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Objective: Laryngomalacia (LM) is the most common congenital anomaly of the larynx. The cause of LM is still largely unknown, but a neurological mechanism has gained the most acceptance. There have not been any studies examining the prevalence of LM in infants with Neonatal Abstinence Syndrome (NAS). The aim of our study is to determine if infants with NAS are more likely to be diagnosed with LM. Methods: This study was a population-based inpatient registry analysis. We examined nationwide neonatal discharges in 2016 using the Kids’ Inpatient Database (KID). Only patients listed as neonates were included. The International Classification of Diseases, 10th revision, Clinical Modification (ICD-10-CM) codes for neonatal withdrawal symptoms from maternal use of drugs of addiction (P96.1) and diagnoses denoting LM were used. To quantify associations between the LM and NAS groups, prevalence rates and odds ratios (ORs) were used. Results: There were 3 970 065 weighted neonatal discharges in the 2016 KID. Among patients included in our dataset, 0.809% (32 128) had NAS and 0.075% (2974) had LM. There was an increased odds ratio for neonates with NAS and LM (OR of 2.85, 95% CI = 2.24-3.63) compared to infants without NAS. Multiple logistic regression accounting for possible confounders produced an adjusted OR of 1.68 (95% CI = 1.29-2.19). Conclusion: Our study found an association between NAS and LM. This suggests that prenatal exposure to opioids or possibly the sequelae of withdrawal symptoms may be risk factors for the development of LM.

Care for pregnant patients with substance use disorder must be provided in a nonjudgmental manner with recognition of addiction as a chronic medical illness in order to establish a therapeutic relationship and improve outcomes. All pregnant patients should be screened for substance use during prenatal care. Screening can be accomplished through several validated screening tools. Patients who screen positive need to be evaluated and referred for treatment as appropriate. This article reviews specific adverse perinatal outcomes associated with the use of a variety of substances and provides guidance on exposure with continued breastfeeding.

Serotonin discontinuation syndrome (SDS) can result in a constellation of symptoms exhibited by infants exposed to selective serotonin reuptake inhibitors or other psychotropic drugs during pregnancy. Currently, there is no consensus regarding the pharmacologic management of SDS. We report our experience with clonidine for the management of a term infant with poor neonatal adaption. The infant exhibited biphasic symptoms of acute toxicity at birth and a plateauing of symptoms, followed by subsequent withdrawal symptomatology requiring the use of clonidine in doses up to 4 mcg/kg/dose every 3 hours for control of symptoms. The 38-week gestation Caucasian male infant was born to a mother with major depressive disorder, which was managed with sertraline, trazodone, venlafaxine, and buspirone throughout her pregnancy. The infant exhibited severe hypertonia at delivery and continued to have hypertonia, tremors, hypoglycemia, and feeding issues upon admission to the NICU. The initial Modified Finnegan Neonatal Abstinence scores were extremely elevated, and clonidine was started at 1 mcg/kg/dose every 3 hours and then the dose was titrated up to 4 mcg/kg/dose. This is the first report documenting the use of clonidine to manage serotonin toxicity at birth followed by subsequent neonatal withdrawal associated with maternal antidepressant drug use during pregnancy.

Neonatal abstinence syndrome (NAS), a constellation of predominantly autonomic, neurological and gastrointestinal symptoms, is caused by neonatal withdrawal from in utero exposure of maternal misuse of illicit or prescribed drugs. The severity of NAS depends on time, type and combination of drugs taken and the feto-maternal metabolic rate. The physical and psychological consequences of NAS are manifold, contributing to the difficulty in its diagnosis and management. Most babies exposed to opioids in utero require some form of treatment, either supportive or pharmacological treatment. Treatment is guided using standardised clinical scoring systems the most common being the Modified Finnegan Score. Although NAS is diagnosed clinically other possible diagnoses must be considered and toxicological confirmation is often helpful. The long-term neurodevelopmental side effects of NAS are yet to be fully explored. Early multidisciplinary intervention is required, and family integrated care should be actively encouraged. This paper summarises the symptomatology, investigations and current proposed management of NAS.

Introduction: A clear picture of neonatal withdrawal signs due to in utero selective serotonin reuptake inhibitor (SSRI) exposure and its consequences is still missing. Objective: A systematic review and a meta-analysis were performed to provide an overview of neonatal withdrawal signs following late in utero exposure to SSRIs and to quantify the corresponding risks. Methods: MEDLINE, Web of Science, and Embase were searched from inception to January 2021. The Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed. English-language observational studies reporting on acute postpartum outcomes following late in utero exposure to SSRIs or SSRIs/venlafaxine were evaluated. Results: Of 2,269 citations reviewed, 79 studies were assessed for eligibility; 13 were included in the qualitative analysis of the literature, which allowed us to identify 26 signs. A meta-analysis was run separately for studies on SSRI exposure (n = 3) and those on SSRI/venlafaxine exposure (n = 6). Hypoglycemia was identified as a withdrawal sign based on the SSRI studies. Tremors, hypotonia, tachycardia, rapid breathing, respiratory distress, and hypertonia were identified as withdrawal signs based on the SSRI/venlafaxine studies. Conclusions: The present work provides a framework for the identification of neonatal SSRI withdrawal syndrome. Tapering and discontinuation of antidepressant drugs before and during the early phase of pregnancy are worth attempting to prevent the occurrence of this syndrome.

