Chlamydia, Group B Streptococcus, Cytomegalovirus (CMV)


Screening is recommended by immunofluorescent and antibody testing for those women at high risk, with treatment of those testing positive. The test should probably be performed in the third trimester, until efficacy for prevention of pre-term labor has been clarified. Chlamydia trachomatis has been generally detected in the cervix of approximately two percent to 13 percent of pregnant women, but the prevalence is as high as 25 percent in selected populations. The prevalence tends to be highest in young women (< age 20 years) and in those with a history of other sexually transmitted diseases. Most infected women are asymptomatic, but Chlamydia may cause urethritis and mucopurulent (nongonococcal) cervicitis. Chlamydia infection is also associated with postpartum endometritis and infertility. Infection may be transmitted from the genital tract of infected mothers to their neonates during birth; 60 percent to 70 percent of neonates born to infected mothers without prophylaxis acquire C. trachomatis. Purulent conjunctivitis occurs in approximately 30 percent to 50 percent of neonates born vaginally to women with chlamydia infection, and neonatal pneumonia occurs in 10 percent to 20 percent.

Important risk factors for chlamydia infection include single marital status, age younger than 20 years, residence in a socially disadvantaged community (e.g., inner city), history or presence of other sexually transmitted diseases, and little or no prenatal care. However, routine screening of all pregnant women for C. trachomatis is not recommended. Treatment should be administered to women with known C. trachomatis infection (i.e., with mucopurulent cervicitis) and to women whose sexual partners have nongonococcal urethritis and who are presumed to be infected when diagnostic tests are not performed. Erythromycin base is the drug of choice (500 mg four times daily for 10 days is effective; alternatively, erythromycin base, 250 mg four times daily for 15 days). Simultaneous treatment of the male partner or partners with tetracycline or doxycycline is an important component of the therapeutic regimen.

Chlamydia infections in the neonate are generally mild and responsive to antimicrobial therapy; prophylactic cesarean delivery is not warranted. Prophylactic instillation of topical erythromycin or tetracycline into the conjunctival sac of the neonate shortly after birth helps to prevent inclusion conjunctivitis. The effectiveness of 0.5 percent erythromycin ophthalmologic ointment in the prevention of chlamydia conjunctivitis in one study has not been confirmed in subsequent studies. C. trachomatis also is susceptible to tetracycline, but studies of clinical efficacy of tetracycline ointment in the prophylaxis of chlamydia conjunctivitis have also given conflicting results. Neither erythromycin nor tetracycline prevents chlamydia pneumonia. Neonates with inclusion conjunctivitis should be managed with drainage/secretion precautions. Those with chlamydia pneumonia should be managed similarly, and they should also be separated from neonates who are uninfected and neonates who are infected with other respiratory agents. Transmission of chlamydia infections within nurseries has been suspected, but not proved.

Group B Streptococcus

Group B Streptococcus (GBS) is the leading cause of perinatal bacterial infection in the United States.

Approximately 15 percent to 40 percent of pregnant women are asymptomatic carriers of GBS. Studies of the distribution of GBS by anatomic site have demonstrated that vaginal and rectal colonization is more common than colonization of the cervix or urinary tract. The rectum may be the depot site for chronic GBS carriage. The colonization rate shows both geographic and individual variability. For instance, vaginal cultures taken serially during pregnancy may be intermittently positive in the absence of specific therapy against GBS.

In the United States, approximately 12,000 proven neonatal GBS infections occur each year. Fifty percent of all perinatal GBS colonization is transmitted from mother to baby at parturition. Colonized infants may be born with or may develop early-onset (#7 days after birth) infections manifested by bacteremia, pneumonia, or meningitis. Of early-onset infections, two thirds are clinically apparent within six hours of birth. As a group, early-onset infections have a mortality rate of 15 percent or higher. While the overall attack rate (infection in colonized infants) for this form of early-onset neonatal sepsis sue to GBS is only 1-3/1,000 live birth, the attack rate is increased to 10/1,000 in babies born to mothers with perinatal vaginal colonization. This attack rate increases to as high as 40/1,000 (1/25) if there are additional risk factors, such as prematurity, prolonged rupture of membranes, amniotic fluid colonization, maternal fever during labor, or an infected prior child.

When neonatal GBS infection occurs after the first few days of life, meningitis becomes a predominant part of the clinical syndrome. The overall attack rate for this late-onset neonatal infection is 0.5-1.0/1,000 live births. The route of transmission in late-onset infections may be from mother to infant intrapartum (approximately 50 percent of cases) or from nosocomial or community sources.

Manifestations of symptomatic maternal infection due to GBS include chorioamnionitis, endomyometritis, cystitis, and pyelonephritis. It has been reported the rate of postpartum fever to be 22 percent in women colonized during the second trimester and only four percent in controls. The incidence of maternal puerperal infection due to GBS on a clinic service was shown to be 13/1,000 deliveries; 95 percent of these infected patients were delivered by cesarean birth. Heavy colonization of the genitourinary tract increases the attach rate for both mothers and babies. Cesarean delivery appears to be a particularly prominent risk factor for postpartum endomyometritis. Additional risk factors reported to have statistical significance include low serum antibody to the capsular antigens of GBS and maternal diabetes.

