Neurologic and Developmental Disability after Extremely Preterm Birth
Nicholas S. Wood, M.B., Ch.B., Neil Marlow, D.M., Kate Costeloe, M.B., B.Chir., Alan T. Gibson, Ph.D., Andrew R. Wilkinson, M.B., Ch.B., for The EPICure Study Group
Background Small studies show that many children born as extremelypreterm infants have neurologic and developmental disabilities.We evaluated all children who were born at 25 or fewer completedweeks of gestation in the United Kingdom and Ireland from Marchthrough December 1995 at the time when they reached a medianage of 30 months.
Methods Each child underwent a formal assessment by an independentexaminer. Development was evaluated with use of the Bayley Scalesof Infant Development, and neurologic function was assessedby a standardized examination. Disability and severe disabilitywere defined by predetermined criteria.
Results At a median age of 30 months, corrected for gestationalage, 283 (92 percent) of the 308 surviving children were formallyassessed. The mean (±SD) scores on the Bayley Mentaland Psychomotor Developmental Indexes, referenced to a populationmean of 100, were 84±12 and 87±13, respectively.Fifty-three children (19 percent) had severely delayed development(with scores more than 3 SD below the mean), and a further 32children (11 percent) had scores from 2 SD to 3 SD below themean. Twenty-eight children (10 percent) had severe neuromotordisability, 7 (2 percent) were blind or perceived light only,and 8 (3 percent) had hearing loss that was uncorrectable orrequired hearing aids. Overall, 138 children had disability(49 percent; 95 percent confidence interval, 43 to 55 percent),including 64 who met the criteria for severe disability (23percent; 95 percent confidence interval, 18 to 28 percent).When data from 17 assessments by local pediatricians were included,155 of the 314 infants discharged (49 percent) had no disability.
Conclusions Severe disability is common among children bornas extremely preterm infants and remains a major challenge inthis group of children.
Most studies that describe the outcome of premature infantsare based on birth weight and thus confound the effects of extremelypreterm birth with those of intrauterine growth restriction.1However, physicians and parents contemplating the prognosisof extremely preterm infants require reliable information basedon gestational age with which to plan care around the time ofbirth and thereafter.2,3 Information from individual hospitalshas been collected from small numbers of infants over a longtime and therefore includes data on infants treated in manydifferent ways.
To collect information relevant to modern perinatal care, weconducted a prospective study of all infants born at 20 through25 completed weeks of gestation in the United Kingdom and Irelandduring a 10-month period beginning in March 1995. We obtainedinformation on clinical findings and hospital outcome for allof the 811 extremely preterm infants born during this periodwho were admitted to neonatal intensive care units and dischargedhome.4
Disability is common among extremely premature infants who survive,5but there are few population-based studies of the developmentof these infants.6,7,8,9 Here we report the results of a neurologicand developmental assessment performed a median of 30 monthsafter the expected date of delivery in the survivors of thestudy cohort.
Methods
Study Subjects
We identified all infants born at 20 through 25 weeks of gestation(as determined by the date of the mother's last menstrual periodand by early ultrasonography) in all 276 maternity units inthe United Kingdom and Ireland from March through December 1995.Of the 4004 infants identified, 1185 had signs of life at birth,and 843 of these were admitted to neonatal intensive care units(the remainder died in the delivery room) (Table 1). For these843 infants, gestation was recalculated by using the date ofthe last menstrual period, by review of ultrasound studies donebefore 20 weeks, or (in the case of 29 infants) on the basisof clinical examination by a pediatrician. Three of these 29infants were considered by the pediatrician to have been bornat 26 weeks or more of gestation and were therefore excluded.If the estimates based on the last menstrual period and on ultrasonographywere both available and were discrepant by at least 14 days,the ultrasound estimate was used; this resulted in the exclusionof an additional 29 infants. Thus, there remained 811 infantsadmitted to the neonatal intensive care unit whose gestationalage was not more than 25 weeks and 6 days. Of these, 497 diedin the hospital and 314 were discharged home. Six infants diedafter discharge, and six left the United Kingdom or Ireland.
Table 1. Summary of Outcomes among Infants Born Alive at 22 through 25 Weeks of Gestation.
Between January 1998 and January 1999, the parents of the 302survivors living in the United Kingdom or Ireland were offeredthe opportunity to have their children undergo a standardizedfollow-up assessment. The parents of 16 children declined theinvitation, and the parents of 3 others failed to bring theirchildren for their prearranged evaluation; thus 283 of the survivors(92 percent) participated in this study. Of the 25 survivingchildren who did not take part, information was available on17 from assessments performed by their local pediatricians atabout 30 months of age corrected for gestation, and on a further6 from assessments performed locally at about 12 months of correctedage. The data obtained were sufficient to allow us to determinewhether the child had a disability. Of these 23 children, 9were classified as severely disabled, 4 as having other disabilities,and 10 as having no disability. Information on outcome was thereforeunavailable for only 2 of 308 surviving children.
The study was approved by each local research ethics committeebefore collection of the original data. All families for whomoutcome is reported gave written informed consent for the examination.