Objectives Neonates delivered by women who were taking psychotropic or anticonvulsant drugs during pregnancy are at increased risk of developing neonatal withdrawal syndrome. We investigated the incidence of neonatal withdrawal symptoms and the effects of multiple maternal medications and breastfeeding on neonatal withdrawal symptoms. Study Design This study examined the overall incidence of neonatal withdrawal symptoms in neonates delivered from 2004 to 2016 by women who were taking oral antipsychotics, antidepressants, anxiolytics, sedatives, or anticonvulsant drugs during pregnancy. Moreover, we compared the incidence of neonatal symptoms between mothers taking single drugs and multiple drugs, and between breastfed and formula-fed neonates. We scored the neonates according to the neonatal withdrawal syndrome checklist created by Isobe et al., which is widely used in Japan. Results We examined 131 mothers and their 134 neonates. Withdrawal symptoms were found in 54.5 % of neonates. Symptoms were found in 32.4 % of neonates delivered by mothers taking single drugs and 62.9 % of neonates delivered by mothers taking two or more drugs (p = 0.0019). One or more withdrawal symptoms developed in 46.4 % of breastfed neonates and 66.1 % of formula-fed neonates (p = 0.034). Five infants had a score of 8 or more points on the withdrawal checklist, which is an indication to consider treatment with pharmacotherapy. All five of these neonates were mainly formula-fed, and their mothers were taking two or more drugs. Conclusions The incidence of withdrawal symptoms was high in neonates delivered by women taking psychotropic or anticonvulsant drugs; however, there were few serious cases. The risk increased when a mother was taking multiple drugs. Breastfeeding appeared to protect against withdrawal symptoms.

Purpose of ReviewThis review describes case reports for patients with kratom-associated adverse events in order to assist clinicians with patient management. A stepwise approach is proposed for assessing active kratom users as well as considerations for the management of toxicities or withdrawal.Recent FindingsMultiple in vitro and in vivo studies illustrate the pharmacologic and toxicologic effects of kratom extract. No randomized controlled trials in humans exist that assess the safety and efficacy of the substance. Cross-sectional surveys from active users and reports from poison control centers have shown acute and chronic physiological and psychological adverse events.SummaryReports of adverse effects associated with kratom use have demonstrated hypothyroidism, hypogonadism, hepatitis, acute respiratory distress syndrome, posterior reversible encephalopathy syndrome, seizure, and coma. Overdose toxidrome leads to respiratory failure, cardiac arrest, and fatalities. Adult and neonatal withdrawal symptoms have also occurred. Clinicians should be aware of the risks and benefits of kratom use.

The incidence of neonatal abstinence syndrome (NAS), a withdrawal syndrome associated with prenatal opioid or other substance exposure (1), has increased as part of the U.S. opioid crisis (2). No national NAS surveillance system exists (3), and data about the accuracy of state-based surveillance are limited (4,5). In February 2018, the Pennsylvania Department of Health began surveillance for opioid-related NAS in birthing facilities and pediatric hospitals* (6). In March 2019, CDC helped the Pennsylvania Department of Health assess the accuracy of this reporting system at five Pennsylvania hospitals. Medical records of 445 infants who possibly had NAS were abstracted; these infants had either been reported by hospital providers as having NAS or assigned an International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) hospital discharge code potentially related to NAS.† Among these 445 infants, 241 were confirmed as having NAS. Pennsylvania's NAS surveillance identified 191 (sensitivity = 79%) of the confirmed cases. The proportion of infants with confirmed NAS who were assigned the ICD-10-CM code for neonatal withdrawal symptoms from maternal use of drugs of addiction (P96.1) was similar among infants reported to surveillance (71%) and those who were not (78%; p = 0.30). Infants with confirmed NAS who were not assigned code P96.1 typically had less severe signs and symptoms. Accurate NAS surveillance, which is necessary to monitor changes and regional differences in incidence and assist with planning for needed services, includes and is strengthened by a combination of diagnosis code assessment and focused medical record review.

