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Intrapartum Antibiotics for GBS Positive Mothers – Still Clear as Mud

September 30th, 2014 by avatar

 In July, 2009, former blog community manager Amy Romano wrote about the Cochrane systematic review of intrapartum antibiotics for mothers with GBS colonization.  The researchers recently went back and did another review of for new literature and updated their research.  Melissa Garvey of the American College of Nurse-Midwives updated the original article with recent information from the June 2014 review and I wanted to share that with you now.- Sharon Muza, Community Manager, Science & Sensibility.

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But sometimes Cochrane reviews leave us with more questions than answers.

Last June, the Cochrane Library released a systematic review evaluating the effectiveness of intrapartum antibiotics for known maternal group B streptococcal (GBS) colonization. And it’s a hot mess.

The 4 included trials that compared IV antibiotics with no treatment in labor collectively had only 852 participants, which we automatically know is far too small to find statistically significant differences in a condition that affects 1 in 2000 newborns, and results in death or long-term complications even less frequently. But small sample sizes were the least of the problems here. The reviewers noted several other problems with the trials:

  • In one study, researchers tracked their findings and halted the trial as soon as a significant difference was found (favoring treatment with antibiotics). This is a blatant form of bias – it is like flipping a penny until you get heads 5% more often than you got tails. If you keep flipping long enough (or stop flipping soon enough) you’ll be able to find that 5% difference simply by chance.
  • In the same study, researchers changed to a different statistical test that allowed them to achieve statistical significance with their data, when the originally planned (and more appropriate) test would have produced a nonsignificant finding.
  • None of the studies used placebos, so women, care providers, and hospital staff knew which women received antibiotics and which did not. This may have altered treatment of the women or the babies, possibly in ways that would make no antibiotics appear safer (for instance, avoiding or delaying membrane rupture in a woman who is GBS+ but not getting antibiotics).
  • One study excluded women who developed fevers in labor. GBS colonization can cause maternal fever and newborn sepsis, so excluding these cases makes no sense.
  • Some women included in the studies were likely GBS negative because methods used to determine GBS status were inadequate.
  • Outcomes were poorly defined.
  • Data on a substantial proportion of women and babies were missing.
  • Groups were mysteriously differently sized.
  • Need I go on?

The Cochrane reviewers, in my opinion, did a respectable job with what they had, but what they had was garbage and as the saying goes, “Garbage in, garbage out.” You can’t make reliable conclusions out of a bunch of bad research, even if you’re a Cochrane reviewer.

So what were the findings? Three trials, which were more than 20 years old, compared ampicillin or penicillin to no treatment and found no clear differences in newborn deaths although the occurrence of early GBS infection in the newborn was reduced with antibiotics.

More, better research is needed, but the Cochrane reviewers are not optimistic:

Ideally the effectiveness of IAP to reduce neonatal GBS infections should be studied in adequately sized double-blind controlled trials. The opportunity to conduct such trials has likely been lost, as practice guidelines (albeit without good evidence) have been introduced in many jurisdictions.

In the meantime, women should be aware that other evidence, albeit not from randomized controlled trials, suggests that antibiotic treatment reduces deaths from early onset GBS disease in newborns. According to the Centers for Disease Control and Prevention, a steady decline in GBS disease has been seen in individual institutions, in the whole US population, and in other countries as antibiotic use has risen. But these population-level data cannot tell us whether antibiotics or some other factor caused the decline.

What other advice can we share with women?

  1. Be aware that antibiotics are not harmless. Severe allergic reactions are possible, and antibiotic use in labor can result in thrush (candida infection) which causes painful breastfeeding and sometimes early weaning. We do not know other possible harmful effects because they have never been studied adequately or at all.
  2. No study confirms the effect of labor practices on GBS infection in newborns, but here we can use our common sense. Care providers should avoid or minimize sweeping/stripping membranes before labor, breaking the bag of waters, vaginal exams, and other internal procedures, especially those that break the baby’s skin and can be a route for infection. These include internal fetal scalp electrodes for fetal heart rate monitoring and fetal blood sampling.
  3. Keep mothers and babies skin-to-skin after birth. This exposes the baby to beneficial bacteria on the mother’s skin, facilitates early breastfeeding, and lowers the likelihood that the baby will exhibit signs or symptoms that mimic infection, such as low temperature or low blood sugar, which could cause the need for blood tests or spinal taps to rule out infection.

