p. 1



# OAR Box 1131 Prepped by Ollie Stewart



### Document

Number: 

# 119)11-1-39 7
Docket Number: 

# A-83-2 2

Printed 4/21/2008 2:34:12 PM

Sheet 119 of 162P. 2 

# #-» i3r 

# jr-*» 7 TH E EFFBCT S O P CUMULATIV E HA D EXPOSUR E O N PREGNANC YOUTCOM E .AN D CHXXDftOO

D DSVBtOPMOl T DOaiN O Ttt S FIRS T FOU H YEA8 8 

## 1



# UL U Mt f ' 3 

## 199 2 EP A Ai R DOCKE

T Graham Vimpani , M O PhD 1 Pate r Baghurs t MS c Pht f Anthony J McMiehaa l M D PhD 3 Evely nRobertso nMD 4 Nai l Wig g M P Russel l Robert a M

Cli nPsych 6
Runnin g head t Por t Plri a Cohor t Study

Preaante dafr

t Advance s i nLea dResearch : laplioetion s fo r Environmenta l Healt h Conferenc e Nationa l institut e o f Environmenta l Healt hScience s

Researc hTriangl e Par k Nort hCarolin a January 9-11 , 198 9

Addres s fo r correspondence ; D r Graham

Vimpani , Departmen t o f Paediatrics , Flinder s Medica l Centre * Bedfor dPark . Sout hAustralia . 504 2 Phon e (618 ) 27 5 991 1 Fa x(618 ) 27 S 945 0

1 Departmen t o f Paediatrics , Plindar s Medica l Centre , Bedfor dPark , Sout hAustrali a Divisio no f Huma nNutrition , Commonwealt hScientifi c andIndustria l Researc hOrganisation , Adelaide , lout h Australi a Departmen t o f communit y Medicine , Universit y o f Adelaide , lout hAustrali a Departmen t o f Chemica l Pathology , Adelaid e Children' s Hospital , Nort hAdelaide , lout hAustrali a Healt hPrograms , Chil dAdolescen t an d Famil y

Healt h Service , Adelaide , Sout hAustrali a Researc hClinica l Psyoholeglat , Chil dAdolescen t an d Famil y Haalt hService , Adelaide , Sout hAuatrali a

20'39« d S33N3I0 S -ISHO D i.2121 68

. 9 Nb fP. 3
J« N0 4 '# 9 09 ; J 7 f^lnefcR S nti»*wH»
. 6 i d «iiJ'*» J

ABSTRAC T Th e Por t Piri e cohor t study i s a long-ttrm

follow-u pstud

y o f th t relationshi p betwee ncumulativ e leadexpoaure , pregnanc y outcome , an

d childhoo dnsurodevel * opment , O f 72 3 pregnancie s followe dt o birth , 60 1 an d 54 8 childre nwer e avail abl e fo r Stud

y S t age s 2 an

d4 year s respectively , Ther e wa s a statisticall y significan t doae-dcpenden t relationshi pbetwee n antenata l bloo dlea dconcentration s and th e ris ko f preter m delivery . Plscen ta l tissue s i nlst e feta l deeth e en dpreterm

aeiiverie e hadhighe r eoncent ratlon s o f lea dtha ni nuncomplicate dpregnancies , Bloo dleadconcentration s sntenatally , a t deliver y an dpostnetall y

a t 6 , I S an d2 4 aenth s o f ag e «•!' * i>«gnllv«l y correlate dwit hmenta l developmen t a t tw o years . Whe nmultipl e covariatas , includin g materna l I Q an dHOM E acor e wer e include di na multipl e regressio nmode l aninvers e relationshi p(p-0.07 ) betwee nPb B endmenta l developmen t a t 2 year a we e eviden t suggestin g tha t « chil dwit ha Pb B o f 30ug/d l a t 6 month a o f ag e woul dhav e a defici t o f approximatel y

