It is estimated that 20% to 30% of all pregnant women are GBS carriers, but colonization can be intermittent or transient. Prenatal screening for GBS at 35 to 37 weeks gestation is recommended by the 2002 national guidelines.

In newborns, the most common GBS infections are sepsis, pneumonia, and meningitis (Fig. 19.1). Early-onset disease occurs within the first week of life; late-onset disease occurs after the first week. Outcome survival has improved recently. For term infants, survival for GBS sepsis is about 98%, but for preterm infants the survival is lower, at 90% for cases at 34 to 36 weeks gestation and 70% for cases at less than 33 weeks.

Risk factors for early-onset disease are maternal GBS colonization, prolonged rupture of membranes, preterm delivery, GBS bacteriuria during pregnancy, birth of a previous infant with invasive GBS disease, maternal chorioamnionitis as evidenced by intrapartum fever, young maternal age, African American race, Hispanic ethnicity, and low levels of antibody to type-specific capsular polysaccharide antigens.

Manifestations of maternal GBS infection include urinary tract infection, chorioamnionitis, endometritis, bacteremia, and stillbirth.

GBS are isolated in 15% of cases of amnionitis, 15% of cases of endometritis, 2% to 15% of infected abdominal wounds after cesarean delivery, and about 15% of cases of bacteriuria in obstetric patients.

The 2002 CDC guidelines provide directions for collecting and processing these specimens (Table 19.1). These guidelines recommend a rectogenital specimen to obtain optimal yield of GBS.

There has been intense interest in tests for rapid identification of GBS. In one study, a polymerase chain reaction
(PCR) test reported excellent sensitivity, specificity, positive predictive value, and negative predictive value when compared with conventional anovaginal cultures. The reported laboratory turnaround time was 40 to 100 minutes for these PCR methods. The FDA approved an intrapartum rapid PCR test (IDI-Strep B, Infection Diagnostic Inc., Quebec, Canada). However, there are “real-world” limitations to this test, including turnaround time on a 24-hour, 7-day per week basis and inability to determine antibiotic susceptibility in women who cannot take penicillin or a cephalosporin. One role for PCR tests may be in testing women whose GBS status is unknown on admission in labor.

Tests from genital specimens other than PCR (such as antigen detection) are not sufficiently sensitive for clinical use.

Because resistance to penicillin or ampicillin has not been detected in GBS, penicillin, because of its narrow spectrum of activity, remains the agent of choice for GBS prophylaxis, with ampicillin as an alternative. Resistance to clindamycin and erythromycin among GBS isolates is widely prevalent, ranging from 7% to 30% for erythromycin and 3% to 15% for clindamycin. Resistance to also has been detected.

These resistance trends led to a revision of the first- and second-line antibiotics (Table 19.2). Because of the possibility of inducible resistance, the 2002 guidelines recommend that clindamycin or erythromycin be used only if a given patient’s GBS isolate was shown to have in vitro susceptibility to both. If there is in vitro resistance to either in a patient at high risk for penicillin anaphylaxis, then vancomycin should be used. For women at high risk of penicillin allergy colonized by clindamycin-resistant or erythromycin-resistant isolates, the 2002 guidelines recommend vancomycin. Because vancomycin use is restricted due to concerns regarding emerging vancomycin resistance, vancomycin should be reserved, in GBS prophylaxis, for highly penicillin-allergic women with isolates of unknown susceptibility and isolates with resistance to either erythromycin or clindamycin.

Because of its uniform activity, penicillin G remains the drug of choice for clinically evident maternal infection with GBS. Ampicillin is used widely and is an acceptable alternative. The usual dose of penicillin G is 5.0 million units intravenously initially, then 2.5 million units intravenously every 4 to 6 hours. Note that for prevention of GBS perinatal infections, the dosing interval is every 4 hours until delivery. For ampicillin, the usual adult dose is 2 g intravenously initially, then 1 g intravenously every 4 to 6 hours. Again, note that for GBS prophylaxis, the dosing interval is every 4 hours until delivery.

The indications for prophylaxis under this universal prenatal screening strategy are shown in Figure 19.2.