Background and PurposeGlobally, five million women are affected by opioid use disorder (OUD). Women with OUD are less likely to breastfeed than the general population, increasing risk of neonatal withdrawal. Theoretical frameworks related to breastfeeding did not address women with OUD. The purpose of this study was to develop a conceptual model to better understand breastfeeding disparities among this vulnerable population.MethodsA grounded theory study was conducted from August 2018 to March 2019 to investigate concepts likely to influence breastfeeding decisions in women with OUD. In-depth interviews were conducted in North Carolina with 10 women in recovery who breastfed, and their six identified support persons. Data were analyzed through iterative coding. This article focuses on maternal perspectives of breastfeeding informed by support persons.ResultsThe overarching theme was breastfeeding decision-making in an addiction trajectory. Two antecedent pathways led to the recovery–relapse cycle. This cycle involved seeking, initiating, and maintaining recovery with episodic relapse. Perceived stigma linked the recovery–relapse cycle with breastworks. Breastworks, an emergent concept, was characterized by learning and knowing, good intentions, and health-care provider sensitivity.Implications for PracticeThis grounded theory model may inform clinicians in caring for women with OUD and support breastfeeding and newborn well-being. Strategies to address research and practice may include the development of a mobile application, having women in recovery on the health-care team, and incorporation of breastfeeding guidelines.

Neonatal opioid dependence is an enormous and growing medical challenge. Newborns exposed to prenatal opioids often experience intense postnatal withdrawal after cessation of the opioid, called neonatal opioid withdrawal syndrome (NOWS). They may also show delays in developmental milestones. Thus, a pharmacotherapy that could be delivered in conjunction with a prenatal opioid, and that could prevent fetal opioid dependence without interfering with pain or opioid use management of the mother, would be highly desirable. In a prior study in mice we demonstrated that the peripherally selective neutral opioid antagonist, 6β-naltrexol (6BN), has properties that make it a promising candidate for such an approach. In the current work we extend our studies of 6BN to pregnant guinea pigs, which are a more suitable model than mice and rats, and allows for the detection of robust spontaneous neonatal withdrawal. We find that prenatal methadone (MTD) significantly aggravates two classic maternal separation stress behaviors in newborn guinea pigs: calling (vocalizing) and searching (locomotion) - natural attachment behaviors thought to be controlled by the endogenous opioid system. In addition, prenatal MTD significantly increases the levels of plasma cortisol in newborns exposed to maternal separation stress, showing that cessation of MTD at birth engages the hypothalamic-pituitary-adrenal (HPA) axis. Most importantly, our work shows that 6BN can prevent all these effects of prenatal methadone with high potency (50% inhibitory dose, ID50, of ~0.02 mg/kg), at doses unlikely to induce maternal withdrawal or to interfere with opioid analgesia based on many prior published studies. This potency is surprising in the face of both the long half-life of methadone and our pharmacokinetic (PK) studies showing slow placental transit of 6BN in guinea pigs. Furthermore, we demonstrate an unexpectedly high potency of 6BN in preventing opioid withdrawal in adult guinea pigs (ID50 = 0.01 mg/kg), in spite of the fact that our PK data in both mice and guinea pigs show the relative exclusion of 6BN from the adult CNS, presumably by virtue of the blood brain barrier and associated extrusion pumps. Thus, novel opioid receptor mechanisms may need to be hypothesized to account for the high potency of 6BN for preventing opioid withdrawal. In conclusion, 6BN is an attractive compound for development of a preventive therapy for NOWS, and guinea pigs are an ideal model to further test it.

BACKGROUND: Most studies examining the relationship between neonatal abstinence syndrome (NAS) and health insurance status in the United States (USA) have used administrative insurance claims data, which is subject to myriad limitations. We examined the association between NAS and health insurance status in a large geographically defined rural population in the United States, using non–claims data. METHODS: We utilized data from a population-based cohort of all newborns born in 2017–2019 in the rural state of West Virginia (WV) and restricted analyses to WV residents’ births (n = 46 213). NAS was defined as neonatal withdrawal from many substances, including opiates and not limited to those cases that require pharmacological treatment. RESULTS: Medicaid covered more than half (52.6%) of all infants’ births in the state of WV. The incidence of NAS was 85.8 and 12.7 per 1000 livebirths in the Medicaid and privately insured groups, respectively. Among all infants diagnosed with NAS, 86.1% were enrolled in the state’s Medicaid programme. The risk of NAS in the Medicaid-insured newborns was higher than privately insured newborns in the unadjusted analysis (risk ratio (RR) 6.76, 95% confidence interval (CI) 5.95, 7.68) and the adjusted analysis (RR 3.00, 95% CI 2.01, 4.49); adjusted risk difference 20.3 (95% CI 17.5, 23.1 cases per 1000 livebirths). CONCLUSIONS: NAS is an important indicator of the immediate effect of the opioid crisis. This study shows the disparity in NAS by health insurance status for a large rural population in the United States, and its burden on the state’s Medicaid programme. Providing timely and accurate estimates of NAS is important for public health policies and decision making.

