DOI: /peds

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1 Cerebrl Plsy Among Very Preterm Children in Reltion to Gesttionl Age nd Neontl Ultrsound Abnormlities: The EPIPAGE Cohort Study Pierre-Yves Ancel, Florence Livinec, Bétrice Lrroque, Stéphne Mrret, Ctherine Arnud, Véronique Pierrt, Michel Dehn, Sylvie N'Guyen, Benoît Escnde, Antoine Burguet, Gérrd Thiriez, Jen-Chrles Picud, Monique André, Gérrd Brért, Monique Kminski nd nd the EPIPAGE Study Group Peditrics 2006;117; DOI: /peds The online version of this rticle, long with updted informtion nd services, is locted on the World Wide Web t: PEDIATRICS is the officil journl of the Americn Acdemy of Peditrics. A monthly publiction, it hs been published continuously since PEDIATRICS is owned, published, nd trdemrked by the Americn Acdemy of Peditrics, 141 Northwest Point Boulevrd, Elk Grove Villge, Illinois, Copyright 2006 by the Americn Acdemy of Peditrics. All rights reserved. Print ISSN: Online ISSN:

2 ARTICLE Cerebrl Plsy Among Very Preterm Children in Reltion to Gesttionl Age nd Neontl Ultrsound Abnormlities: The EPIPAGE Cohort Study Pierre-Yves Ancel, MD, PhD, Florence Livinec, MD,Bétrice Lrroque, MD, PhD, Stéphne Mrret, MD, PhD b, Ctherine Arnud, MD, PhD c, Véronique Pierrt, MD, PhD d, Michel Dehn, MD e, Sylvie N Guyen, MD f, Benoît Escnde, MD g, Antoine Burguet, MD, PhD,Gérrd Thiriez, MD h, Jen-Chrles Picud, MD i, Monique André,MD j,gérrd Brért, MD, PhD, Monique Kminski, MsC, the EPIPAGE Study Group INSERM U149 Reserch Unit on Perintl Helth nd Women s Helth, Villejuif, Frnce; b Hôpitl Chrles Nicolle, Rouen, Frnce; c Reserch Unit on Epidemiology nd Public Helth, INSERM U558, Toulouse, Frnce; d Hôpitl Jenne de Flndre, Lille, Frnce; e Hôpitl Antoine Béclère, Pris, Frnce; f Hôpitl Mère-Enfnt, Nntes, Frnce; g Hôpitl Hutepierre, Strsbourg, Frnce; h Hôpitl Sint-Jcques, Besnçon, Frnce; i CHU Montpellier, Montpellier, Frnce; j Hôpitl Universitire, Nncy, Frnce The uthors hve indicted they hve no finncil reltionships relevnt to this rticle to disclose. ABSTRACT OBJECTIVE. To estimte the prevlence of cerebrl plsy t 2 yers of ge mong children born very preterm, ccording to gesttionl ge, infnt gender, plurlity, nd neontl crnil ultrsound bnormlities. METHODS. All infnts born between 22 nd 32 weeks of gesttion in 9 regions of Frnce in 1997 were included in this prospective, popultion-bsed, cohort study. The min outcome mesure ws cerebrl plsy prevlence t 2 yers. Of the 2364 survivors eligible for follow-up evlution, 1954 (83%) were ssessed t 2 yers of ge. RESULTS. Among the 1954 children ssessed t 2 yers, 8.2% hd cerebrl plsy. Bilterl spstic cerebrl plsy, hemiplegi, nd monoplegi ccounted for 72%, 9%, nd 10% of cses, respectively. Fifty percent of the children with cerebrl plsy wlked independently t the ge of 2, 31% were unble to wlk but could sit independently, nd 19% could not sit (unble to mintin hed nd trunk control). The prevlence of cerebrl plsy ws 20% t 24 to 26 weeks of gesttion, compred with 4% t 32 weeks. On the bsis of ultrsound findings in the neontl period, we found tht 17% of children with isolted grde III intrventriculr hemorrhge nd 25% of children with white mtter dmge (ie, ventriculr diltion, persistent echodensities, or cystic periventriculr leukomlci) hd cerebrl plsy, compred with 4% of children with norml ultrsound scns. CONCLUSIONS. Despite recent improvements in survivl rtes, cerebrl plsy remins highly prevlent mong very preterm children. Severe crnil ultrsound bnormlities predict motor disbility strongly, but one third of infnts with cerebrl plsy hd no ultrsound bnormlities. peds doi: /peds Key Words popultion-bsed study, very preterm infnts, white mtter dmge, intrventriculr hemorrhge, prevlence of cerebrl plsy Abbrevitions PVL periventriculr leukomlci IVH intrventriculr hemorrhge IPH intrprenchyml hemorrhge Accepted for publiction Jul 19, 2005 Address correspondence to Pierre-Yves Ancel, MD, PhD, Epidemiologicl Reserch Unit on Perintl nd Women s Helth, INSERM U149, 16 Ave Pul Villnt-Couturier, Villejuif Cedex, Frnce. E-mil: ncel@vjf.inserm.fr PEDIATRICS (ISSN Numbers: Print, ; Online, ). Copyright 2006 by the Americn Acdemy of Peditrics 828 ANCEL, et l

