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Social touch through infant holding, skin-to-skin contact, and infant carrying (babywearing) decreases infant distress and promotes secure attachment. Unknown is the extent to which these effects are the result of the activation of C-Tactile afferents (CTs), the constellation of nerve fibers associated with affective touch, primarily located in the head and trunk of the body. The purpose of the present study was to compare dynamic touch (CTs activated) to static touch (CTs less activated) during a babywearing procedure among infants experiencing Neonatal Opioid Withdrawal Syndrome (NOWS). NOWS is a spectrum of clinical symptoms, including elevated heart rate (HR), associated with withdrawal from intrauterine opioid exposure. We hypothesized that stroking an infant's head during babywearing would amplify the pleasurable effect of babywearing as measured by changes in infant HR. Twenty-nine infants in a Neonatal Intensive Care Unit (NICU) in the Southwestern USA were worn in an infant carrier starting at five days old (M = 5.4, SD = 2.6; 46.2 % White, 26.9 % Latinx, 11.5 % Native American) and physiological readings were conducted daily; heart rates of infants and caregivers were taken every 15-seconds for 5-minutes, before, during, and after babywearing (30 min per phase). Each day infants alternated (randomly) in a static touch (hands-free babywearing) or dynamic touch condition (stroking the top of the infants' head at a velocity of 3 cm/s while babywearing). On average, infants completed 3 dynamic and 3 static babywearing sessions. Hospital and research staff participated in babywearing when a parent was not available (31.0 % of infants were exclusively worn by volunteers, 27.6 % were exclusively worn by parents). We analyzed the data using Hierarchical Linear Models due to the 3-level nested design (N = 29 infants, N = 191 readings, N = 11,974 heart rates). Compared to baseline (infant calm/asleep and without contact), infant's HRs significantly declined during and after babywearing, controlling for pharmacological treatment. These effects were significantly stronger during the dynamic touch condition (reduction in HR of 11.17 bpm) compared to the static touch condition (reduction in HR of 3.74 bpm). These effects did not significantly vary by wearer (mother, father, volunteer). However, differences between the dynamic and static conditions were significantly stronger in earlier babywearing sessions, potentially indicating a learning effect. There was evidence for a calming effect among caregivers as well, particularly in the dynamic touch condition, when caregivers were engaged in active touch. Activation of CTs appears to be an important mechanism in the physiological benefits of babywearing and in the symbiotic role of caregiver-infant attachment., Competing Interests: Declaration of Competing Interest The authors do not have any conflicts of interest/competing interests. This work is funded as a result of generous financial support from BHHS Legacy Foundation, which is an Arizona charitable organization whose philanthropic mission is to enhance the quality of life and health of those it serves. This work was also funded by a grant from the Ibis Foundation. Ergobaby and Baby K’tan provided the infant carriers used in this study. All aspects of the study received IRB approval and participants actively consented to the study. All authors contributed to the manuscript development., (Published by Elsevier Inc.)

Objective: Infants with neonatal opioid withdrawal syndrome (NOWS) have disrupted neurobehavior that requires hospitalization and treatment. This article aimed to evaluate electroencephalography (EEG) abnormalities using amplitude-integrated EEG (aEEG) in NOWS., Study Design: Eighteen term born infants with NOWS were recruited prospectively for an observational pilot study. aEEG monitoring was started within 24 hours of recruitment and twice weekly through discharge. aEEG data were analyzed for background and seizures. Severity of withdrawal was monitored using the modified Finnegan scoring (MFS) system., Results: Fifteen neonates had complete datasets. Thirteen (87%) had continuous aEEG background in all recordings. None had sleep-wake cyclicity (SWC) at initial recording. Brief seizures were noted in 9 of 15 (60%) infants. Lack of SWC was associated with higher MFS scores. At discharge, 8 of 15 (53%) had absent or emerging SWC., Conclusion: aEEG abnormalities (absent SWC) are frequent and persist despite treatment at the time of discharge in the majority of patients with NOWS. Brief electrographic seizures are common. Neonates with persistent aEEG abnormalities at discharge warrant close follow-up., Key Points: · EEG abnormalities are common and persist after clinical signs resolve in patients with NOWS.. · Short subclinical seizures may be seen.. · aEEG may identify neonates who need follow-up.., Competing Interests: None declared., (Thieme. All rights reserved.)

Newborns with neonatal abstinence syndrome (NAS) display symptoms related to neurologic excitability and autonomic dysfunction that result in increased metabolic demands. These infants also exhibit feeding difficulties and/or hyperphagia. Because the effects of these symptoms and behaviors on growth are unknown, we sought to measure serial body composition measurements over the first 4 months in infants with NAS requiring pharmacologic treatment using air displacement plethysmography. Fourteen infants of singleton birth with appropriate-for-gestational-age (AGA) weight and a gestational age of ≥35 weeks and <42 weeks were evaluated. In mixed-effects models, per week, infants increased in mean fat percent by 1.1% (95% confidence interval [CI]: 0.85-1.43), fat mass by 90 g (CI: 70-100), and fat-free mass by 140 g (CI: 130-150). The subgroup of infants (N = 5) requiring multidrug therapy for symptom control had lower mean fat percent (-1.2%, CI: -5.2-2.1), fat mass (-60 g, CI: -25-13), and fat-free mass (-270 g, CI: -610-80) across time compared to infants requiring monotherapy. We are the first to report how body composition measures change over time in a small group of patients with NAS. Infants with NAS were smaller and leaner in the first several weeks compared to previously reported body composition measurements in term infants, but grew similarly to their healthy counterparts by 16 weeks. Infants with more severe NAS may be at risk for abnormalities in longer term growth.

Background: Neonatal abstinence syndrome (NAS) rates have dramatically increased. Breastfeeding is a nonpharmacological intervention that may be beneficial, reducing NAS symptom severity and thus the need for and duration of pharmacological treatment and length of hospital stay., Objectives: Conduct meta-analysis to determine whether breastfeeding results in better outcomes for NAS infants. Variables included symptom severity, need for and duration of pharmacological treatment, and length of hospital stay., Methods: PubMed, Scopus, Embase, and Cochrane Library were searched from 2000 to 2020, and comparative studies examining breastfeeding for NAS infants were extracted. Randomized trials and cohort studies were included. Data were extracted and evaluated with Review Manager Version 5.3. A random-effects model was used to pool discontinuous outcomes using risk ratio and 95% confidence intervals. Continuous outcomes were evaluated by mean differences and 95% confidence intervals., Results: Across 11 studies, 6,375 neonates were included in the meta-analysis. Using a random-effects analysis, breastfeeding reduced initiation of pharmacological treatment, reduced duration of pharmacological treatment, and reduced length of stay. No differences were detected for severity of NAS symptoms. Most studies only reported one to two variables of interest. For most studies, these variables were not the primary study outcomes. All studies were found to be of low risk and good quality based on the Cochrane Risk Assessment Tools. Varying breastfeeding definitions limit generalizability., Discussion: Breastfeeding is associated with decreased initiation and duration of pharmacological treatment and length of stay., Competing Interests: The authors have no conflicts of interest to report., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc.)

