Moderator: Caroline Cox, Research Director, CEH. Caroline leads CEH’s research on toxic exposures, identifying, analyzing and substantiating the scientific bases for CEH’s work to eliminate threats to children and others expose to dangerous chemicals in consumer products. TOPIC: “Hormonal Activity in Water Samples: Implications for Reproductive Health” We’ll discuss hormonal activity in water near hydraulic fracturing sites, the potential for endocrine disruption, and the resulting health impacts. We’ll look at the influence of chemicals in the fracking process on the human endocrine system, estrogen action, prenatal origins of adult disease and epigenetics. SPEAKER BIO: Susan Nagel, Ph.D., Associate Professor, Obstetrics, Gynecology and Women’s Health, University of Missouri School of Medicine. Dr. Nagel works in the Reproductive and Perinatal Research clinic focusing on developmental origins of adult disease, fetal programming and endocrine disruption. TOPIC: “Adverse Birth Outcomes and Natural Gas Development” We’ll discuss how potential environmental impacts from unconventional natural gas development in Marcellus Shale may influence reproductive health and pregnancy outcomes. SPEAKER BIO: Lisa McKenzie, M.P.H., Ph.D., Research Associate, Colorado School of Public Health, Environmental & Occupational Health. Dr. McKenzie has a background in epidemiology and environmental chemistry. Her research interests include exposure assessment, air pollution and natural gas development.

1. Congenital Heart Defects and
Maternal Proximity to Oil and Gas
Development
Lisa McKenzie, PhD, MPH
lisa.mckenzie@ucdenver.edu
Department of Environmental and Occupational Health
Colorado School of Public Health, University of Colorado

2. A congenital heart defect occurs in 18 out
of every 1000 Colorado births

3. Congenital Heart Defects and
Environmental Exposures
Some studies have associated congenital heart
defects or birth defects in general with maternal
exposure to:
• toluene, xylene, and benzene
• Air pollution
• Stressful life events

4. Weld County. (Denver Post file photo)
Erie Colorado. (RJ Sangosti/ The Denver Post)
Crude oil and condensate spilled into the Poudre River a half mile
east of Windsor, upriver from Greeley, (Marc Stewart, 7News)

5. Oil and Gas Operations
 Can emit many
chemicals
Directly
Diesel Engines
 Toluene and xylene are
teratogens (agents that
cause birth defects)
 Benzene is a mutagen
and a carcinogen
 Cross the placenta

6. ~ 340,000 Coloradoans Live in within one mile of
an oil or gas well drilled since the year 2000.

7. High School
Special needs
housing
Park
Multi-well Pad

8. Our Preliminary Study (McKenzie et al 2012)
Explore the association between maternal
exposure to natural gas development and birth
outcomes, using a dataset with individual-level
birth data and geocoded natural gas well
locations.

9. Retrospective Cohort Study
• Identify a group of subjects (the cohort):
– 124,832 infants born between 1996 and 2009 in
rural Colorado
• Determine exposures that occurred in the past
(retrospective)
– Proximity of mother’s home at the time of birth to
natural gas development
• Follow the cohort after the exposure for
occurrence of a congenital heart defect.

10. 124,832 Infants born between 1996
and 2009
• Rural areas and towns with populations less
than 50,000 (Denver-Metropolitan area, El
Paso County and the cities of Fort Collins,
Boulder, Pueblo, Grand Junction and Greely
excluded)
• White Hispanic and Non-Hispanic Mothers
• Singleton live births

11. Found all gas wells that existed in the infant’s birth
year within 10 miles of where the mother was living on
the birth date of her infant
Ten Miles
Ten Miles
Exposed Unexposed

12. Location of the wells in relation to the mother’s home
matters

13. Measured the distance of each gas well from the
Mother’s home

14. Inverse Distance Weighting (IDW)
inverse distance =
1
𝑑𝑖𝑠𝑡𝑎𝑛𝑐𝑒 𝑜𝑓 𝑤𝑒𝑙𝑙 𝑓𝑟𝑜𝑚 𝑚𝑜𝑡ℎ𝑒𝑟′ 𝑠 ℎ𝑜𝑚𝑒

15. Inverse Distance Weighted Count
• Calculated the inverse distance weight for
each well
• Then added all the inverse distance weights
for wells in the 10 radius around the mother’s
home.
• The closer a well is to the home, the more
influence/weight it has in the count.