Assessment
Each child was examined in a hospital outpatient clinic or healthcenter near the family home (235 children) or at home (48 children).The assessment consisted of a detailed medical history obtainedfrom a semistructured interview with the family; a clinicalexamination, including neurologic assessment10; a classificationof the degree and type of disability11,12; a functional classificationof hearing and visual ability12; and a growth assessment, includingmeasurement of maximal occipitofrontal head circumference witha LASSO-O tape (Child Growth Foundation, London). Developmentwas assessed with use of the Bayley Scales of Infant Development(second edition),13 which yielded scores for mental and psychomotordevelopment with a standardization mean of 100 and standarddeviation of 15 points. Scores over 100 indicated advanced developmentfor age. Development was considered severely impaired if thescores were less than 55, moderately impaired if they were 55to 69, and mildly impaired if they were 70 to 84. There areno standardization data for children in the United Kingdom,but in a study of 850 three-year-olds in the Avon region ofthe United Kingdom, most of whom were born at term, the meanmental development score was 99.3±11.3 (SD) and the meanpsychomotor development score was 96.0±14.7 (unpublisheddata). We used the U.S. standardization norms,13 with a meanof 100 and a standard deviation of 15. Scores were correctedfor gestational age because, even at this age, uncorrected resultswould alter performance by 12.5 to 15.0 percent. If the childwas unable to complete the Bayley assessment (because of poorvision, for example), the pediatrician estimated the child'sdevelopmental level as severely or moderately impaired (equivalentto Bayley scores under 55 or 55 to 69, respectively) or as notimpaired.
Developmental Panel
Ten experienced developmental pediatricians were recruited toperform the assessments. All attended a course in which theywere trained in all aspects of the assessments. A psychologistprovided instruction in the use of the Bayley scales. Afterthe training course, all the pediatricians submitted video recordingsof pilot Bayley assessments, which were scored independently.All the pediatricians reached a prespecified level of agreementof more than 80 percent with the psychologist for individualitems on the Bayley scales before study testing commenced. Furthertapes were submitted at random during the study, and scoringwas rechecked. Overall agreement was reached on 91 percent ofthe items making up the Mental Development Index and 88 percentof the items of the Psychomotor Development Index. One pediatricianleft during the study and was replaced by another, who achievedsimilar levels of agreement for the Bayley assessment. The developmentalpediatricians were unaware of the neonatal courses of the childrenthey evaluated.
Classification of Disability
Disability was classified according to a previously publishedscheme.11 A "severe disability" was defined as one that waslikely to put the child in need of physical assistance to performdaily activities. Disabilities that did not fall into this categorywere referred to simply as "other disabilities." The criteriafor severe and other disabilities in each neurologic domainare shown in Table 2. Cerebral palsy was classified retrospectivelyaccording to the descriptions of function for each limb12 inchildren with abnormal results on neurologic examination.10The categories were diplegia, in which upper-limb function wasbetter than lower-limb function, despite asymmetries; hemiplegia,in which lower-limb function was better than upper-limb function,usually with asymmetry; quadriplegia, in which all four limbsappeared equally affected; and other, nonspastic types of cerebralpalsy, such as hypotonia and dyskinesia. This classificationwas independent of the degree of disability.
Table 2. Neurologic Function at 30 Months in 283 Children Born at 22 through 25 Weeks of Gestation.
Statistical Analysis
Data collected on standardized forms and Bayley records weresent by mail to the study center, where they were encoded forcomputer analysis with SPSS for Windows software (release 8.0.0,SPSS, Chicago). To check for accuracy, the data were double-enteredand the files were compared. The data for each infant were examinedand outliers were verified before the data were combined withthe main study data set for analysis. Categorical outcomes werecompared with use of chi-square tests for trends, as appropriate,or Fisher's exact test. Continuous outcomes were compared withuse of independent Student's t-tests. All statistical testswere two-sided.
Results
The outcome at 30 months of age is summarized in Figure 1, whichis based on the 314 children discharged home and includes allthe information available on the 25 children (8 percent) whowere not assessed or who were abroad. Table 1 uses these datato show the outcome for the whole study cohort summarized accordingto gestational age, with the number of live births as the denominator.Two hundred eighty-three children were formally assessed ata median corrected age of 30 months (range, 28 to 40); 90 percentof the assessments occurred between 29 and 32 months.
Figure 1. Summary of Outcome with Respect to Overall Disability at 30 Months for 314 Children Born at 22 through 25 Weeks of Gestation.
Bayley Assessments
At least one of the two Bayley indexes could be completed for251 of the 283 infants (89 percent). The mean score on the MentalDevelopment Index was 84±12, and the score on the PsychomotorDevelopment Index was 87±13. The range of scores accordingto test scale and gestational age is shown in Figure 2.
Figure 2. Individual Scores on the Bayley Scales at 30 Months According to Gestational Age.
Scores on the Mental Development Index (231 infants) are indicated by solid circles, and scores on the Psychomotor Development Index (225 infants) by open circles. The horizontal lines represent means.