3 Xo nth e Bayle y

MD I relativ e t o a chil dwit hPb B o f 1 0 ug/dl , Th e Pb B a t eac hage , particularl y a t age s 2 and3 year s an dth e integrate d postnata l averag e Pb B war s rslats dt o menta l abilitie s a s assesse db y th e McCarth y Scale s a t ag e fou r years . Multipl e regressio nanalyse s incorporatin g a rang e o f social , obststrl e sn dneonata l faetor s indicate dtha t subject s wit h a naverag e postnsts l Pb B o f 3 0 ug/d l ha d a genera l cognitiv e scor e 7. 2 point s lowe r (93 % confidenc e limit s 0, 3 -13,2 ; mea nscor e 107.1 ) tha nthos e wit ha n averag e concentratio no f 1 0 ug/dl . N o threshol ddos e fo r a noffse t wa s evident . ~ I t l a conclude dtha t postnata l Pb B l a inversel y relate dt o cognitiv e develop men t i nchildren , althoug hon e ous t b s circumspec t i nmakin g causa l Inference s fro m studie s o f thi s rslstlonshl pbecaus e o f th e difficultie s i ndefinin g and controllin g confoundin g effects .


# c b u*,^, ^ 'vftr

V ~- w 

# * -

\*- — $QO 

## K&
;.v.l;-tv+^r [

- \ 

# €

l^^cb , %<-rYWrt. Tu-c/e^ J f 

### r*.hs— ^'"^ Y 

### ' s 

### ' ' 

# f3 o e^Wc/^V^i ^

E0'39b d S3DN3ID S "ISHD n LZ'-Zl

68 . 9 Nb fP. 4
/"* 0 0 5 J <iJ" " ru.'Wtrs s 1'lfc.JvJ.-.K . o l 6 £?S545< 3 P.18'3 2

Tabl e 1 Assessmen t Instrument s bein g use da t 7 year s
Wechsle r Intelligenc e Scal e fo r Childre n- Revise d(WISC-R )

Britis hAbilit y

Scales : WordReedin g Tes t

Mathematic s Tss t Visua l moto r integratio ntes t (Beery ) Auditory Verba l Learnin g tes t (Rev ) Flnger-localieatlo ntea t (Gaffen ) Auditor y Reactio ntin e Dichoti c listenin g tssk s (Geffen ) Audlologlca l screenin g Connor' s Psren t en

dTsschsr s Ratin g Scale s

*0-39d d S33N3ID S "ISHD H 80:2 1 68 , 9 Nb T0 1

I o

C D
O J

0 3 ( 0 Z a JA N 0 6 'B O 09:4 8 FLINDER S PCDI0A

L £ 1 8 275945 0 P . 13/3 2

i n Teal* . 2
I D a a. Me nlea dconcentratioe

m (ug/ g dry

tissue ) togethe r wit h93 Xcoafldafic * Uadta , l a cord * aa

d placamta l tissue e o f differeo t pregnanc y

U ) 

### o z Cor d Placeota l an a Placeata l bod y Worms l 2 2 1.4 2 (0.87-2.32 ) 0.7 8 (0.61-1.00 ) 0.4 8 (0.38-0.61 ) Prematur e ruptur e 18 1.9 1 (0.94-3.88 ) 0.7 2 (0.55-0.95 ) 0.4 1 (0.32-0.53 ) of
o i n Lat e feta l death s 6- 9 1.1 8 (6 ) 2.7 3 (6 ) 0.7 6 (9 ) (0.24-5.77 ) (0.69-10.8 ) (0.44-1.30 ) Preter m birth e 2

3 2.4 7 (1.31-4.03 ) 1.2 4 (0.91-1.67 ) 0.6 6 (0.49-0.90 )JAN 6 "8 9 12:0 8 UCHS L SCIENCE S PAGE.0 6

H«tt . too ) •••o ire ) •O' O

tro ) it' O (O'O ) tt" 0 (ro > »c o (ro > •V O too > zro ir w loo's *

tr p UO' O
(rt ) ~ 1000 >
(re t ioro > (10 ) •r o (r o (00* 0 (01 ) 100*0 (O'O ) tr o (SI ) too o (10 ) cto o (to ) 01 0

' UMVIt* * % ) »nw« d •va t MMM N rt > •• » rt > rn > rt > vn r t * r» » »* » o*v » ri » rt * n o rt > C M I t * •* > if > ri » rt » t't f •' » r t * rt > ri t rt > 0'1 » ro e e-t t ri » 0*1 * ti e It* / r t t Ol f ti e t*t » rt > f t * 0*e > ro t re » or * rtt ti e r» Vtf ro t t*t » r* » 0"i > l'l» r t * r t * r o

