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Obstentrics_Williams. Experience with all of these antiviral agents in pregnant women is limited (Beau, 2014; Beigi, 2014; Dunstan, 2014). hey are Food and Drug Administration category C drugs and thus used when potential benefits outweigh risks. At Parkland Hospital, we start oral oseltamivir treatment within 48 hours of symptom onset-75 mg twice daily for 5 days. Earlyadministration may reduce length of hospital stays (Meijer, 2015; Oboho, 2016). Prophylaxis with oseltamivir, 75 mg orally once daily for 7 days, is also recommended for signiicant exposures. Antibacterial medications are added when a secondary bacterial pneumonia is suspected (Chap. 51, p. 993).


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Obstentrics_Williams. Efective vaccines are formulated annually. Vaccination against inluenza throughout the influenza season, but optimally in October or November, is recommended by the Centers for Disease Control and Prevention (CDC) (2013a) and the American College of Obstetricians and Gynecologists (2016b) for all women who will be pregnant during the influenza season. his is especially important for those afected by chronic medical disorders such as diabetes, heart disease, asthma, or human immunodeficiency virus (HIV) infection. Inactivated vaccine prevents clinical illness in 70 to 90 percent of healthy adults. Importantly, there is no evidence of teratogenicity or other adverse maternal or fetal events (Chambers, 2016; Fell, 2017; Kharbanda, 2017; Polyzos, 2015; Sukumaran, 2015). Moreover, for mothers vaccinated during pregnancy, several studies found lower rates of influenza in their infants up to 6 months of age (Nunes, 2017; Steinhof, 2012; Zaman, 2008). Immunogenicity of the trivalent


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Obstentrics_Williams. mothers vaccinated during pregnancy, several studies found lower rates of influenza in their infants up to 6 months of age (Nunes, 2017; Steinhof, 2012; Zaman, 2008). Immunogenicity of the trivalent inactivated seasonal inluenza vaccine in pregnant women is similar to that in the nonpregnant individual. A live attenuated influenza virus vaccine is available for intranasal use but is not recommended for pregnant women (Cohen, 2015b).


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Obstentrics_Williams. his uncommon adult infection is caused by an RNA paramyxovirus. Because of childhood immunization, up to 90 percent of adults are seropositive (Rubin, 2012). The virus primarily infects the salivary glands but also may involve the gonads, meninges, pancreas, and other organs. It is transmitted by direct contact with respiratory secretions, saliva, or through fomites. Most transmission occurs before and within 5 days of parotitis onset, and droplet isolation is recommended during this time (Kutty, 2010). Treatment is symptomatic, and mumps during pregnancy is no more severe than in nonpregnant adults. Women who develop mumps in the first trimester may have a greater risk of spontaneous abortion. Infection in pregnancy is not associated with congenital malformations, and fetal infection is rare (McLean, 2013).


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Obstentrics_Williams. he live attenuated J eryl-Lynn vaccine strain is part of the MMR vaccine-measles, mumps, and rubella. This vaccine is contraindicated in pregnancy according to the CDC (McLean, 2013). No malformations attributable to MMR vaccination in pregnancy have been reported, but pregnancy should be avoided for 30 da) s after mumps vaccination. The vaccine may be given to susceptible women postpartum, and breastfeeding is not a contraindication.


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Obstentrics_Williams. his is a highly contagious RNA virus of the family Paramyxoviridae that only infects humans. In endemic areas, annual outbreaks of measles, also called rubeola, occur in late winter and early spring, transmission is primarily by respiratory droplets, and the secondary attack rate among contacts exceeds 90 per cent (Rainwater-Lovett, 2015). Resurgences in measles have been linked to clusters of vaccine-eligible but unvaccinated individuals (Fiebelkorn, 2010; Phadke, 2016). Fever, coryza, conjunctivitis, and cough are typical symptoms. he charac teristic erythematous maculopapular rash develops on the face and neck and then spreads to the back, trunk, and extremities.


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Obstentrics_Williams. Koplik spots are small white lesions with surrounding erythema found within the oral cavity. Immediate or delayed neurologi cal sequelae of measles may manifest in several forms, making diagnosis diicult (Buchanan, 2012; Chiu, 2016). Diagnosis of acute infection is most commonly performed by serological evidence of IgM antibodies, although RT-PCR tests are avail able. Treatment is supportive. Pregnant women without evidence of measles immunity should be administered passive immunoprophylaxis with immune globulin, 400 mg/kg intravenously (Centers for Dis ease Control and Prevention, 2017d). Active vaccination is not performed during pregnancy, however, susceptible women can be vaccinated routinely postpartum, and breastfeeding is not contraindicated (Ohji, 2009). he virus does not appear to be teratogenic (Siegel, 1973).


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Obstentrics_Williams. he virus does not appear to be teratogenic (Siegel, 1973). However, rates of spontaneous abortion, pre term delivery, and low-birthweight neonates are increased with maternal measles (Rasmussen, 2015). If a woman develops measles shortly before birth, risk of serious infection developing in the neonate is considerable, especially in a preterm neonate. his RNA togavirus causes rubella, also called German measles, which is of minor importance in the absence of pregnancy. Rubella inection in the irst trimester, however, poses signicant risk or abortion and severe congenital maormations. T ransmission occurs via nasopharyngeal secretions, and the transmission rate is 80 percent to susceptible individuals. he peak incidence is late winter and spring in endemic areas (Lambert, 2015).


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Obstentrics_Williams. Maternal rubella is usually a mild febrile illness with a generalized maculopapular rash beginning on the face and spreading to the trunk and extremities. hat said, 25 to 50 percent of infections are asymptomatic. Other symptoms may include arthralgias or arthritis, head and neck lymphadenopathy, and conjunctivitis. he incubation period is 12 to 23 days. Viremia usually precedes clinical signs by about a week, and adults are infectious during viremia and through 7 days after the rash appears. Up to half of maternal infections are subclinical despite viremia that may cause devastating fetal infection (McLean, 2013).


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Obstentrics_Williams. Rubella virus may be isolated from the urine, blood, nasopharynx, and cerebrospinal fluid for up to 2 weeks after rash onset. The diagnosis is usually made, however, with serological analysis. In one study, 6 percent of nonimmune women seroconverted to rubella virus during pregnancy (Hutton, 2014). Specific IgM antibody can be detected using enzyme-linked immunoassay for 4 to 5 days after onset of clinical disease, but antibody can persist for up to 6 weeks after appearance of the rash. Importantly, rubella virus reinfection can give rise to transient low levels of IgM. With this, fetal infection can rarely occur, but no adverse fetal efects have been described. Serum IgG antibody titers peak 1 to 2 weeks after rash onset. his rapid antibody response may complicate serodiagnosis unless samples are initially collected within a few days after the onset of the rash. If, for example, the first specimen was obtained 10 days after the rash, detection of IgG antibodies would fail to


Obstentrics_Williams

Obstentrics_Williams. samples are initially collected within a few days after the onset of the rash. If, for example, the first specimen was obtained 10 days after the rash, detection of IgG antibodies would fail to diferentiate between very recent disease and preexisting immunity to rubella. IgG avidity testing is performed concomitant with the serological tests above. High-avidity IgG antibodies indicate an infection at least 2 months in the past.


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Obstentrics_Williams. The rubella virus is one of the most complete teratogens, and efects of fetal infection are worst during organogenesis (Adams Waldorf, 2013). Pregnant women with rubella and a rash during the first 12 weeks of gestation have an afected fetus with congenital infection in up to 90 percent of cases (Miller, 1982). At 13 to 14 weeks' gestation, this incidence is 50 percent, and by the end of the second trimester, it is 25 percent. Defects are rare after 20 weeks' gestation. Features of congenital rubella syndrome amenable to prenatal diagnosis are cardiac septal defects, pulmonary stenosis, microcephaly, cataracts, microphthalmia, and hepatosplenomegaly (Yazigi, 2017). Other abnormalities include sensorineural deafness, intellectual disability, neonatal purpura, and radiolucent bone disease. Neonates born with congenital rubela may shed the virus or many months and thus be a threat to other inants and to susceptible adults who contact them. Reports of delayed morbidities associated with


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Obstentrics_Williams. Neonates born with congenital rubela may shed the virus or many months and thus be a threat to other inants and to susceptible adults who contact them. Reports of delayed morbidities associated with congenital rubella syndrome may include a rare, progressive panencephalitis, insulin-dependent diabetes mellitus, and thyroid disorders (Sever, 1985; Webster, 1998).


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Obstentrics_Williams. here is no speciic treatment for rubella. Droplet precautions for 7 days after the onset of the rash are recommended. Postexposure passive immunization with polyclonal immunoglobulin may be of benefit if given within 5 days of exposure (Young, 2015). Although large epidemics of rubella have virtually disappeared in the United States because of immunization, up to 10 percent of women in the United States are susceptible. Cluster outbreaks during the 1990s mainly involved persons born outside the United States, as congenital rubella is still common in developing nations (Centers for Disease Control and Prevention, 20 13f) . To eradicate rubella and prevent congenital rubella syndrome completely, a comprehensive approach is recommended for immunizing the adult population (Grant, 2015).


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Obstentrics_Williams. MMR vaccine should be ofered to nonpregnant women of childbearing age who do not have evidence of immunity whenever they make contact with the health-care system. Vaccination of all susceptible hospital personnel who might be exposed to patients with rubella or who might have contact with pregnant women is important. Rubella vaccination should be avoided 1 month before or during pregnancy because the vaccine contains attenuated live virus. No observed evidence links the vaccine and induced malformations, although the overall theoretical risk is up to 2.6 percent (McLean, 2013; Swamy, 2015). MMR vaccination is not an indication for pregnancy termination. Prenatal serological screening for rubella is indicated for all pregnant women. Women found to be nonimmune are ofered the MMR vaccine postpartum.


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Obstentrics_Williams. Prenatal serological screening for rubella is indicated for all pregnant women. Women found to be nonimmune are ofered the MMR vaccine postpartum. More than 200 antigenically distinct respiratory viruses cause the cominon cold, pharyngitis, laryngitis, bronchitis, and pneumonia. Rhinovirus, coronavirus, and adenovirus are major causes of the common cold. The RNA-containing rhinovirus and coronavirus usually produce a trivial, self-limited illness characterized by rhinorrhea, sneezing, and congestion. he DNA-containing adenovirus is more likely to produce cough and lower respiratory tract involvement, including pneumonia.


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Obstentrics_Williams. The potential teratogenic efects of respiratory viruses are controversial. In a case-control study using data from the Finnish Register of Congenital vlalformations, 393 gravidas with a common cold had a four-to ivefold greater risk of fetal anencephaly (Kurppa, 1991). In another population study of California births from 1989 to 1991, low attributable risks for neural-tube defects were associated with many illnesses in early pregnancy (Shaw, 1998). Adams and colleagues (2012) performed amnionic fluid viral PCR studies in 1191 women undergoing amniocentesis for fetal karyotyping. Viral PCR was positive in 6.5 percent, with adenovirus being the virus most frequently identified. There was an association with fetalgrowth restriction, nonimmune hydrops, foot/hand abnormalities, and neural-tube defects. Adenoviral infection is a known cause of childhood myocarditis. T owbin (1994) and Forsnes (1998) and their associates used PCR tests to identiy and link adenovirus to fetal myocarditis and


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Obstentrics_Williams. defects. Adenoviral infection is a known cause of childhood myocarditis. T owbin (1994) and Forsnes (1998) and their associates used PCR tests to identiy and link adenovirus to fetal myocarditis and nonimmune hydrops.