On the basis of the lower of the scores on the Mental and PsychomotorDevelopment Indexes, and including the estimated scores of thosewho were unable to complete the assessment, 53 children (19percent; 95 percent confidence interval, 14 to 24 percent) hadscores more than 3 SD below the mean. These children were classifiedas severely disabled.11 The scores were from 2 SD to 3 SD belowthe mean (indicating moderately delayed development) in 32 children(11 percent; 95 percent confidence interval, 9 to 17 percent).These children were assigned to the "other disability" category.The variation in Bayley scores according to gestational age,sex, and single or multiple birth is shown in Table 3. The scoresdid not vary substantially with gestational age or multipleas compared with single birth, but boys had significantly lowerpsychomotor scores than girls (mean difference, 5.7; 95 percentconfidence interval, 1.9 to 8.6).
Table 3. Developmental Scores and Degree and Type of Disability at 30 Months According to Gestational Age, Sex, and Frequency of Multiple Birth among Children Born at 22 through 25 Weeks of Gestation.
Neuromotor Function
Overall, 28 children had severe disabilities of neuromotor function(10 percent; 95 percent confidence interval, 7 to 14 percent),and 39 children had other neuromotor disabilities (14 percent;95 percent confidence interval, 10 to 18 percent) (Table 3).Of these 67 children, 50 had a recognizable pattern of cerebralpalsy (18 percent of the study cohort). The degree of disabilityin children with each type of cerebral palsy is shown in Table 4.Of the children with cerebral palsy, 27 had severe disability(54 percent). Boys were more likely to have cerebral palsy thangirls (P=0.009), but there were no differences related to eithergestational age or multiple as compared with single birth.
Table 4. Disability and Distribution of Clinical Signs of Cerebral Palsy among 50 30-Month-Old Children Who Were Born at 22 through 25 Weeks of Gestation.
Sensory Morbidity and Communication Difficulties
Seven children were blind or could see only light; six of thesechildren had received treatment for retinopathy of prematurity(Table 2). Many children had other, less severe, visual impairments:squint was present in 71 (25 percent), and 28 (10 percent) woreeyeglasses. Five children had profound hearing loss that couldnot be corrected with hearing aids, and a further 36 had lesserdegrees of hearing loss. In 18 children there was no recognizablespeech at 30 months of age; hearing was normal in 15 of thesechildren.
Severe Disability
Severe disability in the developmental, neuromotor, or sensoryand communication domains was present in 64 children (23 percent).Twenty-nine children had disabilities in more than one of thethree domains, including 13 with disabilities in each domain.Twenty-seven (10 percent) were classified as having a severedisability on the basis of poor developmental progress withoutsevere neuromotor or sensory and communication problems (onlysix of these children had no other disability), seven had severedisability in the sensory and communication domain (three ofthese had other disabilities), and two had severe neuromotordisabilities without severe disability in other domains (bothchildren had quadriplegia).
Head Growth
Head circumference was measured in 278 children (98 percent)and related to United Kingdom population norms. Overall, themean head circumference was 1.6 SD below the mean for correctedage. Similarly, head circumference was lower in those with anysevere disability than in those with no disability (P<0.001).Among 155 children with no disability, 37 (24 percent) had ahead circumference more than 2 SD below the mean.
Discussion
In this large cohort of extremely preterm infants, we foundthat disability in the domain of mental and psychomotor development,neuromotor function, or sensory and communication function waspresent in about half of all survivors at 30 months of correctedage, with approximately one quarter meeting the criteria forsevere disability. There was no relation between the patternof morbidity and either gestational age or the presence of multiplebirth, but boys were more likely to be disabled than girls.This morbidity must be viewed in the context of mortality inthis particularly vulnerable group. We chose live births, ratherthan total births, as our denominator because infants who arestillborn after therapeutic termination of the pregnancy areincluded among total births (unpublished data). In a study suchas this, with data from a large number of centers of varioussizes and staffing structures and inevitable differences ofapproach to the birth of an extremely preterm infant, we couldneither standardize nor validate definitions of resuscitationattempts; thus, the delivery-room treatment of those reportedto show signs of life but not admitted to the neonatal intensivecare unit was not recorded. It is a matter of conjecture whethera more aggressive universal policy of resuscitation would havealtered these outcomes.
The strengths of this study lie in the fact that the cohortwas drawn prospectively from an entire population over a shortperiod, resulting in findings relevant to current neonatal practicein the United Kingdom and Ireland. Formal assessment data wereavailable on nearly all survivors, and the assessments wereperformed by independent examiners unaware of the children'sneonatal history. We examined the children at 30 months, butwe recognize that some neurologic disabilities may continueto evolve, and assessment at 5 years would probably result ina more accurate measure of final neurologic outcome.14,15,16We chose to continue correcting for prematurity beyond the normallyaccepted age of two years because of the magnitude of the deficitsin this particular group. Had we not used corrected age, themean developmental scores would have been even lower, but thechildren with severe developmental delay would nonetheless havebeen identified.17
The majority of previous studies of extremely preterm infantshave reported outcome according to birth-weight categories,and few have reported outcome according to gestational age.Reporting according to birth-weight categories often leads tothe inclusion of infants who are gestationally more mature butwhose growth was restricted, in addition to those with appropriategrowth for their gestational ages. The inclusion of these moremature, growth-restricted infants confers an artificial neurodevelopmentaladvantage on such a group as compared with a group made up ofinfants with appropriate growth.18,19 In the current publishedliterature, rates of severe disability vary between 18 and 40percent for those born at 25 weeks of gestation or later.5 Muchof this variation in outcome may be attributable to small samples,use of cohorts from tertiary referral centers rather than geographicregions, differing proportions of infants born in or outsidethe hospital, high rates of loss to follow-up, and the inconsistentclassification of disability.
