Neonatal Abstinence Syndrome Research Articles

A statewide system for maternal-infant linked longitudinal surveillance: Indiana's model for improving maternal and child health

Indiana, located in the Midwest region of the United States, faces significant challenges with respect to health, especially maternal and child health (MCH). These challenges include high rates of stillbirth, neonatal abstinence syndrome (NAS) and congenital syphilis (CS). Not only are these often-fatal conditions underreported, but it can also be difficult to track them longitudinally, as mothers and infants are not routinely linked through electronic health records (EHRs). This paper describes the process, structure and planned outcomes of a partnership between Indiana University, Regenstrief Institute and public health partners in support of the U.S. Centers for Disease Control and Prevention's Pregnant People-Infant Linked Longitudinal Surveillance (PILLARS) program. Together, academic, clinical and public health organisations are collaboratively developing an infrastructure and deploying novel methods to surveil stillbirth, CS and NAS longitudinally. The infrastructure includes: (a) deploying deterministic and probabilistic algorithms to link mothers and their infants using multiple, linked data sources; (b) creating and maintaining a registry of maternal-infant dyads; (c) using the registry to perform longitudinal surveillance in collaboration with Indiana public health authorities on stillbirth, NAS and CS and (d) translating information from surveillance activities into action by collaborating with public health and community-based organisations to improve and implement prevention activities in vulnerable Indiana communities. Our long-term goal is to improve outcomes for these conditions and other priority MCH outcomes by expanding our work to additional MCH use cases.

Severe alcohol withdrawal during pregnancy or early postpartum: maternal and fetal outcomes.

Alcohol withdrawal syndrome (AWS) during pregnancy is under-researched despite growing concerns about increased alcohol use among pregnant women. This study aims to explore the severity of AWS and its impact on maternal and fetal outcomes. This retrospective study reviewed the medical records of patients admitted to the Mayo Clinic who underwent the CIWA-Ar protocol for AWS from June 2019 through June 2022. Pregnant women identified in this cohort had their pregnancy, labor, and neonatal data analyzed for alcohol-related complications and outcomes. Out of the medical records reviewed, 8 cases involved pregnant women experiencing AWS. These cases showed a high severity of withdrawal symptoms, with a median peak CIWA-Ar score of 17 (IQR = 14). Maternal complications included a high rate of ICU admissions (37.5%; n = 3) and significant rates of miscarriage and stillbirth (37.5%; n = 3). Fetal outcomes were concerning, with 1 out of 5 (20%) neonates requiring NICU admission and experiencing conditions such as respiratory failure and neonatal abstinence syndrome. Developmental problems were noted in 2 out of 5 (40%) newborns. The findings highlight the severe implications of AWS during pregnancy, impacting both maternal and fetal health. The severity of AWS requires attentive clinical management and preventative interventions. Future research should focus on larger, prospective studies to better understand and address the risks associated with AWS in pregnant women and to improve health outcomes for mothers and their children. • Severe AWS during pregnancy leads to high ICU admissions and adverse neonatal outcomes. • 37.5% of pregnant women with AWS experienced miscarriage or stillbirth. • 20% of newborns from mothers with AWS required NICU admission for serious conditions; 40% of newborns had developmental problems. • Findings underscore the need for specialized treatment protocols to improve outcomes for pregnant women and their newborns.

Current Status of Neonatal Music Therapy Services Within the US

Abstract Over the past 30 years, music therapy services in the neonatal intensive care units (NICUs) have expanded, yet there is still limited literature available that captures current practice trends in this setting. The purpose of this paper was to obtain descriptive data about current demographics, consultation, and clinical practice trends in NICU music therapy clinical practice in the US. A questionnaire was sent to 9,222 Board-Certified Music Therapists. Those providing music therapy services in the NICU and choosing to participate (N = 87) completed the questionnaire. Results showed that a majority of music therapists working in the NICU who responded to the questionnaire have completed additional training to provide specialized services. Most NICU music therapists reported spending less than 20 hr a week on the unit and providing a variety of family-centered interventions to infants starting at 28 weeks postmenstrual age (PMA). Common diagnoses for referral besides prematurity were Neonatal Opioid Withdrawal Syndrome and Chronic Lung Disease. Music therapists are well integrated within treatment teams with a majority reporting collaborating and/or co–treating with other therapies and/or clinical staff.

