low birth weight, it is not known whether the bacterial overgrowth causes these complications, or if it is a marker for intrauterine colonization. Screening for bacterial vaginosis is not recommended for asymptomatic women because current evidence indicates that treatment does not improve pregnancy outcomes. A summary of treatments for the infections discussed is provided in Table 5.
Systemic Infections
An extensive list of systemic infections in pregnant females can be found in Table 2.
Appendicitis
Appendicitis is the most common non-obstetric emergency requiring surgery during pregnancy. Diagnosis of appendicitis is complicated by the physiologic and anatomic changes that occur during pregnancy. This can result in delayed diagnosis, increased risk of morbidity for mother and fetus, and fetal loss. Women who have undergone appendectomy during pregnancy are at higher risk of fetal loss, especially in early pregnancy, of appendiceal perforation, and of premature contractions and labor. Despite the difficulty of diagnosing appendicitis during pregnancy, appendectomy should not be delayed. The incidence of appendicitis during pregnancy ranges from 0.05% to 0.13%; and usually occurs in the second or third trimesters. The rate of appendicitis is the same in pregnant and non-pregnant women; however, pregnant women have a higher rate of perforation.
Difficulty in diagnosing appendicitis during pregnancy arises from the fact that its symptoms are similar to those of pregnancy: anorexia, nausea, and vomiting. Leukocytosis and a diminished tendency to develop hypotension and tachycardia, which are physiologic in pregnancy, add complexity to the diagnosis. Displacement of the appendix by the uterus and increased separation of the visceral and parietal peritoneum, which decreases the ability to localize tenderness on examination, further complicates diagnosis. Abdominal pain, diffuse periumbilical pain migrating to the right lower quadrant, and nausea and vomiting are common symptoms. The most common signs of appendicitis are abdominal tenderness, most often in the right lower quadrant, and rebound tenderness and guarding. Fever has not proved to be a reliable sign of appendicitis, and laboratory findings, including leukocytosis and C-reactive protein, have been found unreliable for diagnosis.
Urinary Tract Infections
Urinary tract infections (UTIs) are common during pregnancy. Increased bladder volume, and decreased bladder tone, along with decreased ureteral tone, contributes to increased urinary stasis and ureterovesical reflux. Increases in urinary progestins and estrogens may lead to a decreased ability of the lower urinary tract to resist invading bacteria. The prevalence of asymptomatic bacteriuria in studies varies between 4% and 7%. Incidence relates to sexual activity, and increases with increasing age and gravidity. It is also higher among patients from lower socio-economic groups. Symptomatic infection occurs in about 1% -2% of pregnant women. Most women acquire bacteriuria before pregnancy. At the first examination, the rates of bacteriuria in pregnant women are similar to those in non-pregnant women with similar risk factors. About 37% - 57% of bactiuria women develop UTIs during pregnancy. An additional 1% of infections occur during pregnancy. Bacteriuria during pregnancy is associated with a significant increase in the number of low-birth-weight infants, preterm births, and neonatal mortality. There are three entities of urinary tract infections in pregnancy, asymptomatic bacteriuria, acute cystitis and acute pyelonephritis.
Urinary tract infection with classic symptoms and signs of urinary frequency, dysuria, and fever is a common cause of fever in pregnancy. The diagnosis is based on clinical findings and a urine specimen containing greater than 105 colony forming U/mL. The majority of UTIs are caused by gastrointestinal organisms. Even with appropriate treatment, the woman may experience a reinfection of the urinary tract from the rectal reservoir. The organisms that cause UTIs during pregnancy are the same as those found in nonpregnant women. Escherichia coli accounts for 80% to 90% of infections. Other Gram negative rods such as Proteus mirabilis and Klebsiella pneumoniae are also common.Enterococci, Gardnerella vaginalis and Ureaplasma ureolyticum, as well as Gram-positive organisms such as group B streptococcus and Staphylococcus saprophyticus are less commonly found. In pregnancy, increased bladder volume, and decreased bladder tone, along with decreased ureteral tone, contributes to increased urinary stasis and ureterovesical reflux. Increases in urinary progestins and estrogens may lead to a decreased ability of the lower urinary tract to resist invading bacteria. Of all risk factors, urethral catheterization contributes most to the incidence of nosocomial urinary tract infections.
Acute pyelonephritis is a serious systemic illness that can progress to maternal sepsis. It tends to occur during the later stages of pregnancy, usually in the last trimester. The incidence of acute pyelonephritis in obstetric patients is about 2%. The diagnosis is made when the presence of bacteriuria is accompanied by systemic symptoms or signs such as fever, chills, nausea, vomiting, and flank pain. Symptoms of lower tract infection, i.e. frequency and dysuria may or may not be present. The major causes of concern are the presence of underlying urological abnormalities and associated risks to the mother and fetus, such as toxaemia, hypertension, prematurity and perinatal mortality. Early, aggressive treatment with appropriate antibiotics such as second- or third-generation cephalosporins, an aminopenicillin, or an aminoglycoside is important in preventing complications from pyelonephritis. Hospitalization, although often indicated, is not always necessary. However, hospitalization is indicated for patients who are exhibiting signs of sepsis and who are vomiting and unable to remain hydrated. Parenteral antibiotic treatment of pyelonephritis should be continued until the patient becomes afebrile. Most patients respond to hydration and prompt antibiotic treatment within 24 to 48 hours. The most common reason for initial treatment failure is resistance of the infecting organism. If fever continues or other signs of systemic illness remain after appropriate antibiotic therapy, the possibility of a structural or anatomic abnormality should be suspected. Persistent infection may be caused by urolithiasis, which occurs in 1in1 500 pregnancies or less commonly, congenital renal abnormalities, or a perinephric abscess.
Skin and Soft Tissue Infections
The clinical presentation of skin and soft tissue infections in pregnancy is similar to of nonpregnant patients. The extremities, buttocks, breasts, vulva or groin, and abdomen can be involved. Please refer to the monograph on cellulitis and necrotizing soft tissue infections for further details on this condition.
