Associations of Birthweight and Maternal Fertility Problems with Childhood Cancers.

Higher birthweight, maternal history of miscarriage and low birth order have been associated with increased risk of childhood leukaemias and some solid tumours. No study has investigated these factors together and differences in disease etiology between girls and boys have been generally overlooked. In a retrospective case-control study, 732 childhood (≤15 yr) cancer cases from the population-based Northern Region Young Persons’ Malignant Disease Registry (NRYPMDR) whose hospital birth records could be accessed and 3723 controls matched for date and hospital of birth were compared. We examined maternal reproductive history and birthweight for gender-specific associations using conditional logistic regression. In univariate analysis, maternal history of miscarriage showed an association with all cancers (OR = 1.29; 95% CI = 1.05 to 1.62, P = 0.02). In individual cancer groups, this association was significant for acute lymphoblastic leukaemia (ALL) (n=225, OR = 1.56; 95% CI = 1.07 to 2.27, P = 0.02), and marginally significant in osteosarcoma and neuroblastic tumours (neuroblastoma and ganglioneuroblastoma). There was no significant association with birth order. Being first born was a weak risk factor for ALL in boys only (OR=1.3, 95% CI = 0.8 to1.8). In boys but not in girls, the risk of ALL increased with birthweight (OR = 1.06 per 100 gr increase; 95% CI = 1.01 to 1.11, P = 0.01). When birthweights were normalized using UK standards for gestational age and gender, the associations were not more marked. A multivariate model for ALL confirmed the independence of associations with miscarriage history and birthweight. Gestational age was not a risk marker and did not explain the associations with birth weight and miscarriage history. Consideration of gender unravelled significant associations of maternal reproductive history and size at birth with childhood cancer markedly different between girls and boys. Most notably, associations with birth weight and miscarriage and the weak association with being first-born in childhood ALL were all stronger in males. The findings for birthweights normalized for gestational age suggested that size at birth rather than in utero growth trajectory is of etiologic importance in childhood ALL.