Chapter 8: The Role of Genetics in Neonatal Abstinence Syndrome

Chapter 8: The Role of Genetics in Neonatal Abstinence Syndrome

Hospital Sequelae, Discharge, and Early Interventions in Infants with Neonatal Opioid Withdrawal Syndrome

Hospital Sequelae, Discharge, and Early Interventions in Infants with Neonatal Opioid Withdrawal Syndrome

Impact of a qualitative assessment approach for neonatal abstinence syndrome management: experience of a European reference center

BackgroundThe management of infants at risk of neonatal abstinence syndrome (NAS) remains challenging. In 2000 Maternidade Bissaya Barreto implemented a strategy based on the qualitative assessment of neonates and in 2018 the Eat, Sleep, Console (ESC) approach, a tool based on similar concepts, was created. The aim is to assess the efficacy of a qualitative assessment of infants at risk, compare it with the ESC approach and report temporal trends of NAS in a European hospital.MethodsRetrospective cohort study of all infants of mothers with a history of drug abuse during pregnancy admitted to a tertiary European centre between January 2010 and December 2021. The therapeutical decision was guided by a qualitative assessment of the newborn’s well-being. The ESC approach was retrospectively determined. Pharmacologic treatment was used as a last resort. The clinical outcomes and therapeutic strategies employed were evaluated. Statistical association was evaluated. The incidence rate per 1000 births was calculated and temporal trend differences were identified.ResultsA total of 79 neonates at risk were included, of whom 40 (50.6%) developed NAS. Consolability was the most affected criterion (35.0%), followed by feeding difficulties (12.5%). Sleep was affected less frequently (5.0%). Overall, 37.5% of infants failed to meet at least one of the criteria. All neonates with a positive ESC failed the qualitative assessment (p = 1.000) After optimization of nonpharmacologic measures, drug therapy was still necessary in four cases (10.0% of infants with the syndrome). The incidence rate of NAS decreased from 3.9 per 1000 births in 2010 to 0.0 per 1000 births in 2021 (p = 0.025).ConclusionThe qualitative assessment of the infant based on the ability to feed, sleep and be consoled correctly identified neonates at risk and led to a significant reduction in the use of drug therapy. The incidence rate of NAS decreased during the study period.

Illicit Fentanyl in the Prenatal Period: A Significant Emerging Risk for Neonatal Opioid Withdrawal Syndrome

Objective This study aimed to evaluate the impact of in-utero illicit fentanyl exposure on neonatal outcomes, including neonatal opioid withdrawal syndrome (NOWS), length of stay (LOS), and treatment requirements. Study Design This study was conducted from March 2020 to December 2022, and focused on neonates born to mothers with opioid use or opioid use disorder (OUD). Maternal opioid use was identified through self-report or umbilical cord tissue (UCT) testing. Severe NOWS was defined as cases requiring pharmacological treatment. Statistical analyses included univariate comparisons, logistic regression, and generalized linear models to assess the associations between fentanyl exposure and neonatal outcomes. Results Forty-seven percent (75/159) of infants had in-utero fentanyl exposure. Fentanyl-positive mothers were older, 31 ± 5 years, compared to non-fentanyl mothers, 29 ± 5, p = 0.01. They were also less likely to receive prenatal care (p < 0.01) and had a higher number of polysubstance used, 5 ± 1 compared to non-fentanyl mothers, 3 ± 1, p < 0.01. Overall, infants exposed to fentanyl had a higher incidence of severe NOWS (odds ratio = 5.8, 95% confidence interval [CI]: 2.49–12.95, p < 0.01) and required earlier NOWS treatment initiation, 1 ± 1 day compared to non-exposed infants 3 ± 2 days, p < 0.01. In adjusted analysis, fentanyl exposure was associated with a nearly three-fold increased risk of NOWS (Mantel–Haenszel combined relative risk = 2.98, 95% CI: 1.94–4.57). Furthermore, fentanyl exposure led to longer LOS, with a 40% increase for preterm neonates (p < 0.01) and a 63% increase for full-term neonates (p < 0.01). Additionally, there was a significant correlation between log fentanyl concentration in umbilical cord tissue and cumulative morphine dose required for NOWS treatment, p = 0.001. Conclusion Prenatal illicit fentanyl exposure is an independent and strong risk factor for severe NOWS presentation in newborns requiring extended hospital stays. Key Points

Clonidine as Monotherapy for Neonatal Opioid Withdrawal Syndrome: A Randomized Trial.

