Part I: GBS (Group Beta Strep)

I had been thinking it was best for moms to test for GBS at 36 weeks.  My rational was not driven by the belief that testing is necessary but rather by the wish to avoid the following scenario; if a mom enters a hospital in our area without a GBS negative result, even if the baby is asymptomatic, the baby will undergo a septic workup, often including a spinal tap, and the baby may be kept for observation and the mom sent home. 

Recently I have realized that the GBS  problem is much more complicated then merely testing and hoping for a negative result.  Testing can lead to a positive result which again leads to the scenario of the septic work up/spinal tap/separation. And testing can imply condoning the existing non-evidenced based GBS protocol (see for example the gold standard Cochrane review). 

You can argue that you should recommend GBS testing so that mom has more information, information that may influence how she care for herself in the last few weeks of her pregnancy.  But isn't that the mom's decision?  More information might be too information for the worry wort. I think the answer is to provide mom with the current research (which is full of gaps) and make space to let mom decide on her own the best path (isn't this always the best, empowering, course of action!). 

The recent Midwifery Today article by Judy Slome Cohain, CNM "Newborn Group B Strep Infection: Top Ten Reasons Not to Culture at 36 Weeks" (Issue 94, Summer 2010) prompted me to contact Judy.  She gave me permission to reprint her article below. I think it is fabulous food for thought as moms begin to navigate the decision making process of deciding whether or not to test.

GBS Disease of the Newborn in 2010:   Top 10 Lists: Things We Know and Things We Don't

By Judy Slome Cohain, reprinted with permission.

1. Culturing at 36 weeks and treating GBS positive women prophylactically in labor has not been shown to decrease newborn GBS disease by RCT study  (1).  The use of risk-based management results in  the same rate of GBS disease as culturing at 36 weeks and treating GBS positive women prophylactically in labor.  “Implementation of universal screening was expected to result in a 30% further decline in the incidence of EOD, with the most dramatic reductions anticipated among term infants, because screening is performed during 35-37 weeks of gestation....The overall EOD incidence rate showed an initial downward trend from 2000 to 2003 (0.52 to 0.31 cases per 1,000 live births), followed by an increase from 2003 to 2006 (0.31 to 0.40 cases per 1,000 live births.....This increase was not anticipated and cannot yet be explained.” (23)

2. Premise that GBS cultures are accurate for 5 weeks is based on a single study of 116 women.(2)  Larger studies failed to reproduce their results and have shown GBS cultures taken 24 hours before the woman gives birth are less than 30% accurate when compared to cultures taken at the time of birth.(3, 4)

3. Reports of Penicillin resistant GBS began to appear in 2007 (5). One study already found 10% of GBS cultured from women Pen-Resistant(6). If Pen-Resis GBS follows the evolution of Pen-Resis Strep pneumoniae which was first isolated in 1972(8),  in 2035, 50% of GBS will be unsusceptible to Penicillin(9). If the evolution of Pen Resistant GBS  were to resemble the development of MRSA, in 2055, 50% of GBS will be unsusceptible to Penicillin(7).   It is unknown whether giving 1 million American women per year mega doses of IV Penicillin in labor will speed the process of the evolution of Penicillin resistance in GBS. There is scant hope for miracle drugs as no new antibiotic families have been discovered since 1960. (10) 

4. 7%-10% of women cannot be given Penicillin due to allergic reactions.    The first line of alternatives is Clindamycin or Erythromycin, however about 50% of GBS is currently ‘resistant’ to the Clindamycin and/or Erythromycin. When the GBS is resistant to Clindamycin and Erythromycin, Vancomycin is given, often causing strong side effects like hypotension, RED MAN syndrome i.e. hives, histamine reaction and feeling lousy.

5. The 2002 CDC GBS protocols declared on page 16 that prophylactic antibiotics are only a temporary solution because of expectation that Penicillin resistant GBS will develop, however a definition for temporary was absent from the protocols.  The only alternative considered so far has been giving newborns routine antibiotics, which caused an increased death rate.

6. A GBS vaccine is never going to happen, because the surface antigens of GBS mutate too quickly to be effective as a vaccine given before pregnancy and the legal liability of giving pregnant women vaccines is too great.