If you would like additional information about GBS treatment, check out Science & Sensibility’s interview with Rebecca Dekker of EvidenceBasedBirth.com and Rebecca’s article “Group B Strep in Pregnancy: Evidence for Antibiotics and Alternatives.”

Reference

Ohlsson A, Shah VS. Intrapartum antibiotics for known maternal Group B streptococcal colonization. Cochrane Database of Systematic Reviews 2014, Issue 6. Art. No.: CD007467. DOI: 10.1002/14651858.CD007467.pub4

Thank  you to Melissa Garvey of ACNM for her reworking of the original article.

 

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Evidence Based Birth Takes on Group B Strep: An Interview with Rebecca Dekker

April 9th, 2013 by avatar

http://flic.kr/p/KCS5

Occasional Science & Sensibility contributor Rebecca Dekker of Evidence Based Birth has spent the last month writing a blog article about Group B Strep and it is finally here! In her painstaking but clear review of the evidence on GBS in pregnancy, Rebecca came to the conclusion that universal screening and treatment for GBS is more effective than treating with antibiotics based on risk factors alone. She also found that although “probiotics, chlorhexadine, and garlic have the potential to reduce vaginal and newborn colonization with GBS, we do not have evidence yet to show that these strategies can prevent early GBS infections, since GBS infection usually occurs when GBS gains access to the amniotic fluid and gets into the fetus’s lungs during labor.”

To read Rebecca’s just released article, Group B Strep in Pregnancy: Evidence for Antibiotics and Alternatives in its entirety, click here.

Today, Rebecca joins us on Science & Sensibility to talk about her latest addition to Evidence Based Birth.

Sharon Muza: What inspired you to write this article?

Rebecca Dekker: I received more requests to write about Group B strep than any other topic! Over the past few months, I had weekly, sometimes daily emails and Facebook messages from women—all asking me to provide them with evidence about antibiotics, hibiclens, or garlic for preventing GBS infections. After about the 50th request, I figured I better set aside my other plans and focus on this topic, because it was clearly weighing heavily on many women’s minds! 

SM: What was the most difficult thing about writing this article?

RD: Probably the most difficult thing was sorting through the stacks and stacks of research articles that have been published about Group B strep in pregnancy. This was one of the reasons it took me almost a year of blogging before I decided to dive into group B strep. I knew it would be a monumental task. And it was. But I was fortunate enough to have an expert in GBS who helped point me to the most important or “landmark” studies.

SM: Who was this expert?

RD: I met Dr. Jessica Illuzzi via email earlier this year. She and I had corresponded about a different blog article, and at that time I found her to be incredibly helpful. I knew that in addition to being an OB, Dr. Illuzzi was a research expert in GBS. So I asked her if she would review my article for me. To be honest, I could not have written this article without her guidance. She read my first draft and basically told me that I needed to go back to the drawing board. She encouraged me to dig deeper into the evidence so that I would really understand it. Whenever I had questions about something, she sent me research articles that immediately answered my question. In the end, I knew the article was ready when she said it was a great summary of the state of the science of GBS. 

I was also lucky enough to have 2 other GBS experts give me feedback on the article—a GBS researcher and a microbiologist. And then I have several physicians who faithfully review all of my articles and give great suggestions. I am very grateful to all of them as well!

SM: I know that you usually begin your articles with an exploration of your own biases, in order to tease the bias out of your writing. Did you have any pre-existing biases about GBS? 

RD: To be honest, I actually had no biases up front. I was fortunate to always test negative for GBS myself, and so I never had to struggle with this issue before. I was pretty open-minded to the entire issue. I was open-minded to antibiotics. I was open-minded to hibiclens or other alternatives. I had no personal agenda. I simply wanted to get to the facts. Hopefully this lack of bias will shine through and help people respect the article even more.

 SM: What surprised you most as you wrote this article?

