Science & Sensibility

Advocates 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

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

Amy Romano systematic review antibiotics, bias, flawed, GBS, interventions, IVs, newborns, no separation, systematic review, tests in pregnancy

In the latest Listening to Mothers Survey 83% of women reported having intravenous (IV) lines in labor or birth. This number is probably not surprising to many of us – IV’s are part of the routine package of care in most settings, even for low-risk women. Their ubiquitous place in modern obstetrics renders them practically invisible. And although the American Society of Anesthesiologists revised its guidelines in 2007 to encourage clear fluids in labor – which would presumably eliminate the need for IVs in most cases – the practice of routine IVs appears to be continuing unabated. Why? Because the medical model presumption is that it’s nice to have that IV access just in case an urgent complication is lurking around the corner. And besides – IVs are relatively harmless, right?

Wrong. In 2007, I was part of a team that conducted a systematic review (PDF, see p. 34S – 36S) of the research on IV fluids in labor. We found that IVs can cause anemia and that they reduce colloid osmotic pressure – which can lead to swelling in the tissues or lungs (pulmonary edema) of both the laboring woman and her infant. In addition, not all IV fluids are created equal: IV fluids with glucose in them were associated with low blood sugar in newborns, and salt-free fluids increased the likelihood of potentially serious electrolyte imbalances. The body of research also confirmed common sense – that women find IVs uncomfortable and that IVs limit mobility. Finally, we failed to find a single study that supported the notion that IV access improves outcomes when urgent problems arise. Despite this nearly universal belief, no one has in fact studied the question.

This week I happened to see two different bits of news blip onto my radar that raise other troubling concerns about the rampant use of IVs on maternity wards. Both pieces looked at possible harmful effects of the chemicals that may leach out of the plastic IV bags and tubing. A recent NPR story reported on an ongoing study looking at sexual maturity in teenagers who were exposed to high levels of phthalates as infants in neonatal intensive care units. The phthalates came from intravenous lines, including those used for extracorporeal membrane oxygenation (ECMO). The Wall Street Journal posted a short blurb about an animal study showing that another chemical found in IV bags and tubing, cyclohexanone, can trigger health problems in the hearts and neurological systems of the rats that were exposed. We can not – and should not - extrapolate the findings of these studies to possible effects on laboring women and their newborns. But they add new fuel to an already compelling case to do away with IVs whenever safely possible. With no evidence that their routine use is beneficial, a small but consistent body of evidence that they can cause harm, and important questions unanswered, a change in practice is long overdue.

For more information about potentially harmful chemicals used in health care settings and ways to reduce the environmental impact of our health care system, visit Health Care Without Harm. Along with other great resources, HCWH published a booklet with the American College of Nurse-Midwives called Green Birthdays (PDF) in 2001.

Citation: Goer, H., Leslie, M. S., & Romano, A. (2007). The Coalition for Improving Maternity Services: Evidence basis for the ten steps of mother-friendly care: Step 6: Does not routinely employ practices, procedures unsupported by scientific evidence. Journal of Perinatal Education (16)1, 32S-64S.

Amy Romano do no harm, new research, research for advocacy interventions, IVs, safety