Trends in congenital clubfoot prevalence and co-occurring anomalies during 1994-2021 in Denmark: A nationwide register-based study of 1,315,282 live born infants

BackgroundCongenital talipes equinovarus (clubfoot) is a common musculoskeletal anomaly, with a suspected multifactorial etiopathogenesis. Herein, we used publicly available data to ascertain liveborn infants with clubfoot delivered in Denmark during 1994-2021, and to classify co-occurring congenital anomalies, estimate annual prevalence, and compare clubfoot occurrence with maternal smoking rates, a commonly reported risk factor. Characterizing this nationwide, liveborn cohort provides a population-based resource for etiopathogenic investigations and life course surveillance. MethodsThis case-cohort study used data from the Danish National Patient Register and Danish Civil Registration System, accessed through the publicly available Danish Biobank Register, to identify 1,315,282 liveborn infants delivered during 1994-2021 in Denmark to Danish parents. Among these, 2,358 infants (65.1% male) were ascertained with clubfoot and classified as syndromic (co-occurring chromosomal, genetic, or teratogenic syndromes) and nonsyndromic (isolated or co-occurring multiple congenital anomalies [MCA]). Annual prevalence estimates and corresponding 95% confidence intervals (CIs) for children with nonsyndromic clubfoot were estimated using Poisson regression and compared with population-based, maternal annual smoking rates obtained from publicly available resources. ResultsInfants most often presented with nonsyndromic clubfoot (isolated=84.6%; MCA=10.9%); limb and heart anomalies were the most frequently identified MCAs. Prevalence (per 1,000 liveborn infants) was 1.52 (CI 1.45 - 1.58) for isolated and 0.19 (CI 0.17 - 0.22) for MCA clubfoot. Prevalence estimates for both isolated and MCA clubfoot remained relatively stable during the study period, despite marked decreases in population-based maternal smoking rates. ConclusionsFrom 1994-2021, prevalence of nonsyndromic clubfoot in Denmark was relatively stable. Reduction in population-level maternal smoking rates did not seem to impact prevalence estimates, providing some support for the suspected multifactorial etiopathogenesis of this anomaly. This nationwide, liveborn cohort, ascertained and clinically characterized using publicly available data from the Danish Biobank Register, provides a population-based clinical and biological resource for future etiopathogenic investigations and life course surveillance.