RD: One of the things that surprised me was how people have such different reactions when they read the evidence about GBS. I had several friends preview the article for me. Some of them instantly said, “Oh yeah, that sounds like a really high risk. I’d definitely take the antibiotics to prevent an infection in my newborn.” Others would say, “Really? That’s all? That’s not a very high risk at all. I wouldn’t take antibiotics for that level of risk.” This is a great example of how everyone perceives risk differently. But at least in this article I have been able to put some evidence-based facts out there. Let people interpret the risks as they may. I only ask that they talk with their health care provider before making any decisions!!

 SM: What do you think is the future of GBS evidence?

RD: Ten years from now I am guessing that I could write a very different article. I would like to think that by then we may have a vaccine on the horizon that could prevent both early GBS infections and GBS-related preterm birth. It would also be nice if the rapid test was affordable and widely available by then. I would also LOVE to see some solid research evidence on the use of probiotics for decreasing GBS colonization rates in pregnant women. As far as I know, probiotics for decreasing GBS hasn’t been studied yet in pregnant women, and I think it deserves further inquiry.  

SM:What makes your blog article about GBS different than all the other blog articles out there on this topic?

Rebecca Dekker

RD: I purposefully didn’t look at any of the other GBS blog articles out there until I finished my article. Yesterday, I read through a variety of blog articles (there are a lot!). Most of them were about 90-95% accurate in their facts. A couple of them had serious errors (in particular, I found one blog article that had inaccurate information about hibiclens). Most didn’t list any references, and I could tell that most of the blog authors had used secondary sources (other blogs or summary articles) instead of looking at the research evidence themselves. This can be fine, but sometimes it’s a bit like playing telephone: You just keep repeating the same facts over and over without checking to see if the evidence has changed or if the summary you are parroting was accurate in the first place. I’d like to think that my blog article is a very accurate assessment of the research evidence on GBS in pregnancy—translated into regular language so that women and their family members can understand the evidence. 

SM: What are you going to write about next?

RD: I don’t know!! What would YOU like to see me write about?

SM: I want to thank you Rebecca, for your contributions to Science & Sensibility and for sharing Evidence Based Birth with the world!  I know that these articles take a huge amount of time and you are very diligent and conscientious about researching the literature and providing only the best analysis possible,  and seeking out experts on the topic to help you really be sure that you are offering the best of the best of information.  I always enjoy reading your blog and find it a great source of information for my doula and CBE students and my birth doula clients as well. I know that I speak for all the readers here on Science & Sensibility when I say, keep on keeping on!  Do please let Rebecca know what you would like her to write about next!   

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When Is Evidence Based Medicine NOT Evidence Based? Inductions for PROM at Term

August 30th, 2009 by avatar

[Editor’s Note: I would like to give a warm welcome to Science & Sensibility’s newest regular contributor, Mayri Sagady Leslie. Mayri has a brilliant mind for making sense of obstetric research and has over a decade of experience putting evidence-based principles into practice as a nurse-midwife, midwifery practice director, and midwifery instructor. You can find out more about Mayri by clicking on the Contributors tab above. And look for more regular contributors joining the Science & Sensibility ranks this fall. – AMR]

Mayri Sagady Leslie

Mayri Sagady Leslie

The release of ACOG Practice Bulletin No. 80, Premature Rupture of Membranes in April of 2007 should be marked as a red letter day in the downfall of evidence-based maternity care in the United States.  The story of this red letter day begins back in June of 1998 with the publication of the ACOG Practice Bulletin Number 1, Premature Rupture of Membranes: Clinical Practice Guidelines for Obstetricians-Gynecologists.  This is the antecedent document which Bulletin 80 replaces.  Both guidelines address the issues, evidence, and suggested management involved when a mother’s  water bag breaks before labor begins  near, at, or beyond her estimated  due date.

All ACOG bulletins address relevant clinical questions, reviewing the current available evidence pertinent to those questions and providing citations to studies referenced.  At the end, specific recommendations are made and graded by letters, with “A” representing recommendations coming from the most trustworthy evidence, usually randomized, controlled trials.

