Objective: Children with orofacial clefts (OFC) may have an increased risk of poor mental health. This study aimed to investigate the risk of psychiatric diagnoses in individuals with OFC, stratified by cleft type. Method: A nationwide register-based cohort of all individuals born with nonsyndromic OFC in Sweden between 1973 and 2012 (n ¼ 7,842) was compared to a matched cohort (n ¼ 78,409) as well as to their unaffected siblings (n ¼ 9,637). The risk of psychiatric diagnoses, suicide attempts, and suicides was examined by crude and adjusted Cox regression models. Effect modification by sex was investigated with interaction terms in the models. Results: Children with cleft lip (CL) had a significantly higher risk of any psychiatric disorder, intellectual disability, and language disorders; children with cleft lip and palate (CLP) had, in addition, an increased risk of autism spectrum disorder (ASD). Children with cleft palate only (CPO) had risk increases for the same diagnoses as children with CL and CLP, but with higher hazard ratios, and also for psychotic disorders, attention-deficit/ hyperactivity disorder (ADHD), and other behavioral or emotional disorders in childhood. Sex stratification indicated higher risk increases among females in CL and CLP but not in CPO. Siblings without OFC were less likely to be diagnosed with any psychiatric disorder, intellectual disability, language disorder, ASD, or ADHD compared to their siblings with OFC. Conclusion: Children with nonsyndromic clefts had a significantly higher risk of neurodevelopmental disorders. This risk is unlikely to be explained by familial influences such as inherited genetic or shared environmental factors.

Objective : To evaluate the importance of dental status for long-term outcome after alveolar bone grafting in patients with unilateral cleft lip and palate. Design : Retrospective longitudinal study. Setting : Cleft lip and palate-craniofacial center, Uppsala University Hospital, Sweden. Patients : A total of 67 consecutive patients with unilateral complete cleft lip and palate. Interventions : Secondary alveolar bone grafting, prior to the eruption of the permanent canine, was performed at the average age of 10.0 years (range, 8.5 to 12.0 years). Main Outcome Measures : Alveolar bone height was evaluated with the modified Bergland index at 1 and 10 years after surgery. Results : Of the patients, 97% had modified Bergland index grade I and the remaining 3% had modified Bergland index grade II at 1 year after surgery. At 10 years' follow-up, 43% showed modified Bergland index grade I; 55%, modified Bergland index grade II; and 2% (one patient), modified Bergland index grade III. The degree of dental anomalies in the cleft area, such as enamel hypoplasia, incisor rotation, incisor inclination, canine inclination, and oral hygiene registered preoperatively, all correlated negatively to the modified Bergland index at 10 years after surgery. Enamel hypoplasia (ρ = 0.70195, P < .0001), followed by canine inclination (ρ = 0.55429, P < .0001), showed the strongest correlation to reduced bone height in the cleft area. Conclusions : In patients with unilateral cleft lip and palate, excellent results from secondary alveolar bone grafting in terms of bone height in the alveolar cleft tend to decrease with time. This seems to be correlated with factors that might to some extent be treated preoperatively through adequate planning and execution of the orthodontic treatment.

To investigate the mechanisms behind the antifibrotic effect associated with epidermal regeneration, the expression of 12 fibroblast genes important for the modulation of the extracellular matrix (ECM), as well as α-smooth muscle actin, was studied in a keratinocyte-fibroblast organotypic skin culture model. The study was performed over time during epidermal generation and in the presence or absence of the profibrotic factor transforming growth factor-β. the Presence of epidermal differentiation markers in the model was essentially coherent with that of native skin. Fibroblast gene expression was analyzed with real-time polymerase chain reaction after removal of the epidermal layer. After 2 days of air-exposed culture, 11 out of the 13 genes studied were significantly regulated by keratinocytes in the absence or presence of transforming growth factor-β. The regulation of connective tissue growth factor, collagen I and III, fibronectin, plasmin system regulators, matrix metalloproteinases and their inhibitors as well as α-smooth muscle actin was consistent with a suppression of ECM formation or contraction. Overall, the results support a view that keratinocytes regulate fibroblasts to act catabolically on the ECM in epithelialization processes. This provides possible mechanisms for the clinical observations that reepithelialization and epidermal wound coverage counteract excessive scar formation.