This chapter deals primarily with APGO Educational Topic Area:
TOPIC 17 MEDICAL AND SURGICAL COMPLICATIONS OF PREGNANCY
Students should be able to identify how pregnancy affects the natural history of various infectious disorders and how a preexisting infectious disorder affects maternal and fetal health. They should be able to describe infectious disorders that are particularly concerning during pregnancy. They should be able to outline a basic approach to evaluation and management of infectious disorders in pregnancy.
Clinical Case
You are seeing a patient with known human immunodeficiency virus (HIV) infection for her routine annual examination, and she tells you that she recently got married. She is interested in having children but has been told she should never get pregnant because she is infected with HIV. She wants to know whether pregnancy would cause her HIV infection to worsen and if there is anything she could do to prevent transmission of HIV to her baby.
Screening for and preventing infectious disease is an integral part of routine prenatal care. Many of these agents can have devastating outcomes for mother, infant, or both. An understanding of the disease course in pregnancy; the maternal and fetal sequelae; and, most importantly, prevention and therapy are key to management of the pregnant patient. Screening recommendations for common sexually transmitted diseases (STDs) in pregnancy are listed in Table 24.1. Infections involving specific organ systems and not associated with significant risk of fetal infection (i.e., urinary tract infections) are covered elsewhere (see Chapters 11, 21, and 22).
GROUP B STREPTOCOCCUS
Group B streptococcus (GBS) (or Streptococcus agalactiae) is an important cause of perinatal infections. Asymptomatic lower genital tract colonization occurs in up to 30% of pregnant women, but cultures may be positive only intermittently, even in the same patient. Approximately 50% of infants exposed to the organism in the lower genital tract will become colonized. For most of these infants, such colonization is of no consequence, but without preventive treatment, GBS sepsis occurs in approximately 1.7 infants per 1,000 live births.
There are two manifestations of clinical infection of the newborn, termed early onset and late onset, occurring at roughly equal frequency. Early-onset infection manifests as septicemia and septic shock, pneumonia, or meningitis and occurs during the first week of life. Early-onset infection is much more common in preterm infants than in term infants. Late-onset infection occurs later, by definition, infants older than 6 days (but has been reported beyond 3 months). GBS disease in newborns may occur as a result of vertical transmission or nosocomial or community-acquired infection.
With prevention strategies, current rates of early-onset GBS disease of the newborn have decreased to approximately 0.28 per 1,000 live births. Currently, the Centers for Disease Control and Prevention (CDC) and the American College of Obstetricians and Gynecologists (College) recommend universal screening for GBS between 35 and 37 weeks of gestation. All women who are GBS positive by rectovaginal culture should receive antibiotic prophylaxis in labor or with rupture of membranes.
If a patient’s culture status is unknown, then prophylaxis should be given if any of the following conditions exists:
• Preterm labor (less than 37 weeks of gestation)
• Preterm premature rupture of membranes (less than 37 weeks of gestation)
• Rupture of membranes 18 hours or longer
• Maternal fever during labor (at or above 38°C [100.4°F])
Women with GBS bacteriuria during their current pregnancy or women who have previously given birth to an infant with early-onset GBS disease also are candidates for intrapartum antibiotic prophylaxis. When culture results are not available, intrapartum prophylaxis should be offered only on the basis of the presence of intrapartum risk factors for early-onset GBS disease. CDC and the College Guidelines include recommended medication regimens.
In the mother, significant postpartum fever may indicate postpartum endometritis; sepsis; and, rarely, meningitis, which may be caused by infection with GBS. With endometritis, the onset is often sudden and within 24 hours of delivery. Significant fever and tachycardia are typically present; sepsis may follow.
HERPES
Herpes simplex virus (HSV) is a double-stranded DNA virus that can be differentiated into HSV type 1 (HSV-1) and HSV type 2 (HSV-2). HSV-1 is the primary etiologic agent of herpes labialis (fever blisters), gingivostomatitis, and keratoconjunctivitis. Most genital infections with HSV are caused by HSV-2, but genital HSV-1 infections are becoming increasingly common, particularly among adolescent and young women. Up to 80% of new genital infections among women may be due to HSV-1, with the highest rates occurring in adolescents and young adults. Herpes infections are categorized as follows:
• Primary occurs in a woman with no evidence of prior HSV infection (seronegative to both HSV-1 and HSV-2).
• Nonprimary first episode occurs in a woman with a history of heterologous infection (e.g., first HSV-2 infection with a prior HSV-1 infection).
