There was a recognizable pattern of malformations and characteristics of infants of diabetic mothers, although there was variation in the pattern among affected infants. Some of the malformations in the diabetic embryopathy can be identified in prenatal screening by ultrasound. More important, their occurrence can be reduced significantly by the mother achieving much better control of her diabetes mellitus prior to conception.

BACKGROUND Valproic acid (VPA) is the most teratogenic anticonvulsant drug in clinical use today. Children exposed prenatally to VPA have previously been shown to have dysmorphic craniofacial features, identified subjectively but not by anthropometric methods. Exposure to VPA has also been associated with an increased frequency of Autism Spectrum Disorder (ASD). An increased cephalic index (the ratio of the cranial lateral width to the cranial anterior-posterior length) has been observed in children with ASD. METHODS Forty-seven children exposed to VPA during the first trimester of pregnancy were evaluated for dysmorphic facial features, identified subjectively and by measurements. Each VPA-exposed child was evaluated for ASD using the SCQ (Social Communication Questionnaire), ADI-R (Autism Diagnostic Interview-Revised) and ADOS (Autism Diagnostic Observation Schedule). The same physical examination was carried out on an unexposed comparison group of 126 children. The unexposed children also had testing for cognitive performance by WISC-III (the Wechsler Intelligence Scale for Children). RESULTS Several dysmorphic craniofacial features, including telecanthus, wide philtrum and increased length of the upper lip were identified subjectively. Anthropometric measurements documented additional findings including an increased cephalic index, decreased head circumference/height index, and increased intercanthal distance. There were no differences between the craniofacial features of VPA-exposed children with and without ASD. CONCLUSIONS An increased frequency of dysmorphic craniofacial features was identified in children exposed to VPA during the first trimester of pregnancy. The most consistent finding was a larger cephalic index, which indicates a disproportion of increased width of the skull relative to the shortened anterior-posterior length.

The surveillance of a large consecutive population of newborn infants, stillbirths, and aborted fetuses can identify with high reliability all infants with one or more malformations. This process of ascertainment of affected newborns can be used to improve genetic counseling, identify "new" phenotypes, and serve as a system for testing new technologies to establish more causes of congenital malformations.