Assistant Professor in Maternal Fetal Medicine, Division of Maternal Fetal Medicine, Department of Gynecology & Obstetrics, Johns Hopkins University School of Medicine, Baltimore
SYNOPSIS: In this cost-effectiveness study, screening for group B streptococcus (GBS) at 36 0/7 to 37 6/7 weeks, with rescreening (if GBS results are negative after five weeks of initial screening), is the most cost-effective strategy.
SOURCE: Williams M, Zantow E, Turrentine M. Cost effectiveness of latest recommendations for group B streptococci screening in the United States. Obstet Gynecol 2020;135:789-798.
Group B streptococcus (Streptococcus agalactiae, or GBS) is an anaerobic gram-positive bacterium that is a normal commensal in the lower genital tract of 5% to 30% of pregnant women.1,2 The prevalence of early-onset GBS disease in the United States varies by state, from 0.1-0.8/1,000 deliveries.3 GBS colonization in the female genital tract at the time of delivery is the most common route of fetal/neonatal infection, but risk factors for GBS during pregnancy include GBS bacteriuria in a current pregnancy, previous neonate with early-onset GBS, maternal pyrexia (> 38°C), prolonged rupture of membranes (> 18 hours), and preterm labor.4,5
GBS is the most common cause of early-onset neonatal sepsis, neonatal morbidity, and mortality in the United States, with case fatality rates as high as 15%.1,6 Because the predictive values of GBS swabs collected at < 36 weeks of gestation do not provide an adequate culture-to-delivery window that can allow for deliveries that occur at 41 0/7 weeks of gestation, the current recommendation is to collect genital swabs for GBS between 36 and 37 weeks of gestation.7 In 2020, the American College of Obstetricians & Gynecologists (ACOG) changed its GBS prenatal screening guidelines, encouraging screening for GBS at 36 to 37 weeks (as opposed to previous guidelines recommending screening at 35 to 37 weeks of gestation).8 To determine if this new gestational age screening window is cost-effective, Williams and colleagues conducted this cost-effectiveness analysis.7
For the purposes of the development of the decision analytic model, the pregnant cohort was divided into two universal GBS screening strategies: strategy A, GBS screening at 35 0/7 to 37 6/7 weeks of gestation, with those screening positive treated in the intrapartum period; and strategy B, GBS screening at 36 0/7 to 37 6/7 weeks of gestation, and rescreening for GBS if five weeks had elapsed from the initial screening (and the woman still was pregnant), with those screening positive treated in the intrapartum period.7 Both screening strategies (A and B) were compared to a reference scenario that treated cases of neonatal GBS disease in the absence of maternal GBS screening during pregnancy (no screening).
To parameterize their Markov model, the authors made a number of assumptions. First, there was no delay in the availability of prenatal GBS results at the time when pregnant women presented during labor; second, GBS culture was 100% sensitive in isolating women whose genital tracts were colonized with GBS; third, antibiotic prophylaxis was universally available at the time of delivery and would be administered for at least four hours during labor; fourth, all women who screened positive to GBS received intravenous antibiotics; and fifth, all women who reported a high risk for anaphylaxis to penicillin would have culture sensitivities performed and those who were penicillin allergic would receive appropriate antibiotic therapy.7 Women with clinical indications for antibiotic prophylaxis at the time of delivery (GBS bacteriuria in a current pregnancy, previous neonate with early-onset GBS, maternal pyrexia [> 38°C], prolonged rupture of membranes [> 18 hours], and preterm labor) were excluded from the analysis.7
In the analysis, the primary measure of effectiveness was neonatal quality-adjusted life years (QALYs). Health-related quality of life scores were calculated as the number of life-years for term neonates with early-onset GBS and long-term sequelae divided by normal life-expectancy.7 Direct medical costs and indirect lifetime costs were obtained from the literature, while the GBS screening culture and antibiotic costs were obtained from the Medicare Clinical Lab Fee Schedule of 2017.7 A one-way sensitivity analysis was performed, varying all base-rate parameters at one time using the lower and upper bounds of reported measures to estimate the minimum and maximum range of estimated costs. Mean incremental cost-effectiveness ratios (ICERs) were used to express cost-effectiveness under a willingness to pay threshold of $100,000/QALY gained. Costs were expressed in 2019 U.S. dollars, and health utilities were expressed in QALYs and discounted at 3% per year. Costs were examined from a healthcare and societal perspective and were derived using the consumer price index for healthcare.7
The authors demonstrated that strategy B (i.e., GBS screening at 36 0/7 to 37 6/7 weeks of gestation, and rescreening for GBS if five weeks had elapsed from the initial screening [and the woman was undelivered]) resulted in 3,723,641 pregnant women being tested (a 3% increase over women screened with strategy A), a 6% increase in neonatal QALYs gained (2,162 vs. 2,037), 12% fewer cases of neonatal deaths (30 vs. 34), and a 10% estimated reduction in total societal healthcare expenditures as the result of early-onset GBS disease ($639 million vs. $707 million) when compared to strategy A.7 These benefits in strategy B required a greater number of pregnant women treated with antibiotics to prevent one case of early-onset neonatal GBS compared to strategy A (261 vs. 245). Earlier onset GBS cases were prevented with strategies A and B compared to no GBS screening. An estimated $1.26 billion (range $682 million to $1.83 billion) in direct and indirect healthcare costs were saved with strategy B when compared to no intervention, while an estimated $73 million (range $39 million to $106 million) in direct and indirect healthcare costs were saved with strategy B when compared to strategy A. Strategy B was most cost-effective for neonatal costs and QALYs gained, with an ICER of $43,205/QALY gained. One-way sensitivity analysis results remained robust and showed mean ICER for costs and probabilities that were lower than a willingness to pay threshold of $100,000/QALYs gained.
