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Background: The 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., Methods: Retrospective 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., Results: A 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)., Conclusion: The 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., (© 2024. The Author(s).)

Objectives: 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., Methods: 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., Results: 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., Conclusions: FI and HI were health-related needs associated with increased anxiety, depression, infant NICU admission, and loss of child custody., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Analyze maternal and infant characteristics by Neonatal Opioid Withdrawal Syndrome (NOWS) status and examine the association between mothers with Hepatitis C Virus (HCV) and infants diagnosed with NOWS., Methods: Hospital discharge diagnoses of low-income women in Tennessee were used to identify NOWS cases (n = 1,369) in 2013 and 2014 and randomly selected controls (n = 1,369) were matched on county of residence and birth year. Maternal and infant characteristics were obtained by linking these data to birth certificate data., Results: Of Tennessee's 683 cases of NOWS in 2013 and 686 in 2014, most (69%) occurred in Eastern Tennessee. Mothers of infants with NOWS were more likely to be older, unmarried, and white than mothers of infants without NOWS. Mothers of infants with NOWS also faced greater health risk: more smoking, HCV, herpes simplex diagnosis, and no or less frequent prenatal care (p < .0001). Infants with NOWS were more likely to present with infection, be admitted into the NICU, have lower birth weight, be enrolled in TennCare, but less likely to be breastfed than infants without NOWS (p < .0001). After adjusting for demographic factors and smoking, compared to mothers of infants without NOWS, mothers of infants with NOWS had an alarmingly increased odds of HCV [OR = 12.97 (95% CI 7.42, 22.66)]., Conclusions: This study emphasizes the complexity of challenges facing families impacted by NOWS, the importance of multifaceted prevention, and the need to conduct HCV testing in NOWS infants., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Importance: Although cases of neonatal opioid withdrawal syndrome (NOWS) increased 5-fold in recent years, no study has examined national hospital readmission rates for these infants., Objective: To examine hospital readmissions for infants with and without NOWS., Design, Setting, and Participants: This retrospective cohort study analyzed serial cross-sectional samples of US hospital discharge records from the Nationwide Readmissions Database for calendar years 2016 to 2020. Infants with NOWS were identified using International Classification of Diseases, Tenth Revision, Clinical Modification codes. The data analysis was performed between January 5, 2023, and May 6, 2024., Exposure: Neonatal opioid withdrawal syndrome., Main Outcome and Measures: Survey-weighted logistic regression was used to examine 90-day all-cause and cause-specific hospital readmissions. Multivariable models adjusted for sex, low birth weight, gestational age, multiple gestation, type of insurance, and year of birth., Results: Of the 13 855 246 newborns identified in this weighted analysis, 89 018 (0.6%) were diagnosed with NOWS, of whom 53.8% were male and 81.1% born full-term (>36 weeks gestation). The 90-day all-cause readmission rate was 4.2% for infants with NOWS compared with 3.0% for those without NOWS (P < .001). After risk adjustment, the odds of all-cause readmission were higher among infants with NOWS (adjusted odds ratio [AOR], 1.18; 95% CI, 1.08-1.29). Infants with NOWS had significantly higher odds of readmissions for seizures (AOR, 1.58; 95% CI, 1.01-2.46), failure to thrive (AOR, 1.99; 95% CI, 1.36-2.93), traumatic brain injury (AOR, 2.95; 95% CI, 1.76-4.93), and skull fractures (AOR 3.72; 95% CI, 2.33-5.93). Infants with NOWS had higher odds of receiving a diagnosis of confirmed maltreatment (AOR, 4.26; 95% CI, 2.19-8.27), including for neglect (AOR, 14.18; 95% CI, 5.55-36.22) and physical abuse (AOR, 2.42; 95% CI, 0.93-6.29); however, the latter finding was not statistically significant., Conclusions and Relevance: In this nationally representative cohort study, infants with NOWS were at increased risk of readmission for any cause as well as for trauma and confirmed maltreatment. These findings may in part reflect the dual stressors that mothers with opioid use disorder face in caring for a newborn with NOWS in the context of a substance use disorder and underscore the need for family-based, in-home services that focus concurrently on substance use treatment and parenting support.

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., (© 2024 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Objective: To estimate trends in maternal opioid use disorder (OUD) and neonatal abstinence syndrome (NAS) in Maine using the most recent data available., Study Design: We used hospital discharge data to estimate the annual prevalence of maternal OUD and NAS between 2016 and 2022. In addition, we used birth certificate-linked Medicaid data to estimate related trends among Medicaid enrollees., Result: From 2016 to 2022, the prevalence of maternal OUD decreased from 35.3 to 18.8 per 1000 deliveries and the prevalence of NAS decreased from 33.2 to 14.0 per 1000 newborns (linear trend p values <0.01). Decreasing trends were also found among Medicaid enrollees., Conclusion: In Maine between 2016 and 2022, there was a decrease in maternal OUD and NAS diagnoses recorded in administrative datasets. These findings should be interpreted with caution due to changes in how OUD and NAS diagnoses are recorded and COVID-related changes in healthcare utilization., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: In the U.S., the opioid epidemic has revitalized national attention to newborns with prenatal substance exposure (PSE). These newborns and their caregivers have specific health and treatment needs and frequently interact with multiple systems, including child protection systems (CPS)., Methods: This study calculated rates of newborns (less than 15 days old) reported to CPS per 1,000 births due to PSE by state and year using data from the National Child Abuse and Neglect Data System (NCANDS). Given the lack of a clear definition of PSE reports in the data, we calculated rates using three different definitions. To examine the relationship between different state laws regarding the mandated reporting of PSE and PSE reports rates, we used panel data analysis., Results: Rates of newborn reports more than doubled between 2011 and 2019. There was extensive state variability of rates including some states that were consistently more than 100 % greater than and others consistently more than 150 % less than the annual national mean. Reporting rates were not associated with state requirements to report PSE, but were positively associated with rates of diagnosed neonatal abstinence syndrome., Conclusion: State-level inconsistencies in identification, reporting, and CPS responses prevent a clear understanding of the scope of the affected population and service needs., Competing Interests: Declaration of competing interest We have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Prenatal opioid exposure is an established public health problem, in particular among Medicaid-covered births. Yet, existing prevalence rates are plausibly underestimated. We leverage extensive linked longitudinal administrative data for all Medicaid-covered live births in Wisconsin from 2010 to 2019 to estimate a range of prevalence rates using an innovative strategy that jointly accounts for both likelihood of exposure and potential risk to prenatal development. We find that 20.8% of infants may have been prenatally exposed to opioids, with 1.7% diagnosed with neonatal abstinence syndrome and an additional 1.2% having a high combined likelihood of exposure and potential risk to prenatal development, 2.6% a moderate combined likelihood and risk, and 15.3% a low or uncertain combined likelihood and risk. We assess improvements in prevalence estimates based on our nuanced classification relative to those of prior studies. Our strategy could be broadly used to quantify the scope of the opioid crisis for pregnant populations, target interventions, and promote child health and development.

