Fundamentals of Epidemiology (EPID 610)

ANSWER KEY
Confounding and Stratified Analysis

Learning Objectives:

 Understand criteria for a confounder

 Assess confounding through stratification and use of the Mantel Haenszel OR by
manual calculations as well as in SPSS

You conduct a case control study to look at the association between prenatal exposure
to hair dye (mother died her hair during pregnancy) with the development of asthma in
the child. You recruit 25 cases of new onset pediatric asthma and 50 healthy
population-based controls. You then ask the children’s mothers whether they dyed their
hair during pregnancy (exposure). You are concerned that maternal age at pregnancy
might be a confounder because: 1. the proportion of women dying their hair is likely to
differ by age; and 2. older maternal age is associated with adverse outcomes in the
child and may be a risk factor for pediatric asthma. Therefore, you want to determine
whether it is a confounder in the association between prenatal exposure to hair dye and
pediatric asthma. Below are the tables you collect for the total sample, as well as
stratified by maternal age:

For the entire study population

Asthma (D+) No Asthma (D-) Total
Hair dye (E+) 17 13 30
No hair dye (E-) 8 37 45
Total 25 50 75

Stratified by maternal age

Maternal age < 35 Maternal age >=35

Total
Asthma No Asthma Asthma No Asthma
(D+) (D-) (D+) (D-)
Hair dye (E+) 4 5 13 8 30
No hair dye (E-) 4 25 4 12 45
Total 8 30 17 20 75

PART 1: Using the tables above, conduct the analysis by hand to

determine whether maternal age is a confounder in the association
between hair dye and asthma.

PART 2: Next, repeat this analysis using SPSS (data available on

Bb- lab9data.sav.”) and then compare these results with the ones

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 Fundamentals of Epidemiology (EPID 610)

you have calculated by hand. Don’t forget to include the 95%

confidence intervals for our ORs.

PART 1: STEPS TO CONDUCT THE ANALYSIS BY HAND

1. Calculate the crude (not stratified on age) OR of the relationship between hair dye
during pregnancy and pediatric asthma. Interpret the OR in words.

Crude OR = (17*37) / (13*8) = 6.0

Women whose children had asthma had 6 times the odds of having used hair
dye during pregnancy as women whose children did not have asthma. This
indicates a greater odds of having used hair dye during pregnancy among
those women whose children had asthma.

2. Calculate the stratum specific ORs of the relationship between hair dye during
pregnancy and pediatric asthma (i.e. calculate the OR for mothers under age 35 and
mothers 35 and older separately). Are they similar to each other? Are they similar
to the crude OR?

For women < 35, OR = (4*25) / (4*5) = 5.0

For women >=35, OR = (13*12) / (8*4) = 4.9

The stratum specific ORs are quite similar to each other, 5.0 and 4.9 are nearly
the same. (Stay tuned for next week, in terms of what we might consider if
they were different from each other). They are also fairly different from the
crude OR of 6.0. This suggests confounding may have occurred, but let’s
calculate the MH adjusted OR to get a precise adjusted estimate and confirm
that confounding is present.

3. The formula for calculating the MH OR is as follows:

(WE WILL NOT TEST YOU ON CALCULATING AN MH OR BY HAND IN THIS
CLASS. THIS HAND CALCULATION WILL ALSO NOT BE ON THE HWs)

MH OR = (a1d1/n1 + a2d2/n2) / (b1c1/n1 + b2c2/n2)

Use a1, b1, c1 and d1 to represent the values of the cells in your first stratum-
specific crosstab. Then use n1 to equal to the total number of participants in your
first stratum specific table. Next use a2, b2, c2, c2 and n2 to represent the cells in
your second stratum- specific crosstab.

Now you can calculate the MH OR for the association between hair dye during
pregnancy and pediatric asthma, adjusting for maternal age. Is the MH OR similar
to your stratum specific ORs? Is it similar to the crude OR? Interpret the MH OR in
words.

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 Fundamentals of Epidemiology (EPID 610)

MH OR = (4*25/38 + 13*12/37) / (4*5/38 + 4*8/37) = 4.9

The MH OR is nearly identical to the stratum specific ORs. This makes sense
as it is a weighted average of the two, and the stratum specific ORs were
nearly identical. The MH OR is different from the crude OR (4.9 vs. 6.0).

Women whose children had asthma had 4.9 times the odds of having used
hair dye during pregnancy, compared to women whose children did not have
asthma, after adjusting for maternal age. This indicates a greater odds of
having used hair dye during pregnancy among those women whose children
had asthma, after adjusting for maternal age.

4. Based on these calculations, do you think the association between hair dye during
pregnancy and pediatric asthma was confounded by maternal age? Why or why
not?