7. 1 in 10,000 women have serious anaphylactic reactions to Penicillin (1)

8. Vaginal GBS is 2 to 3 times more prevalent in the USA than in third world countries (11)

9. Research conducted at NIH (13) found Penicillin use during labor was associated with a 2.6-fold increase in respiratory distress (nasal flaring, grunting, retraction or tachypnea (respiration rate =60 breaths/minute)  within 48 hours after birth in the absence of Early Onset GBS disease among 1,600 colonized newborns >32 weeks gestation.  95% were over 37 weeks gestation. Among colonized newborns of penicillin-treated mothers, 20.4% had respiratory distress compared with 6.9% of colonized newborns of untreated mothers.    In reaction to penicillin, Streptococcus mutans releases phospholipids immediately, which are known to cause pulmonary hypertension in experimental animals.  The increased respiratory distress in newborns colonized with GBS in which the mother was treated with Penicillin in labor may due to the phospholipids used by GBS as a defence to Penicillin. Being heavily or lightly colonized was not a significant factor in the development of early onset GBS or respiratory distress.  All antibiotics during pregnancy may increase allergies and asthma in children(14).

10. Telling 25% of pregnant women they are infected with a bacteria  that may be deadly to their fetus often has a terrifying psychological affect on the mother, which has unexplored affects on the fetus.

Top 10 things about GBS of the newborn for which there is a lack of research:

1.  How many full term babies are permanently injured (not  killed) from GBS disease of the newborn?  How many experience each of the various types (deafness, learning disabilities, CP) of morbidity?

2. Do prophylactic antibiotics to GBS positive women prevent or decrease long term GBS morbidity in full term newborns (vs. mortality)?

3. The presence of GBS antibodies in the mother has been shown to be protective against Newborn GBS(10).  Women with high titers of antibodies to GBS are thought to pass on immunity to GBS to their fetus and thereby have less GBS infected babies. Smokers, drug abusers, obese and immune suppressed women produce less antibodies.  Are they more likely to have a baby with GBS disease? Is some/most/all GBS disease of the newborn associated with women with low titers of antibodies to GBS?

4. There is only one published study asking whether pregnant women who culture GBS positive in urine, also culture positive in rectovaginal culture.  Of 1036 assymptomatic women who underwent routine urine culture in pregnancy, 10.7% had GBS in their urine, of those 70% of those had <10,000 CFU (colony forming units) and 30% had >10,000 CFU which is considered highly colonized. Of the 111 women who had GBS in their urine (bacteriuria), 40% cultured negative for GBS on rectovaginal swabs. Women who were heavily colonized in urine were no more likely than those lightly colonized in urine to have  positive rectovaginal cultures. (16)

Approximately 11% of women colonized positive for GBS in urine and their healthy babies culture positive for GBS than other babies, however no one has ever documented higher rates of GBS DISEASE associated with maternal GBS bacteriuria. GBS in urine has been associated with chorioamnionitis- uterine infections in the mother- which is most closely associated with prolonged labors, as well as frequent vaginal exams, internal monitoring, prolonged ROM, cesareans, and teenage pregnancies,  but to date not documented to be associated with GBS disease of the newborn.

There are many claims that antibiotics during pregnancy given to women wiht GBS bacteriuria can prevent preterm birth, but this data is confounded by studying high risk populations. A RCT study contradicts this claim, found that women with GBS bacteriuria, additional exposure to antibiotics is associated with an increased, not decreased, risk of preterm birth.  In this study the rate of preterm birth for women with bacteriuria was 16% and without GBS bacteriuria was also 16% and 28% among women with GBS bacteriuria who received antibiotics. (17)  All three rates reflect outcomes only seen in extremely high risk populations. Healthy, well fed populations,   the preterm rate is 7%.   Asymptomatic  GBS bacteriuria may not have a role in preterm birth but rather may be a marker for low socioeconomic status which is associated with low birth weight. (18) The quality of even the best studies on asymptomatic bacteriuria in pregnancy is poor. (18)

The unanswered question is: Do heavily colonized full term women have more GBS newborn disease or perhaps less newborn GBS due to higher titers of antibodies against GBS that they pass to the fetus?  Are women who heavily colonized  with GBS, whether in urine or vagina,  more likely or less likely to have babies with GBS disease?  We dont know.

Does giving oral antibiotics to pregnant women with asymptomatic GBS bacteriuria decrease or increase the occurrence of GBS disease of newborn?  

