A Dyadic Framework of Care for Opioid-exposed Birthing Persons and Their Infants and Children.

OBJECTIVE: To develop a dyadic-centered framework focused on clinical care, surveillance, and research for birthing persons with opioid use disorder (OUD) and their infants and children. STUDY DESIGN: Between February and March 2023, an analysis was conducted within the US Department of Health and Human Services (HHS) of activities directed at opioid-exposed birthing persons and their infants and children (the dyad) to identify: 1) number of activities, stratified by type and 2) characteristics across health and supportive activities that serve the dyad vs birthing persons or infants and children individually. Descriptive and thematic analyses were used to assess quantity and characteristics of fiscal year 2023-2024 activities aggregated across eleven HHS agencies. RESULTS: Of 181 activities examined, 75 met inclusion criteria specific to serving birthing persons with OUD and opioid-exposed infants and children. Sixty-two percent of activities were dyad focused. Five categories of dyadic activities were identified: research (45%), education and training (28%), health and supportive services (21%), surveillance (4%), and quality improvement (2%). Eight specific characteristics were key to dyadic activities: a life course and generational approach, emphasis on relationship, dyadic outcomes, service wraparound, payment structures supporting dyadic care, data linkage, and social determinants of health. CONCLUSIONS: This analysis of HHS activities directed at birthing persons with OUD and opioid-exposed infants and children showed that most programs had a dyadic focus. Synthesizing elements identified from activities serving the dyad facilitated the development of a dyadic framework integrating clinical care, public health surveillance, and research.

Comparison of the effect of phenobarbital & levetiracetam in the treatment of neonatal abstinence syndrome (NAS) as adjuvant treatment in neonates admitted to the neonatal intensive care unit: a randomized clinical trial.

BACKGROUND: Infants who are born from mothers with substance use disorder might suffer from neonatal abstinence syndrome (NAS) and need treatment with medicines. One of these medicines is phenobarbital, which may cause side effects in long-term consumption. Alternative drugs can be used to reduce these side effects. This study seeks the comparison of the effects of phenobarbital & levetiracetam as adjuvant therapy in neonatal abstinence syndrome. METHODS: This randomized clinical trial was performed in one year from May 2021 until May 2022. The neonates who were born from mothers with substance use disorder and had neonatal abstinence syndrome in Afzalipoor Hospital of Kerman were studied. The treatment started with morphine initially and every four hours the infants were checked. The infants who were diagnosed with uncontrolled symptoms After obtaining informed consent from the parents were randomly divided into two groups and treated with secondary drugs, either phenobarbital or levetiracetam. RESULTS: Based on the obtained results, it was clear that there was no significant difference between the hospitalization time of the two infant groups under therapy (phenobarbital: 18.59 days versus Levetiracetam 18.24 days) (P-value = 0.512). Also, there was no significant difference between both groups in terms of the frequency of re-hospitalization during the first week after discharge, the occurrence of complications, and third treatment line prescription (P-value = 0.644). CONCLUSIONS: Based on the obtained results, like hospitalization duration time (P-value = 0.512) it seems that levetiracetam can be used to substitute phenobarbital in treating neonatal abstinence syndrome. TRIAL REGISTRATION: The current study has been registered in the Iran registry of clinical trials website (fa.irct.ir) on the date 25/2/2022 with registration no. IRCT20211218053444N2.

Maternal opioid use during pregnancy and the risk of neonatal opioid withdrawal syndrome in the offspring.

