Cent ro de Neurologia Pediát rica - CENEP, Depart ament o de Pediat ria, Hospit al de Clínicas de Curit iba, Universidade Federal do Paraná UFPR Curit iba, PR, Brazil: 1Pediat ra do Depart ament o de Pediat ria da UFPR; 2Neuropediat ra, Prof essor Assist ent e do Depart ament o
de Pediatria da UFPR; 3Neuropediatra, Professora Adjunta do Departamento de Pediatria da UFPR; 4Neonatologista, Professor Assistente
do Depart ament o de Pediat ria da UFPR; 5Cirurgião Pediát rico, Prof essor Adjunt o do Depart ament o de Cirurgia da UFPR; 6Neuropediat ra; 7M édico Cirurgião Pediát rico.
Received 12 February 2004, received in f inal f orm 2 June 2004. Accept ed 6 July 2004.
Dr. Isac Bruck - Rua Floriano Essenf elder 81 - 80060-270 Curit iba PR - Brasil. E-mail: ibruck@t erra.com.br
M YELOM ENINGOCELE
A Brazilian Universit y Hospit al experience
M aria M .M . Ulsenheimer
1, Sérgio A. Ant oniuk
2,
Lúcia H.C. dos Sant os
3, M arcos P. Ceccat t o
4,
Ant ônio Ernest o da Silveira
5, Ana Paula Ruiz
6, Paulo Egger
7, Isac Bruck
2ABSTRACT - We analyzed 31 children with myelomeningocele born between July 1990 and July 2000. Follow-up median w as 24 mont hs (6-68mont hs). Only 2 mot hers had a know n et iologic f act or (diabet es mellit us). Tw elve had t he correct prenat al diagnosis. All children w ere born at t erm; 23 by cesarean; 13 had rupt ure of t he membrane. Surgical correct ion had a 4 days median (1 t o 44 days). Lumbosacral lesions w ere t he most f requent (46% ). Thirt y pat ient s w ere hydrocephalic, shunt w as placed in 27. M eningit is w as 4 t imes more f requent in shunt ed pat ient s. Seven became epilept ic (19.4% ). Denver II t est show ed signif icant delay in gross mot or development . Neurogenic bladder w as diagnosed in 12 pat ient s. Congenit al clubf oot w as t he main ort hopedic malf ormat ion (53% ). Six inf ant s died. Now adays, 17 pat ient s are being f ollow ed. A mult idisciplinary approach probably helps f or a bet t er qualit y of lif e.
KEY WORDS: meningomyelocele, neural t ube def ect s, neurological disabilit ies.
M ielom eningocele: experiência de um hospit al universit ário brasileiro
RESUM O - Avaliamos 31 crianças com mielomeningocele nascidas ent re julho de 1990 e julho de 2000. A mediana de acompanhament o f oi 24 meses (6-68m). Duas mães possuíam conhecido f at or de risco (dia-bet es mellit us). Doze obt iveram corret o diagnóst ico pré-nat al da pat ologia. Todas as crianças nasceram a t ermo; 23 via cesariana; 13 apresent aram rupt ura de membrana. A mediana de correção cirúrgica f oi 4 dias (1-44d). Lesões lombosacras f oram as mais f reqüent es (46% ). Trint a pacient es apresent aram hidroce-f alia, sendo a derivação vent rículo perit oneal (DVP) necessária em 27. M eningit e hidroce-f oi 4 vezes mais hidroce-f requent e em pacient es com DVP. Set e pacient es eram epilépt icos (19,4% ). O t est e de Denver II most rou at raso mot or signif icant e. Bexiga neurogênica f oi diagnost icada em 12 pacient es. Pé t ort o congênit o f oi a malf ormação ort opédica mais comum (53% ). Seis pacient es morreram. At é o moment o, 17 pacient es são acompanhados. Uma abordagem mult idisciplinar provavelment e colabora para melhor qualidade de vida.
PALAVRAS-CHAVE: mielomeningocele, def eit os do t ubo neural, def iciências neurológicas.
