X, PA Buffler, RB Gunier, G Dahl, MT Smith, K Reinier and P Reynolds.
2002. Critical Windows of Exposure to Household Pesticides
and Risk of Childhood Leukemia. Environmental
Health Perspectives 110:955-960.
et al. present results demonstrating a strong relationship
between exposure to indoor pesticides and the risk
of childhood leukemia. The risk of childhood leukemia
is higher with greater exposures, and it is also highest for exposures
that occur during pregnancy, compared to exposures before pregnancy
and after birth. These results should caution families to
be extremely careful about using indoor pesticides, especially during
study is not the first to find a link between childhood leukemia
and in utero pesticide exposure. In fact, most studies
of this sort find the same basic result. Ma et al. avoid
some of the weaknesses of earlier work, however, making their results
that much more compelling.
did they do? This case-control study is one of a series
of investigations carried out by The Northern California Childhood
Leukemia Study (NCCLS).
1995 and 1999, NCCLS developed a registry of recently diagnosed
leukemia patients between the ages of 0 and 14 yrs-old in northern
California. Most patients were added to the registry within 24 hours
of diagnosis. Based on characteristics of the patient (date of birth,
sex, mother’s race (white, black, or other), Hispanicity (either
parent is Hispanic), and mother’s county of residence at the
time of child’s birth). Once the control was selected, commercially-available
searching methods were used to locate the control and invite their
participation in the study. If the initial choice declined, the
search was continued using the same process until a control subject
agreed to participate. Participation was strong: 83% of the cases
and 69% of the eligible controls. A total of 162 matched case-control
pairs formed the basis for the study.
team interviewed the primary care giver shortly after diagnosis
of the cases and controls to establish the pattern of household
pesticide use for different periods: a total of 4 years: 3 months
prior to pregancy, pregnancy, and each of the first 3 years after
birth. The interviews ascertained the types and locations of pesticide
use, as well as the frequency. Ma et al. then used statistical
analyses to evaluate the impact of pesticide use on the likelihood
that a child would develop leukemia, and in particular on how leukemia
risk was affected by timing of pesticide use relative to birth or
the type of pesticide application.
did they find?
pesticide use was quite common. For example, during the first year
after birth, more than half of households used insecticides or indoor
of the children with leukemia used professional pest control services
more commonly than the families of matched controls. This
pattern held for all time periods studied. In fact, the odds-ratio
for professional pesticide applicants exceeded 2 for all of the
time periods except for the 3 months prior to pregnancy. This
suggests that a child in a home using professional pest control
services is more than twice as likely to develop leukemia.
And the odds ratio for a child living in a home that was professionally
treated at any time during the 4-yr period of concern was 2.8.
frequency of application was recorded in the interviews, Ma et
al. were able to ask whether the odds ratios were affected
by frequency of exposure. This is a very rough surrogate for amount
of exposure, or dose. Comparing odds-ratios of children not exposed
during the 4-year period to those with frequency indices of 1-5
and those with >5, Ma et al. found that increased frequency
was associated with increased risk: ORs, respectively, were 1.5
(95% CI 0.6-3.6) and 2.4 (1.2-5.1). Thus, increased use
was associated with increased risk.
striking temporal pattern also emerged from the analysis. The risk
was particularly high for application during pregnancy compared
to other periods, as shown by the following figure.
odds-ratios at different times before, during and after pregnancy,
for indoor vs. outdoor pesticides. Figure adapted from Ma et
contrast to the links between indoor use and leukemia, according
to Ma et al. "the magnitude of association between
exposure to outdoor pesticides and the risk of leukemia was small."
This difference could result from many factors, including the fact
that the suite of pesticides used outdoors (more herbicides) differed
from those indoors (more insecticides). The data set was not large
enough to begin to tease these factors apart.
does it mean? Ma et al.'s work supports suggestions
from previous studies indicating an association between pesticide
use and childhood leukemia. Three patterns stand out:
association between risk and the use of professional applicators
in the home;
increase in risk associated with increased frequency of exposure,
and the enhanced risk during pregnancy.
always, epidemiological studies offer very blunt instruments to
explore the link between contamination and health. Given all the
variables, the relatively limited sample size, and the relative
crudeness of exposure measurements, the magnitude of effects they
observe are quite striking. These factors often obscure real relationships
between exposure and impact in epidemiological studies (that is,
they cause what statisticians call "false negatives").
The fact that Ma et al. detected such a strong signal amidst
all the noise heightens concerns about the role of pesticides in
causing childhood leukemia.
the basis of these results, cautious parents should choose to avoid
household use of pesticides prior to, during, and after pregnancy.