Craniofacial skeletal deviations following in utero exposure to the anticonvulsant phenytoin: monotherapy and polytherapy

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Abstract
Structured Authors – Orup Jr HI, Holmes LB, Keith DA, Coull BA. Objective – To identify and quantify the craniofacial effects from prenatal exposure to phenytoin monotherapy and polytherapy using cephalometric, hand‐wrist, and panoramic radiographs and to determine if such deviations persist with age. Design – Craniofacial structures of 28 anticonvulsant‐exposed individuals were evaluated using 20 landmarks in lateral cephalometric radiographs and 19 landmarks in frontal cephalometric radiographs. Skeletal maturity was assessed using hand‐wrist radiographs. Dental maturity and the presence of dental anomalies were evaluated using panoramic radiographs. Eleven individuals were re‐evaluated 7 years later, on average, to determine the persistence of any measured deviations. Setting and Sample Population – Department of Growth and Development, Harvard School of Dental Medicine and Massachusetts General Hospital. Patients were recruited from several sources. Outcome Measure – The evaluated dimensions included linear, angular, and proportional measures. Results – The most common deviations were decreased height and length of the maxilla, decreased length of the posterior cranial base, length of the mandible, cranial width and level of the cribriform plate, and a decrease in the Wits Appraisal assessment. The deviations were more significant in the polytherapy‐exposed individuals than in the monotherapy‐exposed individuals. These deviations, especially in the maxilla, persisted with age as revealed in a re‐evaluation of 11 individuals. Conclusion – The craniofacial skeletal findings among individuals exposed in utero to phenytoin monotherapy or phenytoin polytherapy, when considered in aggregate, suggest a mild pattern of maxillary hypoplasia that becomes more pronounced with age.