Preventing perinatal transmission of group B streptococcal disease

Jennifer Freer, PA-C, MSPAS

Ms. Freer works at Hamot Primary Care Network in Erie, Pa. The author has indicated no relationships to disclose relating to the content of this article.

Recent data suggest that more can be done to reduce the incidence of early-onset group B strep disease in newborns.

Infection with Streptococcus agalactiae—group B streptococcus (GBS)—is the leading cause of sepsis and meningitis in newborns in the United States.¹ This gram-positive coccus is characterized by the narrow zone of ß-hemolysis that forms when the bacterium is cultured on blood agar.¹ It first emerged as an important pathogen in the 1970s.² GBS is not contagious, although colonization is common in humans, with the pathogen present in the lower intestines of 10% to 35% of healthy adults and in the vagina or lower intestine of 10% to 35% of healthy adult women.³ Rarely, the bacteria invade the body and cause serious infection, known as GBS disease.³

In pregnant women, GBS disease can cause clinical illness ranging from mild urinary tract infection to life-threatening meningitis or sepsis. Aggressive disease in pregnant and postpartum women occurs when GBS is isolated from a normally sterile site, primarily the blood or CSF. Other aggressive maternal infections caused by GBS are osteomyelitis and endocarditis. Noninvasive syndromes in pregnancy and the postpartum period thought to be due to GBS include chorioamnionitis, endometritis, and postcesarean and postepisiotomy wound infections.⁴ The most significant manifestations of GBS disease in infants are sepsis and meningitis,^2,4 although infection with GBS is increasingly recognized as a cause of preterm delivery, with intra-amniotic infection having a role in both spontaneous preterm labor and premature rupture of membranes.⁴

Transmission of GBS to neonates

Neonatal infection with GBS occurs in 1% to 2% of infants whose mothers are colonized with GBS. Transmission usually occurs during labor and delivery as the infant passes through the birth canal or swallows or inhales the bacteria. Approximately 50% of infants born to colonized mothers are themselves colonized on the skin and surface mucosa.¹ Exposure may occur when bacteria enter the uterus from the vagina, and there is evidence that GBS may cross intact membranes, causing in utero exposure.³

The human body has a natural immune response to the presence of GBS involving IgG antibodies and the complement pathway, which may explain why colonization poses little risk of disease for carriers. Only 10% to 20% of women have antibody concentrations sufficient to kill GBS strains, and newborns lack protective levels of necessary antibodies.³ A premature infant of a mother with insufficient antibodies is more vulnerable to GBS disease than an older infant because the transport of IgG across the placenta from mother to baby is reduced early in gestation.⁴

Few infants born with GBS infection appear to be ill during the first few days of life; those who do appear ill exhibit signs of sepsis, pneumonia, or meningitis.^1,4 These signs of early-onset (within the first week of life) GBS disease include grunting, fever, seizures, unusual behavior, stiffness or extreme limpness, and problems with temperature regulation or breathing.³ A neonate who has early-onset GBS disease will have acquired the bacteria that ascended the mother's birth canal and crossed into the amniotic fluid.⁴

Late-onset infection occurs at 1 week to 3 months of age. Although the etiology of late-onset disease is not well understood, most cases are thought to be due to acquisition of the organism during passage through the birth canal.⁴ Meningitis is a more common sequela in late-onset GBS disease. An infant with late-onset disease may present with stiffness, limpness, inconsolable screaming, fever, or refusal to feed.³

Lessons learned in preventing perinatal transmission

Risk factors for GBS colonization in pregnancy and for perinatal transmission are shown in Table 1.

 

TABLE 1 Risk factors for colonization and for perinatal transmission of GBS

Colonization Previous colonization with GBS Low socioeconomic status African-American race Mother <20 y Perinatal transmission Positive GBS culture at 35-37 wk gestation GBS in urine sample Previous delivery of an infant with GBS Invasive obstetric testing or manipulation Preterm delivery (<37 wk) Rupture of amniotic membrane (>18 h) Maternal temperature during labor >38°C (>100.4°F)

Source: Gotoff² and Group B Strep Association.³

In 1996, the CDC, in conjunction with the American Academy of Pediatrics (AAP) and the American College of Obstetricians and Gynecologists (ACOG), published guidelines for preventing intrapartum transmission of GBS from mother to child. The guidelines suggested two strategies that were considered equally acceptable:^2,5-7 a screening approach, using late prenatal screening culture techniques, and a risk-based approach, in which women who had any of the known risk factors for transmitting GBS were given intrapartum IV antibiotics. The women in the risk-based approach were not tested for GBS; the use of antibiotic prophylaxis was based solely on the presence of risk factors for transmitting GBS from mother to baby. Some clinicians also included women who had risk factors for colonization.^2,6,7 Clinicians who chose the screening approach tested women for GBS colonization late in pregnancy, using cultures obtained from the cervix or rectum. Women whose cultures were positive for bacteria were given antibiotic prophylaxis during labor.^7,8