NTt M (0*8

•r o (ri ) I0*S

art ) to o (0* 8 or o (TO ) •s/ o (O'O ) tr o
oro ) St' O Uf » isre >
(rt ) 100* 0

era ) w o >
(rt ) 100* 0 (ro > er o (it ) CD' S (tt ) I00'0> (CO ) or o (it ) (or e (O'O ) tr o ( I D too o
djavn*** ) vmA<J tit l r a m re s i i i 0*l t re t re t i n r t t r a re t et c r t t rt t r a •1 5 Off I'l l •'• f
•V rt t re t rt t r u re t r t t i t t if f m rt t rt t rt t ro t rt t r i t r u r i t r w rn rt t I' M O't f f* t rt t rt t S'i f rt t re t its rt t I K re t rt t O K rt t

•TPTJf ? n*r>*mt»M ere )

tr o (TO ) 01* 0 (Tl ) tr o (O'O ) er o tro ) O' O (ro ) oro
ere ) tr o (re ) w o *
(rt ) too o

erei ) ioro >
(re ) IO0*O> (ro ) 40 0 (CO I00'0> (ri ) I00'0> (fO ) oro

« 0 100'0 > (t'O ) •0 0 (t'O ) •to o

tlMVM*
. • > wnvAj j no t

0(0 1 tts i 1*001 rto i t*00 l •to t I' M no t I N roo t *io i roo t ro w rio t rto t i'COt 1*00 1 rto t no i rt u rto t r a ru ru t no t rto t r»et rtt t ro u rio t rto t r t t rto t rw t t'iO l *to i 0- M rto i roo t t i n rto t rto i r*o t re t I'tO I rto t rc u rto i rto i ra t
•901 *0O I rto t rto t

aW W IM* I IMlwa Q wtwlf t ar e

tr o tr o oro

. tr o tr i tr o tr o 01* 0 •r i •r o ir o ar e or o - i n er o oro tr o 8* 0 m 8* 0 tr o i n V I n o ir o ir o er o or e er o 8* 0 M O SO I tr o oro tr o N' O i n er e ir o H O W O I I I or o e n M'D tr o tr o M' O 96 0 t o 1 00 1 Ot' O C 6 0 er o

rnn«*r* n«t n i«nHv | i 1 L | •sew f «A J OM""* } aaaiuatv pme OHl e etn-ooi t etet^M i 088 * • u • H • A • H t » m » t *e o MMM Q weap o mttMMf\ •HB O tHUmtamatl frS^Biasia! ) TMsaBj" l ti e t l o t ot > t K t*-t * **-t * It-U *t > mmmmm 00 K 001-1 0 oe-i i il > " A • N 0t « «-e t tt » 9m*n p^urara n mms j aalaft U wmm n ti e I I O t ot > •W W •W'tW N >pm»4 llt W

'«w j

; .'SenoiftintoOig*a**«<MPU»AIHAVo.MO •«••««•<»w0.it*u•*«***#"»0*•*»*MA••<*-•—»~» +~~ • 

# L ^ii. ^ i.j

. ^

, . P^^smmsjaafJa l fa»m w
•ees ) aestjajti m
(t)ie1p»mt| | •W*as j SWMM N mm nmmuio nmmZL w mmtamwy
4Mn^l Q
m****jmm4

0 0 •• » -weaUMpt j

MMIHO M

Ot'^w i

• W We*J | •»tp«f l |tffMN V {iX} «1 i i^rwooM mm m»»««^pos j
m « *•» •K*9m
M*! ) •»«p » MIW M •Mipiw a

* n

••»<» ••* >
yr-«f»»- —

' •» *

9 dP. 7



### Tabli 1 0 Mea n MSCA Scores a

tag e 4 year s b y quartil e o f bloo d lea d concentratio n (a teach bloo d samplin g time ) Bloo d lea d quar t •il e
l(low ) 

### 2 3 4(high ) l(low ) 

### 2 3 4(high )
l(low ) 

### 2 3 4(high )
l(low ) 

### 2 3 4(hlgh )

I (low ) 

### 2 3 4(high ) 

## (No. ) Antenatal

aveng e



### 6. 1 8. 6 10. 5 14. 3
108. 8 109. 4 106. 7 104. 3

58. 4 57. 9 56. 5 55. 2

48. 2 49. 4 48. 0 47. 3

54. 4 54. 4 53. 9 52. 5 (534 ) 

### Tim

e o f bloo d samplin g DcUv - Umbll . 