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Obstentrics_Williams. hese RNA viruses are members of the family Bunyaviridae. They are associated with a rodent reservoir, and transmission involves inhalation of virus excreted in rodent urine and feces. Outbreaks of hantaviruses including Sin Nombre virus and Seoul virus have been reported in the United States, the most recent in early 2017 (Centers for Disease Control and Prevention, 2017b). Hantaviruses are a heterogenous group of viruses with low and variable rates of transplacental transmission. Howard and associates (1999) reported the Hantavirus pulmonay syndrome to cause maternal death, fetal demise, and preterm birth. hey found no evidence of vertical transmission of the causative Sin N ombre virus.


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Obstentrics_Williams. hese viruses are a major subgroup of RNA picornaviruses that include coxsackievirus, poliovirus, and echovirus. They are trophic for intestinal epithelium but can also cause widespread maternal, fetal, and neonatal infections that may include the CNS, skin, heart, and lungs. Most maternal infections are subclinical yet can be fatal to the fetus-neonate (Tassin, 2014). Hepatitis A is an enterovirus that is discussed in Chapter 55 (p. 1063). Coxsackievirus infections with group A and B are usually asymptomatic. Symptomatic infections-usually with group B-include aseptic meningitis, polio-like illness, hand foot and mouth disease, rashes, respiratory disease, pleuritis, pericarditis, and myocarditis. No treatment or vaccination is available (Cohen, 2015a). Coxsackievirus may be transmitted by maternal secretions to the fetus at delivery in up to half of mothers who seroconverted during pregnancy (Modlin, 1988). Transplacental passage has also been reported (Ornoy, 2006).


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Obstentrics_Williams. Congenital malformation rates may be slightly increased in fetuses of pregnant women who had serological evidence of coxsackievirus (Brown, 1972). Viremia can cause fetal hepatitis, skin lesions, myocarditis, and encephalomyelitis, all of which may be fatal. Some have reported higher rates of cardiac anomalies and of low-birthweight, preterm, and small-for-gestational-age newborns (Chen, 2010; Koro'lkova, 1989). Maternal-fetal infection has been associated with massive perivillous ibrin deposition and fetal death (Yu, 2015). Finally, a rare association between maternal coxsackievirus infection and insulin-dependent diabetes in ofspring has been described (Viskari, 2012).


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Obstentrics_Williams. Polio viruses cause highly contagious infections that are subclinical or mild. he virus is trophic for the CNS, and it can cause paralytic poliomyelitis (Cohen, 2015a). Siegel (1955) demonstrated that pregnant women not only were more susceptible to polio but also had a higher death rate. Perinatal transmission has been observed, especially when maternal infection developed in the third trimester (Bates, 1955). Inactivated subcutaneous polio vaccine is recommended for susceptible pregnant women who must travel to endemic areas or are placed in other high-risk situations. Live oral polio vaccine has been used for mass vaccination during pregnancy without harmful fetal efects (Harjulehto, 1989).


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Obstentrics_Williams. This B 19 virus causes erythema inectiosum, orith disease. It is a small, single-stranded DNA virus that replicates in rapidly proliferating cells such as erythroblast precursors (Brown, 2015). his can lead to anemia, which is its primary fetal efect. Only individuals with the erythrocyte globoside membrane P antigen are susceptible. In women with severe hemolytic anemia-for example, sickle-cell disease-parvovirus infection may cause an aplastic crisis.


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Obstentrics_Williams. The main mode of parvovirus transmission is respiratory or hand-to-mouth contact, and the infection is common in spring months. The maternal infection rate is highest in women with school-aged children and in day-care workers, but not in schoolteachers. An infected person develops viremia 4 to 14 days after exposure, and an otherwise immunocompetent individual is no longer infectious at the onset of the rash. By adulthood, only 40 percent of women are susceptible. The annual seroconversion rate is 1 to 2 percent but is >10 percent during epidemic periods (Brown, 2015). The secondary attack rate approaches 50 percent.


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Obstentrics_Williams. In 20 to 30 percent of adults, infection is asymptomatic. Fever, headache, and flulike symptoms may begin in the last few days of the viremic phase. Several days later, a bright red rash with erythroderma afects the face and gives a slapped-cheek appearance. The rash becomes lacelike and spreads to the trunk and extremities. Adults often have milder rashes and develop symmetrical polyarthralgia that may persist several weeks. Mayama and associates (2014) described a pregnant woman in whom B 19 infection was associated with hemophagocytic lymphohistiocytosis. No evidence suggests that parvovirus infection is altered by pregnancy. With recovery, IgM antibody is generated 7 to 10 days postinfection, and production persists for 3 to 4 months. Several days after IgM is produced, IgG antibody is detectable and persists for life with natural immunity (American College of Obstetricians and Gynecologists, 2017).


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Obstentrics_Williams. here is vertical transmission to the fetus in up to a third of maternal parvovirus infections (de long, 2011; Lamont, 20 11 b). Fetal infection has been associated with abortion, nonimmune hydrops, and stillbirth (Lassen, 2012; Mace, 2014; McClure, 2009). According to the American College of Obstetricians and Gynecologists (2017), the rate of fetal loss with serologically proven parvovirus infection is 8 to 17 percent before 20 weeks' gestation, and 2 to 6 percent after midpregnancy. Currently, no data support evaluating asymptomatic mothers and stillborn fetuses for parvovirus infection.


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Obstentrics_Williams. Hydrops develops in only approximately 1 percent of fetuses of women infected with parvovirus (American College of Obstetricians and Gynecologists, 2017; Pasquini, 2016; Puccetti, 2012). Still, it is the most frequent infectious agent of nonimmune hydrops in autopsied fetuses (Rogers, 1999). Hydrops usually stems from infection in the irst half of gestation. In one report, more than 80 percent of hydrops cases were found in the second trimester, with a mean gestational age of 22 to 23 weeks (Yaegashi, 2000). At least 85 percent of cases of fetal infection developed within 10 weeks of maternal infection, and the mean interval was 6 to 7 weeks. he critical period for maternal infection leading to fetal hydrops was estimated to be between 13 and 16 weeks' gestation, which coincided with the period in which fetal hepatic hemopoiesis is greatest.


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Obstentrics_Williams. An algorithm for diagnosis of maternal parvoviral infection is illustrated in Figure 64 4. Diagnosis is generally made by maternal serological testing for speciic IgG and IgM antibodies (Bonvicini, 2011; Brown, 2015). Viral DNA may be detectable by PCR in maternal serum during the prodrome and persist for months to years after infection. Fetal infection is diagnosed by detection of B 19 viral DNA in amnionic luid or IgM antibodies in fetal serum obtained by cordocentesis (de long, 2011; Weifenbach, 2012). Fetal and maternal viral loads do not predict fetal morbidity and mortality (de Haan, 2007).


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Obstentrics_Williams. Most cases of parvovirus-associated hydrops develop in the first 10 weeks after infection. Thus, serial sonography every 2 weeks should be performed in women with recent infection (see Fig. 64-4). As discussed in Chapter 10 (p. 214), middle cerebral artery (MCA) Doppler interrogation can also be used to predict fetal anemia (Chauvet, 2011). Fetal blood sampling is warranted with hydrops to assess the degree of fetal anemia. Comorbid fetal myocarditis may induce hydrops with lesser degrees of anemia. Depending on gestational age, fetal transfusion for hydrops may improve outcome in some cases (Enders, 2004). Mortal ity rates as high as 30 percent have been reported in hydropic fetuses without transfusions. With transfusion, 94 percent of hydrops cases resolve within 6 to 12 weeks, and the overall mortality rate is <10 percent. Most fetuses require only one transfusion because hemopoiesis resumes as infection resolves.


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Obstentrics_Williams. Concurrent fetal thrombocytopenia worsens the prognosis (Melamed,r2015). Reports describing neurodevelopmental outcomes in fetuses transfused for B 19 infection-induced anemia are conlicting. In one review of 24 transfused hydropic fetuses, abnormal neurodevelopment was noted in ive of 16 survivors-32 percent-at 6 months to 8 years (Nagel, 2007). Outcomes were not related to severity of fetal anemia or acidemia, and these investigators hypothesized that the infection itself induced cerebral damage. In another study of 28 children treated with intrauterine transfusion, 11 percent had neurodevelopmental impairment during evaluation at a median age of 5 years (de long, 2012). Conversely, Dembinski (2003) found no signiicant neurodevelopmental delay despite severe fetal anemia.


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Obstentrics_Williams. Currently, no parvovirus vaccine is available, and no evidence suggests that antiviral treatment prevents maternal or fetal infection. Decisions to avoid higher-risk work settings are complex and require assessment of exposure risks. Pregnant women should be counseled that risks for infection approximate 5 percent for casual, infrequent contact; 20 percent for intense, prolonged work exposure such as for teachers; and 50 percent for close, frequent interaction such as in the home. Workers at day-care centers and schools need not avoid infected children because infectivity is greatest before clinical illness. Finally, infected children do not require isolation.


