Prenatal opioid use can take various forms, including (1) using prescriptions for pain management, such as fentanyl and oxycodone; (2) medication-assisted treatment for opioid addiction, such as use of methadone and buprenorphine; (3) prescription misuse or abuse (such as using without a prescription, using a different dosage than prescribed, or continuing to use a drug when no longer needed for pain); and (4) illicit opioid use, such as heroin. These types of prenatal opioid use are not mutually exclusive. Women can use opioids in different ways during the course of a pregnancy. A recent study of heroin-dependent individuals in treatment showed most people reported their first regular opioid was a prescription drug. Two recent studies also found that 14 percent of pregnant private health insurance beneficiaries, and almost 22 percent of pregnant Medicaid beneficiaries filled a prescription for opioids during their pregnancy. Medication is considered the standard of care for pregnant women with opioid use disorders. Medications used for such addiction treatment are typically other opioids, such as methadone and buprenorphine, used off- label as neither is approved for use during pregnancy. administered daily as part of a registered, comprehensive substance abuse treatment program that can include prenatal care, counseling, family therapy, nutrition counseling, and other supportive services. Buprenorphine is the only opioid approved for the treatment of opioid use disorders for which physicians can write a prescription outside of a licensed treatment program. It is generally associated with a lower risk of overdose and fewer drug interactions than methadone and does not require daily visits to a treatment program. Experts consider NAS to be an expected and treatable result of pregnant women’s prenatal opioid use. Newborns with NAS may exhibit withdrawal signs and symptoms such as irritability, high-pitched crying, stiffness, sweating, vomiting, diarrhea, poor feeding, seizures, and respiratory distress. NAS is also associated with premature birth and lower birth weight, and can interfere with the mother-infant bonding process. Symptoms of NAS usually develop within 72 hours of birth, but may develop anytime in the first 2 weeks of life, including after hospital discharge. Providers predominantly diagnose NAS using the Finnegan Neonatal Abstinence Scoring Tool, which calculates a score based on a variety of central nervous, metabolic, respiratory, and gastro-intestinal symptoms that might be observed. Off-label use refers to the prescription of a medication for uses other than what the Food and Drug Administration has approved. the infant into a dark and quiet environment, swaddling, rooming with the mother, and providing high-calorie nutrition, among other things. Medication, such as methadone or morphine, may be necessary only for the relief of moderate to severe signs of NAS. Regardless of the type of treatment, a recent study found inconsistency in treatment both across and within particular settings of care. Specifically, the study found that the medications primarily used to treat NAS from 2004 to 2011 varied across hospitals, and that the type of medication used was associated with variations in length of treatment, length of stay, and hospital charges. Even within hospitals, only 5 of the 14 hospitals examined used the same treatment more than 80 percent of the time. Fourteen out of 18 federally funded research projects included a focus on NAS prevention, understanding, or treatment. Fourteen federal programs made direct services available or conducted other activities to address prenatal opioid use or NAS as part of broader program objectives. Eleven federal agencies also addressed prenatal opioid use or NAS through their health systems or other efforts outside of research or programs. From fiscal years 2008 through 2014, federal agencies obligated almost $21.6 million for 18 research projects related to prenatal opioid use or NAS, 14 of which included a focus on prevention and understanding of NAS, treatment of NAS, or both, as individual projects sometimes focused on more than one research area.$13.6 million for eight projects that included a focus on prevention and Federal agencies obligated understanding of NAS and $6 million for seven projects that included a focus on treating NAS. Other topics covered by these 18 projects included the treatment of prenatal opioid use (4 projects), incidence or prevalence of NAS, incidence or prevalence of prenatal opioid use, and costs related to NAS (3 projects each). No projects focused on the prevention or understanding of prenatal opioid use or any costs associated with such use. (See fig. 1.) All of the 18 projects were funded by agencies within HHS. Specifically, 14 of the 18 projects were funded by the National Institutes of Health (NIH) and the remaining 4 were funded by the Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA). (See appendix II for descriptions of all 18 projects.) Projects that included a focus on prevention and understanding of NAS examined, for example, the transfer of drugs from the mother to the fetus or how different drugs used to treat addiction in the mother affected the newborn. Projects that included a focus on treatment of NAS examined, for example, different approaches to treatment such as gentle stimulation of newborns or comparisons of different medications to treat NAS. The