INTRODUCTION: Neonatal opioid withdrawal syndrome (NOWS) is caused by sudden cessation from in utero exposure to opioids. The indications for opioid use during pregnancy are diverse including medication for opioid use disorder and analgesia. The opioid dose typically depends on the indication, with higher doses used for medication for opioid use disorder and lower doses used for analgesia. The aim of this study was to investigate the relationship between maternal opioid dose during pregnancy and the risk of NOWS. MATERIAL AND METHODS: We conducted a historical multicenter cohort study of neonates prenatally exposed to opioids in Eastern Denmark during a six-year period from 2013 to 2018. The data was extracted from reviewing the individual's medical record(s), which were identified through a search of the Danish National Patient Register. Four groups (quartiles) according to maternal opioid dose during the last four weeks prior to delivery were compared. Unadjusted and adjusted logistic regression analyses were conducted to examine the risk of NOWS while controlling for relevant covariates. RESULTS: A total of 130 in utero opioid exposed neonates were included. The majority of the pregnant patients (88%) were treated with opioids for analgesic purposes. Overall, 52% of neonates developed NOWS. The cumulative incidence of NOWS was 21%, 28%, 67% and 91% at maternal average daily dose of morphine milligram equivalent during the last four weeks prior to delivery of 0.7-14 (group I), 14.3-38.6 (group II), 40-90 (group III) and 90.9-1440 (group IV), respectively. Compared to group I the adjusted odds (aOR) of NOWS increased significantly in group III (aOR 10.6 [2.9-39.1]) and group IV (aOR 37.8 [7.6-188.2]) but not in group II (aOR 1.5 [0.4-5.2]). No cases of NOWS were reported at maternal dose less than an average daily dose of five morphine milligram equivalent during the last four weeks prior to delivery. No significant changes in the incidence of NOWS were observed between 2013 and 2018. CONCLUSIONS: The odds of neonatal opioid withdrawal syndrome increased significantly as the maternal average daily dose of morphine milligram equivalent during the last four weeks prior to delivery surpassed 40.

Perinatal Opioid Exposure Results in Persistent Hypoconnectivity of Excitatory Circuits and Reduced Activity Correlations in Mouse Primary Auditory Cortex.

Opioid use by pregnant women results in neonatal opioid withdrawal syndrome (NOWS) and lifelong neurobehavioral deficits including language impairments. Animal models of NOWS show impaired performance in a two-tone auditory discrimination task, suggesting abnormalities in sensory processing in the auditory cortex. To investigate the consequences of perinatal opioid exposure on auditory cortex circuits, we administered fentanyl to mouse dams in their drinking water throughout gestation and until litters were weaned at postnatal day (P)21. We then used in vivo two-photon Ca2+ imaging in adult animals of both sexes to investigate how primary auditory cortex (A1) function was altered. Perinatally exposed animals showed fewer sound-responsive neurons in A1, and the remaining sound-responsive cells exhibited lower response amplitudes but normal frequency selectivity and stimulus-specific adaptation (SSA). Populations of nearby layer 2/3 (L2/3) cells in exposed animals showed reduced correlated activity, suggesting a reduction of shared inputs. We then investigated A1 microcircuits to L2/3 cells by performing laser-scanning photostimulation (LSPS) combined with whole-cell patch-clamp recordings from A1 L2/3 cells. L2/3 cells in exposed animals showed functional hypoconnectivity of excitatory circuits of ascending inputs from L4 and L5/6 to L2/3, while inhibitory connections were unchanged, leading to an altered excitatory/inhibitory balance. These results suggest a specific reduction in excitatory ascending interlaminar cortical circuits resulting in decreased activity correlations after fentanyl exposure. We speculate that these changes in cortical circuits contribute to the impaired auditory discrimination ability after perinatal opioid exposure.SIGNIFICANCE STATEMENT This is the first study to investigate the functional effects of perinatal fentanyl exposure on the auditory cortex. Experiments show that perinatal fentanyl exposure results in decreased excitatory functional circuits and altered population activity in primary sensory areas in adult mice. These circuit changes might underlie the observed language and cognitive deficits in infants exposed to opioids.

Neonatal opioid toxicity: opioid withdrawal (abstinence) syndrome with emphasis on pharmacogenomics and respiratory depression.

