recent (and not so recent) methodological issues in … factor... · 2019. 11. 6. · results from...
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Recent (and not so Recent) Methodological Issues in Environmental
Epidemiology Pam Factor-Litvak, PhD
Small Associations
So you know you are studying
epidemiology when… • Your professor says, “When I say smoking, you say
cancer”
• Professor: “Smoking”
• Class: “Cancer”
• Professor: “Smoking”
• Class: “Cancer”
• But these are the large associations….
Small Reductions in IQ: Shifts on the
Tails of the Distribution
www.environment.ucla.edu
Early Life Exposure to Lead
Defining the Shape of the Exposure – Response Curve
Lanphear et al 2005
Critical Periods of Exposure
What Matters? Timing of Exposure
Parsing Out Mixtures
Organochlorine Compounds, Thyroid
Function and Pregnancy Outcomes
Slight Differences in Structure
Make a Difference
DDT DDE
DDT and Birth Weight
Kezios et al 2013
Spearman correlation coefficients
among OH-PCBs and Parent PCBs.
4-OH-CB107 3’-OH-CB138 4-OH-CB146
PCB118 PCB138 PCB153 PCB187
rs=0.318
p<0.0001
rs =0.292
p<0.0001 rs =0.306
p<0.0001
rs =0.318
p<0.0001
rs =0.351
p<0.0001
rs =0.248
p<0.0001
3-OH-CB153 4-OH-CB187
Among smokers, covariate adjusted mean birth weight within quartiles both 4-OH-CB107 and PCB118 exposure, in a model mutually adjusted for the metabolite and its
parent PCB congener
Q1 Q2 Q3 Q4
4-OH-CB107 3437 3315 3247 3122
PCB 118 3163 3294 3229 3434
2900
3000
3100
3200
3300
3400
3500
3600
3700
3800
Bir
th w
eig
ht
(g)
Early Life Exposure to Phthalates
• 470 million pounds produced or imported in U.S. per
year
• Wildly used in consumer products
• High production chemicals with similar structures
• Exposures are ubiquitous in the U.S. and other
countries
Prenatal Postnatal Child age 7
Cohort = 328 African American & Dominican
mothers & children in Northern
Manhattan/South Bronx
Questionnaire
Medical record
Phthalates in
maternal 3rd
trimester urine
Questionnaire
Phthalates in child
age 3, 5, 7
urine
Wechsler Intelligence
Scale for Children, 4th
editions (WISC-IV)
Enrolled during pregnancy 1998-2006; excluded active smokers,
illicit drug users, women with HIV, hypertension or diabetes
Prenatal Exposure to Specific
Phthalates and Age 7 IQ Reductions
85
90
95
100
105
110
q0 q1 q2 q3 q0 q1 q2 q3 q0 q1 q2 q3
**p ≤ 0.01
7.6 ** 6.6 **
MnBP MiBP MBzP
Models controlled for maternal IQ, Home scale, child sex, race/ethnicity, maternal
prenatal alcohol consumption, education, marital status and specific gravity
*p < 0.05 **p ≤ 0.01
Postnatal Phthalates • Few associations between postnatal phthalates
and childhood IQ at age 7
• No changes in associations between any prenatal
phthalate and childhood IQ when postnatal
phthalates included in the model
Adding Up Mixtures
Rappaport 2011
PCBs and Time to Pregnancy
Results from Weighted Quantile
Approach with 1000 Bootstraps
Categories PCB congener Weights associated with
longer TTPa
Weights associated with
shorter TTPb
Bootstrap
Means
Average Bootstrap
Sum
Bootstrap
Means
Average
Bootstrap
Sum
Group 1:
Estrogenic
101 0.06
16%
0.10
17% 187c 0.01 0.07
201 0.09 0
Group 2A: Anti-estrogenic (AE), dioxin like
66 0.07
22%
0.02
46%
74 0.01 0.11
105d <0.01 0.08
118 0 0.12
156c 0.13 <0.01
167 0 0.12
Group 2B: AE & not dioxin like 138
d 0 <1%
0.06 14%
170 <0.01 0.07
Group 3: Phenobarb, CYP1A, CYP2B inducers
99c 0.02
9%
<0.01
23%
153 0 0.09
180 <0.01 0.04
203 <0.01 0.07
183d 0.07 0.02
Not categorized 56 0.47
54% <0.01
0 146 0.07 0
Mechanisms
Possible Mechanisms: Thyroid Function
Kahn et al 2014
Sex Specific Associations
Morgenstern et al 2017
Lessons Learned about Critical Periods
• Blood lead concentrations ‘tracked’ over
childhood; clearly associations with pre and post
natal exposures
• Urinary phthalate concentrations were not
correlated over time; associations clearly in
prenatal and possibly for one in postnatal period
• Organochlorine compounds are lipid soluble;
unfortunately we did not have repeated measures
in the childhood period
Opportunities • Small Associations
• Defining the Shape of the Dose Response Curve
• Parsing Out Mixtures
• Adding Up Mixtures
• Mechanisms
• Sex specific Associations
Acknowledgements
Acknowledgements • Barbara Cohn
• Piera Cirrillo • Teresa Janevic
• Matt Lamb
• Katrina Kezios
• Linda Kahn
• Keane Tsong
• Erica Lee
• Beverly Insel
• Rachelle Morgenstern
• Robin Whyatt • Julie Herbstman
• Megan Horton • Mary Kilty
• Joe Graziano
• Nancy LoIaconno • Gail Wasserman
• Vesna Slavkovich
• Duscan Popovac
• Jennie Kline
• Zena Stein
• Pat Shrout
• Xinhua Liu
• Pashko Camaj
• Chris Gennings • Katherine Keyes
• Ezra Susser • Myrto Petreas
Funding Sources: National Institute of Environmental Health Sciences, National Institute of Child Health and Development, US Environmental Protection Agency