Neonatal findings and perinatal issues in Down syndrome include several under-emphasized problems that should be added to preventive management checklists. Of 630 families seen in a Down syndrome clinic from May, 1993 to July 1997, 145 patients were identified in which the gestational/neonatal history and physical examination were deemed adequate for analysis. Well-known complications includied congenital heart disease (32%), polycythemia/thrombocytopenia (8%), pneumonia/respiratory complications (8%), duodenal stenosis/atresia (6%), and Hirschsprung disease (1%). Under-emphasized medical problems included neonatal jaundice (54%), feeding problems (40%), constipation (7%), and anal stenosis (10%). Of the 78 patients with hyperbilirubinemia, 35 (24% overall) required phototherapy and none required exchange transfusion. Breast-feeding was associated with more difficulties than bottle feeding, and 8% of infants required tube feedings. Anal stenosis was suspected by a history of pain or straining while stooling and supported by finding soft stool above a narrow rectal opening. Anal stenosis resolved rapidly, perhaps aided by rectal examination, in the 14 affected patients with no long-term complaints or need for additional studies. Analysis of perinatal management revealed that 26% of couples had prenatal diagnostic procedures, with 7% receiving a prenatal diagnosis of Down syndrome. Overall, 89% of infants were diagnosed in the neonatal nursery with 70% having karyotypes and 39% having echocardiography. Negative parental experiences (41%) could be related to the circumstances (e.g., one parent present in 32% of cases) or timing (6% if diagnoses after age 1 month) of counseling. The results demonstrate several beneficial strategies for the perinatal management of Down syndrome, and these are included in a novel flowsheet that combines general and disease-specific preventive care. This checklist format is easily adapted to other chronic illnesses.