5. 50% of GBS disease of the newborn occurs to babies of women with the following risk factors: Premature, IUGR, LBW, ROM > 18 hours, and fever.  The other 50% occurs to babies of women without those risk factors.  Of those women, how many had ROM between 2 and 17.9 hours?  Since prolonged ROM is known to increase the risk of GBS disease, how would eliminating AROM affect the occurrence of GBS disease of newborn? 

Is there a difference in the GBS disease among women with impressive, flowing ROM which fills up pads quickly and women who have a high leak that is leaks 1 to 2 cc per hour?  Is a high leak a risk of newborn GBS at all?

6. On page 11 of the 2002 CDC protocols appears one of several unqualified statement “GBS can cross intact amniotic membranes.”   A study of 550 babies born to GBS positive women, by CS without ROM, and without prophylaxis, demonstrated not a single case of GBS disease, where one would expected 5 sick newborn if GBS crossed membranes, supporting the theory that GBS either never crosses membranes. In vitro study has not been able to demonstrate GBS crossing membranes, even at concentrations of 1,000,000,000 CFU.  (20) Further investigation into how GBS could cross intact membranes demonstrated that GBS failed to invade amnion cells under a variety of assay conditions (21) and fetal membranes demonstrated an inhibitory effect on GBS. (22).  Cases of  colonized infants born by CS in the absence of ruptured membranes could be due to any number of other vectors other than the mother that come in contact with the baby.

7. Over 6 vaginal exams significantly increased rates of GBS disease(15).  Scalp electrodes double the risk of GBS colonization of amniotic fluid (19)

In my practice, with restricted AROM and Vaginal exams and no scalp electrodes, 3% of births the baby’s head comes out in the sac and never makes direct contact with the uterus, cervix or vaginal walls at all. How would restricted AROM, Vaginal exams and scalp electrodes affect GBS disease rates?.among low risk women? Among high risk women?

  

8. When does GBS cause disease? 99% of babies colonized with GBS, dont get GBS disease.  99.99% of women colonized with GBS, dont get GBS vaginitis. Why does GBS sometimes attack and sometimes live in ecological balance?   Why is GBS present in 2-3 times as many women in the USA than in Ireland, Cambodia, Taiwan, Philippines or Africa?  (11)  Why is long term (over 6 months duration) Symptomatic GBS Vulvovaginitis becoming more common in the western world? (12)

9.  How does GBS inhibit lactobacillus growth?

10. How many newborns will die of GBS disease in 10 years? 20 years? 40 years?

In the presence of so many unknowns, current protocols reflect an bias to take action in the presence of a lack of appreciation or humility for the complex habits of GBS and no consideration of the next generation of newborns. 

1. Ohlsson A, Shah VS. Intrapartum antibiotics for known maternal Group B streptococcal colonization. Cochrane Database of Systematic Reviews 2009, Issue 3. Art. No.: CD007467

2. Yancey MK, Schuchat A, Brown LK, Ventura VL, Markenson GR.The accuracy of late antenatal screening cultures in predicting genital group B streptococcal colonization at delivery. Obstet Gynecol 1996;88:811–5.

3. Itakura A.Kurauchi O Morikawaa S, Matsuzawab K Mizutania S, Tomodaa Y. Variability of peripartum vaginal group B streptococcal colonization. International Journal of Gynecology & Obstetrics 55 (1996) 19-22.S

4. Tamerou Asrat, et.al.The accuracy of late third trimester antenatal screening for group B streptococcus in predicting GBS colonization at delivery American Journal of Obstetrics and Gynecology, Volume 195, Issue 6, Supplement 1, December 2006, Page S40

5. Chu YW, Tse C, Tsang GK, So DK, Fung JT, Lo JY. . Invasive group B Streptococcus isolates showing reduced susceptibility to penicillin in Hong Kong. Antimicrob Chemother. 2007 Dec;60(6):1407-9.

6.  Joachim A, Matee MI, Massawe FA, Lyamuya EF. Maternal and neonatal colonisation of group B streptococcus at Muhimbili National Hospital in Dar es Salaam, Tanzania: prevalence, risk factors and antimicrobial resistance. BMC Public Health.;2009: 9:437.