• Recurrent disease occurs in a woman with clinical or serologic evidence of prior genital herpes (of the same serotype).
The primary form poses the greatest risk to the fetus. The fetus/neonate is infected either from ascending infection following spontaneous rupture of membranes or from passage through an infected lower genital tract at delivery. With a primary infection at the time of delivery, the risk of neonatal infection approaches 50%; it is far lower (approximately 3%) with recurrent infection, because the size of the inoculum is much decreased. In utero fetal infection can occur, although this is much less common. Most infants with localized herpes infection ultimately do well; as a rule, infants with disseminated infection do very poorly.
Diagnosis
The diagnosis of HSV infection is suspected when clinical examination shows the characteristic tender vesicles with ulceration followed by crusting (Fig. 24.1). Confirmation is by identification of the virus in cell culture, with most positive results reported within 72 hours. Polymerase chain reaction (PCR) testing is commercially available and is more sensitive than culture. Serologic testing for HSV-1 and HSV-2 immunoglobulin (Ig) is also available and is a helpful ancillary test because cultures of crusted or healing lesions can often be negative. Type-specific serologic testing that accurately distinguishes between anti-HSV-1 and -2 Ig is recommended.
Treatment
All pregnant women should be asked about a history of HSV infection at their initial prenatal visit. If infection with herpes virus is suspected during the course of pregnancy in a woman with undocumented history of HSV, a culture from a lesion should be obtained to confirm the diagnosis. In such patients, or any patient with a history of herpes virus infection, careful inspection of the lower genital tract is important at the onset of labor or when rupture of membranes occurs. If no lesions are identified, vaginal delivery is deemed safe. Cesarean delivery is recommended if herpes (or suspected herpes) lesions are identified on the cervix, in the vagina, or on the vulva at the time of labor or if spontaneous rupture of membranes occurs. This is true whether or not the lesions are associated with primary or recurrent infection due to the severity of neonatal disease.
FIGURE 24.1. Herpes virus infection. Although herpes virus infection is primarily a blistering disease, on thin, moist skin, blisters quickly shear off to produce round, coalescing erosions. (Edwards L. Genital Dermatology Atlas.Philadelphia, PA: Lippincott Williams & Wilkins; 2004:90).
Acyclovir and related compounds are safe in pregnancy and can be used if symptoms are severe. Additionally, in patients with recurrent HSV, these medications should be offered for suppression of outbreaks starting at 36 weeks of gestation to reduce the risk of viral shedding and cesarean delivery due to active lesions. Routine antepartum genital HSV cultures in asymptomatic women are not recommended, insofar as these tests do not predict viral shedding at delivery. Routine type-specific serologic screening for HSV in pregnancy is not currently recommended. However, serologic screening may be considered in certain populations to identify women who may benefit from suppressive therapy or preventive measures.
RUBELLA
Rubella (German, or 3-day, measles) is an RNA virus with important perinatal impact if infection occurs during pregnancy. Widespread immunization programs in the United States over the last 30 years have prevented large epidemics of rubella, but some women of reproductive age lack immunity to this virus and are, therefore, susceptible to infection. Foreign-born women may lack immunity and be susceptible to infection if their country of origin does not have a comprehensive vaccination program. Once infection occurs, immunity is lifelong. A history of prior infection is an unreliable indicator of immunity.
Symptoms
Up to 50% of adult women have had subclinical or asymptomatic infection; symptoms include fever, rash involving the face and spreading to the trunk and extremities, arthralgias, head and neck lymphadenopathy, and conjunctivitis. However, fetal effects are substantial. If a woman develops rubella infection in the first trimester of pregnancy, there is an increased risk of both spontaneous abortion and congenital rubella syndrome. Although most infants with congenital rubella appear normal at birth, many subsequently develop signs of infection. Common defects associated with the syndrome include congenital heart disease (e.g., patent ductus arteriosus), mental retardation, deafness, and cataracts. The risk of congenital rubella is related to the gestational age at the time of infection; it is highest in the first 12 weeks of pregnancy (80% vertical transmission) and decreases with increasing gestational age (25% transmission in the second and third trimesters). Primary infection can be diagnosed by serologic testing for maternal IgM and IgG antibodies during the acute and convalescent stages of infection.
