With respect to short-term neonatal morbidity, we compared survivors with nonsurvivors who lived long enough to become at risk for each morbidity (Table 2). Survivors and at-risk nonsurvivors received a diagnosis of RDS and required exogenous surfactant. All survivors progressed to chronic lung disease. Two of 11 survivors had grade 3 or higher retinopathy of prematurity. Because they died, no nonsurvivor received a diagnosis of chronic lung disease or retinopathy of prematurity.
We did not detect a difference in proportions of survivors and at-risk nonsurvivors diagnosed with necrotizing enterocolitis. One of 11 survivors and 8 of 12 at-risk nonsurvivors developed severe intraventricular hemorrhages (grade 3 or 4) (P = .03). A significant difference in periventricular leukomalacia was also found between survivors and at-risk nonsurvivors: 1 of 11 and 7 of 12, respectively (P = .03) (Table 2). The survivor with severe intraventricular hemorrhage did not develop periventricular leukomalacia. All nonsurvivors admitted to the NICU died after decisions to withdraw care after consultation with the family because of worsening clinical prognoses, rather than after calamitous events and unsuccessful resuscitation.
Cox proportional hazards were calculated to examine the effect on survival of advancing gestation in the 23rd week and antenatal corticosteroids while controlling for gestational age. In a model for gestational age in which the 23 0/7 to 23 2/7 category was the reference group, the survival hazard ratio was statistically significant and improved with each successive gestational age category: 0.26 (95% CI 0.09, 0.76) at 23 3/7 to 23 4/7 weeks (P = .014) and 0.10 (95% CI 0.03, 0.34) at 23 5/7 to 23 6/7 weeks (P < .0001), suggesting successive improvements in survival with advanced gestation in the 23rd week. In the second model, the hazard ratio for corticosteroid administration was initially significant (0.37 [95% CI 0.15, 0.90]) as a bivariate but became nonsignificant with introduction of control variables for gestational age in the 23rd week (0.66 [95% CI 0.25, 1.76]). This change suggests that the apparent beneficial effect of antenatal corticosteroids are a proxy variable for more advanced gestational age.
All survivors in our series developed retinopathy of prematurity and chronic lung disease. It has been suggested that children with chronic lung disease might be at increased risk of death because of sequelae of pulmonary insufficiency.2 However, pulmonary abnormalities also have been reported to resolve in children who survived extremely preterm birth.16 In our study, periventricular leukomalacia and severe intraventricular hemorrhage were present in surviving neonates at rates consistent with those in other studies of 23-week outcomes.3,8,17 The presence of those neurologic findings increases the risk of long-term neurologic sequelae and poor cognitive development.18,19 Most survivors were free of severe intraventricular hemorrhage, whereas most nonsurvivors had it, suggesting that severe intraventricular hemorrhage was a poor prognostic indicator of survival at 23 weeks' gestation. All of the NICU deaths resulted from withdrawal of life support, so the prospect of a poor neurologic outcome in the setting of severe intraventricular hemorrhage might strongly bias parents and practitioners against continued care compared with other morbid conditions in the 23rd week.
The rate of necrotizing enterocolitis was consistent with that published for the same birth weight category.2 Severe retinopathy of prematurity occurred in few neonates and at a rate below that published for the same gestational age.2 The reasons for the lower rate of severe retinopathy of prematurity are unclear and might have been a function of the small sample. Antenatal corticosteroids had no discernable independent effect on survival at 23 weeks. That finding was noted in other studies of extremely preterm neonates2 and may indicate a limitation.
Our analysis was limited by sample size. Negative findings should therefore be interpreted with caution. Our data pertain only to singleton pregnancies and might not apply to 23-week fetuses from multifetal pregnancies. Our study represents the experience at a single institution with an aggressive approach toward perinatal and pediatric intervention. Not all institutions, practitioners, or parents would be comfortable with this level of intervention, especially when long-term outcomes of infants born at 23 weeks' gestation remain unknown.
Our data provide additional information for counseling parturients who present with impending 23-week deliveries and their families. Further research into long-term morbidity and quality of life among these infants is needed before equitable and ethical approaches to viability in the 23rd week of gestation can be agreed on.
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