This edition of The Journal of Perinatal & Neonatal Nursing is dedicated to hot topics and high-risk conditions. While we face many difficult clinical situations in perinatal and neonatal nursing, determining "the right thing to do" when faced with the birth of an extremely low gestational age infant is among the most challenging and high-risk aspects of the care we provide to pregnant women and their infants. Given the clinical interventions currently available for neonatal resuscitation and neonatal intensive care, active treatment at the time of birth for infants before 22 weeks of gestation is generally not recommended. However, the approach for infants born at or after 22 weeks of gestation varies from one hospital to another. Both the American Academy of Pediatrics and the American Congress of Obstetricians and Gynecologists recommend that clinicians and families make individualized decisions about how best to provide care to extremely preterm infants at the time of birth based on parental preferences and the most recent evidence available regarding survival and morbidity.1 In this column, I have summarized some of the most recent evidence available regarding survival and morbidity of the extremely low gestational age infant. Ideally, this summary of the evidence will be translated to clinical practice when caring for pregnant women who are at high risk of delivering an extremely low gestational age infant.
ACTIVE TREATMENT AT THE TIME OF BIRTH IN EXTREMELY LOW GESTATIONAL AGE INFANTS
Extremely low gestational age birth, defined as birth prior to 27 weeks of gestation, occurs in approximately 0.4% to 0.5% of all births. While this number is small, it is significant because these births account for more than 40% of all infant deaths and most neonatal deaths and disproportionately contribute to overall pediatric morbidity.2 According to data reported in 2010 from the NICHD Neonatal Research Network, survival based on gestational age has been estimated as follows: 6% at 22 weeks, 26% at 23 weeks, 55% at 24 weeks, and 72% at 25 weeks.3 While survival has increased over time for infants born at extremely low gestational ages, the data that have been reported by studies conducted since 2000 have highlighted significant variability in outcomes among the studies.4 This variability is associated with nonmodifiable risk factors (race/ethnicity, plurality, sex and birth weight for gestational age) and both modifiable neonatal (initial resuscitation and care) and obstetric (antenatal interventions including corticosteroids, tocolysis, antibiotics, magnesium for neuroprotection, fetal monitoring, and cesarean delivery for fetal benefit) practices.4 One of the major modifiable contributors to the variability in rates of survival is intent to intervene and initiation of active treatment (ie, provision of life-sustaining interventions) at the time of birth. The initiation of active treatment is important to better understand in the context of survival and morbidity because whether or not active treatment is initiated will influence rates of survival and morbidity.
Understanding differences in hospital-specific practices regarding the initiation of either active treatment or comfort care at the time of birth for the extremely low gestational age infant and how this influences survival and morbidity has been an important gap in the literature. A recent study reported in The New England Journal of Medicine1 has evaluated this important aspect of neonatal care. In this study, which was conducted in collaboration with the NICHD Neonatal Research Network and included nearly 5000 infants born prior to 27 weeks at 24 hospitals, the between-hospital variation in initiation of active treatment of extremely preterm infants at birth was analyzed and the influence of this care on survival and survival without impairment among these infants was reported. Active treatment was defined as interventions including surfactant therapy, tracheal intubation, ventilatory support (including continuous positive airway pressure, bag-valve-mask ventilation, or mechanical ventilation), parenteral nutrition, epinephrine, or chest compressions.1 Overall, the study found that there were significant differences in the initiation of active treatment at the time of birth among extremely low gestational age infants. For example, of the 24 hospitals included in the study, 4 never provided active intervention to infants born in the 22nd week of gestation whereas 5 always intervened. The care provided to infants born in the 23rd week of gestation was also highly variable, where rates of active intervention ranged from 25% to 100% of infants. These differences were not noted in the higher gestational ages, where nearly all infants received active treatment at the time of birth. Overall, infants who did not receive active treatment were more likely to be small for gestational age, had Apgar scores of 3 or lower at 1 minute, were less likely to have been exposed to antenatal glucocorticoids, or were likely to have been born by cesarean delivery.1
This study also showed that in addition to variability in initiation of active treatment among hospitals at different gestational ages, there were overall differences in initiation of active treatment based on gestational age. Active treatment was administered on average, as given in Table 1.1
The initiation of active treatment data reported earlier was significantly higher in both 22- and 23-week infants who were born on day 5 or day 6 of the specific gestational week when compared with infants who were born at the beginning of the same week. The authors suggest that this might be explained by both the family and the clinical team tending to "round up" toward the end of the week when making decisions about whether or not to initiate active treatment.1 This finding is curious, especially in light of the fact that outside the setting of in vitro fertilization, best estimates of gestational age are not 100% precise, with a margin of error of at least 5 days.5 Furthermore, this finding suggests that the decision to intervene with active treatment in the extremely low gestational age infant is a complex and not always an evidence-based decision.
