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## ^Origina l Article s 

# eadan dHyperactivit y Revisite d A n Investigatio n o

f Nondisadvantage dChildre n P. 2

examin e whethe r hy poxi c •.SO' J

. iispring . i weU - "

iutio n

see n •Th

e purposes^Tffls"stuly^?efe ^ tractiv e childre n ha d elevate d lea d levels , t o asses s whethe r tad level s wer e associate d wit h poo r psychometri c perform aKei n hyperactiv e children , an d t o replicat e previou s report s tf hyperactiv

e childre n wit h perinata l Insul t havin g lowe r lea d M s tha n thos e wit h norma l perinata l history . Hyperactive , taming-disabled childre n an d norma l sibling s wer e studied . tte hyperactive childre n ha d highe r chelate d urin e lea d level s ten thei r ow n siblings . Othe r contrast s wer e no t significant . Cognitiv e performanc e an d lea d level s wer e weakl y associate d ' sth e hyperactiv e sample . Contrar y t o previou s reports , lea d • •pd s an d perinata l complication s wer e no t negativel y corre - \ Mtd . Thes e result s suppor t th e notio n tha t lea d level s ar e * acakl y associate d wit h hyperactiv e disorders . tfncb Gen Psychiatry

1983;40:827-833 ) ^Ithoug h th e sequela e o f larg e dose s of

lea dar e wel l !/! . known, 1, 2 th e effect s of long-term , lo w level s of absorp

Xm remai n unclear . Mos t studie s hav e reporte dtha t Chil

ia n with raise dlea dlevels , no t formerl y believe dt o b e i n & toxi c range , sho w sligh t bu t ofte n significan t

decre

e t s i n cognitio n an dbehavior . Fo r example , raise dlea d iirel s hav e bee n foun dt o b e associate dwit h lowe r intelli

poore r academi c skills, 6 an dincrease dmoto r activ

-

.•ii i an a

. o r loss . FDavi dan dco-workers 9 reporte dtha t black , inner-city , :. ; t '°y^ c_Sjperactiv e childre n ha dhighe r lea dlevel s tha n nonhyper

- ) T a j ! ', sav e childre n fro mth e sam e area . Lea dlevel s wer e ne ; ; assure di n urin e afte r provocatio n wit h penicillamine , an d •jmbness . jMood . Definin g toxi c urin e lea dlevel s a s greate r tha n '^ J a xrri ; ' USmg/L, Davi de t a l foun dtha t

62 % ofth e hyperactiv e •Tbdomira i Sildren , bu t

onl y 29 % ofth e nonhyperactiv e children , ha d icbse c i dlevel s i n th e toxi c range . Furthermore , amon g th e jperactiv e youngsters , lea dlevel s wer e negativel y associ

ttdwit h perinata l ris k

factors . Davi de t

a l divide dth e 1 pperactiv e childre n int o thre e groups , on e withou t ahis

- <.;:onsni p : ay o f perinata l complication s ( N = 50) , anothe r wit h ahis

nergic

- g y 0 f

seriou s perinata l complication s viewe da s "highl y

~ an dNe ^ J^bl e cau ses " o f

hyperactivit y ( N = 5) , an dathir dgrou p ^bocytopa-& complication s les s sever e tha n thos e of th e "probable " ang e i n j jba p bu t judge dt o b e "possible " cause s of hyperactivit y

- ce . uri

- ', $=<)) . Th e childre n wit h "probable " cause s wer e foun dt o BB significantl y lowe r

lea dlevel s tha n th e othe r tw o roips. Furthermore , th e proportio n o f childre n i n th e toxi c .•tract . •' • ag e differe damon g the . thre e etiologi c subgroups . O f opriate ias

e withou t an y caus e fo r

hyperactivity , 3 1 (62% ) ha d

. ! f G

. a a s

- . si c lea dlevels , an dof thos e wit h probabl e cause , seven ! • 3% ) ha dtoxi c lea dlevels ; i n contrast , on e (20% ) o f thos e |

,.. , ah ahighl y probabl e caus e ha datoxi c lea dlevel . iressatt

• an y 3.Pruso»a»;ltepte dfo

r publicatio n No v 5 , 19S2 . :ou!patien3-^JViji

n the New Yor

k Stat e Psychiatri c Institute , Columbi aUniversity eo f Physician s an dSurgeons , Ne w Yor k (D r Gittelman) ; an dth e Joh n ree Foundatio n an dth e Departmen t o f Epidemiolog y andPubli c Utli , Yal e Schoo l o f Medicine , Ne w Haven , Conn (D r Eskenazi) . 'JtfciM request s t o Ne w Yor

k Stat e Psychiatri c Institute , Columbi a •ersit y Colleg e b

f Physician s an dSurgeons , 722 W 168t h St , New York , 11003 2 (D r Gittelman) . x J . d i Ge n Psychiatry—Vo l 40 , Au g 198 3 Rache l Gittelman , PhD , Brend aEskenazi . Ph D Davi dan dcolleague s conclude dtha t low-leve l lea dintox

icatio n ma y pla y a n etiologi c rol e i n som e case s of hyperac

tivity , notabl y i n childre n withou t perinata l complications . Thei r sampl e sizes , however , wer e to o smal l t o allo w fo r firm conclusions . I n asubsequen t large r study , Davi dan dco workers' " di dno t

replicat e th e significan t differenc e i n lea d level s betwee n hyperactiv e childre n wit h an dthos e withou t perinata l complications , thoug h atren dwa s found . Som e methodologica l problem s complicat e th e interpre

tatio n o f thos e results . Perinata l histor y wa s take n fro m char t review , an dinformatio n wa s derive dfro mroutin e clinica l interview s withou t standardize dprocedures . I n addition , th e socioeconomi c statu s ofth e respectiv e group s wa s no t indicated . Th e associatio n o f lea dlevel s wit h hyperactivit y an dit s putativ e etiologi c subtype s coul db e confounde db y socioeconomi c status. " Eve n i f th e variou s group s wer e equivalen t i n socia l class , th e result s ma y b e specifi c t o sociall y deprive dgroups . Th e purpos e of

th e presen t

stud y wa s t o examin e lea d level s i n nondisadvantage dhyperactiv e childre n wit h well

confirme dsocioeconomi c statu s (SES) . Th e goal s wer e t o asses s (1 ) whethe r

lea dlevel s wer e highe r i n hyperactiv e childre n tha n norma l children ; (2 ) whethe r elevate dlea d level s i n hyperactiv e youngsters , i f found , wer e specifi c t o thi s diagnosti c group ; (3 ) whethe r th e negativ e relationshi p betwee n perinata l complication s an dlea dlevel s i n hyperac

tiv e childre n coul db e replicated ; (4 ) whethe r lea dleve l wa s associate dwit h severit y of hyperactivity ; an d(5 ) whethe r th e negativ e associatio n betwee n cognitiv e performanc e an dlea dexposur e reporte di n norma l children 3 ' 5 8 als o occurre di n hyperactiv e children .