Screening
Because of the serious fetal implications, prenatal screening for IgG rubella antibody is routine. All pregnant women should be screened, unless they are known to be immune based on previous serologic testing. Young women should be vaccinated when they are not pregnant, if they are susceptible. The vaccine induces antibodies in virtually all rubella nonimmune women. Because the vaccine itself is of the live, attenuated type, pregnant women should not be vaccinated. It is recommended that pregnancy be delayed 1 month following immunization, although congenital rubella syndrome following vaccination during an undiagnosed pregnancy has not been reported. In women whose prenatal screen identifies a lack of rubella antibody, vaccination postpartum at the time of hospital discharge is recommended. Such management poses no risk to the newborn or other children; breastfeeding is not contraindicated.
If rubella is diagnosed in a pregnant woman, the patient should be advised of the risk of fetal infection and counseled regarding options for continuing the pregnancy.
Because there is no effective treatment for a pregnant patient infected with rubella, patients who do not have immunity are advised to avoid potential exposure. Although Ig may be given to an infected woman, it does not prevent fetal infection. The absence of clinical signs in a woman who has received Ig does not guarantee that infection of the fetus has been prevented.
HEPATITIS
Viral hepatitis is one of the most common and potentially serious infections that can occur in pregnant women. Six forms of viral hepatitis have now been identified, two of which, hepatitis A and hepatitis B, can be prevented effectively through vaccination.
Hepatitis A
Hepatitis A virus (HAV) is transmitted from person to person primarily through fecal–oral contamination. Good hygiene and proper sanitation are important to prevent infection. However, vaccination is the most effective means of preventing transmission. The hepatitis A vaccine is available as both a single-antigen vaccine and a combination vaccine (containing both HAV and hepatitis B virus [HBV] antigens). Prior to vaccine availability, HAV accounted for one third of cases of acute hepatitis in the United States. HAV infection does not progress to chronic infection. Diagnosis is confirmed by demonstration of anti-HAV IgM antibodies. HAV infection has no specific effects on pregnancy or the fetus. Breastfeeding is not contraindicated in HAV-infected women if appropriate hygienic precautions are followed. Vaccination safety during pregnancy has not been established, but the risk to the developing fetus is minimal because the vaccine contains inactivated purified viral proteins. Vaccination is recommended for individuals who are intravenous (IV) drug users, who have certain medical disorders (e.g., chronic liver disease or receiving clotting factor concentrates), who are employed in specific occupations (e.g., working in primate laboratories or research laboratories), and who travel to countries with endemic HAV infection. HAV Ig is effective for both pre- and post-exposure prophylaxis and can be used during pregnancy.
Hepatitis B
HBV infection is more serious than HAV infection regardless of pregnancy status. HBV is transmitted by the parenteral route and through sexual contact. Ten to fifteen percent of infected adults develop chronic infection, and, of those, some will become carriers. Testing for hepatitis B surface antigen (HBsAg) during pregnancy is routine, as about half of pregnant women infected lack traditional high-risk factors. Vertical transmission of hepatitis occurs to a significant but variable extent and is related to the presence or absence of maternal hepatitis B e antigen (HBeAg): If the patient is positive for the “e” antigen, indicating a high viral load and active viral replication, her fetus has a 70% to 90% risk of becoming infected, and most of such infants will become chronic carriers. The risk of fetal infection is higher if maternal infection occurs in the third trimester. Neonatal infection can also occur via breast milk. Women who are HBsAg negative with risk factors for HBV infection should be offered vaccination during pregnancy.
Patients who have been exposed to HBV should be treated as soon as possible with hepatitis B immunoglobulin (HBIg) and begin the vaccination series. All infants now receive vaccination against hepatitis B, with the initial injection given between 2 days and 2 months of delivery. Infants of mothers who are HBsAg positive should receive the vaccine and HBIg within 12 hours of birth. Breastfeeding is not contraindicated in women who are chronic carriers if their infants have received both the vaccination and HBIg within 12 hours of delivery.
Hepatitis C
Hepatitis C virus (HCV) infection is a growing problem in the United States and has obstetric implications. Similar to HBV in transmission (i.e., sexual, parenteral, and vertical), HCV infection is often asymptomatic. Diagnosis is made by serologic evidence of anti-HCV IgG. However, antibodies may not be detectable until up to 10 weeks after onset of clinical illness. PCR identification of HCV RNA may be a useful adjunct to diagnosis in early and chronic infection. The presence of anti-HCV antibody does not confer immunity or prevent transmission of infection. Fifty percent of infected individuals go on to have chronic infection.