Reviewing the data, and revising the guidelines

Researchers from the CDC analyzed GBS transmission data from 5,144 births reported in 1998 and 1999. Approximately half of the mothers were tested for GBS colonization. The data showed that infants whose mothers were tested for GBS colonization were 54% less likely to develop GBS disease than were infants whose mothers were not tested, leading the researchers to conclude that the screening approach is at least 50% more effective than the risk-based approach and that the screening approach allows clinicians to detect colonization with GBS in the absence of risk factors: 63% of infants in the CDC study who developed GBS were born to mothers who had no risk factors for either colonization or transmission. In 2002, the CDC revised the 1996 guidelines to reflect these findings.

Optimizing prophylaxis

Although administration of antibiotics to the mother during labor and delivery has been shown to reduce the rate of GBS disease in neonates, the timing of testing and administration is important to a successful outcome (see Figure 1).

Click here to view full-size graphic

First, culture specimens collected between 35 and 37 weeks' gestation are more likely to provide a truer assessment of the status of vaginal and GI flora at delivery.² Second, if preterm labor occurs before a culture specimen is collected, the mother's colonization status remains unknown and the risk of transmission of GBS remains. Some experts have suggested adding chemoprophylaxis to preterm labor protocols. Antimicrobial prophylaxis for infants has also been recommended.^2,7,9

The source of the culture specimen is an additional factor. Some clinicians collect only cervical samples, although studies have found that nearly 20% of patients who were colonized with GBS had negative vaginal cultures despite positive rectal cultures.¹⁰ Clinicians should obtain both vaginal and anorectal cultures when screening for GBS in pregnant patients.¹⁰

Penicillin is the recommended first-line agent for GBS prophylaxis, with ampicillin an acceptable alternative. Clindamycin (Cleocin) and erythromycin are some of the acceptable alternatives for women who are allergic to penicillin (see Table 2).⁴

 

TABLE 2 Prophylaxis against GBS disease: Recommended regimens
Regimen	Drug and dosage
Standard	Penicillin G, 5 million U IV initially, then 2.5 million U IV q4h until delivery
Alternative	Ampicillin, 2 g IV initially, then 1 g IV q4h until delivery
If patient is allergic to penicillin and is not at high risk of anaphylaxis	Cefazolin, 2 g IV initially, then 1 g IV q8h until delivery
If patient is at high risk of anaphylaxis and GBS disease is susceptible to clindamycin and erythromycin	Clindamycin, 900 mg IV q8h until delivery OR Erythromycin, 500 mg IV q6h until delivery
If patient is allergic to penicillin and GBS is resistant to clindamycin or erythromycin or susceptibility is unknown	Vancomycin, 1 g IV q12h until delivery
Note: See “Box 2” in source for additional details about these regimens.
Adapted from Schrag S, Gorwitz R, Fultz-Butts K, Schuchat A. Prevention of perinatal group B streptococcal disease. Revised guidelines from CDC. MMWR Morb Mortal Wkly Rep. 2002;51(RR-11):1-22. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5111a1.htm . Accessed February 24, 2004.

Clinical procedures and GBS transmission

Obstetric procedures that promote the ascent of GBS from the vagina to the amniotic fluid (such as chorionic villus sampling, intrauterine monitoring, and vaginal examinations) can increase the risk of transmission. Some procedures such as bladder catheterization or the use of enemas during the intrapartum period can theoretically increase the risk of GBS transmission but have not yet been linked to the disease.⁴ In addition, cesarean delivery will not necessarily prevent GBS transmission from a colonized mother to her newborn; GBS can cross intact membranes, and interventions less invasive than surgery are more effective means of blocking vertical transmission of GBS.⁴

Other practices can provide insight into GBS pathogenesis and prevention. For example, one center attributed its low rate of GBS transmission to the use of systemic penicillin prophylaxis to prevent ophthalmitis neonatorum, compared to the rates at other centers that used a topical drug for this purpose.⁴

The future of prevention

Current research is targeted at developing a GBS vaccine that would stimulate the immune systems of pregnant patients to make antibodies that could cross the placenta later in pregnancy and protect the baby in utero. This immunoprophylaxis approach appears to be the most cost-effective strategy for eliminating the problems related to obtaining culture specimens. Any vaccine would, of course, have to be safe for use in pregnancy.^2,3 Because GBS serotype III causes the majority of GBS disease, vaccine development was concentrated first on this antigen, although clinical trials are currently evaluating combination vaccines that include other serotypes.