3 CEREBRAL PALSY IS one of the most common nd severe sequele of very preterm birth. Becuse of improvements in survivl rtes, very preterm children now ccount for 25% of ll cses of cerebrl plsy. 1 However, there is no evidence of decrese in the prevlence of cerebrl plsy mong very preterm children. 1 Since the erly 1990s, preterm infnts hve benefited gretly from innovtions in perintl cre, including prentl steroids, exogenous surfctnts, nd new ventiltion techniques; the long-term effects of these innovtions re still mtter of debte. Although registries of childhood impirments nd lrge popultionbsed studies conducted in Europe, 2 Western Austrli 3 nd North Americ 4,5 monitor trends in rtes of cerebrl plsy, few give gesttionl ge-specific rtes. Given the limited vilble informtion nd recent chnges in perintl cre, cerebrl plsy is still n importnt issue for very preterm children. Since the erly 1990s, the survivl rtes of very preterm infnts hve incresed s result of innovtions, ie, prentl steroids, exogenous surfctnts, nd in utero trnsfer. However, the effects of these innovtions on lter disbility re more controversil. We report the prevlence of cerebrl plsy mong 2-yer-old, very preterm children born in 1997, in lrge, geogrphiclly defined popultion in Frnce. We studied the prevlence of cerebrl plsy s function of gesttionl ge t birth, infnt gender, plurlity, nd ultrsound bnormlities identified in the neontl period. METHODS Popultion All births tht occurred between 22 nd 32 completed weeks of gesttion in ll mternity units in 9 French regions in 1997 were included in the EPIPAGE study. 6 Of the 2901 children born live, 127 died immeditely fter birth in the delivery room, 2774 were trnsferred to neontl cre unit, nd 2459 were dischrged live. All survivors born before 32 weeks were enrolled in longitudinl follow-up study. Ech region ws given the option of including 1 of every 2 infnts born t 32 weeks in the follow-up study, to reduce their worklod (given the lrge number of children in this group). In 2 regions (Pris re nd Hute-Normndie), one hlf of the infnts born t 32 weeks were excluded rndomly from the follow-up study (n 77). Therefore, the initil popultion enrolled in the follow-up study included 2382 infnts. Eighteen died fter dischrge from the hospitl but before the ge of 2 yers. The prents of 106 (4%) of the 2364 survivors eligible for the follow-up study refused to prticipte. At 2 yers of ge, the treting physicin (peditricin, neontologist, or generl prctitioner) who exmined the infnt ws sked to complete stndrdized questionnire. This questionnire ws completed for 1960 children (83% of the eligible children). The neurologic sttus of 4 children who still required rtificil respirtion t 2 yers ws not known; therefore, these children were excluded. Two cses of cerebrl plsy cused by physicl violence were excluded. Therefore, totl of 1954 children were included in this nlysis. Mesures nd Definition of Cerebrl Plsy t 2 Yers Ech child ws subjected to detiled physicl nd neurologic exmintion ssessing tone, reflexes, posture, nd movements. A precoded stndrdized questionnire, completed by ech treting physicin, ws designed to minimize the risk of mbiguous nswers, nd trined peditricins reviewed questionnires for infnts with bnorml neurologic exmintion results. We used the definition of cerebrl plsy proposed by the Europen Cerebrl Plsy Network. 