The increasing use of opioids in pregnant women has led to an alarming rise in the number of cases of neonates with drug-induced withdrawal symptoms known as neonatal opioid withdrawal syndrome (NOWS). NOWS is a toxic heterogeneous condition with many neurologic, autonomic, and gastrointestinal symptoms including poor feeding, irritability, tachycardia, hypertension, respiratory defects, tremors, hyperthermia, and weight loss. Paradoxically, for the management of NOWS, low doses of morphine, methadone, or buprenorphine are administered. NOWS is a polygenic disorder supported by studies of genomic variation in opioid-related genes. Single-nucleotide polymorphisms (SNPs) in CYP2B6 are associated with variations in NOWS infant responses to methadone and SNPs in the OPRM1, ABCB1, and COMT genes are associated with need for treatment and length of hospital stay. Epigenetic gene changes showing higher methylation levels in infants and mothers have been associated with more pharmacologic treatment in the case of newborns, and for mothers, longer infant hospital stays. Respiratory disturbances associated with NOWS are not well characterized. Little is known about the effects of opioids on developing neonatal respiratory control and respiratory distress (RD), a potential problem for survival of the neonate. In a rat model to test the effect of maternal opioids on the developing respiratory network and neonatal breathing, maternal-derived methadone increased apneas and lessened RD in neonates at postnatal (P) days P0 and P1. From P3, breathing normalized with age suggesting reorganization of respiratory rhythm-generating circuits at a time when the preBötC becomes the dominant inspiratory rhythm generator. In medullary slices containing the preBötC, maternal opioid treatment plus exposure to exogenous opioids showed respiratory activity was maintained in younger but not older neonates. Thus, maternal opioids blunt centrally controlled respiratory frequency responses to exogenous opioids in an age-dependent manner. In the absence of maternal opioid treatment, exogenous opioids abolished burst frequencies at all ages. Prenatal opioid exposure in children stunts growth rate and development while studies of behavior and cognitive ability reveal poor performances. In adults, high rates of attention deficit disorder, hyperactivity, substance abuse, and poor performances in intelligence and memory tests have been reported.

The Alberta Neonatal Abstinence Syndrome Mother-Baby Care ImprovEmeNT (NASCENT) program: protocol for a stepped wedge cluster randomized trial of a hospital-level Neonatal Abstinence Syndrome rooming-in intervention.

BACKGROUND: Neonatal Abstinence Syndrome (NAS), a problem common in newborns exposed to substances in-utero, is an emerging health concern. In traditional models of care, infants with NAS are routinely separated from their mothers and admitted to the Neonatal Intensive Care Unit (NICU) with long, expensive length of stay (LOS). Research shows a rooming-in approach (keeping mothers and infants together in hospital) with referral support is a safe and effective model of care in managing NAS. The model's key components are facilitating 24-h care by mothers on post-partum or pediatric units with support for breastfeeding, transition home, and access to Opioid Dependency Programs (ODP). This study will implement the rooming-in approach at eight hospitals across one Canadian Province; support practice and culture shift; identify and test the essential elements for effective implementation; and assess the implementation's impact/outcomes. METHODS: A stepped wedge cluster randomized trial will be used to evaluate the implementation of an evidence-based rooming-in approach in the postpartum period for infants born to mothers who report opioid use during pregnancy. Baseline data will be collected and compared to post-implementation data. Six-month assessment of maternal and child health and an economic evaluation of cost savings will be conducted. Additionally, barriers and facilitators of the rooming-in model of care within the unique context of each site and across sites will be explored pre-, during, and post-implementation using theory-informed surveys, interviews, and focus groups with care teams and parents. A formative evaluation will examine the complex contextual factors and conditions that influence readiness and sustainability and inform the design of tailored interventions to facilitate capacity building for effective implementation. DISCUSSION: The primary expected outcome is reduced NICU LOS. Secondary expected outcomes include decreased rates of pharmacological management of NAS and child apprehension, increased maternal ODP participation, and improved 6-month outcomes for mothers and infants. Moreover, the NASCENT program will generate the detailed, multi-site evidence needed to accelerate the uptake, scale, and spread of this evidence-based intervention throughout Alberta, leading to more appropriate and effective care and use of healthcare resources. TRIAL REGISTRATION: ClinicalTrials.gov, NCT0522662. Registered February 4th, 2022.

Prenatal Substance Exposure and Neonatal Abstinence Syndrome: State Estimates from the 2016-2020 Transformed Medicaid Statistical Information System.

