Science & Sensibility

In this month’s edition of the Journal of Obstetrics and Gynaecology Canada, the SOGC released a new clinical practice guideline for the management of varicella infection in pregnancy.  Varicella zoster virus (VZV) infection, commonly referred to as chickenpox, is a common childhood disease that can affect the developing fetus if the mother contracts the disease during pregnancy. Here are some of the key points from the guideline that you should be aware of:

Chickenpox in pregnancy: the numbers

• 90% or more of pregnant women are immune to the varicella virus because of childhood exposure or varicella immunization.

• Varicella infection affects 2-3 pregnancies out of 1000 every year. This equates to 700-1050 cases in Canada per year and 8,100-12,100 cases in the US per year.

• Of those pregnant women with an active varicella infection, 5-10% will develop a serious respiratory disease known as pneumonitis.  This means approximately 35-105 women in Canada and 405-1210 women in the US will develop pneumonitis each year. Women who develop pneumonitis may need intubation and mechanical ventilation and are at a much higher risk of death.

• VZV can cross the placenta and lead to congenital varicella syndrome (CVS), a condition that results in malformations and deformations such as partial limb reductions. Fetal infection is rare, with a rate of 0.4% prior to 13 weeks gestation and a rate of 2% between 13-20 weeks gestation. There are about 4 cases per year in Canada and 41 cases per year in the US.

• If the mother contracts chickenpox between 5 days before birth and 2 days after birth, the newborn can develop neonatal varicella.  Varicella in a newborn can develop into disseminated visceral and central nervous system disease, which is often fatal. Approximately 20-30% of babies born to affected mothers at the time of delivery will develop neonatal varicella and it will be fatal in up to 30% of those infants.

Key Recommendations for Women

• If a woman does not recall having chickenpox as a child, then she should receive the varicella immunization prior to conception or after the birth of her child. The SOGC and AAP  recommend waiting at least one month after receiving the immunization before becoming pregnant. However, a pregnancy registry established by the vaccine’s manufacturer shows no cases of CVS in the 362 recorded cases of women who conceived within 3 months of receiving the varicella vaccine.

• If a pregnant woman is not immune to VZV, she should seek immediate medical help if she comes in contact with a contagious person. Treatment with varicella zoster immunoglobin (VZIG) will be given to reduce the risk of complications of maternal infection.

• A pregnant woman who contracts chickenpox should be treated with an antiviral drug.

• If a mother contracted chickenpox within 5 days before and 2 days after delivery, then her child should be treated with VZIG to reduce the risk of neonatal varicella.

Recommendations in the SOGC’s clinical practice guideline are comparable to recommendations from the Center for Disease Control.

A parent-friendly fact sheet on the topic of varicella vaccination has been created by the Organization of Teratology Information Specialists (OTIS).

Information on other immunizations during pregnancy can be obtained through the Center for Disease Control.

And now for today’s question to you, the reader: How will you use this information?

Lisa Baker Evidence Based Medicine, Practice Guidelines Practice Guidelines

[Editor's Note: This is the last in a series of three posts by Dr. Michael Klein regarding the research behind risks, benefits and realities of epidural analgesia.  To read Dr. Klein's first two posts, go here and here.]

Not all women are alike in labour and delivery:
Because the experience of labour pain, including severity, tolerance and contraction patterns, differs greatly among women, so does their ability to cope with the labour process.  In consequence, some women feel the need to receive epidural analgesia prior to the onset of active labour.  In some cases, the use of an early epidural will relax a woman enough to help her labour progress to the active phase and thereby lead to less subsequent medical interventions.  However, if used early without specific indications, a woman may find herself exposed to a larger range of interventions, including a caesarean birth.

Dealing with the reality of the labour ward:
Given this paradox and the severity of some of the side-effects of epidural analgesia, it is time to be honest about the full effects of this excellent technology: there is no such thing as a side-effect. There are only effects, some of which we like and some of which we don’t. When epidurals are used specifically to problem-solve, the risks of complications and other interventions are in fact reduced. When used routinely and mindlessly, epidural analgesia increases problems and adverse outcomes. Women need to be fully informed of this before agreeing to an epidural. Today, women are usually only informed of the direct consequences of epidural analgesia, such as a headache or even very rare neurological complications, but they are not often informed of the consequences that can occur if epidurals are given routinely or too early. They are rarely told about the potential deleterious effects of an epidural on the woman’s labour, nor the cascade of other interventions that might ensue. They are unlikely to be informed that an epidural will increase the demand on their nurse to pay greater attention to the technology and in consequence provide less hands-on support for the labouring woman. They are unlikely to be made aware of an epidural’s purported interference with the initial success of implementing breastfeeding following the baby’s birth.

