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### EP A AI R DOCKE T tunnin g Head : Lea d Exposur e an d Infan t Developmen t

LEA D EXPOSUR E AN D NEUROBEHAVIORAL DEVELOPMEN T I N LATE RINFANC Y

Ki m N . Dietrich , Ph.D. * Pau l A . Succop , Ph.D. * Rober t L . Bornschein , Ph.D. * Kathlee n M . Krafft , Ph.D.** * Ome r Berger , M.D.* * Pau l B . Hammond , D.V.M. , Ph.D. * C . Ralp h Buncher , Sc.D. *

*Fro mth e Universit yo f Cincinnat i Colleg e o f Medicine , Departmen t o f Environmenta l Health , Cincinnati , O H 45267-005 6 **Fro mth e Universit yo f Cincinnat i Colleg e o f Medicine , Departmen t o f Pediatrics , Cincinnati , O H 45267-0056 . ***Fro mE.I . D u Pon t d e Nemour s Inc. , Specialt yServices , Wilmington , D E 19885-0800 .

Presente d a t Advance s i n Lea d Research : Implication s fo r Health , Nationa l Institut e o f Environmenta l Healt h Sciences , Researc h Triangl e Park , NC , Januar y 9 , 1989 .
Corresponding Author : Ki mN . Dietrich , Ph.D . Universit yo f Cincinnat i Colleg e o f Medicin e Departmen t o f Environmenta l Healt h Cincinnati , O H 45267-005 6 

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TITLE : LIA D EXPOSUR E AND NEUROBEHAVIORAL DEVELOPMEN T IN UTE RINFANC Y

AUTHORS : Ki mN . Dietrich , Ph.-D .

Pau l A . Succop , Ph.D . Rober t L . Bornschein , Ph.D . Kathlee n M . Krafft , Ph.D . Ome r Berger , M.D . Pau l B . Hammond , D.V.M. , Ph.D . C . Ralp h Buncher , Sc.D .

KE Y WDTODS : Lead , Fetus , Infant , Development , Growth , Prospective-Studie sP. 4 • - ^.US'-^SfF. -'T<: '^'.'T^ : Sl^f,fi i ^ai^'^l^ v VU^^'.'l.'^ , !^_). J tJ l %^'

ABSTRAC T

A prospectiv e methodolog y wa s use d t o asses s th e neurobehaviora l effect s o f feta l an

d postnata l lea d exposur e durin g th e firs t tw o year s o f life . Lea d wa s measure d i n whol e bloo d prenatall y i n mother s an

d a t quarterl y

interval s i n th e infant . Prenata l bloo d lea d level s wer e lo w ( M - 8. 0 jig/dl) . However , approximatel y

2 5 percen t o f th e stud y infant s had a t leas t on e seria l bloo d lead leve l o f 2 5 M9/d l o r highe r durin g th e second yea r o f life . Multipl e regressio n an d structura l equatio nanalyse s reveale d statisticall y significan t relationship s betwee nprenata l an d neonata l bloo d lea d leve l an d 3 an d 6 mont h Bayle y Menta l and/o r Psychomoto r Developmen t Index . However , b y 2 year s o f ag e n o statisticall y

significan t effect s o f prenata l o r postnata l lea d exposur e o n neurobehaviora l developmen t coul d b e detected . Dat a consisten t wit hth e hypothesi s tha t a postnata l neurobehaviora l growt hcatch-u p occurre d i n infant s expose d fetall y

t o highe r level s o f lead ar e presented .! 'Ja'aK

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Fo r mos t U.S . children , ther e ha s bee na substantia l reductio ni n lea d exposur e a s a direc t resul t © f regulator y policie s governin g acceptabl e level s o f th e meta l i n atmosphere ain ddie t (1) . However , th e leve l o f lea dexposur e a t whic hadvers e effect s t o heailt har e believe dt o occu r ha s bee ncorrespondingl y reduced . Muc ho f thes e ne w dat a on th e healt heffect s o f lo w leve l lea d exposur e hav e come fro m prospectiv e studie s initiate da t th e beginnin g o f thi s decade . Sinc e mos t o f thes e studie s recruite dpregnan t women , th e firs t availabl e report s deal t wit hth e effect s o f feta l lea dexposur e on perinata l outcome s and earl y

postnata l development .

Lowe r leve l feta l lea dexposur e ha s bee nassociate dwit hpoore r neonata l physica l statu s i n severa l prospectiv e studies . Decrease dgestationa l ag e and/o r delaye dfeta l maturatiio n(2,3,4) , lowe r birt hweigh t (5,6) , an d a n increase dris k fo r mino r physica l anomalie s (7 ) hav e bee nassociate dwit hfeta l lea dexposur e a s assesse db y prenatal , umbilica l cord , o r neonata l bloo dlead level s in th e rang e commo narftOTi g wome nan

d neonate s i n develope dcountries .
Lead-relate ddeficit s i n earl y postnata l neurobehaviora l statu s hav e bee n reporte db

y severa l prospectiv e studies . Ernhar t an d he r colleague s hav e reporte da significan t covartate-adjuste drelationshi pbetwee nmaterna l bloo d lea dleve l a t deliver y and thi e Abnorma l Reflexe s cluste r o n th e Brazelto n Neonata l Behaviora l Assessmen t Scale , an d th e Sof t Sign s an

d Muscl e Tonu s scor e onth e Graham/Rosenblit hBehaviora l Examinatio no f th e Neonat e (8) . Thes e sam e investigator s founda significan t covariate-adjuste dnegativ e relationshi p betwee nmaterna l bloo dlea dleve l a t deliver y an d 6 mont hscore s o n th e menta lP. 6

an dpsychomoto r indexe s o f th e Bayle y Scale s o f Infan t Developmen t (9) . However , ther e appeare dt o b e n o significan t covariate-adjuste drelationship s betweenindice s o f feta l o r earl y postnata l lea d exposur e an dBayle y score s a t 1 o r 2 years .

A somewha t differen t patter no f result s wer e reporte db y Bellinge r an

dhi s coworker s inBoston . A s inth e Clevelan dstudy , a significan t covariate adjuste dnegativ e relationshi pbetwee nfeta l lea dexposur e (i nthi s case , cor d bloo dlea d level ) an d6 mont hBayle y

menta l inde xwa s found(10) . However , thes e investigator s late r reporte da continuou s invers e relationshi pbetwee n cor dbloo dlea dleve l an dBayle y menta l inde xthroug h2 year s o f ag e (11,12) . I nou r ow nstudy , we hav e reporte da ninvers e relationshi pbetwee nmaterna l prenata l bloo dleadleve l an dcovariate-adjuste dBayle y menta l inde xscore s a t 3 an d6 months . Thes e effect s appeare dt o b e stronges t inmal e infant s an d infant s fro

m th e poores t families . Inaddition , deficit s o r delay s i nearl y menta l developmen t appeare dt o b e partl y mediate db

y lead-relate dlowe r birt h weight , an

ddecrease dgestationa l maturit y (2) .
Th e prospectiv e studie s substantiall y diffe r fro

m on e anothe r i nterm s o f postnata l lea dexposur e durin g infancy . A t th e lo w en do f th e exposur e spectru m i s th e Bosto nstudy

wher e th e mea nbloo dleadleve l wa s les s tha n8 Mg/d l a t al l age s sample d(12) . Thi s wa s a middle-clas s sampl e a t relativel y low ris k fo r undu e pediatri c lea dintoxication . Th e Clevelan dstud y an dou r ow

nar e somewha t intermediat e interm s o f postnata l bloo dleadlevel . InCleveland , a mea n2 yea r bloo dlea dleve l o f 16.7 4 Mg/d l wa s reporte d(9) , whil e 2 yea r old s inth e Cincinnat i cohor t hada naverag e bloo dleado f 17.4 5 /ig/d l (thi s report) .P. 7

