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Antecedent s an

d Correlate s o f Improved Cognitive Performanc e i nChildre nExpose d i nuter o t o Lo w Level s o f Lea

d

Davi d Bellinge r Ala nLeviton Jon e Sloma n

Children' s Hospita l (Boston ) an d Harvar d Medica l Schoo l (D.B. , A.L. ) an

d Wheeloc k Colleg e (J.S. )

Running Head : Performanc e chang e i nlead-expose d childre n

Presente d a t the conferenc e Advance s i nLead Research : Implication s for Environmenta l Research , Nationa l Institut e o f Environmenta l Healt hSciences , Researc hTriangl e Park , NC , January , 1989 .

Addres s correspondenc e t o : Neuroepidemiolog y Unit , Gardne r House , Children' s Hospital , 30 0 Longwood Avenue , BostonM A 02115-574 7

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Abstrac t U p t o 2 year s o f age , childre nwit humbilica l cord blood lea d level s o f 1 0 t o 2 5 ug/d l achieve significantl y lowe r score s ontest s o f cognitive developmen t thando childre nwit hlowe r prenata l exposures . B

y ag e 5 years , however , the y appea r t o have "recovered " from , o r a t leas t "compensated " for , thi s earl y insult . Chang e i n performanc e betwee n2 4 an d 5 7 month s o f ag e wa s examine d in . relation t o leve l o f postnata l lea d exposur e an

d variou s sociodemographi c factors . Amon

g childre nwit hhig hprenata l lea

d exposure , greate r recovery

o f functionwa s associate d wit hlowe r bloo d lea d leve l a t 5 7 months , highe r socioeconomi c status , highe r H.O.M.E . scores , highe r materna l IQ , an d femal e gender . Th e differenc e betwee nthe score s a t 5 7 month s o f childre nwit h"optimal " an d "les s optimal " value s o nthes e variable s generall y exceede d 1/ 2 SD . Highe r prenata l lea

d exposur e i s associated wit ha nincrease d ris k o f earl y cognitive deficit . Furthermore , th e ris k tha t a defici t wil l persis t throughth e preschoo l year s i s increased among childre nwit hhigh prenata l exposur e an d eithe r hig

hpostnata l exposur e or les s optima l sociodemographi c characteristics .P. 4

I nou r prospective stud y o f lea

d an d cognitive development , childre nwit h"high " umbilica l cord blood lea d level s (1 0 t o 2 5 ug/dl ) achieve d significantl y lowe r Menta l Developmen t Index score s throughtw

o year s o f ag e thandi d infant s whos e cord blood lea d level s wer e "low " (< 3 ug/dl ) o r "medium " (6- 7 ug/dl ) (1) . I ncontras t t o the result s o f the infan t assessments , cord bloo d lead leve l wa s no t significantl y relate d t o children' s performanc e o

nthe McCarth

y Scale s o f Children' s Abilitie s a t ag e 5 7 month s (2) . Thes e dat a ma

y be explaine d i nsevera l ways . First , betwee n 2 4 an d 5 7 month s o f age , childre n"recover " from , o r a t leas t "compensate " for , the insul t represente d b y highprenata l lea d exposure . A

varian t o f thi s i s tha t the exten t o f "recovery " or "compensation " varie s among children . Suc ha contingenc y migh t b e difficul t t o appreciat e using analytica l approache s tha t focu s onl y ondifference s i nth e mea nrecover y o f group s define d b y prenata l exposur e level . Finding tha t th e likelihood o f recovery i s systematicall y

relate d t o som

e characteristi c o r even t woul d b e particularl y

importan t fro

m th e standpoin t o f intervention . Alternatively , persisting impac t o f prenata l exposur e i s obscure d b

y variation s among childre ni npostnata l lead exposure . Finally , th e apparen t attenuationo f th e associationbetwee n prenata l lead exposur e an d developmen t i s a measuremen t artifac t attributabl e t o difference s i nthe mi xo f cognitive skill s tha t contribut e t o a child' s score s o nth e Bayley Scale s an

d th e McCarth

y Scales . Fo r instance , prenata l exposur e may b eP. 5

•i

associate d wit hthe skill s assessed b y the Bayle

y Scale s bu t no t wit hskill s assessed b y the McCarth

y Scales . T o distinguis hamong thes e alternatives , experience s an d characteristic s tha t correlat e wit hchang e i nperformanc e (bot h improvemen t an

d deterioration ) need t o b e identified . I nthi s report , we describ e our searc hfor thes e covariates .

Method s Sampl e O f the origina l cohor t o f 24 9 childre n(3) , 20 4 completed the 2 4 mont hevaluation . No effor t wa s mad e t o asses s a t 5 7 month s 3 childre nwit hseriou s medica l problem s identified i nth e earlie r phas e o f th e study , an d 5 set s o f twins . O f th e 19 1 eligibl e children , we evaluate d 17 0 (89.0%) . Th e media nag e a t assessmen t wa s 57. 8 months . Dat a Collecte d Informationo

na rang e o f potentia l covariate s o f lea d exposur e an

d cognitive functionwer e obtaine d (3) . Thes e included demographics , reproductive history , exposure s during an d characteristic s o f the indexpregnancy , labo r an d delivery , neonata l characteristics , an d measure s o f chil d rearing environmen t an

d practices . Th e outcome s considere d her e ar e a child' s Menta l Developmen t Index(MDI ) scor e fro m th e Bayley Scale s o f Infan t Developmen t (4 ) a t 2 4 month s an d Genera l Cognitive Index(GCI ) scor e fro m the McCarth