M yelomeningocele has a f requency of approx-imat ely 1:1000 new born alive, w it h preponderan-ce in f emales and w hit e rapreponderan-ce1,2. It is a neural t ube
def ect (NTD) t hat result s f rom a f ailure of closure of t he neural t ube during t he f ourt h w eek of em-bryogenesis. It can occur since cervical unt il sacral region. Depending on t he level of t he lesion can cause dif f erent grades of neurological dysf unct i-on2. Et iology is variable, involving bot h genet ic and
environment al f act ors, as f or inst ance an inade-quat e level of f olic acid during embryonary
neuru-lat ion2-8. The cyst ic appearance not ed at t he spinal
cord is easy to diagnose at newborn period and must be repaired w it hin 24 t o 48 hours t o reduce t he risk of inf ect ion. How ever, t reat ment is not limit ed t o t he closure of t he NTD, since ot her syst ems show abnormalit ies, as urinary syst em, f or example2.
ob-served. Thus, it is import ant t hat t he healt h care inst it ut ions and t he societ y as a w hole, be prepare t o receive t hese children and of f er t hem a bet t er qualit y of lif e.
On t his basis, w e review ed t he pat ient s w it h myelomeningocele born or t ransf erred t o t he ma-t ernima-t y of our hospima-t al, ma-t o dema-t ermine ma-t heir clinical prof ile, t he t reat ment approach of f ered t o t hem, and t heir f ollow -up. Special at t ent ion w as paid t o neurological perf ormance, and t o det erminig w e-t her e-t he children w ere able e-t o w alk and e-t o acquire sphinct er cont rol.
M ETHOD
We review ed t he f ollow -up of neonat es born in t he mat ernit y of Universit y Hospit al of Universidade Federal do Paraná bet w een July 1990 and July 2000, as w ell as new borns w it h myelomeningocele t ransf erred t o Neo-nat al Int ensive Care Unit (ICU) of our Hospit al during t he same period. The Et hical Commit t ee of t his Hospit al ap-proved t he st udy.
Prenatal and neonatal data were reviewed from Neona-tal ICU registers. Other data were collected from outpati-ents care register, accomplished by neurologic and surgi-cal teams, composed by resident of third and fouth years under supervision of teachers of the respective disciplines. We analyzed gender, race, f amily hist ory, and mat er-nal aspect s t hat could have some relat ion w it h t he occur-rence of t he disease (drugs in use, age, parit y, educat ion-al level, prenat ion-al care, and basic diseases), as w ell as t ime of diagnosis (pre or post -nat al), perinat al dat a (t ype of delivery, gest at ional age by Parkin, new born w eight , Ap-gar score, head circumf erence, ort hopedic abnormali-ties), characteristics of the lesion (location, presence or not of membrane rupt ure, use of prophylact ic ant ibiot ics) and cent ral nervous syst em (CNS) abnormalit ies, seen t h-rough comput ed t omography (CT) scan or ult rasonogra-phy (US), dat e of surgical correct ion and insert ion of ven-t ricle periven-t oneal shunven-t (VPS). The Denver II Screening ven-t esven-t w as used t o assess t he neuropsychomot or development of t hese pat ient s up t o t he age of 2 years9,10. Ot her dat a
relat ed t o neurological complicat ions have also been indicat ed, such as: epilepsy, meningit is, VPS changes).
Urological f ollow -up est abilished at t he out pat ient clinic of pediat ric surgery w ere also evaluat ed by means of imaging exams such as urography, echography or urodynamic evaluat ion; presence or not of neurogenic bladder, prophylact ic use of ant ibiot ics f or inf ect ion of urinary tract, use of catheterization or not, sphincter con-t rol, abilicon-t y con-t o w alk and renal f unccon-t ion monicon-t orizacon-t ion. Ort hopedic def ormat ions w ere also described.
RESULTS
A total of 36 cases of myelomeningocele were de-t ecde-t ed bede-t w een 20369 liveborn inf ande-t s ade-t our
ma-ternity between July 1990 and July 2000, equivalent t o a prevalence of 1.8 cases/1000 liveborn inf ant s.