INTRODUCTION: Estimating Neonatal Abstinence Syndrome (NAS) and prenatal substance exposure rates in Medicaid can help target program efforts to improve access to services. METHODS: The data for this study was extracted from the 2016-2020 Transformed Medicaid Statistical Information System (T-MSIS) Analytic Files (TAF) Research Identifiable Files (RIF) and included infants born between January 1, 2016 and December 31, 2020 with a either a NAS diagnosis or prenatal substance exposure. RESULTS: Between 2016 and 2020, the estimated national rate of NAS experienced a 18% decline, while the estimated national rate of prenatal substance exposure experienced a 3.6% increase. At the state level in 2020, the NAS rate ranged from 3.2 per 1000 births (Hawaii) to 68.0 per 1000 births (West Virginia). Between 2016 and 2020, 28 states experienced a decline in NAS births and 20 states had an increase in NAS rates. In 2020, the lowest prenatal substance exposure rate was observed in New Jersey (9.9 per 1000 births) and the highest in West Virginia (88.1 per 1000 births). Between 2016 and 2020, 38 states experienced an increase in the rate of prenatal substance exposure and 10 states experienced a decline. DISCUSSION: Estimated rate of NAS has declined nationally, but rate of prenatal substance exposure has increased, with considerable state-level variation. The reported increase in prenatal substance exposure in the majority of US states (38) suggest that substances other than opioids are influencing this trend. Medicaid-led initiatives can be used to identify women with substance use and connect them to services.

What is already known about the topic? Neonatal Abstinence Syndrome (NAS) and prenatal substance exposure are significant risk factors for poor neurodevelopmental and mental health outcomes in early childhood. NAS birth rates have been increasing in the US since 2000 and the majority of NAS births are covered by Medicaid.What this article adds? This article estimates national and state-level prenatal substance exposure and NAS rates among Medicaid-covered infants born between 2016-2020 using data from the Transformed Medicaid Statistical Information System. This is the first study using post-2017 data to estimate national NAS rates. The findings can inform future federal and state policy efforts to improve access to screening, diagnosis and treatment among pregnant women with substance use disorder and infants with NAS.

Evaluation of Administrative Data for Identifying Maternal Opioid Use at Delivery in Florida.

OBJECTIVES: Studies have shown significant increases in the prevalence of maternal opioid use. Most prevalence estimates are based on unverified ICD-10-CM diagnoses. This study determined the accuracy of ICD-10-CM opioid-related diagnosis codes documented during delivery and examined potential associations between maternal/hospital characteristics and diagnosis with an opioid-related code. METHODS: To identify people with prenatal opioid use, we identified a sample of infants born during 2017-2018 in Florida with a NAS related diagnosis code (P96.1) and confirmatory NAS characteristics (N = 460). Delivery records were scanned for opioid-related diagnoses and prenatal opioid use was confirmed through record review. The accuracy of each opioid-related code was measured using positive predictive value (PPV) and sensitivity. Modified Poisson regression was used to calculate adjusted relative risks (aRR) and 95% confidence intervals (CI). RESULTS: We found the PPV was nearly 100% for all ICD-10-CM opioid-related codes (98.5-100%) and the sensitivity was 65.9%. Non-Hispanic Black mothers were 1.8 times more likely than non-Hispanic white mothers to have a missed opioid-related diagnosis at delivery (aRR:1.80, CI 1.14-2.84). Mothers who delivered at a teaching status hospital were less likely to have a missed opioid-related diagnosis (p < 0.05). CONCLUSIONS FOR PRACTICE: We observed high accuracy of maternal opioid-related diagnosis codes at delivery. However, our findings suggest that over 30% of mothers with opioid use may not be diagnosed with an opioid-related code at delivery, although their infant had a confirmed NAS diagnosis. This study provides information on the utility and accuracy of ICD-10-CM opioid-related codes at delivery among mothers of infants with NAS.

From 2010 to 2017, maternal opioid-related diagnoses at delivery increased by 100% in the US. Most prevalence estimates are based on unverified ICD-10-CM diagnosis codes. Evaluations of maternal opioid-related diagnoses at delivery are extremely limited but essential for utilizing prevalence estimates generated from administrative data.

Breastfeeding Experiences in Women from Ten States Reporting Opioid Use Before or During Pregnancy: PRAMS, Phase 8.