Illicit use of opioids is a global health crisis with major implications for women and children. Strategies for managing opioid use disorder (OUD) in pregnancy have been tested over the past 40 years, but studies have focused on maternal and pregnancy outcomes, with less attention given to long-term follow-up of exposed children. Here, we provide a narrative review of recent advances in the assessment and management of neonatal opioid withdrawal syndrome (NOWS), and we summarise evidence from multiple domains-neuroimaging, electrophysiology, visual development and function, neurodevelopment, behaviour, cognition and education-which suggests that prenatal opioid exposure modifies child development. Further studies are required to determine the optimal management of pregnant women with OUD and babies with NOWS. We identify knowledge gaps and suggest that future study designs should evaluate childhood outcomes, including infant brain development and long-term neurocognitive and visual function., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

The public health crisis of pregnant women being exposed to drugs of abuse and of its impact on their unborn children continues to grow at an alarming rate globally. The state of pregnancy is unique, with physiological changes that can lead to changes in the way drugs are handled by the body in both pharmacokinetics and response. These changes place the pregnant woman, fetus, and newborn infant at risk, as many of these drugs can cross the placenta and into breast milk. The substances most commonly linked to harmful effects include alcohol, tobacco, cannabis, stimulants, and opioids. The pharmacological and toxicological changes caused by in utero exposure or breastfeeding exposure are difficult to study, and the full extent of the mechanisms involved are not fully understood. However, these changes can significantly affect the risks of substance abuse and influence optimal treatment of pregnant women with a substance use disorder. In addition, newborns who were exposed to drugs of abuse in utero can experience withdrawal syndromes. Pharmacological management in infants is used to guide and treat withdrawal symptoms, with the goal being to improve the infant's sleep, eating, and comfort. Several barriers may prevent pregnant women from seeking help for substance use, including stigma and interactions with the legal system. Understanding changes in pharmacology, including pharmacokinetic changes that happen during pregnancy, is essential for anticipating the extent of maternal exposure and neonatal adverse effects., (© 2021, The American College of Clinical Pharmacology.)

Aims: The purpose of this scoping review is to provide an overview of developmental outcomes of children diagnosed with neonatal abstinence syndrome (NAS)., Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework was used to guide this scoping review. A comprehensive search of CINAHL, MEDLINE, EMBASE, Web of Science, and PsycINFO was conducted using search terms related to NAS and developmental areas. Full-text screening was completed for 30 articles, and eight studies were included in this review., Results: Cognitive and language development, as well as school performance, social and motor domains, may be areas of concern in children with NAS., Conclusions: The developmental outcomes of infants with NAS cannot be firmly determined due to inconsistent results across reviewed studies. Future research investigating development across various ages is required for rending more appropriate intervention services to this high-risk population.

Prenatal opioid exposure adversely impacts upon fetal growth and places the newborn at risk of neonatal opioid withdrawal. The severity and duration of opioid withdrawal cannot be predicted in the individual baby and may be contributed to by other drugs including benzodiazepines and alcohol as well as cigarette smoking. Mitigating factors include breastfeeding, rooming in and absence of maternal polypharmacy. Less well recognised are a variety of other complications associated with prenatal opioid exposure including epigenetic changes, effects on neurophysiological function and structural alterations to the developing brain. The visual system is significantly affected, with changes to both clinical and electrophysiological function persisting at least to mid-childhood. Longer term neurodevelopmental and behavioural outcomes are confounded by multiple factors including poverty, parent-child interaction and small study numbers, but systematic reviews consistently demonstrate poorer outcomes for those children and young people prenatally exposed to opioids. Crucially, manifestation of neonatal withdrawal is not a prerequisite for important long term problems including behavioural, emotional or motor function disorder, sensory or speech disorder, strabismus and nystagmus. A body of evidence supports an independent adverse effect of prenatal opioid exposure upon fetal brain development, mediated via a systemic neuro-inflammatory process. Children prenatally exposed to opioids should remain under appropriate follow up, at least until school entry, as difficulties may only become apparent in mid-childhood. Future studies of the management of opioid use disorder in pregnancy, including maintenance methadone, must include longer term outcomes for the baby., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Oral feeding is one of the most complex maturational skills of infancy. Difficulties with feeding require specialized attention, and if not well managed, may prolong the newborn's hospital length of stay. This is particularly true for prenatally opioid exposed (POE) infants. A paucity of literature exists characterizing feeding behaviors of POE infants, yet feeding problems are common., Purpose: The purpose of this integrative review was to synthesize and critically analyze the evidence that characterizes feeding behaviors in full-term, POE infants., Methods/search Strategy: The electronic databases of CINAHL, PubMed, Scopus, and PsycINFO were used. Inclusion criteria were studies in English, conducted from 1970 to 2019, with participant samples consisting of infants with prenatal opioid exposure, born full-term, and between 38 and 40 weeks of gestation. Based on the inclusion criteria, our search yielded 557 articles. After further screening, only 4 studies met our full inclusion/exclusion criteria. These studies were analyzed for evidence of infant feeding behaviors, including characterization of problematic feeding behavior for POE infants., Findings/results: Our findings revealed inconsistencies in characterization of feeding behaviors among POE infants. A synthesis of the most common evidence-based behaviors was constructed. Infant feeding behaviors were identified and grouped into 2 major behavior domains: (1) typical feeding behavior and (2) problematic feeding behavior., Implications for Practice and Research: Feeding behaviors related to sucking and behavioral states may be different in POE infants. Further examination of effective assessment methods and the categorization of infant feeding behaviors are warranted for use in the development of evidence-based, targeted intervention.

Background: Neonatal exposure and subsequent withdrawal from maternal substance use disorder are a growing problem and consequence of the current opioid epidemic. Neonatal abstinence syndrome (NAS) is defined by a specified cluster of symptoms with treatment guided by the expression and severity of these symptoms. The mechanisms or pathophysiology contributing to the development of NAS symptoms are not well known, but one factor that may influence NAS symptoms is the gut microbiota., Objectives: The purpose of this integrative review was to examine evidence that might show if and how the gut microbiota influence expression and severity of symptoms similar to those seen in NAS., Methods: Using published guidelines, a review of research studies that focused on the gut microbiome and symptoms similar to those seen in NAS was conducted, using the Cochrane, EMBASE, and Scopus databases, from 2009 through 2019., Results: The review results included findings of aberrant microbial diversity, differences in microbial communities between study groups, and associations between specific taxa and symptoms. In studies involving interventions, there were reports of improved microbial diversity, community structure, and symptoms., Discussion: The review findings provide evidence that the gut microbiota may play a role in modifying variability in the expression and severity of symptoms associated with NAS. Future research should focus on examining the gut microbiota in infants with and without the syndrome as well as exploring the relationship between symptom expression and aberrant gut microbiota colonization in infants with NAS.