Amon g th e publishe dprospectiv e studies , th e highes t postnata l lea d exposure s ar e foundina longitudina l investigatio no f childre nresidin g nea r a primar y lea dsmelte r i nPor t Pirie , Australia . I nthi s cohor t o f ove r 60 0 children , a geometri c mea n2 yea r bloo dleadleve l o f 21. 2 Mg/d l wa s reporte d (13) . Further , thes e investigator s reporte da statisticall y significan t invers e relationshi pbetwee nprenatal , 6 month , an dintegrate dpostnata l bloo dlea d leve l an d2 yea r Bayle y

menta l inde xscore s afte r controllin g fo r 1 4 covariates , includin g materna l intelligence . However , i nregressio nanalyse s controllin g fo r bot hmaterna l intelligenc e an da standar dmeasur e o f caretakin g quality , onl y 6 mont hbloo dleadleve l continue dt o b e inversel y associate dwit hBayle y score s a t borderlin e significanc e (14) .
Ther e appear s t o b e genera l agreemen t amon g th e prospectiv e studie s tha t lo w leve l prenata l lea dexposur e ma y hav e some smal l effec t o nearl y neurobehaviora l developmen t (2,8,9,10,11,12,14) . However , a s other s hav e note d(11) , th e implication s o f thes e advers e low-leve l lea deffect s fo r regulator y polic y depen do nth e magnitud e o f th e invers e relationship s an dthei r stabilit y

ove r time . Therefore , on e o f th e substantiv e issue s fo r leadstudie s i s whethe r suc h earl y deficit s persis t int o late r life . T o addres s thi s importan t question , th e Cincinnat i Lea dProgra m Projec t continue s t o follow stud y subject s int o thei r earl y schoo l year s wit ha variet y o f regula r biomedica l an dneurobehaviora l assessments .
Th e primar y

purpos e o f thi s pape r i s t o repor t o nth e relationshi pbetwee n prenatal/postnata l lea dexposur e an dth e developmenta l statu s o f 2 yea r ol d infant s i nth e Cincinnat i cohort . I t wa s hypothesize dtha t lo w t o moderat e prenata l an

dpostnata l leadexposur e woul db e inversel y associate dwit hindice sT*- ' trv-arwjrr"

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o f 2 yea r neurobehaviora l developmen t afte r adjustmen t fo r relevan t covariate s and/o r confounders .
METHODS

Th e cohor t a t 2 year s o f ag e consiste d o f 29 7 infant s fo r who mdevelopmenta l dat a fro m

th e Bayle yScale s o f Infan t Developmen t wer e available . Thi s sampl e include d 3 set s o f twins . Mother s o f thes e infant s wer e recruite d prenatall y betwee n 197 9 an d 1984 . Studyfamilie s reside d i n predesignate d lead-hazardou s area s o f Cincinnati , Ohio . Thi s geographica l are a ha s a lon g histor yo f case s o f pediatri c lea d poisoning . Result s o f environmenta l studie s wit h thi s cohor t hav e show n conclusivel ytha t lea d fro m paint , dus t an d soi l associate d wit h poo r housin g stoc k i s th e majo r contributo r t o bodyburde n (15,16) . Informe d consen t fo r participatio n i n th e studywa s obtaine d a t prenata l recruitmen t and agai n a t deliver yt o obtai n permissio n fo r infan t follow-up . Wome n known t o b e dru g addicted , alcoholic , diabeti c o r thos e wit h a known neurologica l o r psychologica l disorde r wer e exclude d fro mprenata l recruitment . Infant s wer e exclude d i f the ywer e les s tha n 3 5 week s gestatio n and/o r 1,50 0 gram s birt h weight . Further , eligibl e infant s mus t hav e ha d a n Apga r scor e o f 6 o r greate r a t 5 minute s an d hav e n o seriou s medica l conditio n o r congenita l anomaly . Descriptiv e statistic s o n mother s an d infant s exclude d fro mth e studyan d thos e familie s wh o refuse d t o participat e hav e bee n publishe d elsewher e (2) .
Tabl e 1 present s perinata l statistic s o n infant s fo r who m2 yea r developmenta l dat a wer e available . I n general , studyinfant s wer e healthya t birt h wit h a mea n birt h weigh t o f 3147.9 7 gram s an d gestationa l ag e (17 ) o f 39. 7 weeks . Th e sampl e wa s predominantl yblac k (86.2% ) wit h a nearl yeve n percentag eP. 9

o f mal e an

dfemal e births . Tabl e 2 present s descriptiv e statistic s o nstud y mother s an

dthei r families . Mother s wer e predominantl y fro m th e lowe r socia l classe s (23) , unmarried , ando nsome for m o f publi c assistance .
Bloo dwa s collecte dfo r liea danalyse s prenatall y fro m th e mother , an

da t quarterl y

interval s fro

m th e infan t beginnin g a t 1 0 gestationally-correcte d days . Lea dwa s measure di nwhiol e bloo dusin g anodi c strippin g voltammetry . Th e microanalytica l laborator y a t th e Universit y

o f Cincinnat i Departmen t o f Environmenta l Healt hparticipjate s insevera l qualit y contro l programs . Th e performanc e o f thi s laborator y ha s bee nuniforml y

excellen t throughou t th e cours e o f th e curren t study . Detaile ddescription s o f ou r collectio nmethods , analyti c methodology , an dprecisio nhav e bee npublishe delsewher e (2,18) . Mos t bloo dsample s wer e collecte db y venipuncture , althoug hfinge r stic k an dhee l stic k method s wer e use dwhe nth e physica l o r behaviora l characteristic s o f th e infan t demande dit . Collectio nmethod s othe r tha nvenipunctur e wer e use dmos t ofte nwit hneonate s an dyoungp r infants . Fo r example , a t 1 0 day s onl y 26.2 % o f th e sample s wer e collecte db y venipunctur e whil e a t 2 year s 90.9 % o f th e sample s wer e collecte db

y thi s method s Environmenta l contaminatio no f sample s collecte d b y method s othe r tha nvenipunctur e ha s no t bee na problem inthi s stud

y du e t o th e controlle dclinica l condition s unde r whic hphlebotom y take s plac e (2) .
Tabl e 3 present s descriptiv e statistic s o nbloo dleadvariable s fo r subject s inth e 2 yea r follow-u psample . Prenata l an dneonata l bloo dleadlevel s wer e low , wit honl y

a handfu l reachin g o r exceedin g 2 5 -ig/dl . Mos t subject s reache d thei r highes t bloo dlea dleve' l diurin g th e secondyear . Approximatel y 25 % o f stud y subject s hada t leas t ora e seria l bloo dleaddeterminatio no f 2 5 M9/d l o r greate r durin g th e secondyear .«.V>.V. - .'A'. I AV^/.\A»«WWP A . • *.a.-**v>r