The ef f ect ive number of pat ient s in t he st udy w as 31.26 of t hem originally f rom our mat ernit y and 5 born in ot her mat ernit ies in t he st at e and t ransf erred t o t he neonat al ICU of our Hospit al in t he f irst f ew days of lif e. Ten pat ient s born in our mat ernit y w ere excluded because t hey didnot re-t urn re-t o oure-t pare-t ienre-t clinic f or f ollow -up.
There w as a f rank preponderance of w hit e race (29 pat ient s = 93.5% ) but no dif f erence in gender (16 f emales: 15 males). M ean mat ernal age w as 25 years old (SD7.3 years). Educat ional level ranged f rom 1 t o 11 years of st udy (mean ± SD= 7.7 ± 3.7years). Wit h respect t o f amily origin, 10 w ere f rom Curit iba, 10 f rom met ropolit an region of t he city and 11 from other towns in the State of Parana. Tw o mot hers had diabet es mellit us during preg-nancy, 1 epilepsy, 2 rheumat ic disease, 2 cancer and 2 syst emic hypert ension. None of t hem made use of medicat ion considered t o cause myelomeningo-cele during pregnancy. Tw ent y f ive (80.6% ) cases occurred bet w een t he f irst and second pregnan-cy, and t here w as one case w it h f amily hist ory of first degree relatives. None of the women used folic acid as a mean t o prevent NTD.
Tw elve cases (39% ) w ere diagnosed prenat al-ly. Ten ot her cases (32.2% ) had pre-nat al diagno-sis of hydrocephalus only, as part of NTD. Just one pregnant w oman didnot receive prenat al care. In other 8 (25%), there wasnot information about pre-nat al care on t heir regist ers.
Cesarean sect ion w as t he pref erent ial rout e of delivery (23 cases = 74%). Similar percentage of rup-t ures of rup-t he myelomenigocele membrane occurred w het her delivery w as vaginal or cesarean sect ion (10 among 23 cesarean sect ions = 43% and 3 in t he 8 vaginal delivery = 37.5% ). M ean gest at ional age w as 39 and a half w eeks (SD 1 w eek), and mean inf ant w eight w as 3009gr (SD 573gr). The Apgar score w as below 6 at 5 minut es in only one case.
Table 1. Associat ed cent ral nervous syst em malf ormat ions.
M alf ormat ion N (% ) cases
Arnold Chiari II 10 (32.2% )
Corpus callosum agenesis 4 (12.9% )
Colpocephaly 2 (6.4% )
Holoprosencephaly 2 (6.4% )
M ean head circumf erence at birt h w as 35.5cm (SD 3.6cm). The level of t he lesion w as cervical in 2 cas-es (6% ), t horacolumbar in 10 (32% ), lumbar in 4 (13% ), lumbo-sacral in 14 (46% ) and sacral in one (3% ). Sevent een pat ient s had associat ed clubf oot (53% ), 5 st rabismus (16% ) and 2 congenit al sub-luxat ion of t he hips (6.4% ).
Morphological evaluation of the CNS was perfor-med by cranial US in 20 cases (64.5% ) and CT scan in 11 cases (35.4% ), t he exams being carried out , on average, at 1.5 days of lif e (1-60 days). Thirt y pa-t ienpa-t s show ed apa-t leaspa-t some degree of hydroce-phalus (97%) and ten of them had Chiari type II mal-f ormat ion (32% ). There w ere also ot her kinds omal-f associat ed malf ormat ions, as seen in Table 1.
Correct ion of myelomeningocele w as in medi-an at f our days of lif e (1 t o 44 days). A VPS w as nec-essary in 27 of t he pat ient s (90% ), in a second sur-gical st ep at a median age of 15 days (3 – 270 days), except f or one case w ho w as submit t ed t o t he correct ion of t he myelomeningocele and VPS simult aneously. Eight een pat ient s (58% ) needed at least one reintervention to change the VPS, because of meningit is in 14 of t hem. The f irst episode of meningit is occurred at a median age of 21 days (4 t o 49 days). Among pat ient s w it hout VPS, only 1 had one episode of meningit is. Epilepsy w as diag-nosed in 7 pat ient s (22.5% ); all had VPS and
pre-vious hist ory of meningit is. During t he st udy peri-od, t w o pat ient s show ed a t et hered cord and t hree ot hers, import ant spinal def ormit ies.
