Tracing the long-term legacy of childhood lead exposure: A review of three decades of the Port Pirie Cohort study

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NeuroToxicology xxx (2014) xxx–xxx

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Tracing the long-term legacy of childhood lead exposure:A review of three decades of the Port Pirie Cohort study

Amelia K. Searle a,*, Peter A. Baghurst b,c, Miranda van Hooff a, Michael G. Sawyer c,d,Malcolm R. Sim e, Cherrie Galletly f, Levina S. Clark g, Alexander C. McFarlane a

a Centre for Traumatic Stress Studies, School of Population Health, University of Adelaide, South Australia 5000, Australiab Discipline of Public Health, University of Adelaide, South Australia 5000, Australiac Discipline of Paediatrics, University of Adelaide, South Australia 5000, Australiad Research and Evaluation Unit, Women’s and Children’s Health Network, South Australia 5000, Australiae Department of Epidemiology & Preventive Medicine, Monash University, Victoria 3004, Australiaf Discipline of Psychiatry, University of Adelaide, South Australia 5000, Australiag Psychology Clinic, Flinders University, South Australia 5000, Australia

A R T I C L E I N F O

Article history:

Received 10 October 2013

Received in revised form 28 March 2014

Accepted 21 April 2014

Available online xxx

Keywords:

Low-level lead exposure

Childhood

Prospective

Port Pirie Cohort study

Review

A B S T R A C T

Several prospective cohort studies have demonstrated that childhood lead levels show small but

statistically significant adjusted associations with subsequent development in later childhood and

adolescence. The Port Pirie Cohort study is one of the few prospective cohort studies to follow

participants into adulthood. This paper reviews all childhood and adulthood findings of the Port Pirie

Cohort study to date.

Cohort members (initially, 723 infants born in/around the lead-smelting town of Port Pirie) showed a

wide range of childhood blood lead levels, which peaked around 2 years old (M = 21.3 mg/dL, SD = 1.2). At

all childhood assessments, postnatal lead levels – particularly those reflecting cumulative exposure –

showed small significant associations with outcomes including cognitive development, IQ, and mental

health problems. While associations were substantially attenuated after adjusting for several childhood

covariates, many remained statistically significant. Furthermore, average childhood blood lead showed

small significant associations with some adult mental health problems for females, including anxiety

problems and phobia, though associations only approached significance following covariate adjustment.

Overall, there did not appear to be any age of greatest vulnerability or threshold of effect, and at all ages,

females appeared more susceptible to lead-associated deficits.

Together, these findings suggest that the associations between early childhood lead exposure and

subsequent developmental outcomes may persist. However, as the magnitude of these effects was small,

they are not discernible at the individual level, posing more of a population health concern. It appears

that the combination of multiple early childhood factors best predicts later development. As such,

minimising lead exposure in combination with improving other important early childhood factors such

as parent–child interactions may be the best way to improve developmental outcomes.

� 2014 Published by Elsevier Inc.

Contents lists available at ScienceDirect

NeuroToxicology

192021222324

1. Background

The toxic effects of high exposure to lead in childhood havebeen widely recognised for over 100 years, since the detrimentaleffects of lead-based paint were documented among Australianchildren in 1892 (Gibson, 1892). However, only four decades have

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* Corresponding author at: Level 2/122 Frome Street, Adelaide, South Australia

5000, Australia. Tel.: +61 8 8313 5200; fax: +61 8 8313 5368.

E-mail address: [email protected] (A.K. Searle).

Please cite this article in press as: Searle AK, et al. Tracing the long-terthe Port Pirie Cohort study. Neurotoxicology (2014), http://dx.doi.or

http://dx.doi.org/10.1016/j.neuro.2014.04.004

0161-813X/� 2014 Published by Elsevier Inc.

passed since several large-scale prospective cohort studies beganinvestigating the potential of harmful effects at lower-levelexposures (i.e., below acute poisoning levels, <40 microgramsper decilitre (mg/dL)). Unlike previous studies, these prospectivecohort studies monitored children from a very early age (in someinstances prenatally), and were able to obtain detailed histories ofchildren’s lead exposure at multiple points during childhood, whileconcurrently measuring several other early childhood environ-mental influences (such as maternal intelligence), as well assubsequent developmental outcomes using well-validated mea-sures (e.g., Baghurst et al., 1985; Bellinger et al., 1984; Cooney et al.,

m legacy of childhood lead exposure: A review of three decades ofg/10.1016/j.neuro.2014.04.004


mailto:[email protected]


http://www.sciencedirect.com/science/journal/0161813X


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Table 1Port Pirie Cohort Q9study participation numbers across childhood and adulthood

assessments.

Assessment age Cohort na % retained

Birth 723

6 months 652 90.2

15 months 619 85.6

2 years 601 83.1

4 years 548 75.8

7 years 516 71.4

11–13 years 375 51.9

26–29 years 402 55.6

Developed from McMichael et al. (1985), McMichael et al. (1994), and Tong et al.

(1996).a The number of participants remaining in the cohort at each assessment (the

cohort n) is not necessarily the same as the number of cohort members with full

data on all model variables who were included in final analyses within particular

papers (see Table 4 for these analysis numbers).

A.K. Searle et al. / NeuroToxicology xxx (2014) xxx–xxx2

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89; Dietrich et al., 1987; Ernhart et al., 1989; Needleman et al.,90; Rothenberg et al., 1994; Wasserman et al., 1992). Theajority of these studies documented small but statisticallynificant (i.e., p < .05) associations between higher childhood

ad exposure and subsequent negative developmental outcomescluding lower intelligence, cognitive development, and neuro-ychological performance, and higher emotional and behaviouraloblems. Although these associations were typically attenuatedter adjusting for multiple early childhood covariates, manymained statistically significant.

The findings of these prospective studies, along with otherudies of low-level lead exposure (e.g., Bellinger and Bellinger,06; Canfield et al., 2003) have resulted in significant publicalth reform: the Center for Disease Control’s ‘level of concern’ogressively dropped from 60 mg/dL since 1970 to 5 mg/dL in12, and lead has been removed from petrol in all but a fewtions (Bellinger and Bellinger, 2006; Centers for Disease Controld Prevention, 2012). As a result, average lead levels havebstantially decreased in all age groups (see Bellinger andllinger, 2006).While there is now a wide evidence-base regarding low-level

ad exposure and childhood outcomes, there is much lessidence regarding the long-term legacy of childhood leadposure. The Port Pirie Cohort study is one of the few prospectivehort studies (but see also the Boston and Cincinnati studies:llinger et al., 1984; Dietrich et al., 1987) to have followedrticipants into adulthood (e.g., Baghurst et al., 1985; McFarlane

al., 2013). This cohort study is also one of the oldest of its kind,ith one of the largest initial samples and one of the longestllow-up periods; so far, up to 30 years of data have beenllected. This comprehensive body of information has amounted

approximately two dozen papers published across variousurnals and spanning 28 years. However, none of these papers hasviewed all study findings, making it difficult for readers tompile and interpret the results.The aim of this paper is to summarise and synthesise alldings from the Port Pirie Cohort study to date. This article

troduces the context and scope of the study, and reviews allblished findings from the early childhood and the recentulthood assessments. It was beyond the scope of this paper tonerate new findings through re-analysis of the Port Pirie data.