Objective: This study aimed to evaluate the association between number of prenatal care visits and adverse perinatal outcome among pregnant individuals with opioid use disorder (OUD)., Study Design: This is a retrospective cohort of singleton, nonanomalous pregnancies complicated by OUD that delivered from January 2015 to July 2020 at our academic medical center. Primary outcome was the presence of composite adverse perinatal outcome, defined as one or more of the following: stillbirth, placental abruption, perinatal death, neonatal respiratory distress syndrome, need for morphine treatment, and hyperbilirubinemia. Logistic and linear regression estimated the association between the number of prenatal care visits and the presence of adverse perinatal outcome. A Mann-Whitney U test evaluated the association between number of prenatal care visits and length of hospital stay for the neonate., Results: A total of 185 patients were identified, of which 35 neonates required morphine treatment for neonatal opioid withdrawal syndrome. During pregnancy, most individuals were treated with buprenorphine 107 (57.8%), whereas 64 (34.6%) received methadone, 13 (7.0%) received no treatment, and 1 (0.5%) received naltrexone. The median number of prenatal care visits was 8 (interquartile range: 4-10). With each additional visit per 10 weeks of gestational age, the risk of adverse perinatal outcome decreased by 38% (95% confidence interval [CI]: 0.451-0.854). The need for neonatal intensive care and hyperbilirubinemia also significantly decreased with additional prenatal visits. Neonatal hospital stay decreased by a median of 2 days (95% CI: 1-4) for individuals who received more than the median of eight prenatal care visits., Conclusion: Pregnant individuals with OUD who attend fewer prenatal care visits experience more adverse perinatal outcome. Future research should focus on barriers to prenatal care and interventions to improve access in this high-risk population., Key Points: · Use of prenatal care affects newborn outcomes.. · More prenatal care shortens neonatal hospital stay.. · Prenatal care reduces certain adverse outcomes.., Competing Interests: T.L. received funding from Medicem for a nonrelated research study., (Thieme. All rights reserved.)

Objective: Studies exploring the relationship between neonatal abstinence syndrome (NAS) and congenital anomalies (CA) in the United States are limited given the small sample size or data prior to the opioid epidemic. We aimed to determine if there is an association between NAS and CA in a nationally representative cohort of newborn hospitalization in the United States., Study Design: This was a cross-sectional analysis of NAS-related hospitalizations within the 2016 Kids Inpatient Database. International Classification of Diseases (ICD-10-CM) diagnostic codes were used to identify NAS hospitalizations and those with and without CA. The primary outcome was the odds of CAs in NAS hospitalizations. Multivariate survey logistic regression was used to analyze the relationship between NAS and CA., Results: Among 3.7 million newborn hospitalizations, 25,394 had NAS (6.7 per 1,000). The prevalence of any CA was higher in those with NAS when compared with non-NAS hospitalizations (10.3 vs. 4.9%; odds ratio = 2.27; 95% confidence interval [CI]: 2.13-2.43). Adjusted analysis showed similar results (adjusted odds ratio: = 1.83, CI: 1.71-1.95). NAS hospitalizations with CA had a higher mortality rate (0.6 vs 0.04%, p  < 0.0001) and higher resource use., Conclusion: This nationwide study shows that NAS may be associated with increased odds of CAs, suggesting that NAS may be a risk factor for increased morbidity in the newborn period., Key Points: · 1 in 10 newborns with NAS had at least one congenital anomaly.. · NAS hospitalization with congenital anomalies had higher resource use and mortality.. · Pediatricians caring for newborns with NAS should have a high index of suspicion for birth defects.., Competing Interests: None declared., (Thieme. All rights reserved.)

Limited research has examined a comprehensive set of predictors when evaluating discharge placement decisions for infants exposed to substances prenatally. Using a previously validated medical record data extraction tool, the current study examined prenatal substance exposure, infant intervention (i.e., pharmacologic, or non-pharmacologic), and demographic factors (e.g., race and ethnicity and rurality) as predictors of associations with discharge placement in a sample from a resource-poor state ( N = 136; 69.9% Non-Hispanic White). Latent class analysis (LCA) was used to examine whether different classes emerged and how classes were differentially related to discharge placement decisions. Logistic regressions were used to determine whether each predictor was uniquely associated with placement decisions. Results of the LCA yielded a two-class solution comprised of (1) a Low Withdrawal Risk class, characterized by prenatal exposure to substances with low risk for neonatal abstinence syndrome (NAS) and non-pharmacologic intervention, and (2) a High Withdrawal Risk class, characterized by a high risk of NAS and pharmacologic intervention. Classes were not related to discharge placement decisions. Logistic regressions demonstrated that meth/amphetamine use during pregnancy was associated with greater odds of out of home placement above other substance types. Future research should replicate and continue examining the clinical utility of these classes., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Our objective was to evaluate the trend and to assess the impact of maternal region of residence in Western New York (WNY), on severe neonatal opioid withdrawal syndrome (NOWS)., Study Design: Term infants' born at gestational age greater than or equal to 37 weeks with severe NOWS, defined as withdrawal resulting in the receipt of pharmacologic therapy from WNY admitted to our neonatal intensive care unit (NICU) from January 1, 2008 to December 31, 2016, were included. Severe NOWS admissions to our NICU from the following five regions were controlled with birth and insurance data: (1) Urban North, (2) Erie Coastal, (3) Niagara Frontier, (4) Southern Tier, and (5) Urban South., Results: "Urban South" residence was associated with an increased risk of severe NOWS (adjusted odds ratio = 1.8, 97.5% confidence interval: 1.1-2.9). The trend in admission for severe NOWS doubled between 2008 to 2010 and 2014 to 2016 ( p  = 0.01). More infants born to maternal nonprescribed opioid users were placed in foster care at discharge (36.5 vs. 1.9%, p  < 0.001)., Conclusion: In WNY, neonates born to mothers from the "Urban South" were twice at risk of being admitted for severe NOWS. One-third of infants with severe NOWS after nonprescribed opioid use were placed in foster care. Implementing targeted strategies at the community level may help improve outcomes in NOWS., Key Points: · Maternal region of residence is a risk factor for severe neonatal opioid withdrawal.. · Admissions for severe neonatal opioid withdrawal trended up from 2008 to 2010 to 2014 to 2016.. · One-third of the infants born to mothers on nonprescribed opioids were discharged to foster care.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: The U.S. opioid epidemic has been characterized by increases in opioid misuse, overdose deaths, and neonatal opioid withdrawal syndrome. Research suggests that marijuana legalization has contributed to decreased use of opiates, although many studies had methodological weaknesses and failed to address the pregnant population. Implementation of medical cannabis laws has the potential to reduce maternal opioid use and, therefore, neonatal exposure to the drugs. This study aimed to examine the association between Oklahoma's implementation of state medical marijuana laws and the neonatal exposure to opioids., Study Design: Electronic medical records at two sites (Oklahoma City and Lawton) were searched for results of cord, urine, and meconium screens to detect amphetamines, barbiturates, benzodiazepines, cocaine, ethanol, opiates, phencyclidine, and tetrahydrocannabinol (THC). Two study periods were compared: 19 months before Oklahoma's medical marijuana law took effect and 19 months after legalization began., Results: A total of 16,804 babies were born alive at the two sites during the study period. The rate of positive THC tests per 1,000 liveborn infants significantly increased from 16.2 per 1,000 during the prelaw period to 22.2 per 1,000 during the postlaw period ( p  = 0.004). Neonatal opioid exposure incidence showed a nonsignificant decrease from 7.6 positive tests per 1,000 liveborn infants to 6.8 per 1,000 from prelaw to postlaw period ( p  = 0.542). The number of positive tests for THC and concomitant use of opioids doubled from the prelaw period ( n  = 4) to postlaw ( n  = 9), but there were too few cases for statistical significance. Infants at the more rural site had significantly higher rates for amphetamines, benzodiazepines, and THC, with a trend toward higher rates for opiates., Conclusion: Marijuana legalization was related to significant increases in positive test rates for THC, but no significant change/association was noted for neonatal exposure to opioids., Key Points: · Prior studies have not examined neonatal exposure to opioids following marijuana legalization.. · Oklahoma's new law led to higher neonatal marijuana exposure.. · Legalization of medical marijuana did not change Oklahoma's neonatal opioid positivity rate.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: Sickle cell disease is associated with adverse perinatal outcomes. Aspects of sickle cell disease in pregnancy, such as health care utilization and neonatal abstinence syndrome, are understudied. We aimed to describe contemporary sickle cell disease outcomes in a U.S. hospital system to improve perinatal counseling., Study Design: We conducted a retrospective cohort study of patients with sickle cell disease who delivered at >20 weeks' gestation at two sites within the University of Pennsylvania Health System from May 1, 2017 to August 30, 2020. Descriptive statistics were utilized., Results: Over the study period, 48 patients with sickle cell disease had 52 deliveries of 53 neonates. Sickle cell disease-related morbidity was prevalent prior to pregnancy; 27% had a history of avascular necrosis, and 58% had experienced acute chest syndrome. In the year prior to pregnancy, 52% used daily opioids. During pregnancy, more than half of patients were admitted at least once for sickle cell disease-related complications, spending a median 3 days admitted interquartile range (0-23); >10% spent >70 days of pregnancy admitted. New daily opioids were prescribed during pregnancy for 10% to manage pain crises. Acute chest syndrome was experienced by 23% of patients during pregnancy, and 8% required placement of long-term intravenous access. Preterm delivery <37 weeks occurred in 48%. The primary cesarean rate in nulliparas was 43%. Additionally, 50% experienced a hypertensive disorder of pregnancy, 35% underwent transfusion during delivery admission, and 10% had a perinatal venous thromboembolism. Finally, 53% of neonates were admitted to the intensive care unit. Low birth weight was noted in 34%, severe respiratory distress in 15% of infants, and neonatal abstinence syndrome in 21%., Conclusion: Sickle cell disease remains associated with significant perinatal morbidity and need for hospitalization. These data provide contemporary outcomes to target improvements in the care of patients with sickle cell disease., Key Points: · SCD was associated with significant perinatal morbidity and healthcare utilization.. · Most patients with SCD required hospitalization during pregnancy.. · Neonates of patients with SCD experienced preterm birth, NICU admission, and neonatal abstinence syndrome.., Competing Interests: F.S. received research funding from Agios Pharmaceuticals, Cambridge, MA, Aruvant Sciences, New York, NY, and Novartis, Basel, Switzerland., (Thieme. All rights reserved.)