y Scale s o f Children' s Abilitie s (5 ) a t 5 7 months .P. 6

3 Capillar

y blood sample s wer e collecte d whe nthe childre n wer e 6 , 12 , 18 , an d 2 4 month s ol d an d venou s sample s whe nthe y wer e 5 7 month s old . Analytica l method s use d t o measur e blood lea d level s ar e describe d elsewher e (6-7) . I nstatistica l analyses , postnata l blood lea d level s wer e treate d a s bot hcontinuousl y distribute d an

d a s categorica l variables . Th e sam e cut-of f value s use d t o classif y

cord blood lea

d level s a s "low " (< 3 ug/dl ) an d "high " (>=1 0 ug/dl ) wer e use d t o classif y postnata l levels . Level s betwee n3 an d 1 0 ug/d l wer e classifie d a s "medium" . Dat a Analysi s Th e nul l hypothesi s i s tha t change s i nchildren' s performanc e betwee n2 4 an d 5 7 month s o

ngloba l test s o f cognitive developmen t ar e no t related to : a ) prenata l lea

d exposur e (cor

d blood lea

d level) , b ) postnata l lea

d exposures , o r c ) sociodemographi c characteristic s (famil y socia l class , H.O.M.E . scor e a t 5 7 months , materna l IQ , gender , ethnicity , materna l age ) Usin g populatio nestimate s for th e mea nan d standard deviatio no f MD I an d GC I score s (10 0 an d 16 , respectively) , w e compute d children' s z score s for bot hindices . Additiona l analyse s using sample-base d estimate s o f mea nan d standard deviatio n(115. 6 an d 16. 4 for MDI ; 115. 5 an d 14. 5 fo r GCI ) produce d nearl y

identica l results . A s anindexo f a child' s "developmenta l trajectory " betwee n2 4 an d 5 7 months , chang e i nz scor e (delt a z ) wa s calculate d a s follows :P. 7 -' ' >» i Pf*f * '— T

4 delta s z = » z GCI . 5 7 - ZMDI-2 4 Thus , a chil d wit ha positive delt a z improved i nperformanc e betwee n2 4 an

d 5 7 month s o f age . Z tran s forma t icon

s ar e necessary

i norde r t o compar e score s expresse d o

ndifferen t scales . Becaus e MD I an d GC I have th e sam e expecte d mea nan

d sitandar

d deviation , the analyse s reported coul d have bee nconducted ) o n"delta " score s derive d b y computing the differenc e betwee na child' s MD I an d GC I scores . Th e mor e genera l metho d i s used t o illustrat e it s usefulnes s i nidentifying correlate s o f performanc e chang e an d becaus e som

e additiona l analyse s reported involv e score s measure d o ndifferen t scales . Th e correlationbetwee ndelt a z an d MD I scor e a t 2 4 month s wa s larg e an

d negative i nth e ful l sampl e (-0.55 ) an d withi neach strat a o f cord blood lea d (-0.62 , -0.42 , an d -0.5 8 i nthe low , medium , an

d highgroups , respectively) . Thi s association , du e at leas t i npar t t o regressiont o th e mean , wa s no t attributabl e t o th e disproportionat e influenc e o f outlying observations . Th e relationshi p betwee ndelt a z an d MD I a t 2 4 month s i s linea r wit h approximatel y

egua l delt a z varianc e fo r differen t value s o f MDI . A linea r relationshi p als o hel d withi neac ho f the cord blood lead strata . There f fore , i nregressionanalyse s o f delt a z , MD I a t 2 4 months , a measur e o f "initia l value" , wa s include d a s a predictor . T o asses s th e impac t o f adjusting delt a z fo r MDI , w e compared th e coefficient s assigne d t o variable s i nmodel s withou t MD I t o coefficient s assigne d i nmodel s tha t included th e MD I term .P. 8

Becaus e o f potentia l problem s du e t o multicollinearity , the associationbetwee ndelt a z an d eac hvariabl e wa s adjusted fo r MD I using bot ha one-stag e an d a two-stag e procedure . I nthe two stag e approach , delt a z wa s regresse d onMD I alon e an d th e residual s regresse d onth e variabl e o f interest . I nthe one stag e approach , delt a z wa s regresse d onbot hMD I an d the variable . Th e tw

o approache s yielde d virtuall y identica l results . (Table s ar e availabl e fro m th e authors) . Analysi s proceede d i nthre e phases : (1 ) Th e association betwee ndelt a z an d eachvariabl e wa s examined b y multipl e regressio nanalysi s i nthe complet e sample . (2 ) The exten t t o whic hthe associationbetwee ndelt a z an d a variabl e differe d according t o cord blood lea d stratu

m wa s examine d using tw o strategies : (a ) stratifie d analyse s an d (b ) fitting regression model s tha t included the appropriat e interactionter m t o the dat a fo r th e whol e sample .