The Port Pirie Cohort study

In the context of growing public concern over childhood leadposure in the 1970s, focus turned to the regional Southstralian town of Port Pirie, located about 200 km north of the

ate’s capital city. Port Pirie is the site of the world’s largestimary lead smelter. The smelter is the town’s main industry, ands been operating in some form since 1889. The smelter is located

the northern outskirts of the town, with the town itself locatedmediately downwind. While emissions substantially reducedring the 1970s following tighter controls, they were still nottirely controlled, and a legacy of heavy metal pollution remained

the town’s topsoil and dust. Consequently, when the studyhort was recruited, Port Pirie children’s lead levels werenificantly elevated compared with other Australian children.

1. The Childhood study

The Port Pirie Cohort study began in 1979, the same year as theston and Cincinnati cohort studies (which have also continued

to adulthood) (Bellinger et al., 1984; Dietrich et al., 1987). Theain aim of the Port Pirie Cohort study was to examine thelationship between cumulative lead exposure (experienced

utero and postnatally) and early childhood growth and

Please cite this article in press as: Searle AK, et al. Tracing the long-tethe Port Pirie Cohort study. Neurotoxicology (2014), http://dx.doi.o

development. Pregnant women living in Port Pirie as well asseveral neighbouring townships were recruited, in order to assessvaried levels of lead exposure. While 831 women were recruitedprenatally across a three-year period (May 1979–May 1982), 723singleton infants (after accounting for attrition, spontaneous/induced abortions, stillbirth, twin births, and phantom and molarpregnancies, in descending order) were born into the cohort fromSeptember 1979 to October 1982 (Wigg et al., 1988). This cohortrepresented about 90% of all singleton live births in the region atthe time, estimated from registrations of births (McMichael et al.,1988).

Mothers were assessed prenatally (at 16 and 32 weeksgestation) and at delivery, and the children were assessed atdelivery, 6, 15 and 24 months, then annually until 7 years. Finally, asubsample (only including those assessed at 7 years who were notmissing 3 or more blood lead measurements) was followed-up inearly adolescence (11–13 years) (see Table 1 for participation ratesacross assessments).

Venous blood samples were collected from mothers on severaloccasions prior to and at delivery, cord blood and placenta sampleswere collected at delivery, then capillary blood lead samples werecollected from the children at each postnatal assessment (see alsoBaghurst et al., 1985; McMichael et al., 1988). Average blood leadconcentration at each assessment age for each individual child wasestimated by constructing individual plots of blood lead concen-tration against age, and dividing the area under the curve by thespecified age.

At the time of blood sampling, nurses also completed a standardquestionnaire booklet that contained questions regarding socio-demographic, behavioural, medical and social–environmentalfactors. Several of these factors were examined as potentialcovariates of lead levels, including parental education occupation(using the Daniel Scale of occupational prestige: Daniel, 1984) andsmoking status, child birth weight and gestational age, cognitivestimulation within the home environment (using the HOME scale:Bradley and Caldwell, 1984), breastfeeding duration, and mouth-ing behaviour (e.g., thumb sucking). Table 2 lists the covariates thatwere ultimately included in analysis models at each assessmentage.

Several age-specific developmental measures were usedincluding the Bayley Scales of Mental Development (BSMD) at 2years (Bayley, 1969), the Child Behavior Checklist (CBCL) at 3 years(Achenbach, 1991), the McCarthy Scales of Children’s Abilities(MSCA) at 4 years (McCarthy, 1972), the CBCL at 5 years, the BeeryDevelopmental Test of Visual-Motor Integration (Beery, 1982) andthe Wechsler Intelligence Scale-for Children-Revised (WISC)(Wechsler, 1974) at 7 years, and the WISC and the CBCL againat 11–13 years. Further methodological details can be found in the

rm legacy of childhood lead exposure: A review of three decades ofrg/10.1016/j.neuro.2014.04.004


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Table 2Covariates included within multivariate analyses at each assessment age.

Variables Assessment age (years)

0 2 4 7 11–13 25–29

PrenatalMaternal smoking status x x x x x

Number of parents who smoked x x

Maternal education x x x x x x

Paternal education x x x x x

Maternal relationship status x x x x x

Parents living together x x

Maternal age x x x x x x

Maternal occupation x x x x x x

Paternal occupation x x x x x x

Gravidity x

Maternal relative weight (corrected for height) pre-pregnancy x

Maternal alcohol consumption x

Maternal length of residence in Port Pirie x x

Maternal residence (Port Pirie/surrounds) x

Maternal race x

Maternal country of birth x

Maternal blood pressure x

Maternal prenatal medication use x

NeonatalParity x x x x x

Oxygen administration at birth x x

Apgar score at 5 min x x

Neonatal jaundice x x

Sex x x x x x

Gestational age x

Birthweight x x x x

Size for gestational age x x

Delivery type (occipital, cesaerian, other) x

ChildhoodFeeding style (6 months) x x x x

Months of breastfeeding (6 months) x x x

Mouthing activity (15 months) x x

Maternal IQ (3 years) x x x x

HOME scores (3 years) x x x x x

Age (current) x x

Family size (current) x

Months at school (current) x

School grade (current) x

Prolonged school absences (across school history) x

Maternal psychopathology (13 years) x x

Family functioning (13 years) x

AdulthoodAdverse childhood experiences (retrospective) x

Alcohol use x

Cannabis abuse (lifetime diagnosis) x

Note. While in some instances other factors were initially considered as potential confounders, they were not retained in analyses due to multicollinearity/lack of explanatory

power.

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early childhood publications from the Port Pirie Cohort study (e.g.,Baghurst et al., 1985, 1992a,b,c, 1995; Burns et al., 1999;McMichael et al., 1988; Tong et al., 1996; Wigg et al., 1988).

2.2. The Childhood Cohort

The Port Pirie Cohort was predominantly from working-class,Caucasian, and intact families. This cohort contrasted with thepredominantly Caucasian middle to upper-middle class Bostoncohort (though selective sampling ensured some variability in leadlevels), and the predominantly African-American and sociallydisadvantaged Cincinnati cohort (whose lead exposure resultedfrom their inner-city and low-socioeconomic circumstances).