We sought to determine whether clonidine, a non-opioid α-2-adrenergic agonist, would effectively treat neonatal opioid withdrawal syndrome (NOWS). This was an intention-to-treat randomized clinical trial. Enrollment criteria included prenatal opioid exposure, age ≤7 days, gestational age ≥35 weeks, no other medical condition, and need for pharmacotherapy. Primary outcomes were length of treatment and neurobehavioral performance. A total of 1107 patients were screened for enrollment (645 ineligible, 91 parents or staff unavailable, 216 declined, 155 consented). Of 155 infants, 120 required treatment and were randomized to receive oral clonidine (n = 60) at 1 µg/kg/dose or morphine (n = 60), 0.06 mg/kg/dose, every 3 hours. Infants with no improvement had their doses increased by 25% of the initial dose every 12 to 24 hours. Those without improvement by the fourth dose increase, received adjunct therapy. Length of treatment did not differ between morphine and clonidine, with median (95% confidence interval [CI]) days, respectively, of 15 (13-17) and 17 (15-19), P = .48. More clonidine-treated infants (45%) needed adjunct therapy versus 10% in the morphine group, adjusted odds ratio (95% CI) = 8.85 (2.87-27.31). After treatment completion, the NICU Network Neurobehavioral Scales summary scores did not differ between clonidine-treated and morphine-treated infants. Length of pharmacologic treatment and final neurobehavioral performance were not significantly different between the clonidine- and morphine-treated groups. Clonidine appears to be an effective non-opioid medication to treat NOWS. Future studies are needed to determine the optimal clonidine dosage for a quicker response and obviation of adjunct therapy.

Is Now the Time for Clonidine as a First-Line Agent for Neonatal Opioid Withdrawal Syndrome?

Is Now the Time for Clonidine as a First-Line Agent for Neonatal Opioid Withdrawal Syndrome?

Prediction of site-specific pharmacologic therapy among newborns with neonatal opioid withdrawal syndrome.

To predict pharmacotherapy for NOWS based on factors available shortly after birth. A multi-center, retrospective study of 1377 opioid exposed newborns between 2016 and 2017 dichotomized based on pharmacologic treatment (N = 665 treated, N = 712 not treated) was conducted. A multilevel mixed-effect logistic regression model that considered cluster effect from sites determined significant maternal and newborn factors associated with pharmacotherapy, which were combined in a nomogram to predict probability of treatment for infants at each participating site. Factors predictive of treatment were: no breastmilk (1.76, 1.30-2.39; p < 0.001), male sex (1.39, 1.05-1.83; p = 0.021), polysubstance exposure (1.53, 1.15-2.06; p = 0.004), inadequate prenatal care (1.51, 1.07-2.13; p < 0.018) and Methadone (6.08, 4.03-9.27; p < 0.001) or Buprenorphine (1.86, 1.29-2.69; p < 0.001). A site-specific nomogram provided the probability of treatment for individual newborns. Six factors available shortly after birth can be combined to predict site-specific use of medication for NOWS. If confirmed, the nomogram may identify at-risk newborns.

Evaluating Nutritional Selection and Outcomes in Neonatal Abstinence Syndrome: A Retrospective Review.