Meningitis
Bacterial meningitis has an annual incidence of 4 - 6 cases per 100 000 adults and results in approximately 135,000 deaths worldwide each year. Outcomes for mothers have been confined to case reports, with some quoting fatality rate for women as high as 27%, and in patients who survive the initial insult, neurologic sequelae including seizures, hearing loss, impaired mental status and cognition may occur in as many as 30% of all cases. Local extension from contiguous extracerebral infection (e.g., otitis media, mastoiditis, or sinusitis) is a common cause. Patients with bacterial meningitis usually present soon after the onset of symptoms with a classic triad of fever, neck stiffness, and altered mental status. Other features may include photophobia, vomiting, rash, and dehydration.
Bacterial meningitis is a medical emergency in which early diagnosis and treatment is imperative to prevent death and reduce long-term complications. Lumbar puncture is used to confirm the diagnosis in patients presenting with clinically suspected meningitis; however, imaging should be completed first in patients with new-onset seizures, an immunocompromised state, signs of mass lesion, or moderate to severe level of altered consciousness. If imaging is to be performed before lumbar puncture, empiric therapy should be initiated first as a delay in treatment can result in poor outcomes. Complications include hearing loss, emotional disturbances, aphasia, and hemiplegia. The fetal loss rate from spontaneous abortion, stillbirth, and neonatal death could reach 47%. Some authors suggest that pregnancy predisposes women to pneumococcal meningitis. Although pregnancy does result in a diminished immune response, there is no data to conclude that there is increased risk.
Pneumonia
Pneumonia is the most frequent cause of non-obstetric infection in the pregnant patient. The incidence of pneumonia in pregnancy is no different from that in non-pregnant adults, and has been reported in 1.1 to 2.7 per 1,000 deliveries. Although infrequently seen in this setting, pneumonia constitutes a serious complication of pregnancy. Depending on etiology, particular types of pneumonia can have very different implications for the pregnant woman, especially pneumonia of viral origin. The incidence of pneumonia is particularly high among pregnant women with certain predisposing antecedents, such as a history of smoking or respiratory disease. All diseases in the pregnant host can have an impact on the mother and fetus, contributing to morbidity and mortality when compared to the nonpregnant host.
A number of anatomic changes occur during pregnancy; included is the enlarging uterus causing an elevation of the diaphragm, and increase in the transverse diameter of the chest. Collectively, these alterations decrease the ability of the pregnant woman to clear respiratory secretions. It is important that any evidence of tachypnea be recognized as pathologic because the respiratory rate should remain "normal" during pregnancy. Risk factors for maternal pneumonia are human immunodeficiency virus infection, sickle cell disease, cystic fibrosis, antepartum systemic corticosteroid therapy, asthma, and anemia. Mother's age or parity has not been associated with an increased rate of pneumonia during pregnancy, but the incidence of pneumonia increases with gestational age. Fifty percent to 80% of pneumonias are reported in third trimester in different series.
The clinical manifestations of acute bacterial pneumonia present no differently among gravid and nonpregnant patients, with cough, fever, dyspnea, chills and sputum production being often the chief symptoms. Although mortality from pneumonia in pregnancy is similar to rates in non-pregnant adults, pneumonia increases the risk of maternal complications. Increased risk of respiratory failure and mechanical ventilation has been reported in pregnancy. Mothers with pneumonia are more likely to deliver prematurely, and have infants of lower birth weight. It is quite possible that the cascade of mediators released by the active host inflammatory response to infection exerts distant effects on the uterus, leading to a high rate of preterm labor during the course of pneumonia. Although neonatal mortality rate due to ranges from 1.9% to 12% in different series, anomaly in newborns have not been associated with antepartum maternal pneumonia. Complications in the pregnant woman with pneumonia include anemia, empyema, bacteremia, and death
The relative incidence of individual pathogens in the pregnant patient with pneumonia is similar to those reported in nonpregnant hosts of comparable age. Whether the prevalence of these infectious agents is more common in pregnancy than in the nonpregnant state is unclear, but certain pathogens do represent a greater hazard to the pregnant woman because of the physiologic defects in cell-mediated immunity. The most common pathogens in pregnancy areStreptococcus pneumoniae, Haemophilus influenzae, and Mycoplasma pneumoniae. Legionella pneumophila pneumonia in pregnancy is rare. Viral respiratory infections also can cause maternal pneumonia (about 5% of cases). Fungal pneumonias are rare in pregnancy. Cryptococcus neoformans, Histoplasma capsulatum, Sporothrix schenckii, Blastomyces dermatitidis, and Coccidioides immitis can cause pneumonia that is usually mild and self-limited disease. The atypical pneumonia syndrome with low-grade fever, gradual onset, mucoid sputum and patchy or interstitial infiltrates suggests infection with the atypical pneumonia pathogens. However, recent studies in nonpregnant patients indicate thatLegionella infection can present with an overlap of clinical features common to both syndromes. Additionally, when serious disease is present, Legionella is frequently the inciting pathogen. It is therefore prudent to treat serious pneumonia in this population empirically for both syndromes, regardless of clinical presentation.