Objective: Neonatal abstinence syndrome (NAS) is a set of drug withdrawal symptoms suffered by neonates exposed to drugs in utero. Several studies have widely described NAS incidence and treatment approach; however, little is known regarding the incidence and manifestations of this disease in Puerto Rico (PR). The principal aim of this study was to describe NAS incidence in the neonatal units of hospitals affiliated with the University of PR in terms of occurrence, clinical manifestations, and treatment approaches., Methods: Our study evaluated the medical records of NAS babies diagnosed from 2018 through 2020 at 2 hospitals affiliated with the University of PR Medical Sciences Campus. Descriptive and inferential statistics were employed to analyze trends., Results: We identified 12 neonates diagnosed with NAS, 5 with low birthweights (<2500 g); for a NAS incidence of 2 cases per 1000 admitted for the 3 years of recollected data. The urine toxicology results revealed that 9 had experienced intrauterine polydrug exposure. Phenobarbital loading dose were determined on the day of diagnosis (indicated by Finnegan score). The first manifestation of NAS symptoms varied: 8 neonates showed symptoms within 48 hours after birth, whereas 4 had withdrawal symptoms within 72-120 hours of their births. Differences between dosing practices and guidelines were observed, ranging from a 0.69% to a 25% difference during treatment initiation., Conclusion: Further research on the incidence of NAS in PR (national level) is needed for a deeper understanding that we hope will lead to the development of enhanced treatment protocols in PR.

Background: States have developed action plans to address the "opioid crisis" over the past several years. While sex- and gender-based differences have been identified in complications of opioid use, risks of addiction to opioids, barriers to treatment of opioid use disorder, and associated stigma, it is unknown if or to what extent opioid plans consider or account for these differences. The objectives of this study were to analyze U.S. state opioid action plans and their inclusion of sex- and gender-specific concerns. Methods: A content analysis of 49 state plans was conducted in June 2020, assessing their inclusion of 14 variables covering provider education, pregnancy-related, and sex- or gender-based differences in opioid addiction and treatment. Results: Neonatal opioid withdrawal syndrome was the most common variable, noted in 57% of plans. Only 14% included pregnancy-related stigma, and 4% identified gender-specific stigma. Contraceptives and family-planning were included in 12% and 10% of plans, respectively. Two states included more than half of the variables and five plans made no mention of sex or gender differences. Conclusions: Few state plans contained sex- or gender-specific information, and those that did focused almost exclusively on childbearing, excluding other unique considerations of opioid-using-women of all ages. The results of this study could improve the care of women using opioids by informing the strategies of state agencies and impacting legislative efforts for prevention initiatives, substance use disorder treatment, and law enforcement programs.

Objective: Infants with prenatal substance exposure or neonatal abstinence syndrome (NAS) use health services more often than other children; however, little is known about their use of mental health services and psychotropic medication., Methods: The sample (N=1,004,085) consisted of infants born in 2016 in 38 states who were followed through the fifth year of life and enrolled each year in Medicaid or the Children's Health Insurance Program. Infants with prenatal substance exposure or NAS were identified with ICD-10 diagnosis codes; procedure and revenue codes documented their service use., Results: Rates of any mental health visit and of psychotropic medication use were higher among infants with prenatal substance exposure or NAS compared with infants without either condition; these patterns persisted during most years of the 5-year study., Conclusions: Infants' elevated mental health services use through their first 5 years of life highlights the importance of early screening and subsequent engagement in school-based mental health interventions., Competing Interests: The authors report no financial relationships with commercial interests.