Introduction: Neonatal abstinence syndrome (NAS) in a newborn is a result of the sudden discontinuation of exposure to psychotropic drugs abused by the mother during pregnancy. Since forty decades, the standardized Finnegan Neonatal Abstinence Scoring Tool (FNAST) documents the infant withdrawal, and initiate the appropriate treatment regimen, when elevated scored are reported. Whereas FNAST is successfully applied for opioids NAS, in case of other psychotropic drugs and especially cocaine, the tool is not always efficacious or predictive., Methods: Continuous v-Electroencephalography (vEEG) provides particularly useful information about brain cortical functioning and evaluation of background activity in normal newborns. vEEG allows to properly study and identify clinical manifestations as physiological motor paroxysms, that disappear from birth to infant age in correlation with the neurological development. Due to its feature to be a non-invasive tool continuous vEEG monitoring could be used to describe some clinical manifestations and assess if they can be correlated to possible injuries in critical neonates as those exposed in utero to psychoactive drugs presenting NAS., Results: An example for the potential use of such methodology is discussed in a case of NAS due to prenatal exposure to cocaine as a complementary tool for the evaluation of behavioural state and clinical and neurological signs in newborns in utero exposed to psychoactive drugs, excluding epileptic phenomena., Discussion: Video-EEG recording could be considered an important and objective tool that allows the evaluation of behavioural state and clinical and neurological signs in newborns in utero exposed to psychoactive drugs and the neurophysiological definition of signs and symptoms, which cannot be evaluated by FNAST such as startles and its variability during subsequent days after birth, subclinical seizures or brain injuries.

Importance: Observer-rated scales, such as the Finnegan Neonatal Abstinence Scoring Tool (FNAST), are used to quantify the severity of neonatal abstinence syndrome (NAS) and guide pharmacologic therapy. The FNAST, a comprehensive 21-item assessment tool, was developed for research and subsequently integrated into clinical practice; a simpler tool, designed to account for clinically meaningful outcomes, is urgently needed to standardize assessment., Objectives: To identify FNAST items independently associated with the decision to use pharmacologic therapy and to simplify the FNAST while minimizing loss of information for the treatment decision., Design, Setting, and Participants: This multisite cohort study included 424 neonates with opioid exposure who had a gestational age of at least 36 weeks with follow-up from birth to hospital discharge in the derivation cohort and 109 neonates with opioid exposure from the Maternal Opioid Treatment: Human Experimental Research Study in the validation cohort. Neonates in the derivation cohort were included in a medical record review at the Universities of Louisville and Kentucky or in a randomized clinical trial and observational study conducted at Tufts University (2014-2018); the Maternal Opioid Treatment: Human Experimental Research was conducted from 2005 to 2008. Data analysis was conducted from May 2017 to August 2019., Exposures: Prenatal opioid exposure., Main Outcomes and Measures: All FNAST items were dichotomized as present or not present, and logistic regression was used to identify binary items independently associated with pharmacologic treatment. The final model was validated with an independent cohort of neonates with opioid exposure., Results: Among 424 neonates (gestational age, ≥36 weeks; 217 [51%] female infants), convulsions were not observed, and high-pitched cry and hyperactive Moro reflex had extremely different frequencies across cohorts. Therefore, these 3 FNAST items were removed from further analysis. The 2 tremor items were combined, and 8 of the remaining 17 items were independently associated with pharmacologic treatment, with an area under the curve of 0.86 (95% CI, 0.82-0.89) compared with 0.90 (95% CI, 0.87-0.94) for the 21-item FNAST. External validation of the 8 items resulted in an area under the curve of 0.86 (95% CI, 0.79-0.93). Thresholds of 4 and 5 on the simplified scale yielded the closest agreement with FNAST thresholds of 8 and 12 (weighted κ = 0.55; 95% CI, 0.48-0.61)., Conclusions and Relevance: The findings of this study suggest that 8 signs of NAS may be sufficient to assess whether a neonate meets criteria for pharmacologic therapy. A focus on these signs could simplify the FNAST tool and may enhance its clinical utility.

Background: Neonatal abstinence syndrome is a multisystem disorder resulting from exposure to maternal addictive substance use in pregnancy. Withdrawal is characterized by neonatal tremors, feeding difficulties, and sleep disruption. The aim of this systematic review is to explore the nonpharmacological management of infants at risk of neonatal abstinence syndrome after prenatal exposure., Methods: A systematic mixed-study review was conducted. A search of CINAHL, MEDLINE, AMED, PsycARTICLES, PsycINFO, and Web of Science was performed for relevant articles published between January 2007 and June 2018. Quantitative and qualitative data were extracted and thematic analysis undertaken. The findings were synthesized as a narrative summary., Results: Fourteen studies were included in the review, of which nine were quality improvement initiatives and five explored complementary therapies. The most common components of nonpharmacological management were consolation therapy and rooming-in of mother and baby. Implementation strategies incorporated family integrated care and practitioner training in the evaluation of neonatal withdrawal. When nonpharmacological management was applied, there was a reduction in the need for pharmacotherapy and a shorter hospital stay for newborns. Potential barriers to effective management included unreliable assessment tools, judgmental practitioner attitudes, and limited breastfeeding promotion., Conclusions: Providing and optimizing nonpharmacological management for the infant at risk of neonatal abstinence syndrome improves outcomes by reducing their length of hospital stay and the need for pharmacotherapy., (© 2019 Wiley Periodicals, Inc.)

The growing incidence of neonatal abstinence syndrome (NAS) among newborns is a public health crisis that is a sequela of the national opioid crisis. When fetuses are exposed to opioids in utero, whether through prescription pain medication, illicit substances, or supervised medication-assisted opioid treatment, neonates can experience withdrawal symptoms shortly after birth. Opioid withdrawal manifests with symptoms of central nervous system and autonomic nervous system dysfunction. Treatment of NAS begins with nonpharmacologic interventions, and if a neonate requires more intensive treatment, care will escalate to include pharmacologic treatments, including morphine, methadone, and buprenorphine. When pharmacologic therapy begins, nonpharmacologic intervention is not ceased; rather, the two are used in conjunction in an attempt to reduce the amount of medication required for successful treatment. Herein we review nonpharmacologic nursing interventions, discuss the most common pharmacologic treatments for NAS, and present practice implications for nurses who work with childbearing families., (Copyright © 2019 AWHONN. Published by Elsevier Inc. All rights reserved.)

Background: Infants with neonatal abstinence syndrome (NAS) experience withdrawal that occurs as a result of termination of placental opioid supply following delivery. Common symptoms include restlessness, tremors, agitation and gastrointestinal disturbances. Severe NAS is often treated using opioids and/or sedatives. Although commonly employed effectively in neonatal care, there is a lack of published information regarding nonpharmacological management of the NAS infant., Objective: The purpose of this review was to summarize the current literature on nonpharmacological management of NAS., Methods: A literature search of Medline and EMBASE was performed for articles published between 2000 and June 2107., Results: Nonpharmacological management encompasses "environmental control", "feeding methods", "social integration", "soothing techniques" and "therapeutic modalities". Several interventions, including: breastfeeding, swaddling, rooming-in, environmental control and skin to skin contact have proven to be effective in managing NAS and should be incorporated into standard of care for this population (Level I-III Evidence). These interventions can be effective when offered in combination with pharmacological therapy, or as stand-alone therapy for less severe cases of NAS (Finnegan score <8)., Conclusions: Given the increasing body of evidence on its efficacy and ease of implementation, nonpharmacological treatment should universally be incorporated into standard of care for NAS.

