The use of opioids and other psychiatric drugs during pregnancy is a major public health problem, causing drug withdrawal in infants called Neonatal Abstinence Syndrome (NAS). The incidence of NAS has increased 6 fold in the last decade, now affecting 60-80% of infants exposed to opioids during pregnancy. Infants born to women who take psychiatric medications with opioids have even worse NAS. NAS costs >$1.5 billion per year due to prolonged hospitalizations and treatment. It is difficult to predict which infants will get NAS, so we have to keep them in the hospital and treat them when  they get quite sick (since not all infants require treatment). In addition, we use standard assessment tools to identify NAS and determine when treatment is needed. These tools are 40 years old and highly subjective. We now realize that genetic factors in the mother and infant are very important in NAS. It would be significant if genetic information could be combined with clinical information to better predict which infants will get sick from NAS so we can treat them earlier, improve outcome and lower healthcare costs. It is also essential to develop a better assessment tool to guide earlier identification and treatment of NAS. We think that opioid-exposed infants will have better outcomes when we employ: 1) a prediction tool using clinical and genetic information; and 2) a simplified assessment tool for the evaluation and treatment of NAS. This will be tested by developing a large database of 1,000 mothers taking opioids and other psychiatric drugs (which can make NAS much worse) during pregnancy and their infants. We wish to identify risk factors associated with the development and severity of NAS in 1,000 mothers and their infants. Then we will perform genetic testing on 680 of these infants, put all the information together, and predict the development and severity of NAS. Finally, we will develop a simpler and more accurate NAS assessment tool to help take care of infants with NAS. The present proposal will greatly improve our knowledge of NAS and significantly improve outcome for these vulnerable infants.