### « y

5. 6 8. 3 11. 0 

### 16. 2
109. 5 108. 8 106. 1 104. 2
58. 0 57. 9 56. 2 55. 3
49. 1 49. 5 47. 7 46. 9
54. 9 53. 9 53. 9 52. 4 cord 

### 6

mot . 

## Mea nBloo d 4. 3 7. 3 9. 9 14. 9 

### 8. 4 12. 5 16. 9 24. 4 

### 1 3 mot , 

## a year s


### Lea d fug/d n 12. 0 18. 5 24. 4 34. 9 13. 3 18. 7 

### 24. 4 33. 7 Qoneral_Co«iiitlYfi_Index 108. 6 111. 2 110. 1 109. 3 107. 4 109. 9 104. 7 105. 9 105. 4 106. 3 104. 1 103. 6 

### 112. 4

109. 4 104. 6 102. 3 3 yea n

11. 9 17. 5 22. 5 30. 2
112. 0 109. 0 105. 7 102. 0 PMceptutUPerformane e Scor e 57. 7 57. 7 55. 2 57. 1

49. 3 48. 6 47. 7 47. 2

54. 5 54. 3 52. 9 53. 2 

### (479 ) (474) 59. 2

57. 0 55. 8 55. 6 

### 58. 5 58. 5 56. 1 54. 6 59. 5 58. 3 55. 7 54. 1 Memory, Scor e 49. 8 47. 6 48. 0 47. 2 

### 49. 2 49. 4 47. 1 47. 1 50. 9 49. 0 47. 3 45. 6 

## Moor-Sca n 55. 6 53. 6 53. 4 52. 9 (526 ) 55. 2 54. 0 53. 5 52. 8 (527 ) 55. 6 55. 4 51. 9 52. 2 (534 ) 59. 0 58. 3 56. 7 53. 6
51. 1 48. 3 47. 3 45. 9
55. 9 54. 2 53. 7 51. 5 (525 ) 4 year s Integrate d post-natal*



### 9. 8 14. 7 

### 19. 0 26. 2
111. 1 109. 2 103. 6 104. 7
58. 8 58. 7 54. 9 55. 2
50. 7 48. 3 46. 8 47. 0

t 

### 55. 0 55. 0 52. 0 52, 7 (530 ) 12. 4 17. 6 21. 7 28. 1
112. 6 108. 3 104. 0 103. 0
59. 7 58. 1 55. 6 54. 1
50. 2 48. 1 46. 9 46. 3
56. 0 54. 3 52. 1 52. 8 (463 )

* Thi s I s th e Integrate

d postnata l aveng e bloo d lea d concentratio

n concentration

. 

## <L

. T_.| 3 5 

## u ^ 5 y^zsY

ut^r^e

- er

f /lAP & ^sr/ ^ VMV.W ^ COV

A

## U** L <U~ S 

## M-vwi^ < * • > )0^ ^

i0-39b d S33N3ID S ISHO n 60:2 1 68 . 9 Ntf fP. 8 -^n T T

- ;-^ftf^nf- ' "

».i 6 l i



### Tabl e 9 Hee nMcCarth

y Scal e aeore e b

y se xandplac e o f reeldenc e

MCS A Scal e
Verba l Parcep - Quant . Memor y Moto r perfor m 

### fid

•al t 

### Boy s ( N - 236 ) Girl s ( N - 281 ) Pise * o f residence ! Por tPiri e ( N • 410) Other s ( H • 127) 32. 9 55. 6 50, 2 47. 5 52. 7 105, 7
54. 1 58. 0 50. 7 48. 6 54. 7 108. 3

53. 0 56. 7 50. 3 47. 8 53. 5 106. 3
54. 8 58. 2 51. 3 49. 5 54. 7 110. 2

Al l ( N - 537) S E 53. 5 56. 9 50. 5 46. 2 53. 8 107. 1 0. 4 0. 4 0. 4 0, 4 0. 4 0. 7

80'39« d S3DN3ID S "ISHD O 60:2 1 68

. 9 Ntf fTabl e 8 Partia l linea r regressio ncoefficient s fo r eac hbloodleadmeasur e wit han dwithou t materna l X Q aa dHOM E acor e I nth e mode ? (On e taile dsignificanc e teats )

