Transcript The past, present and future of childhood lead poisoning Two Thousand Years of Lead Poisoning 1st Century AD.

The past, present and future
of childhood lead poisoning
Two Thousand Years of Lead Poisoning
1st
Century AD. Dioscerides: Lead makes the mind give
way
1763.
Benjamin Franklin:Lead in painters, printers
and tinkers
1830 Charles Dickens: Uncommercial Traveler
1892. Brisbane Australia: Childhood lead
poisoning described
1943. Randolph Byers: Long term effects
1991. PHS Strategic Plan
1993: NAS Report
Five Phases of Lead Toxicology
1. There is no such thing as childhood lead
poisoning. (1892)
J Lockhart Gibson
Gibson
Five Phases of Lead Toxicology
 It exists, but if it doesn’t kill you, it doesn’t touch
you (1943)
Byers
Byers
Five Phases of Lead Toxicology
 There are long term effects, but only in children
with severe symptoms (1979)
 Silent lead exposure has long term consequences
 Lead exposure is associated with antisocial
behavior
Flaws in Early Studies
•
•
•
•
Inadequate exposure markers
Screening or group measures of outcome
Inadequate control of confounders
Potential selection bias
Responses to Design Issues
• Replaced blood with dentine
• Tested 3500 teeth from 2500 subjects in primary
•
school
Measured 40 covariates; adjusted for those that
were associated with exposure
Neuropsychological Effects of Lead
•
Classroom Performance
Teacher’s Ratings
90
80
70
60
50
East
West
North
40
30
20
10
0
1st Qtr
2nd Qtr
3rd Qtr
4th Qtr
The Effects of Lead Are
Permanent
The Effects of Lead are
Permanent
Prenatal Lead Exposure
Newer Studies
• Lanphear et al. Cognitive deficits associated with blood
lead concentrations <10 microg/dL in US children and
adolescents.Public Health Rep. 2000
• Canfield et al Intellectual impairment in children with
blood lead concentrations below 10 microg per
deciliter.NEJM 2003
• Bellinger and Needleman Intellectual impairment and
blood lead levels NEJM 2003
Slope of Lead/IQ Regression
Most of the IQ Loss Takes Place
at the Lower Dose
Chiodo et al NTT 2004
T
are
QIFF
uickT
need
(Uim
n
are
T
Q
IFF
uickT
needed
(Uim
ncom
e™
to
pressed)
an
see
d athisdecom
picture.
pressor
T
are
Q
IFF
uickT
needed
(Uim
ncom
e™
to
pressed)
an
see
d athisdecom
picture.
pressor
T
are
Q
IFF
uickT
needed
(Uim
ncom
e™
to
pressed)
an
see
d athisdecom
picture.
pressor
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
Clues to the Lead/Delinquency
link
•Race
•Urban residence
•Low IQ
•ADHD
•Moffit’s studies
Case-Control Study
195 adjudicated delinquents, 155 controls
Bone lead levels
Cases 11ppm±32ppm
Controls 1.5 ± 32ppm
10 variates controlled in the analysis
Odds ratio 4.0 ( 1.4-11.1)
Population attributable risk: 11%-38%
Sales of Leaded Gasoline and Murder Rates
QuickTime™ and a
TIFF (LZW) decompressor
are needed to see this picture.
Robbery and Lead Sales
The Nature of Aging
• A reduction in molecular fidelity over time
exceeding the organism’s repair capability
• Due to the inherent thermodynamic
instability of complex molecules
Processes Associated with the
Aging Process
•
•
•
•
DNA mutations
ROS damage
Mitochondrial damage
Shortening of telomeres
Toxic Expressions of Lead
• Mutations: Klug’s findings
• Mitochondrial damage
– ALAD and mitochondria
– Heme deficiency and neuronal decay
Lead and t RNA
Lead and Telomerase
• Sheng Wu Hua Xue Yu Sheng WU Wu Li
Xue Bao( Shanghai) 2002 34: 240-4
Risk factors Common to
Alzheimer’s and Lead
•
•
•
•
•
Race
Urbanization
Autopsy findings: Niklowitz
Apoptosis
Fetal exposure and later disease
Changes in APP and -actin
RNA
Good Public Health Policy Pays Off
Doing Well by Doing Good
Study
Costs
Benefits
Profit
CDC 1991
$33 Billion
$61 Billion
$28 Billion
CDC 2002
----
$110 Billion319 Billion
Landrigan
$43.4 billion
Reasons for Persistence of
Lead Poisoning
•
•
•
•
•
•
Belief that it is a poor black problem
Belief that it is a problem of poor child rearing
Belief that the problem has been solved
Lack of interest by academic pediatrics
Efforts of lead industry to disguise the problem
Belief that we cannot afford to solve the problem
When a thing was new, people said:
“It’s not true.”
When it was shown to be true, people said:
“It’s not important.”
And when its importance could no longer be
denied, people said:
“Anyway, it’s not new.”
William James