2 Children were clssified s hving spstic cerebrl plsy if they hd 2 ofthe following criteri: bnorml posture or movement, incresed tone, or hyperreflexi. Children with involuntry movements were clssified s hving dyskinetic cerebrl plsy, nd those with loss of coordintion were clssified s hving txic cerebrl plsy. 2 Subtypes of cerebrl plsy were clssified into 4 ctegories, s follows. Group 1 represented hemiplegi (ie, unilterl neurologic bnormlity), nd group 2 represented bilterl spstic cerebrl plsy, including children with diplegi (only the lower limbs ffected) nd qudriplegi (ll 4 limbs ffected). Children with monoplegi nd children with txic or dyskinetic cerebrl plsy were plced in groups 3 nd 4, respectively. There were 4 children dignosed s hving cerebrl plsy for whom the subtype ws not described. Three groups were defined ccording to the severity of hndicp, s follows: group 1, children who could wlk independently; group 2, children who could not wlk but who could sit independently; group 3, children who could not sit independently (unble to mintin hed nd trunk control). Perintl Predictors Gesttionl ge refers to completed weeks of menorrhe nd ws the best obstetric estimte bsed on the dte of the lst menstrul period nd n erly prentl ultrsound scn, which is routine prctice in Frnce. Neontl outcomes were determined by consulting medicl records. In Frnce, crnil ultrsonogrphy is performed routinely for very preterm children dmitted to NICUs. Ech infnt usully undergoes 1 to 3 crnil ultrsound exmintions in the first 2 weeks of life. Therefter, weekly exmintion is dvised for infnts with cerebrl bnormlities nd less-frequent exmintions (every 2 weeks) re recommended for infnts without such bnormlities. 7 Qulified neontologists or rdiologists performed crnil ultrsonogrphy t ll prticipting centers. Intrventriculr hemorrhge (IVH), periventriculr leukomlci (PVL), nd ventriculr di- PEDIATRICS Volume 117, Number 3, Mrch

4 ltion were dignosed on the bsis of crnil ultrsound imges. Infnts were clssified s hving grde I IVH if ny ultrsound exmintion showed subependyml hemorrhge, grde II IVH if n ultrsound exmintion showed IVH without ventriculr diltion, nd grde III IVH if n ultrsound exmintion showed IVH with primry ventriculr diltion. Intrprenchyml hemorrhge (IPH) referred to lrge, unilterl, prenchyml hyperdensity or lrge, unilterl, porencephlic cyst, possibly ttributble to venous hemorrhgic infrction. 8 PVL ws defined s the presence of periventriculr white mtter echolucencies (cystic PVL) or echodensities persisting for 14 dys without cyst formtion. Ventriculr diltion referred to isolted diltion of ventricles with no ssocited IVH. In derived vrible describing ll crnil ultrsound results, infnts with norml ultrsound results were distinguished from those with isolted IVH without intrprenchyml involvement (ie, grde I II [clss 1] nd grde III [clss 2] IVH) nd from those with white mtter bnormlities. The ltter group included infnts with persisting echodensities nd ventriculr diltion (clss 3), unilterl cystic PVL (clss 4), bilterl cystic PVL (clss 5), nd IPH (clss 6), which re considered different forms of white mtter disese. 9,10 Anlysis Results re presented s proportions of the number of survivors ssessed t 2 yers of ge. The sttisticl nlyses were weighted to tke into ccount the differences in the proportions of children who underwent follow-up monitoring ccording to gesttionl ge nd region. Only weighted percentges re shown in the tbles. The Person 2 sttistic ws corrected for the survey design by using the correction described by Ro nd Scott 11 nd ws converted into n F sttistic. Sttisticl nlyses were performed with Stt softwre (Stt Corp, College Sttion, TX). The study ws pproved by the Commission Ntionle de l Informtique et des Libertés. RESULTS Infnts who were ssessed t 2 yers of ge (responders) hd younger gesttionl ge t birth thn did the other children (nonresponders) (Tble 1). There ws no difference between the 2 