News Author: Laurie Barclay, MD
CME Author: Penny Murata, MD
April 16, 2008 — Clinical factors in addition to gestational age that help determine survival and other outcomes in extremely premature infants are sex, exposure to antenatal corticosteroids, single or multiple birth, and birth weight, according to the results of a prospective study reported in the April 17 issue of the New England Journal of Medicine.
"Decisions regarding whether to administer intensive care to extremely premature infants are often based on gestational age alone," write Jon E. Tyson, MD, MPH, from the University of Texas Medical School at Houston, and colleagues from the National Institute of Child Health and Human Development Neonatal Research Network. "However, other factors also affect the prognosis for these patients."
The investigators prospectively studied a cohort of 4446 infants born at 22 to 25 weeks' gestation in the Neonatal Research Network of the National Institute of Child Health and Human Development. Gestational age was determined from the best obstetrical estimate. The goal was to identify risk factors evaluable at or before birth that could predict the likelihood of survival, survival without profound neurodevelopmental impairment, and survival without neurodevelopmental impairment at a corrected age of 18 to 22 months.
Intensive care with mechanical ventilation was provided for 3702 infants (83%). Of the 4192 infants (94%) for whom outcomes were evaluated at 18 to 22 months, 49% had died, 61% had died or had profound impairment, and 73% had died or had some degree of impairment.
Exposure to antenatal corticosteroids, female sex, singleton birth, and higher birth weight (per each 100-g increment) were each associated with reductions in the risk for death and the risk for death or profound or any neurodevelopmental impairment, based on multivariable analyses of infants who received intensive care. These reductions in risk were similar in magnitude to those associated with a 1-week increase in gestational age.
Girls were less likely than boys who had the same estimated likelihood of a favorable outcome to receive intensive care. Using the above factors for infants who underwent ventilation allowed more accurate prediction of outcomes than did use of gestational age alone.
"The likelihood of a favorable outcome with intensive care can be better estimated by consideration of four factors in addition to gestational age: sex, exposure or nonexposure to antenatal corticosteroids, whether single or multiple birth, and birth weight," the study authors write.
Limitations of this study include bias inherent in observational studies, unavailability of data indicating how the obstetrical estimate of gestational age was assigned, inability to determine the outcome for 6% of the study infants, and the use of center-based samples.
"Whatever minimum probability of a favorable outcome is judged to warrant intensive care, consideration of multiple factors is likely to promote treatment decisions that are less arbitrary, more individualized, more transparent, and better justified than decisions based solely on gestational-age thresholds," the study authors conclude. "A simple Web-based tool (http://www.nichd.nih.gov/neonatalestimates) allows clinicians to use our findings in estimating the likelihood that intensive care will benefit individual infants, after considering the extent to which outcomes in their center might differ from those we identified."
The National Institutes of Health supported this study. The authors have disclosed no relevant financial relationships.
N Engl J Med. 2008;358:1672-1681.
Learning Objectives for This Educational Activity
Upon completion of this activity, participants will be able to:- Report factors related to survival, survival without profound neurodevelopmental impairment, and survival without neurodevelopmental impairment in infants born at 22 to 25 weeks' gestation.
- Describe whether gestational age vs other risk factors best predict outcomes in infants born at 22 to 25 weeks' gestation.
Clinical Context
For infants born at 22 to 25 weeks' gestation, the decision to provide intensive care is often dependent on gestational age. But, as noted by Tyson and Stoll in the June 2003 issue of Clinics in Perinatology, limited evidence exists to support this treatment decision.
This cohort study evaluates factors that play a role in the survival and neurodevelopmental outcomes of infants born at 22 to 25 weeks' gestation.
Study Highlights
- 4446 infants born at 22 to 25 weeks' gestation were recruited for 6 years.
- Exclusion criteria were major anomaly, birth weight more than 1000 g or 97th percentile, birth weight less than 401 g, and survival without mechanical ventilation.
- Gestational age was based on last menstrual period, early ultrasonogram, or other prenatal findings.
- Recorded data included type of delivery, single or multiple birth, sex of infant, antenatal corticosteroids within 7 days before delivery, ethnicity, and birth weight.
- Outcomes measured at corrected age of 18 to 22 months were death, death or neurodevelopmental impairment, and death or profound impairment.
- Neurodevelopmental impairment was defined by a score of 70 or lower on the Psychomotor Developmental Index or Mental Developmental Index of the Bayley Scales of Infant Development, moderate or severe cerebral palsy, bilateral blindness, or bilateral hearing loss requiring treatment.
- Profound neurodevelopmental impairment was defined by a Bayley score less than 50 or need for adult assistance to move.
- Gestational age was not significantly linked with other risk factors.
- 3702 infants who received intensive care vs 744 infants who did not receive intensive care were more likely to have higher birth weight (670 vs 536 g; P < .001); greater gestational age (24.2 vs 22.7 weeks; P < .001); exposure to antenatal corticosteroids (80% vs 28%; P < .001); and cesarean delivery (48% vs 9%; P < .001).
- Outcome data were available for 4165 infants, of whom 3421 received intensive care:
- Death occurred in 49%.
- Death or profound impairment occurred in 61%.
- Death or impairment occurred in 73%.
- Multivariate analysis showed that risk for death, death or profound impairment, or death or any impairment was reduced by each of the following: 100-g increase in birth weight, female sex, exposure to antenatal corticosteroids, or singleton birth.
- Reduced risk for outcomes for each factor was similar to reduced risk with 1-week increase in gestational age.
- Outcome predictions were more accurate if based on combined factors of gestational age, birth weight, sex, exposure to antenatal corticosteroids, and single or multiple gestation vs gestational age alone.
- Intensive care use increased with increasing gestational age, birth weight, and exposure to antenatal corticosteroids.
- Intensive care use was not linked to singleton vs multiple births or female vs male sex.
- Total resource use per survivor and per survivor without profound impairment was especially high for lowest gestational ages and for boys vs girls.
- Estimated outcomes of providing intensive care to infants at 22 to 23 weeks' gestation include 1749 or more extra hospital days and 0 to 9 additional survivors per 100 treated infants (0 - 5 without profound impairment; 0 - 3 without impairment).
- Ethnicity was not linked to outcomes.
Pearls for Practice
- Factors related to decreased risk for death or neurodevelopmental impairment in infants born at 22 to 25 weeks' gestation are female sex, exposure to antenatal corticosteroids, singleton birth, and higher birth weight.
- For infants born at 22 to 25 weeks' gestation, survival and neurodevelopmental outcomes are more accurately predicted by multiple risk factors of gestational age, birth weight, sex, exposure to antenatal corticosteroids, and singleton birth vs gestational age alone.
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