The f irst neurological evaluat ion at t he out pa-t ienpa-t clinic occurred w ipa-t h a median of 48 days of lif e (1 - 570 days), and t he pat ient s w ere f ollow ed up f rom 6 t o 68 mont hs (median = 24 mont hs). Of t hese, 21 (68% ) w ere evaluat ed at 1 year of age by Denver II screening t est , t hat show ed a great er delay on gross motor area, with a mean performan-ce corresponding t o t hat of a child of 7 mont hs; w hile in t he ot her areas (f ine mot or adapt ive, lan-guage and personal-social) t he mean age corre-sponded t o t hat of a 10 mont h-old child (see Table 2). The same w as seen in 13 pat ient s (42% ) evalu-at ed evalu-at 2 years of age (see Table 3), f or w hom t he mean age f or gross mot or f unct ion w as 6 mont hs low er t han f or ot her areas (f ine mot or adapt ive, language and personal-social). The language area, w hich is bet t er evaluat ed at t his age, did not show any delay.
Urologic evaluat ion by a pediat ric surgeon w as done in 19 pat ient s (61% ), w it h t he f irst exam be-ing perf ormed w it h a median age of 90 days of lif e. (2 days - 2 years) The pat ient s w ere f ollow ed f or 4 mont hs up t o 60 mont hs (median of 27 mont hs). Twelve patients (38.7%) had the diagnosis of neuro-genic bladder made by urodynamic met hods, w it h a median of 12 mont hs of age (1 - 64 mont hs). The 7 pat ient s w it hout t his diagnosis w ere t hose w ho w ere not submit t ed t o urodynamic st udy.
Fourt een pat ient s (45% ) w ere submit t ed t o imaging st udies (US and/or uret rocyst ography), hy-dronephrosis and vesico-uret heral ref lux w ere diagnosed in 3 of t hem. Treat ment consist ed of intermittent catheterization for these last 3 patients and also f or 4 more pat ient s w ho had import ant vesicle residues. One pat ient had been under int er-mit t ent cat het erizat ion since he w as 6 days old due t o early global vesicle f ormat ion. The associat ion of ant icholinergic medicat ion w as necessary f or 7 pat ient s and w as st art ed at t he median age of 26 mont hs (4 - 58 mont hs). One pat ient required t he combinat ion of doxozym w it h oxybut ynin and anot her one t he combinat ion of imypramine and oxybut ynin. Ten pat ient s had repeat ed episodes of urinary tract infection (UTI), with half of them being submit t ed t o int ermit t ent cat het erizat ion. All pat ient s w it h t he diagnosis of neurogenic bladder w ere t aking a prophylact ic ant ibiot ic against UTI.
Six pat ient s died, all bef ore t he age of 2 years (4 - 20 months): two of meningitis, 1 bronchoaspiration,
Table 2. Neurological evaluat ion by Denver II at 12 mont hs of age (n=21).
Area M ean* St andard deviat ion*
Gross mot or 7 2
Fine mot or 9.43 2.8
Language 10 2.3
Personal-social 10 2.53
* in mont hs
Table 3. Neurological evaluat ion by Denver II at 24 mont hs of age (n=13).
Área M ean* St andard deviat ion*
Gross mot or 15.6 6.9
Fine mot or 22.1 4.37
Language 23 3.1
Personal-social 22.3 3.9
1 pneumonia and 2 due to an unknown etiology. At present , 17 of t he 31 pat ient s are being f ollow ed in our service, all of t hem w it h good preservat ion of renal f unct ion, 8 have sphinct er cont rol and 10 are able t o w alk (communit y ambulat ion) (Table 4).
DISCUSSION
The prevalence of myelomeningocele of 1.8 ca-ses/1000 liveborn neonat es f ound in our service is a lit t le higher t han t he value report ed w orldw ide, w hich is around 1/1000, but agrees w it h t he val-ues report ed in ot her Sout h America count ries1,2.