Risk Factors
Screening for evidence of HCV infection is not routine. However, the CDC recommends routine screening for certain groups (Box 24.1). Vertical transmission occurs in 2% to 12% of cases, with the risk of fetal infection directly related to the quantity of hepatitis C RNA virus in maternal blood. Vertical transmission is rare with an undetectable hepatitis C RNA viral load. Maternal co-infection with human immunodeficiency virus (HIV) is also associated with a higher risk of vertical transmission of HCV. Other risk factors for fetal infection include prolonged rupture of membranes in labor and use of invasive fetal monitoring. Currently, there are no preventive measures known to reduce the risk of mother-to-child transmission; cesarean delivery has not been consistently associated with a decreased rate of vertical transmission and should be performed for usual obstetric indications in HCV-infected women.Breastfeeding is not contraindicated in women with HCV. Newer therapies for HCV infection that clear detectable virus in the blood and normalize transaminase levels are promising in nonpregnant adults. Ig does not contain antibodies to HCV and has no role in post-exposure prophylaxis.
BOX 24.1 Risk Factors for Hepatitis C Virus Screening
The following risk factors warrant routine screening:
• History of injection or intravenous drug abuse
• Human immunodeficiency virus infection
• History of blood transfusion or solid organ transplant before July 1992
• History of receiving clotting factor concentrates produced before 1987
• Long-term dialysis
• Signs and symptoms of liver disease
Adapted from Centers for Disease Control and Prevention, Workowski KA, Berman SM. Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep. 2010;59(RR-12):1–116.
Hepatitis D
Hepatitis D virus (HDV) is an incomplete viral particle that can only cause infection in the presence of HBV. Transmission of HDV is through the parenteral route; chronic infection can occur, resulting in severe disease in 70% to 80% of chronically infected individuals and mortality rates as high as 25%. Vertical transmission has been documented but is uncommon. Diagnosis is made by identification of HDV antigen and anti-HDV IgM in acute disease; IgG antibodies develop but are not protective. No vaccine is currently available. Measures to prevent HBV infection are effective in the prevention of HDV transmission.
Hepatitis E
Hepatitis E virus (HEV) infection is a waterborne disease and is uncommon in the United States. The disease is typically self-limited, but has been associated with higher rates of fulminant hepatitis E and mortality in pregnant women, which can be as high as 20% after infection in the third trimester. Co-infection with HIV results in severe disease and high mortality in pregnancy. Diagnosis is made by serologic testing for HEV-specific antibodies in women with travel exposure. The risk of vertical transmission is very low, but cases have been reported. No vaccine is currently available.
ACQUIRED IMMUNE DEFICIENCY SYNDROME
Worldwide, women account for nearly 50% of those infected with HIV. The CDC estimates that 27% of those living with acquired immune deficiency syndrome (AIDS) in the United States are women. Of these women, 71% were exposed through heterosexual contact and 27% through injection drug use. One percent of those living with AIDS are children under age 13 years, most of whom acquired the infection perinatally.
The usual estimated latency period from untreated HIV to AIDS is about 11 years. HIV infection becomes AIDS as the helper (CD4+) lymphocyte count decreases, and the host becomes more susceptible to other types of infections. With the availability of increasingly effective antiretroviral drugs, lifespan and quality of life have improved dramatically.
Pathophysiology
HIV is a single-stranded, RNA, enveloped human retrovirus that has the ability to become incorporated into the cellular DNA of CD4+ cells such as lymphocytes, monocytes, and some neural cells. Once infected, seroconversion usually occurs within 2 to 8 weeks, but it may take up to 3 months and, in rare cases, 6 months. HIV infection appears to have no direct effect on pregnancy course or outcome. Likewise, pregnancy does not seem to affect the course of HIV. Both HIV and pregnancy may affect the natural history, presentation, treatment, or significance of certain infections, and these, in turn, may be associated with pregnancy complications or perinatal infection. These infections include vulvovaginal candidiasis, bacterial vaginosis, genital herpes simplex, human papillomavirus (HPV), syphilis, cytomegalovirus (CMV), toxoplasmosis, and hepatitis B and C. All women demonstrate a decline in absolute CD4+ cell counts in pregnancy, which is thought to be secondary to hemodilution. On the other hand, the percentage of CD4+ cells remains relatively stable. Therefore, percentage, rather than absolute number, of CD4+cells may be a more accurate measure of immune function for HIV-infected women.
The baseline rate of perinatal HIV transmission without prophylactic therapy is approximately 25% and is generally related to higher viral loads and lower CD4+ counts. With zidovudine monotherapy, perinatal transmission is reduced to ~8%. Currently, with combination antiretroviral therapy and an undetectable viral load, perinatal transmission is reduced to 1% to 2%. There is evidence that transmission can occur antepartum, intrapartum, or postpartum through breastfeeding; however, 66% to 75% of transmission appears to occur during or close to the intrapartum period, particularly in nonbreastfeeding populations.