The Victorian Infant Collaborative Study Group presented datafrom a cohort of 220 infants born in the state of Victoria,Australia, at 27 or fewer weeks of gestation during 1991 and1992 and who were assessed at two years of age.9 The MentalDevelopment Index of the original Bayley Scales was used, andthe results were expressed as standardized normal quotientscalculated on the basis of the means and standard deviationsof scores of normal-birth-weight infants. Severe disability defined as one or more mental development scores 3 SDor more below the mean, cerebral palsy such that the child wasunlikely ever to walk, or bilateral blindness was presentin 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 percentin our cohort. If we reclassify our cohort according to theabove definition, then 15 percent of the children (95 percentconfidence interval, 11 to 20 percent) would be labeled as severelydisabled. This classification fails to consider the importantadditional severe disability imposed by functional disordersof the proximal axial musculature and arms, severe psychomotordelay, and deafness or communication problems. In contrast toour study findings, the Australian study found that the proportionof infants with disability increased with decreasing gestationalage.
The United Kingdom Northern Neonatal Network collected prospectivepopulation-based outcome data between 1983 and 1994 on 580 infantsborn at 27 weeks or less of gestational age.8 The cohort wasassessed at one year, and a more detailed assessment of development,based on the Griffiths Scales of Mental Development,20 was performedat two years for those born in 1983, 1987, and 1991. Disabilitywas defined by the same criteria as in this study.11 At oneyear, severe disability was found in 24 percent of the infantsborn at 25 weeks or less of gestation. At two years, none ofthe nine survivors of those born at 25 weeks or less of gestationhad severe disability that was likely to prevent independentliving; in contrast, severe disability was present in 10 percentof those born at 25 through 27 weeks of gestation. In agreementwith our findings, the investigators found that boys were significantlymore likely to be disabled.
Cerebral palsy is often chosen as an index of long-term outcomeby which changes in neonatal and perinatal care can be measured,because the clinical syndromes are often recognizable by twoyears of age. However, as a means of identifying disability,this method would lead to an underestimation of motor disabilityin the children in our study: of 67 with abnormal motor function,only 50 (75 percent) had a recognizable pattern of cerebralpalsy.
The comprehensive nature of our study allowed us to provideoutcome data for virtually all live births at 25 completed weeksor less of gestation in a whole population. This informationis important for obstetricians, midwives, and pediatriciansto use in discussions with parents. It provides a backgroundto facilitate decision making and eliminates the bias inherentin center-based studies, which may be misleading because ofwide confidence intervals and selective referral of mothersand infants.
Our study documents the outcome of extremely preterm infantsat 30 months of corrected age; our data can provide informationconcerning only the most severe disabilities. Infants born extremelypreterm are also at risk for later behavioral,21,22 fine-motor,23,24and educational25,26 difficulties. The place of interventionearly after discharge to increase developmental performanceis still unclear,27 and the benefits of such intervention maybe only minimal in the short term.28 The prevention or ameliorationof disability in survivors of extreme prematurity remains oneof 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{at}nottingham.ac.uk.
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Appendix
Members of the EPICure Study Group are as follows: DevelopmentalPanel A.J. Bennett, M.J. Cruwys, M.C. Dick, S. Egan,A.F. Livingstone, L.J. Logie, R.H. MacGregor, B. Mallya, M.X.Poblete, J.F. Schulte, N.S. Wood, C. Lawson (psychologist),H. Palmer (administrator), and E.M. Hennessy (statistician);Steering Group P.J. Steer (Chair; London), K. Costeloe(London), A.T. Gibson (Sheffield), I.A. Laing (Edinburgh), M.J.Lewins (Lincoln), N. Marlow (Nottingham), P.O.D. Pharoah (Liverpool),and A.R. Wilkinson (Oxford). The EPICure Study Group also includesthe pediatricians in 276 maternity units in the United Kingdomand Ireland who contributed data to the study.
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(2008). Doctors' and nurses' attitudes towards neonatal ethical decision making in Ireland. Arch. Dis. Child. Fetal Neonatal Ed.
93: F217-F221
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Eichenwald, E. C., Stark, A. R.
(2008). Management and Outcomes of Very Low Birth Weight. NEJM
358: 1700-1711
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Meadow, W., Lagatta, J., Andrews, B., Caldarelli, L., Keiser, A., Laporte, J., Plesha-Troyke, S., Subramanian, M., Wong, S., Hron, J., Golchin, N., Schreiber, M.