Epidural analgesia is clearly an effective form of pain relief but it can also have less desirable consequences. Women need to be accurately and completely informed of their choices for pain relief in labour before they can provide their true consent. No matter how well intended, epidural analgesia increases the likelihood that women will have a variety of other interventions, especially if the epidural is given without specific medical indication. Women need to know that when epidural analgesia is given before the active phase of labour, it more than doubles the probability of a cesarean section.

The importance of timing and setting:
Women also need to be reassured that when epidural analgesia is given in the active phase of labour, it does not increase the cesarean section rate. This may motivate women to use other pain relief modalities and methods to help them, if possible, get to the active phase before requesting an epidural.

Readers of the literature also need to remember the importance of setting when reading about the research on epidural analgesia and any other interventions. All the statistics and outcomes that have been discussed here are in fact specific to the setting or environment from which the individual study or meta-analysis emanate. It is important to remember that adverse effects of epidural analgesia can be mitigated, especially if the setting generally limits the use of interventions. It appears, for example that in settings with low cesarean section rates (below 10%), even early epidurals do not increase the cesarean section rate,(21) but in more typical settings where cesarean section rates are higher than 20%, it does. This illustrates a general principle: For all studies, randomized or not, the reader needs to ask the question: do the caregivers in the studies practice the way that I do? If they do, the study may apply but if not, they may not.

The bottom line is that epidural analgesia has completely transformed birth. This massive change in the way that many women receive care in labour and birth has been based on a technique that, when used selectively and as a back-up tool or second line approach, is an important and valuable technique, among the many ways of assisting women with labour and birth. However, when used routinely as a first line agent, epidural analgesia can create problems that could have been avoided. Our Canadian National Study of the Attitudes and Beliefs of Maternity Care Providers has illuminated the very different ways that different disciplines view birth. (22) Most Canadian younger obstetricians (23)and women approaching their first birth (24) do not even know that epidural analgesia interferes with labour. The older generation of obstetricians knows that it does. They have experienced the changes related to epidural analgesia availability and usage during their many years in practice before and after the common use of epidural analgesia. It is time we told the truth about epidural analgesia – to colleagues and women – and engaged in a truly informed decision-making discussion with women about the optimal use of epidural analgesia.

References for this entire series of posts can be found here: References _ michael klein post

Post by:  Michael C. Klein, MD, CCFP, FAAP(Neonatal-Perinatal),FCFP, ABFP
Emeritus Professor of Family Practice and Pediatrics
University of British Columbia
Senior Scientist Emeritus
Centre Developmental Neuroscience and Child Health
Child and Family Research Institute
4500 Oak Street
Vancouver, V6H 3N1
Tel: 604-875-2000 ext 5078
Fax: 604-875-3569
Email: mklein@interchange.ubc.ca

Michael Klein MD Epidural Analgesia, Evidence Based Medicine, Practice Guidelines, Research, Science & Sensibility, Uncategorized benefits of epidurals, cesarean, epidural analgesia, epidurals, epidurals in active labor, how epidurals have transormed birth, interventions, labor and delivery pain relief, Michael Klein MD, pain, Practice Guidelines, risks of epidurals, Understanding Research

Next week, scientists, policy experts, and advocates will come together for the National Institutes of Health Consensus Development Conference on Vaginal Birth after Cesarean (VBAC). A panel will spend three days reviewing the evidence and hearing public testimony. On Wednesday they’ll announce their findings in a press telebriefing.

The NIH isn’t calling their findings “practice guidelines,” but they’re very likely to be taken as such. I’ll admit: the concept of guidelines, at least as they are developed and used in the United States, is a little troubling to me. On the one hand, guidelines can represent, as the Institute of Medicine suggests, “a move away from unexamined reliance on professional judgment toward more structured support and accountability for such judgment.” But what about their limitations?

Guidelines are seen by the public and by health professionals as objective and scientific, but:

Experts often look at the same body of evidence and come up with different conclusions.

• Chauhan and colleagues have demonstrated significant variation across national guidelines in management of shoulder dystocia and intrauterine growth restriction. In other words, the American Congress of Obstetricians and Gynecologists (ACOG) doesn’t agree with its counterparts in other countries about how these conditions should be diagnosed and treated.
• A study in the current issue of Birth compared VBAC guidelines from six countries and found little agreement not just on practice and management issues, but on the data itself: they found a four-fold variation in the reported upper-end risk of uterine rupture, as well as significant variation in the reported likelihood of vaginal birth in a VBAC labor.
• In 2008, ACOG reversed its position on the safety of expectant management of prelabor rupture of membranes, without citing any new evidence at all (and despite the publication of new evidence that, if anything, strengthens the argument for expectant management.)

Often, experts aren’t even looking at the same body of evidence.