Screening and Testing
Initial screening consists of enzyme-linked immunosorbent assay (ELISA), which is based on an antigen–antibody reaction. In 99% of cases, antibodies to HIV become detectable by 3 months after infection. If results of ELISA are positive, a Western blot test, which identifies antibodies to specific portions of the virus, is performed to confirm the diagnosis. A serologic test is reported as positive only if both the ELISA and the Western blot analyses are positive; this testing has a sensitivity and specificity of over 99%.
Universal, voluntary HIV screening for pregnant women is standard and should be part of the standard prenatal laboratory tests, unless a patient states that she does not want HIV testing. This “opt-out” approach is recommended by both the College and the CDC; however, state and local laws to the contrary may supersede these recommendations. Refusal of testing should be documented.
Additionally, third-trimester repeat screening is recommended for at-risk populations (including women with an STD or women who use illicit drugs, exchange sex for money or drugs, have multiple sexual partners in pregnancy, or have signs or symptoms suggesting acute HIV during pregnancy) as well as for women who declined testing in the first trimester or have undocumented HIV status at the time of labor and delivery.
Rapid HIV testing is a valuable alternative to the conventional testing previously discussed. Results can be available within hours after the blood sample is obtained and, thus, is especially useful when a patient of unknown HIV status presents in labor. A positive rapid HIV test must be confirmed by Western blot analysis or immunofluorescence assay before the woman is deemed HIV positive; however, immediate antiretroviral treatment should be started as soon as a rapid HIV-positive result is noted in a laboring patient, pending further confirmation.
Management
Management involves antiretroviral therapy and taking precautions during delivery to avoid transmission. Antiretroviral therapy in pregnancy is a key component to reduction of perinatal transmission to as low as 1% to 2%.Effective combination antiretroviral therapy should be offered to all HIV-infected pregnant women and is administered in the antepartum and intrapartum period as well as to the neonate. Other than maternal disease status and viral load, risk factors for increased vertical transmission of HIV include chorioamnionitis, prolonged rupture of membranes, invasive fetal monitoring, and mode of delivery.
Awareness of maternal HIV status can help guide management of pregnancy and labor and delivery to minimize risk of transmission to the fetus. During pregnancy, amniocentesis and chorionic villus sampling should be avoided.During labor, the likelihood of transmission increases linearly with increasing duration of rupture of membranes. The use of fetal scalp electrodes or fetal scalp sampling increases exposure of the fetus to maternal blood and genital secretions and may increase the risk of vertical transmission, depending on the serum and genital HIV viral load. These techniques should be avoided. Use of episiotomy or vacuum extraction or forceps may potentially increase risk of transmission by increasing exposure to maternal blood and genital secretions. However, these techniques may help shorten duration of labor or rupture of membranes with vaginal delivery and, thus, may decrease the likelihood of transmission. Finally, cesarean delivery performed before the onset of labor and rupture of membranes significantly reduces the risk of perinatal HIV transmission. Planned cesarean delivery at 38 weeks of gestation to decrease the risk of perinatal transmission of HIV is recommended for women who have a viral load >1,000 copies/mL.
Breastfeeding plays a significant role in perinatal HIV transmission. It is estimated to have accounted for up to 50% of newly infected children globally. Breastfeeding in the setting of established maternal infection has a significant additional risk of transmission. When safe alternatives are available, breastfeeding should be avoided in HIV infection.
The field of HIV care and management is rapidly advancing, and care of HIV-infected pregnant women should be coordinated with a health care provider who regularly cares for HIV-infected women. Comprehensive information is also provided and regularly updated on the U.S. Department of Health and Human Resources Web site AIDSinfo, at www.aidsinfo.nih.gov, under “perinatal guidelines.”
HUMAN PAPILLOMAVIRUS
More than one third of sexually active women have been exposed to at least one type of HPV. Genital wart lesions (condyloma acuminata) often increase in size and area during pregnancy due to relative immune suppression. If extensive, cesarean delivery may be necessary to avoid excessive trauma to the lower genital tract. In pregnancy, cryotherapy, laser therapy, and trichloroacetic acid may be used to treat genital HPV lesions. Podophyllin, 5-fluorouracil, and interferon are not recommended, because they may be toxic to the fetus. Because there are limited data regarding imiquimod use in pregnancy, it is generally avoided. Treatment of genital HPV lesions is often delayed until after pregnancy, insofar as spontaneous resolution may occur. Transmission of HPV from mother to infant is very rare but manifests as laryngeal papillomatosis. Cesarean delivery does not prevent perinatal transmission of HPV.
