Sunday, December 15, 2013

New Terminology for Term Pregnancies

In November, 2013, ACOG released Committee Opinion 579: Definition of Term Pregnancy. The new guideline suggests using the following terms:

  • Preterm: Before 37 0/7 weeks gestation
  • Early term: 37 0/7 - 38 6/7 weeks gestation
  • Full term: 39 0/7 - 40 6/7 weeks gestation
  • Late term: 41 0/7 - 41 6/7 weeks gestation
  • Post-term: Greater than 42 0/7 weeks gestation
The Opinion recommends against referring to all deliveries between 37 and 42 weeks as Term. The new nomenclature emphasizes the primacy of neonatal outcomes between 39 and 41 weeks gestation. 

New Preeclampsia Guidelines

In November 2013, ACOG released a new publication, Hypertension in Pregnancy, which significantly changes a few things about the diagnosis and treatment of hypertension in pregnancy.

The Guideline recognizes four categories of hypertension in pregnancy:
  1. Preeclampsia-eclampsia
  2. Chronic hypertension
  3. Chronic hypertension with superimposed preeclampsia
  4. Gestational hypertension
One of the most fundamental changes is removing the necessity of proteinuria from the diagnosis of preeclampsia. Going forward, preeclampsia is diagnosed when there is:
  • New onset hypertension after 20 weeks greater than 140/90 on two occasions at least four hours apart;
  • Proteinuria of at least 300 mg/24 hours (or this amount extrapolated out from a shorter interval). 
If proteinuria is not present, then the diagnosis can still be made if hypertension plus any of the following are present: 
  • Thrombocytopenia (platelets less than 100,000);
  • Renal insufficiency (serum creatinine greater than 1.1 or a recent doubling of the creatinine in the absence of other renal disease);
  • Impaired liver function (elevation of the transaminases to double normal);
  • Pulmonary edema;
  • Cerebral or visual symptoms. 
Of note, the term mild preeclampsia should give way simply to preeclampsia. 

The diagnosis of preeclampsia with severe features (replacing the term severe preeclampsia) is no longer dependent upon the amount of proteinuria (removing the previous 5g/24 hour criteria). The guideline instead focuses on signs and symptoms of end-organ damage. The following features are used to diagnosis preeclampsia with severe features: 
  • BPs greater than 160/110 on two separate occasions four hours apart;
  • Thrombocytopenia (platelets less than 100,000);
  • Progressive renal insufficiency (serum creatinine greater than 1.1 or a recent doubling of the creatinine in the absence of other renal disease);
  • Impaired liver function (elevation of the transaminases to double normal), severe progressive RUQ or epigastric pain unrelieved by medication and not otherwise explained, or both;
  • Pulmonary edema;
  • New onset cerebral or visual symptoms. 
Of note, growth restriction is no longer used as a criterion for preeclampsia with severe features, and the management of severe growth restriction or abnormal umbilical artery dopplers is the same whether the patient has hypertension or not. 

Gestational hypertension is simply new onset hypertension after 20 weeks without proteinuria or any of the above symptoms. 

The Task Force did not recommend any screening for the prediction of preeclampsia beyond history and physical (such as ultrasounds or biochemical markers). They did recommend starting a low-dose aspirin in women who have had preeclampsia in more than one prior pregnancy or in women who have previously been delivered at or before 34 weeks due to preeclampsia in any pregnancy. Vitamins C and E, bed rest, and salt restriction were not recommended. 

Delivery of women with preeclampsia without severe features is recommended at 37 0/7 weeks. Use of NSAIDs should be avoided if hypertension persists greater than 1 day after delivery due to the effect of nonsteroidals on blood pressure. 

For women with preeclampsia with severe features, delivery should continue at 34 weeks or sooner if any of the following is present:
  • Uncontrolled severe hypertension
  • Eclampsia
  • Pulmonary edema
  • Abruptio placentae
  • DIC
  • Nonreassuring fetal status
  • IUFD
Women with Chronic Hypertension should not be delivered before 38 weeks. For women with chronic hypertension with superimposed preeclampsia, delivery is at 37 weeks or earlier if severe features are present. 

All 99 pages are worth reading and there are many more specific recommendations, but these are the most fundamental changes to what has been standard of care for the last few years.  

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.