The 1998 version of the bulletin on Premature Rupture of Membranes (PROM) gave the following recommendation, based on Level A evidence:

With term PROM, labor may be induced at the time of presentation or patients may be observed for up to 24-72 hours for the onset of spontaneous labor.

However, the 2007 bulletin, nine years later, again based on Level A evidence, made a significant change in their recommendation as follows:

For women with PROM at term, labor should be induced at the time of presentation, generally with oxytocin infusion, to reduce the risk chorioamnionitis.

What’s wrong with this new recommendation? One might assume nothing. Obviously, in those nine years something changed in the Level A evidence. The problem is – nothing changed. No new significant studies were published that favored induction over observation for mothers who had no medical indications to start labor. In fact, both guidelines cite the exact same study.

It gets worse. The study, published by Hannah et al in 1996, known as the TERMPROM Trial, was a large clinical trial which took place from 1992 to 1995 in 72 medical centers throughout 6 countries.  The study examined the effects of induction after PROM with oxytocin or prostaglandins versus waiting up to 4 days for labor to start on its own or inducing with the same 2 agents if labor still had not begun or of other problems developed (such as a fever or non-reassuring fetal heart rate pattern).  The lowest rate of maternal infection was found in mothers that were induced with oxytocin. Presumably, since the Hannah trial is the only study cited as evidence for ACOG’s Clinical Bulletin 80, this is the source of the evidence that induction “ reduce[s] chorioamnionitis”. Yet, this logic is fraught with issues:

  • There was no study protocol for either screening for or treating Group B Streptococcus (GBS)
  • Only 20% of GBS culture results were available at the time of labor and birth management
  • The majority of GBS+ mothers did not receive treatment
  • 30% of all study mothers had vaginal exams at the time of PROM
  • The group with the fewest infections was also the group with the fewest vaginal exams

(For more about these and other problems with the TERMPROM trial, see Henci Goer’s critique, “When Research is Flawed: Should Labor be Induced Immediately with Term Prelabor Rupture of Membranes?”)

To bring these issues into perspective, think about what we now know and how judicious care providers work with women today if their water breaks before labor at term:

  • Unless a woman declines, she is screened for GBS before term, so if her water breaks, we can factor whether she is GBS positive or negative into our recommendation of whether she may be at less risk opting for an induction or waiting.
  • As indicated by guidelines from the Center for Disease Control (CDC), we treat women who are GBS positive with antibiotics prophylatically to reduce the risk of infection for her and her baby.
  • For women who decline screening or whose GBS status is unknown, we follow guidelines from the CDC which suggests that we treat according to the existence of other risk factors such as the length of time the membranes are ruptured, signs of infection in the mother and baby, etc.
  • In either case, we know NOT to do any vaginal exams until we know mom is in active labor and even then to minimize and avoid them until absolutely necessary because vaginal exams themselves are one of the highest risk factors for increasing infections once the water bag has ruptured.

But here’s the tragedy. Bulletin number 80 was released. The recommendation was changed. Based on data that was 11 years old at the time, from one study that had no protocol for screening or treatment regarding maternal infection and was conducted before current guidelines were available or practiced – a new recommendation, focused on preventing infection, was made that represents itself as current and evidenced-based.

Now, this powerful “guideline”  – which drives industry standards, institutional policies and procedures, medical school education, and, potentially, legal judgments – allows for just one option for mothers in this normal physiological condition: induction.

What impact is this having?  As numbers of inductions increase so do the numbers of technological interventions such as electronic monitoring and the mother’s need for pain medications – as these increase her ability to move freely and choose her own positions decline as well. Operative deliveries have also been found to increase with inductions in some studies and with those come increased risks for more severe perineal injuries and lifelong issues with pelvic floor disorders.  While inductions, like all medical interventions have their place and time when indicated – they cannot be justified as a standard procedure for a normal physiological occurrence in a healthy full term pregnancy.

I was giving a talk on this topic recently to a group of providers and a woman’s eyes suddenly lit up with recognition. Here’s what she said:

I was admitting a client recently whose water bag was broken and the attending said we have to induce her. I said why? He said, haven’t you heard, there is new evidence. It’s dangerous now to wait. We have to induce them now. I said no, I hadn’t heard.

