A nationwide analysis of the association between parental age and incidence of cleft lip/palate

Introduction

In several high-income Western countries, parenthood has increasingly been deferred to a higher age. This epidemiological study aimed to assess the relationship between maternal and paternal age and the incidence of non-syndromic cleft lip with or without the presence of a cleft palate (CLP) and cleft palate only (CP) in the United States (US).

Methods

We examined 22,669,736 births using a US-based cohort from 2016 to 2021. Dependent variables were non-syndromic CLP and CP. Independent variables included maternal age, race, education, and cigarette use. A separate set of modeling examined the influence of paternal factors including paternal age, race, and education. Univariate and multivariate logistic regression examined the association between variables using odds ratios and 95% confidence intervals.

Results

There were 11,341 non-syndromic CLP and 3645 CP cases. After adjusting for maternal race, education, pre-pregnancy smoking, and smoking during pregnancy, higher maternal (p = 0.137) and paternal (p = 0.773) age were not significantly associated with increased risk of CLP in the offspring. In adjusted models, higher maternal (p = 0.003) and higher paternal (p = 0.013) age were significantly associated with the increased risk of CP in the offspring.

Conclusion

Increasing maternal and paternal age is significantly associated with increased risk of CP in the offspring. The findings of this study highlight a previously unknown at-risk population with an increasing birth rate, particularly in Western countries.