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