Effect of in utero exposure to anticonvulsants on craniofacial development and growth.

It has been widely reported that some children exposed to anticonvulsants in utero have a characteristic pattern of craniofacial anomalies including a broad, low nasal bridge with a short upturned nose, wide mouth, low set ears, epicanthal folds, and ocular hypertelorism, while others show no evidence of craniofacial abnormalities. The purpose of this paper is to define the craniofacial features in nine exposed children using anthropometric measurements and frontal and lateral cephalometric radiographs. These children were identified at birth as part of a prospective study of infants exposed to anticonvulsants at the Boston Hospital for Women (now part of the Brigham and Women's Hospital). At birth, none of these infants had any major malformations; at 4 to 10 years of age, none demonstrated any growth deficiency or mental deficiency, and all external craniofacial measurements were within the normal range. However, cephalometric analyses demonstrated a pattern of reduced bony interorbital distance, maxillary size, mandibular length, cranial base and skull size, and a reduction in nose dimensions when compared to data of normal populations. This study demonstrates the inadequacy of external measurements in determining the details of underlying craniofacial architecture. The data also suggest that a subtle craniofacial change occurs in exposed children which is characterized by a decrease in bony interorbital distance and the size of the cranial base and maxilla with concomitant decreases in nose and mandibular dimensions.