SUBJECT S AN D METHOD S

Sample s Thre e group s wer e include di n thi s investigation : (1 ) nondisad

vantage dhyperactiv e children ; (2) norma l children ; an d(3 ) non disadvantage dchildre n with adevelopmenta l disorde r othe r tha n hyperactivit y (learning-disable dchildren) . Excep t fo r th e norma l children , al l childre n hadparticipate din clinical trial s betwee n 197 1 an d1975 . Detail s ofth e selectio n procedure s ar e summarize d onl y briefl y sinc e the y appea r elsewhere. 12 ' 1 ' 1 All childre n live di n suburba n area s o

f New Yor k City . Hyperactiv e Children.—Th e hyperactiv e childre n wer e par t o f tw o separat e studie s in whic h slightl y differen t clinical criteri a wer e applied . Bot

h studie s require dth e childre n t o demonstrat e cross-situationa l hyperactivity . A t th e tim e o

f th e first study, 1 2 no objectiv e scal e criteri aha d bee n establishe dt o quantif y hyperactivit y i n th e classroom ; therefore , arbitrar y standard s fo r hyperactivit y wer e applied . Childre n hadt o receiv e aminimu mscor e o f 2 (range , 0 t o 3 ) o n severa l item s ofth e Teache r Ratin g Scale 1 5 tha t

reflec t inattentio n an dimpulsivity . I n addition , childre n wer e accepte donl y i f rate d hyperactiv e b y parent s on th e Home Hyperactivit y Scale, 1 6 o r judge dhyperactiv e in th e clinic . I n th e secon dstudy, 1 3 childre n referre db y school s fo r hyperac

tivit y hadt o receiv e score s o f a t leas t 1. 8 (o f apossibl e maximu mo

f 3.0 ) on th e hyperactivit y facto r o f th e Teache r

Ratin g Scale . Parent s ha dt o confir

mth e presenc e o

f clea r behavio r problem s a t Lea d an d Hyperactivity—Gittelma n & Eskenaz iP. 3



### \~ Tabl e 1.—Weighting s an d Frequencie s o f Perinata l Complications * Complication s Pregnanc y Mil d Materna l ag e >3 0 y rfo rfirstborn , >4 0 y rfo r other s > 3 miscarriage s befor e thi s birt h > 3 miscarriage s afte rthi s birt h Medica l interventio n t o conceiv e thi s chil d Sever e nause a an d vomitin g extendin g int o thir d trimeste r Mil d stainin g afte rfirs t trimeste r Mil d bleeding ; threatene d abortio n durin g firs t trimeste r Mil d bleeding ; threatene d abortio n afte rfirs t trimeste r Mil d toxemi a Mildl yelevate d B P Weigh t gai n of >20. 5 k g Controlle d diabete s Otne rmil d healt n problem s Abdomina l x-ra yfil m Infectiou s diseas e durin g firs t trimeste r Infectiou s diseas e afte rfirs t trimeste r Othe rillnes s afte rfirs t trimeste r Surger ywit h genera l anesthesi a Unusua l medicatio n Mil d physica l traum a Mil d emotiona l stres s Moderat e Moderat e bleeding ; threatene d abortio n afte rfirs t trimeste r Moderat e toxemi a Moderatel yhig h B P Othe rmoderat e heait h problem s Sever e emotiona l stres s No . o f Subject s

8 1 1 1 4 1 5 8 2 3 3 8 4 8 1 1 5 6 3 6 1 1 2 2 1 1 4 3 1 2 Tabl e 1.—Weighting s an d Frequencie s o f Perinata l Complications * (cont ) Complication s No . . Subj c Labo ran d deliver y Mil d Extende d labo r(stage. 1 (o r>2 4 hr , o rstag e 2 fo r > 2 hr ) Precipitat e labo r Prematur e membran e ruptur e (24-4 8 hr ) Cor d aroun d nec k

(no t prolapsed ) Routin e cesarea n deliver y Abnorma l positio n Moderat e Cesarea n deliver ymedicall yindicate d Neonata l conditio n Mil d Delaye d breathin g fo r1- 3 mi n Wea k o rabnorma l cr y Mild/intermitten t cyanosi s Oxyge n give n fo r2 mi n Apga rscor e of 7 o r8 Mil d congenita l defec t Mil d illnes s fo r1 w k R h o rothe rbloo d incompatibilit y Birt h weigh t of 2.0-2. 4 k g Gestatio n of >4 3 w k Moderat e Apga rscor e of 5 o r6 i 3 2 4 6 

### e £ o 

### ">

o Sever e Apga rscor e of 1 o r4 •Complication s no t foun d include d th e following : attemp t t o abor t t h convulsion s durin g pregnancy ; uncontrolle d diabetes ; sever e t moderat e o rsever e stainin g afte rthir d trimester ; sever e othe r problem s durin g pregnancy ; medica l indicatio n t o induc e labor ; < . delayed ; midforcep s o rhig h forcep s delivery ; manua l o rforcep s - . prematur e separatio n o f membrane ; feta l distress ; breathin g de; . mor e tha n thre e minutes ; cr ydelaye d fo rmor e tha n 1 5 minutes ; p c cyanosis ; continuou s oxyge n given ; abnorma l conditio n of hea d fmarks , cephalhematoma) ; an d prolapse d cord . home , an dapsychiatris t ha dt o diagnos e th e chil da s havin g a hyperkineti c reactio n o

f childhood. IT Both studie s require dchildre n t o b e betwee n 6 an d1 2 year s old , t o come fromhome s wher e Englis h wa s spoken , an dt o b e fre e o f a psychoti c o r

neurologica l disorde r

(th e presenc e o

f nonspecifi c neurologica l abnormalitie s o r sign s di dnot

preclud e admission) . Childre n als o ha dt o obtai n an I Q o f a t leas t 8 0 on th e Wechsle r Intelligenc e Scal e fo

r Childre n (WISC) , with eithe r aperformanc e o r verba l I Q o

f a t leas t 85 . Nonhyperactiv e Learning-Disable dChildren.—T o obtai n a grou p with adevelopmenta l disorde r othe r tha n hyperactivity , we recruite dchildre n with readin g disabilities . Thi s grou p seeme d mos t appropriat e sinc e i t

represente darelativel y homogeneous dysfunctio n tha t

i s ofte n assume dt o b e aphenotypi c expressio n o f minimal brai n dysfunction , a s i s hyperactivity. 1 8 T o b e included , childre n hadt o (1 ) b e referre db y schoo l becaus e o f academi c difficultie s exclusively ; (2 ) hav e no complain t o f behavio r problems ; (3 ) receiv e score s belo w 1. 5 o n th e hyperac

tivit y facto r

o f th e Teache r

Ratin g Scale ; (4 ) b e judge db y achil d psychiatris t

a s havin g no psychiatri c disorde r othe r tha n th e learnin g disorder ; (5 ) hav e n o know n neurologica l disorder ; (6 ) hav e a n overal l WIS C I Q o

f SO , with aperformanc e o r

verba l I Q o

f 85 ; (7 ) hav e areadin g leve l a t leas t on e o r tw o year s belo w thei r

age appropriat e grad e (dependin g on IQ ) on th e Wide Rang e Achieve

men t Tes t (WRAT ) an dGray Ora l Readin g (GOR) Test ; an d (8 ) come fromahom

e wher e Englis h wa s spoken . Norma l Children.—T o contro l fo r socioeconomi c status , paren ta l practices , an dothe r

environmenta l factor s tha t migh t influenc e exposur e t o lead , th e norma l sibling s o f th e tw o patien t

group s wer e selecte da s controls . The y wer e betwee n 6 an d1 2 yt- i an dwer e reporte db y parent s t o hav e hadn o behavio r prob ; schoo l an dno histor y o

f academi c difficulties . I f mor e tha n on e normal siblin g w r er e withi n th e appropr i range , all wer e included . No neuropsychologica l testi i conducte don th e siblings . I t seem s reasonabl e t o assum e t l sibling s wer e o

f averag e intelligence , sinc e the y ha dn o hi.