Result s Complet e Sampl e Bot hintrauterin e an d recen t postnata l lea d exposure s ar e associate d wit hth e amoun t an d directiono f chang e i nchildren' s cognitive performanc e betwee nage s 2 4 an d 5 7 month s (Tabl e 1 ; colum nB) . Th e signo f the regressioncoefficien t for cord blood lead leve l (expressed a s a continuou s variable ) i s positive , meaning tha t childre nwit hhighe r prenata l exposure s tende d t o hav e highe r delt a z score s (reflectin g greate r relativeP. 9

6 improvement) . Thi s i s consisten t wit hour previou s findin g o f attenuationb

y 5 7 month s o f th e associationbetwee nprenata l exposur e an

d cognitive development . Using th e regressioncoefficien t o f .0 3 assigne d t o cor d blood lea

d leve l (i.e. , the slop e o f the regressiono f delt a z agains t cord blood lea d level ) an

d the mea ncord blood lea d level s o f childre ni nthe lo w an d hig hprenata l exposur e group s (1. 8 an d 14. 6 ug/dl , respectively) , the mea nchange s in performanc e o f childre ni nthes e tw o group s canbe estimated . Amon g lo w lea d children , the mea nchang e wa s +0.0 5 standard
norma l deviat e unit s (.0 3 X1.8) . Onaninde xwit ha standard deviatio no f 16 , thi s correspond s t o +0. 9 point s (1 6 X.05) . Among highlea

d children , the mea nchang e wa s +0.4 4 standard
norma l deviat e unit s (.03 X14.6 ) o r +7. 0 points . Thus , the ne t gai no f the hig

hlea d childre nbetwee n2 4 an d 5 7 month s wa s 6. 1 point s (7. 0 - 0.9) , a substantia l percentag e o f thei r relative defici t (7. 8 points ) a t ag e 2 4 month s (1) . Th e negative sign s o f the coefficient s for blood lea d leve l
a t 18 , 24 , an

d 5 7 month s indicat e aninvers e relationshi p betwee n delt a z score s an

d the children' s lead level s a t thes e ages . Delt a z score s wer e als o significantl y relate d t o variou s indicator s o f sociodemographi c status . Childre nwit hhighe r H.O.M.E . scores , highe r socia l class , an d mor e intelligent , olde r mother s tende d t o have highe r delt a z scores . Delt a z wa s no t significantl y

associate d wit hgende r o r ethnicity . Th e impac t o f adjusting delt a z for MD I scor e a t 2 4 month sP.1 0

i s eviden t b

ycomparin g th e coefficient s i n column s Aand B o f Tabl e 1 . Thos e variable s significantl yassociate d wit h delt a z befor e adjustmen t fo r MD I remaine d s o whe n MD I wa s include d i n th e mode l (cord bloo d lea d level , bloo d lea d leve l a t 1 8 an d 2 4 months , materna l age) . Althoug h adjustmen t ha d relativel ylittl e impac t o n th e magnitud e o f th e coefficients , th e standar d error s wer e reduced . Fo r severa l othe r variable s (bloo d lea d a t 5 7 months, H.O.M.E . score , socia l class , materna l IQ , and gender) , adjustmen t fo r MD I produce d substantia l increase s i n th e coefficient
. Indeed , fo r al l bu t gender , th e coefficien t becam e statisticall ysignificant
. Th e variabl e ethnicity , expresse d a s a dichotom

y(white/nonwhite) , no t onl yha d th e larges t chang e i n it s coefficient , bu t 'th e sig n fo r white s change d fromnegativ e t o positive
. Thus , thes e analyse s confir m ou r previou s findin g tha t childre n wit h hig h cor d bloo d lea d level s showe d substantia l improvemen t i n performanc e betwee n 2 4 and 5 7 month s and tha t developmen t i n thi s perio d wa s inversel yrelate d t o postnata l lea d exposure . I n addition , performanc e chang e betwee n 2 4 and 5 7 month s bor e th e expecte d relationship s wit h sociodemographi c factors , wit h mor e optima l value s associate d wit h mor e positiv e change .
Stratificatio nb

y Cord Blood Lead Group Fo r severa l variable s (bloo d lea d leve l a t 5 7 months , socia l class , materna l IQ , gender) , th e coefficien t wa s considerabl y8

large r amon

g childre nwit hhig hcor d blood lea

d leve l thanamon

g childre ni nthe othe r prenata l exposur e group s (Tabl e 2) . Th e p valu e for cor

d blood lea

d leve l wa s considerabl y mor e extrem

e among thes e childre nthanamong thos e i nth e othe r groups , bu t thi s appear s t o b e du e mostl y t o difference s i nth e standard
error s o f th e coefficients . Th e restricte d rang e o f prenata l exposure s amon

g childre ni nthe "low " an d "medium " cor

d blood lea d group s may

have contribute d t o difference s acros s strat a i n th e strengt ho f the associationbetwee ncord blood lea d leve l an

d delt a z . Th e associationbetwee ndelt a z an d blood lea

d leve l a t 2 4 month s wa s comparabl e i nthe thre e cor d blood lea

d groups . Thi s reflect s i npar t the fac t tha t i nthe complet e sample , 2 4 mont h blood lea

d leve l wa s mor e strongl y associated wit hGC I thanwa s an y othe r lea

d term . I nthi s cohort , performanc e a t 5 7 month s wa s relate d t o leve l o f lea d exposur e a t 2 4 months , regardles s o f a child' s leve l o f prenata l exposure . Gende r i s a particularl y strikin

g exampl e o f th e dependenc e o f delt a z score s o nleve l o f prenata l exposure . Th e score s o f girl s an

d boy s wer e almos t identica l among childre nwit heithe r lo w o r mediu

m exposures . Among childre nwit hhighprenata l exposures , however , girl s had appreciabl y highe r delt a z score s (Figur e 1) . Althoughthe association s betwee ndelt a z an d othe r variable s appea r t o depen d oninitia l exposur e statu s (i.e. , cor d blood lead level) , interactionterm s constructe d t o asses s th eP.1 2

9 significanc e o f thes e difference s wer e no t statisticall y significant . Th e regressioncoefficient s for man y o f the variable s differe d significantl y fro m zer o onl y

withi nthe hig

h cord blood lea

d group , bu t thes e di d no t necessaril y diffe r significantl y

fro m the corresponding coefficient s i nthe othe r tw o cord blood lea

d strata . Fo r instance , i neac hstratum , childre nabove the media nsocia l clas s tended t o have delt a z score s highe r thanthos e o f thei r peer s belo w the media n(Figure 2 ) . Thi s socia l clas s advantag e wa s greatest , however , amon g childre nwh o had highcord blood lead .