Membrane sweeping (or stripping) among term patients hastens the onset of labor, with no increases in overall perinatal or peripartum infection. However, because studies using this technique did not report GBS status, there are no data to advise whether this procedure should or should not be avoided in GBS-positive women. Nevertheless, because the benefits of membrane sweeping are limited (such as a significantly greater likelihood of onset of labor within 48 hours). The authors avoid membrane sweeping in GBS-positive women. If there is an indication for delivery, there are many alternative interventions to membrane sweeping, such as vaginal prostaglandin preparations.

Immunization holds promise to prevent a larger burden of disease, protecting against both early- and late-onset
infections. Moreover, vaccination may prevent some adverse pregnancy outcomes associated with GBS, such as preterm delivery, spontaneous abortion, or stillbirth, particularly if vaccination of adolescent girls before pregnancy is a viable strategy. Additionally, immunization strategies would not contribute to emerging antimicrobial resistance among GBS. Promising GBS vaccine candidates now exist but are not available commercially.

When exposure occurs in a pregnant woman, it is important to obtain her history regarding prior varicella infection. The diagnostic approach to the pregnant woman with possible varicella exposure is shown in Figure 19.3. With a prior history of typical chicken pox infection, she can be reassured. No serologic confirmation is required. In the setting of an inconclusive maternal history, a VCV immunoglobulin G (IgG) level should be checked urgently. Most laboratories can provide results of this in a day or so. If a woman’s IgG is positive shortly after exposure, this indicates prior immunity and she can be reassured. If her IgG is negative, she is susceptible to infection from the exposure. A significant exposure to varicella consists of a household contact, a face-to-face contact with an infected individual for at least 5 minutes, or an indoor contact with chicken pox or herpes zoster for at least 1 hour. If the woman meets these criteria, her varicella immunoglobulin M (IgM) antibody level should be measured. If her IgM is negative, immune globulin should be given to prevent transmission of the virus or lessen its severity. She should be given postexposure prophylaxis with varicella-zoster–specific immune globulin (VariZIG, FFF Enterprises, Temecula, CA). The adult dosage of VZIG is 625 U and is most effective when given within 96 hours of exposure. If VZIG is not available, 0.6–1.2 mL/kg of intravenous immune globulin (IVIG) can be given. In one trial, administration of VZIG to pregnant women within 96 hours of exposure was demonstrated to be highly efficacious in preventing 80% (20 of 25) of clinical infection. The 16 of 18 women who did not receive VZIG contracted infection. In addition, when VZIG was given between 3 and 10 days after exposure, the same group described attenuation of maternal infection.

Although most pregnant women will have self-limited infection, VZV during pregnancy has been associated with increased morbidity and mortality compared with nonpregnant adult infection (http://www.fda.gov/cber/ infosheets/mphvzig092005.htm). Symptomatic therapy with antipyretics and antipruritic agents that are safe during pregnancy can be used. Because of the high infectivity of
this virus, the patient should be properly isolated from other susceptible pregnant women. When diagnosis of maternal varicella is made, patients should be treated with acyclovir 800 mg orally five times daily for 7 days to decrease severity of infection, as it has been associated with a decrease in time to lesion healing and lessens fever and other symptoms. Five percent of women in the National Institute of Child Health and Development (NICHD) review of maternal varicella developed varicella pneumonia. Women with VZV infections during pregnancy should be given strict respiratory precautions, as a significant minority of women who develop varicella pneumonia will develop respiratory failure warranting mechanical ventilation, and their respiratory status can rapidly decompensate. Respiratory symptoms most likely will develop on the second day of rash, often consisting of dry cough, hemoptysis, pleuritic chest pain, and shortness of breath. Chest radiographs most often will show a miliary or diffuse nodular pattern. Varicella pneumonia should be treated aggressively with acyclovir 10 to 15 mg/kg given intravenously three times daily for 7 days. Higher doses of acyclovir are needed to treat varicella due to its lower specificity for VZV compared with HSV.

Newborn infection can occur if maternal infection with rash and symptoms develop from approximately 5 days before delivery until 2 days after delivery. This is the period in which there is insufficient time for maternal IgG antibody development and passive transfer to protect the fetus. Infection in the neonate usually will occur within 5 to 10 days of life and is of variable course but can be quite severe. Passive immunization of the exposed neonate with 125 U of VZIG is recommended if maternal varicella infection occurs within 5 days of delivery to 2 days following delivery as well as to any exposed neonate born at less than 28 weeks gestation, as IgG antibody transfer at premature gestational ages is less efficient. Although VZIG will not protect all neonates from varicella, it should reduce the severity of infection. Appropriate isolation of exposed infants should occur as well.

