Table 1.

Characteristics of case-control studies of exposure to alcohol from the mother during pregnancy and risk of leukemia in childhood

Reference, country, case recruitment period, cases, controls, study designAge of the childrenMaternal alcohol consumption during pregnancy: categoryOR (95% CI)*Matching factorsAdjusting factorsComments
GLALLAML
van Steensel-Moll et al. (22)0-14 yTotal alcohol: yes1.0 (0.8-1.2)Date of birth, gender, residenceAge, gender
    The Netherlands, 1973-1979
    519 ALL cases from the Nationwide morbidity register of childhood leukemia
    507 population-based controls randomly selected
    Self-administered questionnaire
    Response rate: 90% (cases) and 70/68% (first/replacement controls)
    Assessment of alcohol consumption: not detailed
Severson et al. (23)0-17 yTotal alcohol: ever1.42 (0.91-2.23)Date of birth, race, telephone area code and exchange numberNo interaction with: age of the mother, education of the mother, use of mind altering drugs, gender of the child, ethnicity of the childDose-response P trend = 0.63
    United States, Canada, 1980-19840-2 yTotal alcohol: ever3.00 (1.23-8.35)
    187 AML cases from CCG registration filesTotal alcohol: 1-20 drinks/pregnancy2.1
    187 population-based controls randomly selectedTotal alcohol: >20 drinks/pregnancy2.8
    Exclusion criteria: no telephone, not English speaking3-10 yTotal alcohol: ever0.81 (0.36-1.80)
    Telephone interview11-17 yTotal alcohol: ever1.13 (0.53-2.44)
    Interview rate: 77.9% (cases) and 78.5% (controls)
    Assessment of alcohol consumption: numbers of glasses, cans, bottles or ounces consumed per day, week, or month; trimesters during which consumption occurred
van Duijn et al. (24)0-14 yTotal alcohol: yes2.6 (1.4-4.6)Age, genderGender, age, date of birth, social class, maternal smoking, occupational exposure to hydrocarbons, drugs, ultrasound, radiation, viral infectionsFor ALL, the sample is the same as in the study of van Steensel-Moll et al. (22), but data are stratified by age
    The Netherlands, 1973-1979Total alcohol: 1 drink/wk2.4 (1.3-4.5)
    517 ALL and 80 ANLL cases from registration of the DutchTotal alcohol: >1 drink/wk2.9 (1.1-7.4)
    Childhood leukemia Study Group0-4 yTotal alcohol: yes1.1 (0.8-1.9)2.8 (1.2-6.5)
    240 population-based controls from the same municipality5-9 yTotal alcohol: yes0.8 (0.5-1.5)3.0 (1.1-8.4)
    Self-administered questionnaire10-14 yTotal alcohol: yes1.0 (0.4-2.1)0.8 (0.3-2.3)
    Response rate: 86% (cases) and 66/67% (first/replacement controls)
    Assessment of alcohol consumption: abstainers, occasional drinkers (1 drink/wk), frequent drinkers (>1 drink/wk)
Ross et al. (25)0-1 yBeer: ever0.8 (0.4-1.9)0.7 (0.2-2.1)1.1 (0.3-3.8)E09: year of birth, geography; E14 and E15: year of birth, ethnicity, geographyMaternal educationSee Shu et al. (26)
    United States, 1983-1994Wine: ever1.0 (0.5-2.1)0.8 (0.3-1.9)2.0 (0.6-7.0)
    84 AL, 54 ALL and 30 AML cases from CCG registration filesSpirits: ever1.0 (0.3-3.2)1.0 (0.2-4.2)1.2 (0.2-8.9)
    CCG-E09 (1983-1988), CCG-E14 (1989-1993) and CCG-E15 (1989-1994)
    97 population-based controls randomly selected
    Exclusion criteria: no telephone, not English speaking, Canadian mothers
    Telephone interview
