Selected characteristics of 434 infant leukaemia cases (262 ALL, 172 AML) and 323 controls are shown in . Cases and controls were similar with respect to previous fetal loss, smoking during pregnancy, pre-pregnancy BMI, and infant gender and birth weight. However, compared with mothers of controls, mothers of cases were more likely to be younger (ALL), of Hispanic ethnicity (ALL, AML), of lower income (ALL, AML), and to report morning sickness (ALL). Case mothers were less likely to have completed education beyond high school (ALL), initiated multivitamin use before knowledge of pregnancy (ALL), reported alcohol consumption during pregnancy (AML), and confirmed pregnancy before the third month (AML).
We also evaluated the distribution of cases and controls with regard to analgesic use across selected potential confounders for the two pregnancy periods (data not shown). Before knowledge of pregnancy, acetaminophen was the most commonly (63%) used analgesic, followed by non-aspirin NSAIDs (31%) and aspirin (9%). Compared with non-regular users (
5 times), regular users were more likely to smoke during pregnancy and less likely to have completed education beyond high school or to report an annual household income greater than $75
000. Regular aspirin or non-aspirin NSAID users were more likely to be Caucasian and to drink during pregnancy, whereas regular acetaminophen users were less likely to use multivitamins before knowledge of pregnancy, compared with non-regular users. After knowledge of pregnancy, acetaminophen use increased (69%), whereas the use of aspirin and non-aspirin NSAIDs decreased (3 and 9%, respectively); only 19 case mothers and 13 control mothers used aspirin or non-aspirin NSAIDs regularly (
Possible associations between infant leukaemia and maternal analgesic use, assessed both before and after knowledge of pregnancy, are shown in . There was no association between any use or regular use of aspirin, non-aspirin NSAIDs or acetaminophen with infant ALL, in either pregnancy period. However, for AML, there was a statistically significant or borderline significant reduced risk associated with any use of non-aspirin NSAIDs (OR=0.60, CI: 0.37–0.97) and acetaminophen (OR=0.66, CI: 0.43–1.01), respectively, but not with aspirin (OR=0.55, CI: 0.24–1.26); regular use of each analgesic did not reflect further reduction in risk. These inverse associations were observed only before knowledge of pregnancy, whereas they were attenuated toward the null after knowledge of pregnancy.
Table 2 Association of maternal pain reliever use during pregnancy and the risk of infant leukaemiaa
We also examined whether associations were confined to particular MLL groups of ALL and AML (data not shown). Among ALL cases, 155 were MLL+, 77 MLL−, and 30 with undetermined MLL status, whereas among AML cases there were 68 MLL+, 66 MLL−, and 38 undetermined. For AML, the inverse association observed for non-aspirin NSAIDs and acetaminophen was confined to cases that did not have the MLL gene rearrangement (OR=0.42, CI: 0.20–0.88, and OR=0.57, CI: 0.32–1.02, respectively), whereas ALL showed no association for either MLL subgroup.