High Ambient Temperature in Pregnancy and Risk of Childhood Acute Lymphoblastic Leukemia

Abstract

Background: High ambient temperature is increasingly common due to climate change and is associated with risk of adverse pregnancy outcomes. Acute lymphoblastic leukemia (ALL) is the most common malignancy in children, the incidence is increasing, and in the United States it disproportionately affects Latino children. We aimed to investigate the potential association between high ambient temperature in pregnancy and risk of childhood ALL.

Methods: We used data from California birth records (1982-2015) and California Cancer Registry (1988-2015) to identify ALL cases diagnosed <14 years and 50 times as many controls matched by sex, race/ethnicity, and date of last menstrual period. Ambient temperatures were estimated on a 1-km grid. Association between ambient temperature and ALL was evaluated per gestational week, restricted to May-September, adjusting for confounders. Bayesian meta-regression was applied to identify critical exposure windows. For sensitivity analyses, we evaluated a 90-day pre-pregnancy period (assuming no direct effect before pregnancy) and constructed an alternatively matched dataset for exposure contrast by seasonality.

Findings: Our study included 6,258 ALL cases and 307,579 controls. The peak association between ambient temperature and risk of ALL was observed in gestational week 8, where a 5 °C increase was associated with an odds ratio of 1.09 (95% confidence interval 1.04-1.14) and 1.05 (95% confidence interval 1.00-1.11) among Latino and non-Latino White children, respectively. The sensitivity analyses supported this.

Interpretation: Our findings suggest an association between high ambient temperature in early pregnancy and risk of childhood ALL. Further replication and investigation of mechanistic pathways may inform mitigation strategies.

Figure 1.

Gestational week specific associations between high ambient temperature and risk of childhood acute lymphoblastic leukemia. Results from the two-stage Bayesian meta-regression analysis of ambient temperature and risk of childhood acute lymphoblastic leukemia. Adjusted for race/ethnicity, birth order, maternal and paternal age, maternal education, neighborhood poverty, date of LMP ±7 days (i.e., seasonality and time trend), and offspring sex. Unit of exposure per 5 °C increase in mean weekly ambient temperature. Vertical bars represent 95% confidence intervals. Statistically significant associations between high ambient temperature and childhood acute lymphoblastic leukemia highlighted in red.

Figure 2.

High ambient temperature in gestational week 8 and risk of childhood acute lymphoblastic leukemia, stratified by race/ethnicity and age at diagnosis. Results from the two-stage Bayesian meta-regression analysis of ambient temperature and risk of childhood acute lymphoblastic leukemia in gestational week 8 (identified as most susceptible week of exposure) and stratified by race/ethnicity and age at diagnosis. Adjusted for race/ethnicity, birth order, maternal and paternal age, maternal education, neighborhood poverty, date of LMP ±7 days (i.e., seasonality and time trend), and offspring sex. Unit of exposure per 5 °C increase in mean weekly ambient temperature. Horizontal bars represent 95% confidence intervals. Statistically significant associations between high ambient temperature and childhood acute lymphoblastic leukemia highlighted in bold horizontal bars.

Figure 3.

Non-linear analysis of ambient temperature and risk of childhood acute lymphoblastic leukemia in gestational week 8. Results from cubic spline analysis with 5 knots. Mean weekly ambient temperature of 15 °C used as reference. Adjusted for race/ethnicity, birth order, maternal and paternal age, maternal education, neighborhood poverty, date of LMP ±7 days (i.e., seasonality and time trend), and offspring sex. Dotted lines represent 95% confidence intervals.