    Interview rate: 45% (cases) and 50% (controls)
    Assessment of alcohol consumption frequency: never, <1/mo, 1-3/mo, <1/wk, 1-3/wk, 4-6/wk, daily
Shu et al. (26)0-1.5 yTotal alcohol: ever1.60 (1.18-2.18)1.43 (1.00-2.04)2.64 (1.36-5.06)Year of birth, telephone area code and exchange numberGender, maternal age, maternal education, maternal smoking during pregnancyOnly a subset of cases overlap between the study of Ross et al. (25); 0-1 y, American, E09-E14-E15 and the one of Shu et al.(26); 0-1.5 y, American Canadian and Australian, E09
    United States, Canada, Australia, 1983-1988Total alcohol: ever (Tri 1)1.29 (0.94-1.78)1.18 (0.81-1.72)1.90 (1.00-3.62)
    302 GL, 203 ALL and 88 AML cases from CCG registration filesTotal alcohol: ever (Tri 2)1.50 (1.04-2.16)1.25 (0.81-1.95)2.49 (1.17-5.32)
    558 population-based controls randomly selectedTotal alcohol: ever (Tri 3)1.35 (0.92-1.98)1.13 (0.72-1.78)2.41 (1.05-5.52)
    Exclusion criteria: no telephone, not English speakingTotal alcohol: 1-20 drinks/pregnancy1.77 (1.23-2.55)1.76 (1.14-2.72)2.36 (1.11-5.03)
    Telephone interview using a structured questionnaireTotal alcohol: >20 drinks/pregnancy1.27 (0.80-2.01)0.93 (0.53-1.62)3.13 (1.20-8.06)
    Interview rate: 79.1% (cases) and 75.1% (controls)Beer: 1-4 cans/mo1.16 (0.68-1.98)1.23 (0.65-2.33)1.24 (0.43-3.60)
    Assessment of alcohol consumption: during each trimester of the index pregnancy, type and frequency (0, 1-4 drinks/mo, >4 drinks/mo)Beer: >4 cans/mo0.99 (0.52-1.88)0.68 (0.30-1.54)2.21 (0.70-6.96)
Wine: 1-4 glasses/mo1.39 (0.92-2.10)1.42 (0.86-2.34)1.95 (0.81-4.70)
Wine: >4 glasses/mo1.06 (0.59-1.91)0.71 (0.34-1.49)2.33 (0.72-7.52)
Liquor: 1-4 drinks/mo2.46 (1.41-4.29)1.88 (0.96-3.67)6.37 (1.95-20.80)
Liquor: >4 drinks/mo0.96 (0.37-2.54)0.54 (0.17-1.74)
Petridou et al. (27)0-14 yTotal alcohol: yes0.57 (0.34-0.95)Gender, age, residenceMutually adjusted variables: sociodemographic, lifestyle, environmental, and biomedical variablesNo woman consumed more than a glass of alcoholic beverages per day during her pregnancy
    Greece, 1993-1994
    153 GL cases from the Nationwide network of childhood hematologists/oncologists
    300 controls from the same hospital
    Interview using a structured questionnaire
    Interview rate: 95% (cases) and 96% (controls)
    Assessment of alcohol consumption: no, ≥2 glasses/wk
Schüz et al. (28)0-14 yTotal alcohol: 1-7 glasses/wk0.9 (0.7-1.1)Gender, date of birth, districtGender, date of birth, district
    Germany, 1980-1994 (NI) 1992-1994 (NW)Total alcohol: >7 glasses/wk0.6 (0.3-1.3)
    964 AL cases from a German childhood cancer registry in Mainz, with a nationwide part (NW) and a part living in the vicinity of nuclear installations (NI)
    647 population-based controls randomly selected
    Mailed questionnaire and telephone interview
    Response rate: 80.2/81.7% (NI/NW cases) 61.6/68.6% (NI/NW controls)
    Assessment of weekly alcohol consumption (beer, wine and strong liquor)
Wen et al. (29)0-17 yTotal alcohol: yes1.0 (0.9-1.2)Age, ethnicity, telephone area code and exchange number
    United States, 1989-1993
    1,842 ALL cases from CCG registration files
    1,986 population-based controls randomly selected
    Telephone interview using a structured questionnaire