DIAGNOSTIC OVERVIEW
X-rays in Pregnancy
Maternal illness during pregnancy is not uncommon and sometimes requires radiographic imaging for proper diagnosis and treatment. The patient and her physician may be concerned about potential harm to the fetus from radiation exposure. In reality, however, the risks to the developing fetus are quite small. The accepted cumulative dose of ionizing radiation during pregnancy is 5 rad, and no single diagnostic study exceeds this maximum. Nonurgent radiologic testing should be avoided during this time. Rare consequences of prenatal radiation exposure include a slight increase in the incidence of childhood leukemia and, possibly, a very small change in the frequency of genetic mutations. Such exposure is not an indication for pregnancy termination. Appropriate counselling of patients before radiologic studies are performed is critical. The fetal malformations most commonly caused by high-dose radiation are central nervous system (CNS) changes, especially microcephaly and mental retardation. Until more data are available delineating potential fetal risk, it is prudent to delay non-urgent radiographs during the sensitive period of 10 to 17 weeks of gestation. When a radiographic study is needed for appropriate management of a pregnant patient, the American College of Radiology recommends that "health care workers should tell patients that x-rays are safe and provide patients with a clear explanation of the benefits of x-ray examinations." Diagnostic x-rays during pregnancy are considered safe, yet physicians should use reasonable caution while remaining sensitive to patients' fears and concerns. A factual discussion of the nature of the planned examination and its potential outcomes, and documenting consent are appropriate steps before ordering a study. Asking nonpregnant women with child-bearing potential about the possibility of pregnancy is also an important way to avoid unpleasant surprises. Use of lead shields to protect the abdomen when x-raying the chest, for example, helps to reduce radiation to the fetus. Women exposed to radiation exceeding a cumulative dose of 5 rad and those with particular concerns about their infant's health may require further evaluation or referral. A radiation physicist can calculate the estimated dose of radiation to the fetus to assist in patient counselling. A pregnant woman who is ill and requires radiographic imaging faces potential risks from her disease to her own health as well as that of her developing infant's. These risks almost always outweigh the minor hazards posed by low-dose radiation exposure. Physicians should not hesitate to order a study if an appropriate work-up of the mother requires a specific test to guide diagnosis and treatment. When diagnostic imaging is acutely needed, ultrasonography may represent an alternative to ionizing radiation and is considered safe throughout pregnancy. Patient counselling before radiation exposure will help alleviate anxiety and misunderstandings.
Clinical Evaluation and Diagnosis
In all pregnant women, as in non-pregnant cases, there should be a complete history and physical examination. The examination should be “from head-to-toe”; with special note of the characteristics of the fever, maximum temperature, presence of diurnal variation, and recent travel. The challenge to the clinician is to select investigations with the highest sensitivity and specificity to increase the probability of a correct diagnosis. When the diagnosis continues to be elusive, repeat the history and the physical examination. In cases of a fever in which the cause is unclear, a number of tests may be useful, depending on history and physical examination findings. These tests include initial laboratory studies such as a complete blood count with a differential cell count, electrolytes, blood urea nitrogen and creatinine, glucose, calcium, urinalysis, urine cultures, liver function tests, and ESR. Other blood tests would include tests for human immunodeficiency virus (HIV), rapid plasma reagent (RPR), antistreptolysin-O (ASO) titer, rheumatoid arthritis (RA) factor, and antinuclear antibody (ANA), as well as acute and convalescent phase serology tests for various viruses. In addition bloods should be taken for culture, both aerobic and anaerobic, including thick smear of the blood to evaluate for parasites (e.g., malaria). Where appropriate, swabs such as nasal and throat, sputum, stool, or any body discharge should be taken for microscopy and culture. Diagnostic imaging such as a chest film, abdominal ultrasound, abdominal computed tomography (CT) may aid in select cases; for example, a chest X-ray may reveal a focus of infection in the chest. If required, certain specific tests may be required to clinch the diagnosis, such as a tuberculin skin test for the diagnosis of tuberculosis, a lumbar puncture for cerebrospinal fluid analysis in suspected meningitis, an echocardiogram if there is suspicion of infective endocarditis or aortitis, tagged white cell scans may be used to localize an abscess, and a bone marrow biopsy may be indicated if leukemia or a myelodysplastic syndrome is suspected. Other biopsies if indicated may include the liver, bone marrow, lymph node, skin, muscle, or temporal artery.
An MSU must be taken in patients with pyelonephritis or complicated urinary tract infection. A leukocyte esterase dipstick can be used to detect pyuria, and sticks are available to detect nitrite (produced by bacterial metabolism of urinary nitrate). In healthy patients with recurrent symptoms, it is vital that the diagnosis is confirmed by urine culture and urine microscopy. Table 3 provides a list of diagnoses, appropriate tests and clinical scenario to suggest each listed condition.
DIAGNOSIS OF INDIVIDUAL CLINICAL SYNDROMES
Appendicitis
Ultrasonography, as yet not fully evaluated, was found helpful during the first trimester, but less useful as pregnancy progressed due to displacement of the appendix. Laparoscopy has been described as useful, particularly when diagnosis is uncertain. Helical computed tomography has been found to be a helpful tool in diagnosing appendicitis.
Intra-Amniotic Infections
The diagnostic criteria most commonly used for intra-amniotic infections are shown in Table 4. The diagnosis of intra-amniotic infections may be more difficult in those patients with epidural anesthesia. Many serological and amniotic fluid assays have been studied to diagnose intra-amniotic infections: leukocyte esteraseY, glucose, Limulus amebocyte assay, gas-liquid chromotography, and interleukins, however, there is no reliable gold standard against which to measure any of the diagnostic tests. Gram's stain, culture, and cell count are the most commonly used tests of the amniotic fluid. Maternal leukocytosis, although found frequently, must be interpreted cautiously if the patient is in labor. In a non-laboring patient with intact membranes and fever, but otherwise no signs of intra-amniotic infections, it is reasonable to perform an amniocentesis to help exclude intrauterine infection. The amniotic fluid can be sent for white cell count, Gram staining, and culture tests.
Sexually Transmitted Infections
Testing for HPV is considered useful in the triage of women with atypical squamous cells of undetermined significance on Papanicolaou smear. Diagnosis of genital warts is made by visual inspection. Biopsy may be needed if the diagnosis is uncertain, if the warts do not respond to standard treatment, or if they are pigmented, ulcerated, fixed, or bleeding.
The nucleic acid amplification test (NAAT) is the preferred test for chlamydia because of its high sensitivity and specificity, and its use on specimens obtained noninvasively. It can be performed using cervical or urine specimens. Nonamplified nonculture tests, such as the DNA probe test, remain an option when the NAAT is not available. Repeat testing three weeks after completion of therapy is recommended for pregnant women.
Screening for gonorrhea can be performed with a culture on Thayer-Martin media, which is recommended in a population with a low prevalence of infection. Nucleic acid hybridization tests of cervical specimens and NAATs of cervical specimens or urine are also used, with NAATs being the most sensitive and specific. Culture is the most widely available test and has the advantage of providing antimicrobial susceptibility.
