Young Child In Garden
18 August 2017

Washington University Team Explores Link Between Birth Defects & Pediatric Cancer

Some children who are born with birth defects may be more likely to develop certain types of pediatric cancer, according to a groundbreaking new study from researchers at Washington University in St. Louis. Analyzing the results from 80 research projects conducted around the world, Dr. Kimberly J. Johnson and her colleagues found a strong association between major birth defects and childhood cancers, noting particular risks for children born with neural tube defects and gastrointestinal abnormalities.

Do Congenital Anomalies & Cancer Share Genetic Link?

Pediatric cancer is the leading cause of death in American children between the ages of 1 and 14, claiming around 14,000 lives every year. The last decade of medical research has turned up substantial evidence to support the hypothesis that pediatric cancer, much like a range of birth defects, involves some level of abnormal fetal development, often due to genetic abnormalities. About 8.5% of children with cancer appear to have inherited genetic mutations that predispose them to developing the disease, according to researchers in the New England Journal of Medicine.

Mother Holding Baby Under Tree

More broadly, around 1 in 3 of these children can be considered genetically-predisposed when one expands the definition of predisposition from specific genetic mutations to include a family history of pediatric cancer and co-occurring medical conditions. In short, a strong genetic component seems to be in play, a hypothesis that can also proposed to explain many congenital abnormalities. What, then, is the connection between birth defects and pediatric cancer, if both medical conditions ultimately come down to atypical fetal growth?

Study: Strong Connection Between Pediatric Cancer, Birth Defects

To answer this question, a team at Washington University in St. Louis pooled the data from 80 different epidemiological studies that looked at the potential associations between pediatric cancers and birth defects. Their results were published in the journal PLOS One on July 27, 2017.

While variations in study design make it hard to draw definitive conclusions, a strong trend began to appear as the Washington University researchers pored over their data. The majority of studies, both cohort and case-control, reported positive associations between the presence of birth defects and an increased risk for pediatric cancer.

Neural Tube Defects

Several of the largest studies under review showed that cancer risks were higher in younger children, but began to decline as children aged. Two particularly-comprehensive reports showed a robust association between birth defects and tumors of the nervous system. Children born with nervous system defects (so-called neural tube defects like spina bifida and anencephaly) were nearly 8 times more likely to be diagnosed with cancerous tumors of the central nervous system.

Gastrointestinal Defects

Similar results came for neuroblastoma, a form of cancer that develops from cells in the sympathetic nervous system, a bundle of nerve tissues that run alongside the spinal cord and trigger “fight or flight” responses. The researchers found evidence that, in general, children born with birth defects are more likely to develop neuroblastoma. A strong link to any one type of birth defect proved elusive, with the possible exception of gastrointestinal abnormalities. At least four studies found consistent results to support a link between defects of the GI tract and neuroblastoma.

Additional Findings

Here are some of the study’s other notable findings:

  • Retinoblastoma (Eye Cancer) – Consistent association with birth defects overall and, specifically, structural defects, including cleft palate, club foot and limb abnormalities
  • Wilms Tumor (Kidney Cancer) – Weak or non-existent association with birth defects overall, but strong association with congenital syndromes (including Beckwith-Wiedemann syndrome) already known to cause pediatric kidney cancers
  • Hepatoblastoma (Liver Cancer) – Consistent association with birth defects overall and, specifically, genitourinary abnormalities like hypospadias and obstructive defects of the renal pelvis
  • Bone Cancers – Mixed findings on an association with birth defects overall and, specifically, bone birth defects, including scoliosis and developmental dysplasia of the hip
  • Soft Tissue Sarcoma – Consistent association with birth defects overall
  • Germ Cell Tumors (Sex Cell Cancers) – Relatively consistent association with birth defects overall

A strong association, however, could not be found for leukemia, currently the most common cancer in children and teenagers. Studies that focused on the blood cancer failed to find consistent results, often noting only weak increases in risk among children born with major birth defects. The only exception? Strangely, a number of studies provided consistent evidence that children born with rib abnormalities and minor congenital anomalies were more likely to develop leukemia. In fact, rib abnormalities were associated with a wide range of pediatric cancers, a finding the researchers noted was “intriguing,” however poorly understood.