When is evidence based medicine NOT based on the evidence?  When one can make opposing recommendations based on the same exact study publication.  When one can use findings that are inappropriately outdated and not applicable to current practice to make clinical recommendations.  When is evidence based medicine NOT based on the evidence?  When it’s not.

References:

American College of Obstetricians and Gynecologists. (1998). ACOG practice bulletin. Number 1, June, 1998. Premature rupture of membranes. Clinical management guidelines for obstetrician-gynecologists. International Journal of Gynaecology & Obstetrics, 63(1), 75-84.

American College of Obstetricians and Gynecologists. (2007). ACOG practice bulletin. Number 80: Premature rupture of membranes. Clinical management guidelines for obstetrician-gynecologists. Obstetrics & Gynecology, 109(4), 1007-1019.

Hannah M. E., Ohlsson A., Farine D., Hewson S. A., Hodnett E. D., Myhr T. L., et al. (1996). Induction of labor compared with expectant management for prelabor rupture of the membranes at term. TERMPROM Study Group. The New England Journal of Medicine, 334 (16), 1005-10

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When Research is Flawed: Should Labor Be Induced Immediately with Term Prelabor Rupture of Membranes?

August 30th, 2009 by avatar

[Editor’s Note: Lamaze International is in the process of moving the archives of our When Research is Flawed series to Science & Sensibility. When Research is Flawed is a series of brief critiques of influential studies that have shaped policy and practice, despite having serious flaws, significant limitations, or both. – AMR]

Commentary on: Hannah ME, Ohlsson A, Farine D, Hewson SA, Hodnett ED, Myhr TL, Wang EE, Weston JA, & Willan AR (1996). Induction of labor compared with expectant management for prelabor rupture of the membranes at term. TERMPROM Study Group. The New England journal of medicine, 334 (16), 1005-10 PMID: 8598837

Study design and results: multicenter, multinational randomized controlled trial in developed countries of 5041 women with confirmed PROM at ≥ 37 completed weeks of gestation. Women were not in active labor, had a singleton fetus in cephalic presentation, and had no contraindication to trial participation.

Investigators randomly allocated trial participants to one of four groups: (1) immediate induction with oxytocin, (2) expectant management for 4 days before oxytocin induction or until an indication for induction developed, (3) immediate induction with prostaglandin E2 (PGE2) followed by oxytocin if necessary, or (4) expectant management for 4 days before PGE2 induction or until an indication for induction developed.

Selected background information [Note: These represent ranges in rates reported among the 4 study groups. No significant differences across groups were detected for any of the following:]

  • vaginal exam at trial admission: 35-39% digital, 64-67% speculum
  • number of digital vaginal exams: 49-63% had ≥ 4
  • Group B strep (GBS) status: 9-12% tested positive for GBS
  • median time to active labor in expectant groups: 16-17 h

Selected maternal outcomes:

  • cesarean rate: rates ranged among the 4 groups from 10-11% overall, 14-15% nulliparous women, 4-5% multiparous women
  • any sign of chorioamnionitis:
    – 4.0% induction/oxytocin vs. 8.6 % expectant/oxytocin, p < 0.001 [Absolute difference: 4.6%. Absolute difference for diagnosis based on criteria other than intrapartum fever (fever before labor, elevated white blood cell count, or foul-smelling amniotic fluid): 2.3%.]
    – 6.2% induction/prostaglandin vs. 7.8% expectant/prostaglandin. Difference did not achieve statistical significance, meaning it was likely to be due to chance.

Neonatal outcomes:

  • neonatal infection: rates ranged from 2-3% and were not significantly different across the 4 groups
  • stay in neonatal intensive care unit > 24 h:
    – 7% induction/oxytocin vs. 12% expectant/oxytocin, p < 0.001.
    – 9% induction/prostaglandin vs. 10% expectant/prostaglandin. Difference did not achieve statistical significance
  • antibiotics:
    – 8% induction/oxytocin vs. 14% expectant/oxytocin, p < 0.001.
    – 11% induction/prostaglandin vs. 12% expectant/prostaglandin, p = 0.003.
  • All other neonatal outcomes were similar, including, fetal distress, meconium-stained amniotic fluid, Apgar score < 7 at 1 or 5 min, cord blood pH < 7.1, need for oxygen resuscitation, jitteriness or irritability, seizures, hypotonia, abnormal level of consciousness, apnea, abnormal feeding at 48 h or more, and ventilation after resuscitation.