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Infant s wer e give ndevelopmenta l assessment s a t 3 , 6 , 12 , an d 2 4 month s o f age . Ou r primar y

measur e o f infan t neurobehaviora l developmen t wa s th e Bayle y Scale s o f Infan t Developmen t (19 ) whic hprovide s a thre e par t assessment : A Menta l Developmen t Inde x(MDI ) whic hassesse s sensorimoto r coordinations , perceptua l acuities , objectiv e an d visual-spatia l relations , imitation , prelinguisti c an

d linguisti c behaviors , an d memory , a Psychomoto r Developmen t Inde x(PDI ) designe dt o provid e a measur e o f th e coordinatio no f th e larg e bod y muscle s an

d fine r manipulator y

skill s o f th e hand s an d fingers , an

d a n Infan t Behavio r Recor d(IBR ) whic hi s a 3 0 ite m ratin g scal e complete db y th e psychologis t afte r th e MD I an d PD I examinations . Th e IB R assesse s th e infant' s social , objective , affective , an d motivationa l behaviors . Al l biomedica l an d neurobehaviora l evaluation s too k plac e a t a prenata l an d children' s welfar e clini c locate di n th e hear t o f th e stud y recruitmen t area . .Behaviora l evaluation s alway s occurre dbefor e th e medica l examinatio nan d phlebotomy , an

d car e wa s take nt o insur e tha t th e infan t wa s healthy , fed , an d unmedicate dwhe n tested . Th e Bayle y

scale s wer e administere db y th e firs t autho r (KND ) o r a traine dassistan t wit hwhom adequat e interteste r reliabilit y ha d bee npreviousl y established . Al l examination s wer e conducte dwithou t knowledg e o f th e infant' s prenata l o r postnata l bloo dlea dlevel .
Tabl e 4 present s descriptiv e statistic s on th e performanc e o f study infant s onth e Bayle y

MD I a t eac hage . Th e rathe r dramati c dro pi n MD I a t 2 year s i s no t unusua l fo r lowe r socioeconomi c statu s infants , an d probabl y

reflect s th e relativel y

greate r numbe r o f item s a t thi s ag e whic hrequir e a verba l o r nonverba l respons e t o representationa l stimuli , rathe r tha nsome typ e o f sensorimoto r manipulation .P.1 1

T o reduc e th e Bayle y

IB Rt o a fe

w meaningfu l psychologi c factors , w e facto r analyze dth e 3 0 ratin g variable s an dcalculate dfacto r score s fo r eac hsubjec t usin g th e facto r scorin g coefficients . Fo r example , Tabl e 5 present s result s o f a facto r analysi s o f th e Bayle y IB Ra t 2 4 months . Th e facto r structur e founda t 2 year s reveale d4 interpretabl e behaviora l dimensions : Moo d(Facto r 1) , Activit y Leve l (Facto r 2) , Attentio nSpa n(Facto r 3) , an dReactivit y

(Facto r 4) .
Undu e lea dexposur e i s know nt o covar y

wit ha numbe r o f socia l an dbiologi c risk s whic hma y

mimic , obscure , o r otherwis e interac t wit hth e effect s o f toxican t exposur e o

nchil ddevelopmen t (20,21) . Consequently , a substantia l amoun t o f socia l an

dmedica l backgroun ddat a wer e collecte do nal l subject s an

d teste da s potentia l confounder s o f th e bloo dlead-behaviora l developmen t relationship . Perinata l variable s include dbirt hweight , length , hea d circumference , pondera l index , gestationa l ag e (17) , Obstetrica l an dPostnata l Complication s Scale s (22) , 1 an d5 minut e Apga r scores , materna l age , parity , gravidity , numbe r o f cigarette s smoke dpe r da y durin g pregnancy , composit e index o f tobacc o an

dalcoho l consumptio n( a dichotomou s variabl e indicatin g us e o r non-us e o f tobacc o and/o r alcoho l durin g pregnancy) , materna l tota l iro nbindin g capacit y durin g pregnancy , chil dse x(0=male , l=female ) an dchil drac e (0=white , l=black) . Chil dhealt hvariable s include dcurren t illness , an dironstatu s a s assesse db

y hemoglobin , hematocrit , an dtota l iro nbindin g capacity . Sociohereditar y

variable s include dsocioeconomi c statu s (23) , developmenta l stimulatio ni nth e home (24) , materna l intelligenc e (25) , an dnumbe r o f childre n inth e home . Any

covariabl e bivariatel y associate dwit hBayle y outcome s a t a libera l p . valu e o f 0.1 0 o r les s wa s classifie da s a potentia l covariate . Furthe r an

y covariabl e associate dwit hbot hprenata l and/o r postnata l lea d exposur e and

Bayle y outcome s a t p_=0.1 0 o r les s wa s classifie da s a potentia l confounder .


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DAT A ANALYSE S

Th e dat a analyti c procedure s use di nthi s serie s involve dmultipl e regressio nanalyse s wit hbot hbackwar deliminatio no f nonsignifican t covariate s an dconfounder s (reduce dmodel ) an d multipl e regressio nanalyse s retainin g al l potentia l covariate s an d confounder s regardles s o f thei r statistica l significanc e i nmultivariabl e models . Th e latte r strateg y wa s employe dt o determin e th e statistica l robustnes s o f an y bloo dlead-behavio r relationship , an di f an y positiv e finding s wer e model-specifi c (26) . Dat a analyse s wer e conducte dfo r singleto nbirth s a s wel l a s fo r th e ful l cohor t whic hinclude d3 set s o f twins . Result s o f bot hanalyse s wer e compared . Paramete r estimate s fo r independen t variable s ineithe r reduce do r origina l regressio nmodel s di d no t diffe r a s a functio no f whethe r twin s wer e presen t o r exclude dfro m th e sample .

