Predicting outcomes in extremely preterm infants

Extremely preterm infants (less than 28 weeks gestation) have an increased risk of adverse neurological or developmental outcomes. A new publication from the University of Chicago emphasizes a feature that has been shown before. That among survivors, there is little difference in the proportion with significant long term problems between 23 and 27 weeks gestation.

 Andrews B, Lagatta J, Chu A, Plesha-Troyke S, Schreiber M, Lantos J, Meadow W: The nonimpact of gestational age on neurodevelopmental outcome for ventilated survivors born at 23–28 weeks of gestation. Acta Paediatrica 2012, 101(6):574-578. http://onlinelibrary.wiley.com/doi/10.1111/j.1651-2227.2012.02609.x/abstract

The figure which illustrates this is shown above. The black boxes show the proportion of survivors who are without  major morbidity (defined as a score on the Bayley scales of infant development, either the mental development index or the psychomotor developmental index of less than 70, that is more than 2 SD below the mean). The authors also analyzed the data for more severe delays in development (scores less than 6o and less than 50) and found the same thing.

How this fits in with other studies

Other investigators have in the past shown similar things. It is possible that the failure of Andrews et al to find an impact of gestational age among survivors who were extremely preterm is due to a lack of power. It is also possible that evaluation of these children in later life could show differences according to the gestational week that they were born.

However data from larger cohorts, studied at later postnatal ages such as the EpiCure study, shows generally the same effect. Figure 1 from the 6 year neurologic and developmental outcomes of the EpiCure cohort is below.

Marlow N, Wolke D, Bracewell MA, Samara M, the EPICure Study Group: Neurologic and Developmental Disability at Six Years of Age after Extremely Preterm Birth. N Engl J Med 2005, 352(1):9-19. http://www.nejm.org/doi/full/10.1056/NEJMoa041367

Although the boys, and perhaps the girls appear to have slightly higher mean scores if born at 25 weeks than at 23 or 24 weeks gestation, the differences are not huge, and the numbers with very low scores appear to be about the same (and in fact are very few).

Similarly the Epipage study, a regional cohort from 9 french regions reported outcomes to 8 years of age of very preterm infants, some of whom were extremely preterm.

Larroque B, Ancel PY, Marchand-Martin L, Cambonie G, Fresson J, Pierrat V, Roze JC, Marpeau L, Thiriez G, Alberge C et al: Special care and school difficulties in 8-year-old very preterm children: the Epipage cohort study. PLoS One 2011, 6(7):e21361 .http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0021361#pone.0021361-Larroque1

Using a different outcome measure (schooling difficulties) they again show no substantial difference among survivors between 24-25 weeks and 27 weeks. The total number in the extremely preterm cohort was about 300 initially, with only 10 born at 24 weeks gestation.

What are the implications of this?

As discussed by Andrews and her colleagues, these data should have an impact on how we talk to parents before an extremely preterm delivery. As they state: ‘If mortality in the NICU is the outcome that parents most fear, then physician counselling and public policy pronouncements that rely strongly on gestational age are epidemiologically and ethically appropriate. However, if survival of an infant with severe neurologic impairment is the outcome most feared, then reliance on gestational age appears to be misplaced.’

The authors state earlier in their discussion ‘Some parents find moral worth and emotional solace in ‘giving their child a chance’ and ‘not giving up without a fight’.’

They go on to suggest that for such parents the only negative outcome is survival with neurodevelopmental impairment, and here I would disagree. I don’t think this follows from the previous sentence. One could find moral worth in a trial of therapy, but still not necessarily feel that survival with neurodevelopmental impairment is a negative otucome. Survival with profound handicap may sometimes be considered worse than not surviving (although be aware that parents tend to evaluate the situations differently than health care workers: see Saigal et al below), but having a Bayley score of less than 70 at 2 years of age is not equivalent to profound handicap!

Saigal S, Stoskopf BL, Feeny D, Furlong W, Burrows E, Rosenbaum PL, al. e: Differences in preferences for neonatal outcomes among health care professionals, parents, and adolescents. JAMA : the journal of the American Medical Association 1999, 281(21):1991-1997. http://jama.ama-assn.org/cgi/reprint/281/21/1991.pdf)

About keithbarrington

I am a neonatologist and clinical researcher at Sainte Justine University Health Center in Montréal
This entry was posted in Neonatal Research and tagged . Bookmark the permalink.

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