Culture is the usual method for the diagnosis of GBS colonization. The isolation of GBS may be enhanced by the use of selective broth media that inhibit the growth of other microorganisms. Use of non-selective broth (routine transport medium) and plating onto a non-selective solid medium (e.g., blood agar plates) diminishes the detection of GBS vaginal colonization by 50 percent or more. The only limitation of culture as a method is the time required for a result making its use most practical antenatally. A highly reliable rapid screening test for intrapartum detection of light and heavy GBS colonization of the lower genital tract is not yet available.

Rapid diagnostic tests based on direct identification of the group-specific polysaccharide antigen of GBS have been developed for commercial use. These tests use latex agglutination or enzyme-linked immunosorbent assay (ELISA) technology. In optimal circumstances, the result can be obtained in less than one hour from the time of specimen collection. Some of these tests may be suitable for use at the site of clinical care, rather than in a central laboratory. Rapid antigen tests may enhance clinical decision-making when a prompt decision is needed regarding antibiotics or delivery. However, the clinician should be aware that rapid tests will have both false-positive and false-negative results when compared with cultures.

Antigen tests will outperform the Gram stain, which is not recommended for screening. Both rapid antigen tests and culture methods can be adapted to provide a semi-quantitative measurement of the degree of GBS colonization. It is generally accepted that the likelihood of symptomatic perinatal infection increases with increasing colonization and that both cultures and rapid antigen tests yield more accurate results in patients with high counts of GBS.

No one site has been shown to be exclusively predictive of perinatal infection. Over the course of pregnancy, a positive culture site may spontaneously become negative, while a negative culture site spontaneously becomes positive. However, when antenatal lover vaginal and rectal cultures have been performed concurrently, their predictive value for maternal GBS colonization at delivery is 96 percent. When screening has been done, the patient should be informed of the result and of the factors that will require intrapartum antibiotic administration. The pediatrician should be informed of culture-positive antepartum patients who have had an uncomplicated delivery without antibiotic chemoprophylaxis.

Cytomegalovirus (CMV)

Of women susceptible to CMV, the risk of primary infection during pregnancy is approximately one percent of live births. Primary CMV infections during pregnancy are usually asymptomatic, but the probability of intrauterine transmission of infection to the fetus is approximately 50 percent. Only five percent to 10 percent of these congenitally infected infants have clinically apparent disease. Of those who do, the mortality ranges from 20 percent to 30 percent, and more than 90 percent of survivors develop significant sequelae. Of the congenitally infected infants who do not have clinically apparent infection as newborns, 10 percent develop late complications, with sensorineural hearing loss being the most common. Maternal infection can be either primary or recurrent, and both are associated with risks for the fetus, although these risks are far greater following maternal primary infection. Among susceptible women, namely those seronegative, the risk of seroconversions during pregnancy averages 2.0 percent to 2.5 percent; however, the rate of seroconversion is far higher among middle-and upper-class individuals than other groups. Maternal primary infection leads to fetal infection in approximately 40 percent of cases, and only 11 percent of infected infants have clinical manifestations of disease at birth. The risk of subsequent sequelae in this group is 10 percent. The risk of sequelae is higher when the maternal infection occurred prior to 20 weeks gestation.

Recurrent maternal infection is more common since as many as 10 percent to 12 percent of women who are seropositive can reactivate the virus during gestation. Maternal immunity to CMV, unlike rubella or toxoplasmosis, does not prevent either maternal virus reactivation or transmission of infection to the fetus. In a low socioeconomic population, the frequency of congenital infection as a consequence of maternal reactivation was 1.5 percent. It was significantly lower in a middle-classpopulation, being only 0.19 percent.

No specific recommendations can be made to prevent CMV infections of pregnant women. Routine serologic screening of pregnant women is not recommended because there is no reliable way to determine whether intrauterine infection or fetal disease has occurred, and the incidence is very low. In cases of severe I.U.G.R. it may be appropriate to rule out C.M.V. as an etiologic factor.

In general, the risk of neonatal disease with subsequent complications is higher if the mother has a primary CMV infection during the first half of pregnancy. Neonates of seronegative mothers are at risk of severe morbidity or death if they acquire CMV infection. Although the risk of congenital CMV infection is lower in seropositive mothers, perinatal infection can occur. These infections can be transmitted to neonates by transfusion of blood from seropositive donors or by ingestion of CMV-contaminated milk from human milk banks. Transmission of CMV by these routes can be virtually eliminated by the use of blood or milk from CMV-negative donors or of frozen deglycerolized red blood cells by removal of the buffy coat or by filtration to remove the white blood cells. The use of CMV hyper-immune globulin is under investigation.