Currently, there are no clinical tools available to accurately predict the severity of neonatal withdrawal. Studies of non-exposed neonates suggest that maternal depression and anxiety are predictive of negative short and long-term neonatal outcomes, but research is lacking in the addicted population. We studied of 109 pregnant women in medication-assisted treatment (MAT) and their neonates to determine if psychiatric conditions co-occurring with Substance Use Disorder (SUD) contributed to the severity of neonatal withdrawal. The need for pharmacological intervention, Finnegan scores, length of methadone treatment, and length of hospital stay were used to assess withdrawal severity. Categorical variables were analyzed in Stata14 using Chi Square and continuous variables were analyzed using Wilcoxon Rank Sum. Among the 110 neonates whose outcomes were reviewed, a maternal history of Postpartum Depression (PPD) was found to be correlated with increased severity of withdrawal. The neonates born to mothers with past diagnoses of PPD had more consecutive days of high Finnegan scores (95% confidence interval [CI], P = 0.003), longer length of treatment (95% CI, P = 0.006), and length of hospital stay (95% CI, P = 0.014). There was no apparent relationship between NAS severity and other psychiatric disorders. In a study of pregnant women with SUD and their neonates, we uncovered a relationship between the severity of NAS and maternal history of PPD. Our findings demonstrate that further research into these deleterious outcomes is warranted. Until then, we suggest collection of maternal history of PPD and careful screening for new cases in the SUD population., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: To describe amplitude-integrated encephalogram (aEEG) characteristics of neonates with neonatal abstinence syndrome (NAS)., Methods: This is a prospective observational study. Newborns exposed to prenatal opioids and their gestational matched controls were included. A single-channel aEEG was obtained using Olympic 6000 CFM monitor. The background activity (continuous/discontinuous), the amplitudes (μV) and the presence of sleep-wake cycle (SWC) were documented., Results: A total of 59 infants, 23 with NAS and 36 controls were enrolled. All aEEG were completed within 48 hours of life prior to initiation of treatment. Birth weight and gestational age were similar in both groups. An aEEG was abnormal (discontinuous pattern and/or absent SWC) in 78 % (18/23) of infants with NAS versus only 25% in control group (9/36), [OR 10.8, CI (2.7-46.5) P < 0.001]. 61% of infants with NAS had discontinuous pattern [OR 7.8, CI (2-32) P = 0.001] and 39% had absence of sleep-wake cycle [OR 7.1, CI (1.4-39.4) P = 0.007]., Conclusions: A majority of infants with NAS have abnormal aEEG activity.

Background: Mitragyna speciosa, also known as kratom, is obtained from the coffee plant family 'Rubiaceae.' Kratom is available in the form of capsules, whole, processed and powdered leaves, and as liquids. Secondary to its 'natural herb' status and opioid effects, it is misconceived to be a safe alternative for the treatment of chronic pain. The use of kratom has increased by tenfold in the United States since 2010., Methods and Results: We report a term neonate who was born to a chronic kratom user and required treatment with opiates for neonatal drug withdrawal., Conclusion: Physicians should be aware of these herbal supplements and its potential withdrawal effects in newborn which cannot be picked up by the standard toxicology screen.

Neonatal abstinence syndrome (NAS) is a withdrawal syndrome observed in neonates exposed to drugs in utero, typically opioids, which is associated with symptoms affecting the central and autonomic nervous systems and the gastrointestinal system. West Virginia, particularly the southeastern region of the state, has remarkably higher rates of NAS than similar communities. Our facility is increasingly faced with complex cases of NAS caused by in utero exposure to multiple substances. We present a case report of a neonate born to a 25-year-old mother enrolled in a medication-assisted treatment program for substance use disorder who was noncompliant in prenatal care, using multiple substances throughout the pregnancy, including gabapentin and fentanyl. After birth, the neonate began to exhibit unusual withdrawal symptoms including arching, tongue thrusting, and irregular eye movements, which are typically associated with in utero gabapentin exposure. The parents denied consent to treat with gabapentin, the suggested management for these symptoms; thus, a treatment protocol for methadone and clonidine were followed. This case exemplifies the medical and social complexities involved in treating polysubstance exposure-associated NAS., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Infants with neonatal abstinence syndrome (NAS) initially experience neurologic excitability, poor feeding, and/or hyperphagia in the setting of increased metabolic demand. Because the longitudinal effects of these early symptoms and behaviors on weight trends are unknown, we sought to contrast weight gain patterns through age 1 year for infants diagnosed with NAS with matched controls., Methods: Retrospective cohort of 70 singletons with a gestational age of ≥37 weeks and an ICD-9 or ICD-10 diagnosis of NAS made ≤7 days after birth with institutional follow-up matched to patients without NAS. Infants were matched on gestational age (±2 weeks), birth weight (±20 g), sex (exact), and insurance type (exact). Quantile regression methods were used to estimate 10th, 25th, 50th, 75th and 90th percentiles of weight over time., Results: The mean gestational age for an infant with NAS was 38.8 weeks (standard deviation [SD], 1.3). The mean birth weight was 3.141 kg (SD, 0.510). NAS patients had a median of 24 weights recorded between birth and 400 days (inter-quartile range [IQR], 16-32 weights). Patients without NAS had a median of 12 weights recorded (IQR, 10-16). Growth curves were similar over the first 400 days of life. Patients with NAS had non-significantly higher and lower estimated weights for the 90th and 10th percentiles, respectively., Conclusion: Infants with a diagnosis of NAS grew similarly to controls during their first year. Given the frequently-encountered NAS symptoms of hyperphagia and irritability, future studies may evaluate whether early differences in caregiver feeding exist and whether they have longer-term impacts on growth.

Objectives: To measure the incidence, onset, duration, and severity of neonatal abstinence syndrome (NAS) in infants born to mothers receiving buprenorphine and to assess the association between buprenorphine dose and NAS outcomes., Methods: We reviewed charts of all mother-infant pairs maintained on buprenorphine who delivered in our hospital from January 1, 2000 to April 1, 2016., Results: In 89 infants, NAS incidence requiring morphine was 43.8%. Means for morphine-treated infants included: 55.2 hours to morphine start, 15.9 days on morphine, and 20 days hospital stay. NAS requiring morphine treatment occurred in 48.5% and 41.4% of infants of mothers receiving ≤8 mg/d buprenorphine versus >8 mg/d, respectively (P = 0.39). We found no significant associations of maternal buprenorphine dose with peak NAS score, NAS severity requiring morphine, time to morphine start, peak morphine dose, or days on morphine. Among the other factors examined, only exclusive breastfeeding was significantly associated with neonatal outcomes, specifically lower odds of morphine treatment (odds ratio 0.24, P = 0.003)., Conclusions: These findings suggest higher buprenorphine doses can be prescribed to pregnant women receiving medication therapy for addiction without increasing NAS severity. Our finding of reduced risk of NAS requiring morphine treatment also suggests breastfeeding is both safe and beneficial for these infants and should be encouraged.

