COMMENTARY

The life of people born preterm – what do you want to know?Gorm Greisen (greisen@rh.dk)Department of Neonatology, National University Hospital-Rigshospitalet, Copenhagen, Denmark

CorrespondenceG Greisen, Department of Neonatology,Rigshospitalet, Copenhagen University Blegdamsvej9, 2100 Copenhagen Ø, Copenhagen, Denmark.Tel: +45 35451326 |Fax: +45 3545 5025 |Email: greisen@rh.dk

Received21 March 2013; accepted 22 March 2013.

DOI:10.1111/apa.12250

This issue of Acta Paediatrica holds two articles on the lateoutcome after preterm birth. First, Methusalemsdottiret al.(1) describe quality of life (QoL) in adolescents whowere extremely low birth weight. This study has the virtue ofpresenting a national cohort. Compared with a term-bornreference group, the extremely low birth weight individualsreported a significantly lower QoL in four of ten domains,namely physical, psychological, moods and emotion, andself-perception, but not in domains such as social well beingand participation. The limitation of the study is that thecohort comes from the small population of Iceland and onlycomprised 29 index persons. Therefore, the confidencelimits of the odds ratios are very wide. Second, Ulrichet al. (2) describe health, well being, education and socialstatus in a nearly geographically defined cohort fromSouthern Denmark at 31–32 years of age. Sixty-nine indexindividuals born at 32–36 weeks participated. No statisti-cally significant difference was found comparedwith a largergroup of individuals born at term. The confidence intervalsin this study are also quite wide, and the authors carefullydiscuss the likelihood that there is a problem anyway.

SO, HOW DO THESE TWO STUDIES OF LATE OUTCOME DIFFER?First, the outcomes are not the same. ‘Physical’ QoL isprobably close to ‘health’ as determined by questionnaires,and all the ten QoL domains probably are intercorrelated.‘Health’ is probably also correlated with ‘well being’ andeven with ‘education’ and ‘social status’. But it is a general

problem that the concept of QoL is difficult and thatdifferent tools are used (3).

Second, the Icelanders were much more immature atbirth than the Danes. There are important gestational age/birth weight gradients when it comes to outcomes. Cerebralpalsy, cognitive deficit and psychiatric disorder are all muchmore common in the extremely preterm than in the nearterm. But definitions of target populations vary, so someideas of the influence of gestational age and birth weight arenecessary. This influence, however, differs widely betweencerebral palsy (range 50-fold), cognitive deficit (range five-fold) and psychiatric disorders (range 1.5-fold). We havelittle idea, when it comes to QoL and social status.

Third, the Icelanders were born in 1991–1995, whereasthe Danes were born in 1972–73. This means majordifferences in neonatal care – and likely in the chances ofsurvival and perhaps also in the risk of brain damage. This isan inherent problem to outcome research. The study oflong-term outcome has to wait, and it is by nature outdatedwhen the results become available. Its relevance dependson some form of back projection.

Fourth, Iceland and Denmark are two different countries,with different populations, different social systems anddifferent cultures – although both from the northern,western and affluent part of the world. To which degreecan we assume that we study a biomedical, cultureindependent, cause-and-effect relation? As a minimum,local family structure as well as broader social factors entersthe equation when it comes to ‘self-perception’ and ‘partic-ipation’. To which degree do we all need to establish QoLand social outcomes in our own context or can we dependon research carried out elsewhere?

HOW DO THESE STUDIES COMPARE WITH THE LITERATURE?The literature on health-related QoL in persons bornpreterm has generally been surprisingly positive (4). This

Invited Commentary for Methusalemsdottir et al., Qualityof life of adolescents born with extremely low birth weight,pages 597–601.Invited Commentary for Ulrich et al., On the well-being ofadult expremies in Denmark, pages 602–606.

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may, however, not be really surprising, as children witheven major handicap report QoL that is close to normal (5).Importantly, there is a principal difference between theobjective views on QoL – Can you move freely outdoors?Do you have friends with whom you can talk confidently? –versus the subjective view – How much does it mean to youto be able to move freely outdoors? How much does itmean to be able to talk confidently with friends? Westudied this difference in a cohort of adolescents born withvery low birth weight and found as expected that theproblems in objective QoL score were less significant in thesubjective QoL score (6).

There is also an increasing literature on social outcome inpersons born preterm. Again, these have been surprisinglypositive and generally confirming the statement of Rapindated 1982 on the young adult born preterm:

Those who have acquired adequate social skills,learned a trade and found a niche in the marketplace,which does not penalize them too much for theirdeficits, and those who do not have severe emotionalproblems and do not engage in antisocial behaviourare likely to disappear into the population. (7)

Studies that are adequately powered, however, do find adisadvantage. There is a well-defined gestational age gradi-ent of IQ (8) and school achievement (9), and it would bestrange if this did not translate into some disadvantage ineducation, income and social status in adulthood (10).

