Parental age and the risk of isolated cleft lip: a registry-based study

An increasing number of children in high-income countries have older parents. Several studies have suggested that pregnancy outcomes including cleft lip (CL) are associated with high parental age. CL is a relatively common birth defect, and the prevalence is higher in Norway than in most high-income countries.

We studied the association of parental age with the risk of isolated CL (with or without cleft palate) in 2,449,218 births from the population-based Medical Birth Registry of Norway in the period from 1967 until 2010. Individuals who had other birth defects or died before the age of three were excluded. Generalized additive models were used to estimate associations across the continuum of parent's age. A baseline risk was calculated, for births in the interquartile range for maternal age (24-31 years) and paternal age (26-34 years).

The baseline risk of isolated CL was 1.15 per 1000. Several analyses were conducted for mother's and father's age. The risk increased with the age of both parents, with risk estimates of 1.27 per 1000 and higher for children of parents at an advanced age. In an interaction analysis, the risk was increased only when the age of both parents was high.

Our analyses suggest that the risk of fathering an infant with CL increases with advancing age. Additional analyses showed, however, that the risk was increased only when the age of both parents was high.