To determine the effects of auditory stimulus on skin conductance (SC) in infants with severe neonatal abstinence syndrome (NAS) that required morphine treatment (MT) compared with NAS infants that did not require morphine treatment (non-MT). We prospectively enrolled opiate-exposed term infants without polysubstance exposure. Skin conductance responses to an auditory stimulus (ringing a bell for 3s) near the time of discharge were obtained. Skin conductance was measured before, during, and after the stimulus. Non-parametric tests were used to determine between group and within phase differences. Infants were off MT at the time of SC measurement in response to an auditory stimulus. In a 2-group comparison of MT vs. non-MT infants, there was significantly higher SC responsivity to an auditory stimulus (p <0.05) in the MT group as compared with the non-MT group near discharge. The mean +SE peak morphine dose was 0.85+0.20mg/kg/day in the MT group. The mean Length of Stay (LOS) was 32 vs. 7 (p <0.05) days respectively, for the MT vs. the non-MT group. Our preliminary data suggest that in infants with severe NAS symptoms, higher sympathetic arousal in response to an auditory stimulus persists at discharge, underscoring the need for ongoing evaluation and specialized care at home., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Infants in drug withdrawal have complex physiological and behavioral states, requiring intensive nursing care. The study objectives were to describe acuity, parental needs, and nurse workload of infants in drug withdrawal compared with other infants. The design was cross-sectional and involved secondary nurse survey data from 6045 staff nurses from a national sample of 104 neonatal intensive care units. Nurses reported the care of 15 233 infants, 361 (2.4%) of whom were in drug withdrawal. Three-fourths of hospitals had at least 1 infant in drug withdrawal. In these hospitals, the mean number of infants in drug withdrawal was 4.7. Infant acuity was significantly higher among infants in drug withdrawal. Parents of infants in drug withdrawal required significantly more care to address complex social situations (51% vs 12%). The number of infants assigned to nurses with at least 1 infant in withdrawal (mean = 2.69) was significantly higher than typical (mean = 2.51). Given infant acuity and parental needs, policies legislating patient-to-nurse ratios should permit professional discretion on the number of patients to assign nurses caring for infants in drug withdrawal. Managers and charge nurses should consider the demands of caring for infants in drug withdrawal in assignment decisions and provide support and education.

Background and Aims: The relationship between gestational age at delivery and the severity of neonatal abstinence syndrome (NAS) is poorly understood. Our objective was to compare the length of pharmacotherapy and hospital stay among opioid-exposed infants born during the late pre-term, early term, full term and late term periods., Design: Retrospective cohort study of infants affected by NAS., Setting: MetroHealth Medical Center in Cleveland, OH, USA: an urban tertiary care hospital serving as the referral center for opioid dependency in pregnancy with a level III neonatal intensive care unit., Participants: All deliveries complicated by maternal opioid exposure from January 2000 to October 2014; 403 were eligible to be included [n = 102 late pre-term, 34-36 weeks (LP), n = 158 early term, 37-38 weeks (ET), n = 122 full term, 39-40 weeks (FT), n = 21 late term, ≥41 weeks (LT)]., Measurements: NAS requiring pharmacotherapy with opioids and hospital stay duration were compared between gestational age cohorts. Interaction by type of maternal medication was evaluated., Findings: The necessity for pharmacotherapy for NAS was similar in all gestational age groups [LP n = 45/102 (44%), ET n = 65/158 (41%), FT n = 55/122 (45%), LT n = 9/21 (43%); P = 0.92]. However, the median duration of pharmacotherapy for NAS was significantly different between the groups [LP =16.0 median (interquartile range: IQR = 10.0-24.0) days, ET = 22.5 (IQR = 15.0-40.0), FT = 23.0 (IQR = 6.0-38.0), LT = 22.0 (IQR = 6.0-28.0); P = 0.02]. Neonatal intensive care unit admission for NAS (P = 0.07) and total length of stay (P = 0.27), which includes observation for NAS not requiring medication, were not different. There was no significant interaction between gestational age cohorts and maternal medication assisted treatment therapy on the need for or duration of NAS treatment. The results were unchanged when evaluated for potential confounding variables., Conclusions: Gestational age (pre-term, term or late term) at birth appears to be unrelated to the need for pharmacotherapy to treat neonatal abstinence syndrome (NAS) in late pre-term and term infants. If treatment is needed it may tend to be given for longer in term than pre-term or late term infants., (© 2016 Society for the Study of Addiction.)

Exposure to drugs during pregnancy has the potential to harm offspring. Teratogenic effects are the most feared adverse outcomes in newborns; however, a wide spectrum of less known, usually reversible and often acute, neonatal adverse events can also occur due to drug intake by mothers during pregnancy, particularly in close proximity to delivery. This narrative review is aimed at the description of drugs and drug classes for which licit maternal use in the predelivery period has been associated with neonatal non-teratogenic disorders. For each drug class, epidemiology, clinical features, biological mechanism and management of these adverse reactions have been discussed in detail. Although these adverse reactions have been described mainly for substances used illicitly for recreational purposes, several prescription drugs have also been involved; these include mainly psychotropic medications such as opioids, antidepressants, antiepileptics and antipsychotics. These effects can be partly explained by withdrawal syndromes (defined also as 'neonatal abstinence syndrome') caused by the delivery-related discontinuation of the drug disposition from the mother to the fetus, with symptoms that may include feeding disorders, tremors, irritability, hypotonia/hypertonia, vomiting and persistent crying, occurring a few hours to 1 month after delivery. Otherwise, neonatal neurological and behavioral effects can also be caused by a residual pharmacological effect due to an accumulation of the drug in the blood and tissues of the newborn, with various symptoms related to the toxic effects of the specific drug class, usually developing a few hours after birth. With few exceptions, validated protocols for the assessment and management of withdrawal or residual pharmacological effects of these drugs in neonates are often lacking or incomplete. Spontaneous reporting of these adverse reactions seems limited, although it might represent a useful tool for improving our knowledge about drug-induced neonatal syndromes.

The increase in opioid use among the general population is reflected in pregnant women and neonatal abstinence syndrome (NAS) statistics. This increase has produced an unprecedented focus on NAS from both the political-judicial sphere and the medical community. Under the banner of fetal protection, judges and prosecutors have implemented punitive approaches against women who use prescribed and nonprescribed opioids during pregnancy, including arrest, civil commitment, detention, prosecution, and loss of custody or termination of parental rights. Within the medical community, questions have been raised regarding protocols to detect prenatal drug exposure at delivery, NAS treatment protocols, the need for quality-improvement strategies to standardize care and reduce length of stay for mother and infant, and the benefits of engaging the mother in the care of her infant. It is not uncommon for the expression of strong discordant views on these issues both between and among these political-judicial and medical constituencies. Closely examining the issues often reveal a lack of understanding of substance use disorders, their treatment, and the occurrence and treatment of NAS. This study provides an in-depth examination of NAS, including variations in presentation and factors that impact the efficacy of treatment, and also identifying questions that remain unanswered. Finally, 4 key areas on which future research should focus to guide both medical care and public policy are discussed.

We developed a pilot evidence-based prenatal educational intervention to increase knowledge of neonatal abstinence syndrome (NAS) and early parenting skills for women with opiate dependency who enrolled in a pregnancy buprenorphine clinic. We developed, implemented, and tested modules regarding expectations during newborn hospitalization for observation or treatment of NAS and regarding evidence-based parenting skills in response to NAS behaviors. Testing evaluated baseline knowledge of early parenting skills with newborns at risk for NAS and change from baseline after the educational intervention. No statistically significant difference in composite knowledge scores was observed. A brief survey completed by the participants postpartum affirmed the perception of women that the educational intervention effectively prepared them for the early postpartum period while their newborns were hospitalized., (© 2016 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses.)