Bloodlea

d maasur s
Averag e antenata l Deliver y Cor d 6 month s 1 3 month s 2 4 month s Xntsgrate d peetneta l Regressioncoefficient s

(chang e i nMD I pe r uni t chang e l a bloodlead[ug/dl1 ) Ignoring materna l Controllin g for

materna l X Q
-0.2 6 -0.2 1 40.1 9 40.2 7 40.0 5 40.0 7 -0.2 4 (p-0.01 ) -0.2 4 (p-0.01 ) -0.0 9 -0.0 6 -0.1 6 -0.1 2 -0,2 6 (p.0.03 ) -0.2 2 (p-0.05 ) Controlling fo r materna l I Q aad BOM B scor e -0.0 7 40.2 3 40.1 0 -0.1 6 (p-0.07 ) -0.0 3 -0.0 5 -0.1 2 (p-0.19 )

* Th e mode l contain s the 1 3 eoeloeconoelc i demographic , naonatla l an d behavioura l factor s show ninTabl e 6 . 

# \H1 IttQL- scofQ. 

# rJ^i' ^ * » *

# 1*^ '
eft ipy\ o ^

60'39W d S33N3I3 S ISHD H 0 1 :2 l 68

. 9 NU fP.1 0

» • . 2a/3 i

Tabl e 7 Beyley MD I b y materna l intelligenc e scor e (VAIS )

Materna l VAI S Kumbe r

<8 0 81-9 0 91-10 0 >10 0 refuse do r unavallabl s Al l mother e 5 0

11 7 14 5 9 4
16 3
59 2 Bayley MD I 

### 98. 3 106.7 111. 1 114. 0 108. 1
109. 3 S

B 

### 2. 7 1. 4 1. 3 1. 6 1. 0
0. 6

PI ! " ^Hr l qqr)N3T~. s -tRr-n n PI T :?.\ fifl . 9 NH TP.1 1

j..

. ..,., • tartars with BayUy MDI

Factor Sododemognphi e factor* : Materna l tg e (yean) : <2 t

22-2 9 *3 0 Pather' i iscondary educatio n(yean) ;

unknow n S 3 > 3 Mother' s rwndary educatio n(yean) ;

$ 3 > 3 Father* ! workplace :

office non-offic e Motber' i workplace :

away from hom e hom e Parenta l relationship: livin g togethe r livin g apart Motber' i antenatal surita l itatue:

single , widowed , divorce d married o rdefact o Quid' s Un annk :

flfstbor n Moood born nbssquen t Neonata l Pastors : Neonata l oxyge nus e a tbirth :

required no trequired Aega raeo na t3 nlnutes :

S t 9 o r1 0 Neonata l jaundice :

present absent Us e To rgestational age : small appropriat e large Behavioun l factor . Mouthin g activit

y a tI S momhi : „ frequen

t Inunnedli u never *•• / a.. mm chiMrt*MtvnMDt

SE

10 4 37 7 10 9 7 4 IS O 271 21 6 289 14 7 43 8 23 1 349 53 7 3 2 59 33 1 274 19 9 12 2

17 3 41 1 13 2 44 8 220 366 3 3 48 9 36

24 1 306 4 2 I0S- 7 110- 2 109- 8 99 1 108- 9 112- 3 108- 0 111- 0 111* 8 108 6 Ul- 9 107* 6 110- 2 100-0 101- 2 llfr l 109-9 169* 1 108*1

106* 7 110* 3 105* 2 U0- 4 108* 7 109- 7 101- 2 109* 6 ltl- 6

107- 9 1100 111* 7 1- S 0* 8 1- 3 1*7 1- 0 0- 9 0- 8 0- 9 W 0* 7 1-0 0* 6 

### 0 4 

### 2- 1 2- 0 0* 7 1- 0 1-0 1 3

1*0 0- 6 1*3 0- 7 M 0- 6 2- 9 6- 7 2 0

0- 9 

### 0 4 2 8

t I -39bd S30N3ID S 18HD n 0 1 :2 l 68 . 9 NW fe t • •SPf R *>.12'3 Z 

# 1

w

a a .

i n u z u t o Tabl e 5
o f Bayle y MD I with Woo

d lea d histor y

itratio m Integrate d PBB (ug/dl )
Pereietentl y

high * Intermediate ' Paraiatantl y

low * 

### 5

1 4S 1 6 2 29. 9

18. 4 10. 0 MD I

102. 2 1. 6 109. 7 0. 6 112. 2 1. 6

0 1 I o 3

w a t m to
z a

v • Pb B conceatration a l a th e highea t quartil e o f PbB distributio nO nal l thre e poataata l aamplinga (6 , 1 5 and 2 4 montha) .