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.

Chronic prenatal exposure to opioids often causes fetal opioid dependence that leads to neonatal opioid withdrawal syndrome (NOWS) shortly after delivery. Rat models of NOWS often require quantifying neonatal withdrawal behaviors using time-consuming, labor-intensive manual scoring methods. The goal of this study was to automate quantification of opioid withdrawal in neonatal rat pups. Accordingly, we used the animal behavior software Ethovision® XT to analyze archived videos of rat pups subjected to precipitated opioid withdrawal testing on postnatal day 0. We compared results obtained from Ethovision® XT with those previously obtained from manual scoring. Two endpoints reported by Ethovision® XT, Distance Moved (cm) and Movement Duration (s), had strong positive linear relationships with manually derived global withdrawal scores (GWS; R2 > 0.73). Sensitivity and specificity of each endpoint to discriminate presence and absence of low-grade withdrawal were assessed by receiver operator characteristic curve analysis, which indicated that Distance Moved and Movement Duration had excellent accuracy (AUC > 0.90). Finally, we analyzed main and interaction effects of prenatal treatment (with vehicle or mu opioid receptor full agonists) and postnatal challenge (with saline or an opioid receptor antagonist) on each endpoint and determined they were similar for the manual and automated methods. These results show that Ethovision® XT software can reliably quantify opioid withdrawal in neonatal rat pups with non-inferiority to manual scoring even in videos that were not originally purposed and optimized for Ethovision® XT analysis. This faster and less labor-intensive method of analysis is expected to accelerate progress in preclinical studies of NOWS.

Neonatal withdrawal can be difficult to treat in infants with co-exposure to opiates and gabapentin. Because maternal self-report can underestimate exposures, we evaluated the effect of universal toxicology screening for gabapentin. Identification of co-exposure to opiates and gabapentin increased after implementation of toxicology screening, with implications for improved neonatal care.

PurposeTo compare the effects of morphine and methadone on length of hospital stay (LOS) or treatment (LOT) and adverse effects in infants with neonatal abstinence syndrome (NAS).DesignSystematic review.SamplePubMed, Google Scholar, Cochrane library, CINAHL, IPA, American Academy of Pediatrics, and clinicaltrials.gov were systematically searched to identify randomized controlled trials (RCTs) and observational studies. comparing morphine and methadone for NAS.OutcomesLOS, LOT, adverse effects.ResultsOne RCT, two cohort studies, and two chart reviews met inclusion criteria. Each had a low risk of bias. LOS ranged from 12.08 to 36 days with morphine and 21 to 44.23 days with methadone. LOT ranged from 7.46 to 22.9 days (morphine) and 13.9 to 38.08 days (methadone). Adverse effects were not reported. Clinical evidence comparing morphine to methadone for NAS treatment is limited and conflicting. A recommendation for one over the other cannot be made based on these outcomes.

Background: Breastfeeding rates are typically low for women with a substance-use disorder. This is despite the specific benefits of breastfeeding to alleviate the severity of neonatal abstinence syndrome and the well-documented generic advantages. This study explored the feasibility of in-hospital, tailored breastfeeding support for the substance-exposed mother and baby. Methods: This was a mixed-methods feasibility study undertaken in Scotland from April 2014 to May 2015. Women with a substance-use disorder either received standard Baby-Friendly Initiative care only or were given additional support which included a dedicated breastfeeding support worker, personalized capacity-building approach, and a low-stimuli environment for 5 days. Feasibility outcome measures were maternal recruitment, satisfaction and acceptability of support, breastfeeding on fifth postnatal day, and severity of neonatal abstinence syndrome. Results: Fourteen mother-infant dyads participated. Intervention participants demonstrated higher rates of continued breastfeeding and reported a greater degree of satisfaction with support and confidence in their breastfeeding ability. Maternal experience of health care practices, attitudes, and postnatal environment influenced their perceptions of breastfeeding support. Breastfed infants were less likely to require pharmacotherapy for neonatal withdrawal and had a shorter hospital stay. Conclusions: The findings highlight the feasibility of tailored breastfeeding support for the substance-exposed mother and baby and endorse the promotion and support of breastfeeding for this group. Future research should include a statistically powered randomized controlled trial to evaluate clinical efficacy. Refereed/Peer-reviewed

Infants have the highest rates of maltreatment reporting and entries to foster care. Prenatal substance exposure is thought to contribute to early involvement with child protective services (CPS), yet there have been limited data with which to examine this relationship or variations by substance type. Using linked birth, hospital discharge, and CPS records from California, we estimated the population prevalence of medically diagnosed substance exposure and neonatal withdrawal disorders at birth. We then explored the corresponding rates of CPS involvement during the first year of life by substance type after adjusting for sociodemographic and health factors. Among 551,232 infants born alive in 2006, 1.45% ( n = 7994) were diagnosed with prenatal substance exposure at birth; 61.2% of those diagnosed were reported to CPS before age 1 and nearly one third (29.9%) were placed in foster care. Medically diagnosed prenatal substance exposure was strongly associated with an infant’s likelihood of being reported to CPS, yet significant variation in the likelihood and level of CPS involvement was observed by substance type. Although these data undoubtedly understate the prevalence of prenatal illicit drug and alcohol use, this study provides a population-based characterization of a common pathway to CPS involvement during infancy. Future research is needed to explicate the longer-term trajectories of infants diagnosed with prenatal substance exposure, including the role of CPS.

