In Utero Alcohol Exposure Linked With Childhood AML

Major Finding: A significant association between in utero exposure to alcohol and childhood acute myeloid leukemia was noted in five studies of children diagnosed at age 0-4 years (OR 2.68) when compared with nonexposed controls.

Data Source: Meta-analysis of 21 case-control studies.

Disclosures: The authors had no disclosures to report. The study was funded with a grant from the World Cancer Research Fund.

Alcohol intake during pregnancy was associated with a significant increase in the risk of acute myeloid leukemia in children who were exposed during pregnancy, but not with an increased risk of acute lymphoblastic leukemia, in a review and meta-analysis of case-control studies from numerous countries.

The results “indicate that the risk of childhood AML increases with maternal alcohol consumption during pregnancy,” reported Dr. Paule Latino-Martel of the University of Paris XIII and associates (Cancer Epidemiol. Biomarkers Prev. 2010;19:OF1-23).

This was the first meta-analysis the authors were aware of that investigated the role of in utero exposure to alcohol in relation to childhood leukemia. The studies had limitations, they said, and more studies with detailed information on alcohol exposure are needed.

The 21 studies included in the review comprised 20 different study populations, for a total of 8,128 cases and 10,207 controls. Because data collection varied among the studies, only relevant studies were included in categorical and dose-response meta-analyses.

A meta-analysis of nine studies found the significant positive association between maternal alcohol consumption during pregnancy and the risk of childhood acute myeloid leukemia (AML), with an odds ratio of 1.56. Maternal consumption of alcohol during pregnancy was not significantly associated with an increased risk of acute lymphoblastic leukemia (ALL), compared with no exposure.

A few studies included data that made it possible to do a dose-response analysis, which was “consistent with a stronger association with AML compared with ALL.”

For each increase of one drink per week, the increase in odds ratios was 1.04 for ALL and 1.24 for AML, but the authors said that the results were heterogeneous, and no conclusions could be made about the amount of alcohol intake that was associated with an increased risk. More studies with more details on alcohol exposure are needed, they added.

Examining the data on childhood age, the authors found no association between maternal alcohol intake during pregnancy and ALL that was diagnosed at age 0-4 years.

But the association between in utero exposure to alcohol and AML that was diagnosed in children aged 0-4 years was significant in five studies (OR 2.68), which the authors said was “consistent with the potential role of prenatal exposure to alcohol in the etiology of AML.”

“The biological plausibility of this association is supported by the fact that alcoholic beverages are recognized as carcinogenic for humans and are involved in several fetal alcohol-related diseases,” they said.

But the reason why in utero exposure to alcohol “may specifically modify the risk of AML in young children is unknown,” the authors said. They pointed out that the peak of AML cases in children is earlier than that of ALL, which suggests “a stronger association or shorter latency of AML with prenatal exposures.”

With little information in the studies on the type of alcohol consumed, the authors were not able to determine whether maternal consumption of one type of alcohol over another (beer vs. wine vs. spirits) was associated with a greater risk of leukemia.

The data available did not suggest, however, that one type of alcohol posed a greater risk than did another type, they wrote.

Based on a meta-analysis of those studies that provided information on alcohol intake by trimester, the authors found no association between childhood ALL and alcohol consumption during any trimester.

For AML, the data were limited, but in the two studies that included this information, the odds ratio “tended to be slightly higher when alcohol was consumed in the second and third trimesters compared with the first trimester,” they said.

The association between maternal alcohol intake and the risk of childhood leukemia—particularly AML—should be studied further and in large birth cohort studies, they recommended.

Noting that an estimated 12% of pregnant women in the United States drink alcohol during pregnancy (and 30% in Sweden, 52% in France, 59% in Australia, and 60% in Russia), they urged that efforts to reduce alcohol use be directed toward women during pregnancy as well as before they become pregnant, which might help “contribute to reduce the occurrence of harmful effects including AML in young children,” they said.