Importance: Neonatal abstinence syndrome (NAS) is a medical condition among neonates experiencing substance withdrawal due to the mother's substance use during pregnancy. While previous studies suggest that the overall incidence and annual costs of NAS are increasing, to date, the long-term costs have yet to be demonstrated in Medicaid populations., Objective: To examine the demographic differences and long-term costs of care for neonates diagnosed with vs not diagnosed with NAS., Design, Setting, and Participants: This cohort study used claims data from the Alabama Medicaid Agency for neonates born to Medicaid-eligible mothers between January 1, 2010, and December 31, 2020. Data were analyzed in June 2022., Exposure: A diagnosis of NAS within 30 days of birth., Main Outcomes and Measures: Rate of NAS by demographic and birth characteristics, long-term costs attributable to NAS status and demographic and birth characteristics, and distribution of this expenditure over the enrollment period., Results: A total of 346 259 neonates with Medicaid eligibility were born during the study period (mean [SD] gestational age, 38.4 [2.2] weeks; 50.5%, male), 4027 (1.2%) of whom had an NAS diagnosis within 30 days of birth. A larger percentage of neonates with an NAS diagnosis were male (52.7%) than in the group without NAS (50.5%). Neonates with NAS also weighed less at birth (mean difference, -212.0 g; 95% CI, -231.1 to -192.8 g) and had older mothers (mean difference, 3.4 years; 95% CI, 2.6-4.2 years). An NAS diagnosis had an estimated additional cost of $17 921 (95% CI, $14 830-$21 012) over the enrollment period, and this cost was not evenly distributed over that period., Conclusions and Relevance: In this cohort study of neonates born into the Alabama Medicaid population, those with an NAS diagnosis had a different demographic profile and a higher cost to state Medicaid agencies than those without NAS. These findings warrant further effort to reduce the occurrence of NAS.

Importance: Prenatal opioid exposure (POE) may alter with fetal development of the immune system, which may influence long-term health and susceptibility to immune-related conditions., Objective: To compare the risk of hospitalization and emergency department presentation for immune-related conditions in children with and without POE., Design, Setting, and Participants: This retrospective, population-based cohort study used linked administrative health records of all children born in Western Australia between January 1, 2003, and December 31, 2018 (N = 401 462)., Exposure: Prenatal exposure to prescription opioids (overall and by trimester), neonatal abstinence syndrome diagnosis, and opioid indication (pain or opioid use disorder [OUD])., Main Outcomes and Measures: The main outcome was hospital admissions and emergency department presentations during which a child was diagnosed with an immune-related condition, including infections, conditions associated with an overactive immune system (eg, asthma, eczema, and allergy and anaphylaxis), and autoimmune diseases diagnosed before age 5 years or June 30, 2020. Data were analyzed between August 30, 2022, and February 27, 2023., Results: Neonates with POE (1656 [0.4%]; mean [SD] gestational age, 37.7 [2.1] weeks; 836 females [50.5%]; 820 males [49.5%]) were more likely to be born preterm, have low birth weight for gestational age, and be coexposed to cigarette smoke compared with nonexposed neonates. Perinatal opioid exposure was associated with an increased risk of perinatal infection (adjusted odds ratio [AOR], 1.62; 95% CI, 1.38-1.90) and eczema and dermatitis (AOR, 11.91; 95% CI, 9.84-14.41) compared with nonexposure. Neonatal abstinence syndrome was also associated with both conditions (AOR, 2.91 [95% CI, 2.36-3.57] and 31.11 [95% CI, 24.64-39.28], respectively). Prenatal opioid exposure was also associated with an increased risk of childhood asthma (adjusted hazard ratio [AHR], 1.44; 95% CI, 1.16-1.79), but not allergies and anaphylaxis. It was also associated with an increased risk of childhood eczema and dermatitis, but only in children with POE from opioids used to treat OUD (AHR, 1.47; 95% CI, 1.08-1.99) rather than pain. In contrast, POE from opioids used for pain was associated with an increased risk of infection (AHR, 1.44; 95% CI, 1.32-1.58), but POE to opioids used to treat OUD was not. Autoimmune conditions were rare and were not observed to be associated with POE., Conclusions and Relevance: In this cohort study, POE was associated with an increased risk of infection, eczema and dermatitis, and asthma, but not allergies and anaphylaxis or autoimmune conditions. These findings highlight the importance of further study of opioid-induced immune changes during pregnancy, the potential impact on long-term health in exposed children, and the mechanisms of opioid-induced immune dysregulation.

Objective: The opioid epidemic has led to a surge in diagnoses of neonatal opioid withdrawal syndrome (NOWS). Many states track the incidence of NOWS by using the P96.1 International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) code for "neonatal withdrawal symptoms from maternal use of drugs of addiction." In October 2018, an ICD-10-CM code for neonatal opioid exposure (P04.14) was introduced. This code can be used when an infant is exposed to opioids in utero but does not have clinically significant withdrawal symptoms. We analyzed the effect of the P04.14 code on the incidence rate of NOWS (P96.1) and "other" neonatal drug exposure diagnoses (P04.49)., Methods: We used private health insurance data collected for infants in the United States from the first quarter of 2016 through the third quarter of 2021 to describe incidence rates for each code over time and examine absolute and percentage changes before and after the introduction of code P04.14., Results: The exclusive use of code P96.1 declined from an incidence rate per 1000 births of 1.08 in 2016-2018 to 0.70 in 2019-2021, a -35.7% (95% CI, -47.6% to -23.8%) reduction. Use of code P04.49 only declined from an incidence rate of 2.34 in 2016-2018 to 1.64 in 2019-2021, a -30.0% (95% CI, -36.4% to -23.7%) reduction. Use of multiple codes during the course of treatment increased from an average incidence per 1000 births of 0.56 in 2016-2018 to 0.79 in 2019-2021, a 45.5% (95% CI, 24.8%-66.1%) increase., Conclusion: The introduction of ICD-10-CM code P04.14 altered the use of other neonatal opioid exposure codes. The use of multiple codes increased, indicating that some ambiguity may exist about which ICD-10-CM code is most appropriate for a given set of symptoms., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Improving neonatal abstinence syndrome (NAS) management is an important concern, and objective measures of its physiologic impact remain elusive. We sought to determine whether near-infrared spectroscopy (NIRS)-derived tissue oxygenation (rSO2) and fractional tissue oxygen extraction (FTOE) demonstrated physiologically plausible changes correlating with standard NAS scoring., Methods: Thirty subjects (mean 39 weeks' GA and 3 127 g BW) underwent cerebral and peripheral muscle NIRS monitoring on Days of Life (DOL) Three, Five, and Seven. We examined correlations between NAS scores and FTOE and assessed the impact of non-pharmacologic swaddling and cuddling., Results: No statistically significant correlations between NAS scores and FTOE were observed; however, plausible trends were demonstrated between NAS scores and cerebral measurements. Buprenorphine-exposed babies (57%) showed significantly lower FTOE when swaddled (DOL7)., Conclusions: Tissue oxygenation monitoring demonstrates potential to provide objective, clinically relevant physiologic information on infants at risk for NAS. Further study is required to determine whether NIRS-derived measures could assist in individualizing NAS care.

Background/objectives: To examine prevalence of failed visual assessment at 8-10 years in children born to methadone-maintained opioid dependent (MMOD) mothers and relate this to known in utero substance exposure., Subjects/methods: Follow up of observational cohort study of methadone-exposed and comparison children matched for birthweight, gestation and postcode of residence at birth. Participants were 144 children (98 exposed, 46 comparison). Prenatal drug exposure was previously established via comprehensive maternal and neonatal toxicology. Children were invited to attend for visual assessment and casenotes were reviewed. Presence of acuity poorer than 0.2 logMAR, strabismus, nystagmus and/or impaired stereovision constituted a 'fail'. Fail rates were compared between methadone-exposed and comparison children after adjusting for known confounding variables., Results: 33 children attended in person: data were also derived from casenote review for all children. After controlling for maternal reported tobacco use, methadone-exposed children were more likely to have a visual 'fail' outcome, adjusted odds ratio 2.6, 95% CI 1.1-6.2; adjusted relative risk 1.8 (95% CI 1.1-3.4). Visual 'fail' outcome rates did not differ between methadone-exposed children who had (n = 47) or had not (n = 51) received pharmacological treatment for neonatal abstinence/opioid withdrawal syndrome (NAS/NOWS); fail rate 62% vs 53% (95% CI of difference-11-27%)., Conclusions: Children born to MMOD mothers are almost twice as likely as unexposed peers to have significant visual abnormalities at primary school age. Prenatal methadone exposure should be considered in the differential diagnosis of nystagmus. Findings support visual assessment prior to school entry for children with any history of prenatal opioid exposure., Trial Registration: The study was prospectively registered on ClinicalTrials.gov (NCT03603301), https://clinicaltrials.gov/ct2/show/NCT03603301 ., (© 2023. The Author(s).)