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Obstentrics_Williams. This mosquito-borne RNA flavivirus is a human neuropathogen. It has become the most common cause of arthropod-borne viral encephalitis in the United States (Centers for Disease Control and Prevention, 2017f; Krow-Lucal, 2017). West Nile viral infections are typically acquired through mosquito bites in late summer or perhaps through blood transfusion. The incubation period is 2 to 14 days, and most persons have mild or no symptoms. Fewer than 1 percent of infected adults develop meningoencephalitis or acute laccid paralysis (Granwehr, 2004). Presenting symptoms may include fever, mental status changes, muscle weakness, and coma (Stewart, 2013). Diagnosis of West Nile infection is based on clinical symptoms and the detection of viral IgG and IgM in serum and IgM in cerebrospinal fluid. There is no known efective antiviral treatment, and management is supportive. he primary strategy for preventing exposure in pregnancy is the use of insect


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Obstentrics_Williams. Clinical disease: exposure or infection Sonographic evidence of fetal infection: hydrops fetalis, hepatomegaly, splenomegaly, placentomegaly, elevated FIGURE 64-4 Algorithm for evaluation and management of human parvovirus B 19 infection in pregnancy. eBe = complete blood count; IgG = immunoglobulin G; IgM = immunoglobulin M; MeA = middle cerebral artery; peR = polymerase chain reaction; RNA = ribonucleic acid. repellant containing ,N-diethyl-m-toluamide (DEET). This is infections initially reported to the West Nile Virus Pregnancy considered safe for use among pregnant women (Wylie, 2016). Registry, there were four miscarriages, two elective abortions, Avoiding outdoor activity and stagnant water and wearing proand 72 live births, 6 percent of which were preterm (O'Leary, tective clothing are also recommended. 2006). Three of these 72 newborns were shown to have West


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Obstentrics_Williams. Adverse efects of West Nile viremia on pregnancy are Nile infection, and it could not be established conclusively that unclear. Animal data suggest that embryos are susceptible, and infection was acquired congenitally. Of three major malformaa case report of human fetal infection at 27 weeks' gestation tions possiby associated with viral infection, none was deinidescribed chorioretinitis and severe temporal and occipital lobe tively conirmed. Similar conclusions were reached by Pridjian leukomalacia (Alpert, 2003; Julander, 2006). In 77 maternal and colleagues (2016), who analyzed data from the CDC West Nile Virus Registry. Transmission of West Nile virus through breastfeeding is rare . hese are single-stranded RNA viruses that are prevalent world wide. In 2002, an especially virulent strain of coronavirus


Obstentrics_Williams

Obstentrics_Williams. hese are single-stranded RNA viruses that are prevalent world wide. In 2002, an especially virulent strain of coronavirus China. It rapidly spread throughout Asia, Europe, and North and South America. he case-fatality rate approached 10 percent in the nonpregnant population and was as high as 25 percent in pregnant women (Lam, 2004; Wong, 2004). Although no addi tional cases have been conirmed since 2004, the CDC (2013b) now lists SARS-Co V as a "select agent" that has the potential to pose a severe threat to public health and safety. Another novel regional coronavirus with a high case-fatality coronavirus eMERS-Co ) (Arabi, 2017). Although experience with MERS-Co V is sparse in pregnancy, infection has been reported to cause maternal and perinatal deaths (Assiri, 2016). A member of the RNA Filoviridae family, the Ebola virus is transmitted by direct person-to-person contact (Kuhn, 2015).


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Obstentrics_Williams. A member of the RNA Filoviridae family, the Ebola virus is transmitted by direct person-to-person contact (Kuhn, 2015). Infection produces a severe hemorrhagic fever with pronounced thy. Treatment is supportive, and the mortality rate approaches 50 percent. Data are few concerning Ebola viral infection in pregnancy (Beigi, 2017; Money, 2015; Oduyebo, 2015). The CDC concludes that pregnant women are at increased risk for severe illness and death a amieson, 2014). hat said, no evidence suggests that pregnant women are more susceptible to Ebola virus infection. One report described trophoblast infection (Muehlenbachs, 2017). This RNA virus of the Flavivirdae family has recently been recognized as the first major mosquito-borne teratogen (Rasmussen, 2016). Although Zika virus is primaril) transmitted by mosquito bite, sexual transmission is also possible, and the virus may be detected in body fluids for months following acute infection (Hills, 2016; Joguet, 2017; Paz-Bailey, 2017).


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Obstentrics_Williams. Reminiscent of the rubella epidemic in the 1960s, in adults Zika infection may be asymptomatic or cause mild symptoms of rash, fever, headache, arthralgia, and conjunctivitis lasting a few days. Virus is typically detectable in blood around the time of symptom onset and may persist days to months in pregnant women (Driggers, 2016; Meaney-Delman, 2016). Serum IgM antibodies typically become detectable within the first two weeks after symptom onset and remain a median of four months (Oduyebo, 2017). Rarely, Guillain-Barre syndrome may develop following infection (da Silva, 2017; Parra, 2016).


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Obstentrics_Williams. The fetus can be severely infected whether or not the mother is symptomatic. Honein and coworkers (2017) describe a fetus with congenital Zika infection. Findings shown include a thin cerebral cortex, increased extraaxial space (, dilated ventricles (F,), and absent cavum septum pellucidum. (Reproduced with permission from Driggers RW, Ho (Y, Korhonen EM, et al: Zika virus infection with prolonged maternal viremia and fetal brain abnor malities, N Engl J Med. 2016 Jun 2;374(22):2142-2151.) a 6-percent overall fetal infection rate. In one report of 134 women with positive RT-PCR results, fetal mortality was 7 percent (Brasil, 2016). Among live births, the rate of fetal birth defects ranges from 5 percent-among women with possible Zika infection-to 15 percent among pregnant women with laboratory-confirmed infection in the irst trimester (Reynolds, 2017). In the most severely afected fetuses, a congenital Zika syndrome has been described that includes microcephaly, lissencephaly,


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Obstentrics_Williams. laboratory-confirmed infection in the irst trimester (Reynolds, 2017). In the most severely afected fetuses, a congenital Zika syndrome has been described that includes microcephaly, lissencephaly, ventriculomegaly, intracranial calcifications, ocular abnormalities, and congenital contractures (Honein, 2017; Moore, 2017; Soares de Oliveira-Szejnfeld, 2016). Sonographic findings from a Zika-infected fetus are shown in 64-5.


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Obstentrics_Williams. Diagnosis of this infection in pregnant women is made with detection of Zika virus RNA in blood or urine or by serological testing. Detection of Zika virus RNA by PCR confirms infection. Serological assays for Zika IgM antibodies may cross react with other flaviviruses. Thus, a positive assay result is followed by another assay containing virus-specific neutralizing antibodies (Oduyebo, 2017) . Testing recommendations and interpretation have evolved for pregnant women who are symptomatic and those who are asymptomatic but have ongoing exposure risk. his risk includes living in or traveling to an area with active local transmission. Large-scale screening programs have been described to identiy women at high risk for travelassociated Zika infection (Adhikari, 2017).


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Obstentrics_Williams. Currently, no specific treatment or vaccine is available for Zika infection, although several vaccine candidates are in development (Beigi, 2017; World Health Organization, 2017). Prophylaxis includes protective netting and insect spray to control the vector mosquito and avoidance of sexual contact with partners recently exposed. he CDC has established a pregnancy hotline (770-488-7100) and U.S. Zika Pregnanc) Registry (ZikaPregnancy@cdc.gov) for clinicians with concerns related to management of women with Zika infection or exposure.


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Obstentrics_Williams. Registry (ZikaPregnancy@cdc.gov) for clinicians with concerns related to management of women with Zika infection or exposure. Infections caused by Streptococcus pyogenes are important in pregnant women. his organism is the most frequent bacterial cause of acute pharyngitis and is associated with several systemic and cutaneous infections. S pyogenes produces numerous toxins and enzymes responsible for its local and systemic toxicity. Pyrogenic exotoxin-producing strains are usually associated with severe disease (Shinar, 2016; Wessels, 2015). In most cases, streptococcal pharyngitis, scarlet fever, and erysipelas are not life threatening. Treatment, usually with penicillin, is similar in pregnant and nonpregnant women.


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Obstentrics_Williams. In the United States, S pyogenes infrequently causes puerperal infection. Still, it remains the most common cause of severe maternal postpartum infection and death worldwide, and the incidence of these infections is rising (Deutscher, 2011; Hamilton, 2013; Wessels, 2015). Puerperal infections are discussed in detail in Chapter 37. he early 1990s saw the emergence of streptococcal toxic shock syndrome, manifested by hypotension, fever, and evidence of multiorgan failure with associated bacteremia. Group A puerperal sepsis is seriously complicated in 20 percent of cases (Shinar, 2016). The case-fatality rate approximates 30 percent, and morbidity and mortality rates are improved with early recognition. Treatment includes clindamycin plus penicillin therapy and often surgical debridement (Chapter 47, p. 924). No vaccine for group A streptococcus is commercially available.


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Obstentrics_Williams. Streptococcus agalactiae is a group B organism that can be found to colonize the gastrointestinal and genitourinary tract in 10 to 25 percent of pregnant women (Kwatra, 2016). Throughout pregnancy, group B Streptococcus (GBS) is isolated in a transient, intermittent, or chronic fashion. Although the organism is most likely always present in these same women, their isolation is not always homologous. he spectrum of maternal and fetal G BS efects ranges from asymptomatic colonization to septicemia. S agalactiae has been implicated in adverse pregnancy outcomes that include preterm labor, prematurely ruptured membranes, clinical and subclinical chorioamnionitis, and fetal infections (Randis, 2014). GBS can also cause maternal bacteriuria, pyelonephritis, osteomyelitis, postpartum mastitis, and puerperal infections. It remains the leading infectious cause of morbidity and mortality among infants in the United States (Centers for Disease Control and Prevention, 2010; Schrag, 2016).


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Obstentrics_Williams. Neonatal sepsis has received the most attention due to its devastating consequences and available efective preventative measures. Infection <7 days after birth is deined as eary-onset disease and is seen in 0.21/1000 live births (Centers for Disease Control and Prevention, 2015). Many investigators use a threshold of <72 hours of life as most compatible with intrapartum acquisition of disease (Stoll, 2011). We and others have also encountered unexpected intrapartum stillbirths from GBS infections (Nan, 2015). Tudela and associates (2012) reported that newborns with early-onset CBS infection often had clinical evidence of fetal infection during labor or at delivery.


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Obstentrics_Williams. In many neonates, septicemia involves signs of serious illness that usually develop within 6 to 12 hours of birth. These include respiratory distress, apnea, and hypotension. At the outset, therefore, neonatal infection must be diferentiated from respiratory distress syndrome caused by insuicient surfactant production (Chap. 34, p. 636). he mortality rate with early-onset disease has declined to approximately 4 percent, and preterm newborns are disparately afected. Late-onset disease caused by GBS is noted in 0.32 per 1000 live births and usually manifests as meningitis 1 week to 3 months after birth (Centers for Disease Control and Prevention, 2015). he mortality rate, although appreciable, is less for late-onset meningitis than for early-onset sepsis. Unfortunately, it is not uncommon for surviving infants of both early-and late-onset disease to exhibit devastating neurological sequelae.


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Obstentrics_Williams. As GBS neonatal infections evolved beginning in the 1970s and before widespread intrapartum chemoprophylaxis, rates of early-onset sepsis ranged from 2 to 3 per 1000 live births. By 2010, these outcomes led to a policy of universal rectovaginal culture screening for GBS at 35 to 37 weeks' gestation followed by intrapartum antibiotic prophylaxis for women identified to be carriers. hese outcomes stimulated development of expanded laboratory identiication criteria for GBS; updated algorithms for screening and intrapartum chemoprophylaxis for women with preterm prematurely ruptured membranes, preterm labor, or penicillin allergy; and described new dosing for penicillin G chemoprophylaxis. Following these changes, the incidence of early-onset G BS neonatal sepsis decreased to 0.21 cases per 1000 live births by 2015 (Centers for Disease Control and Prevention, 2015).


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Obstentrics_Williams. hus, during the past three decades, several strategies have been proposed to prevent perinatal acquisition of GBS infections. These strategies have not been compared in randomized trials and are either culture-based or risk-based guidelines (Ohlsson, 2014). hese methods have been adopted in the United States, but not all European countries have guidelines (Di Renzo, 2015).