Approximately 75% of the original cohort remained at the4-year assessment, and just over 50% of the original cohortremained at the 11–13 year assessment (see Table 1). Loss ofparticipants primarily occurred due to families leaving the PortPirie region (this accounted for approximately 80% of attrition). As


a result of this progressive attrition, the remaining cohortmembers showed slightly better socio-demographic profiles thanthe original cohort (see Table 3 for results of attrition analyses): bythe 7 year assessment, remaining cohort members had fatherswith slightly higher occupational prestige, were slightly morelikely to have been breastfed, and slightly less likely to have hadmothers who smoked, compared with those lost to attrition(Baghurst et al., 1992a,b,c). Similar small differences were alsoevident at the 11–13 year assessment (Burns et al., 1999).However, umbilical cord blood lead levels were similar betweenlost and retained cohort members at each assessment.

Cohort members showed considerable individual variation intheir childhood blood lead levels. On average, blood lead levels inthe cohort rose sharply across the first 15 months of life, peaked at24 months (at a geometric mean of 21.3 mg/dL, SD 1.2), and thensteadily declined to 7.9 mg/dL at 11–13 years (SD 1.7), a levelsimilar to that seen in cord blood samples at birth (see Fig. 1).This broad pattern of exposure is consistent with other early



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Table 3Attrition analyses conducted for the childhood and adulthood assessments.

Assessment age Attrition analysis

7 years Baghurst et al. (1995)Responders (n = 516) and cohort members lost to follow-up (n = 207) differed on 3 of the variables examined

Compared with those retained, non-responders had:

� Lower SES (i.e., higher Daniel score): 55.0 (SE 1.2) vs. 52.5 (SE 1.6)

� A greater proportion of maternal smoking during pregnancy: 35.3% vs. 27.2%

� A lower proportion of breastfeeding: 31.8% vs. 37.2%

11–13 years Burns et al. (1999)Responders (n = 370) and cohort members lost to follow-up (n = 353) differed on 3 of the variables examined


� Lower birthweight: 3286 g vs. 3398 g

� Younger mothers (at birth): 25.3 years vs. 26.4 years

� Fathers with a higher amount of secondary education: 3.6 years vs. 3.4 years

Tong et al. (1996)Responders (n = 375) and cohort members lost since the 7-year assessment (n = 119) differed on 1 of the variables examined


� Lower SES (i.e., higher Daniel score): 28.2 (SD 13.1) vs. 26.1 (SD 13.6)

25–29 years McFarlane et al. (2013)The final analysis sample (n = 210) and the remainder of the birth cohort (n = 513) differed on 6 of the variables examined

Compared with the analysis sample, the remainder of the birth cohort had:

� Lower birthweight: 3333.5 g (SD 541.1) vs. 3480.9 g (SD 482.8)

� Lower gestational age: 39.7 weeks (SD 1.9) vs. 40.0 weeks (SD 1.7)

� Younger mothers (at birth): 25.6 years (SD 4.8) vs. 26.4 years (SD 4.4)

� Shorter maternal residence in Port Pirie: 11.9 years (SD 10.8) vs. 14.0 years (SD 11.1)

� A greater proportion of paternal smoking during pregnancy: 55.5% vs. 42.1%

� A greater proportion of maternal smoking during pregnancy: 33.5% vs. 20.2%

Note. Further detail can be found in the original papers referenced within the table.

Figad

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Ad


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ospective studies (e.g., Bellinger et al., 1992; Dietrich et al., 1991,93, Lanphear et al., 2005), supporting the notion that lead intakehighest during toddlerhood (probably due to the combination ofcreased mobility and hand-to-mouth activity). However, whileerage blood lead levels measured at each assessment were

ilar to those in the Cincinnati cohort (Dietrich et al., 1991,93), they were higher than those in the Boston cohort (Bellinger

al., 1992). In the Port Pirie cohort, average blood lead levels ofales and females were quite similar at most assessment ages;wever, at the 11–13 year assessment, levels were slightly higher

r males (8.4 mg/dL, 95% CI 8.0–8.8) than for females (7.5 mg/dL,% CI 7.1–7.9), and this difference was statistically significant

< .02). Cumulative lifetime blood lead levels did not substan-lly or significantly differ between males and females at anysessment point (Table 4).

3. The adult follow-up

The first adult follow-up of the Port Pirie Cohort occurredring 2008–2009, when cohort members were aged 25–29 years

d, and approximately 15 years after they were last assessed
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. 1. Blood lead profile of Port Pirie Cohort members for all childhood and early

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rs.

apted from Baghurst et al. (1995) and Tong et al. (1996).


(predominantly through their parents) in early adolescence.Researchers attempted to recontact all 723 original cohortmembers. Four had died, and eight were deemed ineligible, aslow cognitive functioning prevented them from providing fullyinformed consent and/or completing the research protocol.Altogether, 402 participated, with 340 completing both aquestionnaire and an interview (47% retention). Of the 62 peoplewith partial data, 42 completed the diagnostic interview only, 16completed the questionnaire only, and 4 completed the prelimi-nary demographic interview only. While some explicitly chose tocomplete one component due to time constraints, others providedfull consent yet only completed one response mode (i.e., telephoneor mail) and could not be followed up.

At the time of the adult assessment, cohort members completed anumber of self-reported measures, including the Adult Self-Report(ASR: Achenbach and Rescorla, 2003), assessing levels of beha-vioural, emotional and social problems, the Community Assessmentof Psychic Experiences (CAPE: Stefanis et al., 2002) assessing sub-clinical psychotic symptoms, the Alcohol Use Disorders Identifica-tion Test (AUDIT: Babor et al., 2001) assessing alcohol consumptionand problems, and the Adverse Childhood Experiences survey (ACE:Felitti, 2009) assessing traumatic childhood events. Various socio-demographic characteristics were also assessed, including educa-tional attainment, employment, and household structure. Addition-ally, cohort members completed the Composite InternationalDiagnostic Interview (WMH-CIDI 3.0: Haro et al., 2006) to assesslifetime and 12-month prevalence of mental disorder. Othermeasures assessed but not yet analysed include the InternationalPersonality Disorder Examination (IPDE) screening questionnaire(Loranger et al., 1994) assessing personality disorder symptoms, andThe Symptom Interpretation Questionnaire (SIQ; Robbins andKirmayer, 1991) assessing somatisation. While IQ testing inadulthood was originally planned, it did not occur due to unforseenlogistical issues.

As was seen at the 7- and 11–13-year assessments, cohortmembers participating in adulthood showed slightly better socio-demographic profiles compared with those lost to attrition onseveral variables, including having larger birth weight and



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Table 4A summary of significant Port Pirie Cohort study findings regarding childhood and adulthood outcomes of lead exposure.

Study Age (years) Analysis n Lead exposure measure Developmental outcome Adjusted effect sizea

Childhood outcomesMcMichael et al. (1986) 0 749b Maternal blood lead Pregnancy outcome Risk of preterm birth significantly increased by a factor

of 2.84.

Baghurst et al. (1991) 0 69b Placental body lead Pregnancy outcome Placental body lead was marginally higher for stillbirths

(2.73 mg/g, 95% CI 0.69–10.8) and preterm births

(1.24 mg/g, 95% CI 0.91–1.67), compared with 22

‘normal’ pregnancies (0.78 mg/g, 95% CI 0.61–1.00).