- academi c difficulties . Moreover , thei r hyperactiv e sibling s v norma l IQ , an dwe hav e foun dtha t norma l sibling s o

f hyp o childre n fro

mthi s populatio n hav e highe r IQ s tha n thei r

h ; tiv e siblings. 1 9 Lea d Level s Th e procedur e fo

r evaluatin g lea dlevel s wa s identica l : • reporte db y Davi de t

al. 9 Eac h chil dreceive da t bedtim e 25- : th e chelatin g agen t

penicillamin e (Cuprimine) . Th e first m < urin e specime n wa s collecte din lead-fre e plasti c bottles , men s wer e frozen unti l delivery t o th e Cit y o f New Yor k lab » wher e the y were analyze dfor lea dcontent . (Thi s laborati . selecte dbecaus e it.ha dperforme dth e analyse s fo r th e sn . Davi de t al. 910 ) Analyse s wer e performe dwithou t knowledg e children' s grou p membership . Sinc e atota l night' s uri: - . needed , childre n with enuresi s wer e excluded . Thos e al l penicilli n wer e als o excluded . (Sinc e prospectiv e studie s c i in g children' s bloo dlea dlevel s ove r tim e t o singl e mea.s : chelate dlea dlevel s hav e no t bee n performed , w e canno t b e i tha t th e latte r

accuratel y reflect s body lea dburde n du e u. ter mexposure . Davi de t al reporte dtha t

chelate dleadl

c urin e wer e correlate dwith bloo dlevels . W e foun dtha t cl . 82 8 Arc h Ge n Psychiatry—Vo l 40 , Au g 198 3 Lea d an d Hyperactivity—Gittelma n & E iP. 4

.c-250mg«v?yP eractive s v norma l siblings : r(134 ) = 1.40 . P=.16 ; hyperactive s v "•< morain e Bnirig-disable d children : f(132 ) = 0.45 , P=.65 ; learning-disable d childre n les . Spe c Tia l siblings : f(62 ) = 1.36 , P=.18 . -. laborato ? p. rator y « i

dlevels o f hyperactive s an dthei r

sibling s wer e highl y associ

-

.. e studies ) id , suggestin g tha t th e measur e i s reliable ; nevertheless , it s ledg e o f t i fidity fo r measurin g lea dburde n remain s unestablished. ) urin e w fcr

. ' allergic ! t \

Othe r Clinica l Measure s .'lie s comp l ifainata l Complications.—Pregnancy , labo r an ddelivery , an d measures, ' nata l histor y o f th e hyperactiv e childre n wer e obtaine dfro m • i t b e cert j jjpj ta i records , an dals o frommother s b y mean s o f astandardize d du e t o loflfestionnair

e give n b y asocial worke r o r psychologist . Sinc e

. u dleve^Jkiu i interviewin g wa s possibl e onl y whe n th e researc h staf f was .ha t chelaSfciable , no t

al l mother s wer e questioned . N o systemati c sam Ge n Psychiatry—Vo l 40 , Au g 198 3 plini r bias , however , influence dwhic h mother s were interviewed . Thre e approache s wer e use dt o asses s perinata l difficulties : (1 ) Childre n wer e dichotomize dbetwee n thos e withou t an y repor t o f perinata l insul t

an dthos e w^it

h a t leas t on e abnorma l finding. (2 ) Perinata l complication s wer e weighte dfo r severit y from1 t o 4 , wit h 1 indicatin g nonsignifican t o r no complication ; 2 , mild ; 3 , moderate ; an d4 , severe . Thes e weight s wer e adopte dfromothe r studies. 1 ' " Th e item s with thei r respectiv e weight s ar e presente din Tabl e 1 . Mea

n scor e fo

r eac h perinata l categor y wa s obtaine db y summin g al l severit y score s an ddividin g th e su mb y th e numbe r o f item s rated . (3 ) Base don acomposit e o f prenatal , labo r

an d delivery , an dneonata l complications , th e perinata l historie s wer e classifie dfo

r eac h chil da s clearl y abnormal , borderlin e abnormal , o r unremarkable . Thes e categorie s ar e analagou s t o Davi dan d colleagues ' classification s o f probabl e cause , possibl e cause , an dno history . Severit y o

f Illness.—Th e hyperactivit y facto r o f th e Teache r Ratin g Scale 1 ' ' an daglobal ratin g o f illnes s wer e use da s a n estimat e o

f severit y o

f behaviora l disturbance . Severit y o f illnes s wa s rate dby achil dpsychiatris t afte r adiagnosti c evaluation . I t wa s score dfrom1 t o 7 , highe r score s indicatin g greate r overal l psychiatri c disturbance . Neuropsychologica l Performance.—Hyperactiv e childre n wer e evaluate don abatter y o f neuropsychologica l tests , includin g th e WISC ; th e WRAT , ates t o f wor drecognition , spelling , an d arithmetic ; th e GO

Rtest , ates t

o f paragrap h readin g an dcompre hension;an dth e Beery-Buktenic ates t o f Visua l Moto r Integratio n (VMI) , ates t

o f desig n copying . In addition , th e hyperactiv e childre n wh o participate di n th e first stud y wer e teste don th e Visua l Sequentia l Memor

y Tes t ofth e Illinoi s Tes t

o f Psycholinguisti c Ability an davisua l paired-associ

at e test , arote-learnin g tas k wher e th e chil dwa s require dt o nam e th e objec t

paire dwith eac h o

f te n symbol s (th e scor e wa s th e numbe r o f trial s neede dt o lear n th e te n object-symbo l pairs) . Dat aAnalyses.—Th e dat awer e analyze dt o asses s whethe r th e hyperactiv e children , normal siblings , an dnonhyperactiv e learn

in g disable dchildre n differe dsignificantl y i n (1 ) lea ddistribution ; (2 ) mea n leadlevel ; anc

l (3 ) th e proportio n o

f childre n i n th e rang e define db y Davi de t

al a s toxic , tha t

is , greate r

tha n 0.0 8 mg/L . W e examine dth e possibl e confoundin g effect s o f SES , race , age , an dgende r

on grou p difference s in lea dlevel . Thes e confounder s wer e controlle din th e statistica l analysi s whe n appropriate . T o provid e furthe r

contro l ove r

SES , race , parenta l IQ , an dan y othe r possibl e environmenta l factors , hyperactiv e childre n wer e paire dwit

h on e o f thei r ow n siblings . Th e lea dlevel s o f th e pair s wer e contrasted . Analyse s withi n th e hyperactiv e grou p wer e performe dtq asses s • th e relationshi p betwee n leadexposur e an d(1 ) severit y o f behavio r disturbance , (2 ) perinata l factors , an d(3 ) neuropsychologica l tes t performance . Al l probabilit y value s reporte dar e two-tailed . RESULT S Sampl e Parent s o f 17 3 hyperactiv e o r

learning-disable dchildre n wer e approached . Eigh t

refuse dt o hav e thei r

chil dparticipat e an dthre e childre n refuse dt o cooperate . O f th e remainin g 16

2 children , 2 8 wer e exclude d(four

wer e be dwetter s an d2

4 wer e allergi c t o peni

cillin) . Th e final group s consiste do f 103 hyperactives , 3 1 nonhyper

activ e learning-disable dchildren , an d3 3 norma l siblin g controls . Tabl e 2 present s th e sampl e characteristics . Th e childre n wer e predominantl y male , white , an dabou t 1 0 year s old . Th e proportio n o f boy s wa s significantl y large r in th e hyperactiv e grou p tha n in th e othe r tw o group s (P<.001) . Thi s se x distributio n reflect s th e typica l preponderanc e o

f boy s amon g childre n referre dfo r hyper

activity , a s compare dwit

h childre n referre dfo

r learnin g problems . Grou p Difference s i n Lea d Level s Th e grou p distribution s o f lea dlevel s appea r

in Fi g 1 . Th e overal l proportion s in leadvalue s fo r th e thre e group s di dno t differ significantl y (x"[4 ] = 6.33 , no t significant) . A s show n i

n Tabl e 3 , n

o significan t

difference s in mean lea d level s wer e foundbetwee n hyperactiv e childre n an dth e siblin g control s (£[134] = 1.40 , no t significan t