RESULT S
Earlie r Finding s

Ou r earlies t serie s o f studie s deal t wit hth e relationshi pbetwee nprenata l exposur e t o lea dan

d feta l growth , maturation , an d earl y postnata l neurobehaviora l developmen t (2,5) . W e hav e reporte da statisticall y significan t covariate-adjuste drelationshi pbetwee nfeta l lea dexposur e variable s an d Bayle y MD I score s a t 3 an

d 6 month s (2) . Thes e reporte deffect s appeare dt o be stronges t amon g mal e infant s an d infant s fro

m th e poores t families . Fo r example , Tabl e 6 present s result s o f multipl e regressio nanalyse s examinin g th e relationshi p betwee nprenata l (maternal ) an d neonata l (1 0 day ) bloo dleadleve l an dperformanc e o nth e Bayle y MD I a t 6 months . Inthi s reanalysis , al l



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covariate s andconfounder s wer e retaine dinth e fina l mode l regardles s o f thei r individua l statistica l significance . Lea dvariable s wer e analyze dbot hi n microgram s pe r decilitr e an dtransforme dt o thei r natura l logarithm . Prenata l bloo dlea dwa s significantl y relate dt o 6 mont hMD I afte r statistica l adjustmen t fo r al l 1 0 potentia l covariate s an dconfounder s i nuntrimme dregressio nmodels . However , thi s relationshi pwa s onl y negativ e fo r mal e infant s wh o exhibite da covariate-adjuste dreductio no f 0.86 7 MD I point s fo r eac hMg/d l o f prenata l bloo dlea d(f

i = 0.0105) . Th e paramete r estimat e fo r femal e infant s wa s positiv e an dstatisticall y

insignificant . Neonata l bloo dlea dleve l wa s als o inversel y relate dt o 6 mont hBayle y MD I afte r adjustmen t fo r al l potentia l covariate s an d confounders . I

nthi s instance , th e effec t wa s mos t eviden t amon g thos e infant s fro m th e poores t families . Fo r example , fo r thos e infant s wit hHollingshea d socioeconomi c statu s (S.E.S. ) score s a t o r below th e sample.media no f 17 , ther e wa s a covariat e adjuste dreductio no f 0.75 7 MD I point s fo r eac hM9/d l o f neonata l bloo dlea d(f i = 0.0316) . Th e paramete r estimat e fo r infant s abov e th e sampl e media nwa s negativ e a s well , bu t statisticall y insignificant .

Ina structura l equatio nanalysis , w e als o founda nindirec t effec t o f prenata l bloo dlea do nbot h3 an d6 mont hMD I an

dPD I throug hlead-relate dlowe r birt hweigh t an

ddecrease dgestationa l maturit y (2) . Fo r example , i na structura l analysi s o f relationship s amon g prenata l bloo dlead , covariates , an d 6 mont hBayle y

variables , eac hlo g incremen t i nprenata l bloo dleadwa s associate dwit ha reductio no f 15 7 gram s birt hweight , an dabou t 1/ 2 wee k gestation . I nturn , birt hweigh t andgestatio nwer e positivel y relate dt o bot h Bayle y MD I andPDI . Anothe r structura l analysi s wa s conducte di na ninteri m analysi s o f 1 2 mont hBayle y dat a wit hsimila r result s (28) .



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# 1

Thes e result s hav e bee npreviousl y publishe do r presente da t scientifi c meetings . The y

ar e reviewe dher e inorde r t o pu t ou r ne w finding s int o thei r appropriat e context . Th e primar y focu s o f thi s pape r i s o nth e relationshi p betwee nfeta l andpostnata l lea dexposur e an dth e developmenta l statu s o f infant s i nth e Cincinnat i cohor t a t 2 year s o f age . Th e substantiv e issu e a t handi s whethe r th e lea drelate dreduction s inearlie r indice s o f neurobehaviora l statu s persis t i nevaluation s o f th e olde r infant .

Two-Yea r Follow-U p
Tabl e 7 present s result s o f multipl e regressio nanalyse s examinin g th e relationshi pbetwee nprenata l an dpostnata l bloo dlea dleve l an dperformanc e on th e Bayle y

MD I a t 2 4 months . N o statisticall y significan t relationship s betwee n prenata l o r postnata l bloo dlea dvariable s an dBayle y MD I wer e found . Indeed , inman y case s th e paramete r estimate s wer e positiv e rathe r tha nnegative . Fo r prenata l (maternal ) bloo dlea dexpresse dinMg/d l thi s positiv e relationshi pwa s actuall y statisticall y

significan t (f

i = 0.0217) . Althoug hno t presente di nTabl e 7 , w e als o examine dth e potentia l interaction s amon g prenata l an dpostnata l exposur e variables . Thes e analyse s teste dth e hypothesi s tha t thos e infant s wit hbot hhighe r prenata l an dhighe r postnata l bloo dlea dlevel s ma y exhibi t a defici t i n2 yea r MD I whe ncompare dt o thei r les s expose dpeers . Th e result s forthcomin g fro m thes e statistica l analyse s wer e similarl y insignificant .



### 1

37~J7 :: 7^7-*'77^?--r*TTA7TTTT~T s ^ .- , •%.-*'*-. « • i—"i"

-

Analyse s o f th e relationshi pbetwee nprenata l an d postnata l bloo dlea dleve l an dBayle y IB Rfacto r score s als o yielde dstatisticall y insignifican t results . Unfortunately , w e coul dno t adequatel y examin e th e relationshi pbetwee nlea d exposur e variable s an d 2 yeair Bayle y

PDI , sinc e onl y

17 0 o f thes e examination s coul db e completed . Th e rathe r lengthy an d demandin g natur e o f th e MD I protoco l conducte dfirs t i nth e assessmen t serie s prevente dmany 2 yea r old s fro

m completin g th e PDI . Structura l equatio nanalyse s wer e als o conducte dt o determin e i f ther e wa s a continue dadvers e impac t o f prenata l lea dexposur e on Bayle y MD I throug hfeta l growt han d maturationa l variables . Th e result s o f thes e analyse s wer e consisterntl y negative .
Th e onl y significan t independen t predictor s o f 2 yea r Bayle y MD I wer e chil d sex(Bet a = 5.184 , t = 3.25 , fi = 0.0013 ) wit hfemale s outperformin g males ; birt h lengt h(Bet a = 1.0694 , t = 3.28 , fi = 0.0012) ; an d materna l intelligenc e (Bet a = 0.1860 , t = 2.20 , fi = 0.0288| . Othe r covariable s whic hwer e bivariatel y associate dwit h2 yea r Bayle y MD I bu t eliminate dfro m th e trimme dregressio n model s wer e birt hweight , hea dcircumference , gestationa l age , Postnata l Complicatio nScal e score , an d HOM E score .
Th e lac k o f invers e relationship s betwee nmeasure s o f feta l lea dexposur e an d2 yea r MD I an

d IB Rfactor s suggest s tha t thos e infant s o f mother s wit h highe r prenata l bloo dlea dlevel s ma y hav e recovere dfro

m thei r ver y

earl y developmenta l deficits . Th e phenomeno no f catch-u pinphysica l growt hha s bee n wel l documente db

y auxologist s wh o hav e studie dinfant s compromise db y intrauterin e o r earl y extrauterin e influence s (29) . Further , studie s o f th e neurobehaviora l developmen t o f infan t twin s hav e show ncorrespondin g catch-u p growt hinneurobehaviora l developmen t (30) . 

