GROUP B STREP: SCREENING, DIAGNOSIS, TREATMENT AND MAKING SENSE OF IT ALL
It is a well known fact in this modern era that humans, of any array of shapes and sizes, are inhabited at all times with microscopic organisms, that both dictate either the maintenance of our health or the sicknesses that we develop.
Group B Streptococcus (GBS) is one of those bacterial species that lives naturally in the human body, and is found commonly in the intestinal and vaginal flora. It is estimated that of all pregnant women, 20% are asymptomatically colonized in the vaginal and peri-anal region. Despite its apparently nonchalant behavior in the majority of cases where genital colonization with GBS does not result in clinical symptoms, under certain rare conditions, the bacteria can invade and pose significant harm to the pregnant mother and her baby.
There are certain factors that make a woman predisposed to overgrowth with GBS during pregnancy and cause illness include:
- Colonization with Candida species
- External genital erythema and scaling (a hypersensitivity reaction usually thought to be caused by infectious agents)
- Use of tampons
- Purulent vaginal discharge
- Vaginal pH over 5.0
When it comes to screening and testing women for the presence of GBS, a swab of both the vagina and the rectum is collected. The sample is then taken to a lab where a culture is analyzed for any presence of GBS. Test results are usually available within 24 to 48 hours.
In the unfortunate cases where there is vertical transmission of this bacteria during pregnancy, it may cause newborn babies to develop either of the two syndromes:
- Early-onset GBS disease which occurs in babies less than 7 days old, and
- Late-onset GBS disease which afflicts babies who are 7-90 days old.
Both early and late onset GBS diseases can manifest as bacteremia (the presence of bacteria in the blood), sepsis (a condition caused by the body's response to an infection), pneumonia (lung inflammation caused by bacterial or viral infection) , and meningitis (inflammation of the meninges, caused by viral or bacterial infection). In adults, severe infections can manifest as bacteremia (including sepsis) and soft tissue infections. Pregnancy-related infections include:
- Bloodstream infections (including sepsis)
- Urinary tract infection
Culture Based/Universal Intrapartum Antibiotic Prophylaxis Policy
Following a rather strict policy, Centers for Disease Control (CDC) and The American Congress of Obstetricians and Gynecologists (ACOG) currently recommend testing/screening all women prenatally at 35-37 weeks for their GBS status. If tested positive, the protocol is to start the mother on IV antibiotics during labor for every 4-6 hours until she delivers. This approach is known as screening/culture based protocol. Now if the GBS status of mother is unknown at the start of labor, she is also to receive the IV antibiotics. Moreover, if she is presenting with the following risk factors, this makes her a candidate for the universal antibiotic prophylaxis protocol as well:
- Preterm labor (before 37 weeks),
- Rupture Of Membranes for more than 18 hours,
- Intrapartum (during labor) temperature of 38 C or higher.
One might get the impression that mandating the universal prophylaxis policy across the U.S would reduce incidence rates of GBS disease? A 2009 Cochrane review could not find enough evidence to support the use of prophylactic antibiotics for women with GBS, stating that the studies which showed effectiveness in reducing early onset GBS were "poorly designed" and "had a high risk of bias". It further noted that there "has been no improvement with the Universal Prophylaxis policy" and concluded with the statement, "giving antibiotics is not supported by conclusive evidence".
Echoing along similar lines, a study published in the 2012 issue of Pediatrics Journal noted, "The rate of hospital admission for neonatal sepsis did not change significantly after the 2002 recommendations". [2002 is the year when the screening/culture based policy of universal intrapartum antibiotic administration to GBS positive mothers, regardless of the absence of risk factors, was sanctioned by the CDC].
It is estimated that up to 30-50% of babies born in the U.S alone are exposed to antibiotics during labor or after birth, without any substantial benefits to the mother-baby dyad, while in fact disrupting the acutely sensitive microflora of the newborn's gut. Plenty of immunology researchers have been pointing out that the healthy gut bacteria of a baby--which the baby acquires while passing through the birth canal of the mother--help activate specific genes that play a critical role in affecting mucous membrane function, the overall integrity of the immune system, as well as directing metabolic activities in the baby's body. Evidence is mounting that the bacterial strains first encountered by the nascent newborn gut at the time of birth, tend to persist in our bodies.