[NS]) , betwee n hyperactiv e childre n an dlearning-disable dchildre n (([132 ] = 0.45 , NS) , o r be

twee n learning-disable dchildre n an dsiblin g control s (<[62 ] = 1.35 , NS) . Lea d an d Hyperactivity—Gittelma n & Eskenaz i 82 9P. 5



## 3 3 Tabl e 4.—Sampl e Characteristic s an d Lead Level s o f 2 0 Hyperactive-Siblin g Pair s Age , y r(mea n ± % male * % whit e Lead , mg/ L Mea n sSD f Rang e SD )

Distribution ^

No . o f subject s 0.00-0.0 8 0.09-0.1 6 0.17-0.2 4 >0.2 4 Hyperactive s

10. 0 ±2. 5 8 5 8 0 0.12*0.0 9 0.03-0.3 5 9 8 1 2 Paire d Norma l Sibling s

10.4*1. 9 5 5 8 0 0.0 8 ±0.0 5 0.02-0.2 2 1 3 6 1 0 V(1 ) = 4.3 , P=.04 . tf(19 ) = 2.52 , P=.02 . tFo rlevel s >0.0 8 v

sO.0 8 mg/L , * 2 (1 ) = 1.62 , P = .20 . 0.3 5mg/Lels,Lev

• o taves'>ractHype 0.3 0 0.2 5 0.2 0 0.1 5 0.1 0 0.0 5 0.0 0 0.0 5 0.1 0 0.1 5 0.2 0 0.2 5 0.3 0 0.3 5

Siblings ' Lea d Levels , mg/ L Fi g 2.—Paire d lea d level s o f hyperactiv e childre n an d thei rnorma l sibling s (/'=.69 , P<.01 ) ( N = 2 0 siblings) . Tabl e 5.—Lea d Level s i n Hyperactiv e Hyperactive s Level s >0.0 8 mg/ L Level s =s0.0 8 mg/ L Hyperactive s > Sibling s 9 2 -Siblin g Pairs *

Hyperactive s < Sibling s 2 7 •Fisher' s exac

t test , P = .02 (tw

o tailed) . Fifty-eigh t

percen t o f th e hyperactive s an d39 % o f th e norma l childre n ha dlea dlevel s greate r tha n 0.0 8 mg/

L (x 2 [l ] = 3.57 , P-.06). O

f th e learning-disable dgroup , 55 % ha dlevel s abov e 0.0 8 mg/ L (th e tw o patien t

group s obviousl y di dno t differ ; learning-disable dchildre n v normals : x 2 [l] = 1-53 , NS) .

Possibl e Confounder s Th e relationshi p betwee n lea dlevel s an dSES , race , age , an d gende r wa s examined . SE S an d Race. —Socioeconomi c statu s a s measure db y th e Hollingshea dScale 2 1 di dno t correlat e significantl y with lea dlevel s i n an y o f th e thre e group s (hyperactives : Pearson' s r[100 ] = .15 , P=.13 ; learning-disable dchildren : r[29 ] = .07 , NS ; sibi-"

- r[30]=-.05 , NS) . Th e smal l percentag e o

f blac k childre n di dno t

hav e significa ! highe r lea dlevel s tha n th e whit e childre n in an y o f th e gr o (t = - 1.2 7 t o 0.97) . Sinc e neithe r

SE S no r rac e wa s significa : relate dt o lea dlevels , w e di dno t contro l for

thes e variable s i

n analysi s fo

r grou p contrast s in lea dlevels . Age.—I n th e hyperactiv e group , ag e wa s significantl y n e tivel y correlate dwith lea dlevel , olde r childre n havin g lower

le- . (r[101 ] = - .25 , P= .01) . A nonsignifican t negativ e tren dwa s f

o betwee n ag e an dlea dlevel s i n th e learning-disable dgr - (r[29 ] = .32 , P<.10) . No relationshi p betwee n ag e an dlea dIt

wa s foundin th e norma l sibling s (r[31] = -.17 , NS) . Becaus e o

f th e significan t

relationshi p betwee n ag e an d! level s in th e hyperactiv e group , th e grou p contrast s in mean ! • level s wer e reanalyze di n a n analysi s o

f covarianc e controllin g age . Lea dlevel s fo

r th e thre e group s remaine dindistinguish . (hyperactive s v siblings : F[l,133 ] = 0.47 , NS ; hyperactive

learning-disable dchildren : Ffl , 131 ] = 2.32 , NS ; learning-disa t childre n v siblings : F[l,61 ] = 0.46 , NS) . Gender. —I f

male s hav e an inherentl y greate r propensit

y accumulat e lead , th e disproportionat e numbe r o f boy s i n hyperactiv e grou p migh t

hav e influence dgrou p differences . Th> . fore , we compare dth e leadlevel s o f th e boy s an dgirl s i

n <? : group . Th e mean lea dlevel s o f th e 1 7 mal e an dth e 1 6 fe n sibling s wer e almos t

identica l (0.09±0.0 5 v 0.08±0.0 5 m p respectively ; f.[31 ] = 0.93 , NS) . Th e lea dlevel s o f th e boy s . girl s i n th e hyperactiv e grou p an di n th e learning-disable dgr wer e als o no t

significantl y differen t

(hyperactives : 0.11*0.( r 0.08±0.0 3 mg/L , respectively ; <[101 ] = 1.30 ; learning-disa b children : 0.10 ± 0.0 6 v 0.1 3 ±0.1 2 mg/L , respectively ; £[29 ] = - !

Pairwis e Comparison s o f Lea d Level s I n Hyperactiv e Childre n an d Thei r Sibling s W e wer e abl e t o pai r

20 o f th e hyperactiv e childre n with o n thei r siblings . I f

ahyperactiv e chil dha dmor e tha n on e sib ! whos e lea dleve l hadbee n determined , w e selecte dfo r compar i th e siblin g closes t

i n age . Demographic characteristic s o f hyperactive-siblin g pair s appea r i n Tabl e 4 . Again , ther e v , significantl y mor e boy s i n th e hyperactiv e sampl e (x 2 (17 ) = - F= .04) . Th e distributio n an dmean lea dlevel s for th e pair s ar e show