The United States first embarked on a universal prenatal screening strategy for GBS in 2002, following a publication by the Centers for Disease Control and Prevention (CDC) that demonstrated screening for GBS was cost-effective.9 While universal screening for GBS currently is recommended in the United States at 36 0/7 to 37 6/7 weeks (irrespective of the anticipated route of delivery, vaginal or cesarean), some centers still practice risk-based screening, with the rationale that one-quarter of women who screen positive to GBS prior to 36 to 37 weeks of gestation will screen negative at the time of delivery, and many women who screen GBS positive do not transmit GBS to their fetuses (even when they go untreated).10 Hence, there currently is a debate whether screening for GBS at 36 0/7 to 37 6/7 weeks of gestation is cost-effective.
Williams and colleagues demonstrated that universal screening for GBS at 36 0/7 to 37 6/7 weeks of gestation is cost-effective.7 In addition, screening for GBS meets the Wilson and Jungner’s criteria, which includes that GBS remains an important health problem; GBS infection has a well-described latent stage and natural history; there are suitable testing algorithms for GBS diagnosis and treatment; case finding for GBS involves a continuous process; and the total cost of finding a case of GBS during pregnancy is economically plausible when compared to the alternative of no screening, resulting in early-onset neonatal GBS infection.11
The ACOG practice bulletin recommends intrapartum antibiotic prophylaxis for pregnant women who screen positive for GBS in a current pregnancy.8 Antibiotic prophylaxis also is recommended for pregnant women who are GBS unknown presenting in labor with risk factors for GBS (GBS bacteriuria earlier in pregnancy, preterm labor, history of a previous neonate with early-onset GBS, maternal pyrexia [> 38°C], and prolonged rupture of membranes [> 18 hours]). The recommended treatment regimen is with intravenous benzylpenicillin (penicillin G), 5 million units as a loading dose, followed by 3 million units every four hours until delivery. To optimize the efficacy of intrapartum therapy, the first dose of benzylpenicillin should be at least four hours prior to delivery. Pregnant women with mild penicillin allergy (e.g., rash) are treated with intravenous cefuroxime 1.5-g loading dose, followed by 750 mg every eight hours until delivery, while those with severe penicillin allergy (e.g., hives, anaphylaxis) are best treated with intravenous vancomycin 1 g every 12 hours until delivery. Clindamycin is used in GBS-positive women with low risk for anaphylaxis and confirmation that the GBS is susceptible.8
In conclusion, universal screening for GBS at 36 0/7 to 37 6/7 weeks of gestation, with rescreening (if GBS results are negative after five weeks of initial screening), as recommended by ACOG, is cost-effective, and therefore should be practiced.8
- Raabe VN, Shane AL. Group B Streptococcus (Streptococcus agalactiae). Microbiol Spectr 2019;7:10.
- Campbell JR, Hillier SL, Krohn MA, et al. Group B streptococcal colonization and serotype-specific immunity in pregnant women at delivery. Obstet Gynecol 2000;96:498-503.
- Zaleznik DF, Rench MA, Hillier S, et al. Invasive disease due to group B streptococcus in pregnant women and neonates from diverse population groups. Clin Infect Dis 2000;30:276-281.
- Colicchia LC, Lauderdale DS, Du H, et al. Recurrence of group B streptococcus colonization in successive pregnancies. J Perinatol 2015;35:173-176.
- Turrentine MA, Colicchia LC, Hirsch E, et al. Efficiency of screening for the recurrence of antenatal group B streptococcus colonization in a subsequent pregnancy: A systematic review and meta-analysis with independent patient data. Am J Perinatol 2016;33:510-517.
- Odabasi IO, Bulbul A. Neonatal sepsis. Sisli Etfal Hastan Tip Bul 2020;54:142-158.
- Williams M, Zantow E, Turrentine M. Cost effectiveness of latest recommendations for group B streptococci screening in the United States. Obstet Gynecol 2020;135:789-798.
- [No authors listed]. Prevention of group B streptococcal early-onset disease in newborns: ACOG Committee Opinion, Number 797. Obstet Gynecol 2020;135:e51-e72.
- Cowgill K, Taylor TH Jr, Schuchat A, Schrag S. Report from the CDC. Awareness of perinatal group B streptococcal infection among women of childbearing age in the United States, 1999 and 2002. J Womens Health (Larchmt) 2003;12:527-532.
- [No authors listed]. Prevention of early-onset neonatal group B streptococcal disease: Green-top Guideline No. 36. BJOG 2017;124:
- Wilson JM, Jungner YG. [Principles and practice of mass screening for disease]. Bol Oficina Sanit Panam 1968;65:281-393.