    Interview rate: 92% (cases) and 76.5% (controls)
    Assessment of alcohol consumption: not detailed
Alexander et al. (30)0-1.5 yTotal alcohol: yes1.23 (0.68-2.23)0.63 (0.25-1.60)1.92 (0.90-4.10)Gender, date of birthGender, region of residence
    International: Italy, Greece, Egypt, Brazil, Chile, mainland China, Hong Kong, Japan; period and modalities of recruitment not reported
    136 GL, 49 ALL and 74 AML cases
    266 controls from the same or similar hospitals
    Telephone interview using a structured questionnaire
    Interview rate: >98% (cases) and >90% (controls)
    Assessment of alcohol consumption: not detailed
Costas et al. (31)0-9 yTotal alcohol: ever1.5 (0.54-4.20)Ethnicity, sex, date of birth, age
    United States, 1969-1989
    19 GL from hospitals of Massachusetts
    37 population-based controls randomly selected from residents
    Face to face interview
    Interview rate: 91% (cases) and 97% (controls)
    Assessment of alcohol consumption: not detailed
Infante-Rivard et al. (32)0-9 yTotal alcohol: ever0.7 (0.5-0.9)Age and gender of the childMaternal age, level of schoolingNo woman consumed more than a glass of alcoholic beverages per day during her pregnancy
    Canada, 1980-1993Total alcohol: ever (Tri 1)0.7 (0.5-1.0)
    491 ALL cases from tertiary children cancer care centers of the Province of QuebecTotal alcohol: ever (Tri 2)0.7 (0.5-0.9)
    491 population-based controls selected from family allowance filesTotal alcohol: ever (Tri 3)0.7 (0.5-0.9)
    Telephone interview using a structured questionnaireTotal alcohol: <1 drink/d0.7 (0.5-1.0)
    Participation rate: 96% (cases) and 84% (controls)Total alcohol: ≥1 drink/d0.8 (0.5-1.6)
    Assessment of alcohol consumption (wine, beer or spirits): no, yes, number of glasses during each pregnancy trimester, <1 drink/d, ≥1 drink/dBeer: ever0.7 (0.5-1.1)
Wine: ever0.7 (0.5-0.9)
Spirits: ever0.9 (0.5-1.3)
Mejia-Arangure et al. (33)7.5 y (median age)Total alcohol: yes0.85 (0.15-4.68)Children with DS
    Mexico; from 1995The crude OR being estimated for a 90% CI, it has been calculated for a 95% CI
    27 AL cases from seven children cancer care institutions in Mexico City
    58 controls from institutions that treat children with DS
    Interview using a questionnaire
    Response rate: not mentioned
    Assessment of alcohol consumption frequency: no, <1 beverage/wk, >1 beverage/wk
Clavel et al. (34)0-14 yTotal alcohol: ever1.5 (0.9-2.5)Age, gender, hospital, ethnicityAge, gender, center origin, parental socio-professional categorySee Menegaux et al. (35)
    France, 1995-1999Total alcohol: 1 drink/wk1.4 (0.8-2.6)
    219 AL cases from hospital (Paris, Lyon, Lille, Nancy)Total alcohol: 2 drinks/wk1.7 (0.6-4.7)
    105 controls from orthopedic departmentsTotal alcohol: >2 drinks/wk1.4 (0.6-3.4)
    Face-to-face interview using a standardized questionnaire
    Interview rate: 99% (cases and controls)
    Assessment of weekly alcohol consumption
Menegaux et al. (35)0-14 yTotal alcohol: ever2.0 (1.4-3.0)2.6 (1.2-5.8)Age, gender, hospital, ethnicityStratification variables, age, gender, center origin
    France, 1995-1999Total alcohol: 1 glass/wk2.0 (1.3-3.0)2.8 (1.2-6.6)
    240 ALL and 40 ANLL cases from hospitals (Paris, Lyon, Lille, Nancy)Total alcohol: 2 glasses/wk2.8 (1.3-6.0)
