Body composition during the first 4 months in infants affected by neonatal abstinence syndrome: a pilot study.

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.

A Meta-Analysis of Breastfeeding Effects for Infants With Neonatal Abstinence Syndrome.

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.

Opioids and the developing brain: time to rethink perinatal care for infants of opioid-dependent mothers.

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.

Maternal Exposure and Neonatal Effects of Drugs of Abuse.

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.

Developmental Outcomes of Children Born with Neonatal Abstinence Syndrome (NAS): A Scoping Review.

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.

Feeding Behaviors in Infants With Prenatal Opioid Exposure: An Integrative Review.

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.

Neurophysiological monitoring in neonatal abstinence syndrome from cocaine.

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.

Prenatal opioid exposure - Increasing evidence of harm.

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.

Integrative Review of Gut Microbiota and Expression of Symptoms Associated With Neonatal Abstinence Syndrome.

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.

Association of a Simplified Finnegan Neonatal Abstinence Scoring Tool With the Need for Pharmacologic Treatment for Neonatal Abstinence Syndrome.

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.

Amplitude-integrated EEG in infants with neonatal abstinence syndrome.

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.

Interventions for the Treatment of Neonatal Abstinence Syndrome.

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.

Systematic mixed-study review of nonpharmacological management of neonatal abstinence syndrome.

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.

Nonpharmacological management of neonatal abstinence syndrome: a review of the literature.

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.

Natural drugs, not so natural effects: Neonatal abstinence syndrome secondary to 'kratom'.

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.

Novel Withdrawal Symptoms of a Neonate Prenatally Exposed to a Fentanyl Analog.

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.

History of postpartum depression as a contributor to the severity of 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.

Growth during the first year in infants affected by neonatal abstinence syndrome.

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.