### 1 4:; _ ...-ff.ji;MiTj ^

. _• .*. • f . ^ * . - ar .' . -' . - ".-.•-•**.*T^. T P.1 6

W e examine dth e possibilit y o f lead-relate dcatch-u pneurobehaviora l growt h ina n explorator y

analysis . Bayle y

MD I raw

score s wer e use da s a measur e o f behaviora l "growth" . Bayle y MD I raw

score s represen t th e numbe r o f item s passe d a t th e ag e o f testin g an d thu s provid e a roug hgaug e o f th e accrua l o f sensorimoto r an

d cognitiv e skill s ove r th e firs t 2 year s o f life . A rati o wa s calculate dt o expres s th e relativ e chang e o r increas e i n MD I ra w scor e betwee n3 an d2 4 month s (i.e. , 100*[MDIRA W 2 4 - MDIRA

W 3]/[MDIRAW3]) . Th e mea npercen t increas e in MD I raw

scor e i n th e study

sampl e wa s 275.43%+72.5 . Th e relativ e increas e in MDIRA

W betwee n3 an

d 2 4 month s range dfro m a lo w o f 144.68 % t o a higho f 892.31% .

Ou r primar y

interes t wa s in th e relationshi pamon g thes e chang e score s an d feta l lea dexposure , an d feta l growt han

d maturational variable s suc ha s birt h weigh t an

d gestationa l age . W e wer e particularl y intereste di

n thes e feta l developmenta l factor s becaus e th e effect s o f prenata l lea dexposur e on earl y neurobehaviora l developmen t wer e show nt o b e partl y

mediate dthroug hthe m (2) .
Th e result s o f thes e analyse s ar e presente din Figur e 1 . Fo r thi s analysis , th e variable s o f prenata l bloo dlead , birt hweight , gestation , an d hea d circumferenc e wer e groupe db y quartiles . Th e mean s an d standar ddeviation s fo r group s 1 throug h4 ar e give ni n th e figur e legend . Analysi s o f varianc e reveale dtha t al l 4 perinata l variable s wer e significantl y associate dwit hth e percen t increas e in MD I ra w scor e a t fi < 0.05 . Thos e infant s wit hth e highes t prenata l lea dexposur e o r thos e havin g th e lowes t birt hweight , shortes t gestationa l age , o r smalles t hea dcircumferenc e evidence dth e greates t degre e o f postnata l neurobehaviora l growt hcatch-up .



### 1 5P.1 7 -.-.'.-.••• . .-.'.

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I t i s interestin g t o compar e th e prenata l bloo dlea dan dbirt hweigh t variable s inthi s figure . Thei r relationship s t o th e neurobehaviora l growt h inde xappea r t o mirro r eac hother . Thi s i s a s on e migh t expec t give ntha t prenata l bloo dlea dan dbirt hweigh t wer e relate dt o earl y neurobehaviora l statu s a t 3 an

d6 month s an

dth e influenc e o f prenata l bloo dlea donearl y developmenta l indice s appeare dt o b e mediate dthroug hbirt hweigh t (2) . Thes e finding s ar e consisten t wit ha hypothesi s o f neurobehaviora l catch-u pgrowt hfo r infant s whos e centra l nervou s system growt han

ddevelopmen t ma y

hav e bee n compromise db

y lea dexposur e o r othe r factor s whic hinfluence dprenata l growt h an dmaturation .

DISCUSSIO N

We faile dt o fin

da persisten t effec t o f feta l lea dexposur e oninfan t neurobehaviora l developmen t ove r th e firs t tw o year s o f life . Thes e result s ar e inaccor dwit hon e previou s study (9) , bu t no t wit hstudie s conducte db y Bellinge r andhi s associate s wh o hav e reporte da continuou s invers e relationshi p betwee ncor dbloo dlea dleve l an dBayle y MD I betwee n6 month s an dtw o year s (10,11,12) . Ou r result s als o d o no t confirm thos e reporte db

y Por t Pirie , Australi a investigator s wh o founda significan t invers e relationshi pbetwee n earl y postanta l bloo dlea dleve l an d2 yea r Bayle y

MDI . However , thi s relationshi pwa s no longe r statisticall y significan t afte r th e HOM E variabl e wa s entered .

We als o faile dt o finda statisticall y significan t relationshi pbetwee n indice s o f postnata l lea dexposur e an dBayle y MD I o r IB

Rfactors . Thes e finding s ar e inagreemen t wit hthos e reporte db y th e Clevelan dan

dBosto n


### 1 6.V.-'- i .J-OJ-. P . 1 8 7 1

studie s (9,10,11,12) , bu t ar e somewha t discordan t wit hfinding s fro m th e Por t Pirie , Australi a stud y (14) . Thes e investigator s reporte da statisticall y significan t invers e relationshi pbetwee nintegrate dpostnata l bloo dlea dleve l an d2 yea r Bayle y

MD I afte r adjustmen t fo r 1 4 covariates , includin g materna l intelligence . However , afte r inclusio no f th e HOM E variabl e thi s relationshi p wa s n o longe r statisticall y significant . Th e mor e positiv e natur e o f th e Por t Piri e finding s ma y

sugges t a threshol dfo r a n effec t on 2 yea r Bayle y MD I sinc e mea npostnata l bloo dlea dlevel s i n thi s sampl e wer e somewha t highe r tha nthos e reporte di n th e Clevelan dstudy an d ou r own . Nevertheless , w e wer e somewha t surprise db

y th e absenc e o f an associatio nbetwee npostnata l lea dexposur e an d Bayle y variables , especiall y give nth e fac t tha t a substantia l numbe r o f subject s i n th e Cincinnat i cohor t had a t leas t on e seria l bloo dlea dleve l whic h equalle do r exceede dth e curren t leve l o f concer na s establishe db y th e Center s fo r Diseas e Contro l (31) . Althoug hw e di d no t findan y significan t relationship s betwee nlea dexposur e indice s an

d th e neurobehaviora l statu s o f olde r infants , two caveat s ar e probabl y i n order . First , th e Bayle y scale s ma y

b e somewha t limite din thei r abilit y t o measur e mor e comple xperceptual-performance , informatio nprocessing , an dlinguisti c skill s whic hma y indee db e compromise db y earl y exposur e t o lead . Feta l and postnata l lea dexposur e a t lo w t o moderat e level s ma y produc e advers e neurobehaviora l sequela e whic hma y onl y b e measureabl e i n th e olde r child . Th e evaluatio no f suc heffect s mus t awai t maturatio no f th e Cincinnat i cohort . Second , a t leas t tw

o majo r longitudina l studie s hav e reporte da significan t relationshi pbetwee nearl y lowe r leve l lea dexposur e an d th e neurobehaviora l statu s o f infant s a t 2 year s (12,14) . Publi c healt hofficials , governmenta l



### 1 7P.1 9

•--vr--'-.>.> . -*~- . --'.'.• . -»-.-«v . > . .•.' . . T* \ T KrV . 'frwjr. • i " \ « . Tf. a.'. . .. . r'.'.'.'r.'.' . r'.'•/ • . •.• • .

• '.'.'.•».•..'•: • .. . '. v • • " . .••-. .