• In the comparative study of national VBAC guidelines, 22 individual references were cited for uterine rupture, none of which appeared in all six guidelines. Only two studies were cited in three of the national guidelines and an additional 5 studies were cited in two national guidelines.
• In the shoulder dystocia review only half of eligible references were cited in both of the national guidelines the researchers analyzed.
• In the review of intrauterine growth restriction, only 12% of references were cited in both national guidelines.
• Guideline authors rarely if ever include a rationale for why they included the studies they included and excluded others.

The evidence they are looking at is often limited or flawed.

• In another study, Chauhan and colleagues demonstrated that only 23% of recommendations in obstetric guidelines from ACOG are based on Level A evidence.
• Even when they looked at randomized, controlled trials (RCTs, eg, “Level A evidence”) used in ACOG guidelines, they found that few of the trials adhered to a minimum set of recommendations for reporting RCTs. In other words, the RCTs that ACOG was relying on  when they did cite Level A evidence may have been flawed.

Even when guidelines are evidence-based, they’re often ignored.

• When ACOG issued new guidelines about fetal heart rate monitoring in labor last year, blogs and Twitter went nuts with the news that they had finally admitted that intermittent auscultation is safe and effective, and that continuous electronic fetal monitoring doesn’t live up to its many promises.  I pointed out at Our Bodies, Our Blog that ACOG hadn’t changed a single word of its guidelines with respect to intermittent auscultation and the limitations of EFM; it’s just that their recommendations had been ignored. (No surprise: they’re still being ignored.)

And then there’s the not-so-small issue that guidelines suggest that a “one size fits all” approach will translate into the best care for everyone, which anyone who takes care of patients or has been a patient recognizes is flat-out false. We all have different reasons for making the health choices we do. An individual’s informed consent or refusal can and should trump guidelines, but in practice, guidelines dictate practice and policy for all women. Case in point: the last time ACOG issued VBAC guidelines, hospitals and care providers began banning vaginal birth outright in women with prior cesarean surgery. The VBAC rate in this country plummeted virtually overnight.

The International Cesarean Awareness Network is hosting a blog carnival on the theme, “Why is VBAC a Vital Option?” I suspect we’re going to hear a huge range of responses, along with some stories of the astounding lengths some women have gone to in order to ensure that VBAC remained a viable option for them. Not every woman goes to these lengths – plenty of women are perfectly happy to have repeat cesareans and would make that choice even if VBAC was offered and supported – but these stories underscore the fact that blanket guidelines will not apply to every woman everywhere.

Despite all of this, I’m actually rather optimistic about the NIH VBAC Conference. In my mind, the situation around VBAC has gotten so bad in this country that a fresh look at the issues and the evidence can only help matters. Plus, the meeting comes on the heels of major recommendations for maternity care reform and the conference findings are likely to echo and lend credence to many of these. Judith Rooks shares six more reasons we should be optimistic about the upcoming meeting. And last but not least, there is a huge consumer contingent planning to have their voices heard at this conference either in person or by webcast, and many of them are connected via social networks to a far greater number of consumers. You can hear me and Lamaze President-Elect Debra Bingham on The Feminist Breeder’s Blog Talk Radio Show on Monday, recapping Day One of the proceedings.

Amy Romano Uncategorized ACOG, cesarean, NIH Consensus Conference, Practice Guidelines, VBAC

[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

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

Mayri Sagady Leslie Practice Guidelines ACOG, GBS, induction, infection, Practice Guidelines, PROM, safety

Ahh, the new ACOG induction guidelines, so much to dislike, so little time. Still, others are also commenting, so I will focus on debunking ACOG’s portrayal of misoprostol.

ACOG STATEMENT: “There is . . . a large body of published reports supporting (misoprostol’s) safety and efficacy when used appropriately” (p. 387).

FACT: None of the studies have been big enough either alone or in the aggregate to detect differences in rare, catastrophic events, a point acknowledged by a Cochrane systematic review, and it is those rare, catastrophic events that are the issue with “miso.” And while more disasters will occur with higher doses and in women with prior cesareans, there is no “appropriate” use of misoprostol in terms of safety.

ACOG STATEMENT: “No studies indicate that intrapartum exposure . . . has any long-term adverse health consequences to the fetus in the absence of fetal distress [emphasis mine]. . . .” (p. 387).

FACT: Well, that’s the catch, isn’t it? The long-term adverse health consequences to the fetus occur in the presence of fetal distress subsequent to uterine rupture—including in unscarred uteruses and with moderate doses of misoprostol—and amniotic fluid embolism. In some cases, of course, the fetus doesn’t survive to experience long-term consequences.

ACOG STATEMENT: “Although misoprostol currently is approved by the U.S. Food and Drug Administration (FDA) for the prevention of peptic ulcers, the FDA in 2002 approved a new label on the use of misoprostol during pregnancy for cervical ripening and for the induction of labor. This labeling does not contain claims regarding the efficacy or safety of misoprostol” (p. 387).