Problems include but are not limited to the following:

  • Failure to consider the effect of epidural analgesia on intrapartum fever confounds chorioamnionitis results. Most diagnoses of chorioamnionitis were made on the basis of intrapartum fever. At the time of the trial, the association between epidural analgesia and intrapartum fever was not widely known, and no adjustment was made for this factor. Had this been done, an excess probably would remain in the expectant group, but infection rates might have been lower in all groups.
  • Women who were colonized with GBS were not treated in labor. A secondary analysis looked at the effect of GBS status, based on vaginal swabs obtained at trial entry, on outcomes (Hannah, 1997). Calculations using that study’s data reveal that one-third of neonatal infections were in women testing positive for GBS. GBS also caused one of the four deaths in the expectant group in babies without lethal anomalies. Current standard practice—screening for GBS at the end of pregnancy and providing antibiotics in labor to those who are colonized—would have reduced, and might have eliminated neonatal infections in GBS + women, thus reducing infection rates overall, and it might have prevented the death. It is also possible that GBS status would not have been a factor or would have been less of a factor in neonatal infections were it not for women having vaginal exams at trial entry and multiple exams before delivery. (See next bullet points.)
  • Chorioamnionitis rates were confounded by multiple digital vaginal exams. Leaving aside epidural analgesia as a confounding factor in diagnosing chorioamnionitis, yet another secondary analysis reported that chorioamnionitis increased steadily with number of digital vaginal exams independent of other factors (Seaward, 1997). Compared with less than three, the odds ratio climbed from a 2-fold increase for 3 to 4 exams to a 5-fold increase with more than 8. Seaward (1998) reported in their evaluation of risk factors for neonatal infection that chorioamnionitis had the strongest independent association. The rate among infants of women with chorioamnionitis was 16%, a six-fold increase over those not experiencing chorioamnionitis.
  • Neonatal infection rates were confounded by vaginal exams at trial entry. A secondary analysis of trial data found that having a vaginal exam at trial entry increased the risk of neonatal infection by 250%, even after taking into account GBS status (Hannah, 1997). This difference is likely to be greater than appears because the analysis authors chose to combine digital and speculum exams, although only digital exams are believed to increase the risk of infection.
  • Neonatal infection rates were confounded by multiple digital vaginal exams during labor. According to another secondary analysis, the percentage of infections trended upward with the number of vaginal exams independent of other factors, including time from rupture of membranes to labor onset and length of active labor (Seaward, 1998). It rose from 2% in women with 3 to 4 exams to 5% in women with more than 8. The odds roughly doubled compared with women having fewer than 3 vaginal exams, although the difference only achieved statistical significance when 7 to 8 exams were compared with fewer than 3.

Comment: Based solely on the TermPROM trial, the American College of Obstetricians and Gynecologists (ACOG) recommends immediate induction, generally with oxytocin, for women with term PROM on the grounds that inducing labor will reduce chorioamnionitis, febrile morbidity, and neonatal antibiotic treatments without increasing cesarean rates (ACOG, 2007). The primary argument for immediate induction has always been reducing neonatal infections, which ACOG acknowledges it does not do, and, as can be seen in this deconstruction, with optimal care other benefits are likely to be smaller than currently appear.

By contrast, a Cochrane systematic review published in 2006 also evaluates term PROM management (Dare, 2006). Despite being heavily dependent on the TermPROM trial—three-quarters of the 6800 participants among the 12 trials in total come from the TermPROM trial—the reviewers reach a more tempered conclusion: “Since differences in outcomes between planned and expectant management may not be substantial, women need to be able to access the appropriate information to make an informed choice (p. 12).”

In summary, in the absence of signs of infection, expectant management remains a viable option. Nonetheless, the secondary analyses have given us a more nuanced picture. While the original trial report found no difference in neonatal infection rates between immediate induction and expectant management overall, the secondary analyses make clear that length of time between rupture and delivery matters. They also found that modifiable factors affected infection rates, which means we do not know what they would have been with optimal care.