However, despite the strong link being established between a healthy microbial ecosystem and optimal health, scrupulous and blanket use of antibiotics during labor not only interferes with the mother's microbiome, but also exposes the baby to abundant colonies of yeast, and antibiotic resistant strain of E. coli, resulting in highly imbalanced colonization experience for the baby.
The profound loss of beneficial microflora could have been overlooked if this screening policy had had little to no gaps in its theory. However, it falls through the cracks. Pooling data from ten U.S states, a New England Journal of Medicine research piece exposed that 61% of GBS disease cases occurred in women who were screened, yet tested negative on lab results. As a record, 25-60% of GBS infections occur in women who test negative on the culture. With such high rates of missed cases of GBS infected mothers, the universal prophylaxis protocol is still what is recommended across the board. This policy exposes over a million pregnant women annually to antibiotics in an attempt to prevent a disease which is A. Rare, B. Usually identifiable and C. Generally treatable.
This rhetoric does not imply that women with high risk GBS infections should decline antibiotics, rather that the administration of these drugs should involve mindfully evaluating the clinical picture of the pregnant mother and weighing her odds with a risk vs benefit framework. To illustrate with an example, a woman who carries Group B Strep but has no conditions which raise risk, is by definition not at high risk of having a baby with the disease. The odds in this case of developing GBS disease work out to be less than 5 cases per 1000 live births. Instead of applying the universal prophylaxis approach to this group of low risk women and exposing them to antibiotics, the known risk factors should instead be identified, avoided or remedied appropriately. In essence, wouldn't it be better for the integrity of the mother-baby dyad that conditions that increase risk for infection are identified and steps taken to reduce them, OR waiting for the infection to aggravate to levels that has to be eventually treated with antibiotics during labor to save a baby who may already be infected in utero?
Risk Based Policy
Another approach towards GBS, followed once primarily in the U.K but is now being replaced with the screening based approach of the U.S, is risk factor approach which basically involves testing pregnant women only if they present with the following clinical symptoms:
- Preterm labor (less than 37 weeks gestation),
- Prolonged rupture of fetal membranes (more than 18 hours),
- Intrapartum fever (more than 100.4 F)
- Prior GBS infected infant (not GBS positive culture in a prior pregnancy)
- GBS bacteriuria in current pregnancy
After analyzing the practice of treating women based on if they presented with the above risk factors, it was concluded that this method was not only cost effective but also reduced chances of missing women who should be treated even though they tested negative on the culture. So rather than treating a large number of low risk GBS positive women, this simpler policy was found to prevent more cases of neonatal disease, not just infected with GBS, but also caused by other types of bacteria, and picked up women with false negative results.
A review published in 2019 in the British Medical Journal reviewed that “In 2014-15, under risk based prevention, 138 933 term pregnant women were colonized with GBS, but only 350 term neonates developed early onset infection, meaning screening would have led to over treatment of 138 583 (99.75%) women in labor.”
I would like to conclude this article with the review published in Journal of Tropical Pediatrics comparing Universal screening vs Risk based strategy for prevention of early onset GBS disease: "The present study addressed that there is a continued Early Onset GBS (EOGBS) disease despite the use of a screening and risk-based approaches to Intrapartum Antibiotic Prophylaxis (IAP). This might be caused by problems in prenatal and perinatal clinical practice, accuracy of GBS screening, communication of GBS-screening results, administration of IAP, the identification and treatment of neonates at risk for EOGBS and micro-biologic factors including antibiotic resistance."
And, "Failure to culture GBS even with ideal sampling and culture techniques may also be caused by maternal factors. The use of oral antibiotics or a variety of feminine hygiene products (including douches, vaginal Candidiasis medications and inert lubricants) before specimen collection may inhibit GBS growth in culture and contribute to false-negative results. There was no statistically significant difference between the two strategies (Universal screening vs Risk based approach)."
"Universal antenatal screening for group B streptococcus may cause more harm than good" [BMJ 2019;364:l463]
"Universal Screening vs. Risk-based Strategy for Prevention of Early-onset Neonatal Group-B Streptococcal Disease" [Journal of Tropical Pediatrics, Volume 57, Issue 6, December 2011]
"Evaluation of Universal Antenatal Screening for Group B Streptococcus" [N Engl J Med 2009; 360:2626-2636]
"Group B streptococcal disease in UK and Irish infants younger than 90 days" [The Lancet January 24, 2004]