### agencies , an

d industr y

mus t mak e polic y

decision s base dupo nal l o f th e availabl e scientifi c data , no t an y singl e study . Ou r negativ e finding s a t 2 year s d o no t impl y

tha t lowe r leve l pediatri c leadexposur e i s withou t an y continuin g harmfu l effects .

1 8

# : 

# ^ 1

REFERENCE S

1. ) Annest , J.L. , Pirkle , J.L. , Makuc , D. , Neese , J.W. , Bayse , D.D. , an d Kovar , M.G . Chronologica l trendinbloo dlea dlevel s betwee n197 6 an d 1980 . Af . Engl. J. Med. 23:1373-137 7 (1983) .
2. ) Dietrich , K.N. , Krafft , K.M. , Bornschein , R.L. , Hammond , P.B. , Berger , 0. , Succop , P.A. , an

dBier , M . Lo

w leve l feta l lea dexposur e effec t o n neurobehaviora l developmen t i nearl y infancy . Pediatrics

80:721-73 0 (1987) .
3. ) McMichael , A.J. , Vimpani , G.V. , Robertson , E.F. , Baghurst , P.A. , an d Clark , P.D . Th e Port-Piri e Cohor t Study : Materna l bloo dleadan d pregnanc y

outcome . J. Epidem. Comm. Health 40:18-2 5 (1986) .
4. ) Moore , M.R. , Goldberg , A. , Pocock , S.J. , Meredith , A. , Stewart , I.M. , MacAnespie , H. , Lees , R. , an dLow , A . Some studie s o f materna l an dinfan t lea dexposur e inGlasgow , Scot. Med. J . 27:113-12 2 (1982) .
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dHammond , P.B . Effect s o f prenata l leadexposur e o n infan t siz e a t birth . In : Lea dExposur e an dNeurobehaviora l Effect s i n Children . (M . Smit han dL . Grant , Eds.) , Kluwer , Lancaster , Englan d(in press) .



### 1 9P.2 1

6. ) Ward , N.I. , Watson , R. , an d Bryce-Smith , D . Placenta l elemen t level s in relatio nt o feta l developmen t fo r obstetricall y "norma l births" : A stud y o f 3 7 elements . Evidenc e fo r effect s o f cadmium , lead , an d zin c on feta l growth , an

d fo r smokin g a s a sourc e o f cadmium . Int. J. Biosocial Res. 9:63-8 1 (1987) .
7. ) Needleman , H.L. , Rabinowitz , M. , Leviton , A. , Linn , S. , an d Schoenbaum , S . Th e relationshi p betwee nprenata l exposur e t o lead an d congenita l anomalies . J.A.M.A. 2SJ:2956-295 9 (1984) .
8. ) Ernhart , C.B. , Wolf , A.W. , Kennard , M.J. , Erhard , P. , Filipovich , H.F. , an d Sokol , R.J . Intrauterin e exposur e t o lo w level s o f lead : Th e statu s o f th e neonate . Arch. Environ. Health 47:287-29 1 (1996) .
9. ) Ernhart , C.B. , Morrow-Tlulak , M. , Marler , M.R. , an d Wolf , A.W . Lo

w leve l lead exposur e in th e prenata l an d earl y preschoo l periods : Earl y preschoo l development . Neurotoxicol. Teratol. 9:259-27 0 (1987) .
10. ) Bellinger , D.C , Needleman , H.L. , Leviton , A. , Waternaux , C , Rabinowitz , M.B. , an

d Nichols , M.L . Earl y sensory-moto r developmen t an d prenata l exposur e t o lead . Neurobehav. Toxicol. Teratol. 6:387-40 2 (1984) .
11. ) Bellinger , D. , Leviton , A. , Needleman , H.L. , Waternaux , C , an d Rabinowitz , M . Lo

w leve l lead exposur e an d infan t developmen t i n th e firs t year . Neurobehav. Toxicol. Teratol. 8:151-16 1 (1986) .



### 2 0,.J.,!a^.r?'771WZ^^f^U'J*-&"\^Vt'l''l"l..-±-T--, i. T P.2 2

12. ) Bellinger , D. , Leviton , A. , Waternaux , C , Needleman , H. , an d Rabinowitz , M . Longitudina l analyse s o f prenata l an d postnata l lead exposur e an d earl y cognitiv e development . N. Engl. J. Med. 375:1037-104 3 (1987) .
13. ) McMichael , A.J. , Baghurst , P.A. , Robertson , E.F. , Vimpani , G.V. , an d Wigg , N.R . Th e Por t Piri e Cohor t Study : Blood lea d concentration s in earl y childhood . Med. J . Aust. J43:499-50 3 (1985) .
14. ) Wigg , N.R. , Vimpani , G.V. , McMichael , A.J. , Baghurst , P.A. , Robertson , E.F. , an

d Roberts , R.J . Por t Piri e Cohor t Study : Childhoo d bloo d lea d an d neuropsychologica l developmen t a t ag e two years . J. Epid. Comm. Health 42:213-21 9 (1988) .
15. ) Clark , C.S. , Bornschein , R.L. , Succop , P. , Qu e Hee , S.S. , Hammond , P.B. , an d Peace , B . Conditio nan d typ e o f housin g a s a n indicato r o f potentia l environmenta l lead exposur e an d pediatri c bloo d lead levels . Environ. Res. 38:46-5 3 (1985) .
16. ) Bornschein , R.L. , Succop , P. , Dietrich , K.N. , Clark , CS. , Qu e Hee , S. , an d Hammond , P.B . Th e influenc e o f socia l an d environmenta l factor s o n dus t lead , han

d lead , an

d bloo d lea d level s in youn g children . Environ. Res. 38:108-11 8 (1985) .
17. ) Ballard , J.L. , Novak , K.K. , an d Driver , M.A . Simplifie d scor e fo r assessmen t o f feta l maturatio ni n newl y bor ninfants . J . Pediatr. 95:769-77 4 (1979) .



### 2 1P.2 3

-•rir.j-i ! - ».i->.t-T._ - •' . - ^.- ! - . t v - s nv-VkV.".".- - .•.»*-._jj^_«

_••*> . ..,.-.v . v. * :»:o"jLi. iVvv/.v. , .viv.''.'T'..V--'/..v»v«N't««v.«•»'»''.''•"».•. • »>**>-»•«-,',•. - -

18. ) Roda , S.M. , Greenland , R.D. , Bornschein , R.L. , an d Hammond , P.B . Anodi c strippin g voltammetr y procedur e modifie d fo r improve d accurac y o f bloo d lea d analysis . Clin. Chem. 34:563-56 7 (1988) .
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Yor k (1969) .
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o f childhood : Models , methods , an d implication s fo r intervention . Neurotoxicology 6:165-18 2 (1985) .
21. ) Dietrich , K.N. , Krafft , K.M. , Pearson , D.T. , Harris , L.C , Bornschein , R.L. , Hammond , P.B. , an d Succop , P.A . Contributio no f socia l an d developmenta l factor s t o lead exposur e durin g th e firs t yea r o f life . Pediatrics 75:1114-111 8 (1985) .
22. ) Littman , B. , an d Parmelee , A.H . Medica l correlate s o f infan t development . Pediatrics 57:470-47 4 (1978) .
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24. ) Caldwell , B.M. , an d Bradley , R.H . Home Observatio nfo r Measuremen t o f th e Environmen t (H.O.M.E. ) Manual . Littl e Rock , AK , Universit y o f Arkansa s at Littl e Roc k (1979) .