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Obstentrics_Williams. Culture-Based Prevention. he CDC (2010) GBS guidelines recommend a culture-based approach, which was also adopted by the American College of Obstetricians and Gynecologists (20 16e). Shown in Figure 64-6, this strategy is designed to identiy women who should be given intrapartum antimicrobial prophylaxis. Women are screened for GBS colonization at 35 to 37 weeks' gestation, and intrapartum antimicrobials are given to women with rectovaginal GBS-positive cultures. Selective enrichment broth followed by subculture improves detection. In addition, more rapid techniques such as DNA probes and NAATs are being developed (Helali, 2012). A previous sibling with GBS invasive disease and identiication of GBS Vaginal and rectal GBS screening cultures at 35-37 weeks' gestation for ALL pregnant women (unless patient had GBS bacteriuria during the current pregnancy or a previous infant with invasive GBS disease) Previous infant with invasive GBS disease


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Obstentrics_Williams. Previous infant with invasive GBS disease Positive GBS screening culture during current pregnancy (unless a planned cesarean delivery, in the absence of labor or amniotic membrane rupture, is performed) Unknown GBS status (culture not done, incomplete, or results unknown) and any of the following: Previous pregnancy with a positive GBS screening culture (unless a culture was also positive during the current pregnancy) Planned cesarean delivery performed in the absence of labor or membrane rupture (regardless of maternal GBS culture status) Negative vaginal and rectal GBS screening culture in late gestation during the current pregnancy, regardless of intrapartum risk factors Intrapartum temperature � 1 OOAoF (�38.0°C)


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Obstentrics_Williams. Negative vaginal and rectal GBS screening culture in late gestation during the current pregnancy, regardless of intrapartum risk factors Intrapartum temperature � 1 OOAoF (�38.0°C) FIGURE 64-6 Indications for intrapartum prophylaxis to prevent perinatal group B streptococcal (GBS) disease under a universal prenatal screening strategy based on combined vaginal and rectal cultures obtained at 35 to 37 weeks' gestation. (From Centers for Disease Control and Prevention, 201o0.) bacteriuria in the current pregnancy are also considered indications for prophylaxis.


Obstentrics_Williams

Obstentrics_Williams. Risk-Based Prevention. This approach is recommended for women in labor and whose GBS culture results are not known. It relies on risk factors associated with intrapartum GBS transmission. Intrapartum chemoprophylaxis is given to women who have any of the following: delivery <37 weeks, ruptured membranes � 18 hours, or intrapartum temperature � 100.4°F (�38.0°C). Women with GBS during the current pregnancy and women with a prior infant with invasive early-onset GBS disease are also given chemoprophylaxis.


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Obstentrics_Williams. At Parkland Hospital in 1995-and prior to consensus guidelines-we adopted and continue to use the risk-based approach for intrapartum treatment of women at high risk. Importantly, in addition, all term neonates who were not given intrapartum prophylaxis were treated in the delivery room with aqueous penicillin G, 50,000 to 60,000 units intramuscularly. Rates of early-onset GBS sepsis decreased to 0.4 to 0.66 per 1000 live births (Staford, 2012; Wendel, 2002). Non-GBS early-onset sepsis decreased from 0.66 to 0.24 per 1000 live births (Staford, 2012). Thus, this approach has results similar to those reported by the CDC (2010) for culture-based prevention. Serotype-specific capsular antibody concentrations clinically correlate with GBS neonatal disease. Antibody-producing vaccines have been tested, but none are clinically available (Donders, 2016; Kobayashi, 2016; Madhi, 2016).


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Obstentrics_Williams. Preventive antimicrobials administered 4 or more hours before delivery are highly efective (Fairlie, 2013). Regardless of screening method, penicillin remains the first-line agent TABLE 64-3. Regimens for Intrapartum Antimicrobial Prophylaxis for Perinatal GBS Disease Recommended Penicillin G, 5 million units IV initial dose, then 2.5 to 3.0 million units IV every 4 hours until delivery Alternative Ampicillin, 2 g IV initial dose, then 1 9 IV every 4 hours or 2 g every Patients not at high risk for anaphylaxis Cefazolin, 2 9 IV initial dose, then 1 9 IV every 8 hours until delivery Patients at high risk for anaphylaxis and with GBS Clindamycin, 900 mg IV every 8 hours until delivery susceptible to clindamycin Patients at high risk for anaphylaxis and with GBS Vancomycin, 1 9 IV every 12 hours until delivery resistant to clindamycin or susceptibility unknown


Obstentrics_Williams

Obstentrics_Williams. GBS = group B Streptococcus; IV = intravenous. Data from the Verani, 2010 for prophylaxis, and ampicillin is an acceptable alternative Women undergoing cesarean delivery before labor onset with (T able 64-3). Women with a penicillin allergy and no hisintact membranes do not need intrapartum GBS chemoprophytory of anaphylaxis are given cefazolin (Briody, 2016). hose laxis, regardless of GBS colonization status or gestational age. at high risk for anaphylaxis should have antimicrobial susceptibility testing performed to exclude clindamycin resistance. Clindamycin-sensitive but erythromycin-resistant isolates • Methicillin-Resistant Staphylococcus aureus should have a D-zone test performed to assess for inducible Staphylococcus aureus is a pyogenic gram-positive organism and clindamycin resistance. If clindamycin resistance is conirmed, is considered the most virulent of the staphylococcal species. vancomycin should be administered. Eythromycin is no longer It primarily colonizes the


Obstentrics_Williams

Obstentrics_Williams. If clindamycin resistance is conirmed, is considered the most virulent of the staphylococcal species. vancomycin should be administered. Eythromycin is no longer It primarily colonizes the nares, skin, genital tissues, and oroused or penicilin-alergic patients. pharynx. Approximately 20 percent of normal individuals are


Obstentrics_Williams

Obstentrics_Williams. Further recommendations for management of spontanepersistent carriers, 30 to 60 percent are intermittent carriers, ous preterm labor, threatened preterm delivery, or preterm and 20 to 50 percent are noncarriers (Gorwitz, 2008). Coloprematurely ruptured membranes are shown in Figure 64-7. nization is considered the greatest risk factor for infection Onset of labor orrupture of membranes at < 37 weeks' gestation with significant risk for imminent preterm delivery rectal GBS culture -...for�48hours prophylaxis


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Obstentrics_Williams. Onset of labor orrupture of membranes at < 37 weeks' gestation with significant risk for imminent preterm delivery rectal GBS culture -...for�48hours prophylaxis FIGURE 64-7 Sample algorithm for prophylaxis for women with group B streptococcal (GBS) disease and threatened preterm delivery. This algorithm is not an exclusive course of management, and variations that incorporate individual circumstances or institutional preferences may be appropriate. IV = intravenous. (Adapted from Centers for Disease Control and Prevention, 201o6a.) (Marzec, 2016; Sheield, 2013). Methicillin-resistant 5 aureus (MRSA) colonizes only 2 percent of adults but is a signiicant contributor to the health-care burden (Gorwitz, 2008). MRSA infections are associated with increased cost and higher mortality rates compared with those by methicillin-sensitive 5 aureus (NISSA) (Beigi, 2009; Butterly, 2010).


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Obstentrics_Williams. Community-acquired MRSA (CA-MRSA) is diagnosed when identified in an outpatient setting or within 48 hours of hospitalization in a person without traditional risk factors. Such risk factors include prior MRSA infection, hospitalization, dialysis or surgery within the past year, and indwelling catheters or devices (Dantes, 2013). Hospital-associated MRSA (HA-MRSA) infections are nosocomial. Most cases of \1RSA in pregnant women are CA-MRSA.


Obstentrics_Williams

Obstentrics_Williams. Anovaginal colonization with 5 aureus is identified in 10 to 25 percent of obstetrical patients (Top, 2010). Skin and soft tissue infections are the most common presentation of MRSA in pregnant women (Fig. 64-8). Mastitis and breast abscesses have been reported in up to a fourth of cases of MRSA complicating pregnancy (Laibl, 2005; Lee, 2010). Perineal abscesses, wound infections at sites such as abdominal and episiotomy incisions, and chorioamnionitis are also associated with MRSA (Pimentel, 2009; hurman, 2008). Finally, osteomyelitis has been reported (Nguyen, 2015; Tanamai, 2016). A rise in CA-MRSA infections has been reported in neonatal intensive care units and newborn nurseries. In these settings, infection is frequently associated with maternal and health-care worker skin infections and infected breast milk. Vertical transmission is rare (Jimenez-Truque, 2012; Pinter, 2009).


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Obstentrics_Williams. he Infectious Diseases Society of America has published guidelines for the treatment of MRSA infections (Liu, 2011). Uncomplicated supericial infections are primarily managed by drainage and local wound care. Although historically FIGURE 64-8 This antepartum patient presented with multiple small microabscesses for which culture identified methicillinresistant Staphylococcus aureus. (Used with permission from Dr. Stephan Shivvers.) de-emphasized, recent evidence suggests benefit from antibi otic therapy in addition to incision and drainage of smaller abscesses (Daum, 2017; Forcade, 2012). Severe superficial infections, especially those that fail to respond to local care or those in patients with medical comorbidities, are treated with MRSA-appropriate antibiotics. Purulent cellulitis should be treated empirically for CA-MRSA until culture results are available. Most CA-MRSA strains are sensitive to trimethoprim-sul famethoxazole and clindamycin (\1iller, 2015; T alan, 2016).


Obstentrics_Williams

Obstentrics_Williams. Most CA-MRSA strains are sensitive to trimethoprim-sul famethoxazole and clindamycin (\1iller, 2015; T alan, 2016). for mono therapy. Linezolid, although efective against MRSA, is expensive, and there is little information regarding its use in pregnancy. Doxycycline, minocycline, and tetracycline, although efective for MRSA infections, should not be used in pregnancy. Vancomycin remains the irst-line therapy for inpatient serious MRSA infections.


Obstentrics_Williams

Obstentrics_Williams. he control and prevention of HA-NIRSA and CA-MRSA rely on appropriate hand hygiene and prevention of skin-toskin contact or contact with wound dressings. Decolonization should be considered only in cases in which a patient develops recurrent supericial infections despite optimal hygiene measures or if ongoing transmission occurs among household or close contacts (Liu, 2011). Decolonization measures include nasal treatment with mupirocin, chlorhexidine gluconate baths, and oral rifampin therapy if previous measures have failed. Routine decolonization is not efective in the general obstetrical population. For women with culture-proven CA-MRSA infection during pregnancy, we add single-dose vancomycin to routine beta-Iactam perioperative prophylaxis for cesarean deliveries and higher-order perineal lacerations. Breastfeeding in these women is not prohibited, but optimal hygiene and attention to minor skin breaks is encouraged.


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Obstentrics_Williams. Listeria monocytogenes is an uncommon but probably underdiagnosed cause of neonatal sepsis (Kylat, 2016). This facultative intracellular gram-positive bacillus can be isolated from the feces of 1 to 5 percent of adults. Nearly all cases oflisteriosis are thought to be foodborne. Outbreaks have been caused by raw vegetables, coleslaw, apple cider, melons, milk, fresh Mexicanstyle cheese, smoked ish, and processed foods such as pate, hummus, wieners, and sliced deli meats (Centers for Disease Control and Prevention, 20 13e).