Wigg et al. (1988) 2 595 6 month blood lead Cognitive development

(BSMD scores)

BSMD mental development scores decreased by 1.6

points (p = .07).

McMichael et al. (1988) 4 537 Childhood average

(to age 4) blood lead

Cognitive development

(MSCA scores)

MSCA GCI scores significantly decreased by 15 points

(SE = 7.3).

McMichael et al. (1992) 2 and 4 548 Childhood average


Cognitive development

(BSMD scores

at 2 years, MSCA

scores at 4 years)

In stratified analyses, MSCA GCI scores significantly

decreased by 4.15 points for females, but did not

significantly decrease for males (at 0.4 points).

Baghurst et al. (1992a,b,c) 7 494 Several childhood

average blood lead

measures up to

age 3

IQ (WISC-R scores) Full-scale IQ scores significantly decreased from 5.5

points to 6.4 points (depending on the blood lead

measure).

Verbal IQ scores significantly decreased from 4.4 points

to 5.3 points (depending on the blood lead measure).

Baghurst et al. (1995) 7 494 Childhood average


Visual-motor integration

(Beery VMI scores)

VMI scores significantly decreased by 0.8 points.

McMichael et al. (1994) 7 262 Tooth lead IQ (WISC-R scores) Full-scale IQ significantly decreased by 5.1 points

following a 3 to 22 ppm increase in tooth lead (spanning

90% of the sample).

Tong et al. (1996) 11–13 375 Childhood average

(to 11–13 years)

blood lead

IQ (WISC-R scores) Full-scale IQ significantly decreased by 3.0 points.

Tong et al. (2000) 11–13 375 Childhood average

(to 11–13 years)

blood lead

IQ (WISC-R scores) Full-scale IQ significantly decreased by 7.4 points (95% CI

-13.1 to -1.7) for females, whereas it decreased by only

2.6 points (95% CI -8 to 2.9) for males, which was not

significant.

Burns et al. (1999) 11–13 322 Childhood average

(to 11–13 years)

blood lead

Mental health problems

(CBCL scores)

For males, total problems scores significantly increased

by 2.6 points, and externalising scores by 1.75 points.

For females, total problems scores significantly

increased by 3.1 points, and internalising scores by 1.05

points.

Adulthood outcomesMcFarlane et al. (2013) 25–29 210 Childhood average


Mental disorder

(CIDI diagnoses)

For females (n = 127), the likelihood of a lifetime

diagnosis of specific phobia increased by a factor of 3.39

(95% CI 0.90, 11.81, p = .06)

McFarlane et al. (2013) 25–29 210 Childhood average


Mental health problems

(ASR scores)

For females (n = 127), anxiety problems scores increased

by 1.2 points (SE = 0.6, p = .06)

Galletly et al. (2012) 25–29 210 Childhood average


Psychosis symptoms

(CAPE scores)

CAPE depressive symptom scores significantly

decreased by 0.9 points (95% CI = �1.7 to �0.2)

a Except where otherwise indicated, the adjusted effect size is that associated with a hypothetical blood lead increase of 10 mg/dL, after adjusting for early childhood

covariates. BSMD, Bayley Scales of Mental Development; MSCA, McCarthy Scales of Children’s Abilities; GCI, General Cognitive Index on the MSCA; IQ, intelligence quotient;

WISC-R, Wechsler Intelligence Scale for Children-Revised; CBCL, Child Behavior Checklist; ASR, Adult Self-Report; CIDI, Composite International Diagnostic Interview; CAPE,

Community Assessment of Psychic Experiences.b The sample size for this analysis refers to pregnancies, rather than live born children.


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gestational age, higher levels of stimulation in the home environ-ment, and parents who were less likely to have smoked during theirchildhood (McFarlane et al., 2013) (see Table 3).

3. Results to date

In this section, we review all Port Pirie cohort results relating tolead exposure.1 Studies are grouped first according to their broadassessment stage (i.e., childhood or adulthood), and then accordingto the type of broad developmental outcome being considered(e.g., cognitive development). Findings that are common toseveral studies are addressed more generally in the section‘Overall synthesis of findings’, to avoid repetition. All statistically

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1 Several articles generated from the Port Pirie Cohort study do not focus on lead

exposure and related developmental outcomes (e.g., Baghurst et al., 1992a,b,c;

Sawyer et al., 1996); these studies are beyond the scope of this review.


significant (i.e., p < .05) or marginally significant (i.e., p < .10)results are summarised in Table 1 (with non-significant resultskept to the text). In this table, we have described the size of effect inrelation to a hypothetical 10 mg/dL increase in blood lead in mostinstances (excepting the results of ANOVAs, and of the study usingtooth lead), to serve as a point of comparison between studies. Thisparticular range is used consistently within most Port Pirie articlesas well as in other international studies (e.g., Lanphear et al., 2005),and spans a wide range of blood lead levels.

3.1. Determinants of blood lead

Throughout childhood and early adolescence, blood lead levelswere associated with several social and demographic factors,including residential area (with children living closest to thesmelter having higher lead levels), the nature and locationof paternal employment (with children of fathers employed in



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ue-collar smelter jobs having higher lead levels), lower cognitiveimulation within the home environment, parental smoking, andouthing behaviour (e.g., finger sucking, dirt eating) in toddler-od (Baghurst et al., 1985, 1987, 1992a,b,c, 1999). Some of theseriables might plausibly have acted as proxies for other factors,ch as socio-economic disadvantage, given that characteristicscluding smoking and low parental cognitive stimulation areore likely to occur in contexts of socioeconomic disadvantage.

2. Childhood developmental outcomes

2.1. Lead exposure and pregnancy outcomes

Maternal lead exposure during pregnancy was associated witho of the eight pregnancy outcomes studied, among the 749egnancies that were followed to birth (of at least 20 weeksstation), and the 23 pregnancies resulting in spontaneousortion before the 20th week (Baghurst et al., 1991; McMichael

al., 1986). Specifically, maternal blood lead levels at delivery (butt prenatally) were associated with a small but significant

crease in the risk of preterm (i.e., <37 weeks) deliverycMichael et al., 1986). Additionally, in univariate analyses, lead

the placental membranes (but not the placental body) wasbstantially higher in the few pregnancies resulting in stillbirth

= 6) and preterm birth (n = 23), compared with a random sample 22 ‘normal’ pregnancies, with these results approachingnificance (i.e., p < .10) (Baghurst et al., 1991). However,

aternal blood lead was unrelated to placental lead, suggestingat placental lead was determined by factors additional toaternal lead exposure. The remaining pregnancy outcomes forhich no association with maternal lead levels was detected wereontaneous abortion, low birth weight, intrauterine growthtardation, premature rupture of the membranes, congenitalomalies, and difficulties conceiving. Cord blood levels wereghtly but non-significantly elevated in pregnancies resulting ineterm birth or premature rupture of membranes, compared withe normal pregnancies.