### 2 2P.2 4

25. ) Silverstein , -A.B . Two an d four-subtes t shor t form s o f th e Wechsle r Adul t Intelligenc e Scale-Revised . J. Consulting Clin. Psychol. 50:415-41 8 (1982) .
26. ) SA S User' s Guide : Statistics . SA S Institut e Inc. , Cary , NC (1985) .
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y th e Metho d o f Maximu m Likelihood , User' s Guide . Internationa l Educationa l Services , Chicago , I L (1985) .
28. ) Dietrich , K.N. , Krafft , K.M. , Bier , M. , Berger , 0. , Succop , P.A. , an d Bornschein , R.L . Neurobehaviora l effect s o f feta l lead exposure : Th e firs t yea r o f life . Pape r presente d a t th e EPA/EE C worksho p Lea d Exposur e an d Neurobehaviora l Effect s i nChildren , Edinburgh , Scotland , Septembe r (1986) .
29. ) Tanner , J.M. , Catch-u p growt hinman . British Med. Bull. 37:233-23 8 (1981) .
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y th e Center s fo r Diseas e Control . U.S . Departmen t o f Healt han d Huma nService s publicatio nNo . 99-2230 . Atlanta , Center s fo r Diseas e Contro l (1985) .



### 2 3P.2 5

ACKNOWLEDGEMENT S
Thi s researc hwa s supporte db y a Program

Projec t Gran t fro

m th e Nationa l Institut e o f Environmenta l Healt hScience s (#P01-ES-01566-09) , Dr . Pau l B . Hammond , Principa l Investigator . Th e author s gratefull y acknowledg e th e indispensabl e assistanc e o f Marian a Bier , Lesli e Harris , Susa nNaraine , Holl y Jason , Suzann e Leibee , an dJil l Edward s fo r th e collectio no f behaviora l an d sociodemographi c data , Sandy Rod a an

dRober t Greenlan dfo r bloo dlea danalyses , Terr i Mitchel l fo r phlebotom y an dth e collectio no f biomedica l data , an dJoAn n Grot e fo r subjec t recruitmen t an dpatien t scheduling . Th e author s als o acknowledg e th e assistanc e o f th e Babie s Mil k FundAssociatio nan dFindla y Stree t Clini c staff . Thi s pape r i s dedicate dt o th e memor y o f Tassi e Le e Vaiso n Walker , long-tim e caretake r a t Findla y Clini c an

dgoo dfriendo f th e Cincinnat i Lea dStudy .



### 2 4I I I J !.l-L.b-,l ; l.1JTIA,4UUX X •^I"-^-""^* ' .-»..•

_ J-.'-U-,-'LM . .«-J.-l . -4,W r ^,^W„ ,

FIGUR E LEGEN D Figur e 1 . Percen t increas e i n MD I raw scor e b y feta l biologica l ris k groups . Percen t chang e i n MD I raw scor e betwee n3 an

d 2 4 month s wa s calculate d a s (100*[MDIRAW24-MDIRAW3]/MDIRAW3) . Prenata l bloo d lead i s measure d i n microgram s pe r decilitre , birt hweigh t i n grams , gestationa l ag e i n weeks , an d hea d circumferenc e in centimeters . Grou p means : Prenata l bloo d lead , Grou p 1 , M = 4.25 ± 1.16 , Grou p 2 , M = 6.61 ± 0.61 , Grou p 3 , M - 8.53 ± 0.63 , Grou p 4 , M = 13.00±3.28 ; Birt hweight , Grou p 1 , M - 2553.58±235.32 , Grou p 2 , M. - 2977.43175.29 , Grou p 3 , M = 3303.2 4 ±107.05 , Grou p 4 , M ** • 3757.35±228.26 ; Gestationa l age , Grou p 1 , M = 37.03±0.94 , Grou p 2 , M = 39.26+0.44 , Grou p 3 , M = 41.00±0 , Grou p 4 , M

= 42.3610.50 ; Hea d circumference , Group 1 , M = 31.8910.53 , Grou p 2 , M

= 33.2910.29 , Grou p 3 , M = 34.1710.23 , Grou p 4 , M = 35.5010.83 .



### 2 5

# PERCEN T INCREAS E I N MD I RA W SCOR E B Y FETAL BIOLOGICA L RIS KGROUP S I
•

• •
X :

I \ l \ * \ 

# ' £ s j i >

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### 33 0 32 0 31 0 30 0 29 0 28 0 27 0 26 0 25 0 24 0 ( ^•o* * X



### •

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### Jrou p | X . ^^^^ ^ ^ , —_^^ L ___>r

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### Grou p 2 Grou

p 3 Group s __.__ . .L . a l Prenata l Blood Lea d - # - Birt hHeigh t A Geetatlona l Ag e Hes d Circumferenc e

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TABL E 1 Perinata l Statistic s o n Infant s in Stud

y Sampl e 

# 1

- •.**** » «-- . > v «-V.*» v' fi

Stud yVariabl e Birt h Weigh t Gestationa l Age(a ) Birt h Lengt h (cms ) Birt h Hea d Circumferenc e (cms ) Obstetrica l Complication s Scale(b ) Postnata l Complication s Scale(b ) APGAR Scor e a t Fiv e Minute s Percen t Femal e Percen t Blac k Mea n 3147.9 7 39.5 7 49.2 5 33.7 8

82.6 5

94.4 4 8.8 5 

### 5 2 86 6 % 2 % Standar d Deviatio n

472.9 5 1.6 9 2.4 7 1.3 7

5.7 3

9.4 7 0.4 0 Lowes t

181 4 

### 3 5 

### 4 2 3 0
6 8
3 0 

### 6 Highes t 440 0 

### 4 3 5 6 3 9
9 5


### 10 0 

### 9

(a)A s assesse d b

ystandardize d physica l examinatio n o f th e neonat e (12) . (b)A s assesse d b

yLittman-Parmele e Obstetrica l an d Postnata l Complication s Scale s (22) .