groups regrding crnil ultrsound bnormlities. In contrst, we observed significnt socioeconomic differences between the 2 groups; young mothers, single mothers, nd mothers with low eductionl levels were less likely to prticipte in the follow-up study thn were other mothers (Tble 1). Of the 1954 survivors ssessed, 165 hd cerebrl plsy (8.2%; 95% confidence intervl: %). Spstic cerebrl plsy nd txi nd/or dyskinetic cerebrl plsy ccounted for 91% nd 7%, respectively, of ll cses. Bilterl spstic cerebrl plsy ws present in 72% (diplegi: 44%; qudriplegi: 28%), hemiplegi in 9%, nd monoplegi in 10%. The subtype ws not recorded in 4 TABLE 1 Comprison of Chrcteristics Between Responders nd Nonresponders Proportion, % P Nonresponders (n 404) Responders (n 1960) Gesttionl ge t birth (n 404) (n 1960) wk wk wk wk Infnt gender (n 404) (n 1960).13 Femle Plurlity (n 404) (n 1960).05 Singleton Twins Triplets nd qudruplets Cerebrl hemorrhge (n 377) (n 1935).14 No Grde I II IVH Grde III IVH or IPH Cystic PVL (n 377) (n 1936).37 Yes Mternl ge (n 404) (n 1944) y y y y Prity (n 401) (n 1946) or Mritl sttus (n 299) (n 1745).001 Mrried Nonmrried cohbiting Single Eductionl level (n 277) (n 1646).005 I II III IV Eduction ws clssified into 4 levels, from level I (no schooling or primry level) to level IV (university level). cses. Fifty percent of the children with cerebrl plsy wlked independently t the ge of 2 yers, 31% were unble to wlk but could sit independently, nd 19% could not sit (unble to mintin hed nd trunk control). Among the 1789 children without cerebrl plsy, 1.4% could not wlk t 2 yers of ge. The prevlence of cerebrl plsy decresed with incresing gesttionl ge (Tble 2), ie, 20% t 27 weeks, 12% t 27 to 28 weeks, 8% t 29 to 30 weeks, 7% t 31 weeks, nd 4% t 32 weeks. Cerebrl plsy ws slightly but not significntly more frequent mong boys (9%) thn girls (7%). There ws no difference in cerebrl plsy rtes ccording to plurlity. Neontl crnil ultrsound bnormlities predicted cerebrl plsy to certin extent (Tble 3); 28% nd 60% of children with grde III IVH nd IPH, respectively, developed cerebrl plsy t 2 yers, compred with 7% 830 ANCEL, et l

5 TABLE 2 Cerebrl Plsy Rtes According to Gesttionl Age, Infnt Gender, nd Plurlity No. Proportion With Cerebrl Plsy, % P Totl Gesttionl ge t birth wk wk wk wk wk wk wk wk Infnt gender.10 Mle Femle Plurlity.35 Singletons Twins Triplets nd qudruplets of children without IVH. Cerebrl plsy rtes were 75% mong children with bilterl cystic PVL, 35% mong children with unilterl cystic PVL, nd 17% mong children with persistent echodensities, compred with 5% in the bsence of PVL. Two thirds of children with PVL in the prietl or occipitl lobes were lter dignosed s hving cerebrl plsy. No bnormlities were identified in crnil ultrsound scns for 1238 children; however, in this group, 4.4% of children developed cerebrl plsy (Tble 3). When cerebrl plsy rtes were compred for the 4 gesttionl ge groups, there ws sttisticlly significnt difference in the rtes of cerebrl plsy mong children with no ultrsound bnormlities; the more immture the infnt, the greter ws the likelihood of cerebrl plsy (Tble 4). Among children with isolted IVH, persistent echodensities, or ventriculr diltion, only the most immture hd n incresed risk of cerebrl plsy. There were no sttisticlly significnt differences ccording to gesttionl ge mong infnts with cystic PVL or IPH. The 56 children who hd cerebrl plsy nd norml ultrsound findings ccounted for 35% of the children with cerebrl plsy (Tble 5). Children with isolted IVH nd those with white mtter disese ccounted for 14% nd 52%, respectively, of cerebrl plsy cses. The distribution of ultrsound results vried with gesttionl ge. Only 17% of children born t 27 weeks who developed cerebrl plsy hd no ultrsound bnormlities, compred with 31% t 27 to 28 weeks, 33% t 29 to 30 weeks, nd 48% t 