Serology for syphilis should be checked at the first prenatal visit. Screening is performed with a blood test - the rapid plasma reagin or Venereal Disease Research Laboratories test - and confirmed with a fluorescent treponemal antibody serology and T. pallidum particle agglutination test. A single serologic test is insufficient because false-positives occur with other illnesses. If syphilis is diagnosed after 20 weeks' gestation, ultrasonography should be performed to evaluate for fetal syphilis. Although fetal infection can be cured by treating the mother, treatment failure is much higher in the presence of fetal hepatomegaly, ascites, hydrops, polyhydramnios, and placental thickening, which are signs of fetal syphilis detected on ultrasonography.
Vaginal Infections
Women with symptoms of trichomoniasis should be evaluated with a saline wet mount or culture for the presence of trichomonads. Screening for Trichomonas in asymptomatic women is not recommended.
Pneumonia
Clinical complaints including cough, shortness of breath, fever, chills, pleuritic chest pain or new abdominal pain (especially upper quadrant) should raise the clinical suspicion for pneumonia. The diagnosis is further evaluated by obtaining a chest XR. If clinical concern is present and the XR is negative, either a repeat chest XR should be obtained in 24-48 hours or a CT scan of the chest could be obtained. Please refer to above section on radiographic testing for further details on radiation exposure in pregnancy. Patients admitted for treatment of pneumonia should have blood cultures and a Legionella urine antigen. Patients with productive coughs should also have sputum cultures obtained. Culture data is not generally indicated for those being treated on an outpatient basis.
UTI
An MSU (mid stream urinalysis) and urine culture must be taken in patients with pyelonephritis or complicated urinary tract infection. A leukocyte esterase dipstick can be used to detect pyuria, and sticks are available to detect nitrite (produced by bacterial metabolism of urinary nitrate). The concern for pyelonephritis should also lead one to obtain blood cultures to assist in the evaluation. Imaging either via ultrasound or CT should be determined on an individual basis though if there is a lack of clinical response to proper antibiotics within 48-72 hours, appropriate imaging studies are indicated.
TREATMENT
Appendicitis
Prompt surgery, along with perioperative antibiotics, is recommended to prevent perforation and to improve the overall outcome for mother and fetus. Under appropriate conditions, laparoscopic appendectomy can be as safe as open appendectomy. Rates of fetal loss, complications, and duration of surgery are similar for laparoscopic surgery and open appendectomy. No statistical difference was found between open and laparoscopic appendectomy when compared for gestational duration, Apgar scores, and birth weights.
Pneumonia
The choice of antibiotic therapy in the pregnant patient with pneumonia is dictated by the same principles as in the nonpregnant patient, i.e. the presence or absence of coexisting illness, the severity of illness at presentation, and whether treatment will be instituted as an inpatient or outpatient. As with all medications, fetal toxicities, teratogenicity, and excretion in breast milk are major considerations in determining the appropriate choice of drugs. The penicillins, cephalosporins, and macrolides (excluding erythromycin, because it has been associated with hepatotoxicity in mothers during the second half of pregnancy) are safe. Current antibiotics available for treatment of community-acquired pneumonia include fluoroquinolones, macrolides, and beta-lactams, as well as aminoglycosides, and some miscellaneous agents such as Trimethoprim-sulfamethoxazole. When the pneumococcus is highly resistant, glycopeptides, third-generation cephalosporins, and vancomycin are effective. As usual, the risk associated with therapy in pregnancy must be individualized for each patient. Cefotaxime and ceftriaxone have been successfully used in the treatment of community-acquired pneumonia in patients less than 60 years of age and without comorbidities, which encompasses most of the pregnant population. The decision to add a macrolide in this instance is based on clinical suspicion of atypical infection. If an atypical pathogen is strongly suspected, a macrolide is the therapy of choice. Antiviral therapies can reduce maternal morbidity and mortality from viral pneumonia during pregnancy. Amphotericin B is the antifungal agent of choice during pregnancy. Antibiotics that are contraindicated in pregnancy are shown in Table 6.
Supportive therapy of the pregnant patient with pneumonia follows the same principles as used in the nongravid state; hydration, antipyretic therapy, and supplemental oxygen are key. The goal of oxygen therapy is more aggressive; maintenance of the arterial oxygen tension greater than 70mm Hg is critical because hypoxemia is less tolerated in the pregnant female. In addition, because respiratory alkalosis, a condition often associated with pulmonary disorders such as pneumonia, leads to reduction in uterine blood flow, the work of breathing must be decreased whenever possible in the pregnant pneumonia patient; adequate oxygenation is mandatory for this reason. Respiratory failure requiring mechanical ventilation has occurred in pregnancy and, therefore, close monitoring of both mother and fetus is required. Preterm labor is a well-documented complication of pneumonia, as previously mentioned, and may warrant tocolytic therapy. Influenza and pneumococcal vaccinations are effective in preventing pneumonia in high-risk populations and reducing complications and death.
Intra-Amniotic Infections
Antibiotic treatment should be initiated as soon as the diagnosis of intra-amniotic infections is made, and, delivery is usually indicated. Maternal antibiotic therapy has been shown to lower neonatal morbidity. Broad-spectrum antibiotic coverage is generally effective. The most established treatment regimen is intravenous ampicillin, and gentamicin; penicillin has also been used with gentamicin. Other antibiotics used include cephalosporins, erythromycin,amoxicillin, and amoxicillin-clavulonic acid. Induction of labor usually is indicated if this has not begun spontaneously. If cesarean section is necessary, intravenous clindamycin or metronidazole should be added after cord clamping to improve the coverage of anaerobic organisms. Cesarean section should be reserved for the usual obstetric indications; although operative delivery occurs in up to 40% of affected women. Due to greater tissue injury from cesarean section, antibiotic coverage should be continued until the patient has been afebrile and asymptomatic for 24 to 48 hours. However, the duration of antibiotic use after vaginal delivery is arbitrary. Pre-existing intrauterine infection is still a major risk factor for the development of postpartum sepsis.