In recent years, the clinical definition of neonatal abstinence syndrome (NAS) has been expanded to describe neonates experiencing withdrawal due to in utero exposure to numerous neuroactive substances, not exclusively opioids. Complex NAS cases involving exposure to multiple and unusual narcotics have become widespread. Kratom is one such substance. It is extracted from tropical tree leaves, and can be used both as a recreational drug and to mitigate opioid withdrawal. Although kratom may potentially serve as a viable opioid alternative, its activity and the consequences of controlled use are largely unstudied, particularly in the pregnant population. A newborn male infant was not initially identified as being at risk for withdrawal due to no maternal admission of substance use and maternal urine drug screen was negative. On the first day of life (DOL), the neonate was observed to exhibit significant signs of withdrawal including high-pitched crying, facial grimacing, irregular respiratory pattern, mottling, and mild undisturbed tremors. Upon interview with the mother it was noted that there was heavy caffeine use, daily cigarette smoking, daily use of the “herbal alternative” (kratom) throughout the pregnancy. In this report, we present a case of NAS precipitated by in utero exposure to kratom, discuss the present body of research regarding kratom and consider potential implications of escalating kratom use on the incidence and severity of NAS. For this prenatally exposed neonate, clonidine was successfully used to control withdrawal symptoms. Int J Clin Pediatr. 2018;7(4):55-58 doi: https://doi.org/10.14740/ijcp317w

Background Neonatal abstinence syndrome (NAS) is a postnatal withdrawal syndrome that most commonly results from prenatal opioid exposure. Every 15 minutes, an infant is born in the United States with signs of NAS. The field lacks a standardized clinical definition of NAS, complicating discussions on programmatic and policy development to support opioid-exposed mothers and infants. Objective The goal of this paper is to describe a protocol for a systematic expert panel process to inform the development of a clinical definition of NAS. Methods We will conduct two three-round online modified-Delphi panels using the ExpertLens system and will follow the recommendations for Conducting and REporting of DElphi Studies (CREDES). One panel will focus on developing key components of a clinical definition of NAS, and the second panel will focus on neonatal opioid withdrawal syndrome (NOWS), which is a term that has come into use to differentiate opioid-exposed infants from infants exposed to other substances in utero. However, there is lack of agreement on the precise clinical definition of NOWS and how it is distinct from or overlaps with NAS. Each panel will complete two rating rounds and a discussion round using a similar protocol. We will analyze all rating data descriptively and determine the presence of agreement within and between the two panels. We will also perform thematic analysis of the qualitative comments to contextualize the panel findings. Results The panels were convened between October 29 and December 17, 2020. Their results were disseminated and discussed at a national conference on NAS that took place on March 17-18, 2021. Conclusions A standardized clinical definition of NAS will help to better characterize NAS incidence and to design effective clinical, public health, and policy interventions to support opioid-exposed mother-infant dyads. International Registered Report Identifier (IRRID) DERR1-10.2196/25387

Opioid use and abuse have skyrocketed in the United States over the last decade. As a result, we have seen a substantial increase in neonates who are exposed to opioids in-utero. Anywhere from 55% to 94% of infants exposed to opioids will experience withdrawal, known as neonatal abstinence syndrome (NAS), and will require management of their symptoms in the hospital. It is important to know what to look for in an infant who is experiencing NAS, how to determine if treatment is needed and what type of treatment is indicated, and how to prepare the infant for discharge once they are stable. Unfortunately, there are no standardized care plans in place for the management of this population. Although assessment tools such as the Finnegan scoring systems are available, they are not validated and can be cumbersome and difficult to administer. Other methods of assessment are being studied and may prove to be more useful in the clinical setting of neonatal withdrawal. Neither nonpharmacologic nor pharmacologic interventions are standardized, with individual institutions determining their plan of care. Development of more standardized care could significantly improve the management of these patients. [ Pediatr Ann . 2020;49(1):e3–e7.]