The rising incidence of neonatal abstinence syndrome (NAS) has amplified the importance of nonpharmacological interventions in its management, which include the selection of feedings. With the goal of obtaining an accurate assessment of the effects of current feeding practices in NAS infants in our neonatal intensive care unit, we conducted a retrospective review of NAS infants at our hospital over a 3-year period to determine their nutritional selections and evaluate their length of stay (LOS), length of treatment (LOT), and growth outcomes. Retrospective chart review of term infants (≥37 weeks of gestation) with NAS. Maternal and infant demographics and characteristics were recorded. Infants were grouped based on majority (>50% of total feeding) nutritional selections and LOS, LOT, and growth parameters were evaluated. Linear regression was used to compare group outcomes. Significance was set at a p-value <0.05. A total of 70 infants were included and grouped based on majority feeds into maternal breast milk (MBM), standard term formula (STF), low lactose formula (LLF), and extensively hydrolyzed formula (EHF) groups. Feeding selections were provider-dependent and infants were placed on MBM or STF as an initial selection. In all infants included in our review, LLF was selected as the first choice following MBM or STF for increased gastrointestinal (GI) disturbance-related Finnegan Neonatal Abstinence Scoring scores and changed to EHF if LLF failed to improve the GI-related symptoms. The STF-fed infants had the shortest LOS, and none of these infants required pharmacological treatment. The LOT and LOS were similar in the MBM- and LLF-fed groups. Infants who were EHF fed had the longest LOT and LOS. All feeding groups demonstrated appropriate growth. Nutritional selections in our NAS infants were modified for the severity of their withdrawal symptoms. All nutritional modifications driven by severity of withdrawal symptoms supported favorable growth outcomes in the infants. · Our NAS infants were fed with multiple types of nutrition.. · Infants with severe NAS required more elemental feeds.. · All formula selections supported favorable growth..

Intersection of Community Violence and Prenatal Substance Exposure: A Spatiotemporal Analysis.

Maternal substance use during pregnancy is a known risk factor for poor birth outcomes and lifelong health consequences. In addition, exposure to domestic and community violence can be associated with adverse birth outcomes. Due to limited research examining public health challenges linked to prenatal substance exposure (PSE)/neonatal abstinence syndrome (NAS) at the population level, we examined possible geographic and temporal intersections between (1) community violence and PSE/NAS, and (2) community gun violence and PSE/NAS. We conducted a study using abstracted records of neonates born at a tertiary referral hospital from 2012 to 2019 having a diagnosis code for PSE/NAS (n = 1,523). Cases of community violence were identified using a hospital-based Trauma Registry during the 2012 to 2019 period (n = 1,580). We identified zones of spatial clustering and geographic overlap between community violence and PSE/NAS using emerging hot spot analysis. Geographic and temporal clustering of PSE/NAS occurred. PSE/NAS had statistically significant zones of overlap with community assault cases (New Hot Spot 15 zones, Consecutive 5 zones, Sporadic Hot Spot 62 zones with a p < 0.01). PSE/NAS also clustered with community gun violence (New Hot Spot 11 zones, Consecutive Hot Spot 90 zones, Intensifying Hot Spot 13 zones, Sporadic Hot Spot 20 zones with a p < 0.01). Spatiotemporal overlap occurred between community violence and the adverse neonatal event of PSE/NAS. By allocating resources to identified geographic areas of increased risk, the health of vulnerable communities can be improved. · PSE/NAS geographically and temporally clusters with community violence.. · PSE/NAS geographically and temporally clusters with community gun violence.. · Resources should be provided to communities with increased risk.. · By allocating resources, communities members' health can be improved..

Prenatal Substance Exposure and Infant Discharge Placement: Results From the ACT NOW Study.

It is critical that researchers gather evidence of factors that identify infants at risk of out-of-home placement based on types of substance exposures and demographic characteristics. This study applied a validated medical record data extraction tool on data derived from a multi-site (N = 30) pediatric clinical trials network (ISPCTN) study of Neonatal Opioid Withdrawal (ACT NOW study). Participants included 1808 birthing parent-infant dyads with documented NOWS scoring or prenatal opioid exposure. Non-Hispanic White pregnant persons comprised the largest proportion of the sample (69.8%), followed by Non-Hispanic Black (11.6%), Non-Hispanic Multiracial and Other race (8.5%), and Hispanic (6.2%). Most notably, infant prenatal substance exposure across alcohol, cocaine, meth/amphetamine, and opioids, had the lowest possibility of discharging to parent(s). Additionally, latent class analysis identified distinct classes of substance use during pregnancy that were associated with different probabilities of discharging to parent(s). Specifically, less than half of infants (47%-49%) in the Poly-use and Meth/amphetamine classes were discharged to their parent(s). Severity of infant withdrawal symptoms influenced placement decisions within the Poly-use and Prescription Opioid classes. Findings can inform standard practices for increasing support for pregnant persons and substance-exposed infants including identification, subsequent referrals, communication with Child Protective Services, and plans of safe care.