Meningitis
The choice of initial antimicrobial therapy is based on the most common bacteria causing the disease, according to the patient’s age, the clinical setting, and on patterns of antimicrobial susceptibility. Combination therapy with vancomycin plus a third-generation cephalosporin (ceftriaxone or cefotaxime) has become the standard approach to empirical antimicrobial therapy. Intravenous dexamethasone before, or with, the first dose of antibiotics has been shown to reduce the risk of death and neurologic disability in adults with pneumococcal meningitis.
Sexually Transmitted Infections (STIs)
Principles of Management of STIs
• Treat the patient
• Treat the partner
• Contact tracing and treatment
• Investigate for other STIs
• Evaluate response to treatment
• Patient education
Treatment of syphilis has been with benzathine penicillin G. A Cochrane review concluded that although penicillin is effective for the treatment of syphilis in pregnancy, and the prevention of congenital syphilis, the optimal treatment regimen is uncertain. The CDC recommends benzathine penicillin G 2.4 million units intramuscularly, with desensitization in patients who are allergic to penicillin.
For Chlamydia, tetracyclines are contraindicated in pregnancy because of the risk of bone and tooth abnormalities. Amoxicillin appears to be effective for microbiologic cure, but there are few data on its long-term effectiveness for neonatal infection. A randomized trial comparing azithromycin in a single 1-g dose to erythromycin for seven days found enhanced compliance, fewer gastrointestinal side effects, and equivalent effectiveness with azithromycin. No long-term safety studies on azithromycin in pregnancy have been published; however, azithromycin is U.S. Food and Drug Administration pregnancy category B and is recommended as first-line treatment for chlamydia in pregnancy.
A Cochrane review of treatment for gonorrhea in pregnancy concluded that ceftriaxone 125 mg intramuscularly and spectinomycin 2 g intramuscularly have similar cure rates to oral amoxicillin plus probenecid. One randomized trial found cefixime 400 mg orally to be as effective as ceftriaxone 125 mg intramuscularly for the treatment of gonorrhea in pregnancy. The CDC recommends either of these as the treatment of choice for gonorrhea.
Treatment of human papillomavirus is not recommended in women with no cervical squamous intraepithelial lesions or genital warts.
UTI and Asymptomatic Bacteriuria
General measures to treat UTI include antibiotics, drinking more fluid to increase urine output (unproven), oral treatment (e.g. potassium citrate solution) to alkalinize urine and thereby alleviate symptoms (no effect on bacteriuria), and cranberry juice (unproven). Asymptomatic bacteriuria is defined as two consecutive positive cultures of the same species. It is recommended that pregnant women should be screened for bacteriuria by urine culture at least once in early pregnancy, and they should be treated if results are positive. Treatment should be based on antibiotic sensitivity testing and usually involves a 5- to 7-day course of antibiotics. Follow-up cultures should be obtained 1- 4 weeks after treatment and at least once more before delivery. Failure to treat a urinary tract infection results in persistence of the bacteriuria in about 30% of cases. Short-term therapy is not as established in pregnant women as it is in non-pregnant women, but it is recommended by smaller studies and expert opinion. A Cochrane systematic review has shown that drug treatment of asymptomatic bacteriuria in pregnant women substantially decreases the risk of pyelonephritis and reduces the risk of preterm delivery. However, it is not clear whether single-dose therapy is as effective as longer conventional antibiotic treatment. Most β-lactam antibiotics, including amoxicillin and cephalosporins, and nitrofurantoin are considered safe and effective in pregnancy. It is usual to treat the woman for 1 week and re-culture her urine on follow-up visits. If bacteriuria recurs, or if the women has vesico-ureteric reflux, prophylactic therapy may be necessary. As in non-pregnant women, there is no advantage to be gained by using long-term prophylaxis except for recurrent infections. Low-dose cephalexin (125-250 mg) or nitrofurantoin (50 mg) at night is recommended for prophylaxis against re-infection if indicated, lasting up to and including the puerperium.
Skin and Soft Tissue Infections
Treatment should be based on results of Gram stains and culture of the infected site. In communities in which methicillin-resistant Staphylococcus aureus is endemic or in patients recently hospitalized, MRSA must be considered. If the infection is severe, parenteral antibiotics may be indicated. Beta-lactam agents (antistaphylococcal penicillins or first generation cephalosporins) are preferred pending in vitro susceptibility results. In communities in whichmethicillin-resistant Staphylococcus aureus is endemic or in patients recently hospitalized, vancomyin might be considered.
Vaginal Infections
Metronidazole 2 g orally in a single dose or 500 mg twice per day for seven days is the treatment for trichomoniasis in pregnancy, although many physicians wait until after the first trimester to initiate it. Tinidazole is the other drug available in the United States that is effective against Trichomonas, but is not recommended in pregnancy. The outcome of treating trichomoniasis during pregnancy is uncertain. Some studies have shown that treatment does not reduce the incidence of preterm birth.
PREVENTION of INFECTION in THE PREGNANT HOST
Pre-Pregnancy Counselling and Antenatal Screening
Ideally, all women should consult their health-care provider before conception. Pre-pregnancy testing for infections should include an assessment of rubella immunity, syphilis status, human immunodeficiency virus (HIV) status, and immunity to hepatitis B. Some countries test for varicella IgG antibody to exclude previous infection with chickenpox. Women in close contact with children, such as childcare workers, may be at increased risk of cytomegalovirus (CMV) infection during pregnancy, and should be tested for CMV IgG before conception. A pre-pregnancy visit is also an opportunity to give dietary and other advice on how to reduce the risk of contracting listeriosis and toxoplasmosis, i.e. avoid raw or undercooked meat and meat products; peel or wash raw fruit and vegetables thoroughly to remove contaminating soil, and to wash hands after disposing of cat litter or gardening. The pre-pregnancy session also provides an opportunity for counseling of both partners to avoid casual sexual contact, and intravenous drug use and consequent risk of infection. Women who lack immunity to rubella, hepatitis B, or varicella, should be advised to have inoculation, and pregnancy should be postponed for at least two months after completion of the vaccination.
