Rural communities in the United States have seen a steep rise in opioid use disorder (OUD) during pregnancy, with a parallel increase in neonatal opioid withdrawal syndrome (NOWS). The birthing person-infant dyads affected by OUD and NOWS in rural areas face many barriers to accessing care. Innovative approaches have proven successful in improving health outcomes for affected birthing persons and newborns, but more work is needed to continue to improve access to prevention, treatment, and additional support services for this vulnerable population.
Key points
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Rural areas in the United States are disproportionally impacted by both opiod use disorder (OUD) during pregnancy and neonatal opioid withdrawal syndrome (NOWS).
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Pregnant persons with OUD in rural areas face many barriers to access care; innovative programs that integrate OUD treatment with obstetric care can improve outcomes.
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Increasing evidence supports the use of the Eat, Sleep, Console (ESC) assessment tool in management of NOWS; perinatal quality collaboratives have proven successful in implementing evidence-based care, such as ESC, in rural and community hospitals.
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Local, state, and federal agencies should prioritize policies and programs to meet the unique needs of rural communities.
Introduction
Over the last 2 decades, the United States has witnessed a dramatic increase in opioid use disorder (OUD) among pregnant persons, with a corresponding increase in neonatal opioid withdrawal syndrome (NOWS); both have disproportionately impacted rural areas. , People living in rural communities face numerous barriers to accessing care for OUD and NOWS. Access to prevention, treatment, and other support services is crucial for these birthing person-infant dyads, and solutions to improve care should be tailored to the unique needs of these rural communities.
Definitions
Opioid Use Disorder
OUD is diagnosed using criteria from the Diagnostic and Statistical Manual of Mental Health Disorders, Fifth Edition (DSM-5), and centers on “a problematic pattern of opioid use leading to clinically significant impairment or distress.” Substance use disorder (SUD) is similarly diagnosed, but more broadly includes alcohol, tobacco, and other nonprescribed substances.
Neonatal Opioid Withdrawal Syndrome
Until recently, no standard definition of NOWS existed. In 2022, the US Department of Health and Human Services (HHS), along with experts in the field, led the development of a standard clinical definition for opioid withdrawal in infants, which includes prenatal exposure plus specific evidence-based clinical signs. , Traditionally, this syndrome has been called neonatal abstinence syndrome (NAS), a more general term that may include nonopioid exposure. In this article, the term NOWS is predominantly used in place of NAS.
Epidemiology
Hospital discharge data from the National Inpatient Sample (NIS) compiled by the Healthcare Cost and Utilization Project (HCUP) revealed that OUD documented at the delivery hospitalization quadrupled from 1999 to 2014, and data from 2016 showed that rates of SUD-related deliveries among patients from rural areas was 59% higher than for patients living in urban areas. As expected, the incidence of NOWS has similarly increased during the same time period, , disproportionally affecting rural areas. Data from NIS/HCUP from 2004 to 2013 showed an increase in the national incidence of NOWS from 1.2 to 7.5 cases per 1000 hospital births among rural infants, versus from 1.4 to 4.8 cases among urban infants. Updated data from 2010 to 2017 demonstrated an ongoing increase in the rates of both OUD at birth hospitalization and NOWS, with large state-level variation. NOWS rates ranged from 1.3 cases per 1000 birth hospitalizations in Nebraska to 53.5 cases per 1000 birth hospitalizations in West Virginia, with Maine, Vermont, Delaware, and Kentucky also exceeding 20 cases per 1000 birth hospitalizations. In rural areas, the rate of NOWS increased from 5.0 to 12.1 cases per 1000 birth hospitalizations, versus from 3.6 to 5.4 cases per 1000 birth hospitalizations in large metropolitan areas. In 2017, neonates with NOWS were significantly more likely to be non-Hispanic white, Medicaid-billed, and reside in zip codes with the lowest quartile of median income, and live in nonmetropolitan/rural counties ( Fig. 1 ).