Infant and parent heart rates during a babywearing procedure: Evidence for autonomic coregulation

Babywearing is the practice of carrying an infant in a baby carrier, which may provide an inexpensive, nonpharmacological intervention for the parent-infant dyads to handle mental stressors, such as pain and anxiety, especially among vulnerable infants. This study investigated the influence of babywearing on parent-infant autonomic coregulation based on the changes in the HR of mother-infant and father-infant dyads for infants with neonatal abstinence syndrome (NAS). Guided by the Calming Cycle Theory as the framework, the correlation between parent HR and infant HR and the difference in the mother-infant dyad (n = 17) compared to the father-infant dyad (n = 8) were examined. Although only the mother-infant HRs reached statistical significance during babywearing (r̅ =.52, p = .03), both parent-infant dyads had strong correlations during babywearing (compared to pre- and post-babywearing conditions), indicating that babywearing, for parents and their infants with NAS, may influence autonomic coregulation.

Nursing Students' Attitudes Toward Women With Maternal Substance Use Disorders.

Maternal substance use disorders (SUD) have challenged relationships between women with SUD and their nurses. Nurses have reported biased attitudes toward women with SUD, which can interfere with their care. However, it is not well known how nursing students perceive women with SUD and their infants. This article describes nursing students' attitudes toward women with SUD, which can be used to inform educational strategies. An inductive content analysis was used to analyze 76 reflection papers written by nursing students at a midwestern university. Three main themes were identified: (1) stigma toward women with SUD; (2) concerns for infants with neonatal abstinence syndrome; and (3) influence of clinical experiences on attitudes toward women with SUD. Nursing students need more evidence-based guidance on managing their biases as well as the biases of nurses who work in maternity settings. [J Nurs Educ. 2024;63(10):659-664.].

Variation in NICU utilization: a narrative review and path forward.

Utilization of the Neonatal Intensive Care Unit (NICU) varies widely in the United States. Over recent decades, there has been a growth in NICUs, that varies by region, and has not been correlated to changes in demand or illness severity. Unnecessary NICU admissions are costly, stressful to families, may increase the risk of hospital acquired morbidities, and decrease breast feeding. Most of the variation in NICU utilization is based on the care of late preterm, early term, and term babies and is related to hospital level factors, including financial incentives, driving utilization. Improvement strategies to reduce variation include regionalization of care, certificate of need legislation, improving discharge processes, and caring for babies with some conditions such as Neonatal Opioid Withdrawal Syndrome or those with risk factors for sepsis outside of the NICU.

In pregnant patients receiving treatment for opioid use disorder, does methadone reduce rates of neonatal opioid withdrawal syndrome compared to buprenorphine?

In pregnant patients receiving treatment for opioid use disorder, does methadone reduce rates of neonatal opioid withdrawal syndrome compared to buprenorphine?

Management of neonates exposed prenatally to opioids: Impact of a developmental care program implementation

BackgroundTraditional approaches to management of neonates prenatally exposed to opioids are based on the use of pharmacotherapy (PT), adjusted to evolution of infant symptoms. Newer approaches focused on non-pharmacological care (NPC) are emerging, but there is little evidence on the active policies to implement to ensure their widespread practice. The primary objective of the study was to assess whether the implementation of a developmental care program in our neonatal medicine department had an impact on the management of these infants during hospitalization, notably exposure to NPC. MethodObservational study in a tertiary perinatal center. Data collected during hospitalization for infants with in utero opioid exposure included admission in the parents-infant unit (PIU) of the maternity ward, exposure to NPC and PT, occurrence of neonatal opioid withdrawal syndrome (NOWS), length of hospital stay (LOS) and feeding type at discharge. The impact of the intervention was measured by comparing three 6-year periods, the first preceding the implementation of a formalized developmental care program (2003–2008); the second following implementation of the program (2009–2014); the third after consolidation of the program (2015–2020). Results258 infants prenatally exposed to opioid were recorded. From the first to the third period, admission rate in the PIU was comparable (68 % to 73 %, p = 0. 95). Exposure to NPC (37 % to 84 %, p < 0.001) increased, whereas exposure to PT (40 % to 15 %, p = 0.002) and LOS (13 [9–18] days to 8 [6–11] days, p = 0.003) decreased. NOWS occurred in 141 (55 %) infants (63 % to 47 %, p = 0.10). In these infants, decrease in PT was also observed (64 % to 34 %, p = 0.02). After adjustment for perinatal confounders, hospitalization in the PIU (OR 3.23 [1.36; 7.66]; p = 0.008), and the 2015–2020 period (OR 5.11 [2.06; 12.64]; p = 0.004) were associated with absence of PT. ConclusionsAn active policy, supporting the training and warranting the practice of NPC, is essential to reduce medication usage and length of hospitalization in infants exposed in utero to opioids.

