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Maternal Alcohol Consumption and Risk of Orofacial Clefts
Lixian SunDepartment of Epidemiology
Orofacial Clefts
Birth prevalence of 1-2/ 1,000 births
Defect Type
Cleft lip only (CL) Cleft palate only (CP) Cleft lip with cleft palate (CLP)
Alcohol Consumption
2002 Behavioral Risk Factor SurveillanceSystem found over 50% of women of childbearing age (18-44) reported any alcohol use in previous 30 days of their pregnancies.
Among women who might become pregnant, 55% reported any drinking, 13% reported drink more than 7 drinks per week and 12.4% reported binge drinking (=> 5 at one time)
NBDPSNBDPS
Multi-center (10 centers) study headed by CDC.
Identify risk factors for infants with birth defects.
Over 30 major birth defects were classified
Hypothesis
H0: Periconceptional* alcohol consumption can increase the risk of having oralfacial clefts.
* periconceptional: from one month beforepregnancy to the end of first trimester of the pregnancy
Case/Control Selection
Cases were identified from live births, fetal deaths and elective terminations
Controls included only live births without any major birth defect.
All case and control moms completed telephone interview.
Alcohol Exposure
No alcohol consumption (reference group)
Any alcohol consumption
Sample Size
Cases and Controls using in this project were born from Jan 1 to Dec 31, year 2005
Cases: 286Controls: 789
Methods
Both non-informative priors and informative priors were used
GLM with logit link function was used to estimate the odds ratio
Convergence was checked Potential confounders (Baby’s gender
and Maternal cigarette smoking from B1 to P3) were adjusted
Using Non-informative Priors
Alpha ~ dnorm (0, 0.01) Betas ~ dnorm
(10,0.01)
Running 1000 iterationsAuto correlation
alpha chains 1:3
lag
0 20 40
-1.0 -0.5 0.0 0.5 1.0
beta1 chains 1:3
lag
0 20 40
-1.0 -0.5 0.0 0.5 1.0
beta2 chains 1:3
lag
0 20 40
-1.0 -0.5 0.0 0.5 1.0
beta3 chains 1:3
lag
0 20 40
-1.0 -0.5 0.0 0.5 1.0
History plotsalpha chains 1:3
iteration
1 250 500 750 1000
-30.0
-20.0
-10.0
0.0
beta2 chains 1:3
iteration
1 250 500 750 1000
0.0
10.0
20.0
30.0
BGR Diagnosticbeta1 chains 1:3
start-iteration
51 200 400
0.0
0.5
1.0
beta2 chains 1:3
start-iteration
51 200 400
0.0
0.5
1.0
beta3 chains 1:3
start-iteration
51 200 400
0.0
0.5
1.0
alpha chains 1:3
start-iteration
51 200 400
0.0
0.5
1.0
Re-run 19000 more iterations and burn in 10000
alpha chains 1:3
lag
0 20 40
-1.0 -0.5 0.0 0.5 1.0
beta2 chains 1:3
lag
0 20 40
-1.0 -0.5 0.0 0.5 1.0
alpha chains 1:3
iteration
10001 10500 11000
-1.75
-1.5
-1.25
-1.0
-0.75
Summary of Statistics
node mean sd 2.5%97.5%OR 0.8631 0.1293 0.8541.139
Using Informative Priors
beta1~dnorm(0.0431, 1312) beta2~dnorm(0.3135, 349) beta3~dnorm(0.3593, 249) alpha ~dnorm(-1.298, 528)
Run 1000 iterationsAuto correlation
alpha chains 1:3
lag
0 20 40
-1.0 -0.5 0.0 0.5 1.0
beta1 chains 1:3
lag
0 20 40
-1.0 -0.5 0.0 0.5 1.0
beta2 chains 1:3
lag
0 20 40
-1.0 -0.5 0.0 0.5 1.0
beta3 chains 1:3
lag
0 20 40
-1.0 -0.5 0.0 0.5 1.0
History plot
alpha chains 1:3
iteration
1 250 500 750 1000
-0.6
-0.5
-0.4
-0.3
-0.2
BGR diagnostics
alpha chains 1:3
start-iteration
51 200 400
0.0
0.5
1.0
beta1 chains 1:3
start-iteration
51 200 400
0.0
0.5
1.0
1.5
beta2 chains 1:3
start-iteration
51 200 400
0.0
0.5
1.0
1.5
beta3 chains 1:3
start-iteration
51 200 400
0.0
0.5
1.0
1.5
Re-run 3000 iterations and burn in 1000 iterations
Summary of Statistics
node mean sd 2.5%97.5%OR 1.038 0.0282 0.9837
1.096
Summary
No evidence to show that alcohol is an effect factor of oral facial cleft.
Using informative priors provides narrower credible set
Less iterations were needed if informative prior was used.
More analyses
Examine the effect of alcohol consumption and different phenotype of oralfacial clefts.
Examine the effect of alcohol by alcohol type.
Examine the effect of alcohol by exposure of binge drinking.
Acknowledgements
•All participated families
•Professor Cowles
•Every one in this class
•My daughter for her coming back