2.2. Lead exposure and cognitive functioning

2.2.1. Early cognitive development. At 2 years of age, post-natalut not cord, or delivery) and average antenatal blood lead levelsowed small but significant linear inverse associations withental (but not psychomotor) subscale scores on the Bayley Scales

Mental Development (BSMD) (Wigg et al., 1988). Thesesociations were attenuated after adjusting for 13 early childhoodvariates, but remained significant for blood lead levels measured

6 months, and the integrated childhood (i.e., to 2 years) average.rther adjustment for HOME scores (measuring cognitive

imulation in the home environment) attenuated the association the point where the only association that remained significantas between blood lead at 6 months and BMSD mentalvelopment scores.At 4 years of age, post-natal (but not cord), delivery and average

tenatal blood lead levels showed small but significant linearverse associations with scores on the General Cognitive IndexCI) of the McCarthy Scales (MSCA), as well as the Perceptual-rformance and Memory subscales (McMichael et al., 1988).justing for 16 early childhood covariates substantially attenu-

ed associations, but associations remained significant for thetegrated post-natal average blood lead, and for several of thestnatal blood lead levels.The lead-associated cognitive deficits at 4 years appeared to be

ronger than those seen at 2 years (see Wigg et al., 1988).rthermore, the change in each child’s average blood leadncentration between the first 2 years and the second 2 years

life was unrelated to the change in rank-ordered cognitive


development (between the BSMD and the MSCA) between 2 and 4years of age.

Potential modifiers of the associations between lead levels andcognitive development that were examined included gender,parental smoking, birth weight, infant feeding style, SES (measuredby the father’s occupational prestige), and cognitive stimulation inthe home environment (using the HOME) (McMichael et al., 1992).However, only one significant modification effect was found;covariate-adjusted associations between childhood average (to 4years) lead levels and MSCA GCI scores were stronger for femalesthan for males. While a similar gender-stratified association wasseen for BSMD mental scores at 2 years, it was smaller and non-significant. The slightly stronger association observed betweenblood lead levels and cognitive development at lower levels of SESwas also not significant (McMichael et al., 1992).

3.2.2.2. Childhood intelligence. From the 7-year assessment on-wards, intelligence quotient (IQ) could be measured withreasonable reliability using the Wechsler Intelligence Scale forChildren-Revised (WISC-R), compared with earlier ages (anddevelopmental stages) where more general measures of cogni-tive/mental development needed to be used.

Small but significant linear inverse associations were documen-ted between all antenatal and postnatal blood lead levels and verbal,performance, and full-scale IQ scores at 7 years, measured using theWISC-R (Baghurst et al., 1992a,b,c). After adjusting for 12 earlychildhood covariates, associations were attenuated but remainedsignificant for verbal and full-scale IQ (but not performance IQ) forseveral of the postnatal blood lead measurements. These associa-tions were strongest for the lifetime average at 3 years blood leadmeasure. Although differences between sexes were not statisticallysignificant, it appeared that females were more vulnerable thanmales to lead-associated IQ deficits. Of the 10 WISC-R subscalescores, only 2 were significantly associated with blood lead levels inadjusted analyses: the information (i.e., general knowledge) and theblock design subscales (testing perceptual, spatial, and visual-motorcapabilities).

Cumulative lead exposure at 7 years was additionally measuredby analysing lead levels from children’s naturally shed deciduousincisor teeth (which store lead over a period of many years)(McMichael et al., 1994). The lifetime average (to 7 years) leadlevels from blood and from teeth were correlated at .78. Consistentwith the blood lead findings (Baghurst et al., 1992a,b,c), lead levelsfrom teeth showed small but significant linear inverse associationswith verbal, performance, and full-scale IQ scores, and most of thesubscale scores. While these associations were substantiallyattenuated after adjusting for 14 early childhood covariates, theassociations with full-scale IQ and the block design subscalepersisted. There were no statistically significant interactions withgender, SES, HOME scores, and maternal intelligence. Although theadjusted regression coefficients for blood lead and for tooth leadwere not directly comparable, children in the top and bottom leadexposure tertiles for the two measures showed quite similar IQdifferences.

3.2.2.3. Visual-motor functioning. As further evidence for a visual-motor deficit, small but significant linear inverse associations wereseen between all blood lead measures and scores on the BeeryDevelopmental Test of Visual-Motor Integration (Baghurst et al.,1995). After adjusting for up to 12 covariates chosen using the‘change-in-estimate’ criterion (i.e., a �10% change in the analysisparameter estimate upon covariate control, see Tong and Lu, 2001),these associations were attenuated but persisted, particularly forblood lead levels at 3 and 4 years of age, and for the lifetime (to 7years) average. Adjusting for IQ scores made no appreciabledifference to these associations. Furthermore, these associations



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appeared to be stronger for females (1.99 � 0.77 VMI points per logunit of blood lead compared with �0.92 � 0.79 for males), and forchildren from lower socioeconomic backgrounds (�2.01 � 0.82 VMIpoints per log unit of blood lead compared with �0.97 � 0.77 formore advantaged children); however, these differences were nottested statistically.

3.2.2.4. Early adolescent intelligence. There were small but signifi-cant linear inverse associations between all antenatal andpostnatal (but not cord) blood lead levels and verbal, performance,and full-scale IQ scores at 11–13 years, measured using the WISC-R(Tong et al., 1996). After adjusting for 18 early childhood covariateschosen using the ‘change in estimate’ criterion (but especially afteradjusting for HOME scale scores, SES, and maternal intelligence),associations were substantially attenuated but remained significantbetween most of the postnatal blood lead measurements and bothverbal and full-scale IQ. Of the 12 IQ subscales, 4 were significantlyrelated to lead exposure in adjusted analyses: the information,arithmetic, block design and maze subscales (which assess visual-motor integration, attention, concentration and memory). Adescriptive examination suggested the lead - intelligence associa-tions appeared greater in subgroups across the four variables tested(gender, SES, maternal intelligence, and HOME scores). Specifically,the children who appeared more susceptible to lead-associateddeficits were females (compared with males), those from lowersocioeconomic backgrounds (compared with than those from moreadvantaged backgrounds), those whose mothers had lower intelli-gence (compared with higher maternal intelligence), and those withlower cognitive stimulation in the home environment (comparedwith those with higher levels of stimulation). While the statisticalinteraction term was significant for SES and gender in bivariateanalyses, these effect modification patterns did not remainstatistically significant within adjusted analyses (Tong et al., 2000).

Individual change in blood lead levels across the earlychildhood assessments was unrelated to change in cognitivedevelopment, and one interpretation of this is that the negativeimpact of early lead exposure may not be reversible (Tong et al.,1998). However, given the great statistical power (in particular,sample size) that would be needed within regressions to find thesmall effect seen as statistically significant, this study was almostcertainly underpowered (although power analyses were notreported within the manuscript). Such limited power may haveprevented any real associations between changes in lead levels anddevelopment from being detected.