Association of Food and Housing Insecurity on Outcomes in Pregnant Patients With Substance Use Disorder.

Food insecurity (FI) may be associated with worsened neonatal abstinence syndrome severity in infants born to individuals with substance use disorder. This study evaluates FI and housing insecurity (HI) influence on maternal and neonatal outcomes. This was a cohort study of patients receiving obstetric care through a multispecialty program in Kentucky from 2015 to 2023. Inclusion criteria were: (1) program participants over age 18 consenting to observational research, (2) delivering at University of Kentucky, and (3) not withdrawing from research at any time. Initially, a subset of patients for whom FI and HI concerns were heightened were screened. In 2019, FI and HI screening became standard of care at the clinic. Housing was assessed on enrollment. A validated 2-question Hunger Vital Sign FI screen was utilized for a subset of patients. Maternal and neonatal outcomes, including adverse delivery outcomes, maternal comorbidities, and birth complications, were observed. Fisher's exact and 2 sample t tests were performed. Of 494 participants, 188 (38%) identified at risk for HI. At enrollment, 221 (45%) individuals reported owning their primary residence, 85 (17%) were in group residential treatment, 34 (6.9%) had no housing, and 134 (27%) lived at another's residence. Disposition of a child to a relative or not the patient's own care was greater with HI, 51% versus 47%. Of 155 respondents, 96 (62%) reported FI, associated with increased neonatal intensive care unit (NICU) admission, 86% versus 74%. Using the validated tool, Abuse Assessment Screen, abuse was significantly greater with FI, 76% versus 58%. Edinburgh Postpartum Depression Scales >12 indicating depression were more common with FI, 63% versus 32%, P < .05. Anxiety scores were also higher with FI, P < .05. Patients with FI were more likely to experience abuse. FI and HI were health-related needs associated with increased anxiety, depression, infant NICU admission, and loss of child custody.

The ultrasonic vocalization (USV) syllable profile during neonatal opioid withdrawal and a kappa opioid receptor component to increased USV emissions in female mice.

Opioid use during pregnancy can lead to negative infant health outcomes, including neonatal opioid withdrawal syndrome (NOWS). NOWS comprises gastrointestinal, autonomic nervous system, and neurological dysfunction that manifest during spontaneous withdrawal. Variability in NOWS severity necessitates a more individualized treatment approach. Ultrasonic vocalizations (USVs) in neonatal mice are emitted in isolation as a stress response and are increased during opioid withdrawal, thus modeling a negative affective state that can be utilized to test new treatments. We sought to identify the behavioral and USV profile, brainstem transcriptomic adaptations, and role of kappa opioid receptors in USVs during neonatal opioid withdrawal. We employed a third trimester-approximate opioid exposure model, where neonatal inbred FVB/NJ pups were injected twice-daily with morphine (10mg/kg, s.c.) or saline (0.9%, 20 ul/g, s.c.) from postnatal day(P) 1 to P14. This protocol induces reduced weight gain, hypothermia, thermal hyperalgesia, and increased USVs during spontaneous morphine withdrawal. On P14, there were increased USV emissions and altered USV syllables during withdrawal, including an increase in Complex 3 syllables in FVB/NJ females (but not males). Brainstem bulk mRNA sequencing revealed an upregulation of the kappa opioid receptor (Oprk1), which contributes to withdrawal-induced dysphoria. The kappa opioid receptor (KOR) antagonist, nor-BNI (30 mg/kg, s.c.), significantly reduced USVs in FVB/NJ females, but not males during spontaneous morphine withdrawal. Furthermore, the KOR agonist, U50,488h (0.625 mg/kg, s.c.), was sufficient to increase USVs on P10 (both sexes) and P14 (females only) in FVB/NJ mice. We identified an elevated USV syllable, Complex 3, and a female-specific recruitment of the dynorphin/KOR system in increased USVs associated with neonatal opioid withdrawal severity.