Tabl e 4 . Th e hyperactiv e childre n ha dsignificantl y highe r ir . lea dlevel s tha n thei r

sibling s (paire d([19 ] = 2.52 , P = .02) . 7 proportion s o

f childre n with toxi c lea dlevel s di dnot diffe r sig r cantl y betwee n th e tw o group s (x 2 [2 ] = 2.7 , NS) ; 55 % of " hyperactive s an donly 35 % o f thei r sibling s hadlea dlevel s i n "toxic " range . Figur e 2 plot s th e lea dlevel s o f eac h hyperactiv e chil daga . tha t o f hi s o r he r sibling . Th e lea dvalues ' o f th e hype , tiv e childre n wer e significantl y relate dt o thos e o f thei r sibli : (r[18 ] = .69 , P<.001) . A cubi c functio n provide danotably , not significantly , bette r

fit t o th e dat atha n alinea r fun c (Ffl , 17 ] = 2.76 , P = .ll) . Th e cubi c functio n ha dan inflectio n a ; ordinat e valu e aroun d0.0 8 mg/L . Therefore , th e dat awere . lyze dfurthe r

t o confir

mwhethe r

ther e was adifferenc e i n associatio n o

f lea dlevel s in hyperactive s an dsibling s above ; belo w thi s level . Hyperactiv e childre n wer e divide dbetwee n t h with lea dvalue s abov e an dthos e a t o r belo w 0.0 8 mg/L. Ta

t present s thes e data . A highe r lea dleve l in th e hyperactiv e c : wa s foundalmos t

exclusivel y in th e pair s wher e th e hyperat . child' s lea dleve l wa s abov e 0.0 8 mg/ L (Fi g 2) . A s i n th e grou p analysis , difference s i n se x distributio n ir. . hyperactiv e an dsiblin g pair s coul dconfoundth e associatio n of! : level s an dhyperactivity . Th e numbe r o f hyperactiv e girl s (X

= wa s to o smal l t o enabl e meaningfu l examinatio n o f thi s issu e i

n - 2 0 matche dhyperactiv e children . Amon g th e siblings , mea n le

ofth e 1 1 boy s wer e identica l t o thos e ofth e nin e girl s (O.O8±0.i

0.0 8 i 0.0 6 mg/L , respectively) . Again , thi s resul t suggest s tha: leas t for norma l children , gende r

doe s not affec t lea daccumulate : Althoug h acontras t

betwee n learning-disable dchildre n •: thei r sibling s wa s no t

aprimar y goal ofth e study , w e examined!: . burde n i n learning-disable dchildre n paire dwit h thei r sibl c Only five pair s coul db e generated . Ever y learning-disable dd ha dahighe r

lea dleve l tha n hi s o r

he r sibling . Th e differe::

- betwee n th e group s di dno t reac h significanc e (0.21:1 . v 0.08±0.0 3 mg/L , respectively ; «[4 ] = 2.41 , F= .07 ; sig

n i t Arc h Ge n Psychiatry—Vo l 40 , Au g 198 3 Lea d an d Hyperactivity—Gittelma n & Eske: ;P. 6

. siblings . jL , rnificantly- ' '.h e groups' : igniffcantly

r tble s i n th e ntl y nega - y .ower level* : ! was found

" le dgrou p ' lea dleve b

\ipensit y to l boy s in tisel •nces . There- I •,irl s i n ea<A

! ..c 1 6 female- ; -0.0 5 mg/I . ..i e boy s ani

] cable dgroaj ! O.U±0.08t ! ..ing-disabl a '[29]=-1.0 V

• awit h onei | n on e siblin

g

. - comparisa l ,istie s o f tht]

. ther e we.t | (x 2 (17)=4.J,' .

• ar e shown a

j highe r mea j P = .02) . Th

e :!iffe r signif r • 55 % o f ti e • i level s i n tt e chil dag a ih e hype r Ihei r sibling ! notably , b a .-.ea r functu s •flectio n at i .i t awer e ; ..renc e in >

.. 4 S abov e aa'f

l ietwee n th

o ng/L . Table s j -,tractiv e chfit

l o hyperacti •ibutio n i n t •ciatio n o f l e s girl s (N = hi s issu e in t „s , mea n leve

l

. ; (0.0 8 ± 0.0

4 ii '

. s 'geststhat, « : accumulat e i childre n examine dl e thei r sibling .-disable dci

v h e differen a : e (0.2 1 ±0. 3 .07 ; sig n Tabl e 6.—Relationshi p Betwee n Lea d Level s an d

Perinata l Complication s i n Hyperactiv e Childre n Lead , mg/ L Presenc e of Complicatio n N Mea n S D t • P Pregnanc y Ve s 5 2 0.1 2 0.0 8 1 4 0.0 8 0.0 3 1.4 9 N S Labo r an d delivery Ye s 1 4 0.0 7 0.0 3 3 6 0.1 1 0.0 8 •1.7 3 N S Neonata l Ye s 2 6 0.1 0 0.0 6 N O 3 1 0.1 1 0.0 9 -0.3 6 N S Table 7.—Relationshi p o

f Lead Level s an d Severit yo f Perinata l Complication s

Correlatio n Wit h Lea d Leve l Severity-Weighte d Histor y Pregnanc y .3 7 6 4 .00 2 labor an d delivery -.2 1 4 8 N S Neonatal -.0 2 5 5 N S Tabl e 8.—Example s o

f Perinata l Historie s Rate d Clearl y Abnormal , Borderline , an d Unremarkabl e Clearl y Abnorma l Prematur e ruptur e o f membranes ; oxyge n give n fo r 2 mi n " Mothe r ha d severa l miscarriage s before conceptio n

. Toxemia , Infectio n durin g first trimeste r •HighB P Apga r scor e o f 5 o r 6 Weigh t gai n o f >20. 5 k

g ;.. •Hig h B P ^ Apga r scor e o f 2 Dela y i n breathin g Borderlin e Abnorma l Cor d aroun d neck ; bab y otherwis e health y Emergenc

y cesarea n becaus e o f child' s positio n Apga r scor e o f 7 o r 8

. Precipitat

e labor , membrane s rupture d 24-4 8 h r before delivery Sever e stres s durin g pregnanc y Vomiting throughou t pregnanc y Mothe r i n poo r healt h Unremarkabl

e Routin e cesarea n Mothe r >4 0 y r ol d (n o othe r findings ) X-ra y fil m durin g pregnanc y Miscarriage

s before thi s birt h Difficult y conceivin g Weigh t gai n o f >20. 5 kg ; n o healt h problem s Initia l abnormality o

f fetu s presentation ; self-correcte d durin g labo r =.06) . Thes e result s ma

y hav e bee n confounde db y age , sinc e th e ng-disable dchildre n tende dt o b e younge r tha n thei r

sibling s ?=.07) . (Thes e dat aar e presented , i n spit e o f th e ver y smal l pi e size , for possibl e heuristi c interest. ) Relationshi p Betwee n Lead Level s an d

Severit y o f Illnes s ^Nonsignifican

t correlation s wer e obtaine dbetwee n lea dleve l I hyperactivit

y facto r score s (r[101 ] = . 10

) an dseverit y o

f illnes s JOI]=.00) . Tabl e 9.—Mea n Lea d Level s i n Childre n Wit h Abnormal , Borderline , an d Unremarkabl e Perinata l Complication s Perinata l Complication s Clearl y Abnorma l ( N = 21 ) Borderlin e

( N = 29 ) Absen t

( N = 23 ) Lead , mg/L Mea n *SD * 0.1 2 = 0.0 9 0.1 0 = 0.0 5 0.0 9 = 0.0 7 Rang e 0.06-0.4 5 0.03-0.2 4 0.04-0.3 8 *F(2,70 ) = .79 , P=.46 . Tabl e 10.—Prevalence o

f Toxi c Lead Level s Amon g Childre n Wit h Abnormal , Borderline , an d Unremarkabl e

