Tuesday, February 17, 2009

Hysterotomy Technique

The classical uterine entry technique during cesarean delivery was a vertical incision, which avoided damage to the vessels laterally and provided ample room for delivery of any fetus in any presentation; but the classical vertical incision was complicated by heavier bleeding from the myometrium and significant risk of extension into the bladder and vagina. Compared to low transverse incisions, it also is accompanied by a significantly higher risk of rupture in future pregnancies. 

In 1882, Kehrer recommeded a low transverse incision at the level of the internal os. Later, Fritsch suggested a transverse fundal incision. Neither of these techniques became popular. Other authors began to suggest a transverse lower uterine segment incision (i.e., Kronig in 1911), but this did not become popular until 1926 when Monro Kerr published the results of his study showing this incision's superiority to the classical technique. 

Since the 1950s, Munro Kerr's low transverse incision has been the standard technique. The incision has typically been made making a small entry with a scalpel and then extending the incision laterally with either sharp or blunt dissection. Various studies have shown the benefit (e.g., less blood loss) of blunt extension of the myotomy instead of sharp dissection (as with bandage scissors). Most techniques involve directing the incision upward to minimize both lateral and downward extension. 

Now comes a study by Cromi et al. (AJOG, 2008;199:292e1-292e6) which randomized blunt extension of the low transverse incision to one of two techniques: either with the fingers separating in a transverse direction (the traditional method) versus cephalad-caudad extension. They found that the new method showed a lower rate of unintended extension (7.4% vs 3.7%, p=0.03) and lower incidence of blood loss > 1500 ml (2.0% vs 0.2%, p=0.4). There was also an increased need for additional stitches in the transverse group (33.2% vs. 22.9%, p=0.001). Other non-significant findings included higher rate of uterine vessel injury in the transverse group, greater estimated blood loss, and larger decrease in hemoglobin.

Many of the techniques used in cesarean delivery are the result of tradition alone. Given how few, good randomized trials exist regarding cesarean technique, this current Italian trial should lead to widespread change of practice until better evidence comes forth. 

Monday, February 9, 2009

Magnesium for Prevention of Cerebral Palsy

Wordle: Mag
The role of magnesium sulfate in the treatment of preterm birth continues to be investigated and advocated by some. The use of magnesium sulfate for the treatment of preterm labor has nearly been put to rest, as study after study has failed to show any prolongation of pregnancy or maternal/fetal benefit. However, evidence from some of the studies has strongly suggested the possibility that magnesium causes fetal harm/death.

At the same time, there is controversy among the studies so far regarding the possible role of magnesium for providing a neuroprotective benefit against cerebral palsy (CP). The question has been raised that even if the use of magnesium as a tocolytic is abandoned (which it should be), then perhaps we should continue giving magnesium to protect the fetus against developing cerebral palsy.

Nelson and Grether first suggested in 1995 (Pediatrics,; 95:263-9) that magnesium might serve such a role. They did a retrospective case-control study in California of 150,000 children followed to age 3. They found that 7% of very low birth weight (VLBW) babies developed CP who had been exposed to magnesium in utero compared to 36% of matched peers who had not been exposed to magnesium. These findings led to the MagNET trial.

In MagNET, women in preterm labor were randomized to magnesium vs placebo. The trial was stopped at 15 months because of the high rate of pediatric mortality noted in the magnesium group (10 deaths in the mag group vs 1 in the placebo group; p=0.02). The authors studied the data in this study and found that newborns with higher ionized magnesium levels in umbilical samples were more likely to have intraventricular hemorrhage (IVH) and the perinatal demises were 14.8x as likely to have Grade III hemorrhage (p=0.025).

Scudiero et al. (Obstet Gynec 2000;96:178-182) followed up MagNET with a case-control study which found that exposure to more than 48 grams of magnesium was associated with a 4.72 odds ratio of fetal death. This finding led advocates of magnesium to investigate low-dose magnesium protocols.

Crowther et al. (JAMA 2003;290:2669-2676), in the ACTOMgSO4 study, randomized low-dose magnesium vs placebo to 500 women and found no significant difference in the rate of cerebral palsy. All of the studies were reviewed by the Cochrane Review (Cochrane Database Syst. Rev. 2007 Jul 18[3];CD004661) and they concluded:
antenatal magnesium sulfate therapy as a neuroprotective agent for the preterm fetus is not yet established.
Now comes a study in the New England Journal of Medicine by Rouse et al. (NEJM 2008:359;9) which randomized 2241 women at risk for preterm delivery (mostly with preterm rupture of membranes) to magnesium vs placebo. The primary outcome to be studied was the incidence of moderate or severe cerebral palsy or death, and no significant difference was found between the two groups.