3.2.3. Lead exposure and mental health problems

While research on the Port Pirie Cohort has mainly focussed oncognitive developmental outcomes, a smaller body of evidence haslinked children’s mental health problems with cumulative leadexposure.

At 11–13 years old, average lifetime (i.e., to 11–13 years) bloodlead levels were significantly related to subsequent mother-reported emotional and behavioural problems on the CBCL in earlyadolescence; however, these associations appeared to be gender-specific (Burns et al., 1999). That is, after adjusting for approxi-mately 16 covariates, there were small but significant linearinverse associations between lifetime lead levels and totalproblems and externalising problems, as well as the delinquentand aggressive behaviour subscale scores, for males. In contrast, forfemales, small but significant linear inverse associations were seenbetween lifetime lead levels and total problems and internalisingproblems scales, as well as the withdrawn, anxious, thoughtproblems, attention problems, and aggressive behaviour subscales.Nonetheless, as these lead associations were small, the emotional/behavioural problems of cohort members with higher lead levelswere well below levels of clinical concern.


It is worth noting that these lead exposure associationsremained after adjusting for toddlerhood mouthing behaviour(e.g., finger sucking, pica) in subsidiary analyses. These analysesattempted to address the possibility of reverse causation (i.e., thatproblem behaviour causes higher lead exposure) whereby infantbehavioural problems leading to increased mouthing behaviour intoddlerhood might then lead to ingestion of a greater amounts oflead, thus reflected in higher cumulative lead levels up to 11–13years. Thus, results suggested the lead - behaviour associationcould not be considered spurious due to mouthing behaviour. Evensupposing that these causal hypotheses were incorrect and leadexposure actually caused behaviours like pica, then the leadassociation was still significant even under conditions of over-control.

Additionally, although only published in limited detail,associations between blood lead and mental health problems atearlier ages have also been briefly described (McMichael et al.,1992; Roberts et al., 2001). After adjusting for multiple earlychildhood covariates, significant positive associations were foundbetween post-natal blood lead levels (measured from 15 monthsonwards) and mental health problems (using the CBCL) at the 5-year assessment for the 480 remaining cohort members, but theseassociations were only seen for females, and not for males (Robertset al., 2001). This gender-specific association was also seen for theeight CBCL symptom subscales. As mentioned briefly byMcMichael et al. (1992), a similar pattern was seen at the 3-yearassessment, where the positive associations between blood leadlevels and the occurrence of CBCL behavioural disorders wereconsiderably stronger in females than in males.

3.3. Adulthood outcomes

3.3.1. Mental health problems/disorder

Although 340 participants completed interviews and ques-tionnaires in adulthood, analyses of adult outcomes were limitedto a sample of 210 of these participants who had full data on theexposure, outcome and covariate measures.

Among females, average childhood (to age 7 years) blood leadlevels showed small significant positive linear associations withlifetime diagnoses of drug and alcohol abuse and social phobia onthe CIDI (with results for specific phobia approaching significance),and with levels of anxiety, somatic and antisocial personalityproblems on the ASR (McFarlane et al., 2013). However, adjust-ment for childhood covariates – but particularly stimulationwithin the home environment at 3 years of age, using the HOMEscale – rendered all of these associations non-significant, with onlytwo adjusted associations approaching significance (i.e., p = .06, forspecific phobia and anxiety problems). In some instances, largeradjusted effects were observed for the early childhood covariates(including HOME scores, maternal education, and paternaloccupation) than for lead. No significant or sizeable unadjustedor adjusted associations were seen for males.

3.3.2. Sub-clinical psychotic symptoms

In unadjusted analyses, average childhood (to age 7) blood leadlevels showed small and non-significant linear negative associa-tions with positive, negative and depressive sub-clinical psychoticsymptoms on the CAPE for males (standardised coefficients �.10 to�.13) (Galletly et al., 2012). In contrast, for females, lead levelsshowed near-zero associations with negative and depressivesymptoms, but a small and significant positive association withpositive symptoms (standardised coefficient of .25, p < .01).Within combined-gender regressions that adjusted for severalchildhood (e.g., maternal mental health problems) and adulthood(e.g., alcohol use) covariates, neither lead nor its interaction withgender was a significant predictor of positive symptoms. However,



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ere was a small negative adjusted association between leadvels and depressive symptoms, which may have reflected the

all unadjusted association seen among males. Despite itsatistical significance, this effect was very small, and is unlikely

have any clinical relevance. Instead, maternal mental healthoblems at the 11–13 year assessment, retrospective reports ofrly childhood trauma, and adult substance abuse tended to showe largest adjusted associations with sub-clinical psychoticmptoms.

Discussion

1. Overall synthesis of findings

Despite spanning an approximately 30-year period, consideredgether, the findings of the Port Pirie Cohort study tell aasonably cohesive story. First, in all instances, measures ofst-natal rather than pre-natal lead exposure were moreedictive of later developmental outcomes, with the most highlyedictive measure being cumulative exposure across childhoodd early adolescence (Baghurst et al., 1992a,b,c, 1995; McFarlane

al., 2013; McMichael et al., 1988; Tong et al., 1996; Wigg et al.,88). This, coupled with the fact that decreases in lead levelsross childhood did not predict subsequent changes in develop-ental status (McMichael et al., 1988; Tong et al., 1998), suggestsat long-term lead exposure better predicts developmentaltcomes, and that associations between early childhood leadposure and subsequent developmental outcomes may bersistent rather than transient.Second, similar to many (though not all) other prospective

hort studies, the association between lead and developmentaltcomes was best described as linear, where developmentalficits steadily increased across increasing lead levels, with no

ear evidence of a threshold of effect (Baghurst et al., 1992a,b,c;cFarlane et al., 2013; McMichael et al., 1988; Tong et al., 1996;igg et al., 1988). While in some instances the associationpeared to differ slightly in slope at the lowest and highest levels

lead exposure (Baghurst et al., 1992a,b,c; McFarlane et al., 2013),ere were generally very few observations at these levels,eaning there was much greater error around these estimates.ithout greater numbers available to verify such slight trends,ere is a danger of ‘over-fitting’ the data by assuming non-linearsociations.One of the most consistent findings throughout the Port Pirie

hort is that females appeared more vulnerable to lead-associatedvelopmental deficits, compared with males. Regardless of

atistical significance, this pattern of female vulnerability wasen across cognitive and mental health outcomes, and spannedildhood, early adolescence and adulthood (Baghurst et al.,92a,b,c, 1995; Burns et al., 1999; McFarlane et al., 2013;cMichael et al., 1992; Tong et al., 1996). Despite its internalnsistency, this finding is at odds with much of the internationalospective research, which has generally shown a male vulnera-lity to lead-associated deficits, predominantly in cognitive anduropsychological development (e.g., Bellinger et al., 1985; Cecil