(2008). Just, in Time: Ethical Implications of Serial Predictions of Death and Morbidity for Ventilated Premature Infants. Pediatrics
121: 732-740
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Zeitlin, J., Draper, E. S., Kollee, L., Milligan, D., Boerch, K., Agostino, R., Gortner, L., Van Reempts, P., Chabernaud, J.-L., Gadzinowski, J., Breart, G., Papiernik, E., and the MOSAIC research group,
(2008). Differences in Rates and Short-term Outcome of Live Births Before 32 Weeks of Gestation in Europe in 2003: Results From the MOSAIC Cohort. Pediatrics
121: e936-e944
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Bracewell, M A, Hennessy, E M, Wolke, D, Marlow, N
(2008). The EPICure study: growth and blood pressure at 6 years of age following extremely preterm birth. Arch. Dis. Child. Fetal Neonatal Ed.
93: F108-F114
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Pignotti, M. S., Donzelli, G.
(2008). Perinatal Care at the Threshold of Viability: An International Comparison of Practical Guidelines for the Treatment of Extremely Preterm Births. Pediatrics
121: e193-e198
[Abstract][Full Text]
Arnaud, C., Daubisse-Marliac, L., White-Koning, M., Pierrat, V., Larroque, B., Grandjean, H., Alberge, C., Marret, S., Burguet, A., Ancel, P.-Y., Supernant, K., Kaminski, M.
(2007). Prevalence and Associated Factors of Minor Neuromotor Dysfunctions at Age 5 Years in Prematurely Born Children: The EPIPAGE Study. Arch Pediatr Adolesc Med
161: 1053-1061
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Gianni, M. L., Picciolini, O., Vegni, C., Gardon, L., Fumagalli, M., Mosca, F.
(2007). Twelve-Month Neurofunctional Assessment and Cognitive Performance at 36 Months of Age in Extremely Low Birth Weight Infants. Pediatrics
120: 1012-1019
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Marlow, N., Hennessy, E. M., Bracewell, M. A., Wolke, D., for the EPICure Study Group,
(2007). Motor and Executive Function at 6 Years of Age After Extremely Preterm Birth. Pediatrics
120: 793-804
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Singh, J., Fanaroff, J., Andrews, B., Caldarelli, L., Lagatta, J., Plesha-Troyke, S., Lantos, J., Meadow, W.
(2007). Resuscitation in the "Gray Zone" of Viability: Determining Physician Preferences and Predicting Infant Outcomes. Pediatrics
120: 519-526
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Gray, R., Petrou, S., Hockley, C., Gardner, F.
(2007). Self-Reported Health Status and Health-Related Quality of Life of Teenagers Who Were Born Before 29 Weeks' Gestational Age. Pediatrics
120: e86-e93
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Robertson, C. M. T., Watt, M.-J., Yasui, Y.
(2007). Changes in the Prevalence of Cerebral Palsy for Children Born Very Prematurely Within a Population-Based Program Over 30 Years. JAMA
297: 2733-2740
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Rees, C. M, Pierro, A., Eaton, S.
(2007). Neurodevelopmental outcomes of neonates with medically and surgically treated necrotizing enterocolitis. Arch. Dis. Child. Fetal Neonatal Ed.
92: F193-F198
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Harding, D R, Humphries, S E, Whitelaw, A, Marlow, N, Montgomery, H E
(2007). Cognitive outcome and cyclo-oxygenase-2 gene (-765 G/C) variation in the preterm infant. Arch. Dis. Child. Fetal Neonatal Ed.
92: F108-F112
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Gornall, J.
(2007). Where do we draw the line?. BMJ
334: 285-289
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Msall, M. E.
(2007). The Limits of Viability and the Uncertainty of Neuroprotection: Challenges in Optimizing Outcomes in Extreme Prematurity. Pediatrics
119: 158-160
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Reijneveld, S A, de Kleine, M J K, van Baar, A L, Kollee, L A A, Verhaak, C M, Verhulst, F C, Verloove-Vanhorick, S P
(2006). Behavioural and emotional problems in very preterm and very low birthweight infants at age 5 years. Arch. Dis. Child. Fetal Neonatal Ed.
91: F423-F428
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Ohlinger, J., Kantak, A., Lavin, J. P. Jr, Fofah, O., Hagen, E., Suresh, G., Halamek, L. P., Schriefer, J. A.
(2006). Evaluation and Development of Potentially Better Practices for Perinatal and Neonatal Communication and Collaboration. Pediatrics
118: S147-S152
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Lavin, J. P. Jr, Kantak, A., Ohlinger, J., Kaempf, J. W., Tomlinson, M., Campbell, B., Fofah, O., Edwards, W., Allbright, K., Hagen, E., Suresh, G., Schriefer, J.
(2006). Attitudes of Obstetric and Pediatric Health Care Providers Toward Resuscitation of Infants Who Are Born at the Margins of Viability. Pediatrics
118: S169-S176
[Abstract][Full Text]
Ikeda, K., Hayashida, S., Hokuto, I., Kusuda, S., Nishida, H., on behalf of the Japan Neonatologist Association,
(2006). International Perspectives: Recent Short-term Outcomes of Ultrapreterm and Extremely Low-birthweight Infants in Japan. NeoReviews
7: e511-e516
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Marlow, N, Greenough, A, Peacock, J L, Marston, L, Limb, E S, Johnson, A H, Calvert, S A, for the United Kingdom Oscillation Study Group,
(2006). Randomised trial of high frequency oscillatory ventilation or conventional ventilation in babies of gestational age 28 weeks or less: respiratory and neurological outcomes at 2 years. Arch. Dis. Child. Fetal Neonatal Ed.