    288 controls from orthopedic departmentsTotal alcohol: >2 glasses/wk1.9 (0.9-3.5)2.4 (0.8-7.1)
    Face-to-face interview using a standardized questionnaireBeer: ever1.4 (0.9-2.3)0.7 (0.3-2.1)
    Participation rate: 95% (cases) and 95% (controls)Wine: ever1.4 (1.0-2.1)1.4 (0.7-3.0)
    Assessment of daily alcohol consumption: total number of drinks of any type of alcoholSpirits: ever1.8 (1.3-2.9)1.4 (0.7-3.1)
0-2 yTotal alcohol: ever5.1 (1.5-17.5)Confirmed by authors
Ross et al. (36)0-19 yTotal alcohol: yes0.98 (0.56, 1.74)Age at diagnosisChildren with DS
    United States, 1997-2002
    158 AL cases from registration files of the Children's Oncology Group
    173 controls are children with DS and without leukemia
    Exclusion criteria: no telephone, not English speaking
    Telephone interview using a structured questionnaire
    Interview rate: 75% (cases) and 80.5% (controls)
    Assessment of alcohol consumption: not detailed
Kabuto et al. (37)0-15 yTotal alcohol: yes0.82 (0.59-1.16)0.71 (0.35-1.43)Age, gender, residenceNumbers of cases and controls were used to calculate the crude OR
    Japan, 1999-2001
    250 ALL and 61 AML cases from five major children's cancer study groups
    495 controls population-based controls randomly selected
    Interview using a questionnaire
    Participation rate: 49% (cases) and 28.6% (controls)
    Assessment of alcohol consumption: not detailed
Menegaux et al. (38)0-14 yTotal alcohol: yes1.1 (0.8-1.7)1.3 (0.8-2.0)0.4 (0.1-1.3)Age, gender, regionStratification variables, age, gender, region, socio-professional category, birth orderThe sample does not include cases from hospitals in Paris, Lyon, Lille, and Nancy: no overlap with the sample of the study of Menegaux et al. (35)
    France, 1995-1998Total alcohol: ≤1 glass/d0.8 (0.5-1.3)0.8 (0.5-1.5)0.4 (0.1-1.6)
    472 AL, 407 ALL and 62 AML cases from the National Registry of Childhood MalignanciesTotal alcohol: >1 glass/d2.4 (1.1-5.0)2.8 (1.3-5.9)
    567 population-based controls randomly selectedBeer, wine, cider: any1.3 (0.9-2.1)1.5 (0.9-2.3)0.4 (0.1-1.5)
    Self-administered questionnaireBeer, wine, cider: ≤1 glass/d1.0 (0.6-1.6)1.0 (0.6-1.7)0.5 (0.1-1.7)
    Participation rate: 73% (cases) and 70% (controls)Beer, wine, cider: >1 glass/d2.8 (1.2-5.6)3.3 (1.4-7.6)
    Assessment of daily alcohol consumption of any typeSpirits: any0.6 (0.2-1.8)0.7 (0.2-2.2)
Spirits: ≤1 glass/d0.7 (0.2-2.0)0.8 (0.3-2.4)
Monge et al. (39)0-14 yTotal alcohol: yes0.77 (0.39-1.53)Date of birthNumbers of cases and controls were used to calculate the crude OR
    Costa Rica, 1995-2000
    297 GL cases from the Cancer Registry and Children's Hospital of Costa Rica
    549 population-based controls randomly selected from residents
    Face to face interview and questionnaire
    Participation rate: 90% (cases) and 90.5% (controls)
    Assessment of alcohol consumption: not detailed
MacArthur et al. (40)0-14 yTotal alcohol: yes1.39 (1.01-1.93)1.43 (1.03-1.99)1.34 (0.55-3.27)Age, gender, areaMaternal age at birth, maternal education, household income, ethnicity, number or residences since birthPossibility that a subset of cases overlap with the sample of the study of Infante-Rivard et al. (32): not confirmed by authors who were contacted