Introduction: Wisconsin experienced overlapping and accelerating epidemics of opioid use and COVID-19 after March 2020. We hypothesized that Wisconsin neonatal abstinence syndrome rates increased after March 2020 alongside other markers of opioid burden., Methods: Retrospective cohort analysis examined deidentified Wisconsin census, birth certificate, death certificate, hospital discharge, Prescription Drug Monitoring Program, emergency medical service run, and COVID-19 diagnosis records spanning January 1, 2019, through December 31, 2021. January 2019 through March 2020 was considered before the onset of COVID-19 (pre); April 2020 through December 2021 was considered post-onset of COVID-19 (post). Wisconsin Department of Health Services guidelines defined 5 Wisconsin regions. Rates pre- to post-onset were compared with P values < 0.05 considered statistically significant., Results: Of 1362 patients, 83.3% completed a COVID-19 vaccination series. Younger patients had increased odds of not completing a COVID-19 vaccination series (mean [SD] 46.7 [14.7] vs 54.3 [15.8]; OR 1.03; 95% CI, 1.02-1.04; P  < 0.001). Those who identified as non-White (1.88; 95% CI, 1.16-3.04; P = 0.010) or current smoker (1.85, 95% CI, 1.85-2.79; P = 0.004) had increased odds of not completing a COVID-19 vaccination series. Those who resided in rural ZIP codes (1.81; 95% CI, 1.35-2.43; P  < 0.001), had not received a 2019-2020 influenza vaccine (5.13; 95% CI, 3.79-6.96; P  < 0.001), or had lower comorbidity scores (2.95; 95% CI, 1.98-4.41; P  < 0.001) had higher odds of not completing a COVID-19 vaccination series., Conclusions: Opioid-associated morbidity and mortality increased in Wisconsin during the study period, including among females age 15 to 44 years. Despite increased opioid burden, neonatal abstinence syndrome incidence decreased in the Southeastern Region. Ongoing neonatal abstinence syndrome and opioid analysis may benefit from region-based contextualization., (Copyright© Board of Regents of the University of Wisconsin System and The Medical College of Wisconsin, Inc.)

Objectives: Southern Appalachia is a region of the United States that is disproportionately affected by the opioid epidemic and by increasing rates of neonatal abstinence syndrome (NAS). NAS rates increased approximately 400% between 1999 and 2012. Buprenorphine prescriptions written to treat opioid use disorder also increased dramatically. The present study was undertaken to ascertain any relationship between the number of buprenorphine prescriptions compared with NAS rates in southern Appalachia., Methods: A total of 250 southern Appalachian counties across seven states, including all of West Virginia and portions of Virginia, Kentucky, Maryland, North Carolina, Ohio, and Tennessee were identified. A retrospective cohort analysis of these counties was conducted for the years 2005-2018. All of the data were obtained from publicly accessible sources or direct communication with government offices. Measures from each county in southern Appalachia included annual NAS rates, buprenorphine prescription rates, drug-induced death rates, and opioid prescribing rates. Associations among these variables were examined using a generalized linear regression., Results: Significant linear associations exist between the rising rate of NAS diagnoses and the rising rate of buprenorphine prescriptions ( r = 0.977, R 2 = 95.53%, P < 0.001) and between the rising rate of buprenorphine prescriptions and the increase in drug-induced deaths ( r = 0.712, R 2 = 50.82%, P = 0.031)., Conclusions: This is the first report that documents an association between rising NAS rates and increasing buprenorphine prescribing. Between the years 2010 and 2018, the NAS rate in southern Appalachia rose by 335%, and the number of buprenorphine prescriptions rose by 413%. Discussions regarding the current policies for buprenorphine management during pregnancy are warranted. We suggest a reevaluation of buprenorphine prescribing recommendations during pregnancy and further research on establishing the lowest effective buprenorphine dose for each pregnant patient.

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., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objective: Rates of neonatal abstinence syndrome/neonatal opioid withdrawal syndrome (NAS/NOWS), a withdrawal syndrome from opioids and other substances resulting from intrauterine exposure, have been increasing exponentially in the U.S. To improve health outcomes, it is important to understand population health risks, including rehospitalization and related diagnoses, using current data. This study will compare and describe the rates of rehospitalization, the demographic characteristics and the rehospitalization diagnoses and age at diagnosis between the infants affected by NAS/NOWS to those sampled who were unaffected. This study will also describe the frequency of NAS/NOWS births per year along with a yearly comparison of readmissions in those affected by NAS/NOWS to those who were not (2016-2020)., Methods: Health claims data were used to conduct a case/control study. Diagnosis codes for neonatal withdrawal syndrome/NAS/NOWS (P04.49 or P96.1 and P96.1 alone) from 1 October 2015 to 1 June 2021 were extracted, and controls were case-matched based on month/year of birth. Rehospitalizations following birth and the related diagnoses were described and grouped using the Agency of Healthcare Research Quality Clinical Classifications Software Refined Frequency distribution. The chi-square test of association and generalized estimating equation modeling were used for data analysis., Results: Infants affected by NAS/NOWS are 2.7 times more likely to have a rehospitalization. White, non-Hispanic neonates (OR = 1.5; p  = .007) and those infants residing in rural areas (OR = 1.9; p  < .001) were disproportionately affected. We identified a host of admission diagnoses with increased prevalence in infants affected by NAS/NOWS when compared to those who were not affected (e.g. infectious diseases, feeding disorders)., Conclusions: Infants with NAS/NOWS are at increased risk of rehospitalization with a host of diagnoses, and specific demographic groups (White, rural) are more highly affected.

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., (© 2023. The Author(s).)