For those choosing expectant management, the question arises of how long to wait before inducing labor if one prefers to set a limit. Consider the following: Seaward (1998) reported that time from membrane rupture to labor onset of 24-48 hours versus less than 12 hours was an independent predictor of neonatal infection. Infection rates with 24 hours or more to onset of labor were 4% versus the background 2% rate. Hannah (1996) reported that the median time to active labor, not labor onset, after membrane rupture was 16-17 hours. It therefore seems reasonable to wait about 18 hours before inducing labor. Half the group of women will have achieved active labor by this time, and, if induced, the remaining half are likely to have started labor by the 24-hour cut point.

Women with PROM at term who are GBS + constitute a special subset. The Centers for Disease Control (2002) guidelines for management of GBS + women say nothing about inducing women with ruptured membranes at term, which suggests that awaiting spontaneous labor is acceptable provided that antibiotic therapy is initiated. And given that it takes time to instill the recommended dose of antibiotics, common sense dictates that women who prefer not to wait for labor should delay induction until they have an adequate dose of antibiotics on board.

In any case, regardless of GBS status or decisions around whether or when to induce, to minimize the risk of infection, women should avoid digital vaginal exams until established in labor, and their use should be minimized during labor. Data also suggest that oxytocin is the induction agent of choice. It appears to reduce infection rates compared with PGE2 without any offsetting disadvantages.

References:
ACOG Committee on Practice Bulletins-Obstetrics (2007). ACOG Practice Bulletin No. 80: premature rupture of membranes. Clinical management guidelines for obstetrician-gynecologists. Obstetrics and gynecology, 109 (4), 1007-19 PMID: 17400872

Schrag S, Gorwitz R, Fultz-Butts K, & Schuchat A (2002). Prevention of perinatal group B streptococcal disease. Revised guidelines from CDC. MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control, 51 (RR-11), 1-22 PMID: 12211284

Dare MR, Middleton P, Crowther CA, Flenady VJ, & Varatharaju B (2006). Planned early birth versus expectant management (waiting) for prelabour rupture of membranes at term (37 weeks or more). Cochrane database of systematic reviews (Online) (1) PMID: 16437525

Hannah ME, Ohlsson A, Wang EE, Matlow A, Foster GA, Willan AR, Hodnett ED, Weston JA, Farine D, & Seaward PG (1997). Maternal colonization with group B Streptococcus and prelabor rupture of membranes at term: the role of induction of labor. TermPROM Study Group. American journal of obstetrics and gynecology, 177 (4), 780-5 PMID: 9369819

Seaward PG, Hannah ME, Myhr TL, Farine D, Ohlsson A, Wang EE, Haque K, Weston JA, Hewson SA, Ohel G, & Hodnett ED (1997). International Multicentre Term Prelabor Rupture of Membranes Study: evaluation of predictors of clinical chorioamnionitis and postpartum fever in patients with prelabor rupture of membranes at term. American journal of obstetrics and gynecology, 177 (5), 1024-9 PMID: 9396886

Seaward PG, Hannah ME, Myhr TL, Farine D, Ohlsson A, Wang EE, Hodnett E, Haque K, Weston JA, & Ohel G (1998). International multicenter term PROM study: evaluation of predictors of neonatal infection in infants born to patients with premature rupture of membranes at term. Premature Rupture of the Membranes. American journal of obstetrics and gynecology, 179 (3 Pt 1), 635-9 PMID: 9757963

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The New GBS Cochrane Review: A Hot Mess!

July 30th, 2009 by avatar

The Cochrane CollaborationAdvocates for evidence based care feel our ears perk up when we hear about a new Cochrane systematic review. Cochrane Review = Evidence! Right? Indeed, systematic reviews represent the top of the “evidence pyramid” and Cochrane systematic reviews are the gold standard for their rigor and transparency. A Cochrane review can even conclusively settle important clinical controversies.

But sometimes Cochrane reviews leave us with more questions than answers.