Certain HPV types cause abnormal Pap test results and cervical dysplasia. Management of abnormal Pap test results in pregnancy is similar to that in nonpregnant women; however, biopsies and other excisional procedures are often deferred until the postpartum period. Close follow-up which may include a repeat Pap smear and/or colposcopy in pregnancy is often performed instead. HPV infection and abnormal Pap smears as well as recommendations regarding the HPV vaccine are discussed elsewhere in the text (see Chapters 29 and 47).
SYPHILIS
Syphilis is a systemic disease caused by the motile spirochete Treponema pallidum. The spirochete is transmitted by direct contact, invading intact mucous membranes or areas of abraded skin. A painless ulcer at the site of inoculation follows, usually within 6 weeks following exposure. The ulcer is firm, with elevated edges; it lasts for several weeks. One to three months later, a skin rash occurs or, in some patients, raised lesions (condyloma lata) appear on the genitalia.
T. pallidum is generally considered to cross the placenta to the fetus after 16 weeks of gestation. Transmission can occur at any stage of maternal infection and has been documented at as early as 6 weeks of gestation.
Spontaneous abortion, stillbirth, and neonatal death are more frequent in any untreated patient, whereas neonatal infection is more likely in primary or secondary rather than latent syphilis. Newborns with congenital syphilis may be asymptomatic or have the classic signs of the syndrome, although most infants do not develop evidence of disease for 10 to 14 days after delivery. Early evidence of the disease includes a maculopapular rash, “snuffles,” mucous patches on the oropharynx, hepatosplenomegaly, jaundice, lymphadenopathy, and chorioretinitis (Fig. 24.2). Later signs include Hutchinson teeth, mulberry molars, saddle nose, and saber shins.
Screening
Congenital syphilis is readily preventable with prompt and appropriate maternal treatment. Therefore, all pregnant women should be screened serologically as early as possible and again at delivery (and if exposed to an infected partner). Serologic testing is the mainstay of diagnosis. Nontreponemal screening tests (Venereal Disease Research Laboratory [VDRL] and rapid plasma reagin [RPR]) are sometimes falsely positive; treponemal-specific tests(fluorescent treponemal antibody absorbed and T. pallidum particle agglutination) are used to confirm infection and identify antibodies specific for T. pallidum. A positive treponemal-specific test result indicates either active disease or previous exposure; regardless of treatment, the test remains positive for life in most individuals.
FIGURE 24.2. Congenital syphilis. Note the mucous patches on the oropharynx and the characteristic “snuffles.” CDC/Dr. Norman Cole.
Treatment
Therapy differs by stage of disease and is generally the same as that recommended for nonpregnant adults. There are no proven alternative therapies to penicillin for treating syphilis in pregnancy. Therefore, patients with penicillin sensitivity require skin testing, followed by desensitization for those with a true penicillin allergy. The Jarisch-Herxheimer reaction occurs most often among patients with early syphilis and is an acute febrile reaction that typically occurs in the first 24 hours after treatment. In pregnancy, this reaction may precipitate preterm labor or cause fetal distress and may warrant close observation of mothers after treatment. Posttreatment titers (RPR or VDRL) should be followed serially for at least 1 year. A fourfold increase in serologic titer, or persistent or recurrent signs or symptoms, may indicate inadequate treatment or re-infection. Retreatment is indicated in either case. Response to therapy is again evaluated by following serologic titers.
GONORRHEA
Antepartum screening for Neisseria gonorrhoeae should be performed early in pregnancy for women with risk factors or symptoms and repeated in the third trimester for women at high risk (see Table 24.1).Rates in pregnancy range from 1% to 7%, depending on the population. Diagnosis is made by PCR. All cases of gonorrhea must be reported to health care officials.
Treatment is with an extended spectrum or third-generation cephalosporin. Tetracyclines and fluoroquinolones are contraindicated in pregnancy.
Infection above the cervix (i.e., of the uterus, including the fetus, and the fallopian tubes) is rare after the first weeks of pregnancy. At delivery, however, infected mothers may transmit the organism, causing gonococcal ophthalmiain the neonate. All neonates receive routine prophylactic treatment with sterile ophthalmic ointment containing erythromycin or tetracycline, which is generally effective in preventing neonatal gonorrhea.
