Premature delivery following premature rupture of membranes: increasing frequency with disappointing outcome.

Over 4,000,000 infants are born each year in the United States. Preterm delivery, primarily as a result of preterm labor (PTL) and preterm premature rupture of the membranes (PPROM), is the greatest contributor to newborn and infant morbidity and mortality, far exceeding other complications of pregnancy. In spite of many innovations in the management of pregnancy and threatened preterm labor, the risk of preterm delivery continues to rise. In 2004, 12.5% of all deliveries were preterm. (1) That represents a 32% increase since 1952, and a 15% rise in preterm deliveries since 1990.

The risk of preterm delivery is inversely proportional to the gestational age. Infants that are categorized as "very preterm," those born at less than 32 weeks gestational age and/or 1,500 g (3 lb 4 oz), are at greatest risk. While the number of infants born at less than 32 weeks gestation is about 2% (82,300 births nationally), they represent greater than 80% of the morbidity and mortality in the newborn.

Over the past 20 years, many developments in the care of the preterm newborn have dramatically improved the survival rate of preterm infants. In addition to better survival, the morbidity associated with prematurity has diminished as well. However, tremendous challenges still face the management of the extremely preterm infant, those born near the threshold of viability. Infants born prematurely at the gestational ages of 22 to 26 weeks face incredible risks directly related to their gestational age. Obstetricians caring for patients at risk for such an early delivery face difficult challenges in how aggressively to manage their patient to prevent delivery. Maternal risks have to be measured against newborn benefits, which are often difficult to define at very early gestational ages. Utilization of tocolytic drugs to delay delivery, corticosteroids to enhance fetal lung maturity, and antibiotics to reduce the risk of infection all pose some maternal risk. Furthermore, aggressive management may include cesarean delivery, often for limited fetal benefit.

Recent data has compounded the complexity of decision-making at these early gestational ages. While "survival" data is often biased by the endpoint of measurement, there has been a gradual increase in survival at very early gestational ages. Recent survival rates for Austrian newborns that survived to reach the neonatal intensive care unit (NICU) were 17%, 24%, 57%, 74%, and 87% for 22, 23, 24, 25, and 26 weeks gestational ages respectively. (2) It should be noted that 27% did not live long enough to reach the NICU, thus improving the newborn survival rates reported. However, rates of cerebral palsy among survivors were 33%, 50%, 33%, 26%, and 25% for 22, 23, 24, 25, and 26 weeks gestation. Similar data is reported from the United States, with striking differences in outcome based upon the presence of neonatal infection following delivery. (3)

The largest study yet published that follows extremely preterm infants to school age is very disappointing. (4) The study included all infants born extremely preterm in the United Kingdom and Ireland in 1995. The authors were able to follow outcomes for a very high proportion (78%) of survivors until school age. Neonatal survival to discharge was 1%, 11%, 26%, and 44% at 22, 23, 24, and 25 weeks gestation. Importantly, the proportion of survivors with no disability at 6 years of age were 5%, 6%, 12%, and 24% at 22, 23, 24, and 25 weeks gestational ages at delivery. Only 20% of all of these extremely premature infants had no disability at 6 years of age, and 41% had serious impairment in cognitive function. Sadly, many infants demonstrated deterioration in testing results from infancy until beginning school. A very high percentage of these pregnancies and newborns received aggressive care, with antenatal steroids, pulmonary surfactant, and developmental assistance following hospital discharge.

The results of this recent study are disturbing, as it suggests that we may not have effective tools to prevent the significant, lifelong morbidity associated with extremely preterm delivery. Some studies suggest that immaturity associated with such early deliveries, especially involving the developing CNS, may be a critical compromise to intact survival. (5) Extreme immaturity results in a very high risk of injury to the CNS, and may limit postnatal development.

We continue to see the preterm delivery rate increase in this country each year. We do not have effective methods to prevent PTL or PPROM from resulting in preterm delivery. Furthermore, we seem unable to address the root causes of PTL, especially in the singleton gestation. Unfortunately, preterm delivery at very early gestations creates tremendous risk of mortality and lifelong morbidity. It is unlikely that these risks will diminish. We must find better ways to reduce the risk of preterm delivery in our health care system.

References

1. Hamilton B, Martin J, Ventura S, et al. Births: Preliminary data for 2004. National Vital Statistics Reports. Vol 54, No. 8. Hyattsville, Maryland, National Center for Health Statistics, 2005.

2. Weber C, Weninger M, Klebermass K, et al. Mortality and morbidity in extremely preterm infants (22 to 26 weeks of gestation): Austria 1999-2001. Wien Klin Wochenschr 2005;117:740-746.

3. Stoll B, Hansen N, Adams-Chapman I, et al. Neurodevelopmental and growth impairment among extremely low-birth-weight infants with neonatal infection. JAMA 2004;292:2357-2365.

4. Marlow N, Wolke D, Bracewell M, et al. Neurologic and developmental disability at six years of age after extremely preterm birth. N Engl J Med 2005;353:9-19.

5. Huttenlocher P, Dabholkar A. Regional differences in synaptogenesis in human cerebral cortex. J Comp Neurol 1997;387:167-178.

At twilight, nature is not without loveliness, though perhaps its chief
use is to illustrate quotations from the poets.
--Oscar Wilde

John D. Yeast, MD, MSPH 

From the Department of Obstetrics and Gynecology, University of Missouri Kansas City, and the Department of Medical Affairs, Saint Luke's Hospital of Kansas City, Kansas City, MO.

Reprint requests to John D. Yeast, MD, MSPH, University of Missouri Kansas City, 4401 Wornall Road, Kansas City, MO 64111. Email: [e-mail]

Accepted March 24, 2006.