T o understan

d ingreate r detai l the correlate s o f performanc e chang e among childre nwit hhig hcord blood lea

d levels , we examine d th e least-square s mea ndelt a z score s i n differen t postnata l lea d exposur e an

d sociodemographi c strat a (Tabl e 3) . Fo r lea

d level s a t 2 4 an

d 5 7 month s an

d al l sociodemographi c variables , childre nwit hmor e optima l value s ha d mor e positive delt a z score s thandi d childre nwit hles s optima l values . Th e difference s i nGC I score s for childre ni ndifferen t strat a canbe estimate d using the table d value s o f delt a z . Fo r instance , among childre nwh o had highcord blood lea d bu t lo

w blood lead a t 5 7 months , th e mea ndifferenc e betwee nGC I an d MD I
z score s wa s +0.45 . Among childre nwit hhighblood lea d level s o

n bot hoccasions , th e mea ndifferenc e wa s -0.16 . Therefore , i f tw o childre nwit hhighcord blood lea d achieve d th e sam e MD I scor e a t 2 4 months , bu t on e had a lo w blood lead leve l a t 5 7 month s whil e th e othe r had a highlevel , th e chil d wit hlowe r exposur e woul dP.1 3

1 0 b e expecte d t o hav e a GC I scor e tha t i s 0.6 1 standar d norma l deviat e unit s highe r (0.4 5 minu s -0.16) . Viewe d i n term s o f a standar d deviatio n o f 16 , thi s correspond s t o a differenc e o f 9. 8 points
. Additiona l Analyse s W e attempte d t o asses s th e exten t t o whic h th e association s betwee n delt a z score s and bloo d lea d and sociodemographi c characteristic s reflec t difference s i n th e skill s measure d b yMD I
and GC I score s rathe r tha n contingencie s tha t gover n th e persistenc e an d recover yo f earl ylead-associate d deficit
. T o mak e score s a t 2 4 and 5 7 mor e closel yresembl e repeate d measurements , eac h chil d wa s assigne d a "nonverbal " scor e base d
o n hi s o r he r performanc e o n a se t o f 2 2 item s typicall y administere d a s par t o f th e Bayle yScale s a t ag e 2 4 month s (#122

- 3 , 125 , 129 , 131 , 133-5 , 137 , 140 , 142-3 , 147 , 151 , 153-7 , 159

- 61) . Mos t o f thes e asses s a child' s visual-moto r coordinatio n an d integratio n skill s (e.g. , abilit yt o cop ybloc k structures , spee d
an d accurac yi n completin g formboards , perceptio n o f part-whol e relationships)
. Sample-base d estimate s o f mea n an d standar d deviatio n wer e use d t o transfor mth e tota l numbe r o f item s passe d t o a z score . Adelt a z scor e wa s compute d bysubstractin g thi s scor e fro ma sample-base d z scor e transformatio n o f a child' s scor e o n th e Perceptual-Performanc e subscal e o f th e McCarth y Scales . Th e se t o f analyse s describe d abov e wer e applie d t o thes e "delt a z : nonverbal " scores . Amon g childre n wit h highcord bloo d lea d levels , "optimal "PJ 4

1 1 postnata l lea

d exposur e an

d sociodemographi c statu s wer e associate d wit hhighe r delt a z:nonverba l score s (Tabl e 4) . I n general , the antecedent s an d correlate s o f delt a z:nonverba l score s ar e very

simila r t o thos e note d for delt a z score s base d o nMD I an

d GC I (Tabl e 3) . Additiona l table s (analogou s t o Table s 1 an d 2 ) ar e availabl e fro m th e authors .
i Thes e result s wit hdelt a z:nonverba l score s shoul d no t be viewe d a s a definitive tes t o f the hypothesi s tha t the patterno f result s observe d i nthe mai nbod y o f analyse s i s du e t o difference s i nthe mi xo f skill s measure d b y the Bayle

y Scale s an d McCarth

y Scales . T o the exten t tha t w e canevaluat e thi s hypothesis , however , the evidenc e suggest s tha t the improvemen t wit htim

e i s no t a

nartifac t o f difference s i ntesting instruments . Discussion A nassociatio nbetwee noptima l sociodemographi c characteristic s an d reduce d likelihood o f poo r outcom e ha s bee n demonstrate d fo r man y earl y nervou s syste

m insults , including lo w birthweigh t (8-9) , prenata l infection(10) , failur e t o thrive (11) , an

d Dow nSyndrom

e (12) . A

simila r phenomeno nha s bee n observe d wit hrespec t t o lea d exposur e (13-15) . I npreviou s analyse s o f ou r cohort , we reporte d tha t i nth e secon d yea r o f lif e childre nfro

m lowe r socia l classe s expresse d defici t a t lowe r level s o f prenata l lea d exposur e thandi d childre nfro m the highes t socia l clas s (16) . Thes e observation s rais e th e questiono f whethe r children' sEJ5 . •a •ssiff = s ^p^—' ^ • - • • •