INTRODUCTION: Evidence of opioid use at hospital delivery has increased over the past two decades, increasing risk of neonatal withdrawal. Breastfeeding may improve infant outcomes, but little is known about breastfeeding experiences of women who have a history of opioid use prior to or during pregnancy. This study aimed to determine if self-reported opioid use prior to or during pregnancy impacted breastfeeding, specifically attempt to breastfeed, duration of breastfeeding, assessment of prenatal breastfeeding intention, source of breastfeeding information, and early hospital experiences. METHODS: Data from ten states (n = 10,550) that evaluated opioid use in the 2016 Pregnancy Risk Assessment Monitoring System survey were included. Weighted univariate and multivariate linear and logistic regression were calculated. The multivariate regression also included adjustment for covariates. RESULTS: Among the overall sample, 939 participants reported opioid exposure before or during pregnancy. We found no significant difference in breastfeeding attempt. Breastfeeding for at least 6, 10, or 20 weeks was significantly less likely in participants reporting opioid exposure. Exposure correlated with lower odds of skin-to-skin contact, infant being fed in the first hour, exclusive breastfeeding in the hospital, and feeding on demand. Hospital pacifier use was associated with opioid exposure. CONCLUSION: While we found no difference in breastfeeding attempt, we did observe significant differences in breastfeeding duration and early hospital experiences which may represent modifiable gaps in clinical practice. Future work should focus on optimizing early hospital experiences and support when breastfeeding is clinically indicated.

Demographics, Birth Parameters, and Social Determinants of Health Among Opioid-Exposed Mother-Infant Dyads Affected by Neonatal Abstinence Syndrome in Pennsylvania, 2018-2019.

OBJECTIVES: To characterize demographics, birth parameters, and social determinants of health among mother-infant dyads affected by neonatal abstinence syndrome (NAS) in Pennsylvania. METHODS: We linked 2018-2019 NAS surveillance data to birth record data using probabilistic methods and then geospatially linked to local social determinants of health data based on residential address. We generated descriptive statistics and used multivariable mixed-effects logistic regression to model the association between maternal characteristics, birth parameters, social determinants of health, and NAS. RESULTS: In adjusted models maternal age > 24, non-Hispanic white race/ethnicity, low educational attainment, Medicaid as payor at delivery, inadequate or no prenatal care, smoking during pregnancy, and low median household income were associated with NAS. We found no significant associations between NAS and county-level measures of clinician supply, number of substance use treatment facilities, or urban/rural designation. CONCLUSIONS FOR PRACTICE: This study characterizes mother-infant dyads affected by NAS using linked non-administrative, population data for Pennsylvania. Results demonstrate a social gradient in NAS and inequity in prenatal care receipt among mothers of infants with NAS. Findings may inform implementation of state-based public health interventions.

Adverse Maternal Experiences and Neonatal Abstinence Syndrome.

OBJECTIVES: To propose a measure for adverse maternal experiences (AMEs) and examine if AMEs are independently associated with delivery of a neonatal abstinence syndrome (NAS) diagnosed infant. METHODS: Using the Pregnancy Risk Assessment Monitoring System (PRAMS) stressful life events questions, we constructed a composite measure of AMEs. We conducted a retrospective analysis of linked Birth Certificate Data, Hospital Discharge Data and PRAMS data for 2012-2018 using the composite measure. Our analytic sample included 6358 singleton deliveries. We calculated prevalence of NAS and AMEs and prevalence odds ratio (POR) for delivery of an NAS-diagnosed infant adjusting for maternal sociodemographic characteristics, pre-pregnancy depression, prescription medicine 12 months prior to pregnancy, and smoking during pregnancy. RESULTS: The overall prevalence of NAS in Delaware during 2012-2018 was 2.2% (95% CI 1.8-2.6); 9.5% (95% CI 8.7-10.2) of women reported AMEs. After adjustment, women with AMEs had 1.1 times greater odds (aPOR 2.1; 95% CI 1.3-3.3) to deliver a NAS-diagnosed infant as compared with women without AMEs. CONCLUSIONS: Although the cross-sectional nature of the study limits drawing any causal inferences, there are co-occurring factors that support plausibility of an association between AMEs and delivering NAS-diagnosed infants. Addressing AMEs, mental health and substance use screening and treatment as part of preconception and prenatal care may mitigate risks.

Prediction model for nonopiate-induced neonatal abstinence syndrome.