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TABL E 2 Descriptiv e Statistic s o n Familie s i n StudySampl e

Stud yVariabl e
Materna l Ag e a t Birt h o f Chil d Materna l I.Q.(a ) Socioeconomi c Status(b ) Numbe r o f Childre n i n th e Hom e Tota l H.O.M.E . Score(c ) Percentag e Unmarrie d Mea n
22.5 5 

### 7 5
17.4 2 2.5 7 32.7 1 

### 8 3 Standar d Deviatio n

4.4 0 9.4 8 5.6 9 1.3 8 5.2 7 

### 3 % Lowes t


### 15 5 5 

### 8 1 1 4 Highes t


### 3 7 

### 11 0 5 3 

### 9 4 3

(a)Wechsle r Adul t Intelligenc e Scale-Revise d (Shor t Form ) (25 ) (b)Hollingshea d Fou r Facto r Inde x o f Socioeconomi c Statu s (23 ) (c)Hom e Observatio n fo r Measuremen t o f th e Environmen t (HOME ) (24 )



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TABL E 3 Descriptiv e Statistic s o n Bloo d LeadVariables^ )

Bloo d Lea d Variabl e
Prenata l (Maternal ) Bloo d Lea d Neonata l (1 0 Day ) Bloo d Lea d Neonata l ( 3 Month ) Bloo d Lea d Maximu mFirs t Yea r Bloo d Lea d Maximu mSecon d Yea r Bloo d Lea d 2 4 Mont h (Concurrent ) Bloo d Lea d N

26 1 

### 29 7 29 7 29 7 29 7 29 7 Mea n
8.0 9 4.7 6 6.1 8 15.8 5 21.1 1 17.4 5 Standar d Deviation

3.6 4 3.1 5 3.7 5 8.1 7 11.3 8 9.1 6 Lo

w

1 

### 1 1 5 6 4 Hig h
2 7 

### 2 6 2 6 5 6 8 5 70 ( a 

### )l n microgram s pe r decilitre , whol e blood . Al l value s hav e bee n norma l ize d t o a standar d hematocri t o f 3 5 percen t packe d cel l volume .

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### TABL E 4 Descriptiv e Statistic s on Bayle y Menta l Developmen t Index a t 3 , 6 , 12 , an

d 2 4 Months* 8 

### ) Bavle v Variabl e 3 Mont hMD I 6 Mont hMD I 1 2 Mont hMD I 2 4 Mont hMD I 

### N

27 3 288 29 6 28 4 Mea n 100.3 8 107.6 9 111.8 9 88.0 8 Standar d Devi

9.9 1 16.2 8 14.4 6 13.7 7 ation 

### Lo

w 6 0 6 1 5 0 5 0 Hig h 

### 12 5 15 0 13 7 13 2 ( a 

### )Th e Bayle y

Scale s o f Infan t Developmen t hav e a standardize d populatio nmea nan

d standar ddeviatio no f 10 0 1 16 .

3 0

### r 

# " 1

TABL E 5 Facto r Analysi s o f th e Bayley Infan t Behavio r Recor d a t Twenty-Fou r Month s (a )

* Bayle y Variabl e Emotiona l Ton e Enduranc e Socia l Orientatio n T o Examine r Cooperativenes s Fearfulnes s Manipulatio no f Object s Goa l Directednes s Imaginativ e Us e o f Toy s Vocalization s Activit y Leve l Bod y Motio n Energy Bangin g Toy s Fin e Moto r Coordinatio n Socia l Orientatio n T o Person s Attentio nSpa n Socia l Orientatio n T o Mothe r Interes t I

nSound s Objec t Orientatio n Reactivit y Tensio n Facto r 1 0.7 9 0.7 5 0.7 2 0.6 8 -0.6 2 0.3 4 0.3 3 0.3 2 0.3 1 Facto r 2

0.3 1 -0.4 4

0.4 8 0.8 7 0.8 7 0.8 0 0.4 6 Facto r 3

0.3 5

0.5 1 0.3 1 0.3 3

-0.4 1 0.5 9 0.5 5 0.5 1 0.4 9 0.4 1 0.3 6 Facto r 4

0.3 5

.

0.3 4

0.4 8 0.5 7 0.5 4 ( a )lnfan t Behavio r Recor d variable s wit hfacto r loading s o f 0.3 0 o r greate r ar e shown .



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TABLE 6 Result s o f Multipl e Regressio n Analyse s Examinin g th e Relationshi p Betwee n Prenata l and Neonata l Bloo d P b (PbB ) Leve l an d Performanc e o n th e Bayle yMenta l Inde x a t 6 Month s o f Age( a )

Bloo d P b Variabl e
Lo g Prenata l Pb B Lo g Prenata l Pb B b yChil d Se x
Prenata l Pb B (Mg/dl ) Prenata l Pb B (/xg/dl ) b yChil d Se x

Lo g Neonata l Pb B Lo g Neonata l Pb B b yS.E.S . Neonata l Pb B (/ig/dl ) Neonata l Pb B (/xg/dl ) b yS.E.S . N 24 9



### 28 3 Bet a -5.910 3 11.248 1 -0.885 9 1.533 5

-11.930 1 0.583 6 -3.154 4 0.162 6 Standar d Erro r

2.675 8 4.068 6 0.340 0 0.514 6

5.018 8 0.282 0 1.299 9 0.076 2 

### t

-2.2 1 2.7 6 -2.6 0 2.9 8

-2.3 8 2.0 7 -2.4 3 2.1 3 

### P 0.028 1 0.006 1 0.009 9 0.003 2

0.018 1 0.039 5 0.015 9 0.033 8 ( a )Covariate s and confounder s i n regressio n model s include d birt h weight , gestationa l age , Obstetrica l Complication s Scale , Postnata l Complication s Scale , chil d sex , chil d race , Composit e Inde x o f Tobacc o and Alcoho l Consumption , materna l age , socioeconomi c status , and parity .



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TABL E 7 Result s o f Multipl e Regressio nAnalyse s Examinin g th e Relationshi p Betwee nPrenata l an

d Postnata l Bloo d P b(PbB ) Leve l an d Performanc e onth e Bayley

Menta l Inde xa t 2 4 Month s o f AgeU J

Bloo d PbVariabl e

Log Prenata l PbB Prenata l Pb

B (Mg/dl )
Log Neonata l 1 0 Day Pb B Neonata l 1 0 Day PbB (^g/dl )
Log Neonata l 3 Mont hPbB Neonata l 3 Mont h PbB (Mg/dl )
Log Maximu

m Pb B 1s t Yea r Maximu m Pb B 1s t Yea r (Mg/dl )
Log Maximu

m PbB 2n d Yea r Maximu m PbB 2n d Yea r (Mg/dl )
Log PbB 2 4 Month s PbB 2 4 Month s (Mg/dl ) 

### N

23 7

270

270

270

270

270 Bet a
3.295 6 0.505 8

0.243 4 -0.016 2

1.345 2 0.235 1

2.215 5 0.133 8

2.322 7 0.096 1 3.196 9 0.127 0 

### Standar dErro r

1.712 3 0.218 8

1.204 9 % 0.248 3

1.330 6 0.209 0

1.627 7 0.096 2

1.649 8 0.069 2 1.697 1 0.087 7 

### t

1.9 2 2.3 1

0.2 0 -0.0 7

1.0 1 1.1 2

1.3 6 1.3 9

1.4 1 1.3 9 1.8 8 1.4 5 

### P
0.055 5 0.021 7
0.840 0 0.948 0

0.312 9 0.261 8

0.174 7 0.165 5

0.160 3 0.166 3 0.060 7 0.149 0 ( a )othe r significan t covariate s an d confounder s i n reduce d regressio n model s include d chil d sex , materna l intelligenc e (I.Q.) , an d birt h length . 3 3