' f
1 2 sociodemographi c characteristic s ar e als o related t o th e likelihood o f "recovery " fro m a defici t alread

y expressed . Th e dat a pertaining t o thi s issue ar e limited t o studie s showing tha t at-ris k infant s who receive additiona l cognitive and/o r psychosocia l stimulationfar e bette r developmentall y tha nd o childre nreceiving onl y standard medica l car e (17-19) . Throughth e firs t tw o year s o f life , th e childre ni nou r sampl e wit h"high " cor d blood lea

d level s achieve d significantl y lowe r MD I score s thandi d childre nwit hlowe r prenata l exposures . Th e associatio nbet-wee nhighprenata l exposur e an d lowe r performanc e persiste d beyon d ag e 2 , althoug

hno t a s a "mai n effect" . Rather , the degre e t o whic hdefici t persiste d varie s among subgroup s o f childre nwit hdifferen t sociodemographi c characteristic s an d postnata l lea

d exposur e profiles . Th e association s betwee n"performanc e trajectory " betwee nage s 2 4 an d 5 7 month s an

d severa l o f thes e characteristics , including hig h socia l class , highH.O.M.E . score , an d highmaterna l IQ , ar e consisten t wit hthe hypothesi s tha t "environmenta l enrichment " facilitate s th e rat e an d exten t o f "recovery " o r "compensation" . Th e mor e positive developmenta l trajectorie s displaye d b y girl s i s consisten t wit hpreviou s suggestion s tha t boy s ar e a t greate r ris k fo r man

y neuropsychiatri c adversitie s (20) . Difference s betwee nchildre nwit h"optimal " an d "suboptimal " covariat e value s tende d t o b e greate r among childre nwit hhighprenata l exposur e tha namong childre nwit hlo w o r mediu

m prenata l exposure . Childre nalread

y stressed b

y sociodemographi c disadvantag e may beP.1 6

1 3 les s abl e t o weathe r th e additiona l stres s o f "high " prenata l lea d exposure . "Les s optimal " i s somewha t o f a misnome r i n ou r relativel y advantage d cohort , referrin g onl yt o value s belo wth e media n (se e footnote s b- f i n Tabl e 3 fo r criteria)
. Mos t familie s classifie d
a s "les s optimal " woul d probabl yb e amon g th e mos t advantage d familie s i n othe r lea d stud ycohort s (15,21) . Ou r findin g tha t childre n fro mfamilie s wit h th e mos t optima l sociodemographi c characteristic s "recover " fro mth e insul t o f hig h prenata l lea d exposur e ma yb e les s relevan t t o thes e othe r cohort s tha n i s ou r findin g tha t childre n wit h les s optima l value s ma ycontinu e t o expres s som e degre e o f developmenta l deficit
. Th e rat e o f recover yma yno t b e th e sam e i n differen t cognitiv e domains
. Fo r instance , followin g nutritiona l rehabilitation , severel ymalnourishe d childre n sho wslowe r gain s i n languag e tha n i n visual-spatia l skill s (17) . Th e associatio n betwee n famil ycharacteristic s an d a child' s respons e t o stres s i s no t th e sam e fo r al l outcome s (22) . W e canno t determin e fro m ou r observation s ho wrat e o f recover yfro mearl ylea d exposur e ma ydiffe r amon g cognitiv e an d perceptua l functions
.

Summary T o date , w e hav e observe d th e followin g association s betwee n lea d exposur e an d developmen t i n ou r cohort : 1 . "High " level s o f prenata l lead exposur e (>1 0 ug/d l i n cor d blood ) ar e associate d wit h les s rapi d cognitiv e development , a tP.1 7

1 4 leas t throug

h2 4 month s o f ag e (1) . 2 . A substantia l percentag e o f childre nwit hhighprenata l exposur e contribut e t o thi s association(23) . 3 . Childre nbelo

w the media ni nsocia l clas s expres s defici t a t lowe r level s o f prenata l exposur e thand o childre nfro m mor e socioeconomically-advantage d familie s (16) . 4 . A t 5 7 month s o f age , th e mea nperformanc e o f childre nwit h highprenata l exposur e i s indistinguishabl e fro m th e mea n performanc e o f childre nwit hlowe r prenata l exposure . Performanc e a t thi s ag e is , however , inversel y related t o blood lea d leve l measure d a t ag e 2 4 month s (2) . 5 . Childre nwit hhighprenata l exposur e wh o als o experienc e highe r level s o f concurren t exposur e o r wh o have les s favorabl e sociodemographi c characteristic s (e.g. , lowe r socia l class , H.O.M.E . score , o r materna l IQ , mal e gender ) do no t improv e in performanc e betwee n2 4 an d 5 7 month s t o th e sam e exten t a s childre nwh o have comparabl e level s o f prenata l lea d exposur e bu t ar e fre e o f thes e additiona l adversities .'T-,
- P.1 8



### 1 5 Acknowledgment s
Supporte d b

y grant s HD08945 , HD17407 , HD20381 , an d P30-HD1865 5 ( a Menta l Retardatio nCente r Grant ) fro m the Nationa l Institut e o f Chil d Healt han

d Huma nDevelopment , an d gran t ES0013 8 ( a Researc h Caree r Developmen t Award t o th e senio r author ) fro m the Nationa l Institut e o f Environmenta l Healt hSciences . Othe r member s o f our researc hgroup includ e Herber t L . Needleman , Michae l Rabinowitz , Christin e Waternaux , an d Elizabet hAllred .P.1 9