BACKGROUND: Neonatal abstinence syndrome (NAS) induced by opiate use is common worldwide. Psychiatric drugs are a more common cause of NAS in Japan but infants of mothers taking psychiatric medications do not always develop NAS. The purpose of this study was to develop a practical model for predicting the onset of nonopiate-induced NAS, using variables available at birth. METHODS: In this diagnostic study, prediction models were developed using multivariable logistic regression with retrospective data collected at our hospital between 2010 and 2019. The NAS diagnosis was based on the Isobe score, and maternal medications were converted to dose equivalents. RESULTS: A total of 164 maternal and infant dyads met the inclusion criteria; 91 were included in the analysis, of whom 29 infants (32%) were diagnosed with NAS. Final models were created with and without the drug indices. The model without the drug indices consisted of neonatal head circumference in z-scores and Apgar scores at 5 min < 9, and the model with the drug indices included these, as well as antipsychotics and hypnotics indices. The C-statistics were 0.747 (95% CI: 0.638-0.856), and 0.795 (95% CI: 0.683-0.907), respectively, indicating that the models possessed good predictive accuracy for NAS onset. CONCLUSIONS: This study developed models that predicted nonopiate-induced NAS accurately. They may be further improved through the use of drug indices.

A review of the literature: How does prenatal opioid exposure impact placental health and fetal brain development?

In recent years, there has been a sixfold increase in the number of pregnant people with opioid use disorder (OUD). Rates of neonatal opioid withdrawal syndrome (NOWS), previously known as neonatal abstinence syndrome (NAS), have significantly increased in virtually every state and demographic group (Healthcare Cost Utilization Project, HCUP, 2010). NOWS is a condition resulting from chronic exposure to either therapeutic opioid use (e.g., medication for OUD, chronic pain conditions) or nonprescribed opioid use. To date, there is no known prenatal treatment to help decrease the risk of infants developing NOWS and subsequent neurodevelopmental outcomes. Given the increasing support for how placental signaling, or placental programming, may play a role in downstream pathology, prospective research investigating how the placenta is affected by chronic opioid exposure morphologically, histologically, and at the cellular level may open up potential treatment opportunities in this field. In this review, we discuss literature exploring the physiological roles of nitric oxide and dopamine not only in the vascular development of the placenta, but also in fetal cerebral blood flow, neurogenesis, neuronal differentiation, and neuronal activity. We also discuss histological preclinical studies that suggest chronic opioid exposure to induce some combination of placental dysfunction and hypoxia in a manner similar to other well-known placental pathologies, as denoted by the compensatory neovascularization and increased utilization of the placenta's supply of trophoblast cells, which play an essential role in placental angiogenesis. Overall, we found that the current literature, while limited, suggests chronic opioid exposure negatively impacts placental function and fetal brain development on a cellular and histopathological level. We conclude that it is worthwhile to consider the placenta as a therapeutic target with the ultimate goal of decreasing the incidence of NOWS and the long-term impacts of prenatal opioid exposure.

Otolaryngologic conditions in children with neonatal abstinence syndrome: A descriptive study.

PURPOSE: Literature on otolaryngologic sequelae of children with neonatal abstinence syndrome (NAS) has been scarce to date. Prior reports suggest some otologic conditions associated with long-term NAS outcomes, but no comprehensive exploration of these relationships currently exists. This study aims to characterize the breadth of otolaryngologic conditions diagnosed in children with NAS. METHODS: This is a retrospective descriptive study conducted at a tertiary care hospital. We identified 524 children with NAS born between 1/1/2014 and 12/31/2019 who were evaluated by the otolaryngology department. Diagnoses were categorized as otologic, oropharyngeal, sinonasal, and laryngeal. Additional diagnoses of obstructive sleep apnea (OSA) and congenital abnormalities of head and neck were noted separately. Descriptive statistics were calculated, and ANCOVA testing analyzed for differences in mean number of diagnoses. RESULTS: 680 total otolaryngologic diagnoses were analyzed across 524 patients. Otologic conditions comprised 39.7 % of total diagnoses, oropharyngeal conditions 26.8 %, sinonasal conditions 18.4 %, laryngeal conditions 5.3 %, OSA 1.5 %, and congenital abnormalities 8.3 %. After adjusting for covariates, there were a significantly higher number of otologic diagnoses compared to the other subcategories with mean (standard deviation) of 0.46 (0.83), followed by oropharyngeal 0.35 (0.55), sinonasal 0.24 (0.49), and laryngeal 0.07 (0.29). Thirty total otolaryngology-related procedures were performed in our sample, with myringotomy with tube insertion as the most common. CONCLUSION: Understanding the otolaryngologic sequelae of children with NAS is important as these conditions impact children's early development. Our study also highlights various socioeconomic factors that may impact pediatric ENT care and the follow-up of patients born with NAS.