16. Examples for 4 wells
• All wells 1 mile away: IDW = 1/1 + 1/1 + 1/1 +
1/1 = 4
• All wells 5 miles away: IDW = 1/5 + 1/5 + 1/5
+ 1/5 = 0.8
• 2 wells 1 mile away, 2 wells 2 miles away = 1/1
+ 1/1 +1/2 +1/2 = 2.4

17. Tertiles
Exposed
Group
Low (1 to
3.62 wells
per mile)
High (126
to 1400
wells per
mile)
Medium
(3.63 to
125 miles
per mile)

18. Odds Ratios
• Calculated with a logistic regression
• Compares the prevalence of the birth outcome in the
exposed groups (tertiles) to the birth outcome in the
unexposed group
– Greater than one indicates a positive association
– Less than one indicates a negative association
– 1 indicates no association
• Adjusted for other things that may cause the
congenital heart defect (Mother’s smoking, alcohol
use, education, age, and ethnicity, elevation of
mother’s home, parity, and infant gender).

19. Between 1996 and 2009,
47 Percent of Births in Rural Colorado to Mothers
with Wells within 10 miles of Residence

20. Congenital Heart Defects
Low = first tertile, 1 to 3.62 wells per mile, medium = second tertile, 3.63 to 125 wells per mile, high = third
tertile, 126 to 1400 wells per mile. Adjusted for maternal age, ethnicity, smoking, alcohol use, education, and
elevation of residence, as well as infant parity and gender.

21. Specific Heart Defects
Ventricular Septal Defects Pulmonary Artery and Valve Defects
Tricuspid Valve Defects

22. Current Study
Goal: Develop rigorous exposure assessment
approaches that will link specific well activity
and emissions models to birth data to estimate
maternal exposures in the three months before
conception and in the first two months of her
pregnancy.

23. Five Case Control Studies
Figure 1. Cases and Controls
175533 births
200 Ventricular
Septal Defects
42 Tricuspid
Valve Defects
200 Pulmonary
Artery and
Valve Defects
200 Aortic
Artery and
Valve Defects
126
Conotruncal
Defects
200
Controls
252
Controls
168
Controls
200
Controls
200
Controls

24. Three months before and first two
months of pregnancy

25. Air Toxics Emission Intensity for each well and other air
pollution sources
• How much Oil,
Condensate and Gas
Produced
• Phase of production
• Use of green completions

26. Ask about possible confounders

27. Why is this important?
Oil and gas development operations, which are rapidly increasing and emit
known and suspected teratogens, may be associated with congenital heart
defects, which have significant health consequences. The human fetus is
especially sensitive to environmental chemical exposures and our
preliminary work indicates that congenital heart defects may increase as
maternal proximity to natural gas development increases. Our current study
will address several limitations in the preliminary study.
Multi-well Pad

28. Acknowledgements
• CSPH Colleagues: Roxana Witter, John Adgate, Lee Newman, Ruixen Guo, David Savitz,
Brown University
• Colorado Department of Public Health (CDPHE) and Environment’s Health Statistics and
Colorado Responds to Children with Special Needs Sections provided outcome data for
this study. CDPHE specifically disclaims responsibility for any analyses, interpretations,
or conclusions.
• Funding for preliminary study from the Colorado School of Public Health Department of
Environmental and Occupational Health
• Funding for current study is supported by an award from the American Heart
Association
I have no conflicts of interest to declare

29. McKenzie L.M., Guo, R., Witter R.Z., Savtiz, D.A. Newman L.S., Adgate J.L.,
“Birth Outcomes and Maternal Residential Proximity to Natural Gas
Development in Rural Colorado.” Environmental Health Perspectives. 2014;
122 (4): 412-417.
http://ehp.niehs.nih.gov/1306722/