The opioid crisis in Canada is a complex issue with devastating consequences for individuals, families and communities. Pan-Canadian data that provide a better understanding of the crisis are a high priority to help guide efforts for reducing opioid-related harms. The objective of this study is to summarize recent trends of opioid-related harms and opioid prescribing across Canada. Opioid-related harms examined in this study include opioid poisonings, opioid use disorders, adverse reactions to opioids and infants born with neonatal withdrawal symptoms. Data are reported at the pan-Canadian, provincial and community levels.

To describe longitudinal health care utilization of Medicaid-insured children with a history of neonatal abstinence syndrome (NAS) compared with similar children without NAS.Retrospective, longitudinal cohort study. Data were extracted from the Medicaid Analytic eXtract files for all available states and DC from 2003-2013. Subjects were followed up to 11 years. In total, 17 229 children with NAS were identified using the International Classification of Diseases, Ninth Revision code 779.5. Children without NAS, matched on demographic and health variables, served as the comparison group. Outcomes were number of claims for inpatient, outpatient, and emergency department encounters, numbers of prescription claims, and costs associated with these services. Linked claims were identified for each subject using a unique, within-state ID.Children with NAS had increased claims for inpatient admissions (marginal effect [ME] 0.49; SE 0.01) and emergency department visits (ME 0.30; SE 0.04) through year 1; increased prescriptions (ME 1.45; SE 0.08, age 0) (ME 0.69; SE 0.11, age 1 year) through year 2; and increased outpatient encounters (ME 20.13; SE 0.54, age 0) (ME 3.95; SE 0.62, age 1 year) (ME 2.90; SE 1.11, age 2 years) through year 3 after adjusting for potential confounders (P .01 for all). Beyond the third year, health care utilization was similar between those with and without NAS.Children with a diagnosis of NAS have greater health care utilization through the third year of life. These differences resolve by the fourth year. Our results suggest resolution of disparities may be due to shifts in developmental health management in school-age children and inability to track relevant diagnoses in a health care database.

Objective: Maternal drug abuse may influence neonatal outcomes. We compared neonatal outcomes of patients with urine screened positive for commonly abused drugs (CAD) versus those who were screened negative, and reviewed the pattern of drugs detected at a university teaching hospital. Methods: Urine samples collected from babies with suspected illicit drug exposure who were admitted to the neonatal unit were sent for comprehensive drug screen (CDS) performed by liquid chromatographytime- of-flight mass spectrometry (LC-TOF/MS). The screening library can detect more than 300 drugs and their metabolites. Fluorescence polarization immunoassay (FPIA) was also used to screen for cannabinoids which were not detected by the present LC-TOF/MS method. Symptoms suggestive of drug exposure and history of maternal substance misuse were recorded. Results: Commonly abused drugs (CAD) including methadone, morphine, codeine, methamphetamine, ketamine, midazolam and heroin were present in the urine specimens of 46 (24.2%) of 190 neonates. Eighty-one (42.6%) urine samples screened positive for other drugs, which include antibiotics, lidocaine and pethidine administered during delivery. Drugs were undetectable in 33.2% samples. Urine positive for CAD was independently associated with maternal history of substance misuse (p

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.

Drug involvement in child maltreatment may reveal itself in any of the classical syndromes of sedative, stimulant or opioid intoxication, in diagnostically challenging drug-induced factitious illness or in cryptic illnesses consequent on designer drug exposure. The primary drug user may be the parent, with consequences for the child that include fetal alcohol spectrum disorder, neonatal withdrawal syndromes and abuse and neglect by an intoxicated, psychiatrically disturbed parent. Malicious intent may underlie drug-related death in childhood. Identifying the culprit drug requires that drug causation is suspected early, followed by timely collection of appropriate specimens. Positive identification provides proof on which to build the medical, social and legal management of the child and family. This is particularly important in managing the defensiveness and rehabilitation needs of drug- or alcohol-impaired parents.

Parenting: attachment, separation and loss Transition to extrauterine life Newborn screening and immunization Examination of the newborn Hereditary problems and genetics Infant feeding Neonatal skin care Thermal care of the newborn Care of the jaundiced baby Infection in the newborn period Neonatal respiratory problems Neonatal withdrawal syndromes Birth injury Cultural and religious aspects of neonatal care Teaching resuscitation to parents Frequently asked questions

Objective To describe healthcare use over time of children with a history of neonatal abstinence syndrome (NAS) compared with children without NAS. Study design In this retrospective, longitudinal cohort study, data were obtained from MarketScan Commercial Claims and Encounters database from 2005 to 2014. Children with and without NAS based on International Classification of Diseases, Ninth Revision diagnostic codes were followed until 8 years or disenrollment (mean: 35 months). Numbers of claims for inpatient, outpatient, and emergency department encounters; prescription drugs; and costs associated with these encounters were evaluated. Results Children with NAS had a significantly greater number of claims per year from age 1 to 8 for inpatient hospitalizations (adjusted mean ratio 3.20; 95% CI 1.74-5.90), outpatient encounters (1.23; 1.08-1.41), and emergency department visits (1.46; 1.25-1.70) after we adjusted for confounders. Subsequently, adjusted mean annualized costs were nearly double for all healthcare services in children with NAS (1.86; 1.34-2.60) and >4 times as high as for inpatient hospitalizations (4.34; 2.03-9.30) compared with children without NAS. Conclusions Children with a diagnosis of NAS have significantly greater rates of healthcare use through age 8 years compared with children without NAS. These findings suggest that children affected by NAS have medical disparities that linger well beyond early infancy.

Drugs can exert major effects on the developing central nervous system (CNS). In the broadest sense, drugs may disturb specific developmental events in the brain and, in turn, produce teratogenic effects. In addition, maternal ingestion of certain drugs can result in passive addiction of the fetus and postnatally lead to a neonatal withdrawal or abstinence syndrome. Although some effects may be transient, most are likely to persist in some form into childhood and adolescence with multiple systems affected spanning cognition, motor function, language, and behavior. This chapter provides a comprehensive overview of the neurological effects of a range of licit and illicit drugs on the infant and growing child. Drugs reviewed include fetal exposure to alcohol, antiepileptic drugs, stimulants, opioids, selective serotonin reuptake inhibitors (SSRIs), sedatives, anesthetics, and marijuana. Clinical considerations in the evaluation and care of the drug-exposed neonate are also discussed.

Objective We aimed to evaluate whether depression in pregnancy in women with opioid dependency negatively impacts adherence with prenatal care. Methods This was a retrospective chart analysis of opioid-dependent pregnant women over a 6-year period at 2 large referral and tertiary care centers. The primary outcome was adherence with prenatal care based on the concurrent diagnosis of depression. Adherence was assessed by looking at the number of observed versus expected prenatal visits. Secondary outcomes included neonatal intensive care unit (NICU) stay, and incidence and severity of neonatal abstinence syndrome (NAS). Results A total of 74 patient charts were reviewed. 45/74 (60.8%) of the opioid-dependent pregnant patients were either diagnosed with depression (n = 41), anxiety (n = 2), or scored >10 on the Edinburgh Prenatal Depression Scale (n = 1). Patients with a diagnosis of depression were significantly less adherent with prenatal care; 80% adherent (73% vs 93%; P = 0.03), 90% adherent (62% vs 93%; P = 0.003). A higher number of patients in the depression group had an infant treated for withdrawal (62% vs 38%; P = 0.041), and had longer NICU stays (27% vs 21%; P = 0.018). Analysis of the whole cohort of opioid dependent gravidas revealed Buprenorphine maintenance therapy had the lowest mean NAS score 6.5 ± 4.4, compared with methadone maintenance 10.6 ± 3.6, and no maintenance therapy 9.4 ± 4.0 (P = 0.008). Conclusion Depression negatively impacts adherence with prenatal care and was significantly associated with a higher incidence of neonatal withdrawal and longer NICU stays. Buprenorphine therapy had the lowest incidence and severity of NAS when compared with methadone and no maintenance therapy.

Objectives To improve awareness and knowledge of problematic substance use in pregnancy and to provide evidence-based recommendations for the management of this challenging clinical issue for all health care providers. Options This guideline reviews the use of screening tools, general approach to care, and recommendations for the clinical management of problematic substance use in pregnancy. Outcomes Evidence-based recommendations for screening and management of problematic substance use during pregnancy and lactation. Evidence Updates in the literature were retrieved through searches of Medline, PubMed, and The Cochrane Library published from 1996 to 2016 using the following key words: pregnancy, electronic cigarettes, tobacco use cessation products, buprenorphine, and methadone. Results were initially restricted to systematic reviews and RCTs/controlled clinical trials. A subsequent search for observational studies was also conducted because there are few RCTs in this field of study. Articles were restricted to human studies published in English. Additional articles were located by hand searching through article reference lists. Values The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. Recommendations for practice were ranked according to the method described in that report. Benefits, Harms, and Costs This guideline is intended to increase the knowledge and comfort level of health care providers caring for pregnant women who have substance use disorders. Improved access to health care and assistance with appropriate addiction care lead to reduced health care costs and decreased maternal and neonatal morbidity and mortality. Recommendations 1.All pregnant women and women of child-bearing age should be asked periodically about alcohol, tobacco, prescription, and illicit drug use (III-A). 2.When testing for substance use is clinically indicated, urine drug screening is the preferred method (II-2A). Informed consent should be obtained from the woman before maternal drug toxicology testing is ordered (III-B). 3.Policies and legal requirements with respect to drug testing of newborns may vary by jurisdiction, and caregivers should be familiar with the regulations in their region (III-A). 4.Health care providers should employ a flexible and harm reduction approach to the care of pregnant women who use alcohol, tobacco, or drugs. Pregnant women at risk for problematic substance use should be offered brief interventions and referral to community resources for further psychosocial interventions (II-2B). 5.Women should be counselled about the risks of periconception, antepartum, and postpartum substance use (III-B). 6.Health care providers should offer smoking cessation interventions to all pregnant smokers. Psychosocial interventions should be considered first-line (I-A). Nicotine replacement therapy and/or pharmacotherapy can be considered if counselling is not successful (I-A). 7.The standard of care for the management of opioid use disorders during pregnancy is opioid agonist treatment with methadone or buprenorphine. Other sustained-release opioid preparations are also an option if methadone or buprenorphine is not available (I-A). 8.Opioid detoxification should be reserved for selected women because of the high risk of relapse to opioids (II-2B). 9.Opioid-dependent women should be informed that neonates exposed to heroin, prescription opioids, methadone, or buprenorphine during pregnancy are monitored closely for symptoms and signs of neonatal withdrawal (neonatal abstinence syndrome) (II-2B). Hospitals providing obstetric care should develop a protocol for assessment and management of neonates exposed to opioids during pregnancy (III-B). 10.Women who become pregnant while on methadone should continue on methadone maintenance therapy and should not switch to buprenorphine due to the risk of opioid withdrawal (I-A). 11.Women who become pregnant while on buprenorphine/naloxone should be switched to buprenorphine monoproduct. Combination product should be continued until the monoproduct becomes available. Women taking buprenorphine should only switch to methadone if the buprenorphine monoproduct is not accessible and/or the woman feels that she is not responding to the current treatment (II-1A). 12.Health care providers should advise pregnant women to abstain from or reduce cannabis use during pregnancy to prevent negative long-term cognitive and behaviour outcomes for exposed children (II-1A). 13.Antenatal planning for intrapartum and postpartum analgesia may be offered for all women in consultation with appropriate health care providers (III-B). 14.Pregnant women on opioid agonist treatment should be encouraged to breastfeed regardless of the maternal dose, in the absence of an absolute contraindication (II-2B). Women with active substance use should be encouraged to discontinue alcohol or other drug use while breastfeeding, and the risks and benefits of breastfeeding versus breast milk exposure to substances should be discussed (II-2B).

Objective. Compare developmental outcomes in infants treated with morphine versus methadone. Method. Retrospective chart review of newborns identified through use of ICD-9 code for neonatal abstinence syndrome (NAS). Thirty-six infants were evaluated—17 treated with methadone and 19 treated with morphine. Assessment was completed following treatment using the Bayley Scales of Infant and Toddler Development–Third Edition (Bayley-III). Scores in Cognitive, Language, and Motor domains were compared. Results. Comparison of scores between morphine- and methadone-treated groups revealed differences in mean Cognitive Composite (91.3 vs 83.0; P = .03410) and mean Total Motor Composite Scores (96.3 vs 89.6; P = .0149). Conclusion. Newborns with NAS treated with morphine had significantly higher scores in Cognitive and Gross Motor domains compared to infants treated with methadone. Development screening should be pursued to determine if this difference persists throughout early childhood. Results may influence accepted treatment protocols for NAS.

Aims Depression affects 7%–15% of pregnant women. Selective serotonin reuptake inhibitors (SSRIs) are the most commonly used pharmacological treatment, but there are concerns regarding neonatal withdrawal symptoms and an increased risk of persistent pulmonary hypertension of the newborn (PPHN). Our aim was to assess the management of babies born to mothers on SSRIs at our hospital. Methods We retrospectively audited the management of babies born to mothers on SSRIs between August 2015-March 2016. Our audit standard was the hospital guideline which was to observe babies on the postnatal ward for 48–72 hours for signs of withdrawal and to do pre and post ductal oxygen saturations to exclude PPHN. Results A total of 24 babies were identified. Limited data was available for six babies. Table 1 shows the duration of hospital stay, with 91% of babies staying in hospital for at least 48 hours. The most common withdrawal symptoms occurred in the first 24 hours and included tremors/jittery (8 babies), snuffly (8 babies) and vomiting (5 babies). No baby developed significant withdrawal symptoms (defined as Finnegan score >4) or required intervention for withdrawal. Only two babies had both pre and post ductal oxygen saturations recorded before discharge but none of the babies were admited to the neonatal unit with PPHN. Conclusion The majority of babies stayed for a minimum of 48 hours but none developed significant SSRI withdrawal. Following the results of this audit we have proposed a new guideline to monitor babies in hospital for 24 hours and, if asymptomatic at this point, to discharge home with daily community midwife visits until day 3 of life. Further work including making the guideline more accessible and educating midwives is required to ensure pre and post ductal oxygen saturations are done before discharge.