Perinata l Histories *

Perinata l Histor y Abnorma l Borderlin e Unremarkabl e No . O f Childre n Lea d Leve l N >0.0 8 mg/ L 2 1 1 5 2 9 2 0 2 3 1 1 Lea d Leve l s0.0 8 mg/ L 6 9 1 2 'Overall : x 2 (2 ) = 3.31 , no t significant ; abnorma l plu s borderlin e v unre markable : x 2 (1 ) = 331 , P<.10 ; abnorma l v borderlin e plu s unremarkable : X Z(1 ) = 0.73 , no

t significant . tions . Th e mean lea dlevel s o f hyperactiv e childre n withou t an y pregnancy , labo r

an ddelivery , an dneonata l complication s an d thos e wit h a t

leas t on e complicatio n di dno t differ significantly (Tabl e 6) . Th e associatio n betwee n lea dleve l an dmean severit y scor e ofth e perinata l complication s wa s examine d(Table s 1 an d7) . Childre n wit h greate r

mean severit y score s o

f pregnanc y complication s wer e mor e likel y t o hav e highe r lea dlevels . Neithe r

mea n severit y scor e o f labo r an ddeliver y complication s no r th e mea n o

f neonata l conditio n wa s significantl y associate dwith lea dlevel . Socioeconomi c statu s wa s not correlate dsignificantl y wit h lea d level s i n th e hyperactiv e childre n (r[98 ] = . 15 , P= . 13 ) o r wit h mean severit y o f pregnanc y complication s (rf62 ] = .04) , labo r an ddeliv

er y complication s (r[46]=.03) , o r neonata l conditio n (r[53 ] = .08) . Nevertheless , th e dat awer e reanalyzed , partialin g out SE S score s t o estimat e i

f aconfoundha dbee n introduce din . th e correlatio n betwee n lea dlevel s an dperinata l factors . Th e correlation s be

twee n lea dlevel s an dmean severit y o f perinata l complication s generate db y th e partialin g an db y th e Pearso n correlatio n tech

nique s wer e identical . Th e perinata l historie s o f 2 1 hyperactiv e childre n wer e catego rize da s clearl y abnormal , 2 9 a s borderlin e abnormal , an d2 3 a s unremarkable . Example s o f perinata l historie s judge da s clearl y abnormal , borderline , an dunremarkabl e (althoug h som e abnor

mality wa s reported ) ar e show n in Tabl e 8 . O f th e 2 1 mother s • considere dt o hav e clearl y abnorma l pregnanc y histories , te n ha d toxemi adurin g pregnancy . A s show n i n Tabl e 9 , lea dlevel s o f hyperactiv e childre n wit h clearl y abnormal , borderline , o r unremarkabl e perinata l historie s di dno t differ significantl y (F[2,70 ] = 0.79 , P = .46) . I n addition , w e examine dwhethe r childre n with clearl y abnor

mal , borderline , an dunremarkabl e perinata l historie s wer e dis

tribute ddifferentiall y abov e an dbelo w '"toxic " lea dlevels . Tabl e 1 0 present s thes e data . A nonsignificantl y highe r proportio n o

f childre n with abnorma l prenata l historie s (clear an dborderlin e abnormalities ) hadtoxi c lea dlevel s compare dwit h childre n wit h norma l perinata l historie s (x 2 fl ] = 3.31 , P<.10) .

Relationshi p Betwee n Lead Level s an d Cognitiv

e Tes t Performance i n Hyperactive s Ag e wa s partiale dout

o f thos e test s not

alread y ag e standard

ized , ie , GORtest , VMI test , an dpaired-associat e test . A significan t

relationshi p wa s observe dbetwee n SE S an dth eP. 7



# 1 i

• WIS C ful l an dverba l IQ s (r

f 100] = - .31 . P<.01) . N

u othe r neuro psychologica l measur e correlate dwith SES . A s Tabl e 1 1 indicates , leadlevel s di dno t correlat e significantl y wit h WIS C IQ score s whe n SE S wa s controlled , althoug h childre n wit h lower

IQ s tende dt o hav e highe r leadlevels . (Significan t correlation s o

f lea dwit h WIS C full-scal e I Q [r=.19 . . " = .05 ] an d verba l I Q fr=.20 , F= .05 ] wer e obtaine dwhe n SE S wa s no t partiale dout. ) Non e o

f th e achievemen t

tes t score s wa s signifi

cantl y associate dwith leadlevels . Ther e wa s atren dbetwee n th e WRAT readin g leve l an dlea dlevels , indicatin g tha t poo r reader s tende dt o hav e highe r

lea dvalue s (r[100 ] = - . 16 , P=. 10) . COMMEN T 

### Thi s stud y faile dt o findhighe r lea dlevel s i n alarg e grou p o f hyperactiv e childre n whe n compare dwith norma l chil

dren . Yet , th e result s canno t b e construe da s altogethe r negative . W

e foundatren dfo

r agreate r

proportio n o

f hyperactiv e childre n tha n normal s t o hav e lea dlevel s abov e 0.0 8 mg/L ( P = .06) , an dhyperactiv e childre n hadsignifi

cantl y highe r

lea dlevel s tha n thei r

ow n sibling s ( P = .02) . Thus; , lea dlevel s ma

y b e associate dwith hyperactivit y in middle-clas s children . However , th e associatio n i s weak . It s detectio n require dth e stud y o f geneticall y relate dgroup s tha t provide dinheren t

control s fo

r amultitud e o

f environ

menta l factors , suc h a s housing , neighborhoo do f residence , an dsocial class . W e foundno clear-cu t

relationshi p betwee n lea dlevel s and . cognitiv e performanc e o f th e hyperactiv e children . Correlatio n coefficient s wer e al l in th e expecte ddirection , indicatin g tha t

highe r leadvalue s wer e slightl y associate d with wors e performance . I n spit e ofth e wea k associatio n o

f lead , level s an dIQ , th e consistenc y ofth e result s in differen t populations 3 

### " 5 

### suggest s tha t th e detrimenta l effect s o f low

leve l lea dexposure , thoug h minimal , canno t b e entirel y dis

counted . Compariso n Wit h Previou s Finding s 

### Thi s stud y wa s designe dt o replicat e previou s observa

tion s b y Davi dan dco-workers" 1 

### " o f elevate durin e lea d level s i n hyperactiv e children , especiall y i n thos e childre n withou t an y othe r

know n caus e fo

r thei r hyperactivity . Ou r dat agiv e suppor t

t o thei r observatio n tha t

aleve l exceedin g 0.0 3 mg/L ma

y represen t

arelativel y toxi c urin e lea dlevel , tha t is , w e foundan inflectio n a t tha t valu e in th e distribu

tio n o f lea dlevel s o

f hyperactive s an dthei r

sibling s (Fi g 2) . Othe r results , however , ar e no t consisten t

with Davi dan d colleagues' ; we faile dt o find asignifican t elevatio n o

f lea d level s i n hyperactiv e children , excep t whe n paire dwit h thei r siblings ; w e foundonl y atren dfo r hyperactiv e chil

dre n t o hav e toxi c lea dlevel s (>0.0 8 mg/L) ; an dlea dlevel s an dperinata l insul t

wer e no t

negativel y associate di n ou r hyperactiv e sample . Th e technique s fo

r assessin g lea dleve l wer e identica l t o thos e use db y Davi dan dco-worker s an dtherefor e canno t accoun t for difference s in th e results . Th e tw o studies , how

ever , differe din racia l composition , ag e ofth e sample , diag

nosti c criteri aemployed , an dth e manne r in whic h perinata l informatio n wa s obtained . Race. —Davi dan dcolleagues ' sampl e wa s blac k an d lower class ; our s wa s mostl y whit e an dmiddl e class . It " i s ver y unlikely , however , tha t lea dexposur e interact s wit h rac e t o produc e hyperactiv e behavio r i n onl y on e racia l group . Diagnosti c Criteria. —Ou r sampl e wa s selecte dfo

r re searc h purposes , wit h systemati c evaluation s an dobjectiv e diagnosti c criteria . Th e ver y hig h rat e o f clinical respons e t o methylphenidat e in th e hyperactiv e childre n in th e presen t stud y (80 % t o 90 % improvemen t with th e drug , an donl y 15 % wit h placebo 12 

