Medics have called for more to be done to establish the reasons behind why some babies are born with defects after a study concluded that most cases do not have diagnosed causes.
Experts from the University of Utah School of Medicine set out to assess the causes of birth defects among a group of children born in the United States.
They were only able to establish a definite cause in one in every five infants they studied.
The research, published in The British Medical Journal (BMJ), examined data on 270,878 children born in Utah from 2005 to 2009.
Two percent of these babies were born with a major birth defect.
A definite cause was assigned in 20.2% cases.
Of these, chromosomal or genetic conditions accounted for 94.4% of cases, environmental exposure for 4.1%, and conditions associated with twins for 1.4%
The remaining 79.8% (4,391 cases) were classified as "unknown etiology".
Major birth defects are common, occurring in one in 33 births, the authors wrote.
"Understanding the etiology of birth defects should be both a public health and research priority," the authors wrote.
"Our findings underscore the large gaps in current knowledge of the causes of birth defects.
"For clinicians and parents, it is important to understand what can be done today to prevent birth defects, in particular the role of preconception care focusing on optimal women's health (including screening/treating chronic illnesses, attaining folic acid sufficiency, etc)."
They added: "For the causes that are known, such as smoking or diabetes, assigning causation in individual cases remains challenging.
"Nevertheless, the ongoing impact of these exposures on fetal development highlights the urgency and benefits of population-based preventive interventions."