Prenatal opioid exposure is a major health concern in the United States, with the incidence of neonatal opioid withdrawal syndrome (NOWS) escalating in recent years. NOWS occurs upon cessation of in utero opioid exposure and is characterized by increased irritability, disrupted sleep patterns, high-pitched crying, and dysregulated feeding. The main pharmacological strategy for alleviating symptoms is treatment with replacement opioids. The neural mechanisms mediating NOWS and the long-term neurobehavioral effects are poorly understood. We used a third trimester-approximate model in which neonatal outbred pups (Carworth Farms White; CFW) were administered once-daily morphine (15 mg/kg, s.c.) from postnatal day (P) day 1 through P14 and were then assessed for behavioral and transcriptomic adaptations within the nucleus accumbens (NAc) on P15. We also investigated the long-term effects of perinatal morphine exposure on adult learning and reward sensitivity. We observed significant weight deficits, spontaneous thermal hyperalgesia, and altered ultrasonic vocalization (USV) profiles following repeated morphine and during spontaneous withdrawal. Transcriptome analysis of NAc from opioid-withdrawn P15 neonates via bulk mRNA sequencing identified an enrichment profile consistent with downregulation of myelin-associated transcripts. Despite the neonatal behavioral and molecular effects, there were no significant long-term effects of perinatal morphine exposure on adult spatial memory function in the Barnes Maze, emotional learning in fear conditioning, or in baseline or methamphetamine-potentiated reward sensitivity as measured via intracranial self-stimulation. Thus, the once daily third trimester-approximate exposure regimen, while inducing NOWS model traits and significant transcriptomic effects in neonates, had no significant long-term effects on adult behaviors., Competing Interests: Declaration of competing interest This work was supported by U01DA050243. We have no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Competing Interests: None declared

Objective: To evaluate the association between prenatal prescription opioid analgesic exposure (duration, timing) and neonatal opioid withdrawal syndrome (NOWS)., Methods: We conducted a retrospective cohort study of Wisconsin Medicaid-covered singleton live births from 2011 to 2019. The primary outcome was a NOWS diagnosis in the first 30 days of life. Opioid exposure was identified with any claim for prescription opioid analgesic fills during pregnancy. We measured exposure duration cumulatively in days (1-6, 7-29, 30-89, and 90 or more) and identified timing as early (first two trimesters only) or late (third trimester, regardless of earlier pregnancy use). We used logistic regression modeling to assess NOWS incidence by exposure duration and timing, with and without propensity score matching., Results: Overall, 31,456 (14.3%) of 220,570 neonates were exposed to prescription opioid analgesics prenatally. Among exposed neonates, 19,880 (63.2%) had 1-6 days of exposure, 7,694 (24.5%) had 7-29 days, 2,188 (7.0%) had 30-89 days, and 1,694 (5.4%) had 90 or more days of exposure; 15,032 (47.8%) had late exposure. Absolute NOWS incidence among neonates with 1-6 days of exposure was 7.29 per 1,000 neonates (95% CI 6.11-8.48), and incidence increased with longer exposure: 7-29 days (19.63, 95% CI 16.53-22.73); 30-89 days (58.96, 95% CI 49.08-68.84); and 90 or more days (177.10, 95% CI 158.90-195.29). Absolute NOWS incidence for early and late exposures were 11.26 per 1,000 neonates (95% CI 9.65-12.88) and 35.92 per 1,000 neonates (95% CI 32.95-38.90), respectively. When adjusting for confounders including timing of exposure, neonates exposed for 1-6 days had no increased odds of NOWS compared with unexposed neonates, whereas those exposed for 30 or more days had increased odds of NOWS (30-89 days: adjusted odds ratio [aOR] 2.15, 95% CI 1.22-3.79; 90 or more days: 2.80, 95% CI 1.36-5.76). Late exposure was associated with elevated odds of NOWS (aOR 1.57, 95% CI 1.25-1.96) when compared with unexposed after adjustment for exposure duration., Conclusion: More than 30 days of prenatal prescription opioid exposure was associated with NOWS regardless of exposure timing. Third-trimester opioid exposure, irrespective of exposure duration, was associated with NOWS., Competing Interests: Financial Disclosure Russell S. Kirby disclosed money was paid to his institution from the Florida Department of Health (partly pass through from the CDC); NIH-NIEHS, and the Department of Defense - project with Baylor College of Medicine. He serves on three foundation boards (ACEREF, 37th Street, and Perinatal Foundation) as well as on the boards of Tampa area market board for March of Dimes and the Wisconsin Association for Perinatal Care. The other authors did not report any potential conflicts of interest., (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Rural communities in the United States face unique challenges related to the opioid epidemic. This paper explores the substances and substance-related health problems that pose the greatest concern to rural communities that received funding to address the opioid epidemic and examines their reported capacity to address these challenges., Methods: This paper analyzed data collected as part of quarterly progress reporting from multisector consortiums across 2 cohorts of grantees funded to reduce the morbidity and mortality of opioids. Consortium project directors ranked the top 3 issues in their community in each of the following categories: (1) drugs of concern; (2) drugs with the least capacity to address; (3) related problem areas of concern (eg, neonatal abstinence syndrome [NAS]); and (4) related problem areas with the least capacity to address., Findings: Methamphetamines, fentanyl, and alcohol were the substances rated as most problematic in rural communities funded to address the opioid epidemic across all reporting periods. Over 40% of respondents ranked methamphetamine as a top concern and the substance they had the least capacity to address. This was nearly double the percentage of the next highest-ranked substance (fentanyl). Overdoses, NAS, and viral hepatitis constituted the top-ranking related concerns, with limited capacity to address them., Conclusions: Multiple drug and concomitant problems coalesced on rural communities during the opioid epidemic. Funding communities to address substance use disorders and related problems of concern, rather than targeting funding toward a specific type of drug, may result in better health outcomes throughout the entire community., (© 2023 JBS International, INC. The Journal of Rural Health published by Wiley Periodicals LLC on behalf of National Rural Health Association. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background: Evidence on neonatal withdrawal syndrome following antidepressant intrauterine exposure is limited, particularly for antidepressants other than selective serotonin reuptake inhibitor (SSRIs)., Methods: In our case/non-case pharmacovigilance study, based on VigiBase ® , the WHO database of suspected adverse drug reactions, we estimated reporting odds ratio (ROR) and the Bayesian information component (IC) with 95% confidence/credibility intervals (CI) as measures of disproportionate reporting of antidepressant-related neonatal withdrawal syndrome. Antidepressants were first compared to all other medications, then to methadone, and finally within each class of antidepressants: SSRIs, tricyclics (TCA) and other antidepressants. Antidepressants were ranked in terms of clinical priority, based on semiquantitative score ratings. Serious v. non-serious reports were compared., Results: A total of 406 reports of neonatal withdrawal syndrome in 379 neonates related to 15 antidepressants were included. Disproportionate reporting was detected for antidepressants as a group as compared to all other drugs (ROR: 6.18, 95% CI 5.45-7.01, IC: 2.07, 95% CI 1.92-2.21). Signals were found for TCAs (10.55, 95% CI 8.02-13.88), followed by other antidepressants (ROR: 5.90, 95% CI 4.74-7.36) and SSRIs (ROR: 4.68, 95% CI 4.04-5.42). Significant disproportionality emerged for all individual antidepressants except for bupropion, whereas no disproportionality for any antidepressant was detected v. methadone. Eleven antidepressants had a moderate clinical priority score and four had a weak one. Most frequent symptoms included respiratory symptoms ( n = 106), irritability/agitation ( n = 75), tremor ( n = 52) and feeding problems ( n = 40)., Conclusions: Most antidepressants are associated with moderate signals of disproportionate reporting for neonatal withdrawal syndrome, which should be considered when prescribing an antidepressant during pregnancy, irrespective of class.

