Although significant progress has been made in identifying the etiology of some birth defects, approximately 65% have no known or identifiable cause. These are referred to as sporadic, a term that implies an unknown cause, random occurrence regardless of maternal living conditions, and a low recurrence risk for future children. For 20-25% of anomalies there seems to be a "multifactorial" cause, meaning a complex interaction of multiple minor genetic anomalies with environmental risk factors. Another 10–13% of anomalies have a purely environmental cause (e.g. infections, illness, or drug abuse in the mother). Only 12–25% of anomalies have a purely genetic cause. Of these, the majority are chromosomal anomalies.

The CDC and National Birth Defect Project studied the incidence of birth defects in the US. Key findings include:

- Down syndrome was the most common condition with an estimated prevalence of 14.47 per 10,000 live births, implying about 6,000 diagnoses each year.

- About 7,000 babies are born with a cleft palate, cleft lip or both.