project that was provided the largest amount of funds (nearly $4.6 million during the period we reviewed) was the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study, which included a focus on prevention and understanding of NAS as well as treatment of NAS. This eight-site randomized clinical trial compared the effects of pregnant women’s use of buprenorphine to methadone on the severity and duration of NAS. It found that newborns born to women who received buprenorphine for opioid addiction treatment during pregnancy required significantly less morphine to treat withdrawal symptoms, had significantly shorter hospital stays, and required a significantly shorter duration of treatment for NAS, compared to newborns born to women who received methadone during pregnancy. Agency officials identified 14 federal programs on substance abuse prevention or treatment, maternal and child health, or family and child welfare services that addressed prenatal opioid use or NAS in fiscal years 2013 or 2014 as part of broader program objectives. Through a Web- based questionnaire, officials from 8 of these 14 programs reported making direct services available to women, infants, or their families, and 11 reported conducting other activities such as public education or providing technical assistance, with 5 reporting both. (See fig. 2.) These 14 programs were run by five different agencies, with 12 of these programs administered by agencies within HHS. Nine of the 14 programs had been in existence for more than 5 fiscal years.more details on these programs.) Outside of research and programs, officials from 11 federal agencies— mostly within HHS— reported that their agencies made direct services available through their health systems or engaged in other efforts that addressed prenatal opioid use or NAS during fiscal years 2008 through 2014. Four of the 11 agencies reported making relevant direct services available through their health systems and 10 agencies reported engaging in other efforts, such as provider education and knowledge- sharing groups, while three agencies reported doing both. (See fig. 4.) Officials from four of the 11 agencies—the Indian Health Service (IHS) within HHS, the Bureau of Prisons (BOP) within the Department of Justice (DOJ), the Department of Defense (DOD), and the Department of Veterans Affairs (VA)—reported that their health systems made direct services available to women who use opioids, their newborns, or their families, as part of each agency health system’s broader efforts to provide care to its beneficiaries.abuse screening and referral, medication-assisted treatment for opioid use disorders, behavioral treatment services, and case management or recovery support services may be available through their health systems, among other services. The State Children’s Health Insurance Program is a federal-state program that provides coverage to low-income children whose household incomes are above the threshold for Medicaid eligibility. which include guidance for DOD and VA health care providers on screening for drug use and offering treatment during pregnancy. Some agencies also published relevant reports or fact sheets that included information on prenatal opioid use or NAS. For example, SAMHSA recently published a fact sheet on pregnant teenagers admitted to substance abuse treatment facilities that, in part, discusses opioid use. (See appendix V for more information on agency efforts to address prenatal opioid use or NAS outside of research and programs.) The research and program gaps most commonly cited by federal agency officials and other experts were related to treatment of pregnant women with opioid use disorders or newborns with NAS. Research gaps cited focused on treatment of opioid use during pregnancy, including the effectiveness of various drugs, and the long-term effects of prenatal opioid exposure on children. The program gap most frequently cited was the lack of available treatment programs for both pregnant women and newborns with NAS. Other gaps cited included a lack of guidance and coordination in efforts to address prenatal opioid use or NAS. Agency officials and other experts we interviewed most often cited research gaps on treatments of opioid use during pregnancy and understanding the long-term impact on children exposed to opioids prenatally. Specific research gaps related to the treatment of prenatal opioid use included a lack of knowledge about best practices for initiating medication-assisted treatment during pregnancy, and an understanding of the barriers to accessing opioid use disorder treatment for pregnant women. Agency officials and experts said that there has not been adequate research comparing different types of treatment approaches and that research is needed on how best to treat a pregnant woman with an opioid use disorder so that the treatment is most effective for the woman while offering minimal risk to the fetus. The other research gap most frequently cited by agency officials and experts was research on the long-term effects of prenatal drug exposure, which officials and experts said is needed to understand the impact of prenatal exposure to opioids on children through adolescence. Other research gaps cited by agency officials and experts were related to studies of the treatment of NAS, screening and diagnosis of NAS, and understanding of NAS, such as the impact of opioid exposure on infants and severity of NAS.