Background: Infants born to mothers with opioid use disorder (OUD) and prenatally treated with buprenorphine have a significantly lower incidence of neonatal opioid withdrawal syndrome (NOWS), its treatment duration, and hospital length of stay compared with methadone. However, risk of NOWS remains and clinicians continue to lack an objective methodology to predict NOWS severity among these infants., Objective: The purpose of this study was to assess the relationship between buprenorphine exposure, umbilical cord tissue (UCT) concentrations, and NOWS development and severity., Methods: A single-center retrospective observational cohort study from March 2018 through June 2020 of newborns exposed to buprenorphine in utero. Associations between quantified buprenorphine exposure, neonatal UCT concentrations, NOWS diagnosis, and severity were made using regression analyses., Results: A total of 24 mothers and 25 neonates were included. Length of maternal buprenorphine therapy (months) positively correlated to norbuprenorphine ( r 2 = 0.234, P = 0.019) and buprenorphine + norbuprenorphine UCT concentrations ( r 2 = 0.203, P = 0.031). A positive relationship was seen between active metabolite concentrations and cumulative morphine dose (mg/kg) for treatment of severe NOWS ( r 2 = 0.471, P = 0.007). A 0.36 ng/g buprenorphine + norbuprenorphine UCT (CI = 0.002-0.72, P = 0.049) equated in a 1-point increase in modified peak Finnegan score., Conclusion and Relevance: Buprenorphine and norbuprenorphine UCT concentrations can allow for quantification of in utero fetal exposure and demonstrate an association with a longer duration of exposure with the severity and treatment of NOWS in exposed infants.

Objectives: The US opioid epidemic contributes to a growing population of children experiencing neonatal abstinence syndrome (NAS) and adverse childhood experiences (ACEs). A review of the developmental impacts of the opioid crisis highlights that both prenatal exposure to teratogens and ACEs can result in developmental delay and disabilities. Training for the early intervention/early childhood (EI) systems is needed to enable them to meet the needs of this growing population., Methods: To address this, an IRB-approved online training on best practices for NAS, developmental monitoring and referral, and trauma-informed care was created for Ohio EI providers who provided informed consent to participate. The feasibility of utilizing an online training was assessed. Knowledge on opioid addiction, NAS, ACEs, and early intervention provider characteristics were collected for 2973 participants., Results: Within 6 months, the training reached providers in all Ohio counties and seventeen other states. 57% of providers reported caring for one or more children with a caregiver who has confirmed opioid use. 31% reported these children had experienced four or more ACEs. Providers' ACEs awareness was moderately associated with their experiences with prenatally-exposed youth. There was a significant increase in knowledge following training. Differences in post-training knowledge differed only by county-level opioid death rates, where those providers with low-medium opioid death rates reported more awareness of children with prenatal opioid exposure compared to participants who lived in a county with medium and medium-high opioid death rates., Conclusions: Online-training is feasible for closing gaps in the early intervention system., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Importance: The risk of serious long-term outcomes for infants born to individuals with opioid use disorder (OUD) is not fully characterized, nor is it well understood whether risks are modified by infant diagnosis of neonatal opioid withdrawal syndrome (NOWS)., Objective: To characterize the risk of postneonatal infant mortality among infants with a NOWS diagnosis or born to individuals with OUD., Design, Setting, and Participants: The study team conducted a retrospective cohort study of 390 075 infants born from 2007 through 2018 to mothers who were enrolled in Tennessee Medicaid from 183 days prior to delivery through 28 days post partum (baseline). Maternal and infant baseline characteristics were measured using administrative claims and birth certificates, and infants were followed up from day 29 post partum through day 365 or death. Deaths were identified using linked death certificates through 2019. These data were analyzed from February 10, 2022, through March 3, 2023., Exposure: Infant exposures included birth to an individual with OUD or postnatal diagnosis of NOWS. The study team defined a pregnant individual's OUD status (maternal OUD) as having OUD diagnosis or a maintenance medication prescription fill during baseline; this study defined NOWS as having NOWS diagnosis up to day 28. Groups were categorized by exposures as maternal OUD with NOWS (OUD positive/NOWS positive), maternal OUD without NOWS (OUD positive/NOWS negative), no documented maternal OUD with NOWS (OUD negative/NOWS positive), and no documented maternal OUD or NOWS (OUD negative/NOWS negative, unexposed)., Main Outcome and Measures: The outcome was postneonatal infant death, confirmed by death certificates. Cox proportional hazards models were used, adjusting for baseline maternal and infant characteristics, to estimate adjusted hazard ratios (aHRs) and 95% CIs for the association between maternal OUD or NOWS diagnosis with postneonatal death., Results: Pregnant individuals in the cohort had a mean (SD) age of 24.5 (5.2) years; 51% of infants were male. The study team observed 1317 postneonatal infant deaths and incidence rates of 3.47 (OUD negative/NOWS negative, 375 718), 8.41 (OUD positive/NOWS positive, 4922); 8.95 (OUD positive/NOWS negative, 7196), and 9.25 (OUD negative/NOWS positive, 2239) per 1000 person-years. After adjustment, the risk of postneonatal death was elevated for all groups, relative to the unexposed: OUD positive/NOWS positive (aHR, 1.54; 95% CI, 1.07-2.21), OUD positive/NOWS negative (aHR, 1.62; 95% CI, 1.21-2.17), and OUD negative/NOWS positive (aHR, 1.64; 95% CI, 1.02-2.65)., Conclusions and Relevance: Infants born to individuals with OUD or with a NOWS diagnosis had an increased risk of postneonatal infant mortality. Future work is necessary to create and evaluate supportive interventions for individuals with OUD during and after pregnancy to reduce adverse outcomes.

Background: The rate of infants born with neonatal abstinence syndrome (NAS) increased by more than 500% between 2004 and 2016. Although feeding problems among infants diagnosed with NAS have been documented, the risk of feeding problems among infants diagnosed with NAS has not been estimated., Purpose: This study evaluates the extent to which feeding problems among infants diagnosed with NAS differ from thise in infants without an NAS diagnosis., Methods/search Strategy: A matched retrospective cohort study (2008-2017) of infants diagnosed with NAS in the United States was conducted using hospital admission data from the Cerner Health Facts Database. Multivariable logistic regressions controlling for confounders were used to assess whether an NAS diagnosis is associated with hospital admission due to feeding problems., Findings/results: Infants with NAS were nearly 3 times as likely (OR = 2.81; 95% CI, 2.68-2.95) to have feeding problems compared with infants without NAS after adjusting for infant and hospital characteristics. Lower birth weight, higher infant age, Hispanic ethnicity, and hospital location in the Midwest region were also associated with higher odds of feeding problems. Infants diagnosed with NAS who had feeding problems had slightly lower odds of being offered lactation services than infants without NAS who had feeding problems., Implications for Practice: These findings suggest the need for targeted feeding interventions., Implications for Research: Future research on infants with NAS may build on these findings by assessing the role of maternal factors such as nutrition and substance use to understand how parental characteristics also influence the risk for hospitalization., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2021 by The National Association of Neonatal Nurses.)