31 to 32 weeks (Tble 5). Conversely, the percentges of isolted IVH decresed with gesttionl ge, but there ws little vrition in the percentges of white mtter bnormlities. However, TABLE 3 Cerebrl Plsy Rtes in Reltion to Neontl Crnil Ultrsound Abnormlities No. Proportion With P Cerebrl Plsy, % Ultrsound bnormlities.001 No Isolted grde I II IVH Isolted grde III IVH White mtter bnormlities b Persistent echodensities or ventriculr diltion Unilterl cystic PVL Bilterl cystic PVL IPH Cerebrl hemorrhge.001 No Grde I IVH Grde II IVH Grde III IVH IPH Ventriculr diltion.59 No Yes PVL.001 No Persistent echodensities Cystic PVL Unilterl Bilterl Prietl or occipitl Other locliztion P.001; the P vlue indictes significnt difference in cerebrl plsy rtes ccording to ultrsound bnormlities (with cystic PVL nd IPH grouped). b White mtter bnormlities included persistent echodensities, ventriculr diltion, cystic PVL, nd IPH. subtypes of white mtter bnormlities seemed to vry with gesttionl ge; persistent echodensities nd ventriculr diltion were more common t 24 to 26 weeks thn fter tht ge. There were no sttisticlly significnt differences in the distributions of cerebrl plsy subtypes mong children with norml ultrsound findings, isolted IVH, or white mtter bnormlities (Tble 6). Although bilterl spstic diplegi ws more common mong children with bilterl cystic PVL (88%) thn mong children with unilterl cystic PVL or IPH, numbers were very smll. Among infnts with cerebrl plsy, 35% of infnts with white mtter bnormlities could wlk nd 31% could not sit, compred with 13% nd 63%, respectively, of infnts with bilterl cystic PVL (Tble 7). In comprison, 55% of infnts with isolted IVH nd 71% of infnts without crnil ultrsound bnormlities could wlk independently. DISCUSSION In this study, we estimted the risk of cerebrl plsy for lrge smple of very preterm children born between 22 nd 32 weeks in The popultion of the EPIPAGE PEDIATRICS Volume 117, Number 3, Mrch

6 TABLE 4 Prevlence of Cerebrl Plsy According to Gesttionl Age nd Crnil Ultrsound Abnormlities Gesttionl Ultrsound Abnormlities, No. (%) Age, wk None Isolted IVH b Echodensities or Ventriculr Diltion Cystic PVL or IPH Totl Smple (10.9) 50 (20.0) 36 (27.8) 36 (41.7) 144 (20.8) (7.5) 82 (4.9) 70 (12.9) 24 (58.3) 337 (11.6) (4.4) 100 (6.0) 65 (9.2) 26 (61.5) 511 (8.2) (3.4) 115 (2.4) 91 (13.3) 20 (61.9) 962 (5.4) Comprison of cerebrl plsy rtes ccording gesttionl ge within ech group of crnil ultrsound dignosis yielded the following: no ultrsound bnormlities, P.05; isolted IVH, P.05; echodensities or ventriculr diltion, P.09; cystic PVL or IPH, nonsignificnt. b Isolted IVH ws isolted grde I, II, or III IVH. TABLE 5 Neontl Ultrsound Abnormlities According to Gesttionl Age Among Children With Cerebrl Plsy Ultrsound Abnormlities Proportion of Cerebrl Plsy Cses, % wk (n 30) wk (n 39) wk (n 42) wk (n 53) Totl (n 164) None Isolted IVH b White mtter bnormlities c Persistent echodensities or ventriculr diltion Unilterl cystic PVL Bilterl cystic PVL IPH P.01, result of the test compring the distribution of ultrsound bnormlities (none, isolted IVH, or white mtter bnormlities, ie, persistent echodensities, ventriculr diltion, cystic PVL, nd IPH grouped) ccording to gesttionl ge. b Isolted IVH ws isolted grde I, II, or III IVH. c White mtter bnormlities included persistent echodensities, ventriculr diltion, cystic PVL, nd IPH. TABLE 6 Subtypes of Cerebrl Plsy According to Neontl Crnil Ultrsound Abnormlities Ultrsound Abnormlities No. Proportion, % Bilterl Spstic Hemiplegi Monoplegi Other Cerebrl Plsy None Isolted IVH b White mtter bnormlities c Persistent echodensities or ventriculr diltion Unilterl cystic PVL Bilterl cystic PVL IPH Nonsignificnt, result of the test compring the distribution of cerebrl plsy subtypes ccording to ultrsound bnormlities (none, isolted IVH, or white mtter