CLINICAL OUTCOMES BY GESTATIONAL AGE BASED ON INITIATION OF ACTIVE TREATMENT
The study reported by Rysavy and colleagues1 is novel and of value because it provides new information about clinical outcomes for the extremely low gestational age infant based on whether or not active treatment was initiated at the time of birth. This information is most notable in the lower gestational age groups, where the outcomes were most different based on the difference between infants who received active treatment and all infants. For example, in all infants at 22 weeks of gestation, the survival, survival without severe impairment, and survival without moderate or severe impairment was on average 5.1 (95% confidence interval [CI], 3.2-7.9), 3.4 (95% CI, 1.9-5.9), and 2.0 (95% CI, 0.9-4.1), respectively. This was in contrast to 23.1 (95% CI, 14.9-34.0), 15.4 (95% CI, 8.8-25.4), and 9.0 (95% CI, 4.3-17.9) in infants who received active treatment. Notable differences in the same outcomes (survival, survival without severe impairment, survival without moderate or severe impairment) were also seen in infants born at 23 weeks of gestation who did or did not receive active treatment at the time of birth. For example, survival increased from an overall average rate of 23.6 (95% CI, 20.7-26.9) to 33.3 (95% CI, 29.4-37.5), survival without severe impairment increased from and overall average rate of 17.9 (95% CI, 15.3-20.9) to 25.5 (95% CI, 21.7-29.2), and survival without moderate or severe impairment increased from average rate of 11.3 (95% CI, 9.2-13.9) to 16.0 (95% CI, 13.1-19.4).1 These differences drop off almost entirely in the infants born at 24, 25, and 26 weeks of gestation because the majority of infants who are born at these gestational ages receive active treatment.
TRANSLATING EVIDENCE FOR CLINICAL PRACTICE: COUNSELING THE PREGNANT WOMAN AT HIGH RISK OF DELIVERING AN EXTREMELY LOW GESTATIONAL AGE INFANT
What do the recent data reported on variation in treatment and outcomes in extremely low gestational age infants teach us about how best to intervene at the time of birth for these high-risk women and infants? I think it tells us that we should not consider all outcomes equally in the lowest gestational age groups and that comparing between survival and survival without impairment must account for the type of treatment provided at the time of birth and early in the neonatal period. When this is accounted for, the outcomes, which are still influenced negatively by gestational age, are better in infants who received active treatment. For example, the survival rate in infants born during the 22nd week of gestation who receive active treatment increases more than 4 times (from 5.1 to 23.1) when compared with all infants. This difference persists when survival without moderate or severe impairment is analyzed, where the rate increases from 2.0 in all infants to 9.0 in infants who receive active treatment. While these study findings should not be interpreted to mean that we should provide active treatment to all infants born at 22 weeks of gestation regardless of parental preferences, it does suggest that overall clinical outcomes for the extremely low gestational age infants are positively influenced by the provision of active treatment at the time of birth. That said, these study findings should inform how we council families about the anticipated outcomes associated with extremely low gestational age birth and the influence of initiation of active treatment at the time of birth. Along with clinical policies, procedures, and guidelines relevant to initiation of active care in the extremely low gestational age infant within a specific hospital setting, these findings should be made available to families so that they can make an individualized decision about where to seek care that will best meet the wishes they have for their infant at the time of birth.
-Katherine E. Gregory, PhD, RN
Senior Nurse Scientist
Department of Pediatric Newborn Medicine
Department of Nursing
Brigham and Women's Hospital
Boston, Massachusetts
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