Abstract
BackgroundMany epidemiological studies have examined associations between birth defects (BDs) and pediatric malignancy over the past several decades. Our objective was to conduct a systematic literature review of studies reporting on this association.MethodsWe used librarian-designed searches of the PubMed Medline and Embase databases to identify primary research articles on pediatric neoplasms and BDs. English language articles from PubMed and Embase up to 10/12/2015, and in PubMed up to 5/12/2017 following an updated search, were eligible for inclusion if they reported primary epidemiological research results on associations between BDs and pediatric malignancies. Two reviewers coded each article based on the title and abstract to identify eligible articles that were abstracted using a structured form. Additional articles were identified through reference lists and other sources. Results were synthesized for pediatric cancers overall and for nine major pediatric cancer subtypes.ResultsA total of 14,778 article citations were identified, of which 80 met inclusion criteria. Pediatric cancer risk was increased in most studies in association with BDs overall with some notable specific findings, including increased risks for CNS tumors in association with CNS abnormalities and positive associations between rib anomalies and several pediatric cancer types.ConclusionsSome children born with BDs may be at increased risk for specific pediatric malignancy types. This work provides a foundation for future investigations that are needed to clarify specific BD types predisposing toward malignancy and possible underlying causes of both BDs and malignancy.
Highlights
Pediatric cancer is diagnosed in >14,000 U.S children per year from the ages of 0–19 years and is the leading cause of disease-related death among children aged 1–14 years [1, 2]
Pediatric cancer risk was increased in most studies in association with birth defects (BDs) overall with some notable specific findings, including increased risks for CNS tumors in association with CNS abnormalities and positive associations between rib anomalies and several pediatric cancer types
Some children born with BDs may be at increased risk for specific pediatric malignancy types
Summary
Pediatric cancer is diagnosed in >14,000 U.S children per year from the ages of 0–19 years and is the leading cause of disease-related death among children aged 1–14 years [1, 2]. A few risk factors have been conclusively identified, including exposure to high dose radiation and certain genetic syndromes, the etiology underlying most cases remains unknown. Evidence accumulated over several decades suggests positive associations between birth defects (BDs) and pediatric malignancy. Major anomaly examples include spina bifida, cleft lip palate, and Down Syndrome [4]. Minor anomaly examples include low set ears, epicanthal folds, and simian crease [5]. Certain genetic syndromes are known to increase pediatric cancer risk (e.g. Down Syndrome and leukemia), other BDs (including major and minor), independent of known cancer predisposition syndromes, may be associated with an increased risk. Many epidemiological studies have examined associations between birth defects (BDs) and pediatric malignancy over the past several decades. Our objective was to conduct a systematic literature review of studies reporting on this association
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