Varicella has been shown to cause fetal effects. Although first-trimester infection is associated with a low risk for miscarriage and anomalies (0.4%), the second trimester between approximately 12 and 20 weeks is the highest risk for vertical transmission causing serious fetal abnormalities (congenital varicella syndrome). Although vertical transmission has been estimated to be as high as 10%, more recent studies suggest this risk to be less than 2%. Fetal abnormalities include skin scarring, a variety of fetal central nervous system (CNS) abnormalities,
ophthalmologic effects, limb anomalies, and gastrointestinal abnormalities. These fetal effects are thought to be as a result of immaturity of the fetal immune system as well as intrauterine herpes zoster resulting in a predilection for neuronal cells and their downstream innervated tissues. There is no clear information regarding whether maternal administration of VZIG or acyclovir will lessen or prevent these fetal effects.

Approximately 4 to 6 weeks following resolution of maternal varicella infection, detailed ultrasound exams to evaluate for fetal effects should be performed. A subsequent ultrasound should be performed between 8 and 12 weeks to look for delayed effects.

Herpes zoster represents a reactivation of VZV and is commonly known as shingles. Although herpes zoster may be contagious to a nonimmune person by skin-to-skin contact, it is not spread by respiratory secretions. Fetal effects are not reportedly seen, as most herpes zoster infections do not result in viremia. Depending on dermatomal reactivation, intrauterine infection theoretically could be possible if the uterus were involved with reactivation of T10-L1 (which innervates the uterus). In most recent reviews, in utero transmission has not been reported without dissemination. These painful infections should be treated with acyclovir.

Postpartum vaccination of varicella-nonimmune women should be offered when breast-feeding has been completed. Since it is a live, attenuated vaccine, the ACOG and AAP recommended that women avoid conception for 1 month following vaccine administration, although the manufacturer recommends a 3-month delay (http://www. merck.com/product/usa/pi_circulars/v/varivax/varivax_pi.pdf). However, since vaccine virus has not been found to be excreted into breast milk, it has been suggested that vaccine administration not be delayed in nonimmune breast-feeding women.

Erythema infectiosum and fifth disease are two common names for parvovirus B19 infection. B19 is the only parvovirus known to cause human infection. It was not until 1984 that parvovirus B19 was first described as a cause of fetal infection and nonimmune hydrops. Only 30% to 60% of adults are immune to this virus. The incidence of parvovirus B19 seroconversion during pregnancy is 1% to 2% but may be higher than 10% during epidemics.

Parvovirus is a highly contagious infection, with an attack rate of 60% to 80% of susceptible household contacts, whereas only 20% to 30% of susceptible schoolteachers or day care workers will become infected following exposure. Infection is most common in late winter or spring and is transmitted by respiratory droplets and contaminated blood. Transplacental fetal transmission occurs in one third of cases, with risk of adverse fetal outcome in approximately 10%. Parvovirus is a strong inhibitor of hematopoietic cells, including liver, myocardium, and erythroid precursor cells. The P antigen on the red blood cell is a receptor for parvovirus B19; fetal cardiac myocytes are another receptor for the P antigen. Although maternal infection can be asymptomatic, some will develop symptoms including fever, myalgias, and malaise initially followed by arthralgias and sometimes pruritis and rash—commonly a “slapped cheek”–appearing rash in children. Uncommonly, meningoencephalitis, hepatitis, or myocarditis may occur with seroconversion. Symptomatic fetal infection is seen in approximately 10% and is associated with myocarditis; nonimmune hydrops; fetal demise; spontaneous loss; and rarely, neurologic complications. When hydrops occurs, it usually does so within 2 to 6 weeks of fetal infection, although the reported range is 1 to 12 weeks, with the maximal risk for development of fetal hydrops between 17 and 24 weeks gestation. Although the mechanism behind development of hydrops is incompletely understood, severe anemia leading to high-output cardiac failure is the likely pathophysiologic mechanism.