91: F320-F326
[Abstract][Full Text]
Dyet, L. E., Kennea, N., Counsell, S. J., Maalouf, E. F., Ajayi-Obe, M., Duggan, P. J., Harrison, M., Allsop, J. M., Hajnal, J., Herlihy, A. H., Edwards, B., Laroche, S., Cowan, F. M., Rutherford, M. A., Edwards, A. D.
(2006). Natural History of Brain Lesions in Extremely Preterm Infants Studied With Serial Magnetic Resonance Imaging From Birth and Neurodevelopmental Assessment. Pediatrics
118: 536-548
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Khan, N. Z., Muslima, H., Parveen, M., Bhattacharya, M., Begum, N., Chowdhury, S., Jahan, M., Darmstadt, G. L.
(2006). Neurodevelopmental Outcomes of Preterm Infants in Bangladesh. Pediatrics
118: 280-289
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Forcada-Guex, M., Pierrehumbert, B., Borghini, A., Moessinger, A., Muller-Nix, C.
(2006). Early Dyadic Patterns of Mother-Infant Interactions and Outcomes of Prematurity at 18 Months. Pediatrics
118: e107-e114
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Wang, C. J., McGlynn, E. A., Brook, R. H., Leonard, C. H., Piecuch, R. E., Hsueh, S. I., Schuster, M. A.
(2006). Quality-of-Care Indicators for the Neurodevelopmental Follow-up of Very Low Birth Weight Children: Results of an Expert Panel Process.. Pediatrics
117: 2080-2092
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Watts, J L, Saigal, S
(2006). Outcome of extreme prematurity: as information increases so do the dilemmas.. Arch. Dis. Child. Fetal Neonatal Ed.
91: F221-F225
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Srinivasan, L., Allsop, J., Counsell, S.J., Boardman, J.P., Edwards, A.D., Rutherford, M.
(2006). Smaller Cerebellar Volumes in Very Preterm Infants at Term-Equivalent Age are Associated with the Presence of Supratentorial Lesions. Am. J. Neuroradiol.
27: 573-579
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Ancel, P.-Y., Livinec, F., Larroque, B., Marret, S., Arnaud, C., Pierrat, V., Dehan, M., N'Guyen, S., Escande, B., Burguet, A., Thiriez, G., Picaud, J.-C., Andre, M., Breart, G., Kaminski, M., and the EPIPAGE Study Group,
(2006). Cerebral Palsy Among Very Preterm Children in Relation to Gestational Age and Neonatal Ultrasound Abnormalities: The EPIPAGE Cohort Study. Pediatrics
117: 828-835
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Saigal, S., Stoskopf, B., Streiner, D., Boyle, M., Pinelli, J., Paneth, N., Goddeeris, J.
(2006). Transition of Extremely Low-Birth-Weight Infants From Adolescence to Young Adulthood: Comparison With Normal Birth-Weight Controls. JAMA
295: 667-675
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Counsell, S. J., Shen, Y., Boardman, J. P., Larkman, D. J., Kapellou, O., Ward, P., Allsop, J. M., Cowan, F. M., Hajnal, J. V., Edwards, A. D., Rutherford, M. A.
(2006). Axial and Radial Diffusivity in Preterm Infants Who Have Diffuse White Matter Changes on Magnetic Resonance Imaging at Term-Equivalent Age. Pediatrics
117: 376-386
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Kaempf, J. W., Tomlinson, M., Arduza, C., Anderson, S., Campbell, B., Ferguson, L. A., Zabari, M., Stewart, V. T.
(2006). Medical Staff Guidelines for Periviability Pregnancy Counseling and Medical Treatment of Extremely Premature Infants. Pediatrics
117: 22-29
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Mikkola, K., Ritari, N., Tommiska, V., Salokorpi, T., Lehtonen, L., Tammela, O., Paakkonen, L., Olsen, P., Korkman, M., Fellman, V., for the Finnish ELBW Cohort Study Group,
(2005). Neurodevelopmental Outcome at 5 Years of Age of a National Cohort of Extremely Low Birth Weight Infants Who Were Born in 1996-1997. Pediatrics
116: 1391-1400
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Williams, F. L. R., Ogston, S. A., van Toor, H., Visser, T. J., Hume, R., with collaboration from the Scottish Preterm Thyro,
(2005). Serum Thyroid Hormones in Preterm Infants: Associations with Postnatal Illnesses and Drug Usage. J. Clin. Endocrinol. Metab.
90: 5954-5963
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Caravale, B, Tozzi, C, Albino, G, Vicari, S
(2005). Cognitive development in low risk preterm infants at 3-4 years of life. Arch. Dis. Child. Fetal Neonatal Ed.
90: F474-F479
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MacKendrick, W., Caplan, M.