al., 2011; Dietrich et al., 1987; Ernhart et al., 1989). However, atast one other study has shown a greater susceptibility amongmales (Rabinowitz et al., 1991), some studies have found nonder differences (e.g., Bouchard et al., 2009), and others did noten examine gender as a potential effect modifier (e.g., Fergusson

al., 1993). Furthermore, a female lead susceptibility has beenmonstrated in animal research (e.g., Abazyan et al., 2013;rgolini et al., 2006). Given this disparity between studies,oader conclusions regarding gender susceptibility to lead should

made with caution. It is possible that circumstances specific toe Port Pirie sample may explain why females have consistently


appeared more vulnerable. While this was not further exploredstatistically, several reasons for the ‘female susceptibility’ specificto the Port Pirie cohort were postulated based on previousliterature, including the wider range of lead levels and the earlytiming and chronicity of lead exposure in the Port Pirie cohort, aswell as other co-occurring environmental circumstances. A moredetailed discussion of these possibilities is provided in the originalpublications (see McMichael et al., 1992; Tong et al., 2000).

While no other significant effect modifiers were found, thesame non-significant trends were seen across several reportswhich were in the expected directions, and were also consistentwith significant effects seen in the international literature (seeWeiss and Bellinger, 2006). Specifically, participants who appearedmore vulnerable to developmental deficits following lead exposureincluded those from lower socioeconomic backgrounds, thosewhose mothers had lower IQ, and those with lower cognitivestimulation in the home environment (e.g., McMichael et al., 1992;Tong et al., 1998). Interaction effects within regression arenotoriously underpowered, and ‘real’ interaction effects may notbe found statistically significant due to factors including smallsample size, low variability in both the independent and modifiervariables, and low numbers within subgroups (McClelland andJudd, 1993). Whether this was indeed the case for the Port PirieCohort remains to be seen.

The Port Pirie results together provide incremental evidence forthe apparent negative effects of low-level lead exposure, which isfurther substantiated by the vast body of international prospectiveresearch. Nonetheless, as observational studies they still areunable to unequivocally conclude that lead exposure causes

developmental deficits, as residual confounding and reversecausation may still be operating within this study design. However,it seems unlikely that reverse causation can explain theseassociations, where young children with developmental deficitssuch as lower IQ and higher behavioural problems inhale/ingesthigher quantities of lead due to increased mouthing behaviour.This is because IQ in early childhood was unrelated to later leadlevels in early adolescence (Tong et al., 1996), and adjusting formouthing behaviour in toddlerhood did not attenuate the leadassociations with early adolescent behavioural problems (Burnset al., 1999). Furthermore, the possibility of a causal association isgiven credence when considering the Port Pirie evidence alongsidethe numerous other prospective cohort studies of the last threedecades that have consistently demonstrated small negativeassociations with IQ, cognitive functioning and emotional andbehavioural problems, which have been confirmed within meta-analyses (Lanphear et al., 2005; Marcus et al., 2010), as well as thevarious animal experiments demonstrating lead’s neurotoxiceffects (e.g., Guilarte et al., 2003; Virgolini et al., 2006).

It is notable that across several developmental outcomes, andfor both childhood and adulthood assessments, the lead associa-tion has always been small, and even more so following covariateadjustment. This means that any lead-associated deficits are morenoticeable at a population rather than an individual level;however, even small deficits are concerning at a population levelgiven that a slight shift in the population mean on a developmentaloutcome (e.g., IQ) will result in a substantially greater proportionof children scoring in ‘abnormal’ ranges and requiring intensiveservices and support. While not all of these small adjusted effectshave remained statistically significant, we can speculate thatfactors such as sample size and statistical power may at least partlyaccount for this, particularly for the latter assessments. Forexample, while none of the associations seen in adulthoodremained significant following confounder adjustment, thisassessment had the lowest sample size (and thus would alsohave the least statistical power) of all of the cohort analyses,especially when analyses were stratified by gender. Thus, we



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would assume that power to detect such small effects as significantwithin multivariate regression analyses would be limited based onthis sample size. Specifically, the standardised regression coeffi-cient for the association between lead exposure and adult anxietyproblems among females of .20 was only approaching significance,even though its effect size was not trivial, and is entirely consistentwith the statistically significant effect sizes documented in earliercohort analyses.

In all analyses, adjusting for potential confounders has been anextensive process, which often involved adjusting for up to 16different early childhood factors. It has been acknowledged thatthis is, if anything, an overly cautious approach to the examinationof lead-associated deficits, given the exact role of these ‘con-founders’ is not certain. For example, factors such as stimulationwithin the home environment may themselves partly contribute toa child’s lead burden: parents who pay less attention to creatingstimulating and child-friendly environments may also pay lessattention to minimising childhood lead exposure through regularhousehold cleaning, and without close adult supervision, childrenmay then have greater interaction with lead-contaminatedhousehold objects. If such scenarios were true, such covariatesshould not be considered to explain any lead effects on childdevelopment. If the lead effect was over-adjusted, it is possible that‘real’ effects might be somewhat stronger than those presented.However, generally only a handful of the early child covariatesattenuated most of the lead effect; beyond these few variables, theinclusion of additional covariates did not have a large impact onresults (Baghurst et al., 1995; McFarlane et al., 2013; Tong and Lu,2001).

While the exact number of covariates included in analyses hasdiffered somewhat between assessments, the overall patternsuggests variations on a theme, with the same core shortlist ofearly childhood factors identified. Across assessments, socioeco-nomic status (using father’s occupational prestige), stimulationwithin the home environment (using HOME scores), breastfeedingstatus, parental smoking, and maternal IQ were consideredsignificant covariates as they substantially attenuated the leadcoefficients, as were (to a lesser extent) maternal age at birth,marital status, birth weight, and gestational age. This list is broadlysimilar to other prospective studies (e.g., Bellinger et al., 1985;Dietrich et al., 1992; Lanphear et al., 2005). These results suggestthat lead exposure and aspects of the broader early childhoodenvironment may not be independent, and thus need to beconsidered together when examining their associations withsubsequent developmental outcomes (Weiss and Bellinger,2006). Solely considering the discrete role of each factor may beless relevant from an intervention perspective: unique effects thatare determined through statistical adjustment do not translate toreal-life circumstances, where factors co-occur (to varyingdegrees) in a child’s life, and so are inextricably entwined (Weissand Bellinger, 2006). It is possible that it is the combination of leadexposure and broader environmental factors that is related tosubsequent development.