• V i s Reference s

1 . Bellinger , D. , Leviton , A. , Waternaux , C. , Needleman , H. , and Rabinowitz , M . Longitudina l analyse s o f prenata l and postnata l lea d exposur e and earl ycognitiv e development . Ne wEngl . J . Med . 316 : 1037-104 3 (1987) . 2 . Bellinger , D. , Sloman , J. , Leviton , A. , Waternaux , C. , Needleman , H. , and Rabinowitz , M . Low-leve l lea d exposur e and chil d development : assessmen t a t ag e 5 o f a cohor t followe d from birth
. In : Heav

yMetal s i n th e Environment , Vo l 1 (S . Lindber g and T . Hutchinson , Eds.) , CE P Consultant s Ltd , Edinburgh , 1987 , pp . 49-53 . 3 . Bellinger , D. , Needleman , H. , Leviton , A. , Waternaux , C , Rabinowitz , M. , and Nichols , M . Earl ysensory-moto r developmen t
an d prenata l exposur e t o lead . Neurobehav . Toxicol
. Teratol . 6 : 387-40 2 (1984) . 4 . Bayley , N . Th e Bayle yScale s o f Infan t Development . Th e Psychologica l Corporation , Ne wYork , 1969 . 5 . McCarthy , D . Th e McCarth yScale s o f Children' s Abilities
. Th e Psychologica l Corporation , Ne wYork , 1972 . 6 . Rabinowitz , M. , an d Needleman , H . Tempora l trend s i n th e lea d concentration s o f umbilica l cor d blood . Scienc e 216 : 1429-143 1 (1982) . 7 . Rabinowitz , M. , Leviton , A. , an d Needleman , H . Variabilit yo f bloo d lea d concentration s durin g infancy
. Arch . Environ
. Healt h 39 : 74-7 7 (1984) . 8 . Slater , M. , Naqvi , M. , Andrew , L. , an d Haynes , K .P.2 0

1 7 Neurodevelopmen t o f monitore d versu s nonmonitore d ver ylo wbirt h weigh t infants : th e importanc e o f famil yinfluences
. J . Dev . Behav . Pediatr
. 8 : 278-28 5 (1987) . 9 . Shoham-Yakubovich , I. , and Barell , V . Materna l educatio n a s a modifie r o f th e associatio n betwee n lo wbirthweigh t an d infan t mortality
. Int . J . Epi
. 17 : 370-37 7 (1988) . 10 . Hanshaw , J. , Scheiner , A. , Moxley , A. , Gaev , L. , Abel , V. , and Scheiner , B . Schoo l failur e and deafnes s afte r 'silent ' congenita l cytomegaloviru s infection
. Ne wEngl . J . Med . 295 : 468

- 47 0 (1976) . 11 . Singer , L. , an d Fagan , J . Cognitiv e developmen t i n th e failure-to-thriv e infant : Athree-yea r longitoriiina l study . J . Ped . Psychol . 9 : 363-38 3 J1984) . 12 . Kopp , C , and Parmelee , A . Prenata l an d perinata l influence s o n infan t behavior
. In ? handboo k o f Infan t Developmen t (J . Osofsky , Ed. ) Joh n Wile y& Sons , Ne wYork , 1979 , pp.29-75 . 13 . Winneke , G. , and Kraemer , U . Neuropsychologica l effect s o f lea d i n children : Interaction s wit h socia l backgroun d variables
. Neuropsychobiolog y11 : 195-20 4 (1984) . 14 . Harvey , P. , Hamlin , M. , an d Kumar , R . Bloo d lead , behavior , an d intelligenc e tes t performanc e i n pre-schoo l children
. Sci
. Tota l Environ
. 40 : 45-6 0 (1984) . 15 . Dietrich , K. , Krafft , K. , Bornschein , R. , Hammond , P. , Berger , 0. , Succop , P. , and Bier , M . Low-leve l feta l lea d exposur e effec t o n neurobehaviora l developmen t i n earl yinfancy
. Pediat r 80 : 721-73 0 (1987) . 16 . Bellinger , D. , Leviton , A. , Waternaux , C , Needleman , H. , andP.2 1

1 8 Rabinowitz , M . Low-leve l lea d exposure , socia l class , an d infant development . Neurobehav . Toxicol . Teratol . i npress . 17 . Cravioto , J. , an d Arrieta , R . Malnutritioni nchildhood . In : Developmenta l Neuropsychiatry (M . Rutter , Ed. ) The Guilford Press , Ne

w York , 1983 , pp . 32-51 . 18 . Grantham-McGregor , S. , Schofield , W. , an d Powell , C . Developmen t o f severel y malnourishe d childre nwh o receive d psychosocia l stimulation : Six-yea r follow-up . Pediat r 79 : 247-25 4 (1987) . 19 . Rauh , V. , Achenbach , T. , Nurcombe , B. , Howell , C. , an d Teti , D . Minimizing advers e effect s o f lo w birthweight : four-yea r result s o f a

nearl y interventionprogram . Ch . Dev . 59 : 544-55 3 (1988) . 20 . Gualtieri , T . Feta l Antigenicit y an d materna l immunoreactivity : factor s i nmenta l retardation . In : Toxi c Substance s an

d Menta l Retardation(S . Schroeder , Ed.) , Monograph s o f the America nAssociationo nMenta l Deficiency , 8 , 1987 , pp . 33-69 . 21 . Ernhart , C , Morrow-Tlucak , M. , Marler , M. , an d Wolf , A . Lo

w leve l lea

d exposur e i nthe prenata l an d earl y

preschoo l periods : earl y preschoo l development . Neurobehav . Toxicol . Teratol . 9 : 259-27 0 (1987) . 22 . Masten , A. , Garmezy , N. , Tellegen , A. , Pellegrini , D. , Larkin , K. , an

d Larsen , A . Competenc e an d stres s i nschoo l children : th e moderating effect s o f individua l an d famil y qualities . J . Chil d Psychol . Psychiat . 29 : 745-76 4 (1988) . 23 . Bellinger , D. , an d Needleman , H . Neurodevelopmenta l effect s•-T^awm^mmw**-

