In this large cohort of extremely preterm infants, we found that disability in the domain of mental and psychomotor development, neuromotor function, or sensory and communication function was present in about half of all survivors at 30 months of corrected age, with approximately one quarter meeting the criteria for severe disability. There was no relation between the pattern of morbidity and either gestational age or the presence of multiple birth, but boys were more likely to be disabled than girls. This morbidity must be viewed in the context of mortality in this particularly vulnerable group. We chose live births, rather than total births, as our denominator because infants who are stillborn after therapeutic termination of the pregnancy are included among total births (unpublished data). In a study such as this, with data from a large number of centers of various sizes and staffing structures and inevitable differences of approach to the birth of an extremely preterm infant, we could neither standardize nor validate definitions of resuscitation attempts; thus, the delivery-room treatment of those reported to show signs of life but not admitted to the neonatal intensive care unit was not recorded. It is a matter of conjecture whether a more aggressive universal policy of resuscitation would have altered these outcomes.
The strengths of this study lie in the fact that the cohort was drawn prospectively from an entire population over a short period, resulting in findings relevant to current neonatal practice in the United Kingdom and Ireland. Formal assessment data were available on nearly all survivors, and the assessments were performed by independent examiners unaware of the children's neonatal history. We examined the children at 30 months, but we recognize that some neurologic disabilities may continue to evolve, and assessment at 5 years would probably result in a more accurate measure of final neurologic outcome.14,15,16 We chose to continue correcting for prematurity beyond the normally accepted age of two years because of the magnitude of the deficits in this particular group. Had we not used corrected age, the mean developmental scores would have been even lower, but the children with severe developmental delay would nonetheless have been identified.17
The majority of previous studies of extremely preterm infants have reported outcome according to birth-weight categories, and few have reported outcome according to gestational age. Reporting according to birth-weight categories often leads to the inclusion of infants who are gestationally more mature but whose growth was restricted, in addition to those with appropriate growth for their gestational ages. The inclusion of these more mature, growth-restricted infants confers an artificial neurodevelopmental advantage on such a group as compared with a group made up of infants with appropriate growth.18,19 In the current published literature, rates of severe disability vary between 18 and 40 percent for those born at 25 weeks of gestation or later.5 Much of this variation in outcome may be attributable to small samples, use of cohorts from tertiary referral centers rather than geographic regions, differing proportions of infants born in or outside the hospital, high rates of loss to follow-up, and the inconsistent classification of disability.
The Victorian Infant Collaborative Study Group presented data from a cohort of 220 infants born in the state of Victoria, Australia, at 27 or fewer weeks of gestation during 1991 and 1992 and who were assessed at two years of age.9 The Mental Development Index of the original Bayley Scales was used, and the results were expressed as standardized normal quotients calculated on the basis of the means and standard deviations of scores of normal-birth-weight infants. Severe disability — defined as one or more mental development scores 3 SD or more below the mean, cerebral palsy such that the child was unlikely ever to walk, or bilateral blindness — was present in 9 percent (95 percent confidence interval, 4 to 18 percent) of those who were born at 25 or fewer weeks of gestation.
This percentage appears considerably less than the 23 percent in our cohort. If we reclassify our cohort according to the above definition, then 15 percent of the children (95 percent confidence interval, 11 to 20 percent) would be labeled as severely disabled. This classification fails to consider the important additional severe disability imposed by functional disorders of the proximal axial musculature and arms, severe psychomotor delay, and deafness or communication problems. In contrast to our study findings, the Australian study found that the proportion of infants with disability increased with decreasing gestational age.
The United Kingdom Northern Neonatal Network collected prospective population-based outcome data between 1983 and 1994 on 580 infants born at 27 weeks or less of gestational age.8 The cohort was assessed at one year, and a more detailed assessment of development, based on the Griffiths Scales of Mental Development,20 was performed at two years for those born in 1983, 1987, and 1991. Disability was defined by the same criteria as in this study.11 At one year, severe disability was found in 24 percent of the infants born at 25 weeks or less of gestation. At two years, none of the nine survivors of those born at 25 weeks or less of gestation had severe disability that was likely to prevent independent living; in contrast, severe disability was present in 10 percent of those born at 25 through 27 weeks of gestation. In agreement with our findings, the investigators found that boys were significantly more likely to be disabled.
Cerebral palsy is often chosen as an index of long-term outcome by which changes in neonatal and perinatal care can be measured, because the clinical syndromes are often recognizable by two years of age. However, as a means of identifying disability, this method would lead to an underestimation of motor disability in the children in our study: of 67 with abnormal motor function, only 50 (75 percent) had a recognizable pattern of cerebral palsy.
The comprehensive nature of our study allowed us to provide outcome data for virtually all live births at 25 completed weeks or less of gestation in a whole population. This information is important for obstetricians, midwives, and pediatricians to use in discussions with parents. It provides a background to facilitate decision making and eliminates the bias inherent in center-based studies, which may be misleading because of wide confidence intervals and selective referral of mothers and infants.
Our study documents the outcome of extremely preterm infants at 30 months of corrected age; our data can provide information concerning only the most severe disabilities. Infants born extremely preterm are also at risk for later behavioral,21,22 fine-motor,23,24 and educational25,26 difficulties. The place of intervention early after discharge to increase developmental performance is still unclear,27 and the benefits of such intervention may be only minimal in the short term.28 The prevention or amelioration of disability in survivors of extreme prematurity remains one of the most important challenges in medicine.
Supported by Serono Laboratories UK and Baby Life Support Systems.
* Members of the EPICure Study Group are listed in the Appendix.
Source Information
From the School of Human Development, University of Nottingham, Nottingham (N.S.W., N.M.); St. Bartholomew's and the Royal London School of Medicine and Dentistry, Queen Mary and Westfield College, University of London, London (K.C.); Jessop Hospital for Women, Sheffield (A.T.G.); and the Department of Paediatrics, University of Oxford, Oxford (A.R.W.) — all in the United Kingdom.
Address reprint requests to Dr. Marlow at the Academic Division of Child Health, Level E East Block, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom, or at neil.marlow@nottingham.ac.uk
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