FACT: A reader can be forgiven for assuming from this convoluted phrasing that the FDA now approves of using misoprostol to induce labor. The reader would be wrong. The FDA removed the “black box” designation prohibiting use in pregnant women, but it takes a much dimmer view of “miso” than merely not claiming it is safe. Here is an excerpt from the FDA’s 2002 statement (PDF):

A major adverse effect of the obstetrical use of Cytotec is hyperstimulation of the uterus which may progress to uterine tetany [uterus contracts and doesn't let go] with marked impairment of uteroplacental blood flow, uterine rupture (requiring surgical repair, hysterectomy, and/or salpingo-oophorectomy [removal of the ovaries and Fallopian tubes]), or amniotic fluid embolism [maternal and infant mortality is very high from this]. Pelvic pain, retained placenta, severe genital bleeding, shock, fetal bradycardia [profound slowing of the fetal heart], and fetal and maternal death have been reported.

There may be an increased risk of uterine tachysystole [contractions coming too fast], uterine rupture, meconium passage, meconium staining of amniotic fluid, and Cesarean delivery due to uterine hyperstimulation with the use of higher doses of Cytotec; including the manufactured 100 mcg tablet. The risk of uterine rupture increases with advancing gestational ages and with prior uterine surgery, including Cesarean delivery. Grand multiparity [usually defined as more than four births] also appears to be a risk factor for uterine rupture.

What actually happened was this: ACOG held that “misoprostol is one of the most important medications in obstetrical practice. . . . The real victims in this scenario [i.e., prohibition in pregnancy] are pregnant women who receive treatment in hospitals that will not allow the use of misoprostol” (Hale 2001, p. 59). Lobbied by ACOG, the FDA rescinded the black box designation on the grounds that obstetricians were using it to induce labor, a rationale that amounts to “but all the kids are doing it.”

ACOG STATEMENT: “The majority of adverse maternal and fetal outcomes associated with misoprostol therapy resulted from the use of doses greater than 25 mcg” (p. 387).

FACT: The “majority” of adverse outcomes is hardly reassuring. What about the minority? Not to mention that obstetricians may ignore recommended dosages, and even the guidelines say “Misoprostol in higher doses (50 mcg every 6 hours) may be appropriate in some situations” (p. 390). In any case, misoprostol is formulated in 100 mcg tablets for use as an oral ulcer medication. Getting a 25 mcg dose means cutting an unscored tablet in quarters. It’s anybody’s guess what dosage is really delivered.

The real kicker is that according to the Cochrane systematic review, misoprostol is no more effective than the FDA approved medication, PGE2 (a.k.a dinoprostone, trade names Cervidil and Prepidil). More vaginal deliveries happened within 24 hours after administration, but cesarean rates overall did not differ between groups. Cesarean rates in trials comparing misoprostol with with intravenous oxytocin (trade names Pitocin or “Pit” and “Syntocinon”) were more variable, but not all of them found reductions in cesarean rates with misoprostol. Meanwhile, misoprostol results in higher rates of uterine hyperstimulation and uterine hyperstimulation with adverse changes in the fetal heart rate than other agents. And misoprostol has yet another major disadvantage: Oxytocin has a short half-life. If contractions get too strong or too close together, turn the I.V. drip down or off, and within a little while, contractions fade. If misoprostol hyperstimulates the uterus, you are stuck. Moreover, lurking in the “miso works faster” benefit is a problem not captured in the trials because they only measure major morbidity: some women are thrown into violent labors. These labors should have given researchers pause, though, if for no other reason than they are the precursor, the shark fin in the water, of misoprostol’s potential for severe fetal distress, massive hemorrhage, uterine rupture, and amniotic fluid embolism.

Why, then, are obstetricians so enamored of misoprostol? The answer is summed up by this obstetrician enthusiast:

The best part about it is that you can block-schedule your nurses so that you have enough on hand. . . [I]f we start our inductions at 7 a.m., we know that we’re going to have X number of patients in labor being admitted by 4 p.m. That’s helped our hospital tremendously, . . . [Cytotec is] a great agent. It works very, very efficiently. . . . And it’s ungodly inexpensive: 27 cents per tablet.

In other words, Cytotec’s real benefits are convenience for obstetricians and helping the hospital’s bottom line. For women and babies, though, it’s a roll of the dice. Most times things go fine, but sometimes the dice come up snake eyes.

Reference:

Hale, R. W., & Zinberg, S. (2001). Use of misoprostol in pregnancy. N Engl J Med, 344(1), 59-60.

Henci Goer Uncategorized ACOG, induction, misoprostol, Practice Guidelines, safety