The preponderance of w hit e race f ound in our st udy may ref lect only t he race dist ribut ion of our populat ion. The apparent equal gender dist ribu-t ion is f alse, since if w e included ribu-t he 12 paribu-t ienribu-t s born in our mat ernit y w ho didnot ret urn t o nerological evaluat ion and w ere excluded of t he st u-dy, t he number of f emales w ould be higher t han t he number of males, as has been described by Greene at al11.
In 62% of our patients the level of the lesion was lumbar or lower, this probably being one of the
rea-sons w hy many pat ient s w ere able t o w alk, al-though patients with myelomeningocele at high le-vel can also achieve communit y ambulat ion w hen t hey receive good care, as report ed by Charney at all12. (Table 4). Environment al f act ors may play a
ro-le in t he higher risk of t he pat hologic embryo de-velopment, as occurred in 2 cases of gestational dia-bet es, w hich is know n t o act as a cof act or of NTD2.
The genet ic cont ribut ion t o malf ormat ion of neu-ral t ube is suggest ed by t he predominance of it s occurrence in t he f irst and second gest at ion. This emphasizes t he import ance of prevent ion of recur-rences in f amilies at higher risk t o have a second child affected by the same NTD malformation, what can be achieved by simple measures such as t he use of f olic acid bef ore an during pregnancy3-8.
The major reason w hy part of t he pat ient pop-ulat ion w as lost t o f ollow -up w as t he f act t hat 30% of t he pat ient s’ f amilies lived in t ow ns out -side Curit iba and it s met ropolit an region. M ost of t he mot hers had a st able st at us, since 24 (77.41% ) of t hem w ere married and t his f act or associat ed w it h a reasonable educat ional level are import ant
Tabela 4. M ain clinical f eat ures.
N Age* Sex Lesion level CNS malf ormat ion Sphinct er Ambulat ion
cont rol
1 68 F Lumbosacral Yes Yes
2 14 F Lumbosacral Abscence of 4t h vent ricle No No
3 36 M Lumbosacral Colpocephaly and arqueduct al st enosis No No
4 26 F Lumbar Arnold Chiari II and corpus callosum agenesis No Yes
5 35 F Lumbar No No
6 23 M Lumbosacral Yes Yes
7 11 F Lumbar No No
8 16 F Cervical No No
9 26 M Thoracolumbar Yes Yes
10 10 F Thoracolumbar Arnold Chiari II Yes Yes
11 17 M Lumbosacral No No
12 49 M Lumbosacral No Yes
13 24 M Lumbar Yes Yes
14 92 M Lumbosacral Corpus callosum agenesis Yes Yes
15 18 M Lumbosacral Abscence of 4t h vent ricle No No
16 60 M Cervical Holoprosencephaly Yes Yes
17 61 M Thoracolumbar Yes Yes
for the cognitive development, as has been demon-st rat ed by Bier et al13.
A prenat al diagnosis by US is dif f icult t o be es-tablished, and it usually identifies only the hydroce-phalus and t heir dist ort ions, as w e saw in t he pres-ent st udy. To be visualized, t he def ect must be lo-cat ed in t he vert ebral column, since t he cyst ic-like sac can not be seen by US14,15. There is no
agree-ment about t he best rout e of delivery, but it seems t hat cesarean sect ion bet t er prot ect s t he sac mem-brane f rom rupt ure2,16,17. In t he present st udy t here
w ere no dif f erences in t he number of rupt ure of t he membrane bet w een cesarean sect ion and vagi-nal delivery. All neonat es w ere f ull t erm, in con-t rascon-t con-t o con-t he licon-t eracon-t ure w hich reporcon-t s a higher preva-lence of NTD among premat ure inf ant s. Also, 20% of t he inf ant s st udied w ere of low birt h w eight (≤2500gr), as also report ed by Aguiar et al3.
