Clinical Context

Although childhood cancer is relatively rare, it is still the leading cause of death past infancy among children in the United States. Infants and children are especially susceptible to prenatal and early-life exposures. Maternal exposures before and during pregnancy (eg, obesity) could therefore have a significant effect on the health of the child, including a risk for cancer development.

The goal of this registry study by Stacy and colleagues was to evaluate the association of maternal anthropometric characteristics derived from birth certificates with an increased risk for development of cancer in childhood after adjustment for known maternal and infant risk factors.

Study Synopsis and Perspective

Obesity has been linked to an increased risk for cancer in adults, but its potential role in childhood cancers is less clear. New findings suggest that infants born to obese mothers are more likely to develop cancer in early childhood.

An analysis of data from almost 2 million infants found that the offspring of women who were severely obese (body mass index [BMI] >40 kg/m²) were twice as likely to develop leukemia before age 5 years than the offspring of women who were of normal weight.

After adjusting for confounders such as maternal age and race, which are 2 established risk factors for childhood cancer, maternal obesity was associated with the risk for childhood cancer.

"Right now, we don't know of many avoidable risk factors for childhood cancer," said lead author Shaina Stacy, PhD, postdoctoral scholar in the University of Pittsburgh and the University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, Pittsburgh, Pennsylvania.

"My hope is that this study can be, in a way, empowering and also motivating for weight loss," she said in a statement.

The study was published online in the American Journal of Epidemiology.

For the study, Dr Stacy and colleagues used data from the Pennsylvania Department of Health. They identified 1,827,875 infants who were born between 2003 and 2015.

A total of 2352 children were diagnosed with any type of cancer, and 747 children were diagnosed with leukemia before age 14 years.

The most common diagnoses were acute lymphoblastic leukemia (ALL) and neuroblastoma.

Older maternal age was associated with a higher risk for any childhood cancer, including leukemia. Nonwhite race was associated with a lower risk. The analyses were adjusted for these risk factors.

The offspring of women with a BMI ≥40 kg/m² had a 1.32 times higher risk of developing any type of cancer and 1.57 times higher risk for leukemia compared with children born to mothers with BMIs of 18.5 to 24.9 kg/m².

In addition, children born to mothers with prepregnancy weights of 90 to 99 kg and ≥100 kg had a 46% and 42% higher risk for leukemia, respectively.

With respect to infant factors, the authors found that those infants whose birth weight was 30% lower than expected or 30% higher than expected had a 37% and a 116% higher risk for any childhood cancer, respectively, as compared with infants who were within 10% of their expected weight (P _{curvilinearity} <.0001).

Infants whose birth weight was ≥30% higher than expected had an 84% higher risk of developing leukemia. Infants who were large for gestational age also had a greater risk for any cancer and leukemia in comparison with infants who were of appropriate size.

"We are dealing with an obesity epidemic in this country," said senior author Jian-Min Yuan, MD, PhD, professor of epidemiology at University of Pittsburgh Public Health and coleader of the Cancer Epidemiology and Prevention Program at UPMC Hillman Cancer Center, in a statement.

"From a prevention point of view, maintaining a healthy weight is not only good for the mother but also for the children, too," he said.

Weighing in on the study, Maria Chang Swartz, PhD, MPH, RD, LD, assistant professor, department of pediatrics-research, The University of Texas MD Anderson Cancer Center, Houston, Texas, noted that, overall, the findings from this study point to an area that needs further investigation.

"I agree that at this time, the biological mechanisms are still unknown," she said. "The authors' conjecture regarding the role of insulin-like growth hormone factor is an area that is receiving a lot of attention, especially given that stronger evidence is showing an association between high prepregnancy BMI and risk for childhood obesity."

Nonetheless, she did not feel there is enough evidence at this time to include a discussion of a risk for childhood leukemia during the prepregnancy consults for women with high BMIs, "[b]ut maintaining a healthy weight is important, because obesity is associated with many health issues," Dr Swartz said. "Given that stronger evidence is showing an association between high prepregnancy BMI and risk for gestational diabetes as well as risk for childhood obesity in their offspring, there is a need to emphasize maintenance of healthy weight among women of childbearing age," she said.

The study was partially supported by the Arnold Palmer Endowment Fund. Stacy was supported by the National Cancer Institute of the National Institutes of Health. The other authors have disclosed no relevant financial relationships.

Am J Epidemiol. Published online May 20, 2019.^[1]

Clinical Implications

• Prenatal exposure to maternal obesity- and fetal growth–related factors appears to increase the risk for development of childhood leukemia and other cancer, according to a registry study by Stacy and colleagues.
• If the findings are confirmed by studies in other populations, it would provide a rationale for weight control among women planning to conceive as a possible preventive measure against cancer risk in their children.
• Implications for the Healthcare Team: Regardless of the potential risk for cancer in the offspring, women of childbearing age should maintain a healthy weight because obesity is associated with many health problems, including gestational diabetes and a risk for childhood obesity in the offspring.

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