Obstentrics_Williams

Obstentrics_Williams. Listerial infections are more common in pregnant women, immunocompromised patients, and the very old or young. he incidence of such infections in pregnancy is estimated to be up to 100 times that in the general population (Kourtis, 2014; Rouse, 2016). In 1651 cases reported in 2009 to 2011, the CDC found that 14 percent were in pregnant women (Silk, 2013). It is unclear why pregnant women still account for a significant number of these reported cases. One hypothesis is that pregnant women are susceptible because of decreased cellmediated immunity (Baud, 2011).


Obstentrics_Williams

Obstentrics_Williams. Listeriosis during pregnancy may be asymptomatic or may cause a febrile illness that is confused with influenza, pyelonephritis, or meningitis (Centers for Disease Control and Prevention, 2013e). he diagnosis usually is not apparent until blood cultures are reported as positive. Occult or clinical infection also may stimulate labor. Discolored, brownish, or meconiumstained amnionic fluid is common with fetal infection, even in preterm gestations. VIaternalrlisteriosis causes fetal infection that characteristically produces disseminated granulomatous lesions with microabscesses (Fig. 64-9). Chorioamnionitis is common, and placental lesions include multiple, well-demarcated macroabscesses. Early-and late-onset neonatal infections are similar to group B streptococcal sepsis. In a review of 222 cases, infection resulted in abortion or stillbirth in 20 percent, and neonatal sepsis developed in 68 percent of surviving newborns (Mylonakis, 2002). In one large, prospective cohort study, 24


Obstentrics_Williams

Obstentrics_Williams. 222 cases, infection resulted in abortion or stillbirth in 20 percent, and neonatal sepsis developed in 68 percent of surviving newborns (Mylonakis, 2002). In one large, prospective cohort study, 24 percent of mothers experienced fetal loss, but none after 29 weeks' gestation (Charlier, 2017). However, a neonatal-case fatality rate of 21 percent has been reported (Sapuan, 2017).


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Obstentrics_Williams. FIGURE 64-9 The pale placenta (A)and stillborn infant (B) resulted from maternal listeriosis. Treatment with ampicillin plus gentamicin is usually recommended because of synergism against Listeria species (Rouse, 2016). T rimethoprim-sulfamethoxazole can be given to penicillin-allergic women. Maternal treatment in most cases is also efective for fetal infection (Chan, 2013). No vaccine is available. Prevention is by washing raw vegetables, cooking all raw food, and avoiding the implicated foods listed previously (American College of Obstetricians and Gynecologists, 2016d).


Obstentrics_Williams

Obstentrics_Williams. Infections from Salmonella species continue to be a major cause of foodborne illness (Peques, 2012). Six serotypes, including Salmonella subtypes yphimurium and enteritidis, account for most cases in the United States. Nontyphoid Salmonella gastroenteritis is contracted through contaminated food. Symptoms that include nonbloody diarrhea, abdominal pain, fever, chills, nausea, and vomiting begin 6 to 48 hours after exposure. Diagnosis is made by stool studies (Chap. 54, p. 1048). Intravenous crystalloid solutions are given for rehydration. ntimicrobials are not given in uncomplicated infections because they do not commonly shorten illness and may prolong the convalescent carrier state. If gastroenteritis is complicated by bacteremia, antimicrobials are given as discussed below. Rare case reports have linked Salmonella bacteremia with abortion (Coughlin, 2002).


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Obstentrics_Williams. Typhoid fever caused by Salmonela yphi remains a global health problem, although it is uncommon in the United States. Infection is spread by oral ingestion of contaminated food, water, or milk. In pregnant women, the disease is more likely to be encountered during epidemics or in those with HIV infection (Hedriana, 1995). In former years, antepartum typhoid fever resulted in abortion, preterm labor, and maternal or fetal death (Dildy, 1990). Fluoroquinolones and third-generation cephalosporins are the preferred treatment. For enteric (typhoid) fever, antimicrobial susceptibility testing is important because of the development of drug-resistant strains (Crump, 2015). Typhoid vaccines appear to exert no harmful efects when administered to pregnant women and are given in an epidemic or before travel to endemic areas.


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Obstentrics_Williams. Bacillary dysentery caused by Shigela is a relatively common, highly contagious cause of inlammatory exudative diarrhea in adults. Shigellosis is more common in children attending daycare centers and is transmitted via the fecal-oral route. Clinical manifestations range from mild diarrhea to severe dysentery, bloody stools, abdominal cramping, tenesmus, fever, and systemic toxicity. Although shigellosis may be self-limited, careful attention to treatment of dehydration is essential in severe cases. We have cared for pregnant women in whom secretory diarrhea exceeded lO•Ll day! Antimicrobial therapy is imperative, and efective treatment during pregnancy includes fluoroquinolones, ceftriaxone, or azithromycin. Antimicrobial resistance is rapidly emerging, and antibiotic susceptibility testing can help guide appropriate therapy (Centers for Disease Control and Prevention, 2016). Shigellosis can stimulate uterine contractions and cause preterm birth (Parisot, 2016).


Obstentrics_Williams

Obstentrics_Williams. Also known as leprosy, this chronic infection is caused by Mycobacterium leprae and is rare in this country. Diagnosis is confirmed by PCR. Multidrug therapy with dapsone, rifampin, and clofazimine is recommended for treatment and is generally safe during pregnancy (Gimovsky, 2013; Ozturk, 2017). Duncan (1980) reported an excessive incidence oflow-birthweight newborns among infected women. The placenta is not involved, and neonatal infection apparently is acquired from skin-to-skin or droplet transmission (Duncan, 1984). Vertical transmission is common in untreated mothers (Moschella, 2004).


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Obstentrics_Williams. Caused by the spirochete Borrelia burgdoeri, Lyme disease is the most commonly reported vectorborne illness in the United States (Centers for Disease Control and Prevention, 2017c). Lyme borreliosis follows tick bites of the genus Ixodes. There are three stages (Steere, 2015). Early infection-stage I-causes a distinctive local skin lesion, erythema migrans, which may be accompanied by a flulike syndrome and regional adenopathy. If untreated, disseminated infection-stage 2-follows in days to weeks. Multisystem involvement is frequent, but skin lesions, arthralgia, myalgia, carditis, and meningitis predominate. If still untreated after several weeks to months, late or persistent infection-stage 3-manifests in perhaps half of patients. Native immunity is acquired, and the disease enters a chronic phase in about 10 percent. Some patients remain asymptomatic, but others in the chronic phase develop various skin, joint, or neurological manifestations (Shapiro, 2014).


Obstentrics_Williams

Obstentrics_Williams. Clinical diagnosis is important because serological and PCR testing has many pitfalls (Steere, 2015). IgM and IgG serological testing is recommended in early infection and is followed by Western blotting for conirmation. Ideally, acute and convalescent serological evaluation is completed if possible, however, false-positive and -negative rates are high. Optimal treatment of Lyme disease was published by the Infectious Diseases Society of America (Sanchez, 2016). For early infection, treatment with doxycycline, amoxicillin, or cefuroxime is recommended for 14 days, although doxycycline is usually avoided in pregnancy. A 14-to 28-day course of IV ceftriaxone, cefotaxime, or penicillin G is given for complicated early infections that include meningitis, carditis, or disseminated infections. Chronic arthritis and post-Lyme disease syndrome are treated with prolonged oral or IV regimens, however, symptoms respond poorly to treatment (Steere, 2015).


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Obstentrics_Williams. No vaccine is commercially available. Avoiding areas with endemic Lyme disease and improving tick control in those areas is the most efective prevention. Self-examination with removal of unengorged ticks within 36 hours of attachment reduces infection risk (Hayes, 2003). For tick bites recognized within 72 hours, a single 200-mg oral dose of doxycycline may reduce infection development. Several reports describe Lyme disease in pregnancy, although large series are lacking. Transplacental transmission has been confirmed, but no congenital efects of maternal borreliosis have been conclusively identiied (Shapiro, 2014; Walsh, 2006). Prompt treatment of maternal early infection should prevent most adverse pregnancy outcomes (Mylonas, 201l). Diagnosis and management of tuberculosis during pregnancy is discussed in detail in Chapter 51 (p. 995).


Obstentrics_Williams

Obstentrics_Williams. Diagnosis and management of tuberculosis during pregnancy is discussed in detail in Chapter 51 (p. 995). The obligate intracellular parasite Toxoplasma gondii has a life cycle with two distinct stages (Kim, 2015). he eline stage takes place in the cat-the deinitive host-and its prey. Unsporu lated oocysts are excreted in feces. In the non eline stage, tissue cysts containing bradyzoites or oocysts are ingested by the inter mediate host, including humans. Gastric acid digests the cysts to release bradyzoites, which infect small-intestinal epithelium. Here, they are transformed into rapidly dividing tachyzoites, which can infect all cells within the host mammal. Humoral and cell-mediated immune defenses eliminate most of these, but tissue cysts develop. Their lifelong persistence is the chronic form of toxoplasmosis.


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Obstentrics_Williams. Human infection is acquired by eating raw or undercooked meat infected with tissue cysts or by contact with oocysts from cat feces in contaminated litter, soil, or water. Prior infection is conirmed by serological testing, and its prevalence depends on geographic locale and parasite genotype. In the United States, seroprevalence in persons aged 10 to 19 years is 5 to 30 per cent, and this can exceed 60 percent in those older than 50 (Kim, 2015). Thus, a significant segment of pregnant women in this country are susceptible to infection. The incidence of prenatal infection resulting in birth of a newborn with con genital toxoplasmosis varies from 0.8 per 10,000 live births in the United States to 10 per 10,000 in France (Cook, 2000). Between 400 and 4000 cases of congenital toxoplasmosis are diagnosed annually in the United States Oones, 2014).


Obstentrics_Williams

Obstentrics_Williams. Between 400 and 4000 cases of congenital toxoplasmosis are diagnosed annually in the United States Oones, 2014). Most acute maternal infections are subclinical and are detected only by prenatal or newborn serological screening. In some cases, maternal symptoms may include fatigue, fever, headache, muscle pain, and sometimes a maculopapular rash and posterior cervical lymphadenopathy. In immunocompetent adults, initial infection confers immunity, and prep regnancy infection nearly eliminates any risk of vertical transmission. Infection in immu nocompromised women, however, may be severe, and reactiva tion may cause encephalitis, retinochoroiditis, or mass lesions. Maternal infection is associated with a fourfold increased pre term delivery rate before 37 weeks (Freeman, 2005).


Obstentrics_Williams

Obstentrics_Williams. Maternal infection is associated with a fourfold increased pre term delivery rate before 37 weeks (Freeman, 2005). The incidence and severity of fetal toxoplasmosis depend on gestational age at the time of maternal infection. Risks for fetal infection rise with gestational age. A metaanalysis estimated the risk to be 15 percent at 13 weeks, 44 percent at 26 weeks, and 71 percent at 36 weeks (SYROCOT Study Group, 2007). Conversely, the severity of fetal infection is much greater in early pregnancy, and these fetuses are much more likely to have clinical findings of infection (American College of Obstetricians and Gynecologists, 2017).