CHLAMYDIA
Antepartum screening for Chlamydia trachomatis should be performed early in pregnancy and repeated in the third trimester based on risk factors (see Table 24.1). It has been detected in 2% to 13% of pregnant women, depending on the population, and is generally found in 5% of all populations. In pregnant women, infection is often asymptomatic but may cause urethritis or mucopurulent cervicitis. Like gonorrhea, infection of the upper genital tract is uncommon during pregnancy, although Chlamydia infection has been associated with postpartum endometritis and infertility. Diagnosis is made by culture, direct fluorescent antibody staining, ELISA, DNA probe, or PCR.
Maternal Chlamydia infection at the time of delivery results in colonization of the neonate in 50% of cases. Neonates colonized at birth may go on to develop purulent conjunctivitis soon after birth or pneumonia at 1 to 3 months of age. Routine prophylaxis against neonatal gonococcal ophthalmia is not generally effective against chlamydial conjunctivitis; systemic treatment of the infant is necessary. Fortunately, neonatal chlamydial ophthalmia and pneumonia are becoming less common with the institution of universal prenatal screening and treatment. Recommended treatment of genital infection with C. trachomatis in pregnancy includes azithromycin or amoxicillin. Doxycycline and ofloxacin are contraindicated during pregnancy.
Repeat testing to confirm successful treatment, preferably by culture performed 3 to 4 weeks after completion of therapy, is recommended in pregnancy.
CYTOMEGALOVIRUS
Approximately 1% of all neonates are infected with CMV in utero and excrete CMV at birth. Although the majority of CMV infections are asymptomatic, 5% of infected neonates show symptoms at birth. A DNA herpesvirus, CMV may be transmitted in saliva, semen, cervical secretions, breast milk, blood, or urine. CMV infection is often asymptomatic, although it can cause a short febrile illness. Similar to HSV, CMV may have dormant periods, only to reactivate at a later time. There are multiple serotypes, and the presence of anti-CMV IgG does not confer immunity; recurrent infection may occur with a new strain of virus. The prevalence of antibodies to CMV is inversely proportional to age and socioeconomic status.
The risk of neonatal infection is significantly higher with primary maternal infection than with recurrent infection; with recurrent infection the risk of neonatal infection is much lower, at 2% or less. Intrauterine growth restriction is sometimes noted. Most infants are asymptomatic at birth; when signs occur, they include petechiae, hepatosplenomegaly, jaundice, thrombocytopenia, microcephaly, chorioretinitis, or nonimmune hydrops fetalis. Long-term sequelae include severe neurologic impairment and hearing loss.
There is no effective vaccine or treatment for maternal or fetal infection. Therefore, routine serologic screening for CMV in pregnancy is not recommended. Testing is generally limited to women in whom CMV infection is suspected and is done by culture or PCR. Amniocentesis for CMV DNA PCR may be performed to confirm fetal infection. Antiviral agents have been used to treat neonatal infection but remain experimental.
TOXOPLASMOSIS
Infection with the intracellular parasite Toxoplasma gondii occurs primarily through ingestion of the infectious tissue cysts in raw or poorly cooked meat or through contact with feces from infected cats, which contain infectious sporulated oocytes. The latter may remain infectious in moist soil for more than 1 year. Only cats that hunt and kill their prey are reservoirs for infection; those that eat prepared cat food are not. In immunocompetent adult humans, infection is most commonly asymptomatic, and disease is self-limited. Prior infection confers immunity, unless the individual is immunosuppressed. Approximately 15% of reproductive-age women have antibodies to toxoplasmosis.
Although congenital infection is more common following maternal infection in the third trimester, the sequelae following first-trimester fetal infection are more severe. Over half of infants whose mothers are infected during the last trimester of pregnancy have serologic evidence of infection, but three fourths of these show no gross evidence of infection at birth. Signs of congenital infection include severe mental retardation, chorioretinitis, blindness, epilepsy, intracranial calcifications, and hydrocephalus.
Screening
In some regions with high prevalence of disease (e.g., France and Central America), screening is routine in pregnancy. In the United States, routine screening in pregnancy is not recommended except in the presence of maternal HIV infection. Because identification of the organism in tissue or blood is complex and infection is usually asymptomatic, diagnosis depends on demonstration of seroconversion. A positive IgG titer indicates infection at some time. A negative IgM effectively rules out recent infection; however, IgM may persist for long periods and a positive test is not reliable in assessing duration of disease. In addition, false-positive IgM results are common with commercially available assays. Confirmatory testing in pregnancy should be performed in a Toxoplasma reference laboratory prior to initiating any therapy.