' Al l excep t highaa d lo w grou p
+ PbB eoaeeatratloa e l a lowes t quartil e onal l thre e occasion sTTpir^ ' (TTirn^ ' JM 3

W < O b



### Tabl e 4

Correlation s betwee nbloo dlea deonceatretlen e a t auccessiv s sgs s an

dBayle y developmenta l indice s a t 2 4 month s

Pearso ncorrelatio n coefficien t
Bloodaaapl e 

### MD I PD I No

. Maternal t14-2 0 week

agestatio n afte r20 week

s gestatio n averag e antepartu

m a tdeliver y Child tumbilica l cor d 6 month s 1 5 month s 2 4 nonth s integrate d postnata l averag e 

### -0.0 6 -0.08 * -0.11 * -0.0 3 

### 4.0 4 -0.12 * -0.12 * -0.18 1 -0.15 1 -O.0

5 -0.0 2 -0.0 6 -0.0 2 -0.0 4 4.0 7 -0.0 2 -0.0 2 -0.0 1 50

9 56 0 56 6 52 4 520 57 5 579 . 586 494

* <0.0 5 #<0.0 1

E I -39b d S3DN3I0 S -.SHO D I I-.2 1 68

. 9 Nb ffeaampmj^B^'ammmmma i •*• • mm-^s m ICBIO C * m i-»-•-*»•• • P . » 3 2

Tabl e 3

< x a . Perccntage a daaalfle d relative , risk ao f

t o materna l bloo d a tdeliver y deliver y

ooncentretl c

U I o z 

### o if)

m i 

### o 3 Bloo d lea d («s/di )

< 8 B - 1 1 1 1 -14 . >1 4 X o f

p*'v-lm « birth *
1. 7 3. 4 A. 7 3. 8 Ctiad v

Imlmtiv * rin k
1. 0 2. 0 2. 7 3. 4 adjusted *

Relativ e rlm k
1. 0 2. 1 3. 0 4. 4

* Adjuate dfo r mother' a age , gravidity , aoela l atatua , occupatio nan d smokin g bebit e b

y multipl e logiatl c regreeelon )

C O

C D
1 0

• *:-
. MP.1 5 r TW T--rwTn r"

• '.-- #x: Tabi c 1 2 Estimate d Coefficient s o t Lo g Bloo d Lmmd Conoontretlo n fro m Simpl e an d Multipl e Regressio n Analyse s o f MSC A Score s a t th e Ag e o f Pou r Years. * Biooo SAMH. 1 OINBKA L COGNITIV E Ihot a

OMFU a MaTiA L PiacirruAk-PuraaMANc i SCALB IIMPL B PASTIA L MtMoa y SCAL B
UMPt a PASTU L eottfeliiii ±SE(t

VQIU ' Antcnoti ! (average

) Deliver y Cor d 6 M o 15 M o 2 4 M o 3 6 M o 4 8 Mo 

### Integrate d postnatal averag e -15.1*4. 7

(0.001 ) -10.4*3 9 (0.008 ) -6.1*3. 4 (0.08 ) -13.1*3. 8 «0.001 ) -14.3*3. 8 (<0.00l ) -23.8*4. 3 (<0.001 ) -23.1*4. 3 «0.001 ) -20.1*4. 1 (<0.00l ) -28.9*5. 3 (<0.00t) -1.8*5, 7

(0.75 ) -0.4*4. 5 (0.93 ) 3.3±4. | (0.42 ) -8.3*4. 4 (0.05 ) -3;3*4. 8 (0.46 ) -11.1*3. 4 (0.04 ) -13.1*5. 6 (0.02 ) -5.5*5. 1 (0.29) -13.0*7, 3 (0.04 ) -9.5*2. 7 «0.001 ) -5.1*2. 3 (0.03) -3.0*2. 0 (0.13) -7.8*2. 2 (<0.001 ) -8.2*2. 2 «0.001 ) -13.3*1 3 (<0.001 ) -13.6*2. 3 «0.001 ) -11.2*2. 4 (<0.00l ) -13.1*3. 2 «0.00l ) -4.1*3. 3