Only one of the patients had an Apgar score bel-low 6 at 5 minut es, a f act excluding t he possibili-t y of perinapossibili-t al asphyxia as possibili-t he cause of delayed de-velopment18. Head circumf erence w as w it hin
nor-mal values at delivery, alt hough hydrocephalus was already present, and decompensation occurred later on, after correction of the myelomeningocele. Hydrocephalus is present in nearly 90% of t he cas-es at t he age of 4 mont hs, as w as also t he case in t he present st udy13. Regarding ot her
complica-t ions, Chiari II malf ormacomplica-t ion, complica-t ecomplica-t hered cord, orcomplica-t ho-pedic and urologic def ect s w ere t he most prepon-derant , as also report ed in t he lit erat ure2,15.
Alt hough t he correct ion of myelomeningocele should be perf ormed as soon as possible, pref eren-t ially w ieren-t hin eren-t he f irseren-t 72 hours of lif e, in some of t he present pat ient s t he correct ion w as made up to 44 days of life. A ventriculoperitoneal shunt, indi-cat ed t o t he pat ient s w it h hydrocephalus, w as per-f ormed in 90% oper-f t hem in a second st age in order t o reduce t he chance of CNS inf ect ion2,19. Even so,
how ever, episodes of meningit is w ere responsible f or reint ervent ions in order t o change t he VPS in 14 pat ient s, usually bef ore one mont h of it s place-ment . The large number of CNS inf ect ions t hat occurred in our sample could be most ly explained by t he delay in correct ing t he myelomeningocele in many of t hem (af t er 72 hours)2,20-22. The mort
alit y rat e w as relat ively low despalit e delays in correct -ing t he NTD, t hanks t o t he use of prophylact ic ant ibiot ic20,22. The associat ion of epilepsy and
mye-lomeningocele in t he present st udy w as probably relat ed t o t he presence of VPS t hat compensat es
for hydrocephalus, plus previous episodes of menin-git is, also ment ioned by ot her aut hors23-25.
Denver II Test show ed t hat t he major delay in t he development al milest one of our pat ient s occur-red in t he gross mot or area, direct ly aff ect ed by t he myelomeningocele. The int elligence quot ient (IQ) w as not available f or most of t he pat ient s and t heref ore it w as impossible t o assess t heir cognit ive level but , based on Fobe et al, a normal IQ can be achieved up t o 80% of t he pat ient s21. Denver II
Screening Test in children at risk, in w hich t here is up t o one f ailure at t he age of 2 years, w as f ound an IQ>80, by WPSSI-R, in 70% of t hese children at the age of 5 years, according to Frankenburg et al.10
and Bruck et al. (personal comunicat ion). The
lan-guage area, w hich is bet t er evaluat ed at 2 years old did not show any delay, indicat ing t hat t he prob-lem mainly concerns t he gross mot or area.
It w as an agreeable surprise t o observe t hat , al-though the diagnosis of bladder dysfunction was ma-de w it h a ma-delay in many of t he pat ient s, all show ed preservat ion of renal f unct ion, and many of t hem w ere socially compet ent (dry f or 3 hours) (Table 4). We w ould like t o emphasize t hat t he lit erat ure rec-ommends intermittent catheterization during the first year of lif e, and even st art ing at birt h because t his procedure does not involve major side eff ect s, and is of great benef it . Thus, it should be rout inely used even in t he absence of bladder dysf unct ion26-28.
We could see t hat many of t he mot hers looked f or urologic evaluat ion only lat t er on, because of t heir concern about t heir children being unable t o leave diapers at t he age supposed t o do it .
The mort alit y rat e in our sample w as 19% , gre-at er t han t hgre-at described by Brau gre-at al. (10-15% ) and all of t hem happened bef ore 2 years, w hich is t he age of great er risk20.
In conclusion t he present st udy represent s only a small sample of children w it h myelomeningocele and it is necessary more st udies made in ot her cent ers in order t o have a bet t er idea of how are t he Brazilian children w it h t his pat hology. been managed. We w ould like t o ment ion t hat t he Bra-zilian government is planning to enrich wheat flour w it h f olic acid, as a prophylact ic measure t o pre-vent pregnant w omen f rom having an of f spring w it h myelomeningocele29. These children if w ell
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