Opioid use disorder in pregnancy
Untreated OUD during pregnancy poses significant risk to both the pregnant person and the developing fetus , including overdose death, reluctance to obtain prenatal care, preterm birth, and low birth weight. The American College of Obstetricians and Gynecologists (ACOG) recommends opioid agonist pharmacotherapy, also referred to as medication-assisted treatment (MAT), for pregnant persons with an OUD. Methadone and buprenorphine, which target mu -opioid receptors, are both safe and effective options to treat OUD in pregnancy. Methadone can only be administered through designated opioid treatment programs, whereas buprenorphine can be prescribed in office-based settings. Previously, buprenorphine could only be prescribed by providers who underwent specialized training and received a waiver from the Drug Enforcement Administration (DEA), but in 2023 the Consolidated Appropriations Act (also known as the Omnibus bill) removed the federal waiver requirement. Now all practitioners who have a current DEA registration that includes section III authority can prescribe buprenorphine for OUD if their practice is permitted by state law. The decision to initiate methadone versus buprenorphine for OUD should be individualized based on multiple factors. There is emerging evidence that compared with methadone, the use of buprenorphine in pregnancy may be associated with lower risk of adverse neonatal outcomes, such as preterm birth, small for gestational age, and low birth weight ( Table 1 ).
| Methadone | Both | Buprenorphine | |
|---|---|---|---|
| Mechanism |
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| Administration |
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| Rural barriers |
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| Risk of NOWS |
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| Breastfeeding |
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Unfortunately, pregnant persons, especially those residing in rural areas, face many barriers in accessing OUD care. In general , rural areas tend to have decreased access to opioid treatment programs and a decreased supply of buprenorphine-prescribing providers. Acceptance of insurance, willingness to treat pregnant persons, and long wait times can pose additional barriers to care. , Pregnant persons in rural areas may also face challenges in accessing obstetric care itself. A recent report from the Center for Healthcare Quality and Payment Reform revealed that over the past decade, more than 200 rural hospitals in the United States have stopped delivering babies, and now 55% of rural hospitals in the United States do not even offer labor and delivery services.
One way to improve access to OUD care involves assembling multidisciplinary care teams that integrate treatment for OUD with obstetric care. , Given high rates of comorbid mental health diagnoses, such as depression and post-traumatic stress disorder, coordinating care with behavioral health providers further supports retention to treatment and improved outcomes. A meta-analysis found that integrated obstetric and OUD care was effective in reducing substance use, although studies were small and heterogeneous. A retrospective cohort study from a rural academic center in New England found that receiving integrated treatment was associated with increased engagement in obstetric care, lower risk for substance use at time of delivery, reduced preterm birth rates, and shorter infant hospital stays. As the authors point out, “these findings have important implications for future prospective research and clinical program design especially in rural communities where access to obstetric and substance use care are impacted by lack of public transportation and economic vulnerability.”
Screening/testing
ACOG recommends universal screening for substance use at the first prenatal visit, using validated verbal screening tools, and a caring and nonjudgmental approach; if a pregnant person screens positive, follow-up should involve offering a brief intervention, and referring for specialized care as needed. Urine drug testing is not routinely recommended, but it can be used to detect or confirm suspected substance use when performed with the patient’s consent and in compliance with state law. Routine urine drug testing is controversial, as a positive result does not reveal information regarding timing, patterns, or severity of use, and there is a risk for false-negative and false-positive results. Health care providers should also be aware of their laboratory’s urine drug testing characteristics, as immunoassay techniques are the most common initial method used but can lead to false-positive results, especially for amphetamines and opioids. Positive results from any immunoassay test should be considered presumptive, and confirmatory testing should be performed via gas-chromatography-mass spectrometry, or high-performance liquid chromatography.