Unlabelled: The aims of this study were to compare the skin conductance (SC) of newborns with opiate-induced neonatal abstinence syndrome (NAS) to that of unexposed newborns and to evaluate the potential of SC readings to detect distress in the context of NAS objectively. The SC of 12 newborns with NAS and 12 unexposed newborns was measured at nine specific times during their first 6 weeks of life. The number of SC fluctuations per second (NSCF/s), the amplitude of SC fluctuation, and the mean level of SC were recorded and analyzed. The SC of newborns treated for symptoms of NAS differed significantly from the SC of unexposed newborns with regard to the NSCF/s (p = 0.04). With the mean level of SC, we observed an interaction between groups over time (p value for interaction = 0.02). With increasing postnatal age, we observed higher values in all three SC parameters., Conclusion: The NSCF/s and the mean level of SC appear to be suitable to reflect the distress of newborns suffering from NAS. As it is known that the sensitivity of SC increases with the level of stress experienced, its potential to indicate elevated stress levels in infants with NAS should be investigated in future studies evaluating different therapy regimens., What Is Known: • Skin conductance is a result of the filling of palmar and plantar sweat glands innervated by the sympathetic nervous system • Skin conductance can be used as a measure of stress and pain in newborns What is New: • Skin conductance of newborns with neonatal abstinence syndrome (NAS) differs significantly from the SC of non-substance-exposed newborns during the first 6 weeks of life • Skin conductance appears to reflect the increased distress of infants with NAS.

Neonatal abstinence syndrome (NAS) from in utero opioid exposure has reached epidemic levels in the United States. Although nonpharmacologic therapies form the foundation of care, many neonates require pharmacotherapy. Morphine represents the most widely used first-line agent and effectively treats the symptoms of withdrawal. However, methadone or buprenorphine may facilitate earlier discharge. Although phenobarbital is traditionally used when opioids fail, clonidine may be a more appropriate adjunctive agent to minimize negative neurodevelopmental impact. Consideration of the available data allows hospitals to generate effective pharmacologic strategies to manage NAS while further research continues.

Introduction: Gabapentin, an anticonvulsant, neuroleptic, and pain medication, is widely used in both adults and children for management of epilepsy, bipolar illness, and neuropathic pain. Gabapentin use has also been recommended for hyperemesis gravidarum and restless leg syndrome in pregnant mothers., Objective: Although gabapentin use is deemed safe during pregnancy, no clinical reports of gabapentin withdrawal syndrome in a neonate have been described., Results: We present a newborn who showed signs of withdrawal after prolonged in utero exposure to gabapentin., Clinical Implications: Clinicians should be aware of possible withdrawal symptoms from drugs such as gabapentin, administered to mothers during pregnancy. We also encourage the gradual tapering of gabapentin in neonates over weeks to months similar to the adult population., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: Opioid exposure during pregnancy is a potential risk factor for the developing central nervous system of the fetus. We studied evoked responses in buprenorphine-exposed newborns who displayed neonatal abstinence syndrome (NAS) to elucidate the possible alterations in functioning of the somatosensory and auditory systems., Methods: We compared somatosensory (SEFs) and auditory evoked magnetic fields (AEFs), recorded with magnetoencephalography (MEG), of 11 prenatally buprenorphine-exposed newborns with those of 12 healthy newborns. Peak latencies, source strength and location of SEFs or AEFs were recorded., Results: AEFs were present in all buprenorphine-exposed newborns without significant differences from those of healthy newborns. In contrast, though no group level differences in SEFs existed, at individual level the response deviated from the typical neonatal morphology in four buprenorphine-exposed newborns., Conclusions: Although buprenorphine exposure during pregnancy does not seem to cause constant deficiencies in somatosensory or auditory processing, in some newborns the typical development of somatosensory networks may be - at least transiently - disrupted.

Neonatal abstinence syndrome (NAS) is a result of the sudden discontinuation of fetal exposure to substances that were used or abused by the mother during pregnancy. Withdrawal from licit or illicit substances is becoming more common among neonates in both developed and developing countries. NAS continues to be an important clinical entity throughout much of the world. NAS leads to a constellation of signs and symptoms involving multiple systems. The pathophysiology of NAS is not completely understood. Urine or meconium confirmation may assist the diagnosis and management of NAS. The Finnegan scoring system is commonly used to assess the severity of NAS; scoring can be helpful for initiating, monitoring, and terminating treatment in neonates. Nonpharmacological care is the initial treatment option, and pharmacological treatment is required if an improvement is not observed after nonpharmacological measures or if the infant develops severe withdrawal. Morphine is the most commonly used drug in the treatment of NAS secondary to opioids. An algorithmic approach to the management of infants with NAS is suggested. Breastfeeding is not contraindicated in NAS, unless the mother is taking street drugs, is involved in polydrug abuse, or is infected with HIV. Future studies are required to assess the long-term effects of NAS on children after prenatal exposure., (Copyright © 2014 by the American Academy of Pediatrics.)

Nationally, there has been a steady increase in the number of infants born with neonatal abstinence syndrome or drug withdrawal. Many of these infants remain in the hospital because their signs of withdrawal require pharmacologic management. The length of hospital stay can range from 1 week to several months depending on the severity of withdrawal. One way to decrease the length of stay and reduce the cost of care is to discharge the infant from the hospital sooner. To discharge infants sooner, their neonatal abstinence syndrome must be accurately assessed so that appropriate pharmacologic management can be administered. One way to increase the accuracy of assessing withdrawal signs is to implement an interobserver reliability protocol. This approach will allow healthcare professionals to gain consistency and accuracy in assessing infants for signs of withdrawal that may facilitate earlier discharge from the hospital.

Developmental features of the P2 auditory ERP in a change detection paradigm were examined in infants prenatally exposed to methadone. Opiate dependent pregnant women maintained on methadone replacement therapy were recruited during pregnancy (N = 60). Current and historical alcohol and substance use, SES, and psychiatric status were assessed with a maternal interview during the third trimester. Medical records were used to collect information regarding maternal medications, monthly urinalysis, and breathalyzer to confirm comorbid drug and alcohol exposures. Between birth and 4 months infant ERP change detection performance was evaluated on one occasion with the oddball paradigm (.2 probability oddball) using pure-tone stimuli (standard = 1 kHz and oddball = 2 kHz frequency) at midline electrode sites, Fz, Cz, Pz. Infant groups were examined in the following developmental windows: 4-15, 16-32, or 33-120 days PNA. Older groups showed increased P2 amplitude at Fz and effective change detection performance at P2 not seen in the newborn group. Developmental maturation of amplitude and stimulus discrimination for P2 has been reported in developing infants at all of the ages tested and data reported here in the older infants are consistent with typical development. However, it has been previously reported that the P2 amplitude difference is detectable in neonates; therefore, absence of a difference in P2 amplitude between stimuli in the 4-15 days group may represent impaired ERP performance by neonatal abstinence syndrome or prenatal methadone exposure., (© 2013 Wiley Periodicals, Inc.)

Substance misuse in pregnancy is not a new problem, but although impaired foetal growth and the risk of developing neonatal abstinence syndrome are widely appreciated, relatively little attention has been paid to longer term consequences for the infant. Available evidence indicates that prenatal exposure to opioids and other drugs of misuse is detrimental to the developing foetal brain; consistent with this, poor in utero head growth, delayed infant visual maturation and impaired general neurodevelopmental progress independent of social confounders are increasingly being recognised. This review considers current evidence and discusses best practice in the neonatal management and follow-up of affected babies. More studies are required to explore alternatives to methadone maintenance in pregnancy and to define optimal treatment for neonatal abstinence syndrome. All infants born to drug-misusing mothers must be considered vulnerable, even if they have not required treatment for neonatal abstinence syndrome., (© 2013 Elsevier Ireland Ltd. All rights reserved.)