(2005). Ensuring Accurate Knowledge of Prematurity Outcomes for Prenatal Counseling. Pediatrics
116: 1053-1054
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Hack, M., Taylor, H. G., Drotar, D., Schluchter, M., Cartar, L., Wilson-Costello, D., Klein, N., Friedman, H., Mercuri-Minich, N., Morrow, M.
(2005). Poor Predictive Validity of the Bayley Scales of Infant Development for Cognitive Function of Extremely Low Birth Weight Children at School Age. Pediatrics
116: 333-341
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Keenan, H. T., Doron, M. W., Seyda, B. A.
(2005). Comparison of Mothers' and Counselors' Perceptions of Predelivery Counseling for Extremely Premature Infants. Pediatrics
116: 104-111
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Hintz, S. R., Kendrick, D. E., Vohr, B. R., Poole, W. K., Higgins, R. D., for the National Institute of Child Health and Hum,
(2005). Changes in Neurodevelopmental Outcomes at 18 to 22 Months' Corrected Age Among Infants of Less Than 25 Weeks' Gestational Age Born in 1993-1999. Pediatrics
115: 1645-1651
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Bell, J. E., Becher, J.-C., Wyatt, B., Keeling, J. W., McIntosh, N.
(2005). Brain damage and axonal injury in a Scottish cohort of neonatal deaths. Brain
128: 1070-1081
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Haines, L, Fielder, A R, Baker, H, Wilkinson, A R
(2005). UK population based study of severe retinopathy of prematurity: screening, treatment, and outcome. Arch. Dis. Child. Fetal Neonatal Ed.
90: F240-f244
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Field, D., Elbourne, D., Truesdale, A., Grieve, R., Hardy, P., Fenton, A.C., Subhedar, N., Ahluwalia, J., Halliday, H.L., Stocks, J., Tomlin, K., Normand, C., on behalf of the INNOVO Trial Collaborating Group,
(2005). Neonatal Ventilation With Inhaled Nitric Oxide Versus Ventilatory Support Without Inhaled Nitric Oxide for Preterm Infants With Severe Respiratory Failure: The INNOVO Multicentre Randomised Controlled Trial (ISRCTN 17821339). Pediatrics
115: 926-936
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Wilson-Costello, D., Friedman, H., Minich, N., Fanaroff, A. A., Hack, M.
(2005). Improved Survival Rates With Increased Neurodevelopmental Disability for Extremely Low Birth Weight Infants in the 1990s. Pediatrics
115: 997-1003
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Blanco, F., Suresh, G., Howard, D., Soll, R. F.
(2005). Ensuring Accurate Knowledge of Prematurity Outcomes for Prenatal Counseling. Pediatrics
115: e478-e487
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Ho, S., Saigal, S.
(2005). Current Survival and Early Outcomes of Infants of Borderline Viability. NeoReviews
6: e123-e132
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Laptook, A. R., O' Shea, T. M., Shankaran, S., Bhaskar, B., and the NICHD Neonatal Network,
(2005). Adverse Neurodevelopmental Outcomes Among Extremely Low Birth Weight Infants With a Normal Head Ultrasound: Prevalence and Antecedents. Pediatrics
115: 673-680
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Wood, N S, Costeloe, K, Gibson, A T, Hennessy, E M, Marlow, N, Wilkinson, A R, for the EPICure Study Group,
(2005). The EPICure study: associations and antecedents of neurological and developmental disability at 30 months of age following extremely preterm birth. Arch. Dis. Child. Fetal Neonatal Ed.
90: F134-F140
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Inder, T. E., Warfield, S. K., Wang, H., Huppi, P. S., Volpe, J. J.
(2005). Abnormal Cerebral Structure Is Present at Term in Premature Infants. Pediatrics
115: 286-294
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Marlow, N., Wolke, D., Bracewell, M. A., Samara, M., the EPICure Study Group,
(2005). Neurologic and Developmental Disability at Six Years of Age after Extremely Preterm Birth. NEJM
352: 9-19
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Ombelet, W., De Sutter, P., Van der Elst, J., Martens, G.
(2005). Multiple gestation and infertility treatment: registration, reflection and reaction--the Belgian project. Hum Reprod Update
11: 3-14
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Colvin, M., McGuire, W., Fowlie, P. W
(2004). Neurodevelopmental outcomes after preterm birth. BMJ
329: 1390-1393
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Msall, M. E.
(2004). Developmental Vulnerability and Resilience in Extremely Preterm Infants. JAMA
292: 2399-2401
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Annas, G. J.
(2004). Extremely Preterm Birth and Parental Authority to Refuse Treatment -- The Case of Sidney Miller. NEJM
351: 2118-2123
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CRYO-ROP Cooperative Group,
(2004). Health-Related Quality of Life at Age 10 Years in Very Low-Birth-Weight Children With and Without Threshold Retinopathy of Prematurity. Arch Ophthalmol
122: 1659-1666
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Boyle, R. J.
(2004). Ethical Issues in the Care of the Neonate: Overview. NeoReviews
5: e471-e476
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Fowlie, P. W, McGuire, W.