1 9

o f Xea d i nchildren . In : HunanLea d Exposur e (H . Needleman , Ed. ) CRC Press , Inc. , Boc a Raton , FL , i npress .

### 20 Tabl e 1 Regressio ncoefficients , standard error s (SE ) an d probabilit y

value s for predictor s o f delt a z i n model s wit han

d withou t a ter

m for MD I a t 2 4 month s P.2 3



### B

Predicto r
Bloo d lea d cord a 6 month s 1 2 " 1 8 " 2 4 " 5 7 " Covariate s H.O.M.E . socia l c

l materna l materna l gender d b

*

scor e .ass c I Q ag e
ethnicity e Unadjuste d fo r MD I coefficien t S E

.0 4 -.0 2 -.0 3 -.2 2 -.2 3 -.1 7

.0 2 -.0 5 .0 0 .0 3 .0 5 -.4 1 .0 1

.0 8 .0 8 .0 9 .0 9 .1 2

.0 2 .0 7 .0 0 .0 2 .1 4 .3 1 P

.00 3 .8 1 .7 5 .01 8 .01 2 .1 6

.3 0 .5 0 .7 2 .04 5 .7 2 .1 8 Simultaneou s

Adjustmen t fo r MD I coefficien t S E

.0 3 .0 0 -.0 8 -.2 1 -.2 2 -.2 3

.0 7 -.2 2 .0 1 .0 4 .1 8 .1 5 i

.0 1 .0 7 .0 7 .0 8 .0 8 .1 0

.0 1 .0 6 .0 0 .0 1 .1 2 .2 7 P

.01 6 .9 6 .2 3 .00 7 .00 5 .02 8

.000 1 .000 2 .00 3 .00 3 .1 3 .5 7
a measure d cord blood lea d level , no t category bnatura l log o f measure d postnata l blood lea d level s c Hollingshea d Two-Facto r Index(lowe r score s represen t highe r socia l clas s d mal e code d "0" ; femal e coded "1 " e nonwhit e code d "0" ; whit e code d "1 "P.2 4

--'W» H.(kWMMpi-
. < Pp^^ff F " Tp^ytT

- ""UTr ^

2 1 Tabl e 2 Regressio n coefficients , standar d error s (SE) , and probabilit yvalue s fo r predictor s o f delt a z i n eac h cor d bloo d lea d stratu m

Predicto r Bloo d lea d cord a 6 months* 3 1 2 " 1 8 " 2 4 " 5 7 " Covariate s H.O.M.E . socia l class c materna l I Q materna l ag e gender 0
- ethnicity e coef f

.0 4 -.0 1 -.1 8 -.1 3 -.1 6 -.1 6

.0 3 -.1 6 .0 0 .0 4 -.0 4 .0 4 lo w s e

.1 1 .1 0 .0 9 .0 9 .0 8 .1 4

.0 2 .0 8 .0 0 .0 2 .1 6 .2 7 P

.7 2 .9 4 .06 3 .1 6 .05 7 .2 6

.2 6 .03 9 .4 2 .05 8 .8 1 .8 8 Cor d Bloo d Lea d

medium coef f

.1 0 .0 2 .0 3 -.3 4 -.3 1 -.1 4

.1 3 -.1 2 .0 1 .0 3 .0 2 .3 7 s e

.2 9 .1 2 .1 3 .1 5 .1 6 .2 2

.0 4 .1 2 .0 1 .0 2 .2 3 .6 0 Categor y

P

.7 4 .8 8 .8 4 .02 8 .06 5 .5 2

.00 1 .2 9 .1 7 .2 4 .9 4 .5 4 hig h

coef f s e

.0 7 .0 1 -.1 8 -.1 6 -.2 8 -.4 6

.0 7 -.3 0 .0 2 .0 5 .5 5 -.0 8 i .0 4 .1 3 .1 4 .1 6 .1 6 .1 8

.0 2 .1 0 .0 1 .0 3 .2 2 .6 3 P

.0 7 .9 5 .2 0 .3 3 .07 9 .01 3

.00 2 .00 4 .01 1 .06 1 .01 7 .9 0
a measure d cor d bloo d lea d level , no t categor y b natura l lo g o f measure d postnata l bloo d lea d level s c Hollingshea d Two-Facto r Inde x (lowe r score s represen t highe r socia l clas s d mal e code d "0" ; femal e code d "1 " e nonwhit e code d "0" ; whit e code d "1 "• V •" , 2 2 Tabl e 3