bnormlities, ie, persistent echodensities, ventriculr diltion, cystic PVL, nd IPH grouped). b Isolted IVH ws isolted grde I, II, or III IVH. c White mtter bnormlities included persistent echodensities, ventriculr diltion, cystic PVL, nd IPH. study ws defined geogrphiclly, which eliminted the referrl bis inherent in studies recruiting only from selected perintl centers. Obstetricins estimted gesttionl ges ccording to the best vilble informtion (ultrsound scn results nd dte of lst menstrul period). Becuse n erly scn is stndrd prctice for lmost ll pregnnt women in Frnce, 12 we cn ssume tht this estimtion of gesttionl ge is relible nd of good qulity. This is n importnt point becuse recruitment bsed on birth weight leds to overrepresenttion of more-mture children with restricted growth. 13 Moreover, gesttionl ge is better predictor thn birth weight of mortlity nd morbidity rtes. 14 Loss to follow-up monitoring is n importnt issue in longitudinl studies, becuse it cn bis the results. We hd informtion for 83% of the eligible survivors. Tin et l 15 showed tht children monitored with difficulty re more likely to hve severe disbility thn those monitored without difficulty. In our study, children lost to follow-up monitoring hd n older gesttionl ge t birth but did not differ from the group not lost to follow-up monitoring with respect to neontl cerebrl 832 ANCEL, et l

7 TABLE 7 Severity of Cerebrl Plsy According to Neontl Crnil Ultrsound Abnormlities Ultrsound No. Severity of Abnormlities Cerebrl Plsy, % b Wlk Sit Cnnot Sit None Isolted IVH c White mtter bnormlities d Persistent echodensities or ventriculr diltion Unilterl cystic PVL Bilterl cystic PVL IPH P.01, result of the test compring the severity of cerebrl plsy ccording to ultrsound bnormlities (none, isolted IVH, or white mtter bnormlities, ie, persistent echodensities, ventriculr diltion, cystic PVL, nd IPH grouped). b Severity of cerebrl plsy ws clssified s follows: wlk, ble to wlk independently; sit, unble to wlk but ble to sit independently; cnnot sit, unble to mintin hed nd trunk control. c Isolted IVH ws isolted grde I, II, or III IVH. d White mtter bnormlities included persistent echodensities, ventriculr diltion, cystic PVL, nd IPH. lesions. This suggests tht they were not t higher risk of neurologic disbilities thn monitored children. It is difficult to compre the rtes of cerebrl plsy between studies becuse the rtes vry ccording to number of fctors, including definition, ge nd method of scertinment, nd yer of birth. To fcilitte comprisons, we used the criteri recommended by the Surveillnce of Cerebrl Plsy in Europe network 2 to dignose cerebrl plsy. However, becuse our study took plce in 9 regions of Frnce, mny physicins were involved nd the bility to dignose cerebrl plsy might hve vried. Furthermore, the children were ssessed t 2 yers, wheres ssessment t 5 yers would probbly result in more ccurte mesures of finl neurologic outcomes. 2 Although this might hve led to n underestimtion of mild nondisbling cses of cerebrl plsy, the Victorin Infnt Collbortive Study Group 16 showed tht ssessments of young children might be too pessimistic. However, chnges in neurologic clssifiction with ge occur infrequently. 17 The EPIPAGE study provides the opportunity to investigte the neuromotor outcomes of infnts born very or extremely preterm who hve benefited from prentl corticosteroids, exogenous surfctnt, nd in utero trnsfer. 18,19 Since the Bvrin Longitudinl Study 20 nd the Project On Preterm nd Smll for Gesttionl Age Infnts in the Netherlnds 21 were performed in the 1980s, no equivlent, lrge, popultion-bsed studies hve exmined the neurodevelopmentl outcomes of this popultion. In our study, 20% of infnts born before 27 weeks developed cerebrl plsy, ccounted for 18% of very preterm children with cerebrl plsy. The EPICure popultion-bsed study showed tht 18% of the 283 survivors born before 26 weeks hd cerebrl plsy t 30 months. 