All evidence combined, it seems that the small effects of low-level lead exposure in early childhood have persisted throughoutcohort members’ childhood years, and even perhaps intoadulthood, if only for females, although statistical power waslimited at this assessment. Importantly, the results of the Port PirieCohort Study highlight that lead exposure cannot be consideredwithout regard to the child’s wider environment. Many other earlychildhood factors co-occur alongside lead exposure and contributeto subsequent development in some way, and may even serve tomodify any effect of lead. Thus, simply focussing on statisticallyadjusted effects will not suitably translate in reality. Thus, themessage is that many childhood factors – including but not limitedto lead exposure – must be improved to achieve the best possible


outcome. Healthy development may be best promoted through aconcerted focus on multiple childhood factors, simultaneously.

4.2. Ongoing challenges

As the Port Pirie Cohort moves into its fourth decade, a key issuecritical for continued examination of the life-course persistence ofany lead-associated deficits is retaining participants across periodsof several decades. Samples of adequate size are necessary to retainenough statistical power to find any small ‘real’ effects asstatistically significant. This is especially the case given that leadeffects documented in either the Port Pirie or other prospectivecohort studies have always been small. Relatedly, other importantissues within lead research, such as adverse effects at lower leadlevels, effect modification (e.g., by gender), and mediation ofeffects, all require sizeable samples, so it is possible that over timegreater limits will be placed on such analyses, with little elsepossible beyond simple regressions.

Without adequate sample retention, it is also possible thatresults may not be entirely representative of their targetpopulation. By the adult Port Pirie assessment, only 50% of theonce-large cohort remained, and after accounting for missing data,just over one-third of the original cohort members were includedin analyses. It is unclear how these results might extrapolate to theentire cohort, and affect study validity. From the 7-year assess-ment onwards, remaining cohort members appeared to come fromslightly more socially advantaged backgrounds, suggesting somedegree of non-response bias may have affected study validity. Asother studies have suggested that more socially disadvantagedchildren appear more vulnerable to the negative effects of lead, theprogressively ‘higher functioning’ of the Port Pirie cohort may haveattenuated the lead-associated deficits that were seen (Silva et al.,1988). In fact, sensitivity analyses (e.g., McFarlane et al., 2013;Tong et al., 1996) showed that correlations between lead levels anddevelopment in early childhood were similar although slightlystronger in the participants who were subsequently lost to follow-up, suggesting that this attrition is likely to have resulted in a slightunderestimation of the association, though not in a substantivelydifferent interpretation of results. Considering this, and alongsidethe fact that only a few small demographic (and not blood lead)differences were ever seen between responders and non-respond-ers across the course of the 30-year study, it would seem that thesample was not unduly influenced by selective attrition.

These retention issues are not unique to the Port Pirie CohortStudy – other prospective birth cohort studies that have continuedinto adulthood have also been hampered by considerable attrition,which is unsurprising given the long time periods involved, and theneed to recruit the now-adult participants for the first time, insteadof simply re-assessing their parents (Brubaker et al., 2010; Cecilet al., 2008, 2011; Mazumdar et al., 2011, 2012; Wright et al., 2008,2009). Thus, investigating long-term effects of childhood leadexposure is likely to remain an ongoing challenge.

4.3. The community impact of the Port Pirie Cohort study

Since the first findings of the Port Pirie Cohort were releasedabout 30 years ago, much has changed in Port Pirie. The smelter hasundergone extensive clean-up and redevelopment, and is subjectto heavy restrictions and continual monitoring. Recently, in-principle funding and support agreement for a major smelterredevelopment (forecast for 2016) was reached between smelteroperators and State and Commonwealth Governments, with theaim of significantly reducing lead emissions. Extensive environ-mental clean-up including revegetation, and rehabilitation andcleaning of old houses has also occurred. Concurrently, whole-of-community initiatives (e.g., ‘Thumbs up for Low Levels’) have



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ised awareness of how to minimise lead exposure throughactices such as regular sweeping and mopping of floors, leavingoes outside, and washing produce before consumption, althougheir impact on blood lead levels has been debated. Finally, Portrie children’s blood levels are continually monitored by the Statevernment. As a result, lead levels of Port Pirie children haveamatically reduced (see Maynard et al., 2003). At last testing, theerage blood lead level of the 0–4 year old children tested was6 mg/dL, with almost 70% of the children’s levels below 10 mg/dLA Health, 2013). However, as this testing is voluntary, less than aird of the estimated population were included in these figures,hich thus may not be representative of all Port Pirie children. Iny case, childhood lead levels in Port Pirie today are vastlyfferent from those of the Port Pirie Cohort, and so it is unclearhether these results have much import for children currentlyowing up in Port Pirie. Instead, results may be more relevant forildren exposed prior to these reforms, and for children inveloping countries where lead exposure is poorly regulated.The Port Pirie Cohort study is distinct from the other

ospective lead exposure studies continued to adulthood, as itcuments lead levels that are considerably higher than nationalerages (unlike the Boston study), and these high lead levels can

predominantly attributed to one localised source (unlike thencinnati study).2 Port Pirie residents have had to live with thellout of this research. Due to continuing media interest over thears, with some misinformed headlines and insensitive publicewpoints, residents have grown up with controversy anddured constant scrutiny. It is not uncommon for people togard the smelter and, by extension, the regional town of Portrie itself as ‘toxic’. It is entirely possible that, as a corollary,ctors like excessive parental worry and the experience of socialigma may also negatively impact on Port Pirie children’svelopmental outcomes. Throughout and despite this, Port Piriesidents continue to live their lives and support their children’svelopment. While the smelter may represent a small threat toman development, it must also be remembered that it also

presents the livelihood of many residents. As such, its completemoval would constitute a great threat to the economic success ofe town, and the development of the children within it. In sum,e issue of low-level childhood lead exposure is complex, withth direct (e.g., health) as well as diffuse (e.g., economic)plications for Port Pirie children, and it therefore needs to be

anaged with a high degree of sensitivity.

4. Conclusions

The Port Pirie Cohort study has made an important contribution the low-level lead exposure literature by consistently illustrat-g the small though significant negative impact of childhood leadposure. Importantly, it also highlights the various other earlyildhood influences that are equally if not more important tobsequent development than lead exposure. Thus, working toprove multiple factors in early childhood, including reducing

ad exposure, but also improving other early childhood experi-ces including early stimulation and parenting practices, mayve the most beneficial impact on healthy development.

nflict of interest

The authors declare that there are no conflicts of interest.
888889890891892
The Port Pirie cohort study is not the only study to assess children living near a

d smelter, with the Yugoslavia Study of Environmental Lead Exposure surveying

ildren in a similarly-affected area with high blood lead concentrations

asserman, 1998; Wasserman et al., 1992). However, the Port Pirie study is

e only one to follow the children of a smelting community into adulthood.


Transparency document

The Transparency document associated with this article can befound in the online version.

Uncited references Q8

Wechsler (1981).

Appendix A. Supplementary data

Supplementary data associated with this article can be found, inthe online version, at http://dx.doi.org/10.1016/j.neuro.2014.04.004.

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Tracing the long-term legacy of childhood lead exposure: A review of three decades of the Port Pirie Cohort study