Baclofen is a gamma-aminobutyric acid agonist used primarily as a muscle relaxant to treat spasticity in children and adults. Withdrawal of oral baclofen is known to cause a withdrawal syndrome in adults. Only one previous case describes a withdrawal syndrome in a term infant, manifested by seizures, associated with the use of oral baclofen in the mother. This case describes a withdrawal syndrome and the unique use of baclofen for withdrawal in a preterm infant.

This article is an overview of NEC in term neonates and also summarizes data from 52 cases within Intermountain Healthcare during the last 11 years. In all 52, NEC occurred among neonates already admitted to a neonatal intensive care unit for some other reason; thus, NEC invariably developed as a complication of treatment, not as a primary diagnosis. The authors speculate that the incidence of term NEC can be reduced by identifying neonatal intensive care unit patients at risk for NEC and applying appropriate-volume human milk feeding programs for these patients., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Pupil diameter is a frequently assessed objective index of the pharmacodynamic effects of opioids in adults, but to our knowledge has never been examined in infants. Such a measure could improve assessment and treatment of neonates exposed to opioids in utero. The present study examined changes in pupil diameter after opioid administration in opioid-exposed infants who required pharmacological treatment for neonatal abstinence syndrome (NAS) to test the feasibility of using pupil diameter as a measure of opioid effects in these infants., Methods: Ten infants (2-7 days old) receiving methadone (0.4-0.5 mg every 12 h) for the treatment of NAS participated. A picture of one of each infant's eyes was taken under controlled illumination conditions with a standard digital camera just prior to dosing and 0-1, 2-4, 5-7, and 8-10h after dosing. The diameters of the pupil and iris were measured and relative pupil diameter (pupil diameter expressed as a percentage of iris diameter) was analyzed., Results: Mean (±SE) relative pupil diameter decreased significantly after dosing from 41±2% to 29±2%. After dosing, a significant increasing linear trend was observed over time, with values of 29±2%, 33±3%, 38±3%, and 41±3% at 0-1, 2-4, 5-7, and 8-10h after dosing., Conclusions: Infant pupils respond to opioid administration in the same sensitive, orderly manner as is commonly observed in adults. Pupil diameter appears to be an objective, sensitive measure of neonatal response to opioids that may be a useful complement to, or perhaps at times a replacement for, observer-rated scale scores., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objective: Effects on child neurodevelopment of neurotransmitter reuptake inhibitors used as antidepressants during pregnancy have not been adequately studied. The authors compared the effects of prenatal exposure to venlafaxine (serotonin-norepinephrine reuptake inhibitor), selective serotonin reuptake inhibitors (SSRIs), and maternal depression., Method: A cohort derived from a prospectively collected database included four groups of children born to 1) depressed women who took venlafaxine during pregnancy (N=62), 2) depressed women who took SSRIs during pregnancy (N=62), 3) depressed women who were untreated during pregnancy (N=54), and 4) nondepressed, healthy women (N=62). The children's intelligence and behavior outcomes were evaluated with standardized instruments at one time point between the ages of 3 years and 6 years, 11 months., Results: The children exposed to venlafaxine, SSRIs, and maternal depression during pregnancy had similar full-scale IQs (105, 105, and 108, respectively). The IQs of the venlafaxine and SSRI groups were significantly lower than that of the children of nondepressed mothers (112). The three groups exposed to maternal depression had consistently, but nonsignificantly, higher rates of most problematic behaviors than the children of nondepressed mothers. Severity of maternal depression in pregnancy and at testing predicted child behavior. Maternal IQ and child sex predicted child IQ. Antidepressant dose and duration during pregnancy did not predict any cognitive or behavioral outcome., Conclusions: Factors other than antidepressant exposure during pregnancy strongly predict children's intellect and behavior. Depression during pregnancy is a significant risk factor for postpartum depression. Children of depressed mothers may be at risk of future psychopathology.

Aim: To determine the effects of in utero exposure to methadone or buprenorphine on infant neurobehavior., Design: Three sites from the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study, a double-blind, double-dummy, randomized clinical trial participated in this substudy., Setting: Medical Centers that provided comprehensive maternal care to opioid-dependent pregnant women in Baltimore, MD, Providence, RI and Vienna, Austria., Participants: Thirty-nine full-term infants., Measurements: The Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale (NNNS) was administered to a subgroup of infants on postpartum days 3, 5, 7, 10, 14-15 and 28-30., Findings: While neurobehavior improved for both medication conditions over time, infants exposed in utero to buprenorphine exhibited fewer stress-abstinence signs (P < 0.001), were less excitable (P < 0.001) and less over-aroused (P < 0.01), exhibited less hypertonia (P < 0.007), had better self-regulation (P < 0.04) and required less handling (P < 0.001) to maintain a quiet alert state relative to in utero methadone-exposed infants. Infants who were older when they began morphine treatment for withdrawal had higher self-regulation scores (P < 0.01), and demonstrated the least amount of excitability (P < 0.02) and hypertonia (P < 0.02) on average. Quality of movement was correlated negatively with peak NAS score (P < 0.01), number of days treated with morphine for NAS (P < 0.01) and total amount of morphine received (P < 0.03). Excitability scores were related positively to total morphine dose (P < 0.03)., Conclusion: While neurobehavior improves during the first month of postnatal life for in utero agonist medication-exposed neonates, buprenorphine exposure results in superior neurobehavioral scores and less severe withdrawal than does methadone exposure., (© 2012 The Authors, Addiction © 2012 Society for the Study of Addiction.)

Aims: To compare the profile of signs of neonatal abstinence syndrome (NAS) in methadone- versus buprenorphine-exposed infants., Design, Setting and Participants: Secondary analysis of NAS data from a multi-site, double-blind, double-dummy, flexible-dosing, randomized clinical trial. Data from a total of 129 neonates born to opioid-dependent women who had been assigned to receive methadone or buprenorphine treatment during pregnancy were examined., Measurements: For 10 days after delivery, neonates (methadone = 72, buprenorphine = 57) were assessed regularly using a 19-item modified Finnegan scale. Data from neonates who required pharmacological treatment (methadone = 41, buprenorphine = 27) were included up to the time treatment was initiated. The incidence and mean severity of the total NAS score and each individual sign of NAS were calculated and compared between medication conditions, as was the median time until morphine treatment initiation among treated infants in each condition., Findings: Two NAS signs (undisturbed tremors and hyperactive Moro reflex) were observed significantly more frequently in methadone-exposed neonates and three (nasal stuffiness, sneezing, loose stools) were observed more frequently in buprenorphine-exposed neonates. Mean severity scores on the total NAS score and five individual signs (disturbed and undisturbed tremors, hyperactive Moro reflex, excessive irritability, failure to thrive) were significantly higher among methadone-exposed neonates, while sneezing was higher among buprenorphine-exposed neonates. Among treated neonates, methadone-exposed infants required treatment significantly earlier than buprenorphine-exposed infants (36 versus 59 hours postnatal, respectively)., Conclusions: The profile of neonatal abstinence syndrome differs in methadone- versus buprenorphine-exposed neonates, with significant differences in incidence, severity and treatment initiation time. Overall, methadone-exposed neonates have a more severe neonatal abstinence syndrome., (© 2012 The Authors, Addiction © 2012 Society for the Study of Addiction.)