Routine antenatal screening generally should be offered to all pregnant women after obtaining informed consent. Selective screening based on risk factors is unreliable — eliciting risk factors for all relevant infections is time-consuming and unlikely to identify all those at risk. If the patient declines testing, the physician should discuss her objections and continue to strongly encourage testing. Other screening tests for sexually transmitted infections that are recommended for pregnant women include HIV, hepatitis B, syphilis, and Chlamydia trachomatis. Women at risk should be tested for Neisseria gonorrhea and hepatitis C.
Vaccination During Pregnancy
The administration of vaccines during pregnancy poses a number of concerns to physicians and patients about the risk of transmitting a virus to a developing fetus. This risk is primarily theoretic. Live-virus vaccines are therefore generally contraindicated in pregnant women. According to the CDC, if a live-virus vaccine is inadvertently given to a pregnant woman, or if a woman becomes pregnant within four weeks after vaccination, she should be counseled about potential effects on the fetus. Inadvertent administration of these vaccines, however, is not considered an indication for termination of the pregnancy. There is no evidence to show an increased risk to the fetus from vaccinating pregnant women with inactivated virus or bacterial vaccines, or toxoids. Therefore, if a patient is at high risk of being exposed to a particular disease, if infection would pose a risk to the mother or fetus, and if the vaccine is unlikely to cause harm, the benefits of vaccinating a pregnant woman usually outweigh the potential risks. Physicians should consider vaccinating pregnant women on the basis of the risks of vaccination versus the benefits of protection in each particular situation, regardless of whether live or inactivated vaccines are used. Vaccines commonly administered by family physicians, and their indication for use during pregnancy, are summarized in Table 6. Women of childbearing age often are concerned about whether breastfeeding is safe during immunization. Physicians should reassure their patients that no vaccines are contraindicated during breastfeeding.
Routine vaccines that generally are safe to administer during pregnancy include diphtheria, tetanus, influenza, and hepatitis B. Other vaccines, such as meningococcal and rabies, may be considered. Vaccines that are contraindicated, because of the theoretic risk of fetal transmission, include measles, mumps, and rubella; varicella; and BCG (Table 7). A number of other vaccines have not yet been adequately studied; therefore, theoretic risks of vaccination must be weighed against the risks of the disease to mother and fetus. Side effects after a vaccination vary from none, to those that may occur up to three weeks after vaccination. These may include soreness and redness at injection site, headache, fatigue, low-grade fever, non-contagious rash, swelling of neck glands, pain and stiffness of joints, and severe allergic reaction in very rare cases.
Complications
Preterm labor is a complication of appendicitis during pregnancy. There have been reports of appendectomy during pregnancy being associated with a decrease in mean birth weight and an increase in the number of live-born infants dying within the first week of life. Complications of appendicitis, including perforation, increase by trimester, and a ruptured appendix results in increased fetal morbidity and mortality. The rate of fetal loss in uncomplicated appendicitis ranges from 0 to 1.5% and in ruptured appendicitis from 20% to 35%. Maternal mortality is extremely unusual, but can increase up to 4% with advanced gestation and perforation.
Antepartum antibiotics may decrease, but do not eliminate, the neonatal morbidity of intraamniotic infection. The preterm fetus is most profoundly affected, for example, the incidence of respiratory distress is doubled and the mortality rate increased fourfold among 28-32 week infants whose mothers had preterm premature rupture of membranes, and in whom intraamniotic infectiondeveloped. Other studies have found a higher rate of neonatal sepsis, mortality, intraventricular hemorrhage, meningitis, necrotizing enterocolitis, and respiratory distress syndrome. There has been growing belief that intrauterine infections may predispose to neurodevelopmental impairment, and cerebral palsy.
SUGGESTED READING
1. Gilbert GL. Infections in pregnant women. Med J Aust 2002;176(5):229-236. [PubMed]
2. Gilbert GL. Routine antenatal screening and prenatal diagnosis of vertically transmissible infection. Baillieres Clin Obstet Gynaecol 1993;7:1-23.[PubMed]
3. Goldenberg RL, Hauth JC and Andrews WW. Intrauterine infection and Preterm Delivery. NEJM 2000;342:1500-1507. [PubMed]
4. Hurley R. Fever and infectious diseases. 1995. In: de Swiet (ed) Medical disorders in obstetric practice. Blackwell Scientific Publications, Oxford.
5. Hurley R. Infection in pregnancy. In: Chamberlain G (ed) Turnbull’s Obstetrics 2nd ed. London: Churchill Livingstone, 1995:471- 488.
6. Ledward RS, Ahmed BA. Viral infections in pregnancy. Update 1995; 42-48.
7. Maharaj D. Puerperal pyrexia: a review. Part I. Obstet Gynecol Surv 2007; 62(6):393- 399. [PubMed]
8. Maharaj D. Puerperal pyrexia: a review. Part II. Obstet Gynecol Surv 2007; 62(6):400-406. [PubMed]
9. Majeroni BA, Ukkadam S. Screening and Treatment for Sexually Transmitted Infections in Pregnancy. Am Fam Physician 2007;76(2):265-70. [PubMed]
10. Seminars in Fetal and Neonatal Medicine. Congenital and Opportunistic Infections - Congenital and Opportunistic Infections 2007; Volume 12, Issue 3.