Treatment and Prevention
Treatment of acutely infected pregnant women with spiramycin may reduce the risk of fetal transmission but does not prevent sequelae in the fetus if infection has occurred. This medication is only available through the Food and Drug Administration. If fetal infection has already been noted (through ultrasound findings or confirmed with testing of fetal blood or amniotic fluid), pyrimethamine and sulfadiazine therapy may decrease the risk of congenital infection and the severity of manifestations.
Prevention of infection should be an important part of prenatal care, including counseling regarding thoroughly cooking all meats, careful handwashing after handling raw meats, washing of fruits and raw vegetables before ingestion, wearing gloves when working with soil, and keeping cats indoors and feeding them only processed foods. If a cat is kept outside, someone other than a pregnant woman should feed and care for the cat and dispose of its waste.
VARICELLA
Congenital varicella (chicken pox) infection can be serious, but it is very uncommon due to high rates of immunity in women of reproductive age. Risk of congenital varicella syndrome (i.e., skin scarring, limb hypoplasia, chorioretinitis, and microcephaly) is limited to maternal infection occurring in the first half of pregnancy. Most patients are immune, even if they or their families do not recall the patient having been infected. A pregnant patient exposed to varicella can have serologic testing (IgM and IgG) and can be given varicella zoster immune globulin within 72 hours of exposure to reduce the severity of maternal infection. A pregnant patient who develops the characteristic varicella rash can be given oral acyclovir within 24 hours of the rash to decrease symptoms and duration of disease (Fig. 24.3).However, maternal acyclovir has not been shown to decrease the rate or severity of fetal infection.
If clinical infection occurs in a patient from 5 days prior to delivery to 2 days after delivery, neonatal infection can be severe, even deadly. Varicella zoster Ig is given to infants in such situations, though protection is not complete.
Severe complications of varicella including pneumonia and encephalitis are much more common in adults than in children. Varicella pneumonia seems to occur more frequently with varicella infection during pregnancy and is associated with maternal mortality. Treatment is with IV acyclovir. Effective vaccination against varicella has been available since 1995 and should be offered to susceptible nonpregnant women. The vaccine is a live attenuated virus and should be avoided in pregnancy and within 1 month of conception; however, no adverse outcomes have been reported if given in pregnancy. Vaccination of susceptible household contacts of pregnant women is safe.
FIGURE 24.3. Varicella. Chickenpox lesions on day 6 of the illness. CDC/J. D. Millar.
PARVOVIRUS
Maternal parvovirus B19 infection can cause devastating fetal outcomes such as spontaneous abortion, fetal nonimmune hydrops fetalis, and even death. Seroprevalence increases with age and is >60% in adolescents and adults. For susceptible pregnant women, the risk of seroconversion ranges from 20% to 50%, depending on closeness to the infectious contact (higher risk for closer contacts such as family members); however, the risk of transplacental infection is low. Maternal immune status can be determined by serologic testing; IgM reflects recent infection and IgG indicates infection in the past and immunity. Routine serologic screening in pregnancy is not recommended. Exposed pregnant women should be offered B19-specific IgM and IgG serologic testing. If IgM is positive or seroconversion is confirmed, ultrasound testing for 10 weeks to look for evidence of fetal hydrops (ascites and edema), placentomegaly, and growth disturbances is performed. Intrauterine transfusions may be necessary if hydrops develops. There is no specific treatment for parvovirus infection. If hydrops does not develop in the fetus, long-term outcomes are good with apparently normal development.
Clinical Follow-Up
You set up an appointment for preconception counseling with your patient and discuss the implications of human immunodeficiency virus (HIV) infection in pregnancy for the mother and fetus. You explain that, fortunately, pregnancy does not appear to worsen disease for the mother. However, there is a substantial risk of transmission of HIV from mother to infant if the mother is not on combination antiretroviral therapy during pregnancy and labor and delivery and if her HIV infection is not well controlled. There are also measures that can reduce the risk of transmission during labor and delivery. Fortunately, most antiretroviral agents have not been associated with fetal harm. With careful planning, effective therapy, good prenatal and intrapartum care, and avoiding breastfeeding if safe alternatives are available, she can reduce the risk of transmission of HIV to her baby from 25% or higher to less than 1% to 2%.
thePoint Visit http://thepoint.lww.com/activate for an interactive USMLE-style question bank and more!