Objective: The objective of this paper is to describe the trend of newborn hospitalizations with neonatal abstinence syndrome (NAS) in Canada, between 2010 and 2020, and to examine severity indicators for these hospitalizations., Methods: National hospitalization data (excluding Quebec) from the Canadian Institute for Health Information's Discharge Abstract Database, from January 2010 to March 2021, and Statistics Canada's Vital Statistics Birth Database were used. Analyses were performed to examine NAS hospitalizations by year and quarter, and by severity indicators of length of stay, Special Care Unit admission and status upon discharge. Severity indicators were further stratified by gestational age at birth., Results: An increasing number and rate of NAS hospitalizations in Canada between 2010 (n = 1013, 3.5 per 1000 live births) and 2020 (n = 1755, 6.3 per 1000 live births) were identified. A seasonal pattern was observed, where rates of NAS were lowest from April to June and highest from October to March. Mean length of stay in acute inpatient care was approximately 15 days and 71% of NAS hospitalizations were admitted to the Special Care Unit. Hospitalizations for pre-term births with NAS had longer durations and greater rates of Special Care Unit admissions compared to term births with NAS., Conclusion: The number and rate of NAS hospitalizations in Canada increased during the study, and some infants required a significant amount of specialized healthcare. Additional research is required to determine what supports and education for pregnant people can reduce the incidence of NAS hospitalizations., (© 2022. Crown.)

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., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objective: Aim to reduce healthcare utilization (HU) for infants at risk of neonatal opioid withdrawal syndrome (NOWS) by 30% in 1 year and sustain for 2 years., Study Design: Baseline data from three Level I & II newborn nurseries from January 2016 to June 2018 informed PDSA cycles from August 2018 to December 2021. Shewhart process control charts evaluated length of stay (LOS), pharmacologic treatment (PT) rates, direct cost (DC), process, and balancing measures for special cause variation (SCV)., Results: Two hundred and seventeen infants showed downward SCV in LOS (12.6 to 4.4 days), PT (53% to 17%) and DC ($12593.82 to $5219.17). Onset of the COVID-19 pandemic coincided with reversible SCV. DC varied by provider specialty., Conclusion: Transition from MFNASS to ESC led to decrease in healthcare utilization for infants at risk of NOWS. QI methodology identified persistent drivers of variability, including the COVID-19 pandemic and provider specialty., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Objective: Determine the accuracy of diagnostic codes in identifying Prenatal Opioid Exposure (POE) and Neonatal Opioid Withdrawal Syndrome (NOWS)., Study Design: A cross-sectional study of 374,222 mother-infant dyads with delivery from 01/01/2010 to 12/31/2019. We ascertained maternal diagnostic codes for opioid use during pregnancy and infant diagnostic codes for drug exposure and withdrawal. We assessed sensitivity and positive predictive value (PPV) for POE and NOWS, defined using laboratory, pharmacy, and clinical data., Results: Maternal codes had low sensitivity (36.4%) and PPV (34.7%) for POE. Infant codes for drug exposure were neither sensitive for POE (14%) nor NOWS (31.6%) and had low PPV. Codes for newborn withdrawal had low sensitivity (31.6%) for detecting NOWS, but high PPV (85%). Sensitivity improved (95.1%) for NOWS requiring pharmacologic treatment., Conclusions: Diagnostic codes identify POE and NOWS poorly. Improved case identification would include pharmacy and laboratory results, and clearly defined criteria for evidence of withdrawal., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Illicit drug use during pregnancy is a concern worldwide, with many international studies describing attempted strategies to mitigate this problem. Drug misuse during pregnancy is associated with significant maternal as well as perinatal complications, which include a high incidence of stillbirths, fetal distress, neonatal abstinence syndrome (NAS) and increased neonatal mortality. Unfortunately, the identification of a drug-exposed mother or neonate is challenging. Maternal disclosure of drug use is often inaccurate, principally due to psychosocial factors including behavioral denial or the fear of the consequences resulting from such admissions. Likewise, many infants who have been exposed to drugs in utero may appear normal at birth and initially show no overt manifestations of drug effects. Thus, the identification of the drug-exposed infant requires a high index of clinical suspicion. Conversely, analytical testing is an objective means of determining drug exposure when it may be necessary to document proof of the infant's exposure to illicit drugs. The review will discuss the different matrices that are most commonly used for testing (e.g., maternal urine, neonatal urine, meconium, and umbilical cord), the strengths and limitations for each matrix, which drugs and metabolites are appropriate for testing, the various testing methods, and the advantages and disadvantages of each method., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

The opioid epidemic in the United States has resulted in a significant increase in opioid use disorder among pregnant women and a concomitant increase in the incidence of neonatal opioid withdrawal syndrome. The long-term consequences of prenatal opioid exposure on neurodevelopmental outcomes are not fully understood. Animal studies indicate increased neuronal apoptosis and decreased neuronal proliferation and myelination with opioid exposure in-utero. Meta-analyses of human studies suggest decreased cognition and psychomotor performance in infancy and deficits in cognition and language in preschool. However, current studies have primarily focused on heroin or methadone exposure and have been limited by small sample size, inadequate comparison groups, and the inability to account for additional risk factors and exposures such as polysubstance abuse, poor prenatal care, neonatal withdrawal and treatment with opioids, and unsupportive home environment. Future studies should aim to better understand the potential impact of these confounding factors on the neurodevelopmental trajectory of exposed infants. This review discusses the up-to-date literature, current gaps in knowledge, and considerations for future studies in the arena of prenatal opioid exposure and neurodevelopmental outcomes., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: The use and misuse of opioids in pregnancy have been increasing and are a major public health issue. Opioid use in pregnancy and during lactation has been associated with increased maternal and neonatal morbidity and mortality., Objective: This review aims to summarize the existing literature and current recommendations for opioid use while pregnant or lactating., Evidence Acquisition: A PubMed, Cochrane Library, and Google Scholar literature search using the following terms was performed to gather relevant data: "opioids," "opioid maintenance therapy," "opioid use disorder," "suboxone," "buprenorphine," "methadone," "medication for opioid use disorder," "fetal outcomes," "perinatal outcomes," "pregnancy," "lactation," and "neonatal abstinence syndrome.", Results: Available studies on opioid use in pregnancy and during lactation were reviewed and support association with increased odds of maternal death, placental insufficiency, cardiac arrest, preterm birth, neonatal intensive care unit admission, low birth weight, and small for gestational age infants. Studies were also reviewed on pharmacotherapy options in pregnancy and promising prenatal care models., Conclusion and Relevance: There is a critical need for research on the effects of opioid use and related pharmacotherapy options in pregnancy. Once the adverse perinatal effects of opioid exposure are identified and well-characterized, patient education, intervention, and antenatal surveillance can be developed to predict and mitigate its impact on maternal and fetal health.

The world has been experiencing an opioid epidemic for over 20 years, and rates of use and overdose among women, including during pregnancy, have risen markedly. Women receive more prescriptions for opioids compared to men. Data suggest that 20% of women filled at least one prescription for an opioid during their pregnancy, and the prevalence of prenatal exposure averaged 14%. Opioid use by women, especially during pregnancy and while breastfeeding, and management and treatment is complex for healthcare providers, especially related to methadone treatment, pain management during labour, neonatal opioid withdrawal syndrome, nutritional issues and maternal withdrawal. Opioid use during pregnancy has been associated with maternal, foetal and infant complications, and overdose has become a leading cause of death in post-partum women in some countries. Universal screening for opioid use disorder (OUD) is recommended in pregnancy, and prevention and treatment programs that meet the specific needs of women are important to understand and consider as the world continues to try to anticipate and respond to the realities of the opioid epidemic., Competing Interests: Declaration of competing interest The author does not have any conflict of interest., (Copyright © 2022. Published by Elsevier Ltd.)