Obstentrics_Williams

Obstentrics_Williams. Importantly, most infected fetuses are born without obvious stigmata of toxoplasmosis. Clinically afected neonates usually have generalized disease expressed as low birthweight, hepatosplenomegaly, jaundice, and anemia. Some primarily have neurological disease with intracranial calciications and with hydrocephaly or microcephaly (Dhombres, 2017). Many eventually develop chorioretinitis and exhibit learning disabilities. This classic triad-chorioretinitis, intracranial calcifications, and hydrocephalus-is often accompanied by convulsions. Infected neonates with clinical signs are at risk for long-term complications (Abdoli, 2014; Wallon, 2014).


Obstentrics_Williams

Obstentrics_Williams. With IgG antibody conirmed before pregnancy, there is no risk for a congenitally infected fetus. he American College of Obstetricians and Gynecologists (2017) does not recommend prenatal screening for toxoplasmosis in areas of low prevalence, including the United States. Screening should be performed in immunocompromised pregnant women, including those with HIV infection. In areas of high toxoplasmosis prevalence-for example, France and Austria-routine screening has resulted in diminished congenital disease (Kim, 2015; Wallon, 2013).


Obstentrics_Williams

Obstentrics_Williams. Pregnant women with suspected toxoplasmosis should be tested. he parasite is rarely detected in tissue or body fluids. Antitoxoplasma IgG develops within 2 to 3 weeks after infection, peaks at 1 to 2 months, and usually persists for lifesometimes in high titers. Although IgM antibodies appear by 10 days after infection and usually become negative within 3 to 4 months, they may remain detectable for years. hus, IgM antibodies are not used alone to diagnose acute toxoplasmosis (Dhakal, 2015). Best results are obtained with the Toxoplasma Serologic Proile performed at the Palo Alto Medical Foundation Research Institute (ww.toxolab@pamf.org). Toxoplasma IgG avidity increases with time. hus, if a high-avidity IgG result is found, infection in the preceding 3 to 5 months is excluded. Multiple tests are available that allow high avidity results to conirm latent infection with a 100-percent positivepredictive value (Villard, 2013).


Obstentrics_Williams

Obstentrics_Williams. Congenital toxoplasmosis is suspected when sonography reveals findings such as hydrocephaly, intracranial or hepatic calciications, ascites, placental thickening, hyperechoic bowel, and growth restriction. Prenatal diagnosis of congenital toxoplasmosis is performed using PCR ampliication of toxoplasma DNA in amnionic luid (Filisetti, 2015; Montoya, 2008). he sensitivity of PCR varies with gestational age and is lowest before 18 weeks (Romand, 2001). No randomized clinical trials have assessed the benefit and eicacy of treatment to decrease the risk for congenital infection. A systematic review of data from 1438 treated pregnancies found weak evidence for early treatment to reduce congenital toxoplasmosis risks (SYROCOT Study Group, 2007). Treatment has been associated with a reduction in rates of serious neurological sequelae and neonatal demise (Cortina-Borja, 2010).


Obstentrics_Williams

Obstentrics_Williams. Prenatal treatment is based on two regimens-spiramycin alone or a pyrimethamine-sulfonamide combination given with folinic acid (American College of Obstetricians and Gynecologists, 2017). These two regimens have also been used consecutively (Hotop, 2012). Little evidence supports the use of a speciic regimen (Montazeri, 2017; Valentini, 2015). hat said, most experts will use spiramycin in women with acute infection early in pregnancy to reduce vertical transmission. Because it does not cross the placenta, spiramycin may not be used to treat fetal infection. Pyrimethamine-sulfadiazine with folinic acid is selected for maternal infection after 18 weeks' gestation or if fetal infection is suspected.


Obstentrics_Williams

Obstentrics_Williams. There is no vaccine for toxoplasmosis, so avoidance of infection is necessary if congenital infection is to be prevented. Eforts include: (1) cooking meat to safe temperatures; (2) peeling or thoroughly washing fruits and vegetables; (3) cleaning all food preparation surfaces and utensils that have contacted raw meat, poultry, seafood, or unwashed fruits and vegetables; (4) wearing gloves when changing cat litter, or else delegating this duty; and (5) avoiding feeding cats raw or undercooked meat and keeping cats indoors. Although these preventive steps are recommended, no data support their efectiveness (American College of Obstetricians and Gynecologists, 2017; Di Mario, 2015).


Obstentrics_Williams

Obstentrics_Williams. his protozoan infection remains a global health crisis and causes 2000 deaths per day worldwide (White, 2015). Malaria has been efectively eradicated in Europe and in most of North America, and worldwide mortality rates have fallen more than 25 percent. In the United States, most cases of malaria are imported-some in returning military personnel (Mace, 2017). Transmitted by infected Anopheles mosquitoes, six species of Plasmodium cause human disease-alciparum, vivax, two species of ovale, malariae, and knowlesi.


Obstentrics_Williams

Obstentrics_Williams. Pregnant women have increased susceptibility to malarial infections (Kourtis, 2014). Antibodies to the parasite surface antigen VAR2CSA mediate placental accumulation of infected erythrocytes and lead to the harmful efects of malaria (Mayor, 2015). hrough this mechanism, some immunity accrues with parity and is called pregnancy-specic antimalarial immuniy. Ironically, malaria treatment dampens this immunity, and resurgence in pregnancy has been documented in Mozambique (Mayor, 2015).


Obstentrics_Williams

Obstentrics_Williams. Clinical findings are fever, chills, and flulike symptoms including headaches, myalgia, and malaise, which may occur at intervals. Symptoms are less severe with recurrences. Malaria may be associated with anemia and jaundice, and aciparum infections may cause kidney failure, coma, and death. That said, many otherwise healthy but infected adults in endemic areas are asymptomatic because of partial immunity. Pregnant women, although often asymptomatic, are said to be more likely to develop traditional symptoms (Desai, 2007) . infections during pregnancy-whether symptomatic or asymptomatic-are associated with higher rates of perinatal morbidity and mortality (Menendez, 2007; Nosten, 2007). Adverse outcomes include stillbirth, preterm birth, low birthweight, and maternal anemia. The latter two are documented most frequently (Machado Filho, 2014; McClure, 2013). Maternal infection is associated with a 14-percent rate of low-birthweight newborns worldwide (Eisele, 2012). These


Obstentrics_Williams

Obstentrics_Williams. FIGURE 64-10 Photomicrograph of placental malaria. A.Multiple infected red blood cells (long black arrow) are seen in the intervillous space of this placenta. Multiple villi cut in cross section are shown, and three are highlighted (short arrows). B. Increased magnification of image (A). Multiple infected erythrocytes are seen, and two are identified (arrows). adverse perinatal outcomes correlate with high levels of placental parasitemia (Rogerson, 2007). The latter occurs when parasitized erythrocytes, monocytes, and macrophages accumulate in the vascular areas of the placenta (Fig. 64-10). Infections with P aciparum are the worst, and early infection raises the risk for abortion. The incidence of malaria increases signiicantly in the latter two trimesters and postpartum (Diagne, 2000). Despite this, congenital malaria occurs in <5 percent of neonates born to infected mothers.


Obstentrics_Williams

Obstentrics_Williams. Identiication of parasites by microscopical evaluation of a thick and thin blood smear remains the gold standard for diagnosis. In women with low parasite densities, however, the sensitivity of microscopy is poor. Malaria-speciic antigens are now being used for rapid diagnostic testing. Not only is their sensitivity still an issue in pregnancy, but these tests are not routinely available (Kashif, 2013; White, 2015). For treatment, the most frequently used antimalarial drugs are not contraindicated in pregnancy. The World Health Organization recommends that all infected patients living in or traveling from endemic areas be treated with an artemisinin-based regimen for uncomplicated falciparum malaria (Taming, 2016). The CDC (2013c) recommends using atovaquone options are not available or tolerated.


Obstentrics_Williams

Obstentrics_Williams. nosed with uncomplicated malaria caused by P vivax, malariae, ovale, and chloroquine-sensitive P aciparum should be treated with chloroquine or hydroxychloroquine. For women infected with multidrug-resistant P aciparum, one irst-line agent for nonpregnant persons is artemether-Iumefantrine. Another primary option is artesunate plus meRoquine or artesunate plus dihydroartemisinin-piperaquine (White, 2015). he PREGACT Study Group (2016) recently compared four artemisinin-based drugs in 3428 pregnant women with falciparum malaria and reported no serious maternal or perinatal adverse efects. Second-line treatment regimens are artesunate; quinine plus either tetracycline, doxycycline, or clindamycin; or atovaquone-proguanii. Chloroquine-resistant P vivax should be treated with meRoquine. Chloroquine-sensitive P vivax or P ovale should be treated with chloroquine throughout pregnancy and then primaquine postpartum. Resistance to all the antimalarial drugs has been reported, including the


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Obstentrics_Williams. P vivax or P ovale should be treated with chloroquine throughout pregnancy and then primaquine postpartum. Resistance to all the antimalarial drugs has been reported, including the recently added artemisinin-based compounds.


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Obstentrics_Williams. Treatment regimens for uncomplicated and severe malarial infections in pregnancy are detailed at: ww.cdc.gov/malaria/ diagnosis_treatment. he CDC also maintains a malaria hotline for treatment recommendations (855-856-4713). Malaria control and prevention relies on chemoprophylaxis when traveling to or living in endemic areas. Vector control is also important. Insecticide-treated netting, pyrethroid insecticides, and D EET -based insect repellent lower malarial rates in endemic areas. hese are well tolerated in pregnancy (Menendez, 2007). If travel is necessary, chemoprophylaxis is recommended.


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Obstentrics_Williams. Chloroquine and hydroxychloroquine prophylaxis is safe and well tolerated in pregnancy. Prophylaxis lowers placental infection rates from 20 percent to 4 percent in asymptomatic infected women in areas without chloroquine resistance (Cot, 1992). For travelers to areas with chloroquine-resistant P aciparum, meRoquine prophylaxis is recommended (Freedman, 2016). One evaluation compared prophylaxis during pregnancy with either sulfadoxine-pyrimethamine or dihydroartemisinin-piperaquine and found the latter to be more efective (Kakuru, 2016). Primaquine and doxycycline are contraindicated in pregnancy, and data are insuicient for atovaquone/proguanil use. The latest chemoprophylaxis regimens for pregnancy can be obtained from the CDC Travelers' Health website at: ww.cdc.gov/malaria/ travelers/drugs.htmi. The CDC also publishes Health Inormation or Intenational Travel (The Yellow Book) at: ww.cdc. gov/yellowbook. For women living in endemic areas, intermittent preventive treatment was


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Obstentrics_Williams. The CDC also publishes Health Inormation or Intenational Travel (The Yellow Book) at: ww.cdc. gov/yellowbook. For women living in endemic areas, intermittent preventive treatment was found to be superior to intermittent screening with treatmet (Desai, 2015).