Yes, maternal age appears to be a confounder in the association between hair

dye and pediatric asthma. First, we can see that the stratum-specific ORs are
similar when we compare the OR for maternal age <35 (OR=5.0) with the
stratum specific OR for maternal age >=35 (OR = 4.9). Next, we can see that
these stratum-specific ORs are different from the crude (OR =6.0), and this is
confirmed when we calculate the Mantel Haenszel Adjusted OR =4.9 which is
also ‘appreciably’ different from the crude OR (Note it is based on our
subjective judgment what qualifies as ‘appreciably’ different. We use the 10%
rule for this. If crude OR is more than 10% different than the adjusted OR,
then confounding is likely present. See Lab 10 for the 10% rule calculation).

PART 2: STEPS TO CONDUCT THE ANALYSIS USING SPSS

Now let’s repeat this analysis using SPSS (with the new addition of also having 95%
confidence intervals for our ORs). The data are available on Blackboard in today’s
folder, called “lab9data.sav.” Using stratified analysis, answer the following questions.

freq vars=exposure disease age.

crosstabs tables = exposure by disease / cells=count row / stats=risk.
crosstabs tables = exposure by disease by age / cells = count row / stats=risk cmh.

(Note the syntax for running stratified tables, includes ‘cmh’ which is asking SPSS to
calculate the MH OR).

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 Fundamentals of Epidemiology (EPID 610)

5. What is the crude OR and 95% CI for the association between pediatric asthma and
maternal hair dye use during pregnancy? How do you interpret this?

The crude OR=6.0 (95% CIs 2.1, 17.3). The odds of using hair dye among women
whose children developed asthma is 6.0 times (95% CIs 2.1, 17.3) the odds of
using hair dye among women whose children did not develop asthma. This
indicates a greater odds of having used hair dye during pregnancy among those
women whose children had asthma. Because the 95% CI does not include 1, this
association is statistically significant at the 0.05 level. But, since the width of the
interval is wide, the estimate is not precise which means there is a lot of random
error. Increasing the sample size may result in a more precise measurement.

Mother used hair dye during pregnancy * Asthma Crosstabulation

Asthma

Case Control Total

Mother used hair dye during Exposed Count 17 13 30

pregnancy % within Mother used hair 56.7% 43.3% 100.0%
dye during pregnancy

Unexposed Count 8 37 45

% within Mother used hair 17.8% 82.2% 100.0%

dye during pregnancy
Total Count 25 50 75

% within Mother used hair 33.3% 66.7% 100.0%

dye during pregnancy

Risk Estimate

95% Confidence Interval

Value Lower Upper

Odds Ratio for Mother used 6.048 2.113 17.308

hair dye during pregnancy
(Exposed / Unexposed)
For cohort Asthma = Case 3.188 1.580 6.431
For cohort Asthma = Control .527 .342 .811
N of Valid Cases 75

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 Fundamentals of Epidemiology (EPID 610)

6. What are the stratum-specific ORs & 95% CIs when stratified on age
category (i.e. what is the OR for the association between pediatric asthma and
maternal hair dye for women with a maternal age under 35, versus for women with a
maternal age of 35 and over)?

Age <35: OR=5.0 (95% CIs 0.9, 27.0)

Age>=35: OR=4.9 (95% CIs 1.2, 20.4)

Mother used hair dye during pregnancy * Asthma * Age Crosstabulation

Asthma

Age Case Control Total

>=35 Mother used hair dye during Exposed Count 13 8 21

pregnancy % within Mother used hair 61.9% 38.1% 100.0%
dye during pregnancy

Unexposed Count 4 12 16

% within Mother used hair 25.0% 75.0% 100.0%

dye during pregnancy

Total Count 17 20 37

% within Mother used hair 45.9% 54.1% 100.0%

dye during pregnancy
<35 Mother used hair dye during Exposed Count 4 5 9
pregnancy % within Mother used hair 44.4% 55.6% 100.0%
dye during pregnancy
Unexposed Count 4 25 29
% within Mother used hair 13.8% 86.2% 100.0%
dye during pregnancy
Total Count 8 30 38
% within Mother used hair 21.1% 78.9% 100.0%
dye during pregnancy
Total Mother used hair dye during Exposed Count 17 13 30
pregnancy % within Mother used hair 56.7% 43.3% 100.0%
dye during pregnancy

Unexposed Count 8 37 45

% within Mother used hair 17.8% 82.2% 100.0%

dye during pregnancy

Total Count 25 50 75

% within Mother used hair 33.3% 66.7% 100.0%

dye during pregnancy

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 Fundamentals of Epidemiology (EPID 610)

Risk Estimate

95% Confidence Interval

Age Value Lower Upper

>=35 Odds Ratio for Mother used 4.875 1.162 20.451

hair dye during pregnancy
(Exposed / Unexposed)