### ) indirectl y confirm s th e accurac y o f th e diagnosis . Althoug h Davi de t a l als o use dobjectiv e criteria , 83 2 Arc h Ge n Psychiatry—Vo l 40 , Au g 198 3 Tabl e 11.—Correlation s of Lea d Level s an d Neuropsychologica l Performanc e i n Hyperactiv e Childre n

Wechsle rIntelligenc e Scal e fo rChildre n Verba l I Q Performanc e I Q Full-scal e I Q Wid e Rang e Achievemen t Tes t (standar d score ) Readin g Arithmeti c Spellin g Gra yOra l Readin g Tes t (grad e level ) Paired-associat e learnin g tes t (trials ) Visua l Sequentia l Memor yTes t Visua l Moto r Integratio n (Beery-Buktenica ) Tes t menta l age , y r N 10 2 10 2 10 2 10 2 10 0 10 0 10 0 7 9 68 9

9 7 Scor e Mea n 103. 3 101. 9 103. 0 98. 8 94. 8 93. 6 2. 7 7. 7 19. 6

6. 8 S D 13. 4 11. 8 11. 4 14. 0 9. 5 10. 6 1. 9 3. 3 4. 5

1. 4 Correlatio n

Wit h Lea d Leve l r P -.16 * 1C

- .08 * N

S -.16 * . K -.1 6 . K

- .0 2 NS -.1 5 N ; -.12 f N :

- .06 t N

S -.1 5 N

S

-.12 t N

S •Socioeconomi c statu s wa s partiale d ou t o

t th e correlation . fPartia l correlation s controllin g fo rage . 

### ther e wa s no suc h confirmatio n o f th e diagnosis . Age.—Th e childre n i n ou r stud y wer e olde r

tha n the

Davi dan dcolleagues' . Olde r childre n ha dlower

che! . lea dlevels , probabl y becaus e th e sam e dos e o f chela- ' agen t wa s use dregardles s o

f weight . A uniformdos e v< chelat e mor e lea dfro msmalle r individuals , leadin g r

. artifactua l negativ e relationshi p betwee n lea dlevel s age . Sinc e w e foundtha t

lea dlevel s wer e negativel y correi . wit h age , th e lea dlevel s ofth e somewha t olde r hypera i childre n i n ou r

stud y (9. 8 ±2. 8 years ) woul db e expt. t o b e lower

tha n thos e o

f Davi dan dcolleague s (7. 7 ye ; a s wa s found . Th e magnitud e o f thi s difference , how

t wa s asmal l one , abou t

25 % o f th e S D reporte di

n vi dan dco-workers ' hyperactiv e sampl e (0.1 0 ±0. 0 0.1 4 ±0.1 4 mg/L , respectively) . I n th e presen t

study , th e hyperactiv e grou p di dnot c significantl y i n ag e fromth e controls ; ag e discrepa m therefore , do no t

appea r sufficien t

t o explai n th e la

v significan t

difference s i n lea dlevel s betwee n group s ii : investigation . Perinata l Histories. —Unlik e Davi de t al , w e u

s structure dquestionnair e an dwher e possibl e examine d pita l records . Perinata l historie s wer e blindl y coded . S Davi dan dco-worker s reliedexclusivel y on wha t seer m b e a h unstructure dmedical intak e interview , th e histc : complication s ma

y hav e bee n underestimate dan di \ bia s ma y pla y arol e in th e results . I n fact , 78 % o ; hyperactiv e childre n in th e earlie r study 9 

### o f Davi de t a ; 50 % o f th e childre n i n th e late r

large r study 1 0 

### ha dhist

c negativ e fo

r perinata l insult ; onl y 19 % ofth e hyperacti v ou r study , however , hadno perinata l complication . Th e evaluatio n o

f perinata l historie s present s difficu ! I t ma y no t b e possibl e t o generat e aclear-cut , vali destir . o f perinata l risk . Unfortunately , ther e i s no t a n aj . approac h fo

r rankin g severit y o

f perinata l insul t

tha t * reflec t impac t o n neurodevelopment . Onl y th e ver y ext r Lea d an d Hyperactivity— Gittelma n & Esk ;nr—tiiiur a

Nation ' .Vit h •j Leve l

,' t N S 5 T N S •

'2 t N S 

### s are unequivoca l fo r adeterminatio n o

f abnormality , as ver y lo w Apga r

scores . Associatio n o f Lea d Level s Wit h Hyperactivit y 

### i indeed , lea dlevel s ar e associate dwit h hyperactivity , question arise s a s t o th e natur e o f thi s relationship . o n thei r findin g tha t

childre n withou t

an y othe r caus e o f hyperactivit y ha dhighe r lea dlevel s tha n Js , Davi de t

a l hypothesize dtha t

lea dplay s a n ogicrol e i n hyperactivity . A n equall y plausibl e hypoth

implie s tha t

increase dlea daccumulatio n may resul t hyperactivity : childre n wit h highe r activit y level s may emore air , "kic k

up " mor e dust , o r

b e mor e ap t

t o dis

pic a(eatin g pain t

chip s o r dirt) . Th e associatio n o

f lea d wit h hyperactivity , however , ma y b e neithe r caus e affect . Lea dlevel s may b e relate dt o hyperactivit y onl y g h thei r associatio n with athir dvariable . , da s aCaus e o f

Hyperactivity.—Unlik e Davi de t al , foundn o evidenc e t o sugges t tha t lea dplaye da n logi c rol e i n hyperactiv e childre n withou t ahistor y o

f ita l complications . Instead , childre n with prenata l iication s wer e mor e likel y t o hav e higher lea dlevels . resul t i s consisten t

with tha t

o f Winnek e e t

al, ~ wh o foundaslightl y highe r

prevalenc e o

f perinata l ris k N S •> r s 

### ' n a

### grou p of

childre n wit h hig h toot h lea dlevels . lea dwer e acaus e o

f hyperactivity , w e migh t expec t severit y o f hyperactivit y woul db e associate dwit h lea d i; however , n o associatio n wa s found . Ou r grou p con o f relativel y sever e hyperactiv e children . I t i s con Je tha t differen t result s woul demerg e i f

childre n wit h fer rang e o f hyperactivit y wer e studied . als o foun dconsiderabl e overla p i n th e lea dvalue s o f ' tractiv e childre n an dthei r

norma l siblings . Conse

-

. itiy , "high " lea dlevel s canno t b e construe da s sufficien t

. 1 those s lyperactiv e disorder s t o occur . Thi s i s hardl y surpris

chelat ajfti

s mos t likel y tha t

hyperactivit y i s multidetermined ; ihelao q result

, on e woul dno t

expec t asingl e factor , suc h a s lea d •s e vv 0 

### • tare, t o b e it s sol e o r majo r cause . ngto aereasedLea dLevel s Resultin g Fro mHyperactiv

- •vel s an j :j f childre n b y natur e of

bein g mor e activ e ar e expose d ! reate r amount s o

f ambien t lead , the n hyperactiv e .•re^a a^ n shoul dhav e ha dhighe r lea dlevel s tha n th e grou p o f ng-disable dchildre n wh o wer e no t hyperactive . Thi s otfoun dt o b e th e case : th e mean , range , an ddistribu