11. Seminars in perinatology. Perinatal Infectious Disease 1998: Volume 22, Issue 4.
12. Shlyakhov E, Segev S, Rubinstein E. Main viral diseases with in utero transmission of pathogen during pregnancy: epidemiology, pathological features and outcome. Acta Obstet Gynecol Scand 1998; 77: 875-882. [PubMed]
Tables
Table 1. Causative Agents, Transmission, and Effects on Mother and Fetus/Neonate
Infecting Agent |
Transmission |
Potential Effects on Mother |
Potential Effects on Fetus/Newborn |
|---|---|---|---|
VIRAL |
|||
Mostly intrauterine |
Herpangina; hand, foot, mouth disease; myocardiopathy, aseptic meningitis, Bornholm disease
|
Abortion, stillbirth, neonatal sepsis,myocarditis-meningoencephalitis, ? gastrointestinal, cardiac and urogenital defects |
|
|
|
Mostly intrauterine. 50% in primary maternal infection (25% symptomatic) |
Usually asymptomatic. Sometimes moderate to high fever in primary infection |
|
|
Rash may resemble rubella; mimics appendicitis and abruption placenta |
Neonatal Sepsis, disseminated infection (hepatic necrosis), late stillbirth |
|
|
Non-specific febrile illness, abdominal pains |
||
Intrauterine, postnatal, mostly perinatal. Risk of perinatal infection if mother HBAg +ve is 90% |
Asymptomatic chronic carrier state, acute hepatitis
|
Chronic carrier, rarely acute fulminant neonatal hepatitis |
|
Intrauterine, mostly perinatal. 0%-6.2% depending on HCV RNA-titres. Up to 19.4% in HCV/HIV +ve patients |
Acute hepatitis, cirrhosis, hepatocellular carcinoma.
|
Unknown effects
|
|
Intrauterine & perinatal. 40-50% risk of severe neonatal infection after primary maternal genital infection, and 8% risk after secondary infection |
Oral or genital papular eruptions; more severe in pregnancy
|
Abortion after primary infection, fatal disseminated infection, prematurity, congenital malformations, stillbirth, intrauterine growth restriction |
|
Human Immunodeficiency viruses (HIV-1&2) |
Intrauterine, postnatal, mostly perinatal. 2%-40% transmission depending on treatment, and breastfeeding |
Asymptomatic, unless had AIDS
|
? Infantile disease, viremia
|
Intrauterine & postnatal
|
Up to 54% mortality in pandemics
|
Uncertain. ? CNS malformations, neural tube defects, ? circulatory malformations, ? cleft lip, ? reductive deformities |
|
Mostly intrauterine
|
Meningitis/meningo-encephalitis
|
Congenital disease |
|
Mostly intrauterine |
May be complicated by pneumonia & CCF. More severe. May be fatal |
Congential measles, ? increased mortality |
|
Intrauterine |
Nonspecific effects |
? increased mortality, ? endocardial fibroelastosis |
|
Poliomyelitis |
|
Increased severity, mortality |
Stillbirth, neonatal disease |
Rubella (German measles)
|
Mostly intrauterine, postnatal. 40%-60% risk of severe defects in months 1&2, 30%-35% in month 3, 10% in month 4. rare fetal damage after 20 weeks |
Mild nonspecific symptoms |
Congenital malformations, abortions, fetal death, chronic infection
|
Parvovirus B19 |
Intrauterine |
Asymptomatic “slapped-cheek” rash, erythema infectiosum (Fifth disease) |
Second trimester abortions, hydrops fetalis due to severe anemia, ?myocarditis, ?hepatitis, haematological effects in late pregnancy, |
Varicella zoster(Chickenpox) |
Intrauterine & perinatal. No accurate figures; estimated 0.7%-2.2% transmission |
More severe; maternal death |
Varicella embryopathy, congenital varicella syndrome, infantile zoster, microcephaly, focal brain calcification, optic atrophy, skin scarring, limb atrophy |
Bacterial |
|||
Intrauterine. 0.02%–4.5%, but varies in regions
|
Primary (asymptomatic, chancre, lymphadenopathy), secondary (rash, condylomata, alopecia, arthritis, periostitis, optic neuritis, intersitial keratitis, iritis, uveitis, meningitis)& tertiary (cardiovascular, neurological, joint disorders, gummas, dementia) |
Abortion, stillbirth, premature birth, non-immune hydrops, intrauterine growth restriction, perinatal death, congenital disease |
|
|
|
Mostly intrauterine, postnatal.
|
9% of all deaths of women of reproductive age. Malaise, night sweats, weight loss, usually respiratory symptoms |
Abortion, premature birth, stillbirth |
Mostly intrauterine, Perinatal. Soil, food, animals |
Headache, myalgia, fever, loin pains, pharyngitis, gastrointestinal symptoms |
Fetal death, chronic intrauterine, congenital or perinatal infection, prematurity, meningoencephalitis |
|
Borrelia burgdorferi(Lyme disease) |
Intrauterine |
3 stages: early localized, early disseminated, and late disease. Erythema migrans, rash, palsies of the cranial nerves, meningitis,conjunctivitis, carditis, arthritis, Meningoradiculoneuritis (Bannwarth syndrome). Systemic symptoms, such as arthralgia, myalgia, headache, fatigue |
Miscarriage, stillbirth, neonatal deaths,congenital Lyme disease hydrocephalus, cardiovascular anomalies, neonatal respiratory distress, hyperbilirubinemia, intrauterine growth restriction, cortical blindness |
Protozoal |
|||
Intrauterine. 15% -40%. Acquired through eating raw or undercooked meat or ingesting soil contaminated with toxoplasma oocysts, which are excreted in the faeces of infected cats. |
Usually asymptomatic or mild, non-specific symptoms. Posterior cervical lymphadenopathy
|
Hydrocephalus, intracranial calcification,chorioretinitis. Jaundice, anemia, hepatosplenomegaly, lymphadenopathy
|
|
Intrauterine. Placental malaria rates 4.7%-74% in endemic areas |
Increased susceptibility. Maternal death, anemia |
Abortion, stillbirth, premature delivery,intrauterine growth restriction, low birth weight. |
|
Table 2. Infectious and Non-infectious Causes of Fever in the Mother
| Systemic diseases | Bacterial infections | Non-infectious diseases |
|---|---|---|
1. Tuberculosis 2. Gall bladder
3. Abscesses
4. Gastrointestinal
6. Retroperitoneal infection 7. Septicemia