Bloo d lea d Mean s and standar d error s (SE ) o f delt a z score s o f childre nwit hhig hcor d bloo d lead : stratifie d b y postnata l lea d level s an d sociodemographi c variable s Differenc e i nGC I score s o f low/hig h o r optimal/les s optima l group s Postnata l Exposur e Grou p low medium

hig h
5 7 months a mea n

S E .4 5

.2 1 1 4

1 4 -.1 6

.2 0 9. 8
2 4 month s mea n

S E .5 5

.2 1 0 5

,1 3 .0 8

.2 3 10. 1

Covariate s H.O.M.E. 0 mea n

S E socia l class 0 mea n

S E materna l IQ ^ mea n

S E Mor e optima l

.4 9 .1 4 .4 6 .1 2 .3 9 .1 3 Les s optima l -.1 9 .1 2 -.3 7 .1 5 -.1 6 .1 4 10. 9

13. 2
8. 8

materna l age e mea n

S E 2 5

1 4 .0 1 .1 5 4. 2 gender J mea n

S E 3 4

1 4 -.1 4 .1 5 7. 7

a natura l lo g o f measure d postnata l bloo d lea d level s b- e "mor e optimal " define d a s value s abov e th e median , a s follows :

H.O.M.E. : >5 2 socia l class : clas s 1 i nth e Hollingshea d Two-Facto r Inde x materna l IQ : > 12 9 materna l age : >3 0 f "female " i s th e optima l valu eP.2 6

ail
Tabl e 4 Mean s and standar d error s (SE ) o f delt a z score s o f childre n wit h hig h cor d bloo d lead : stratifie d by postnata l lea d level s and sociodemographi c variable s

Bloo d lea d
5 7 months 0 mea n

S E Postnata l Exposur e Grou p

lo wmediumhig h 4 6 ,2 7 3 5

1 8 -.2 9

.2 7 Differenc e i n score s o f low/hig h o r optimal / les s optima l groups 3

6. 5 2 4 month s mea n 1.0 4

S E .2 6 0 2 1 6 -.0 9

.3 0 9. 8
Sociodemographic s Mor e optimal 0 Les s optima l H.O.M.E . socia l clas s materna l I Q materna l ag e gende r mea n

S E mea n S E
mea n S E
mea n S E mea n S E .6 4

.1 8 .5 3 .1 6 .4 2 .1 8 .3 5 .1 8 .4 2 .1 8 -.1 6

.1 7 -.2 5 .2 1 .0 0 .1 9 .0 9 .2 0 -.0 6 .1 9 7. 0

6. 8
3. 7
2. 3
4. 2

a difference s i n score s o n th e Perceptual-Performanc e subscal e o f th e McCarthyScale s o f Children' s Abilitie s a t ag e 5 7 months , compute d usin g sample-base d estimat e o f 8. 7 a s th e standar d deviatio n b natura l lo g d f measure d postnata l bloo d lea d level s c criteri a fo r "mor e optimal " score s ar e th e sam e a s thos e liste d i n footnote s b- f o f Tabl e 3P.2 7

2 4
Figur e 1 : Leas t square s mea n delt a z score s fo r childre n stratifie d b

ycor d bloo d lea d categor yand gender . Erro r bar s represen t on e standar d erro r (an d fo r clarit yar e shown extendin g i n on e directio n only) . Mean s wer e obtaine d bymodelin g delt a z scor e a s a functio n o f Menta l Developmen t Inde x scor e a t 2 4 month s o f age , cor d bloo d lea d categor y(low , medium , high) , chil d gender , and th e interactio n betwee n cor d bloo d lea d categor yand chil d gender . Th e differenc e o f 7. 7 point s betwee n th e scor e o f boy s and girl s wit h hig h cor d bloo d lea d level s wa s obtaine d bycalculatin g th e differenc e betwee n th e mea n delt a z score s o f childre n i n th e tw o group s (.4 8 standar d norma l deviat e units ) and expressin g i t i n term s o f performanc e o n a tes t wit h a standar d deviatio n o f 16 .2 5 P.2 8

•• C D k

_ O
IS I C 

### •fi l C D |s . ct j o f * •* * G J C D 

## 0. 6 r 

## 0. 4 0. 2 0 -0. 2 -0.4 - •female s

o males

7. 7 point s



## -0. 6 LowMediu m Hig h

Cor d Bloo d Lea d Categor yP.2 9

fc . , •- / 2 6

Figur e 2 : Leas t square s mea n delt a z score s fo r childre n stratifie d b

ycor d bloo d lea d categor yand famil ysocia l class . Erro r bar s represen t on e standar d erro r (an d fo r clarit yar e shown extendin g i n on e directio n only) . Mean s wer e obtaine d b y modelin g delt a z scor e a s a functio n o f Menta l Developmen t Inde x scor e a t 2 4 month s o f age , cor d bloo d lea d categor y(low , medium , high) , famil ysocia l clas s (above/belo wmedian) , an d th e interactio n betwee n cor d bloo d lea d categor yand socia l class . Th e differenc e o f 13. 3 point s betwee n th e score s o f lowe r clas s and uppe r clas s childre n wit h hig h cor d bloo d lea d level s wa s obtaine d b

ycalculatin g th e differenc e betwee n th e mea n delt a z score s o f childre n i n th e tw o group s (0.8 3 standar d norma l deviat e units ) and expressin g i t i n term s o f performanc e o n a tes t wit h a standar d deviatio n o f 16 .>>••>' P.3 0

2 7


## 0. 6 r

O 

# %£ N c 

## ^ o 

## ±E 

## 2 o C C M C O C D 

## 2 0. 4 0. 2 

## 0 -0. 2 -0. 4 -0. 6 •uppe r socia l clas s

o lowe r socia l clas s

13. 3 point s



## Lo wMediu m Hig h Cor d Bloo d Lea d Categor y