SO, WHAT DO YOU WANT TO KNOW?First – probably – you are interested in the outcome afterextremely preterm birth, most likely of the infants in yourown, contemporary context. If you are a neonatologistcaring for such infants, you will need this information tocouncil parents before and after the birth of their child, andif the clinical condition of the newborn infant becomes tooadverse, you may need it to qualify a decision of whether tocontinue or discontinue life support. Here, the problemslisted above – outcome measures, gestational age gradient,secular trends and local relevance – are all cruciallyrelevant.

I think that much of the motivation in outcome researchin people born preterm is due to this idea that there may bea choice. If the end result is too bad, we can somehowdecide not to do it. The extremely preterm newborn infant isin a continuum from the late miscarriage and perhaps thelate termination of pregnancy. This may explain whyoutcome research in this field is thriving. This particularpopulation may actually be the one most studied as regardslate outcome.

Second – if you are not a neonatologist, you may becurious about the limits of extreme prematurity, how smallis still compatible with growing up to a normal life.

More generally, a motivation may be linked to the factthat the preterm infant is an exteriorized 3rd trimesterfoetus. By learning about the late outcome in people born

preterm, we learn about human brain development ingeneral.

Finally, if you are an obstetrician, the risks of near-termpreterm birth should be of interest. Many infants aredelivered after a judgement of the risks and benefits ofphysician-induced delivery. How to balance the risks ofintrauterine growth restriction, sudden intrauterine death,and complications of delivery against the risks of neonatalmorbidity, death and impaired late outcome? Here, ran-domized trials will not be able to deliver the answers due tothe numbers needed and the delay of the answers.

CAN LATE OUTCOME BE MODIFIED?Late outcome is the last joint in a chain of causations. Canthis chain be twisted to the better? Parents are central.There is some evidence that they in general adapt well. Theparents may display a sensitivity to their children that issimilar that others and that this sensitivity is important forchild development (11). Parental sensitivity is key tostriking the balance between shielding and protection onone side and exposure and challenge on the other. The sumof evidence now suggests that professional support postdis-charge may help in the short term (12) although it still hasto be shown if the effects last into adolescence andadulthood.

More principally, do the needs for children born pretermdiffer from those of other children? Probably, all childrenwould benefit from better nurturing. Is there something likea preterm developmental phenotype? Something that couldbe modified by specific interventions? The studies quotedabove address the risk of problems, not really their causalpathways.

References

1. Methusalemsdottir H, Egilson S, Valdimarsdorrir U,Gudmundsdottir R, Georgsdottir I. Quality of life ofadolescents born with extremely low birth weight. ActaPaediatr 2013; 102: 597–601.

2. Ulrich M, Mortensen EL, Jensen C, Kamper J. On the well-being of adult expremies in Denmark. Acta Paediatr 2013; 102:602–6.

3. Saigal S. Quality of life of former premature infants duringadolescence and beyond. Early Hum Dev 2013; 89: 209–13.

4. Saigal S, Feeny D, Rosenbaum P, Furlong W, Burrows E,Stoskopf B. Self-perceived health status and health-relatedquality of life of extremely low-birth weight infants atadolescence. JAMA 1996; 276: 453–9.

5. Dickinson HO, Parkinson KN, Ravens-Sieberer U, Schirripa G,Thyen U, Arnaud C, et al. Self-reported quality of life of 8-12-year-old children with cerebral palsy: a cross-sectionalEuropean study. Lancet 2007; 369: 2171–8.

6. Dinesen SJ, Greisen G. Quality of life in young adults with verylow birth weight. Arch Dis Child Fetal Neonatal Ed 2001; 85:F165–9.

7. Rapin. I . Children with brain dysfunction. New York: RavenPress, 1982.

8. Lagercrantz H. The hard problem. Acta Paediatr 2008; 97:142–3.

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9. Mathiasen R, Hansen BM, Andersen AM, Forman JL,Greisen G. Gestational age and basic school achievements: anational follow-up study in Denmark. Pediatrics 2010; 126:e1553–61.

10. Mathiasen R, Hansen BM, Nybo Anderson AM, Greisen G.Socio-economic achievements of individuals born very pretermat the age of 27 to 29 years: a nationwide cohort study. DevMed Child Neurol 2009; 51: 901–8.

11. Hoff B, Munck H, Greisen G. Assessment of parentalsensitivity towards pre-school children born with very lowbirth weight. Scan J Psychol 2004; 45: 85–9.

12. Spittle A, Orton J, Anderson P, Boyd R, Doyle LW. Earlydevelopmental intervention programmes post-hospitaldischarge to prevent motor and cognitive impairments inpreterm infants (review). Cochrane Database of Syst Rev 2012;12: CD005495.

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