8. Endocarditis 9. Breast
10. Other |
1. Gonococcal
3. Gas gangarene 4. Tetanus 5. Opportunistic – associated with immune deficiency syndrome – |
1. Neoplasms
2. Connective tissue disease
3. Other
|
Table 3. Investigation of Symptomatic Infective Illness During Pregnancy
| Diagnosis | Diagnostic tests | Clinical Scenario |
|---|---|---|
Primary CMV infection, primary toxoplasmosis |
IgG & IgM (paired sera) | Mono-like illness |
| Listeriosis | Culture of faeces, blood and/or urine | Meningitis |
| Other viral infections | Culture, serology | Nonspecific fever |
| Rubella, Parvovirus infection | Culture, serology | Rash, exposure |
| Enterovirus infection | Throat swab or faecal culture | Non-specific fever, respiratory symptoms |
| Varicella | Lesion swab & serology | Rash |
Urinary tract infection (cystitis, pyelonephritis) |
Urine microscopy & culture | Any fever, dysuria |
| Genital herpes | First episode: lesion swab, HSV1 & HSV2 IgG & IgM (paired with stored serum if available) |
Genital lesions |
| Chlamydia, gonorrhoea | Cervical swab, Gram stain & culture; urine PCR (if positive, check syphilis, HBV& HIV serology) |
Vaginal discharge, diagnosis of other STI |
| Chorioamnionitis | Vaginal Gram stain & culture (for group B streptococci or abnormal vaginal flora associated with bacterial vaginosis) |
Abdominal pain |
| Pneumonia | Chest x-ray, sputum for stain & culture | Cough, dyspnea |
| Malaria | Peripheral blood smear, antigen detection techniques (PfHPR-2), fluorescent staining, PCR based assay, antibody test |
Fever after returning from an endemic country |
| Typhoid | Antigen detection | Fever after returning from an endemic country. |
| Hepatitis | HBsAg, HBeAg, Hepatitis C-RNA (PCR) | Fever and abdominal pain, abnormal LFT’s |
Table 4. Clinical Diagnosis of Intra-Amniotic Infection
Clinical criteria |
|---|
|
Table 5. Treatment of STIs in Pregnancy
Condition |
Treatment options |
|---|---|
Bacterial vaginosis* |
Metronidazole 500 mg orally two times per day for seven days |
Azithromycin 1 g orally in a single dose Amoxicillin 500 mg orally three times per day for seven days |
|
Ceftriaxone 125 mg intramuscularly in a single dose Cefixime 400 mg orally in a single dose |
|
Highly active antiretroviral therapy (individualized) |
|
|
Valacyclovir 1 g orally once per day for five days
Valacyclovir 500 mg orally once per day |
Benzathine penicillin G 2.4 million units intramuscularly Primary: single dose Positive serology, no symptoms: three doses one week apart Desensitization recommended in patients who are allergic to penicillin |
|
Metronidazole 2 g orally in a single dose |
STI = sexually transmitted infection; HIV = human immunodeficiency virus; HSV = herpes simplex virus.
*-Bacterial vaginosis is not an STI, but it is more common in sexually active women.
Table 6. Antibiotics That Can Cause Problems During Pregnancy *
| Antibiotic | Problem |
|---|---|
| Chloramphenicol | Gray baby syndrome In women or fetuses with glucose-6-phosphate dehydrogenase (G6PD) deficiency, the breakdown of red blood cells |
| Ciprofloxacin | Possibility of joint abnormalities (seen only in animals) |
Kanamycin, Streptomycin, |
Damage to fetal ear, resulting in deafness |
| Nitrofurantoin | In women or fetus with G6PD deficiency, the breakdown of red blood cells |
| Sulfonamides | Jaundice, and possibly brain damage in the newborn (much less with sulfasalazine).
In women or fetus with G6PD deficiency, the breakdown of red blood cells |
| Tetracycline | Deposit on bone causing reduced bone growth in fetus. Permanent yellowing of teeth, and increasing susceptibility to cavities in children. Occasionally, liver failure in pregnant women. |
* Most drugs appear in breast milk but usually in tiny amounts. However, even in tiny amounts, some drugs can harm the baby.
Some drugs appear in breast milk, but the baby usually absorbs so little of them that they do not affect the baby.
Examples are the antibiotics, kanamicin, streptomycin, tetracyclines, and chloramphenicol.
Table 7. Immunization During Pregnancy
Immunobiologic agent |
Type of agent |
Pregnancy Indications for immunization |
Comments |
|---|---|---|---|
Live virus vaccine |
|||
| Measles | Attenuated (Measles-Mumps-Rubella) | Contraindicated | Given post-partum. Breastfeeding not contraindicated |
| Mumps | Attenuated | Contraindicated | Given postpartum |
| Poliomyelitis | Attenuated. (Oral, and enhanced potency inactivated) | Not routinely recommended, except women at increased risk of exposure | Indicated for susceptible women travelling to endemic areas |
| Rubella | Attenuated | Contraindicated | Teratogenicity is theoretic. Postpartum |
| Yellow fever | Attenuated | Contraindicated except if exposure is unavoidable | Postponement of travel is preferable to vaccine |
| Varicella | Attenuated | Contraindicated | Postpartum. No reported adverse outcomes if given in pregnancy |
Other |
|||
| Influenza | Inactivated | All women in the 2nd & 3rd trimesters during the ‘flu season; women at risk for pulmonary complications regardless of trimester | - |
| Hepatitis A | Inactivated | Pre- & post-exposure for at-risk women; international travellers | - |
| Hepatitis B | Recombinant purified surface antigen | Pre- & post-exposure for at-risk women | Used with immunoglobulin in some exposures |
Inactivated bacterial |
|||
| Pneumococcus | Polyvalent polysaccharide | In women with asplenia; metabolic, renal, cardiac, pulmonary disease; immunosuppressed; smokers | - |
| Meningococcal | Quadrivalent polysaccharide | Not altered by pregnancy | - |
| Typhoid | Killed or live attenuated | Except in exposure or travel to endemic areas | Oral vaccine preferred |
Toxoids |
|||
| Tetanus-diphtheria | Combined toxoids | Lack of primary series, or no booster within past 10 years | - |