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Obstentrics_Williams. Approximately 10 percent of the world population is infected with Entamoeba histo6ltica, and most are asymptomatic (Andrade, 201r5). Amebic dysentelY, however, may take a fulminant course during pregnancy, with fever, abdominal pain, and bloody stools. Prognosis is worse if complicated by a hepatic abscess. Diagnosis is made by identiying E histoytica cysts or trophozoites within a stool sample. herapy is similar to that for the nonpregnant woman, and metronidazole or tinidazole are the preferred drugs for amebic colitis and invasive disease. Noninvasive infections may be treated with iodoquinol or paromomycin. Disseminated fungal infection-usually pneumonitis-during pregnancy is uncommon with coccidiomycosis, blastomycosis, cryptococcosis, or histoplasmosis. heir identification and management are considered in Chapter 51 (p. 995).


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Obstentrics_Williams. Pregnant travelers face general medical, obstetrical, and potentially hazardous destination risks. Several sources provide travel information (Freedman, 2016). he International Federation for Tropical Medicine has comprehensive information available at ww.iftm-hp.org, and the International Society of Travel Medicine publishes information at www.istm.org/ bodyofknowledge. lso, 1he Yelow Book, mentioned earlier, by the CDC has extensive travel information regarding pregnancy and breastfeeding.


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Obstentrics_Williams. The concept ofbioterrorism involves the deliberate release ofbacteria, viruses, or other infectious agents to cause illness or death. hese natural agents are often altered to increase their infectivity or their resistance to medical therapy. Health-care providers should be alert for signiicant increases in the number of persons with febrile illnesses accompanied by respiratory symptoms or with rashes not easily associated with common illnesses. Clinicians are urged to contact their state health department or the CDC for current information and recommendations. The merican College of Obstetricians and Gynecologists (2016a) has addressed disaster preparedness for obstetricians. It provides both general considerations and recommendations for hospital readiness and obstetrics-specific issues.


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Obstentrics_Williams. he variola virus causes smallpox and is considered a serious weapon. The virus is highly transmissible and carries an overall 30-percent case-fatality rate. The last case of smallpox in the United States was reported in 1949, and worldwide it was reported in Somalia in 1977. Nishiura (2006) has reviewed the severe perinatal and maternal morbidity and mortality caused by smallpox. The case-fatality rate of smallpox in pregnancy is 61 percent if the pregnant woman is unvaccinated. Rates of stillbirth, abortion, preterm labor and delivery, and neonatal demise rise significantly in pregnancies complicated by this infection.


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Obstentrics_Williams. Because the smallpox vaccine currently available is made with live vaccinia virus, pregnancy should be delayed for 4 weeks in recipients. It is generally not given to pregnant women because of the risk of fetal vaccinia, a rare but serious complication. Inadvertent smallpox vaccination during pregnancy has not, however, been convincingly associated with fetal malformations or preterm birth (Badell, 2015). Moreover, no cases of fetal vaccinia have been reported with second-generation smallpox vaccine exposure. The Smallpox Vaccine in Pregnancy Registry remains active, and vaccinated women are still being enrolled: DOD .NHRC-birthregistry@mail.mil.


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Obstentrics_Williams. Bacillus anthracis is a gram-positive, spore-forming, aerobic bacterium. It can cause three main types of clinical anthrax: inhalational, cutaneous, and gastrointestinal (Centers for Disease Control and Prevention, 2017a). The bioterrorist anthrax attacks of 2001 involved inhalational anthrax (Inglesby, 2002). Spores are inhaled and deposited in the alveoli. They are engulfed by macrophages and germinate in mediastinal lymph nodes. The incubation period is usually less than 1 week but may be as long as 2 months. Within 1 to 5 days of symptom onset, the second stage is heralded by the abrupt onset of severe respiratory distress and high fevers. Mediastinitis and hemorrhagic thoracic lymphadenitis are common. Chest radiographs show a widened mediastinum. Case-fatality rates with inhalational anthrax are high, even with aggressive antibiotic and supportive therapy (Holty, 2006).


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Obstentrics_Williams. Anthrax afecting pregnant women and its treatment were reviewed by Meaney-Delman and coworkers (2012, 2013). They reported data on 20 pregnant and postpartum women. The overall mortality rate was 80 percent, with a 60-percent fetal or neonatal loss rate. Of note, most cases were published before the advent of antibiotics. Regimens for postexposure anthrax prophylaxis are given for 2 months. The CDC recommend that asymptomatic pregnant and lactating women with documented exposure to B anthracis be given postexposure prophylaxis with ciproloxacin, 500 mg orally twice daily for 60 days (Hendricks, 2014; Meaney-Delman, 2013). Amoxicillin, 500 mg orally three times daily, can be substituted if the strain is proven sensitive. In the case of ciproloxacin allergy and either penicillin allergy or resistance, doxycycline, 100 mg orally twice daily, is given for 60 days. Risks from anthrax far outweigh any fetal risks from doxycycline (lvleaney-Delman, 2013).


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Obstentrics_Williams. The anthrax vaccine is an inactivated, cell-free product that requires three injections over 28 days. Vaccination is generally avoided in pregnancy because safety data are limited. Inadvertent vaccination of pregnant women with the vaccine has not been linked with a significant increase in fetal malformation or miscarriage rates (Conlin, 2015; Ryan, 2008). The anthrax vaccine is an essential adjunct to postexposure antimicrobial prophylaxis, even in pregnancy. Other category A bioterrorism agents include Francisella tularemis-tularemia, Clostridium botulinum-botulism, Yersinia pestis-plague, and viral hemorrhagic fevers-for example, Ebola, Marburg, Lassa, and Machupo. The guidelines for these biological agents are evolving and are detailed at the CDC Bioterrorism website: emergency.cdc.gov/bioterrorism/index.asp. Abdoli A, Dalimi A, Arbabi M, et al: Neuropsychiatric manifestations of latent toxoplasmosis on mothers and their ofspring. J Matern Fetal Neonatal Med 27(13):1368,t2014


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Obstentrics_Williams. Abdoli A, Dalimi A, Arbabi M, et al: Neuropsychiatric manifestations of latent toxoplasmosis on mothers and their ofspring. J Matern Fetal Neonatal Med 27(13):1368,t2014 Adams LL, Gungor S, Turan S, et al: When are amniotic luid viral PCR studies indicated in prenatal diagnosis? Prenat Diagn 32(1):88, 2012 Adams Waldorf KM, McAdams M: Inluence of infection during pregnancy on fetal development. Reproduction 146(5):R151, 2013 Adhikari EH, Nelson DF, Johnson A, et al: Infant outcomes among women with Zika virus infection during pregnancy: results of a large prenatal Zika screening program. Am J Obstet Gynecol 216:292.e1, 2017 Ahn KH, Park YJ, Hong SC, et al: Congenital varicella syndrome: a systematic review. J Obstet Gynaecol 36(5):563, 2016 Alpert SG, Fergerson J, Noel LP: Intrauterine West Nile virus: ocular and systemic indings. Am J Ophthalmol 136(4):733,2003


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Obstentrics_Williams. Alpert SG, Fergerson J, Noel LP: Intrauterine West Nile virus: ocular and systemic indings. Am J Ophthalmol 136(4):733,2003 American College of Obstetricians and Gynecologists: Hospital disaster preparedness for obstetricians and facilities providing materniry care. Committee Opinion No. 555, March 2013, Reairmed 2016a American College of Obstetricians and Gynecologists: Inluenza vaccination during pregnancy. Committee Opinion No. 608, September 2014, Reaffirmed 2016b American College of Obstetricians and Gynecologists: Integrating immunizations into practice. Committee Opinion No. 661, Aprilt2016c American College of Obstetricians and Gynecologists: Management of pregnant women with presumptive exposure to Listeria monocytogenes. Committee Opinion No. 614, December, 2014, Reairmed 2016d American College of Obstetricians and Gynecologists: Prevention of earlyonset group B streptococcal disease in newborns. Committee Opinion No. 485, April 2011, Reairmed 2016e


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Obstentrics_Williams. American College of Obstetricians and Gynecologists: Prevention of earlyonset group B streptococcal disease in newborns. Committee Opinion No. 485, April 2011, Reairmed 2016e American College of Obstetricians and Gynecologists: Cytomegalovirus, parvovirus B9, varicella zoster, and toxoplasmosis in pregnancy. Practice Bulletin No. 151, June 2015, Reairmed 2017 Andrade M, Reed SL: Amebiasis and infection with free-living amebas. In Kasper DL, Fauci AS, Hauser SL, et al (eds): Harrison's Principles ofInternal Medicine, 19th ed. New York, McGraw-Hill, 2015, p. 1363 Arabi YM, Balkhy HH, Hayden FG, et al: Middle East respiratory syndrome. N Engl J Med 376(6):584,t2017 Arvin AM, Fast P, Myers M, et al: Vaccine development to prevent cytomegalovirus disease: report from the National Vaccine Advisory Committee. Clin Infect Dis 39:233, 2004


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Obstentrics_Williams. Arvin AM, Fast P, Myers M, et al: Vaccine development to prevent cytomegalovirus disease: report from the National Vaccine Advisory Committee. Clin Infect Dis 39:233, 2004 Assiri A, Abedi GR, Al Masri M, et al: Middle East respiratory syndrome coronavirus infection during pregnancy: a report of 5 cases from Saudi Arabia. Clin Infect Dis 63(7):951, 2016 Auriti C, Piersigilli F, De Gasperis MR, et al: Congenital varicella syndrome: still a problem? Fetal Diagn Ther 25(2):224, 2009 Azam AZ, Vial Y, Fawer CL, et al: Prenatal diagnosis of congenital cytomegalovirus infection. Obstet Gynecol 97:443, 2001 Badell ML, Meaney-Delman D, Tuuli MG, et al: Risks associated with smallpox vaccination in pregnancy: a systematic review and meta-analysis. Obstet Gynecol 125(6):1439,t2015 Bates T: Poliomyelitis in pregnancy, fetus and newborn. Am J Dis Child 90: 189, 1955 Baud D, Greub G: Intracellular bacteria and adverse pregnancy outcomes. Clin Microbiol Infect 17: 1312, 2011


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Obstentrics_Williams. Bates T: Poliomyelitis in pregnancy, fetus and newborn. Am J Dis Child 90: 189, 1955 Baud D, Greub G: Intracellular bacteria and adverse pregnancy outcomes. Clin Microbiol Infect 17: 1312, 2011 Beau AB, Hurault-Delarue C, Vial T, et al: Sfery of oseltamivir during pregnancy: a comparative study using the EFEMERIS database. BJOG 121(7):895,2014 Beigi RH: Emerging infectious diseases in pregnancy. Obstet Gynecol 129(5):896,t2017 Beigi RH, Bunge K, Song Y, et al: Epidemiologic and economic efects of methicillin-resistant Staphylococcus aureus in obstetrics. Obstet Gynecol 113:983, 2009 Beigi RH, Venkataramanan R, Caritis SN: Oseltamivir for inluenza in pregnancy. Semin PerinatoIt38(8):503, 2014 Bonvicini F, Puccetti C, Salfi NC, et al: Gestational and fetal outcomes in B19 matenal infection: a problem of diagnosis. J Clin MicrobioI49(10):3514, 201t1 Brasil P, Pereira JP, Moreira ME, et al: Zika virus infection in pregnant women in Rio de Janeiro. N Engl J Med 375(24):2321,t2016