(2004). Immediate care of the preterm infant. BMJ
329: 845-848
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Harding, D. R., Dhamrait, S., Whitelaw, A., Humphries, S. E., Marlow, N., Montgomery, H. E.
(2004). Does Interleukin-6 Genotype Influence Cerebral Injury or Developmental Progress After Preterm Birth?. Pediatrics
114: 941-947
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Mirmiran, M., Barnes, P. D., Keller, K., Constantinou, J. C., Fleisher, B. E., Hintz, S. R., Ariagno, R. L.
(2004). Neonatal Brain Magnetic Resonance Imaging Before Discharge Is Better Than Serial Cranial Ultrasound in Predicting Cerebral Palsy in Very Low Birth Weight Preterm Infants. Pediatrics
114: 992-998
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Tucker, J., McGuire, W.
(2004). Epidemiology of preterm birth. BMJ
329: 675-678
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Vanhaesebrouck, P., Allegaert, K., Bottu, J., Debauche, C., Devlieger, H., Docx, M., Francois, A., Haumont, D., Lombet, J., Rigo, J., Smets, K., Vanherreweghe, I., Overmeire, B. V., Reempts, P. V., for the EPIBEL Study Group,
(2004). The EPIBEL Study: Outcomes to Discharge From Hospital for Extremely Preterm Infants in Belgium. Pediatrics
114: 663-675
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Gardner, F., Johnson, A., Yudkin, P., Bowler, U., Hockley, C., Mutch, L., Wariyar, U., on behalf of ELGA Steering Group,
(2004). Behavioral and Emotional Adjustment of Teenagers in Mainstream School Who Were Born Before 29 Weeks' Gestation. Pediatrics
114: 676-682
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Boyle, R J, Salter, R, Arnander, M W
(2004). Ethics of refusing parental requests to withhold or withdraw treatment from their premature baby. J. Med. Ethics
30: 402-405
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Hess, C. R., Papas, M. A., Black, M. M.
(2004). Use of the Bayley Infant Neurodevelopmental Screener with an Environmental Risk Group. J Pediatr Psychol
29: 321-330
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Strunk, T, Hartel, C, Schultz, C
(2004). Does erythropoietin protect the preterm brain?. Arch. Dis. Child. Fetal Neonatal Ed.
89: F364-F366
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Lucey, J. F., Rowan, C. A., Shiono, P., Wilkinson, A. R., Kilpatrick, S., Payne, N. R., Horbar, J., Carpenter, J., Rogowski, J., Soll, R. F.
(2004). Fetal Infants: The Fate of 4172 Infants With Birth Weights of 401 to 500 Grams--The Vermont Oxford Network Experience (1996-2000). Pediatrics
113: 1559-1566
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Kattwinkel, J., Boyle, R.
(2004). Is the Glass 10% Empty or 90% Full?. Pediatrics
113: 1846-1847
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Johansson, S., Montgomery, S. M., Ekbom, A., Olausson, P. O., Granath, F., Norman, M., Cnattingius, S.
(2004). Preterm Delivery, Level of Care, and Infant Death in Sweden: A Population-Based Study. Pediatrics
113: 1230-1235
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Marlow, N
(2004). Neurocognitive outcome after very preterm birth. Arch. Dis. Child. Fetal Neonatal Ed.
89: F224-F228
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Larroque, B, Breart, G, Kaminski, M, Dehan, M, Andre, M, Burguet, A, Grandjean, H, Ledesert, B, Leveque, C, Maillard, F, Matis, J, Roze, J C, Truffert, P
(2004). Survival of very preterm infants: Epipage, a population based cohort study. Arch. Dis. Child. Fetal Neonatal Ed.
89: F139-F144
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Verlato, G., Gobber, D., Drago, D., Chiandetti, L., Drigo, P.
(2004). Guidelines for Resuscitation in the Delivery Room of Extremely Preterm Infants. J Child Neurol
19: 31-34
[Abstract]
Olischar, M., Klebermass, K., Kuhle, S., Hulek, M., Kohlhauser, C., Rucklinger, E., Pollak, A., Weninger, M.
(2004). Reference Values for Amplitude-Integrated Electroencephalographic Activity in Preterm Infants Younger Than 30 Weeks' Gestational Age. Pediatrics
113: e61-66
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Petrou, S., Mehta, Z., Hockley, C., Cook-Mozaffari, P., Henderson, J., Goldacre, M.
(2003). The Impact of Preterm Birth on Hospital Inpatient Admissions and Costs During the First 5 Years of Life. Pediatrics
112: 1290-1297
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Wood, N S, Costeloe, K, Gibson, A T, Hennessy, E M, Marlow, N, Wilkinson, A R
(2003). The EPICure study: growth and associated problems in children born at 25 weeks of gestational age or less. Arch. Dis. Child. Fetal Neonatal Ed.
88: F492-500
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Saigal, S., Ouden, L. d., Wolke, D., Hoult, L., Paneth, N., Streiner, D. L., Whitaker, A., Pinto-Martin, J.
(2003). School-Age Outcomes in Children Who Were Extremely Low Birth Weight From Four International Population-Based Cohorts. Pediatrics
112: 943-950
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