22 Estimtes of the prevlence mong children born before 27 weeks vry from 11% to 35%. 23,24 Differences in smple size (rnge: children), ge t ssessment (2 5 yers), nd distribution of gesttionl ges mke it difficult to compre rtes between studies or to estimte precisely the cerebrl plsy rte t the lowest gesttionl ges. An importnt finding of our study is tht cerebrl plsy rtes remin high mong children born fter 27 weeks. On the bsis of dt from Europen registries, the gesttionl ge-specific rte of cerebrl plsy ws 5% to 6% for children born t 28 to 31 weeks. 1,3,25 Becuse these children ccount for more thn two thirds of cerebrl plsy cses mong very preterm children, dditionl studies re needed regrding this group. It is likely tht different subtypes of cerebrl plsy hve different cuses. 26 On the bsis of MRI findings, Colver nd Sethumdhvn 27 rgued tht cerebrl injuries responsible for qudriplegic, triplegic, nd diplegic syndromes re very similr nd should be grouped together, defining bilterl spstic cerebrl plsy. According to this clssifiction, 72% of the children with cerebrl plsy in our popultion hd bilterl spstic form nd 9% hd hemiplegi. These vlues re very similr to the percentges (75 83% nd 9 13%, respectively) estimted for other preterm popultions. 1,22,28 In our study, we evluted the severity of the hndicp ccording to the bility to wlk nd sit independently; 50% of infnts with cerebrl plsy were unble to wlk t the ge of 2 yers nd 40% of these children were severely disbled (unble to mintin hed nd trunk control). According to the literture, the rtes of moderte/severe motor disbility vry from 10% to 50%, 22,28,29 nd there is no evidence tht the functionl severity of cerebrl plsy is declining mong very preterm or very low birth weight children. 28,29 Our study showed how the risk of cerebrl plsy vries ccording to the presence nd type of crnil ultrsound bnormlities dignosed in the neontl period. In review of 15 studies, Holling nd Leviton 30 showed tht 59% of children with echolucencies developed cerebrl plsy subsequently. Our results re prticulrly interesting becuse they re popultion-bsed. Of the 76 children with cystic PVL, 44 (58%) developed cerebrl plsy, which is very similr to the estimte by Holling nd Leviton. 30 As expected, the risk of cerebrl plsy ws higher when cystic PVL ws bilterl nd loclized in the prietl nd occipitl lobes. 30 We found tht the incresed risk of cerebrl plsy with decresing gesttionl ge ws prtly ttributble to n excess of cerebrl bnormlities mong the most immture infnts (Tble 4). In one recent study, neurodevelopmentl outcomes were independent of gesttionl ge when ech lesion ws considered seprtely. 31 In our study, cerebrl plsy rtes incresed with decresing gesttionl ge, even mong children with no ultr- PEDIATRICS Volume 117, Number 3, Mrch

8 sound bnormlities nd mong those with isolted IVH, echodensities, or ventriculr diltion. Although it could be speculted tht gesttionl ge in itself hs n independent effect on neurodevelopmentl outcomes, deficiencies of ultrsonogrphy in detecting subtle white mtter pthologic conditions should be considered. Almost 4% of children with norml ultrsound findings developed cerebrl plsy, ccounting for one third of ll cses of cerebrl plsy (nerly 50% of cerebrl plsy cses t weeks). However, those children were less disbled thn infnts with ultrsound bnormlities, which suggests tht they suffer from subtle nd less extensive cerebrl lesions. One explntion for the low sensitivity of ultrsonogrphy t the oldest gesttionl ges my be tht such children undergo fewer scns thn children born t younger gesttionl ges. 6 Difficulties in the dignosis of cerebrl lesions re ssumed to be ttributble to the limittions of the technique itself. However, the qulity of scnning nd scn interprettion re possible components of this problem. In recent study, only 59% of doctors interpreted correctly high-resolution scnned imges of 6 mjor neontl ultrsound bnormlities. 