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Determining the Optimal Time to Deliver
AbstraCt & Commentary
By John C. Hobbins, MD, Professor and Chief of Obstetrics, University of Colorado Health Sciences Center, Denver, is Associate Editor for OB/GYN Clinical Alert.
Dr. Hobbins reports no financial relationship to this field of study.
Synopsis: Neonatal mortality and morbidity are not inconsequential after late preterm birth (34-36 weeks) and, with the exception of macrosomia, infant morbidity increases with each week after 39 weeks of gestation.
Source: McIntire DD, Leveno KJ. Neonatal mortality and morbidity rates in late preterm births compared with birth at term. Obstet Gynecol 2008;111:35-41.
The stars were aligned when four papers appeared in two obstetrical journals within a month of each other dealing with the optimal time in gestation to deliver. Although I will initially be focusing on the index article by McIntire and Leveno, the others will be touched upon later.
McIntire and Leveno reviewed singleton records from Parkland Hospital in Dallas from 1988 through 2005. Since they were particularly interested in neonatal morbidity and mortality in the late preterm infant (34-36 weeks), they compared outcomes in this group with those born later in gestation. During this time the overall preterm birth rate was 9% at this hospital, but 75% of these were contributed by births between 34-36 weeks (representing 133,022 infants).
Looking at neonatal mortality per 1000, the authors found this to be 0.2 in those born at 39 weeks, compared with 1.1 at 34 weeks, 1.5 at 35 weeks, and 0.5 at 36 weeks. Morbidity was described as: respiratory distress syndrome (RDS) requiring mechanical ventilation, transient tachypnea of the newborn, grade 1 or 2 intraventricular hemorrhage, need for sepsis workup and/or positive cultures, intubation, or use of phototherapy for hyperbilirubinemia. One or more of these were present in 34% at 34 weeks, 24% at 35 weeks, and 17% at 36 weeks.
The authors concluded that being born at 34-36 weeks is not great for one's health and obviously can be expensive, but when one looks for nuggets in the data to help with prevention, one comes up empty. For example, 80% of the late preterm births resulted from "idiopathic" preterm labor. The remaining 20% were delivered because of "obstetrical complications."
This article, and another in the October issue of the American Journal of Obstetrics and Gynecology by Bastek et al,1 points out that one should not be cavalier about a birth that is a week or two less than 36 weeks, but what about the risks to the neonate of birth at the very end of pregnancy? Another paper in the same issue of American Journal of Obstetrics and Gynecology by Cheng et al dealt with this question.2 The authors sifted through data from the U.S. Vital Statistics Birth Certificate Registry for 2003, concentrating on deliveries occurring between 37-41 weeks. When comparing those born at 37 weeks vs 39 weeks, they found a two-fold greater need for mechanical ventilation and a 70% greater chance for low 5 minute Apgar scores at 37 weeks. Rates of macrosomia went up every week after 37 weeks and neonatal injury rose at 40 weeks. The cesarean section rate increased appreciably at 41 weeks, as well as the incidence of meconium aspiration. With the exception of macrosomia, all adverse outcomes were lowest at 39 weeks.
The above studies suggest that the further birth is away from 39 weeks (in either direction), the greater are the neonatal mortality and morbidity, but this information needs to be put into proper perspective. In the McIntire study, 80% of the late preterm births resulted from "idiopathic" labor or premature rupture of membranes. We now know from the comprehensive research in preterm labor in the perinatal division of the NICHD that 19% of patients in preterm labor with intact membranes and 34% of those with premature rupture of membranes have positive amniotic fluid cultures, and the earlier in pregnancy these events occur, the greater is the chance of intrauterine infection. It has also recently become clear from work by the same group that antibiotics might temporarily discourage uterine contractions in the face of intrauterine infection, but they provide no deterrent to the infection itself or to bacteria's detrimental effect on the fetal brain through cytokine elaboration. So, if we are thinking that aggressively attempting to stop all labors occurring between 34 and 36 weeks will remedy prematurity, in some cases we may be exchanging an infant with less need for mechanical ventilation for one who later develops cerebral palsy. Regarding steroids, no study has shown their efficacy in preventing the 34-36 week infant from getting RDS, but the prevalence of bona fide RDS is so low in this group of infants that one would need a huge randomized clinical trial to show any benefit.
Although recent evidence indicates that most tocolytics are ineffective or, in some cases, harmful, there is some suggestion that calcium channel blockers (nifedipine) may actually work. Then we should do everything possible to rule out infection before attempting to extend a 34-35 week pregnancy when preterm labor occurs. However, my gut feeling is that a good portion of the neonatal morbidity does not come from prematurity per se as much as from the reasons for their mothers having preterm labor.
One way to make sure that a fetus is not less mature than expected is to make every attempt to document dates early in pregnancy. The RADIUS study showed us that if we depended upon well-remembered last menstrual period (LMPs) alone, more than 1 out of 10 times we would be off by more than one week, as indicated by second trimester ultrasound examinations.3 Since decisions regarding whether to stop labor, whether to induce labor, or even whether to do a cesarean section, can be very dependent upon gestational age, unexpected prematurity should not be surprising in a pregnancy that is less than scrupulously dated.
At the end of pregnancy there has been a general trend toward earlier deliveries. A few years ago, there was an ongoing debate about empirically delivering all post-term patients (42 weeks or more) or managing them expectantly. However, recently it seems that the definition of "post-term" has evolved to include pregnancies that have extended past 40 menstrual weeks by one minute. Now, simply based on a statistical trend, the authors of the above paper showing optimal outcome at 39 weeks are suggesting greater use of "stripping membranes and induction" rather than even waiting for 40 weeks, the average time for labor to spontaneously ensue. Based on this mindset, it is no wonder that our cesarean section rate is now 30.5%, and, as Ken Leveno has pointed out in a companion commentary in Obstetrics & Gynecology, births at 40 weeks have declined by 29% and the average birthweight has dropped in the United States.4
Last, two studies from San Antonio and Canada have shown increased rates of the need for mechanical ventilation in neonates delivered by cesarean section at 36-39 weeks. One wonders how many of these infants were really as old as they were thought to be.
The point is that in every pregnancy dates should be confirmed as early as possible and, in the absence of evidence-based proof of benefit, interventions such as induction should be employed for more compelling reasons than "designer timing." On the other hand, in a patient with preterm labor, every attempt should be made to rule out an underlying cause that may have a detrimental long-term affect on the fetus if left in the uterus.