Maternal Body Mass Index, Diabetes, and Gestational Weight Gain and Risk for Pediatric Cancer in Offspring: A Systematic Review and Meta-Analysis

Abstract

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 pre-pregnancy 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 15th, 2021. Eligible studies reported risk estimates, 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. Pre-pregnancy BMI was positively associated with leukemia risk in offspring (OR per 5-unit BMI increase =1.07 [95% CI = 1.04–1.11] I2 = 0.0%). Any maternal diabetes was positively associated with acute lymphoblastic leukemia (ALL) risk (OR = 1.46 [95% CI = 1.28–1.67] I2 = 0.0%), even after restricting to birthweight-adjusted analyses (OR = 1.74 [95% CI 1.29–2.34] I2 = 0.0%), and inversely associated with risk of central nervous system tumors (OR = 0.73 [95% CI = 0.55–0.97] I2 = 0.0%). Pre-gestational diabetes (OR = 1.57 [95% CI = 1.11–2.24] I2 = 26.8%) and gestational diabetes (OR = 1.40 [95% CI = 1.12–1.75] I2 = 0.0%) were also positively associated with ALL 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.

Maternal Body Mass Index, Gestational Weight Gain, and Risk of Cancer in Offspring: A Systematic Review and Meta-Analysis

“…In 2010, a meta-analysis performed by Alam et al suggested that higher maternal weight did not increase testicular cancer risk in offspring, which is inconsistent with our findings [ 24 ]. Furthermore, a meta-analysis of 34 studies published in 2022 found pregnancy BMI was positively associated with leukemia risk in offspring (odds ratio [OR] per 5-unit BMI increase = 1.07, 95% CI: 1.04–1.1), which is consistent with our study [ 47 ]. In comparison, our meta-analysis not only included pediatric cancer but also cancer in adults, which is thought to be more comprehensive.…”

Perinatal folate levels do not influence tumor latency or multiplicity in a model of NF1 associated plexiform-like neurofibromas

“…Therefore, current results may differ from previous analyses due to folate being administered perigestationally versus directly to offspring. Although previous findings [30, 31] demonstrated associations between maternal folate and adverse events in offspring [31], and it is established that the maternal intrauterine environment can impact offspring cancer risk [47–49], it is possible that maternal conditions are not as critical to plexiform-like neurofibroma formation relative to other tumors. Future studies on the effects dietary folate levels throughout life may reveal a role in peripheral nerve sheath tumor development.…”

Associations between birth defects with neural crest cell origins and pediatric embryonal tumors

“…Although we were able to use the large GOBACK study, we still had insufficient sample size to thoroughly investigate EMM because the sample size within the strata of covariates became sparse. Our selection of covariates was primarily limited to demographic variables from the birth certificate, precluding investigation of health‐related factors such as maternal smoking, alcohol use, or diabetes, which have been shown to be associated with pediatric cancers 22,34,41,42 . As a general limitation of registry studies, children who moved from their state of birth would be lost to follow‐up.…”

“…Our selection of covariates was primarily limited to demographic variables from the birth certificate, precluding investigation of healthrelated factors such as maternal smoking, alcohol use, or diabetes, which have been shown to be associated with pediatric cancers. 22,34,41,42 As a general limitation of registry studies, children who moved from their state of birth would be lost to follow-up.…”