Objective-To determine the proportion of infant deaths occurring in the setting of a confirmed genetic disorder.Study Design-A retrospective analysis of the electronic medical records of infants born from January 1, 2011 to June 1, 2017 who died prior to one year of age.Results-573 deceased infants were identified. 117 were confirmed to have a molecular or cytogenetic diagnosis in a clinical diagnostic laboratory and an additional 7 were diagnosed by research testing for a total of 124/573 (22%) diagnosed infants. 67/124 (54%) had chromosomal disorders and 58/124 (47%) had single gene disorders (one infant had both). The proportion of diagnoses made by sequencing technologies, such as exome sequencing, increased over the years.

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.