Residential mobility in early childhood and the impact on misclassification in pesticide exposures.

Studies of environmental exposures and childhood cancers that rely on records often only use maternal address at birth or address at cancer diagnosis to assess exposures in early childhood, possibly leading to exposure misclassification and questionable validity due to residential mobility during early childhood. Our objective was to assess patterns and identify factors that may predict residential mobility in early childhood, and examine the impact of mobility on early childhood exposure assessment for agriculturally applied pesticides and childhood cancers in California. We obtained the addresses at diagnosis of all childhood cancer cases born in 1998-2011 and diagnosed at 0-5 years of age (n = 6478) from the California Cancer Registry (CCR), and their birth addresses from linked birth certificates. Controls were randomly selected from California birth records and frequency matched (20:1) to all cases by year of birth. We obtained residential histories from a public-record database LexisNexis for both case (n = 3877 with age at diagnosis 1-5 years) and control (n = 99,262) families. Logistic regression analyses were conducted to assess the socio-demographic factors in relation to residential mobility in early childhood. We employed a Geographic Information System (GIS)-based system to estimate children's first year of life exposures to agriculturally applied pesticides based on birth vs diagnosis address or residential histories based upon Lexis-Nexis Public Records and assessed agreement between exposure measures using Spearman correlations and kappa statistics. Over 20% of case and control children moved in their first year of life, and 55% of children with cancer moved between birth and diagnosis. Older age at diagnosis, younger maternal age, lower maternal education, not having a Hispanic ethnic background, use of public health insurance, and non-metropolitan residence at birth were predictors of higher residential mobility. There was moderate to strong correlation (Spearman correlation = 0.76-0.83) and good agreement (kappa = 0.75-0.81) between the first year of life exposure estimates for agricultural pesticides applied within 2 km of a residence relying on an address at birth or at diagnosis or LexisNexis addresses; this did not differ by outcome status, but agreement decreased with decreasing buffer size, and increasing distance moved or age at diagnosis. These findings suggest that residential addresses collected at one point in time may represent residential history in early childhood to a reasonable extent; nevertheless, they exposure misclassification in the first year of life remains an issue. Also, the highest proportion of women not captured by LexisNexis were Hispanic women born in Mexico and those living in the lowest SES neighborhoods, i.e. possibly those with the higher environmental exposures, as well as younger women and those with less than high school education. Though LexisNexis only captures a sub-population, its data may be useful for augmenting address information and assessing the extent of exposure misclassification when estimating environmental exposures in large record linkage studies. Future research should investigate how to correct for exposure misclassification introduced by residential mobility that is not being captured by records.

Caesarean delivery and risk of childhood leukaemia: a pooled analysis from the Childhood Leukemia International Consortium (CLIC).

BACKGROUND: Results from case-control studies have shown an increased risk of acute lymphoblastic leukaemia (ALL) in young children born by caesarean delivery, and prelabour caesarean delivery in particular; however, an association of method of delivery with childhood leukaemia subtypes has yet to be established. We therefore did a pooled analysis of data to investigate the association between childhood leukaemia and caesarean delivery. METHODS: We pooled data from 13 case-control studies from the Childhood Leukemia International Consortium done in nine countries (Canada, Costa Rica, Egypt, France, Germany, Greece, Italy, New Zealand, and the USA) for births from 1970-2013. We analysed caesarean delivery overall and by indications that probably resulted in prelabour caesarean delivery or emergency caesarean delivery. We used multivariable logistic regression models, adjusted for child's birthweight, sex, age, ethnic origin, parental education, maternal age, and study, to estimate odds ratios (ORs) and 95% CIs for the risk of ALL and acute myeloid leukaemia (AML) in children aged 0-14 years at diagnosis. FINDINGS: The studies provided data for 8780 ALL cases, 1332 AML cases, and 23 459 controls, of which the birth delivery method was known for 8655 (99%) ALL cases, 1292 (97%) AML cases, and 23 351 (>99%) controls. Indications for caesarean delivery were available in four studies (there were caesarean deliveries for 1061 of 4313 ALL cases, 138 of 664 AML cases, and 1401 of 5884 controls). The OR for all indications of caesarean delivery and ALL was 1·06 (95% CI 0·99-1·13), and was significant for prelabour caesarean delivery and ALL (1·23 [1·04-1·47]; p=0·018). Emergency caesarean delivery was not associated with ALL (OR 1·02 [95% CI 0·81-1·30]). AML was not associated with caesarean delivery (all indications OR 0·99 [95% CI 0·84-1·17]; prelabour caesarean delivery 0·83 [0·54-1·26]; and emergency caesarean delivery 1·05 [0·63-1·77]). INTERPRETATION: Our results suggest an increased risk of childhood ALL after prelabour caesarean delivery. If this association is causal, maladaptive immune activation due to an absence of stress response before birth in children born by prelabour caesarean delivery could be considered as a potential mechanism. FUNDING: National Cancer Institute.