32 As suggested by De Vries et l, 33 very preterm infnts need to undergo scnning until dischrge nd the equivlent of term ge. In their study, 30% of children who developed cerebrl plsy fter mjor ultrsound bnormlities would hve not been dignosed if ultrsound scns hd been restricted to the first 4 weeks fter birth. Our lrge popultion-bsed study of very preterm children born in 1997 showed tht 1 of every 12 very preterm children hd cerebrl plsy; this rte is t lest 80 times higher thn tht mong term children. As expected, the risk of cerebrl plsy decresed with incresing gesttionl ge t birth, lthough 7% of children born t 28 to 32 weeks were ffected. Prdoxiclly, very few studies hve investigted this popultion, lthough these children represent 85% of surviving very preterm infnts 6 nd two thirds of very preterm children with cerebrl plsy. Lstly, it would be of gret interest to investigte the impct of neontl injuries on sensorineurl, cognitive, nd fine motor functions. Dt collected t 5 yers of ge should mke it possible to nswer these questions. ACKNOWLEDGMENTS Funding for this study ws obtined from INSERM (French Ntionl Institute of Helth nd Medicl Reserch), Merck-Shrp, Dohme-Chibret, l Fondtion de l Recherche Médicle (Medicl Reserch Foundtion), nd l Direction Générle de l Snté du Ministère des Affires Sociles (Directorte Generl for Helth of the French Ministry for Socil Affirs). The EPIPAGE Study Group ws s follows: INSERM U149: B. Lrroque (ntionl coordintor), P. Y. Ancel, B. Blondel, G. Brért, M. Dehn, M. Grel, M. Kminski, F. Millrd, C. du Mzubrun, P. Missy, F. Sehili, K. Supernnt; Alsce: M. Durnt, J. Mtis, J. Messer, A. Treisser (Hôpitl de Hutepierre, Strsbourg); Frnche- Comté: A. Burguet, L. Abrhm-Lert, A. Menget, P. Roth, J-P. Schl, G. Thiriez (CHU St Jcques, Besnçon); Hute-Normndie: C. Lévêque, S. Mrret, L. Mrpeu (Hôpitl Chrles Nicolle, Rouen); Lnguedoc- Roussillon: P. Boulot, J-C. Picud (Hôpitl Arnud de Villeneuve, Montpellier), A-M. Dondio, B. Ledésert (ORS Montpellier); Lorrine: M. André, J-L. Boutroy, J. Fresson, J. M. Hscoët (Mternité Régionle, Nncy); Midi-Pyrénées: C. Arnud, S. Bourdet-Loubère, H. Grndjen (INSERM U558, Toulouse), M. Rollnd (Hôpitl des Enfnts, Toulouse); Nord-Ps-de-Clis: C. Leignel, P. Lequien, V. Pierrt, F. Puech, D. Subtil, P. Truffert (Hôpitl Jenne de Flndre, Lille); Pys de l Loire: G. Boog, V. Rouger-Bureu, J-C. Rozé (Hôpitl Mère-Enfnts, Nntes); Pris-Petite-Couronne: P-Y. Ancel, G. Brért, M. Kminski, C. du Mzubrun (INSERM U149, Pris), M. Dehn, V. Zupn (Hôpitl Antoine Béclère, Clmrt), M. Vodovr, M. Voyer (Institut de Puériculture, Pris). REFERENCES 1. 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10 Cerebrl Plsy Among Very Preterm Children in Reltion to Gesttionl Age nd Neontl Ultrsound Abnormlities: The EPIPAGE Cohort Study Pierre-Yves Ancel, Florence Livinec, Bétrice Lrroque, Stéphne Mrret, Ctherine Arnud, Véronique Pierrt, Michel Dehn, Sylvie N'Guyen, Benoît Escnde, Antoine Burguet, Gérrd Thiriez, Jen-Chrles Picud, Monique André, Gérrd Brért, Monique Kminski nd nd the EPIPAGE Study Group Peditrics 2006;117; DOI: /peds Updted Informtion & Services References Cittions Subspecilty Collections Permissions & Licensing Reprints including high-resolution figures, cn be found t: This rticle cites 29 rticles, 14 of which you cn ccess for free t: This rticle hs been cited by 8 HighWire-hosted rticles: s This rticle, long with others on similr topics, ppers in the following collection(s): Premture & Newborn n Informtion bout reproducing this rticle in prts (figures, tbles) or in its entirety cn be found online t: Informtion bout ordering reprints cn be found online: