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

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

Neonatal Opioid Withdrawal Syndrome Following Prenatal Use of Supplements Containing Tianeptine.

Tianeptine is an opioid receptor agonist that is prescribed as an antidepressant in many countries. In the United States, tianeptine is not approved for medical use because of its potential for abuse and addiction. Nonetheless, products containing tianeptine are easily obtainable and are marketed as dietary supplements. There are increasing reports of adverse effects and fatal toxicities resulting from tianeptine use among adolescents and adults. This emerging public health threat could escalate the opioid epidemic and drive increased newborn perinatal exposure. The impact of in utero exposure to tianeptine has not been studied, and to our knowledge, the authors of only 1 report have documented possible neonatal effects. Here, we describe a case of chronic prenatal exposure to tianeptine in the setting of maternal dependence on dietary supplements. This infant developed signs of severe withdrawal shortly after birth that were refractory to treatment with oral phenobarbital but responded to subsequent oral morphine therapy. On further questioning, the mother revealed the use of a tianeptine-containing dietary supplement. We did not perform confirmatory toxicology testing because tianeptine is not assayed by usual urine drug screening tests. For infants with clinical signs of opioid withdrawal without known etiology, we suggest that the maternal interview should inquire about the use of neurotropic over-the-counter drugs.

Neonatal abstinence syndrome: Effectiveness of targeted umbilical cord drug screening.

OBJECTIVE: This study sought to determine if targeted drug screening of newborns was effective in identifying a positive drug test result. STUDY DESIGN: This was a retrospective cross-sectional study. A total of 340 infants met criteria for drug screening. Sensitivity and specificity were used to evaluate each of the potential risk factors in terms of their ability to predict a positive drug test result. Two-sample t-tests were used to compare differences in Finnegan scores between babies with a positive drug test result and those with a negative one. RESULT: The risk factor with the highest sensitivity was maternal history of drug use. The difference in the Finnegan scores between groups was statistically significant. CONCLUSION: The risk factors associated with this study were not very sensitive. The only way to identify all infants at risk of NAS is to standardize the screening process and apply to all infants.

Reconceptualizing non-pharmacologic approaches to Neonatal Abstinence Syndrome (NAS) and Neonatal Opioid Withdrawal Syndrome (NOWS): A theoretical and evidence-based approach. Part II: The clinical application of nonpharmacologic care for NAS/NOWS.

There has been increasing emphasis on the importance of the development of self-regulatory capacities of the individual as the cornerstone of development. The caregivers' abilities to manage their own attention, emotions, physiology and behaviors influence the development of the child's self-regulatory and interactive capacities, and thereby their overall development. Newborns prenatally exposed to psychoactive substances and/or to other prenatal stressors such as maternal poor nutrition, increased maternal stress, trauma, difficult and/or impoverished environments, in tandem with genetic predispositions, can result in alterations to their neurodevelopment that predispose them to self-regulatory problems that can be expressed at any stage of life. The care of infants with Neonatal Abstinence Syndrome (NAS)/Neonatal Opioid Withdrawal Syndrome (NOWS) and their mother/caregiver is a window of opportunity to assess the regulatory and co-regulatory capacities of both, and to provide holistic interventions with the goal of empowering the mother/caregiver in their own self-knowledge/self-regulation capacities and their crucial role in promoting the healthy development of their children. Non-pharmacologic care for the infant with NAS/NOWS is the first line of treatment and of paramount importance. Yet, current approaches are based on a limited scope of infant functioning, and the scoring systems in current use do not result in individualized and specific non-pharmacologic care of the infant, which can result in excessive or insufficient medication and a lack of caregiver appreciation for the infant's strengths, difficulties and early development. The interventions described here are based on the infant's signs of dysregulation in four neurobehavioral subsystems that can be dysregulated by NAS/NOWS, the infant's adaptive or maladaptive responses to return to a regulated functioning, and the co-regulatory behaviors of the infant and the mother/caregiver. In Part I of this two-part series on re-conceptualizing non-pharmacologic care for NAS/NOWS we laid the foundation for a new treatment approach, one grounded in developmental theory and evidence-based observations of infant and interpersonal neurobiology. Here, in Part II, we outline actionable, individually tailored evaluations and approaches to non-pharmacologic NAS/NOWS treatment based on strategies to support the regulatory capacities and development of 4 key domains: 1) autonomic; 2) motor/tone; 3) sleep/awake state control; and 4) sensory modulation subsystems.

Maternal Poppy Seed Tea Ingestion and Ensuing Neonatal Abstinence Syndrome.

The incidence of neonatal abstinence syndrome has been rising in the USA. Nonpharmacological treatments resulting in similar withdrawal states in the newborn have also been described. We report an infant with neonatal abstinence syndrome born to a mother with daily poppy seed tea ingestion for the self-treatment of nausea. A sample of poppy seed tea was replicated using the mother's self-reported recipe. The sample was analyzed using liquid chromatography tandem mass spectrometry. This recipe produced a result of approximately 7.8 mg of morphine per serving which she reported to have drank 5-6 days per week, for an estimated 7 months during the course of her pregnancy.

Neonatal Abstinence Syndrome: Advances in Diagnosis and Treatment.

IMPORTANCE: Neonatal abstinence syndrome, which occurs as a result of in utero opioid exposure, affects between 6.0 and 20 newborns per 1000 live US births. There is substantial variability in how neonatal abstinence syndrome is diagnosed and managed. OBJECTIVE: To summarize key studies examining the diagnosis and management (both pharmacologic and nonpharmacologic) of neonatal abstinence syndrome published during the past 10 years. EVIDENCE REVIEW: PubMed, Web of Science, and CINAHL were searched for articles published between July 1, 2007, and December 31, 2017. Abstracts were screened and included in the review if they pertained to neonatal abstinence syndrome diagnosis or management and were judged by the authors to be clinical trials, cohort studies, or case series. FINDINGS: A total of 53 articles were included in the review, including 9 randomized clinical trials, 35 cohort studies, 1 cross-sectional study, and 8 case series-representing a total of 11 905 unique opioid-exposed mother-infant dyads. Thirteen studies were identified that evaluated established or novel neonatal abstinence syndrome assessment methods, such as brief neonatal abstinence syndrome assessment scales or novel objective physiologic measures to predict withdrawal. None of the new techniques that measure infant physiologic parameters are routinely used in clinical practice. The most substantial number of studies of neonatal abstinence syndrome management pertain to nonpharmacologic care-specifically, interventions that promote breastfeeding or encourage parents to room-in with their newborns. Although these nonpharmacologic interventions appear to decrease the need for pharmacologic treatment and result in shorter hospitalizations, the interventions are heterogeneous and there are no high-quality clinical trials to support them. Regarding pharmacologic interventions, only 5 randomized clinical trials with prespecified sample size calculations (4 infant, 1 maternal treatment) have been published. Each of these trials was small (from 26 to 131 participants) and tested different therapies, limiting the extent to which results can be aggregated. There is insufficient evidence to support an association between any diagnostic or treatment approach and differential neurodevelopmental outcomes among infants with neonatal abstinence syndrome. CONCLUSIONS AND RELEVANCE: Evidence pertaining to the optimal diagnosis and treatment strategies for neonatal abstinence syndrome is based on small or low-quality studies that focus on intermediate outcomes, such as need for pharmacologic treatment or length of hospital stay. Clinical trials are needed to evaluate health and neurodevelopmental outcomes associated with objective diagnostic approaches as well as pharmacologic and nonpharmacologic treatment modalities.

Tailoring a NICU-Based Tobacco Treatment Program for Mothers Who Are Dependent on Opioids.

OBJECTIVE: To collect formative information to design a tailored tobacco treatment intervention for women with newborns treated or evaluated for neonatal abstinence syndrome and to explore current tobacco use behaviors and facilitators and barriers to smoking cessation. DESIGN: Qualitative descriptive study. SETTING: An academic medical center in the southern United States. PARTICIPANTS: Mothers (N = 11) of newborns who were treated or evaluated for neonatal abstinence syndrome at birth within the preceding 3 months. Women recruited were older than 18 years and reported opioid dependence and smoking during pregnancy. METHODS: Participants took part in semistructured individual interviews that lasted approximately 1 hour. Interviews were professionally transcribed and analyzed in MAXQDA using content analysis. RESULTS: Five themes emerged from the data: Strategizing to Reduce Risk, Desire to Quit Smoking in the Future, Holding on to Smoking While Working Through Recovery, Feeling Judged by Nurses, and Feeling Supported and Empowered by Nurses. Participants reported that they to reduce risk to their newborns by avoiding second- and thirdhand smoke exposure. Participants wanted to stop smoking but reported many barriers, including multiple life stressors compounded by their newborns' extended stays in the hospital. However, most participants described overall positive experiences and the support of health care providers. CONCLUSION: Holistic tobacco treatment programs that incorporate stress relief and social support and are led by trusted health care providers have the potential to be effective to reduce smoking in new mothers with histories of opioid dependence disorders and smoking and whose newborns are in the NICU.