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Obstentrics_Williams. Centers for Disease Control and Prevention (CDC): Rubella and congenital rubella syndrome control and elimination-global progress, 2000-2012. MMWR 62(48)983, 2013f Centers for Disease Control and Prevention: Active Bacterial Core surveillance (ABCs): group B Streptococcus, 2015. Available at: http://www.cdc.gov/ abcslreports-indingsl survreportsl gbs 15. pdf. Accessed October 6, 2017 Centers for Disease Control and Prevention: Shigella-shigellosis. 2016. Available at: https:/ Iwww.cdc.gov/shigella/general-information.html. Accessed October 7, 2017 Centers for Disease Control and Prevention: Anthrax. 2017a. Available at: https:llwww.cdc.gov/anthrax/index.html. Accessed ,t2017 Centers for Disease Control and Prevention: Hantavirus. 20 17b. Available at: https:!lwww.cdc.gov/hantavirus.l Accessed October 7, 2017 Centers for Disease Control and Prevention: Lyme disease: data and statistics. 2017c. Available at: https:llwww.cdc.gov/lyme/stats/index.html. Accessed October 7,t2017


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Obstentrics_Williams. Centers for Disease Control and Prevention: Lyme disease: data and statistics. 2017c. Available at: https:llwww.cdc.gov/lyme/stats/index.html. Accessed October 7,t2017 Centers for Disease Control and Prevention: Measles (rubeola): for healthcare professionals. 2017 d. Available at: https:llwww.cdc.gov/measles/hcp/index. html. Accessed October ,t2017 Centers for Disease Control and Prevention: Seasonal influenza (flu): guidance for clinicians on the use of rapid influenza diagnostic tests. e. Available at: http://www.cdc.gov/flu/professionals/diagnosis/clinician_guidance_ridt. htm. Accessed October 7, 2017 Centers for Disease Control and Prevention: West Nile virus. 2017f. Available at: https:llwww.cdc.gov/westnile/index.html. Accessed October 7, 201


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Obstentrics_Williams. Centers for Disease Control and Prevention: West Nile virus. 2017f. Available at: https:llwww.cdc.gov/westnile/index.html. Accessed October 7, 201 Chambers CD, Johnson DL, Xu R, et al: Safery of the 2010-11, 2011-12, 2012-13, and 2013-14 seasonal inluenza vaccines in pregnancy: birth defects, spontaneous abortion, preterm delivery, and small for gestational age infants, a study from the cohort arm ofVAMPSS. Vaccine 34(37):4443, 2016 Chan BT, Hohmann E, Barshak MB, et al: Treatment of listeriosis in first trimester of pregnancy. Emerg Infect Dis 19:839, 2013 Chandra Pc, Patel H, Schiavello HJ, et al: Successful pregnancy outcome after complicated varicella pneumonia. Obstet Gynecol 92:680, 1998 Charlier C, Perrodeau E, Leclercq A, et al: Clinical features and prognostic factors oflisteriosis: the MONALISA national prospective cohort study. Lancet Infect Dis 17:510,t2017


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Obstentrics_Williams. Charlier C, Perrodeau E, Leclercq A, et al: Clinical features and prognostic factors oflisteriosis: the MONALISA national prospective cohort study. Lancet Infect Dis 17:510,t2017 Chauvet A, Dewilde A, homas D, et al: Ultrasound diagnosis, management and prognosis in a consecutive series of cases of fetal hydrops following maternal parvovirus B19 infection. Fetal Diagn her 30(1):41,t2011 Chaves SS, Gargiullo P, Zhang JX, et al: Loss of vaccine-induced immuniry to varicella over time. N Engl J Med 356: 1121, 2007 Cheeran MC, Lokensgard JR, Schleiss MR: Neuropathogenesis of congenital cytomegalovirus infection: disease mechanisms and prospects for intervention. Clin Microbiol Rev 22(1):99, 2009 Chen H, Lin HC, Lin HC: Increased risk of adverse pregnancy outcomes among women afected by herpangina. Am J Obstet Gynecol 203(1):49. e1,t2010 Chiu MH, Meatherall B, Nikolic A, et al: Subacute sclerosing panencephalitis in pregnancy. Lancet Infect Dis 16(3):366, 2016


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Obstentrics_Williams. Chiu MH, Meatherall B, Nikolic A, et al: Subacute sclerosing panencephalitis in pregnancy. Lancet Infect Dis 16(3):366, 2016 Cohen JI: Enterovirus, parechovirus and reovirus infection. In Kasper DL, Fauci AS, Hauser SL, et al (eds): Harrison's Principles ofInternaltvIedicine, 19th ed. New York, McGraw-Hill, 2015a Cohen YZ, Dolin R: Influenza. In Kasper DL, Fauci AS, Hauser SL, et al (eds): Harrison's Principles of Internal Medicine, 19th ed. New York, lcGrawHill,t2015b Conlin M, Bukowinski AT, Gumbs GR, et al: Analysis of pregnancy and infant health outcomes among women in the National Smallpox Vaccine in Pregnancy Registry who received anthrax vaccine adsorbed. Vaccine 33(36):4387,t2015 Cook AJ, Gilbert E, Bufolano W, et al: Sources of toxoplasma infection in pregnant women: European multicentre case-control study. mvIJ 321: 142, 2000


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Obstentrics_Williams. Crespo AC, van der Zwan A, Ramalho-Santos J, et al: Cytotoxic potential of decidual NK cells and CD8+ T cells awakened by infections. J Reprod ImmunoItI19:85,t2017 Crump JA, Sjolund-Karlsson M, Gordon A, et al: Epidemiology, clinical presentation, laboratory diagnosis, antimicrobial resistance, and antimicrobial management of invasive salmonella infections. Clin Microbiol Rev 28(4): 901, 2015 da Silva IRF, Frontera JA, Bispo de Filippis AN, et al: Neurologic complications associated with the Zika virus in Brazilian adults. JlA Neurol 74(10):1190,t2017 Dantes R, Mu Y, Belflower R, et al: National burden of invasive methicillinresistant Staphylococcus aureus infections, United States, 2011t. JAv1A Intern Med 173(21):1970,t2013


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Obstentrics_Williams. Dembinski J, Eis-Hubinger vf, Maar J, et al: Long term follow up of serostatus after maternofetal parvovirus B19 infection. Arch Dis Child 88:219, 2003 Desai M, Gutman J, L'lanziva A, et al: Intermittent screening and treatment or intermittent preventive treatment with dihydroartemisinin-piperaquine versus intermittent preventive treatment with sulfadoxine-pyrimethamine for the control of malaria during pregnancy in western Kenya: an open-label, three-group, randomised controlled superiority trial. Lancet 386(10012): 2507, 2015 Desai M, ter Kuile F, Nosten F, et al: Epidemiology and burden of malaria in pregnancy. Lancet Infect Dis 7:93, 2007 Deutscher M, Lewis M, Zell ER, et al: Incidence and severity of invasive Streptococcus pneumoniae, group A Streprococcus, and group B Streptococcus infections among pregnant and postpartum women. Clin Infect Dis 53(2):114,t201t1


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Obstentrics_Williams. Dhakal R, Gajurel K, Pomares C, et al: Signiicance of a positive toxoplasma immunoglobulin M test result in the United States. J Clin MicrobioIt53(11): 3601,t2015 Dhombres F, Friszer S, Maurice P, et al: Prognosis of fetal parenchymal cerebraltlesions without ventriculomegaly in congenital toxoplasmosis infection. Fetal Diagn Ther 41(1):8,t2017 Diagne N, Rogier C, Sokhna CS, et al: Increased susceptibility to malaria during the early postpartum period. N Engl J Med 343:598, 2000 Dildy GA III, Martens MG, Faro S, et al: Typhoid fever in pregnancy: a case report. J Reprod Med 35:2 3, 1990 Di Mario S, Basevi V, Gagliotti C, et al: Prenatal education for congenital toxoplasmosis. Cochrane Database Syst Rev 1, 2015


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Obstentrics_Williams. Di Renzo GC, Melin P, Berardi A, et al: Intrapartum GBS screening and antibiotic prophylaxis: a European consensus conference. J Matern Fetal Neonatal Med 28(7):766, 2015 Donders GG, Halperin SA, Devlieger R, et al: Maternal immunization with an investigational trivalent group B streptococcal vaccine: a randomized controlled trial. Obstet GynecoIt127(2):213, 2016 Driggers RW, Ho CY, Korhonen EM, et al: Zika virus infection with prolonged maternal viremia and fetal brain abnormalities. N Engl J Med 374(22):2142,t2016 Duncan ME: Babies of mothers with leprosy have small placentae, low birth weights and grow slowly. BJOG 8 :461, 1980 Duncan ME, Fox H, Harkness A, et al: The placenta in leprosy. Placenta 5:189,t1984 Dunstan HJ, Mill AC, Stephens S, et al: Pregnancy outcome following maternal use of zanamivir or oseltamivir during the 2009 influenza AlH 1 N 1 pandemic: a national prospective surveillance study. BJOG 121(7):901,t2014 Duryea EL, Sheield JS: Influenza: threat to maternal


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Obstentrics_Williams. use of zanamivir or oseltamivir during the 2009 influenza AlH 1 N 1 pandemic: a national prospective surveillance study. BJOG 121(7):901,t2014 Duryea EL, Sheield JS: Influenza: threat to maternal health. Obstet Gynecol Clin North Am 42(2):355,t2015


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Obstentrics_Williams. Egana-Ugrinovic G, Gonce A, Garcia L, et al: Congenital cytomegalovirus infection among twin pairs. J Matern Fetal Neonatal Med 29(21):3439, 20t16 Eisele TP, Larsen DA, Anglewicz PA, et al: Malaria prevention in pregnancy, birthweight, and neonatal mortality: a meta-analysis of 32 national crosssectional datasets in Africa. Lancet Infect Dis 12:942,t2012 Enders G, Bader U, Lindemann L, et al: Prenatal diagnosis of congenital cytomegalovirus infection in 189 pregnancies with known outcome. Prenat Diagn 21:362,t2001 Enders G, Miller E, Cradock-Watson J, et al: Consequences of varicella and herpes zoster in pregnancy: prospective study of 1739 cases. Lancet 343: 1548, 1994 Enders M, Weidner A, Zoellner I, et al: Fetal morbidity and mortality after acute human parvovirus B 19 infection in pregnancy: prospective evaluation of 1018 cases. Prenat Diagn 24:513, 2004