Childhood cancer risk is associated with maternal health during pregnancy. Anemia in pregnancy is a common condition, especially in low-income countries, but a possible association between maternal anemia and childhood cancer has not been widely studied.
We examined the relation in a population-based study in Denmark (N = 6420 cancer cases, 160,485 controls). Cases were taken from the Danish Cancer Registry, and controls were selected from national records. We obtained maternal anemia diagnoses from the National Patient and Medical Births registries. In a separate analysis within the years available (births 1995–2014), we examined cancer risks among mothers taking prescribed vitamin supplements, using data from the National Prescription Register. We estimated the risks of childhood cancer using conditional logistic regression.
The risks of neuroblastoma [odds ratio (OR= 1.83, 95% confidence interval (CI): 1.04, 3.22] and acute lymphoblastic leukemia (OR= 1.46, 95% CI 1.09, 1.97) were increased in children born to mothers with anemia in pregnancy. There was a two-fold increased risk for bone tumors (OR= 2.59, 95% CI: 1.42, 4.72), particularly osteosarcoma (OR= 3.54, 95% CI 1.60, 7.82). With regards to prescribed supplement use, mothers prescribed supplements for B12 and folate deficiency anemia (OR= 4.03, 95% CI 1.91, 8.50) had an increased risk for cancer in offspring.
Our results suggest that screening for anemia in pregnancy and vitamin supplementation may be an actionable strategy to prevent some cases of childhood cancer.
- • Pregnancy anemia was related to greater risk for offspring cancer.
- • Neuroblastoma, acute lymphoblastic leukemia, and osteosarcoma had increased risk.
- • Offspring of mothers prescribed folate/B12 had a fourfold increased risk of cancer.
Anemia occurs as a result of a decrease in the body’s concentration of hemoglobin. During pregnancy, maternal anemia primarily arises due to folate, iron deficiency, and sometimes other causes such as vitamin B12 deficiency and chronic infections. Maternal anemia is common because of the natural increases in dietary needs of the mother during the pregnancy period. On average, a mother requires a daily intake of 400 g folate, 2.20 g of vitamin B12, and over the course of her pregnancy, a total of 1200 mg of iron . Severe maternal anemia can affect the fetus because of its effects on placental structure, oxygenation of the developing fetal systems and organs, nutrient absorption, brain development, and formation of red blood cells .
The global prevalence of anemia during pregnancy is 41.8% and in Denmark, the World Health Organization estimates the prevalence of anemia to be 16% . Maternal anemia is associated with negative birth outcomes such as low birth weight and preterm deliveries. Research also suggests that anemia may be linked to cancer in adults. Folate deficiency changes gene expression as a result of DNA hypomethylation, which can result in malignancies . In Denmark, the Danish National Board of Health recommended universal iron supplementation among pregnant women (50–70 mg daily starting in week 20 of gestation) in 1998. Iron supplements are widely available over the counter, and an estimated 77% of Danish women ever take them during pregnancy . Similarly, since 1997, the Danish Health and Medicines Authority recommended that Danish pregnant women take 0.4 mg of folic acid supplementation daily, beginning at least one month before conception and continued through the first 12 weeks of pregnancy. However, only 10.4% of Danish women adhere to this recommendation .
Cancer is the second leading cause of mortality in children in high-income countries . Although the etiology of childhood cancers is largely unknown, known risk indicators include low or high birth weight, older parental age, birth defects, genetic syndromes, and ionizing radiation. Exposures in-utero are believed to play an etiologic role .
The literature on the relations between maternal anemia and childhood cancers is sparse. While studies have been limited and results conflicting, the most consistent findings suggest associations between childhood leukemia, neuroblastoma, and retinoblastoma with maternal anemia during pregnancy . The aim of the present study was to further examine the potential relation between maternal anemia during pregnancy and childhood cancers in a population-based study in Denmark.