Measurement of neonatal abstinence syndrome: Evaluation of short forms.

OBJECTIVES: 1) How well do the short forms previously developed from the Maternal Opioid Treatment: Human Experimental Research (MOTHER) neonatal abstinence syndrome (NAS) scale (MNS) discriminate between neonates untreated and treated for NAS? (2) Can a short form be developed that is superior to other short forms in discriminating between the two groups? DESIGN/PARTICIPANTS: This secondary analysis study used data from 131 delivered neonates in the MOTHER study, a randomized controlled trial comparing neonatal and maternal outcomes in opioid-dependent pregnant women administered buprenorphine or methadone. SETTING: Comprehensive care was provided at seven university hospitals. OUTCOME MEASURES: A 19-item instrument measuring neonatal abstinence signs. RESULTS: A five-item index proved superior to the previous indices (ps < 0.01) and discriminated between the treated and untreated NAS groups as well as did the MNS total score (p=0.09). CONCLUSIONS: A short form developed from the MNS shows promise as a possible screening measure.

Development of auditory event-related potentials in infants prenatally exposed to methadone.

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.

Neonatal opiate withdrawal and rooming-in: a retrospective analysis of a single center experience.

AIM: To evaluate our treatment of neonatal abstinence syndrome (NAS), our experience with rooming-in of opiate-dependent mothers and to examine the influence of rooming-in on short term outcome of infants exposed to opiates in utero. METHOD: Retrospective analysis of maternal and perinatal data of newborn infants with NAS treated between 2004 and 2011 in a level 3 academic children's hospital in a German metropolis. Therapy of NAS and duration of therapy, length of hospital stay and costs were considered in particular. FINDINGS: Data of 77 newborns with NAS were analysed. 84.6% of infants were treated with tincture of opium (79.2% rooming-in, 88.7% no rooming-in). Infants with rooming-in (n=24) had a 17% shorter median duration of therapy [27.0 d (IQR 24.0-38.5), no rooming-in (n=53) 32.5 d (IQR 25.0-54.5)] and shorter median length of hospital stay [33.0 d (IQR 28.0-48.0), no rooming-in 41.5 d (IQR 30.3-54.5)]. Demographic data was comparable between newborns and mothers with or without rooming-in. Costs were median 13 457 € (IQR 8 967-17 494)/patient [rooming-in: 9 547 € (IQR 7 024-16 135), no rooming-in: 14 486 € (IQR 9 479-19 352)]. CONCLUSIONS: Rooming-in in NAS should be encouraged to shorten duration of therapy and length of hospital stay and thereby reduce costs. No major problems arose in the care of the infants with NAS when parents stayed with their infants but close monitoring of the newborn and strict instruction of parents are required.

Use of tincture of opium compared to oral morphine for the treatment of neonatal abstinence syndrome.

OBJECTIVE: To evaluate the difference in time until medical clearance when comparing tincture of opium (TO) to oral morphine (OM) in the treatment of neonatal abstinence syndrome (NAS). DESIGN: Retrospective chart review conducted from May 2007 to July 2011. SETTING: Level III Neonatal Intensive Care unit at Morristown Medical Center in Morristown, New Jersey. PATIENTS, PARTICIPANTS: Clinical Drug Utilization reports identified 26 neonates who were treated with TO and 25 neonates who were treated with OM for NAS. No patients were excluded. INTERVENTIONS: Patients were treated with either TO or OM for the indication of NAS. MAIN OUTCOME MEASURE(S): The primary outcome is to compare the time it takes for a baby being treated with TO versus OM for NAS to be medically cleared for discharge. RESULTS: The median time until medical clearance for those treated with TO was 29.5 days compared to 37 days for those treated with OM (p = 0.14). CONCLUSION: There was no statistically significant difference in the time it takes for a baby being treated with TO versus OM for NAS to be medically cleared for discharge. There are a number of safety benefits in using OM compared to TO. Until further data are collected, it is appropriate to continue treatment of neonates with NAS with OM.

[Symptoms of neonatal abstinence syndrome. Case report]. / Zespól objawów glodu narkotycznego u noworodka. Opis przypadku.

A case of the neonatal narcotic abuse syndrome is presented. A newborn baby additionally suffered from the congenital infection. Marked symptoms of narcotic withdrawal required an administration of the opiates and tranquillizers for three weeks.