Last week, the Cochrane Library released a systematic review evaluating the effectiveness of intrapartum antibiotics for known maternal group B streptococcal (GBS) colonization. And it’s a hot mess.

The four included trials that compared IV antibiotics with no treatment in labor collectively had only 500 participants, which we automatically know is far too small to find statistically significant differences in a condition that affects 1 in 2000 newborns, and results in death or long-term complications even less frequently. But small sample sizes were the least of the problems here. The reviewers noted several other problems with the trials:

  • In one study, researchers tracked their findings and halted the trial as soon as a significant difference was found (favoring treatment with antibiotics). This is a blatant form of bias – it is like flipping a penny until you get heads 5% more often than you got tails. If you keep flipping long enough (or stop flipping soon enough) you’ll be able to find that 5% difference simply by chance.
  • In the same study, researchers changed to a different statistical test that allowed them to achieve statistical significance with their data, when the originally planned (and more appropriate) test would have produced a nonsignificant finding.
  • None of the studies used placebos, so women, care providers, and hospital staff knew which women received antibiotics and which did not. This may have altered treatment of the women or the babies, possibly in ways that would make no antibiotics appear safer (for instance, avoiding or delaying membrane rupture in a woman who is GBS+ but not getting antibiotics).
  • One study excluded women who developed fevers in labor. GBS colonization can cause maternal fever and newborn sepsis, so excluding these cases makes no sense.
  • Some women included in the studies were likely GBS negative because methods used to determine GBS status were inadequate
  • Outcomes were poorly defined.
  • Data on a substantial proportion of women and babies were missing.
  • Groups were mysteriously differently sized.
  • Need I go on?

The Cochrane reviewers, in my opinion, did a respectable job with what they had, but what they had was garbage and as the saying goes, “Garbage in, garbage out.” You can’t make reliable conclusions out of a bunch of bad research, even if you’re a Cochrane reviewer.

So what were the findings?

Three trials, which were around 20 years old, compared ampicillin or penicillin to no treatment and found no clear differences in newborn deaths although the occurrence of early GBS infection in the newborn was reduced with antibiotics.

More, better research is needed, but the Cochrane reviewers are not optimistic:

Ideally the effectiveness of intrapartum antibiotics to GBS colonized women to reduce neonatal GBS infections should be studied in adequately sized double blind controlled trials. The opportunities to conduct such trials have likely been lost as practice guidelines have been introduced in many jurisdictions. (p. 11)

Source: Centers for Disease Control and Prevention. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5111a1.htm

Source: Centers for Disease Control and Prevention. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5111a1.htm

In the meantime, women should be aware that other evidence, albeit not from randomized controlled trials, suggests that antibiotic treatment reduces deaths from early onset GBS disease in newborns. According to the Centers for Disease Control and Prevention, a steady decline in GBS disease has been seen in individual institutions, in the whole U.S. population, and in other countries as antibiotic use has risen. But these population-level data cannot tell us whether antibiotics or some other factor  caused the decline.

What other advice can we share with women?

  1. Be aware that antibiotics are not harmless. Severe allergic reactions are possible, and antibiotic use in labor can result in thrush (candida infection) which causes painful breastfeeding and sometimes early weaning. We do not know other possible harmful effects because they have never been studied adequately or at all.
  2. No study confirms the effect of labor practices on GBS infection in newborns, but here we can use our common sense. Care providers should avoid or minimize sweeping/stripping membranes before labor, breaking the bag of waters, vaginal exams, and other internal procedures, especially those that break the baby’s skin and can be a route for infection. These include internal fetal scalp electrodes for fetal heart rate monitoring and fetal blood sampling.
  3. Keep mothers and babies skin-to-skin after birth. This exposes the baby to beneficial bacteria on the mother’s skin, facilitates early breastfeeding, and lowers the likelihood that the baby will exhibit signs or symptoms that mimic infection, such as low temperature or low blood sugar, which could cause the need for blood tests or spinal taps to rule out infection.

Citation: Ohlsson A, & Shah VS (2009). Intrapartum antibiotics for known maternal Group B streptococcal colonization. Cochrane database of systematic reviews (Online) (3) PMID: 19588432

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