Universal urine drug testing of birthing persons has been proposed as a means to increase detection of neonates at risk for NOWS, and to decrease bias in testing, but may be problematic for several reasons. One single-center cohort study at a community hospital that implemented universal maternal urine toxicology testing at delivery hospitalization found improved rates of detection of substance use compared with their risk-based testing protocol, with 20% of opioid-positive urine tests recorded in birthing people without screening risk factors. These results are limited, however, because the study did not utilize a validated verbal screening tool in a comparison group. Universal testing approaches can also exacerbate racial and socioeconomic disparities in care. Studies have shown that Black women are reported to child protective services at a significantly higher rate than white women, despite similar rates of substance use among the 2 groups. ,
The American Academy of Pediatrics (AAP) does not recommend routine newborn toxicology testing, unless it will inform clinical management. Because of a lack of national guidelines to inform newborn toxicology testing, there is wide variability in practice, which risks inequities in care. At 1 academic center, the birthing persons of infants who underwent toxicology testing were significantly younger, identified as single, lived in the lowest income zip codes, and were less likely to identify as white.
Similarly, the Academy of Breastfeeding Medicine (ABM) does not recommend routine urine drug testing to guide breast feeding decision making. If urine drug testing is pursued, results “must be interpreted within the clinical context including patient history and collateral information, and this should inform need for further confirmatory testing (eg, with gas chromatography).”
Pathophysiology of neonatal opioid withdrawal syndrome
NOWS develops in the setting of chronic in utero exposure to opioids, and clinical presentation varies depending on the opioid type, as well as various factors associated with the birthing person, including other drug exposures, metabolism, and placental drug transfer. Although higher cumulative in utero exposure to short-acting opioids may increase the risk of developing NOWS, the dose of maintenance opioids does not appear to alter the risk. A meta-analysis of observational studies did not reveal a significant relationship between severity of NOWS and high- versus low-dose methadone. Similarly, there is no dose-related relationship between buprenorphine and various neonatal outcomes, including NOWS severity. Other factors that may increase the risk of NOWS include the birthing person’s use of tobacco, selective serotonin reuptake inhibitors, and benzodiazepines. ,
Clinical presentation of neonatal opioid withdrawal syndrome
The clinical presentation of NOWS includes signs and symptoms of central nervous system irritability, autonomic over-reactivity, and gastrointestinal tract dysfunction; specific examples include tremor, feeding difficulty, diarrhea, and seizures. The onset of symptoms varies depending on the half-life of the opioid, but generally occurs within the first 12 to 24 hours for a neonate exposed to a short-acting opioid like heroin, versus at 24 to 72 hours for long-acting methadone and buprenorphine ( Table 2 ). ,
| Central Nervous System Irritability | Autonomic Over-reactivity | Gastrointestinal Tract Dysfunction |
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Neonatal opioid withdrawal syndrome management
The management of NOWS involves a period of observation, combined with nonpharmacologic care (such as parental engagement, rooming-in, skin-to-skin, low-stimulation environment, and breastfeeding), and in severe cases the addition of medication to improve signs of withdrawal. There is a lack of strong evidence to support a standard approach to management of NOWS, resulting in wide variability of inpatient care, length of stay (LOS), and cost. A 2015 survey of hospitals in the Better Outcomes Through Research For Newborns (BORN) network found significant variation in observation periods for short- and long-acting opioids, pharmacologic and nonpharmacologic management, and breastfeeding practices. Data from the Pediatric Health Information System also reveal wide variation in hospital rates of pharmacotherapy for management of NOWS (ranging from 13%-90%) and the type of medication chosen for management of withdrawal. ,
Nonpharmacologic Management
All infants with chronic in utero exposure to opioids should be observed in the hospital for at least 72 hours to monitor for signs and symptoms of withdrawal. There is limited evidence to guide observation periods, but generally the recommendation is 3 days for infants exposed to short-acting opioids, versus 4 to 7 days for long-acting opioids like buprenorphine and methadone.
