Maternal body mass index, diabetes, and gestational weight gain and risk for pediatric cancer in offspring: A systematic review and meta-analysis

Background: Pediatric cancer incidence has steadily increased concurrent with rising adult obesity, but associations between maternal obesity and associated comorbidities and pediatric cancer risk remain understudied. We aimed to quantitatively characterize associations of pediatric cancer risk with maternal prepregnancy body mass index (BMI), gestational weight gain, and maternal diabetes. Methods: We performed a comprehensive and systematic literature search in Ovid and EMBASE from their inception to March 15, 2021. Eligible studies reported risk estimates and sample sizes and provided sufficient description of outcome and exposure ascertainment. Random effects models were used to estimate pooled effects. Results: Thirty-four studies were included in the analysis. Prepregnancy BMI was positively associated with leukemia risk in offspring (odds ratio [OR] per 5-unit BMI increase =1.07, 95% confidence intervals [CI] = 1.04 to 1.11; I-2 = 0.0%). Any maternal diabetes was positively associated with acute lymphoblastic leukemia risk (OR= 1.46, 95% CI =1.28 to 1.67; I-2 = 0.0%), even after restricting to birthweight-adjusted analyses (OR = 1.74, 95% CI = 1.29 to 2.34; I-2 = 0.0%), and inversely associated with risk of central nervous system tumors (OR = 0.73, 95% CI = 0.55 to 0.97; I-2 = 0.0%). Pregestational diabetes (OR = 1.57, 95% CI = 1.11 to 2.24; I-2 = 26.8%) and gestational diabetes (OR= 1.40, 95% CI =1.12 to 1.75; I-2 = 0.0%) were also positively associated with acute lymphoblastic leukemia risk. No statistically significant associations were observed for gestational weight gain. Conclusions: Maternal obesity and diabetes may be etiologically linked to pediatric cancer, particularly leukemia and central nervous system tumors. Our findings support weight management and glycemic control as important components of maternal and offspring health. Further validation is warranted.