(0.22 ) 0.2*2. 7 (0.95 ) 1.6*2.4 (0.50 ) -4.8*2. 5 (0.06 ) -3.2*2. 8 (0.26 ) -6.2*3. 2 (0.03) -7.7*3. 3 (0.02 ) -4.0*3. 0 (0.18) -8.3*4. 1 (0.03) -4.8*2. 7

(0.07 ) -4.9*2. 2 (0.03) -3.0*2. 0 (0.12 ) -4.9*2. 2 (0.03) -5,3*2. 2 (0.01 ) -13.4*2. 4 (<0.001 ) -12.7*2. 4 (<0.001 ) •* • 10.3*2. 3 (<0.00l ) -13.3*3. 1 (<0.001 ) 2.0*3. 3

(0.54 ) -0.4*2. 6 (0.89 ) 2.6*2. 4 (0.27 ) -2.4*2. 5 (0.34 ) -0.5*2. 7 (0.87 ) -7.3*3. 1 (0.02 ) -7.2*3, 2 (0.27 ) -4.1*3. 0 (0.17 ) -7.9*4. 2 (0.06 ) *Tb e pettle l legrmto n eeefnclcnt t ar e fro m analyse* incorporatin g al l th e eovarlates l a Tabl e 2
. Th e P values ar c fo r aateisment i o fth e two»alded hypothea m tha t th e estimates are wo

t aers .
^ e~ U I Li^ e , ~ Meo i leJ
- TUs ~ <* - " ^ &S<> 

# r <*w
.

S I '39b d S3DN3I0 S ISHD n 2 1 '2 1 68
. 9 Ntt fP.1 6



### Birt h fc- 4 <eer d A maternal ) - placent a 0^1 » 4 g t we d .amp.asx, ^ , a , j , « t 

## 7 9 8 0 8 1 8 2 8 3 8 4 8 8 8 8 8 7 8 8 8 8 YEA R Piiur e 1 Th e Por

tPirie Cohor

tDat aCoNeetlo n8oheo\jle . 

# £v A **** * Vx-a-A j Sjjt 0 * ^ 1 »



# ^ 

# ,V1 )

9 1 '39b d S33N3ID S 18HD n 3 t :3 I 68

. 9 Nd fP.1 7



## 23 1 2 2 

# € 21 h O S 

# r 20 1 

# | 1 9 ! 

# § 1 8

& 

## * o o o 1 7 1 6 3 

# 161 - 1 4 1 3 h i •»•.•..• . •« •



## 8 

# 1 1 5 2 4 3 8 age (months

) 4 8 

# 6 0

Figur e 1 1 Coonetpl c mea

n bloo d lea d concentratio n ( w gydi ) A( td 9 3 i)5rcen t confidenc

e Intervals , b

y se xand age .

JA N 5 '8 9 isia o e t e 173945 0 - • ««.- - ~ . il-39b d S30N3ID 9 ISHD H 21:2 1 68

. 9 NttfP.1 8

••-
. -ir-Tii-'TT^wrff "

/.*
. Oi - 'Oi * OV't t <wt'«M.iv
. rM.t<Ur«
. t l c -•-•>-••* • •. J -



### G >



### 0) 12 0 n

11 0 -
100 -
9 0 -
8 0 - 

# 2 7 0 McCarthy Scale ; -• > Verba l Quantitativ

e Percep-Per

f Cognitiv e (QCI ) Memor y Motor

8 0 -
5 0 -
4 0 1 0 2 0 3 0



# Blood lea d concentratio n —r 4 0

Figur e 11 1

8 1 '39tt d S30N3ID S "ISHO n E l :2 t 68

. 9 Nb fI

P I



### fit coef l = -15S )

I U l



### . ChangefciPb B j 

# Bloo d lea d concentratio n frig/dl) z
O )

ro 1 I D
ro
c o

c o i n

i n o
z o i n

T J D o

" ) 4 Figwr e i v