It is widely accepted that maternal drug-exposed infants demonstrate excessive early weight loss, but this has not previously been quantified. Among 354 term, substitute methadone-exposed infants, median maximal weight losses were 10.2% and 8.5% for breast- and formula-fed infants, respectively (p=0.003). Weight loss was less in small for gestational age compared to appropriately grown infants (p<0.001). There was no association between maximal weight loss and plasma sodium concentration (p=0.807). Relative to non-drug exposed infants, weight loss was more marked in formula-fed infants, 48% of whom demonstrated weight loss in excess of the 95th centile (compared to 23% of exclusively breastfed infants; p<0.001). Median weight loss nadir was on day 5, excepting those infants exclusively breastfed (day 4). These data suggest that excessive neonatal weight loss among breastfed infants of drug-misusing mothers does not necessarily reflect poorly established lactation and may help to guide management of breast feeding in this population.

Objective: Phenobarbital crosses the placenta quickly, and the balance between maternal and fetal blood is achieved in a few minutes. Data on the clinical outcomes of infants born to mothers under phenobarbital treatment during pregnancy show that they are at risk of adverse events, such as sedation and abstinence syndrome. The aim of this study was to analyse the correlation between serum levels of phenobarbital and clinical features of neonates., Study Design: Twenty-three infants born between 2001 and 2008 were studied. Maternal, neonatal and pharmacological variables were considered., Results: Eleven infants displayed symptoms related to phenobarbital. Withdrawal syndrome was seen in seven infants and sedation syndrome was seen in four infants. One infant had severe cardiorespiratory depression at birth. None of the infants had severe neonatal abstinence syndrome. No statistically significant differences were found between symptomatic and asymptomatic infants. At birth, the mean serum level of phenobarbital of the 23 infants was 15.4 [standard deviation (SD) 6.2] μg/ml. A peak (16.1 μg/ml, SD 5.5) was seen on Day 3, followed by a gradual decrease to non-therapeutic levels (<10 μg/ml) by Day 8 (9.3 μg/ml, SD 1.0). Phenobarbital levels were higher in symptomatic infants than asymptomatic infants, although the difference was not statistically significant., Conclusions: Serum levels of phenobarbital remained in the therapeutic range for both mothers and infants, and reduced gradually in infants. However, some infants displayed symptoms related to phenobarbital. As such, a clinical pharmacological surveillance protocol is necessary., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Tolerance has been recognized for some time where chronic exposure to certain drugs, particularly benzodiazepines and opioids, is associated with apparent tachyphylaxis. When these drugs are stopped or progressively reduced as in 'tapering', withdrawal symptoms may result. Tolerance and the flip side of the coin, withdrawal, are the determinants of addiction. It is increasingly apparent that tolerance can occur acutely, even within the time span of a single anesthetic for a surgical procedure. Addiction is caused by agents, foreign to the body, that provoke adaptation by homeostatic biological processes. When these agents are withdrawn, the adaptive mechanisms, devoid of substrate, take time to diminish and produce symptoms recognizable under the term of 'withdrawal'. Children may be exposed to these agents in different ways; in utero, as a result of substances that the mother ingests by enteral, parenteral or inhalational means that are transmitted to the infant via the placenta; as a result of an anesthetic for surgery; or as a result of sedation and analgesia administered to offset the stresses and trauma inherent from intensive care treatment in the neonatal intensive care unit or pediatric intensive care unit. Additionally, anesthetic and intensive care staff are exposed to powerful and addictive drugs as part of everyday practice, not simply by overt access, but also by subliminal environmental exposure., (© 2010 Blackwell Publishing Ltd.)

Objective: Determine whether infants exposed to chronic maternal methadone with abnormal intrapartum fetal heart rate (FHR) patterns are more likely to require treatment for neonatal abstinence syndrome (NAS)., Study Design: Intrapartum FHR tracings analyzed in 104 pregnancies at ≥ 34 weeks gestation for FHR variability, accelerations, and decelerations. FHR patterns compared between neonates based on treatment with methadone for NAS. Secondary analysis included relation between maternal methadone dose and intrapartum FHR patterns, initiation of methadone, age at methadone initiation, and total neonatal methadone dose. Study powered to detect 30% increase in NAS incidence in neonates with abnormal FHR tracings., Results: Seventy-six (73%) of 104 neonates required methadone treatment for NAS. Neonates who required methadone had higher average baseline FHR (131 vs. 126 bpm; p < 0.04) in active labor and less likely to have FHR tracings without accelerations (1.7% vs. 20.3%; p = 0.007) in latent labor. No significant associations between neonate's need for methadone and intrapartum FHR variability or FHR decelerations. No association between maternal methadone dose (range 30-280 mg) and treatment for NAS., Conclusion: The need for an infant to require methadone treatment for NAS was not reliably predicted by the intrapartum FHR patterns or the maternal methadone dose.

Abuse of drugs by pregnant women both in the United States and worldwide has raised many questions regarding the effects of prenatal drug exposure on the developing fetus and subsequent child outcomes. Studies using the neurobehavioral teratology model have been undertaken to determine specific prenatal drug effects on cognitive and behavioral development. Here we summarize the findings of studies that have investigated the developmental effects of prenatal exposure to tobacco, marijuana, stimulants, and opiates. These studies consider the timing and amount of prenatal exposure; other drug exposures; maternal characteristics; and other health, nutritional, and environmental factors. We review treatment options for pregnant, substance-dependent women and therapeutic interventions for exposed children.

Background: Neonatal abstinence syndrome (NAS) expression is widely variable among affected infants and the reasons for this variability are largely unknown; mechanisms that predispose infants to NAS expression are not understood. It has been postulated that the regulatory problems of prenatally drug exposed infants are manifested in dysfunctional vagal regulation of autonomic processes. The current study examines whether cardiac vagal tone, an indicator of parasympathetic neuroregulation, provides a marker for autonomic dysregulation subsequently expressed as NAS in prenatally opioid-exposed newborns., Methods: Heart period (HP) and cardiac vagal tone (V) were derived from electrocardiogram data collected from 64 methadone-exposed infants on postnatal days 1 and 3. The postpartum NAS course was assessed serially., Results: Infants with lower V on day 1 had significantly higher NAS symptomatology on day 3. Boys had more severe NAS symptoms than girls through the first 4 days of life and, among infants receiving pharmacologic treatment for NAS, boys required longer treatment course and hospitalizations. Greater poly-drug exposure, detected through toxicology screening throughout pregnancy, and cocaine use in particular, were associated with lower V and shorter HP (faster heart rate) in newborns. Multiple regression models accounted for 25-35% of the variance in NAS symptoms and duration of hospitalization in methadone-exposed infants. Significant predictors included infant sex, SSRI/SNRI use, and cigarette smoking., Conclusions: Results support the hypothesis of a biologic vulnerability of autonomic regulatory functioning in methadone-exposed infants and greater male infant vulnerability to maternal methadone use., (Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.)