1. www.alcoholandhealth.org1 Journal Club Alcohol and Health: Current Evidence May-June 2006

2. www.alcoholandhealth.org2 Featured Article Maternal coffee and alcohol consumption during pregnancy, parental smoking and risk of childhood acute leukemia Menegaux F, et al. Cancer Detect and Prev. 2005;29:487–493.

3. www.alcoholandhealth.org3 Study Objective To examine the association between… –alcohol use, coffee drinking, and smoking during pregnancy and –childhood acute lymphoid leukemia (ALL) and acute nonlymphoid leukemia (ANLL)

4. www.alcoholandhealth.org4 Study Design Case-control study of children hospitalized with… –newly diagnosed acute leukemia (n=280) or –for a disease other than cancer/birth defect (n=288) All subjects from the same hospitals; controls mainly from orthopedic departments Interviews of mothers that covered alcohol use during pregnancy and other topics (e.g., medical history) Analyses adjusted for potential confounders

5. www.alcoholandhealth.org5 Assessing Validity of an Article About Harm Are the results valid? What are the results? How can I apply the results to patient care?

6. www.alcoholandhealth.org6 Are the Results Valid? Did the investigators demonstrate similarity in all known determinants of outcomes? Did they adjust for differences in the analysis? Were exposed patients equally likely to be identified in the two groups? Were the outcomes measured in the same way in the groups being compared? Was follow-up sufficiently complete?

7. www.alcoholandhealth.org7 Did the investigators demonstrate similarity in all known determinants of outcomes? Did they adjust for differences in the analysis? Cases and controls were compared on demographic factors (they were similar). Analyses were adjusted for these factors while examining effects of alcohol use, smoking, and coffee drinking separately. Other risk factors for leukemia were not reported.

8. www.alcoholandhealth.org8 Were exposed patients equally likely to be identified in the two groups?  Researchers described use of standardized questionnaires and similar interviewing conditions for both groups.  But, recall bias may have made identifying the exposure more likely in mothers of children with leukemia.  When asked about exposures during pregnancy, a mother with a child with newly diagnosed leukemia may be more likely to recall the exposures than would a mother of a child with an acute injury.

9. www.alcoholandhealth.org9 Were the outcomes measured in the same way in the groups being compared? Cases and controls were drawn from the same hospitals.

10. www.alcoholandhealth.org10 Was follow-up sufficiently complete? There was no follow-up. –This was a retrospective case-control study.

11. www.alcoholandhealth.org11 What are the Results? How strong is the association between exposure and outcomes? How precise is the estimate of the risk?

12. www.alcoholandhealth.org12 How strong is the association between exposure and outcomes? Odds Ratios (ORs)* and 95% Confidence Intervals Exposure During PregnancyALLANLL Any alcohol use2.0 (1.4–3.0)2.6 (1.2–5.8) <=3 cups of coffee/day1.1 (0.7–1.8)1.6 (0.6–4.3) 4–8 cups of coffee/day2.4 (1.3–4.7)2.8 (0.7–10.4) Any smoking0.9 (0.6–1.4)1.0 (0.4–2.3) *Compared with no use and in analyses adjusted for age, sex, hospital, and ethnicity

13. www.alcoholandhealth.org13 How strong is the association between exposure and outcome? (cont.) Results did not differ when analyses were adjusted for… –any of the substances examined, –profession, –education, –early infection history, –breast-feeding, –maternal history of fetal loss, or –familial history of cancer.

14. www.alcoholandhealth.org14 How precise is the estimate of the risk? Confidence intervals: –for any alcohol use and ALL: 1.4–3.0 –for any alcohol use and ANLL: 1.2–5.8 –for drinking 4–8 cups of coffee per day and ALL: 1.3–4.7 These intervals do not include 1, indicating statistical significance. However, they are wide, particularly in the cases of alcohol and ANLL and coffee and ALL.

15. www.alcoholandhealth.org15 How Can I Apply the Results to Patient Care? Were the study patients similar to the patients in my practice? Was the duration of follow-up adequate? What was the magnitude of the risk? Should I attempt to stop the exposure?

16. www.alcoholandhealth.org16 Were the study patients similar to the patients in my practice? The children were identified in 4 hospitals in France. How they might differ from other children with leukemia, aside from geography, is not known. Most of the children were Caucasian.

17. www.alcoholandhealth.org17 Was the duration of follow-up adequate? There was no follow-up. Children with leukemia were younger than controls. Although unlikely, it is possible that… –results might have been different if follow-up (time since pregnancy and prenatal exposure) had been similar.

18. www.alcoholandhealth.org18 What was the magnitude of the risk? The risk of leukemia was 2–3 times greater for children of women who… –drank alcohol or 4 – 8 cups of coffee per day during pregnancy.

19. www.alcoholandhealth.org19 Should I attempt to stop the exposure? Pregnant women should not drink alcohol. This recommendation is primarily because of the risk of fetal alcohol effects and syndrome. Leukemia may represent an additional, but rarer, risk of alcohol consumption.

20. www.alcoholandhealth.org20 Should I attempt to stop the exposure (cont.)? Both the alcohol and coffee findings should be considered hypothesis generating. This study alone should not determine choices around coffee consumption. –Data are sparse in this area, and further study is needed.