For cohort Asthma = Case 2.476 .994 6.168

For cohort Asthma = Control .508 .275 .939

N of Valid Cases 37
<35 Odds Ratio for Mother used 5.000 .926 26.990
hair dye during pregnancy
(Exposed / Unexposed)
For cohort Asthma = Case 3.222 1.003 10.349
For cohort Asthma = Control .644 .353 1.177
N of Valid Cases 38
Total Odds Ratio for Mother used 6.048 2.113 17.308
hair dye during pregnancy
(Exposed / Unexposed)

For cohort Asthma = Case 3.188 1.580 6.431

For cohort Asthma = Control .527 .342 .811

N of Valid Cases 75

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 Fundamentals of Epidemiology (EPID 610)

7. Use the results above to assess confounding in the association between hair dye
and pediatric asthma. Does maternal age appear to be a confounder? Describe
the procedure you followed to reach your conclusion. Which OR would you report?

Yes, maternal age appears to be a confounder in the association between hair

dye and pediatric asthma. First, we can see that the stratum-specific ORs are
similar when we compare the OR for maternal age <35 (OR=5.0) with the stratum
specific OR for maternal age >=35 (OR = 4.9). Next, we can see that these
stratum-specific ORs are different from the crude (OR =6.0), and this is confirmed
when we use SPSS to calculate the Mantel Haenszel Adjusted OR =4.9 which is
also different from the crude OR by more than 10% (See Lab 10 Answer Key).

Therefore, since maternal age appears to be a confounder in the association

between hair dye and asthma, we need to report the adjusted OR (OR=4.9) instead
of the crude OR (OR=6.0).

Mantel-Haenszel Common Odds Ratio Estimate

Estimate 4.922
ln(Estimate) 1.594
Std. Error of ln(Estimate) .559
Asymp. Sig. (2-sided) .004
Asymp. 95% Confidence Common Odds Lower Bound 1.645
Interval Ratio Upper Bound 14.728
ln(Common Odds Lower Bound .498
Ratio) Upper Bound 2.690
The Mantel-Haenszel common odds ratio estimate is asymptotically normally distributed under the common odds
ratio of 1.000 assumption. So is the natural log of the estimate.

8. What is the Mantel Haenszel Adjusted OR (i.e. the OR adjusted for age) with 95%
confidence interval? How do you interpret these results?

MH Adjusted OR=4.9, 95% CI=1.6-14.7

(Note: MH Adjusted OR is the WEIGHTED average of the two stratum-specific

ORs identified in Q2 above).

Women whose children had asthma had a 4.9 times the odds of having used hair
dye during pregnancy, compared to women whose children did not have asthma,
after adjusting for maternal age. This indicates a greater odds of having used
hair dye during pregnancy among those women whose children had asthma, after
adjusting for maternal age. Because this 95% CI does not include 1, the
association is statistically significant at the 0.05 level. But, since the width of the
 Fundamentals of Epidemiology (EPID 610)

interval is wide, the estimate is not precise which means there is a lot of random
error. Increasing the sample size may result in a more precise measurement.

Mantel-Haenszel Common Odds Ratio Estimate

Estimate 4.922
ln(Estimate) 1.594
Std. Error of ln(Estimate) .559
Asymp. Sig. (2-sided) .004
Asymp. 95% Confidence Common Odds Lower Bound 1.645
Interval Ratio Upper Bound 14.728
ln(Common Odds Lower Bound .498
Ratio) Upper Bound 2.690
The Mantel-Haenszel common odds ratio estimate is asymptotically normally distributed under the common odds
ratio of 1.000 assumption. So is the natural log of the estimate.
 Fundamentals of Epidemiology (EPID 610)

SPSS INSTRUCTIONS

CROSSTAB:
1. Crude OR
 Go to ANALYZE and select DESCRIPTIVE STATISTICS and the CROSSTABS
 Put the exposure in the ROW box and the outcome in the COLUMN box.
 Click on STATISTICS and check the box next to RISK. Hit CONTINUE
 Click on OK and the results will open in the OUTPUT window, or
o Click on PASTE, then highlight and run the syntax you just pasted into the
SYNTAX WINDOW, and the results will open up in the OUTPUT window
2. Stratified & Adjusted OR
 Go to ANALYZE and select DESCRIPTIVE STATISTICS and the CROSSTABS
 Put the exposure in the ROW box and the outcome in the COLUMN box, and
put the confounder in the LAYER box
 Click on STATISTICS and check the box next to RISK and next to COCHRAN’S
& MANTEL HAENSZEL STATISTICS. Hit CONTINUE
 Click on OK and the results will open in the OUTPUT window, or
o Click on PASTE, then highlight and run the syntax you just pasted into the
SYNTAX WINDOW, and the results will open up in the OUTPUT window