Historically, the Finnegan Neonatal Abstinence Scoring Tool, or a modified version of it, has been used to assess the severity of neonatal withdrawal symptoms and guide decisions on pharmacologic treatment. Because of concern that this assessment tool leads to highly variable and potentially unnecessary opioid treatment for babies with NOWS, in 2014 Grossman and colleagues proposed a novel approach called Eat, Sleep, Console (ESC). This care focuses on nonpharmacologic interventions, including parental presence, swaddling/holding, feeding on demand, and a low-stimulation environment to promote essential newborn functions-namely, the baby’s ability to eat sufficient quantities, to sleep uninterrupted for at least 1 hour, and to be consoled within 10 minutes. ,
A recent cluster-randomized controlled trial at 26 US hospitals that compared the ESC approach to usual care found a significant decrease in time until infants were medically ready for discharge by a mean of 6.7 days among the ESC group (8.2 versus 14.9 days; adjusted mean difference, 6.7 days; 95% confidence interval [CI], 4.7–8.8); infants in the ESC group were also treated with opioids less often (19.5% among ESC group versus 52% in usual care group), without increasing any adverse safety outcomes through 3 months of age. This study included academic medical centers and community hospitals, and selected sites that were geographically diverse. Given that the ESC approach emphasizes parental involvement in care, and is often less resource intensive, it is primed for success in rural communities.
Pharmacologic Management
If an infant continues to display severe withdrawal symptoms despite optimization of nonpharmacologic interventions, pharmacologic therapy should be considered. There is variability surrounding decisions to initiate pharmacotherapy. For institutions using the Finnegan or similar scoring tool, pharmacologic treatment is generally initiated when single or serial withdrawal scores exceed a prespecified threshold. For infants being monitored with the ESC Care Tool, the approach often involves a multidisciplinary team huddle to discuss pharmacologic treatment if the infant has issues eating, sleeping, or consoling despite maximizing nonpharmacologic interventions. The first-line agent for management of neonatal opioid withdrawal symptoms is an opioid. , Most commonly oral morphine is used, but methadone and buprenorphine are also utilized, and there is insufficient evidence to recommend 1 agent over another. However, across multiple studies, buprenorphine was consistently associated with shorter LOS.
Perinatal Quality Collaboratives
Rural regions in the United States are often served by community hospitals, and many infants with NOWS are transferred from community hospitals to academic medical centers, which can disrupt maternal-infant bonding and family support. In 1 observational study of 2 rural community hospitals that used a standardized care protocol for assessment and treatment of NOWS, there was no significant difference between mean LOS, LOS due to NOWS, and duration of NOWS treatment in the community setting compared with academic practice settings.
A strategy to improve care among rural and community hospitals involves utilizing Perinatal Quality Collaboratives (PQCs), which are “state or multistate networks of teams working to improve the quality of care for mothers and babies.” PQCs are primed to leverage their strengths to support the creation and dissemination of rural birthing person and infant health improvements. The Northern New England Perinatal Quality Improvement Network (NNEPQIN) is 1 such collaborative that includes most of the birth hospitals in New Hampshire, Vermont, and Maine. In 2018, NNEPQIN utilized their regional network to implement the ESC care tool in hospitals across the region, many of which are located in rural areas.
From 2017 to 2019, the Massachusetts state Perinatal-Neonatal Quality Improvement Network (PNQIN) successfully implemented an ESC NOWS Care Tool across multiple hospitals, resulting in a decrease in pharmacotherapy and LOS, without an increase in short-term adverse events; sustained changes were noted in both tertiary and community hospital settings. Similarly, from 2017 to 2019, the Colorado Hospitals Substance Exposed Newborn Quality Improvement Collaborative (CHoSEN QIC) standardized the care of opioid exposed newborns (OENs) among birthing hospitals in the state, which included using the ESC approach, and also found a decrease in pharmacotherapy and LOS. A secondary analysis of this quality improvement initiative investigated disparities in care by Hispanic ethnicity, and found that Hispanic newborns experienced a delay of 3 calendar quarters in achieving decreased LOS, and a 1-quarter delay to lower pharmacotherapy compared with non-Hispanic newborns. This highlights the ability of quality improvement networks to evaluate health care disparities and mitigate them by developing initiatives that are tailored to the unique needs of diverse populations, including rural populations ( Fig. 2 ).