Diagnosis of maternal parvovirus B19 infection initially is made by serologic methods with enzyme immunoassay of B19 IgM and IgG. Antibodies of the IgM class will become measurable in 7 to 10 days following maternal infection, peaking at about 14 days then declining over 2 to 3 months. The IgG antibodies will rise more slowly, not peaking until about 4 months following acute infection. When IgG is positive on the initial specimen following exposure and IgM is negative, the patient demonstrates evidence of past infection. Immunity is lifelong, and she can be reassured that there is no fetal risk. If the first serum sample demonstrates negative IgM and IgG, acute seroconversion still may be occurring. Thus, repeat titers should be repeated 1 to 2 weeks after the initial titers were collected to study the evolution of the titers. To compare the sets of IgM/IgG antibodies most accurately, the laboratory should freeze the serum after running the first specimen to run together with the second specimen. Maternal B19 viremia will be present during acute seroconversion by DNA PCR, but persistent low-level viremia may persist for years following acute seroconversion. Thus, PCR testing for the virus is a less specific and a more expensive method of detection. New on the horizon include parvovirus B19 IgG avidity assays as well as IgG epitope specificity assays. These assays likely will be most useful in those patients with low-level parvovirus B19 IgM levels that may signify nonrecent seroconversion and may be associated with less, if any, fetal risk. Because fetal immunologic response is less pronounced, fetal and cord blood examinations should be confined to B19 DNA PCR.

Following confirmation of acute maternal seroconversion, fetal ultrasound examinations should be serially performed for 10 to 12 weeks following seroconversion to evaluate for fetal anemia as well as hydrops and other signs of fetal viral infection such as calcifications in the liver and myocarditis. Similar to Rh isoimmunization, anemic fetuses from parvovirus B19 infection will demonstrate increased blood velocity, as measured by peak systolic velocity in the middle cerebral artery. Ultrasound evidence of anemia usually will precede the development of fetal hydrops, allowing for optimization of fetal procedures such as percutaneous umbilical blood sampling (PUBS) and intrauterine transfusion (IUT). Hydrops, defined as fluid in two or more fetal body cavities, traditionally was defined as pleural effusions, pericardial effusions, ascites, and scalp edema but also may manifest as placental edema and be accompanied by amniotic fluid abnormalities. IUT to support the fetus during the parvovirus B19 suppression of hematopoiesis can prevent hydrops formation or cause it to resolve. Resolution of hydrops may take weeks despite correction of fetal anemia with IUT. Spontaneous recovery of parvovirus-induced hydrops has been described but is uncommon. Fetal mortality is higher when hydrops is present and is lessened with IUT. Prognosis following fetal recovery from in utero parvovirus infection usually is quite good, and only rare neurodevelopmental, cardiac, and hematologic sequelae have been reported.

T. gondii has a worldwide distribution and has been reported from wherever cats are found. It is somewhat more common in tropical and coastal regions and is less common in regions that are cold, warm and arid, or at high elevation. The infection rate in the United States is significantly lower than that in France. Within the United States, seroprevalence rates are lower in the western central and mountain states and higher in eastern Atlantic and eastern central states.

Acute toxoplasmosis generally is well tolerated in immunocompetent adults but may result in vertical infection to the fetus and lead to potentially serious consequences. In the immunocompetent adult host, symptoms usually are mild or inapparent. In about 10%, fever, fatigue, malaise, headache, myalgias, and lymphadenopathy will be present. These symptoms will resolve in weeks to months without specific therapy. In immunosuppressed adult patients, signs and symptoms often will be more pronounced and can result in significant ocular and CNS abnormalities. Reactivation infection in immunosuppressed pregnant women also can cause fetal infection.

T. gondii exists in three forms: trophozoites or proliferative form (Fig. 19.4), tissue cysts, and oocytes. The organism undergoes a substantial portion of its life cycle in the cat, where after between 5 and 8 days of infection, there is peak oocyte production. As many as ten million oocysts per day can be shed in feces for periods varying between 7 and 20 days. These oocytes sporulate within 1 to 3 days and can remain infectious for several months in moist soil. At that point, they may be carried from point of deposition by other animals (e.g., flies) and deposited in food. It also has been suggested that they can become airborne from a dried-out litter box and lead to human infection. Eating undercooked or raw meat that contains tissue cysts causes approximately one half of infections in most humans. In the human, the trophozoite form of T. gondii is seen in the acute phase of the infection, and it is during this phase that host cells are invaded. Thereafter, the organism multiplies every 4 to 6 hours until the cytoplasm becomes so filled with trophozoites that the cells rupture, releasing organisms to invade other cells.