"Will My Baby Be OK?" A Qualitative Analysis of Pregnant Women's Suboxone® Online Forum Posts.

BACKGROUND: Intentional or accidental drug-overdose is a leading cause of mortality in U.S. women of child-bearing age. Opioid use during pregnancy is not only associated with maternal overdose, but with low birth weight at term and neonatal abstinence syndrome (NAS). Buprenorphine was approved as a medication for opioid use disorder (MOUD) in the United States in 2002 and is for many women, a preferred treatment option versus methadone. Buprenorphine is relatively safe during pregnancy and is associated with lower rates of NAS than methadone. Given the importance of MOUD during pregnancy, relatively little information exists regarding patients' questions and concerns about buprenorphine treatment, including the psychological challenges they face. AIMS: The purpose of the study was to describe the perinatal concerns of women with opioid use disorder who posted to an online suboxone forum. METHODS: Qualitative descriptive design to analyze some 170 posts from mothers with OUD to an online Suboxone® support forum over the period 2016-2021. RESULTS: The analysis of the interview data revealed 4 important themes: (a) Stigma resulting in self-deprecation, low self-esteem, and low self-efficacy; (b) stigma from family members and loved ones; (c) stigma from the medical profession; and (d) stigma from the community at-large (social stigma). CONCLUSIONS: There is compelling evidence to emphasize the importance of open communication and support between medical personnel and patients to ensure optimal outcomes for mother and baby.

A population-based descriptive study of neonatal abstinence syndrome using hospital discharge and birth certificate data.

BACKGROUND: Neonatal abstinence syndrome (NAS), largely a consequence of prenatal opioid exposure, results in substantial morbidity. Population-based studies of NAS going beyond Medicaid populations and hospital discharge data (HDD) alone are limited. Using statewide Tennessee (TN) HDD and birth certificate (BC) data, we examined trends and evaluated maternal and infant factors associated with NAS. METHODS: We conducted a population-based descriptive study during 2013-2017 in TN. NAS infants were identified with International Classification of Diseases (ICD)-9-Clinical Modification (CM) and ICD-10-CM codes in HDD and linked to BC data using iterative deterministic matching algorithms. Descriptive analyses were conducted for infant and maternal factors (exposures) by NAS (outcome). Multivariable logistic regression models were used to estimate adjusted ORs and 95% CIs. RESULTS: NAS incidence increased from 13.4 to 15.4 per 1,000 live births between 2013-2017 (15% increase; ptrend<0.001), but remained stable in 2017. In adjusted models, maternal factors associated with reduced odds of NAS included breastfeeding (OR:0.55, 95%CI:0.52-0.59) and prenatal care (OR:0.36, 95%CI:0.32-0.41). Smoking, preterm birth and lower birthweight were associated with increased odds of NAS. CONCLUSIONS: This study highlights the value of utilizing surveillance data to monitor trends and correlates of NAS to inform prevention efforts and targeting of public health resources.

Trajectories of Prescription Opioid Utilization During Pregnancy Among Prepregnancy Chronic Users and Risk of Neonatal Opioid Withdrawal Syndrome.

Little is known about the impact of dose, duration, and timing of prenatal prescription opioid exposure on the risk of neonatal opioid withdrawal syndrome (NOWS). Using a cohort of 18,869 prepregnancy chronic opioid users nested within the 2000-2014 Medicaid Analytic eXtract, we assessed average opioid dosage within biweekly gestational age intervals, created group-based trajectory models, and evaluated the association between trajectory groups and NOWS risk. Women were grouped into 6 distinct opioid use trajectories which, based on observed patterns, were categorized as 1) continuous very low-dose use, 2) continuous low-dose use, 3) initial moderate-dose use with a gradual decrease to very low-dose/no use, 4) initial high-dose use with a gradual decrease to very low-dose use, 5) continuous moderate-dose use, and 6) continuous high-dose use. Absolute risk of NOWS per 1,000 infants was 7.7 for group 1 (reference group), 28.8 for group 2 (relative risk (RR) = 3.7, 95% confidence interval (CI): 2.8, 5.0), 16.5 for group 3 (RR = 2.1, 95% CI: 1.5, 3.1), 64.9 for group 4 (RR = 8.4, 95% CI: 5.6, 12.6), 77.3 for group 5 (RR = 10.0, 95% CI: 7.5, 13.5), and 172.4 for group 6 (RR = 22.4, 95% CI: 16.1, 31.2). Trajectory models-which capture information on dose, duration, and timing of exposure-are useful for gaining insight into clinically relevant groupings to evaluate the risk of prenatal opioid exposure.