However, two secondary analyses were performed: death alone and moderate or severe cerebral palsy alone. For death alone, there was an excess of 10 fetal deaths in the magnesium group but this did not rise to the level of statistical significance. For moderate or severe cerebral palsy alone, there was an excess of 18 cases of CP in the placebo group and this was significant (p=0.03). However, when surviving twins (one twin died, one survived) who developed CP are excluded from each group, then the magnesium group had an excess of 12 deaths, and the placebo group had an excess of 15 cases of CP. If it can be assumed that had the excess 12 deaths lived they would have developed CP, then the whole study is a wash.

So really, this study is like the studies that have come before it: it suggests that CP may be reduced because the total number of survivors are reduced. The appropriate outcome to be studied was the combined outcome of death and CP, which again showed no significant difference. Another way of looking at the data is to think about the total number of intact survivors in each arm of the study: 88.7% of the infants in the magnesium group were intact, whereas 88.3% of the survivors in the placebo group were intact. And if we take out the 4 sets of twins with death/CP that were distributed unevenly, then those numbers change to 88.75% and 88.56% respectively. Neither set of these numbers is anywhere near statistically significant.

Many will criticize this analysis of these numbers by pointing out that the increased rate of death found in this study was not statistically significant; true - but that may be simply because the study was underpowered to study that particular outcome. The study was powered for the combined primary outcome of death + CP, and for this it showed no significant difference.

Saturday, February 7, 2009

Laparoscopic Entry Techniques

A wide variety of opinions exist regarding the best method for initial laparoscopic trocar entry. The three techniques commonly used are: open laparoscopy, which involves layer-by-layer dissection and then anchoring the trocar into the fascia; Veress needle insufflation, where the Veress needle is used to insufflate the peritoneal cavity prior to placing the trocar; and direct entry laparoscopy, where the trocar is inserted directly into the abdomen. The last technique can be done with an optical-entry trocar, which allows the surgeon to see the layers of tissue while pushing the trocar in. 

The issue over which technique is best centers around two main categories of injury: major vascular injury and bowel injury. Both of these injuries are rare but dozens of studies, both prospective and retrospective, have been done to give us solid numbers regarding the injury rate. 

Molloy et al. (Aust N Z J Obstet Gynaecol 2002: 42: 3: 246) have performed a meta-analysis of 51 studies performed before the year 2000. They found the following rates of injury per 1000 cases:
Veress Open Direct
Bowel injury 0.4 1.1 0.5
Vascular injury 0.4 0 0
Combined injury 0.8 1.1 0.5

These rates of injury are basically the same in the prospective studies as well. When patients were studied prospectively to Open vs the Direct entry techniques (eliminating the selection bias for patients at high risk for bowel injury), the following rates were found per 1000 patients: 

Open Direct
Bowel injury 0.82 0.31
Vascular injury 0 0
Combined injury 0.82 0.31

So Direct Entry wins again. 

Interestingly, virtually every vascular injury in the dozens of studies available occur with Veress needle entry. So both Open and Direct entry virtually eliminate the risk of major vascular injury. But the Open technique, first described by Hasson in 1971, poses a relative risk of 2.6x the rate of bowel injury vs the direct entry technique. 

Two additional things may tip the scales toward direct entry even more. First, more than half of the bowel injuries with direct entry occur in patients with previous vertical abdominal laparotomy incisions or previous multiple infra- or intra-umbilical incisions. Use of an alternative site, such as Palmer's point, 3 cm below the costal margin on the left side at the midclavicular line, would theoretically reduce the rate of bowel injury with direct entry by half. Secondly, use of optical trocars, allowing the surgeon to survey the layers of tissue during the entry, may afford a reduction in injuries as well. 

And there are other advantages of direct entry: smaller incisions (typically a 5mm port) which lead to less pain, less bleeding, and easier closure (usually just with Dermabond); quicker abdominal entry and shorter OR time; and no cases of gas embolism, which is a problem with Veress needle entry and which leads to 1 patient death in roughly every 5000 cases employing the Veress needle. 

So the clear winner seems to be direct entry laparoscopy, probably with an optical trocar. This contradicts years of traditional teaching and what purports to be common sense regarding avoiding major injuries at the time of initial port placement. Unfortunately, what the evidence holds out as the safest option is also the least used, with only about 10% of surgeons/gynecologists routinely using this technique.  

