Extreme preterm survival and outcomes

There are frequently publications about the outcomes of extreme preterm infants; as a community I think we should be proud of our investment in outcome research. Indeed, neonatologists invented the entire field of outcomes research (Barrington KJ, Saigal S. Long-term caring for neonates. Paediatr Child Health. 2006;11(5):265-6). When very preterm babies started surviving, the obvious question was: how will they do in the long term? With the survival of extremely preterm (24-28 weeks) and now profoundly preterm (<24 weeks) infants the questions continue.

Multiple cohorts have been extremely informative, and give an opportunity to perform comparisons between those cohorts. A new publication comparing babies from France, Canada, and New Zealand has just been published. (Chevallier M, et al. Mortality and significant neurosensory impairment in preterm infants: an international comparison. Arch Dis Child Fetal Neonatal Ed. 2021). As a disclosure, the first author, Marie Chevallier, was one of the excellent fellows in our programme, and has gone on to be a neonatologist and researcher in Grenoble; the last author, Thuy Mai Luu, is a colleague and friend from my hospital.

They and an international groupd of researchers compared outcomes from 3 cohorts born in 2011. The Canadian cohort have their data collected in CNN, with standardized examinations and data collection in the Canadian Neonatal Follow-Up Network (CNFUN) at 18 – 21 months corrected age. The Australian and New Zealand Network is a similar prospective database with outcome data also being collected at 2 to 3 years, but without the same structured follow-up and data collection. The data from France are derived from EPIPAGE-2, with outcomes at 2 years corrected age derived from questionnaires.

The authors have focussed survival and on long term neurosensory impairments, which I think was wise, given the differences in ages and methodologies. Disabling cerebral palsy, blindness and deafness and relatively stable outcomes, and probably less affected by methods of data collection than, for example, developmental delay.

There are 3 findings of note, I think. One of which is not discussed in the article, that being the proportion of babies by completed week of gestational age, which was much lower at 24 weeks in France than the other 2 cohorts.

Birth and antenatal characteristicsANZNNCNNEPIPAGE-2P value
n=960n=1019n=1076
Gestational age, mean (SD), weeks25.7 (1.1)25.8 (1.1)25.9 (1.0)<0.01
 24 weeks, n (%)182 (19.0)159 (15.6)102 (9.5)<0.01
 25 weeks, n (%)218 (22.7)235 (23.1)258 (24.0)0.78
 26 weeks, n (%)254 (26.5)314 (30.8)361 (33.6)<0.01
 27 weeks, n (%)306 (31.8)311 (30.5)355 (33.0)0.48
Birth weight, mean (SD), g856 (201)864 (216)843 (172)0.05
Male sex, n (%)519 (54.1)537 (52.8)557 (51.8)0.58
Maternal age, mean (SD), years29.3 (6.5)30.7 (5.8)29.4 (5.9)<0.01
Complete course of antenatal steroids, n (%)601 (63.1)692 (70.0)622 (60.2)<0.01

I don’t think there is any biological reason why French women would have fewer deliveries at 24 weeks, this difference is probably because of a relatively lower willingness to provide active obstetrical and neonatal care to babies born at this gestation.

Keeping in mind that there are somewhat fewer of the highest risk babies in France, the outcomes, the primary and the various parts of the primary are here:

OutcomesANZNN, n/N (%)CNN/CNFUN, n/N (%)EPIPAGE-2, n/N (%)P value
Mortality or sNSI204/960 (21.3)210/1019 (20.6)305/1076 (28.4)<0.01
Mortality179/960 (18.7)177/1019 (17.4)283/1076 (26.3)<0.01
Any sNSI among survivors25/578 (4.3)33/621 (5.3)22/659 (3.3)0.22
Cerebral palsy with GMFCS >214/565 (2.5)14/610 (2.3)15/659 (2.3)0.97
Disabling hearing loss12/568 (2.1)14/607 (2.3)7/641 (1.1)0.23
Visual impairment4/570 (0.7)12/562 (2.1)2/623 (0.3)0.01

Mortality is substantially higher in France, but impairments are very similar; apart from more visual impairment in Canada. (But remember that the CNN/CNFUN have formal visual testing, which was not the case in France or in the ANZNN, so this may not be directly comparable).

One general implication of these results is that having a less “aggressive” intervention policy does not select babies who are more likely to have unimpaired outcomes. It just leads to fewer survivors.

These data are, of course, from babies born 10 years ago. Even though neonatal clinical science has not changed that much, attitudes can change much more quickly! In Canada in 2012 about 9% of babies delivering alive at 24weeks gestation had palliative care instituted at birth, in 2019 that was 6%. The CNN doesn’t detail why such babies did not receive active intensive care, but many would have been because of serious congential anomalies or severe growth restriction. It has become quite unusual in Canada for an infant born at 24 weeks gestation to not be admitted for active NICU care in the absence of such additional complications. (CNN annual reports available here, and the CNFUN annual reports here)

From what I have seen, the attitudes in France have also changed, and many more babies born at 24 weeks or profoundly preterm (using the Barrington classification above) now receive active intensive care. These data suggest that such “interventionism” should lead to more survivors, with a similar proportion of survivors having neurosensory impairments.

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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