7. Klevens RM, Morrison MA, Nadle J, et al.Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA. 2007 Oct 17;298(15):1763-71.

8. Appelbaum, P. C. 1992. Antimicrobial resistance in Streptococcus pneumoniae: an overview. Clin. Infect. Dis. 15:77-83.

9. Jacobs, M. R., S. Bajaksouzian, A. Zilles, G. Lin, et al. 1999. Susceptibilities of Streptococcus pneumoniae and Haemophilus influenzae to 10 oral antimicrobial agents based on pharmacodynamic parameters: 1997 U.S. Surveillance study. Antimicrob. Agents Chemother. 43:1901-1908.

10. Walsh CT Fischbach MA New ways to squash superbugs. Scientific American, 2009. 301:32.

11. Whitney CG. et.al.The International Infections in Pregnancy Study: group B streptococcal colonization in pregnant women. The Journal of Maternal–Fetal and Neonatal Medicine 2004;15:267–274.

12. Cohain, JS. Long term Symptomatic GBS Vulvovaginitis – 8 cases resolved with freshly cut garlic. European Journal of OBGYN Reprod Biology. 2009;146(1):110-1. 

13.   Lin FY, Troendle JF. Hypothesis: Neonatal respiratory distress may be related to asymptomatic colonization with group B streptococci. Pediatr Infect Dis J. 2006 Oct;25(10):884-8.

14.  McKeever TM, Lewis SA, Smith C, Hubbard R. . The importance of prenatal exposures on the development of allergic disease: a birth cohort study using the West Midlands General Practice Database. Am J Respir Crit Care Med. 2002 Sep 15;166(6):827-32.

15.  P T Heath,1 G F Balfour,1 H Tighe,1 N Q Verlander,2 T L Lamagni,3 A Efstratiou Group B streptococcal disease in infants: a case control study. Arch Dis Child 2009 94: 674-680.

16. Centelles-Serrano MJ, Pérez-Moreno MO, Llovet-Lombarte MI, Cortell-Ortolá M, Jardí-Baiges AM, Buj-González JI.Effectiveness of systematic investigation for Group B Streptococcus in urine samples to identify colonized pregnant women. Enferm Infecc Microbiol Clin. 2009 Aug-Sep;27(7):394-8.

17. Anderson BL, Simhan HN, Simons K, Wiesenfeld HC. Additional antibiotic use and preterm birth among bacteriuric and nonbacteriuric pregnant women. Int J Gynaecol Obstet. 2008;102(2):141-5.

18 .  Smaill F, Vazquez JC. Antibiotics for asymptomatic bacteriuria in pregnancy. Cochrane Database Syst Rev. 2007; 18;(2):CD000490.

19. Keski-Nisula L, Kirkinen P, Katila ML, Ollikainen M, Saarikoski S. Cesarean delivery. Microbial colonization in amniotic fluid.J Reprod Med. 1997;42(2):91-8.

20. Kjaergaard N, Helmig RB, Schønheyder HC, Uldbjerg N, Hansen ES, Madsen H. Chorioamniotic membranes constitute a competent barrier to group b streptococcus in vitro. Eur J Obstet Gynecol Reprod Biol. 1999 Apr;83(2):165-9.

21. Winram SB, Jonas M, Chi E, Rubens CE. Characterization of group B streptococcal invasion of human chorion and amnion epithelial cells In vitro. Infect Immun. 1998 Oct;66(10):4932-41.

22. Kjaergaard N, Hein M, Hyttel L, Helmig RB, Schønheyder HC, Uldbjerg N, Madsen H. Antibacterial properties of human amnion and chorion in vitro. Eur J Obstet Gynecol Reprod Biol. 2001;94(2):224-9.

23. Centers for Disease Control and Prevention (CDC). Trends in perinatal group B streptococcal disease - United States, 2000-2006. MMWR Morb Mortal Wkly Rep. 2009 Feb 13;58(5):109-12.

A big thank you to Judy Slome Cohain for giving me permission to reprint the above article. Stay tuned for more posts about GBS...

Comments

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Thanks for your post. This is an important topic and I look forward to part 2.

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Thanks! I hope you enjoy the second one, http://empoweredbirth.typepad.com/empowering_birth_blog/2010/07/part-2-so-youve-decided-to-test-for-gbs-you-still-have-options.html.

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