Thursday, February 5, 2009

How safe is home birth, really?

A lot of interest has been given recently to the safety of home birth attended by Certified Professional Midwifes (CPMs) and other lay- and nurse- midwives. A recent position statement from the American College of Obstetricians and Gynecologists (ACOG) endorsed by the AMA states that: 
. . . the safest setting for labor, delivery, and the immediate postpartum period is in the hospital, or a birthing center within a hospital complex . . . 
This statement has been vilified by many different groups who advocate for home birth, and even recently in an editorial by Nancy Lowe in the Journal of Obstetric, Gynecologic & Neonatal Nursing (2009;38:1). But is this statement inaccurate? Certainly the vast majority of low-risk births attended or even unattended at home will end well for both mother and baby. The graphic below shows some problems which can occur during labor, along with interventions and possible consequences of these problems. These are listed from most common to least common with the appropriate incidences as a percentage. Note that many of these interventions can only be provided in the hospital setting (e.g., cesarean section) and many of these problems cannot be anticipated prior to labor (e.g., abruption, shoulder dystocia, or anaphylactoid syndrome of pregnancy): 

As far as the safety of home birth is concerned, home birth advocates frequently cite a study from the British Medical Journal in 2005 (330:1416) by Johnson and Daviss. Indeed, this paper is the strongest study yet and is referenced directly or indirectly in both professional and lay literature frequently (see Ricki Lake's movie, The Business of Being Born) to establish the safety of home birth in North America. 

This paper analyzed 98% of home births in Canada and the United States in the year 2000 which were attended by CPMs. They analyzed major outcomes and transfers to hospitals and concluded:
Planned home births for low risk women in North America using certified professional midwives was associated with lower rates of medical interventions but similar intrapartum and neonatal mortality to that of low risk hospital births in the United States. 
But the data in the study has been shrewdly manipulated with surprisingly very little academic scrutiny. Of 5418 births of women who intended to deliver at home, they found that 12.1% were transferred to the hospital for various reasons. They also claimed 1.7 neonatal deaths/1000 planned home births and state that this compares favorably to hospital births in North America. 

However, they excluded babies with life-threatening congenital anomalies (though these infants were not excluded from the comparison group) and they did not compare the home-births to hospital births occurring in the US in the year 2000, even though that data was and is readily available from the CDC and they even cite other data from the same CDC report in their paper. Instead, the largest data set regarding hospital births used in this study comes from 1989 in California, with no matching of patient characteristics. They also excluded deaths occurring in breech deliveries at home (even though this was an intent-to-treat study). 

If we use their data from the study and include deaths from breeches, the rate rises to 2.0/1000. If we add back anomalous infants, the death rate rises to 3.32/1000. Using CDC data regarding all births in the hospital in the United States in the year 2000, and including only infants weighing > 2500 grams (99% of the home births in the report were > 2500 grams), then we find the following rates: 

Even this comparison, which shows 0.65/1000 neonatal deaths in the hospital compared to 2.0/1000 at home among non-anomalous infants, is not entirely accurate. The babies born in the hospital in this data set include all-comers, both low-risk and high-risk, healthy and not healthy. Yet, the babies born at home were necessarily a low-risk, healthy population (or else the CPMs would not have endeavored to deliver these women at home in the first place). The point is, a randomized trial using matched, healthy patient populations of only low-risk pregnancies would likely reveal a rate of neonatal death much lower than 0.65/1000 in the hospital.

What does this all mean? Well, there were 3,427 neonatal deaths in the United States among this demographic (term women) in the year 2000. If the same cohort of women had home births instead (at least if that was the intent-to-treat), then there would have been 12,443 neonatal deaths in the year 2000, which is an excess of 9,016 deaths. This calculation is based on the data reported in Johnson and Daviss' study! To put this in perspective, in the year 2002 in the US, there were only 12,008 deaths from all causes among children aged 1-14. So we would effectively double the death rate of children under the age of 14 in the United States. 

Of course, these projections do not account for other significant outcomes, such as the rates of permanent neurological injury from shoulder dystocia or hypoxia (Erb's or Cerebral Palsy), or post-neonatal mortality which tends to rise proportionately with neonatal mortality (in other words, this is the excess death caused in the first month of life). 

So the statement of ACOG and the AMA that the safest place to have a baby in the US is in the hospital is true. In fact, using Johnson and Daviss' paper, it is at least 3x as safe (0.65 vs 2.0/1000) using neonatal mortality alone as an outcome. Still, home-birth will always have strong anecdotal support since, fortunately, more than 99% of home or hospital births end well.