- .' th e lea dlevel s o f learning-disable dchildre n wer e ["simila r t o thos e of

hyperactiv e children , an dbot h sha dlevel s somewha t

highe r tha n thos e ofth e norma l s . I t may b e tha t

lea dcontributes , i n part , t o adiver

f developmenta l disorders . Unfortunately , th e scar rfnormal sibling s ofth e learning-disable dgrou p di dno t fus t o investigat e thi s issu e fully . Jternativ e Relationship.—Elevate dlea dlevel s ma y i he r caus e no r effec t o f hyperactivity ; instead , hyper- ] 

### /an dlea dlevel s may b e relate dthroug h thei r associ

J'wit h athir dfactor . Perinata l stres s ma y leav e th e chil d able t o othe r

factor s tha t

coul db e detrimenta l t o de

nent . Fo r example , th e impaire dorganis mmay b e |l e t o metaboliz e o r

excret e lead . Th e findin g tha t se f o f pregnanc y complication s wa s positivel y associate d lea dlevel s i s consisten t

with thi s hypothesis . Sourc e o f Lea d Exposur e 

### itor y of pic ama y hav e bee n mor e commo n amon g th e :tive childre n tha n thei r siblings . W

e coul dno t thi s information . I t

i s mos t unlikel y tha t

pic awa s a i n ou r group s sinc e al l childre n live di n post-Worl d housin g i n suburb s wher e dilapidate dwall s with lea d ips , amajo r

sourc e of

lea dintoxication , ar e virtu

lexisten t (pic ao f leade ddir t

ma y stil l b e asource) . i n whic h th e childre n lived , however , i s congeste d Eska S

1 Psychiatry—Vo l 40 , Au g 198 3 

### e us e lined ! with automobil e traffic , an dai r lea dconten t

wa s probabl y on e o f th e highes t

i n th e Unite dState s a t

th e tim e o

f th e study . Th e significant

correlatio n o

f lea dlevel s of

hyperactiv e childre n an dthei r

sibling s suggest s tha t

environmenta l ex posur e o r share dgeneti c inabilit y t o excret e lea dar e pri

mar y factor s i n lea daccumulation . Th e questio n remain s wh y hyperactiv e childre n hadhighe r lea dlevel s tha n thei r siblings , give n tha t

th e water , air , an dhom e environmen t vver e th e sam e fo r

thes e children . i Th e finding s sugges t

tha t lea di s no t

salient , bu t

no t negligible , a s acontributo r t o hyperactivit y an dpossibl y learnin g disability , i n nondisadvantage dchildren . Never

theless , whethe r

lea dput s childre n a t

risk fo r develop

menta l disorders , albei t

asmal l one , remain s a n importan t publi c healt h issue . Thi s investigatio n wa s supporte di n par t b y grant s MH1857 9 fro mth e Publi c Health Servic e an d5-T32-ES708 6 fromth e Nationa l Institut e o f Environmenta l Health Sciences . Donal dF . Klein , MD , provide dcomments . Bet h Landa , PhD , performe d dat aanalyses . Milli e Heimlic h coordinate dth e dat acollection . Bernar d Davidow . MD , an dth e Departmen t o f Health , Cit y of

Ne w York , performe d th e urinalyses . 

### Reference s 1 . Byer s RK , Lor dEE : Lat e effect s o f lea dpoisonin g o

n menta l development . Am J

Dis Child

1943;66:471-494 . 2 . Chisol mJJ , Kaplan E : Lea dpoisonin g i n childhood : Comprehensiv e managemen t

an dprevention . J

Pediatr 1968,73:942-950 . 3 . D e l aBurd e B, Choat e MS : Earl y asymptomati c lea dexposur e an d developmen t

a t schoo l age . J

Pediatr 1975;87:638-642 . 4 . Landriga n PJ , Whitworth KH , Balo h RW , e t al : Neuropsychologica l dysfunctio n i n childre n with chroni c low-level lea dabsorption . Lancet 1975;2:70S-712 . 5 . Perin o J , Ernhard t

CB : Th e relatio n o

f subclinica l lea dleve l t o cognitiv e an dsensorimoto r impairmen t

i n blac k preschoolers . J

Learning Disabil 1974;7:26-30 . 6 . Pih l RO , Parke s M : Hai r elemen t conten t i n learnin g disable dchildren . Science 1977;198:204-206 . 7 . Balo h R , Stur mR , Gree n B , e t al : Neuropsychologica l effect s o f chroni c asymptomati c increase diea dabsorption . Arch Neurol 1975;32:326

- 330 . 8 . Needlema n HL , Gunno e C , Levito n A , e t al : Deficit s i n psychologica l

.' an dclassroo mperformanc e o f childre n wit

h elevate ddentin e lea dlevels . , N EnglJ Med 1979;300:689-695 . 9 . D;.vi dO , Clark

J , Voelle r K : Lea dan dhyperactivity . Lancet 1972:2 : 900-903 . 10 . Davi dOJ , Hoffma

n SP , Sver dJ , e t

al : Lea dan dhyperactivity : Lea d level s amon g hyperactiv e children . J Abnonn Child

Psychol 1977;5:405

- , 416 . I 11 . Rutte r

M : Raise dleadlevel s an dimpaire dcognitive/behavioura l functioning : A revie w o f th e evidence . Dec Med Child Neurol 1980 ; , 22(suppl):l-26 . \ 12 . Gittelman-Klei n R , Klei n DF , Kat z S , e t al : Comparativ e effect s o f I methylphenidat e an dthioridazin e i n hyperkineti c children . Arch Gen I Psychiatry 1976;33:1217-1231 . I 13 . Gittelma n R , Abikof f H , Pollac k

E , e t al : A controlle dtria l o

f behavio r modificatio n an dmethylphenidat e i n hyperactiv e children , i n Whale n C , Henke r B : Hyperactive Children. New Vork , Academi c Pres s Inc , 1980 , p p 221-243 . 14 . Gittelma n R . Feingol dI : Efficac y o f remediatio n i n readin g disable d children . J

Child Psychol Psychiatry 1983:24:167-191 . 15 . Cor.ner s CK : A teache r ratin g scal e for

us e i n dru g studie s with children . Ain J

Psychiatry 1969;126:152-156 . 16 . Werr y J : Hyperactivity , i n Costell o C G (ed) : Symptoms ofPsychopathology. Ne w York , Joh n Wile y & Son s Inc , 1970 , p p 397-417 . 17 . Diagnostic and

Statistical

Manual of Mental Disorders, e d2 . Washington , DC , American Psychiatri c Association , 1968 . 18 . Wende r

P : Minimal

Brain Dysfunction in Children. Ne w York , Joh n Wiley & Son s Inc , 1971 . 19 . Halperi n JM . Gittelma n R : D o hyperactiv e childre n an dthei r sibling s diffe r i n I Q an dacademi c achievement ? Psychiatr Res 1982;6:253-258 . 20 . Woerne r

MG, Pollac k

M , Klei n DF : Pregnanc y an dbirt h complica

tion s i n schizophrenics , personalit y disorders , an dthei r siblings . Acta Psychiatr Scand 1973:49:712-731 . 21 . Hollingshea dAB , Redlic h FC : Social Class and

Mental Illness: A Community Study. Ne w York , Joh n Wile y & Son s Inc , 1958 . 22 . Winneke GA , Hrdin aKG , Broekhau s A : Neuropsychologica l studie s i n childre n with elevate dtooth-lea dconcentrations : I . Pilo t Study . Int

Arch Occup Environ Health 1982;51:169-183 .

Lea d an d Hyperactivity—Gittelma n & Eskenaz i 83 3



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