The initial approach to GBS immunization was to administer a vaccine during the second trimester, after organogenesis is complete but early enough to permit antibody production. Another approach is to administer the vaccine as part of routine adolescent immunization regimens. Some investigators have even suggested that GBS vaccines be administered with childhood immunizations, since vaccine delivery systems in the United States are efficient in reaching this age group.⁴ Although widespread use of a vaccine is still years away, protecting infants and others from this bacterial infection with a vaccine looks promising.³

 

The word on GBS prevention—and getting it out The Centers for Disease Control and Prevention (CDC) offers access to a wealth of information about group B streptococcal (GBS) disease for patients, providers, and laboratories. Go to www.cdc.gov/groupbstrep , click on "Hospital & Health Care Providers," and link to • "New Guidelines" for the new guidelines in their entirety, as published in Morbidity & Mortality Weekly Report; 2002;51(RR-11):1-22 • "Professional & Patient Resources" for patient handouts, instructions for performing a genital swab, sample prenatal testing cards for tracking screening results, and a list of readings, among other information. This screen also provides a link to the Web site of the American College of Obstetricians and Gynecologists (ACOG), from which you can order a patient pamphlet entitled "Group B Streptococcus and Pregnancy." Another link, to the American College of Nurse-Midwives (ACNM) site, provides access to a list of frequently asked questions about GBS and their answers • "Slide Sets & Other Tools" for access to slide presentations on clinical issues and an introduction to the new guidelines and recommendations for laboratory processing of specimens • "For More Information" for a list of patient brochures and flyers about GBS and reprints of the complete GBS guidelines that can be ordered from the CDC

 

KEY POINTS in this article Candidates for intrapartum antimicrobial prophylaxis against group B strep transmission are identified using a single strategy—prenatal screening. Specimens should be collected from all pregnant women who are between 35 and 37 weeks' gestation; intrapartum antibiotic prophylaxis is used for mothers whose cultures are positive. Intrapartum antimicrobial prophylaxis regimens center on the use of penicillin; second-line agents can be used in women with penicillin allergy.

REFERENCES

1. Schuchat A. Prevention effectiveness case study: Institutionalizing prevention of group B streptococcal infections. Available at: http://www.phppo.cdc.gov/dls/pdf/institute/schuchat.pdf . Accessed January 13, 2004.

2. Gotoff SP. Group B streptococcal infections. Pediatr Rev. 2002;23:381-386.

3. Group B Strep Association. Awareness of group B streptococcus infection during pregnancy: help protect your baby and yourself. Available at: http://www.groupbstrep.org/gbs/Files/pamphlet.pdf . Accessed January 13, 2004.

4. Schuchat A. Epidemiology of group B streptococcal disease in the United States: shifting paradigms. Clin Microbiol Rev. 1998;11:497-513.

5. Keenan C. Prevention of neonatal group B streptococcal infection. Am Fam Physician. 1998;57:2713-2720,2725.

6. Towers CV, Rumney PJ, Minkiewicz SF, Asrat T. Incidence of intrapartum maternal risk factors for identifying neonates at risk for early-onset group B streptococcal sepsis: a prospective study. Am J Obstet Gynecol. 1999;181(5 pt 1):1197-1202.

7. Eschenbach DA. Prevention of neonatal group B streptococcal infection. N Engl J Med. 2002;347:280-281.

8. Schrag SJ, Zell ER, Lynfield R, et al. A population-based comparison of strategies to prevent early-onset group B streptococcal disease in neonates. N Engl J Med. 2002;347:233-239.

9. Berner R. Group B streptococci during pregnancy and infancy. Curr Opin Infect Dis. 2002;15:307-313.

10. Quinlan JD, Hill DA, Maxwell BD, et al. The necessity of both anorectal and vaginal cultures for group B streptococcus screening during pregnancy. J Fam Pract. 2000;49:447-448.

 

Jennifer Freer. Preventing perinatal transmission of group B streptococcal disease. JAAPA March 2004;17:47-50.

Copyright © 2004, Advanstar Medical Economics Healthcare Communications at Montvale, NJ 07645-1742. All rights reserved.

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