Does gestational age matter?

Taking a break from the SUPPORT brouhaha for a moment, here is a great systematic review from Greg Moore and colleagues in Ottawa. (Moore GP, Lemyre B, Barrowman N, Daboval T: Neurodevelopmental outcomes at 4 to 8 years of children born at 22 to 25 weeks’ gestational age: A meta-analysis. JAMA Pediatrics 2013,)

I have mentioned many times on this blog the problems with relying on the 18 month or 2 year Bayley score for determining if outcomes are seriously limited or not. Most ex-preterm infants with a Bayley MDI under 70 at 2 years do not have a cognitive impairment when you retest them at school age. Even infants with very low scores (under 50) will often be in the normal range if you test them later, at an age when they are old enough that you can really say something about intellectual ability. Testing later, say at 3 years, and using more extreme cutoffs makes the testing more predictive, but there is still a lot of uncertainty, once children approach school age then testing becomes better at discriminating between children with serious limitations and those without.

A lot of the previous research has shown very little effect of week by week changes in gestational age on outcomes. Epicure follow up at 6 years, for example, showed almost no gradient of outcomes between 23 and 25 weeks. Even large regional studies such as Epicure may, however, be suffering from a lack of power.

So Greg Moore and his co-authors did a systematic review of all the good quality studies that they could find that studied extremely preterm infants at early school age (4 to 8 years). They looked for cohort studies published after 2004, with follow up rates over 65% using standardized testing.

The results I want to concentrate on are the effects of increasing gestational age on the prevalence of impairment.

The authors divide impairment into moderate (more than 2SD below the mean on IQ testing, ambulant cerebral palsy, GMFCS 2 or 3, substantial visual impairment (worse than 20/40) or hearing restored with amplification) and severe impairment (IQ more than 3 SD below the mean, CP with GMFCS 4 or 5, no useful vision worse than 20/200 or profound hearing loss). There are nearly 900 babies in all in the 9 cohorts reported with gestational ages from 22 to 25 weeks.

When you have this large a number of patients, there is some reduction in rates of moderate impairment from 22 to 25 weeks, the frequency is around 24% for babies born at 25 weeks and increases by 6.5% for each week less, a statistically significant increase at p<0.01, but a smaller increase than you might think.

When you look at severe impairment, there was no significant effect of weeks of gestational age, being 14% at 25 weeks, up to 17% at 23 weeks, (the numbers at 22 weeks are really too small to say anything (n=12)).

So the majority of survivors are unimpaired or mildly impaired at any gestational age, and few (too many, but still few) are severely impaired.

This is very interesting data, which helps to clarify the outcomes of these patients. I think such a low frequency of severely abnormal outcomes, and the lack of an effect of gestational age are very important. If there is no substantial effect of the number of weeks of gestation, and the proportion who are severely impaired is small (and the individuals affected unpredictable before birth) then this should not be part of our considerations about whether or not we should start intensive care.

Interestingly, both this article and the editorial which goes with it, discuss the question of using long-term outcome data as an issue in the decisions of whether to initiate intensive care for the extreme preterm.

I am coming to the opinion that the incidence of profound disability is so low (and I am the first to recognize that 15% is way too high), so unpredictable before birth, and so poorly correlated with gestational age, that we should not include this as a consideration in our decision making.

My good friend and colleague Bill Meadow has an article shortly to be published in ‘Neoreviews’ I hope he won’t be upset with me if I steal his closing paragraph, but he expresses, much better than I can, an opinion which is so close to mine, and which indeed reflects my own personal experience as a parent of an extremely preterm baby. We were incredibly fortunate to have Sophie Nadeau, Gene Dempsey, and the rest of the team at the Royal Victoria Hospital in Montreal helping us through those very difficult times.

Perhaps antenatal consults oughtn’t really be about helping parents make life-and-death decisions at all.  Perhaps they should be about reassurance and human kindness.  We (the neonatology team) are here for you in your moment of unexpected and indescribable fear.  We may not be able to help you with your decision prior to delivery – the data are just too ambiguous.  But we’ll be with you every step of the way.  And if things turn bad during the NICU stay, we’ll be there – supporting your autonomy and helping you make the difficult decision of what is now in your baby’s ‘best interests’.  That may be the best we can do.

That sounds to me like a pretty good ‘best’.

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.

6 Responses to Does gestational age matter?

  1. N. Ambalavanan says:

    Nice post. The prediction of preterm infant mortality is much more accurate, but the prediction of neurodevelopmental outcomes is not accurate, even for the 2 yr outcome. All predictions are basically a probability estimate, and individual outcomes may or may not fit with predictions. As we have shown recently, evaluating postnatal events to develop an “outcome trajectory” for individual infants is probably better than using GA (either alone or combined with other variables) at birth.

    • I absolutely agree, individual prognostication prior to birth is extremely inaccurate, both for survival but most particularly for long term serious outcomes. Your models, and we need to develop others to confirm or refine your data, will be a great help in trying to figure out what the likelihood of survival and serious impairment is as we progress after birth. It would be interesting to consider the effects of each additional complication. Also I think for a parent the implications of death and of survival with serious impairment are so different that we should try and separate them out when we create tools to help us in making decisions.

  2. Gregory Moore says:

    Dear Keith,
    Thank you for all the writing and thoughts you are providing in this blog post and others. The work on this meta-analysis taught me a lot; the largest lesson was around the fact that at the present time, there is definitely not enough solid data to create any strong recommendations for what ‘should’ or ‘shouldn’t’ be done for a particular baby based on some sort of categorization (e.g. gestational age). If data is used (because some parents certainly do want it), then its limitations must be explicitly expressed while communicating with the parents. I’m looking forward to being a part of changing things so neonatologists (and other health professionals) truly help parents and work with them to make decisions in the best interests of their baby.
    Greg

  3. Alison Epps says:

    Hello Keith, I was hoping to read the full article you mentioned in closing, but I do not have access to Neoreviews. I am not in the medical field, just a mom of a former micro, doing research. Do you know if the article written by Bill Meadows is available to read in anywhere else? Thanks for your help.

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