Clinical and basic research investigations into the long-term effects of prenatal opioid exposure on brain development.

Coincident with the opioid epidemic in the United States has been a dramatic increase in the number of children born with neonatal abstinence syndrome (NAS), a form of withdrawal resulting from opioid exposure during pregnancy. Many research efforts on NAS have focused on short-term care, including acute symptom treatment and weaning of the infants off their drug dependency prior to authorizing their release. However, investigations into the long-term effects of prenatal opioid exposure (POE) on brain development, from the cellular to the behavioral level, have not been as frequent. Given the importance of the perinatal period for human brain development, opioid-induced disturbances in the formation and function of nascent synaptic networks and glia have the potential to impact brain connectivity and cognition long after the drug supply is cutoff shortly after birth. In this review, we will summarize the current state of NAS research, bringing together findings from human studies and preclinical animal models to highlight what is known about how POE can induce significant, prolonged deficits in brain structure and function. With rates of NAS continuing to rise, particularly in regions that already face substantial socioeconomic challenges, we speculate as to the most promising avenues for future research to alleviate this growing multigenerational threat.

Maternal and iatrogenic neonatal opioid withdrawal syndrome: Differences and similarities in recognition, management, and consequences.

Opioids are potent analgesics used to manage pain in both young and old, but the increased use in the pregnant population has significant individual and societal implications. Infants dependent on opioids, either through maternal or iatrogenic exposure, undergo neonatal opioid withdrawal syndrome (NOWS), where they may experience withdrawal symptoms ranging from mild to severe. We present a detailed and original review of NOWS caused by maternal opioid exposure (mNOWS) and iatrogenic opioid intake (iNOWS). While these two entities have been assessed entirely separately, recognition and treatment of the clinical manifestations of NOWS overlap. Neonatal risk factors such as age, genetic predisposition, drug type, and clinical factors like type of opioid, cumulative dose of opioid exposure, and disease status affect the incidence of both mNOWS and iNOWS, as well as their severity. Recognition of withdrawal is dependent on clinical assessment of symptoms, and the use of clinical assessment tools designed to determine the need for pharmacotherapy. Treatment of NOWS relies on a combination of non-pharmacological therapies and pharmacological options. Long-term consequences of opioids and NOWS continue to generate controversy, with some evidence of anatomic brain changes, but conflicting animal and human clinical evidence of significant cognitive or behavioral impacts on school-age children. We highlight the current knowledge on clinically relevant recognition, treatment, and consequences of NOWS, and identify new advances in clinical management of the neonate. This review brings a unique clinical perspective and critically analyzes gaps between the clinical problem and our preclinical understanding of NOWS.

Standardizing the Clinical Definition of Opioid Withdrawal in the Neonate.

OBJECTIVE: To standardize the clinical definition of opioid withdrawal in neonates to address challenges in clinical care, quality improvement, research, and public policy for this patient population. STUDY DESIGN: Between October and December 2020, we conducted 2 modified-Delphi panels using ExpertLens, a virtual platform for performing iterative expert engagement panels. Twenty clinical experts specializing in care for the substance-exposed mother-neonate dyad explored the necessity of key evidence-based clinical elements in defining opioid withdrawal in the neonate leading to a diagnosis of neonatal abstinence syndrome (NAS)/neonatal opioid withdrawal syndrome (NOWS). Expert consensus was assessed using descriptive statistics, the RAND/UCLA Appropriateness Method, and thematic analysis of participants' comments. RESULTS: Expert panels concluded the following were required for diagnosis: in utero exposure (known by history, not necessarily by toxicology testing) to opioids with or without the presence of other psychotropic substances, and the presence of at least two of the most common clinical signs characteristic of withdrawal (excessive crying, fragmented sleep, tremors, increased muscle tone, gastrointestinal dysfunction). CONCLUSIONS: Results indicate that both a known history of in utero opioid exposure and a distinct set of withdrawal signs are necessary to standardize a definition of neonatal withdrawal. Implementation of a standardized definition requires both patient engagement and a mother-neonate dyadic approach mindful of program and policy implications.