    Canada, 1990-1995Total alcohol: 1-2 drinks/wk1.57 (1.11-2.23)1.57 (1.10-2.25)1.93 (0.77-4.84)
    395 AL, 348 ALL and 38 AML cases from pediatric oncology treatment centers (British Columbia, Alberta, Saskatchewan, Manitoba, and Quebec) and cancer registriesTotal alcohol: >2 drinks/wk0.74 (0.39-1.44)0.88 (0.46-1.67)
    393 population-based controls randomly selected from provincial government health insurance or family allowance rollsTotal alcohol: yes (Tri 1)0.96 (0.63-1.45)0.95 (0.62-1.45)0.79 (0.23-2.68)
    Face to face interview using a standardized questionnaireTotal alcohol: 1-2 drinks/wk (Tri 1)1.05 (0.63-1.74)0.99 (0.58-1.67)1.12 (0.27-4.67)
    Participation rate: 90% (cases) and 76% (controls)Total alcohol: >2 drinks/wk (Tri 1)0.76 (0.40-1.47)0.82 (0.42-1.59)0.44 (0.05-3.76)
    Assessment of weekly alcohol consumption of any typeTotal alcohol: yes (Tri 2)0.93 (0.58-1.48)0.88 (0.54-1.43)1.34 (0.43-4.24)
Total alcohol: 1-2 drinks/wk (Tri 2)1.06 (0.61-1.83)0.94 (0.53-1.69)2.26 (0.67-7.66)
Total alcohol: >2 drinks/wk (Tri 2)0.68 (0.30-1.54)0.76 (0.33-1.73)
Total alcohol: yes (Tri 3)0.82 (0.51-1.33)0.78 (0.47-1.28)1.10 (0.32-3.78)
Total alcohol: 1-2 drinks/wk (Tri 3)0.91 (0.51-1.60)0.79 (0.43-1.45)1.87 (0.51-6.86)
Total alcohol: >2 drinks/wk (Tri 3)0.67 (0.29-1.52)0.75 (0.33-1.71)
Rudant et al. (41)0-14 yTotal alcohol: yes1.1 (0.9-1.4)1.4 (0.9-2.2)Age, genderStratification variables, age, gender, parental professional category, maternal age at child's birth
    France, 2003-2004Total alcohol: ≤1 glass/wk1.1 (0.9-1.4)1.5 (0.9-2.4)
    647 ALL and 102 AML cases from pediatric oncology hospital departments and the French national registry of childhood blood malignanciesTotal alcohol: 2-6 glasses/wk1.1 (0.8-1.7)1.2 (0.4-2.6)
    1,681 population-based controls randomly selectedTotal alcohol: ≥7 glasses/wk1.0 (0.7-1.7)1.4 (0.5-3.6)
    Face to face interview using a standardized questionnaireBeer: yes1.3 (1.0-1.8)1.2 (0.7-2.2)
    Participation rate: 91% (cases) and 71.2% (controls)Wine: yes1.1 (0.9-1.4)1.6 (1.0-2.5)
    Assessment of alcohol consumption: number of drinks of any type per day or per weekSpirits: yes1.3 (1.1-1.7)0.8 (0.4-1.5)
Liu et al. (42)0-20 yTotal alcohol: ever1.2 (0.12-11.62)Age and genderAge and gender (no confounding was seen with: maternal age, birth weight, breast-feeding, parental education levels, parental and subjects' smoking history, maternal vitamins and iron supplements intake status, and all the other food items)Data concerning maternal drinking during pregnancy (data not shown in the article) were communicated by the authors. None of the mothers of AML cases and the matched controls reported alcohol drinking during pregnancy
    Taiwan, 1997-2005
    112 ALL and 33 AML cases from large referral hospitals (Kaohsiung) and registration files of the Department of Health of Kaohsiung
    370 population-based controls randomly selected from the same area
    Face to face interview using a standardized questionnaire
    Participation rate: 94% (cases) and 56% (controls)
    Assessment of alcohol consumption: never, ever (≥1 beverage/wk for >6 mo)

Abbreviations: ANLL, acute non-lymphoblastic leukemia; CCG, Children's Cancer Group; Tri, trimester of pregnancy.

  • *Reference group is the nonconsumers.