8/27/2018. Katie Brooks, DO, FAAP CHI Health St. Elizabeth. I have nothing to disclose

Transcription

1 Katie Brooks, DO, FAAP CHI Health St. Elizabeth I have nothing to disclose 1

2 Briefly review the history of NAS and current prevalence Understand definition of NAS and which motherbaby dyads should be screened Describe the scoring system used for neonates at risk of NAS Understand the management options for NAS First reported case in 1865 and first treated case in 1903 Not a new problem! Became a national focus in the 1950s 1960s with heroin epidemic In the 1970s methadone became mainstay of treatment for pregnant women with opioid addiction 2

3 Large increase in incidence of maternal use 1.19 per 1000 hospital births in per 1000 hospital births in 2009 As many as 1.1% of pregnant women abused opioids in 2011 Another study found as many as 27 per 1000 NICU admissions in 2009 Up from 7 per 1000 in 2004 Resultant increase in incidence of NAS From 1.2 per 1000 in 2000 to 6 per 1000 in 2012 Most recent data from 23 hospitals, 20 per 1000 in 2016! Wachman et al 2018 Some states have even higher reported cases of maternal use and neonates with NAS Opioid addiction is likely underreported Some states take legal action against pregnant women Women risk losing custody of their infants NAS is often only diagnosed if requiring treatment 3

4 Increased risk of NAS if prenatal exposure > 30 days Increased risk of NAS if late prenatal exposure vs early prenatal exposure 90 days prior to delivery = late exposure Increased risk of NAS if maternal history of Alcohol abuse Exposure to non opioid psychotropic meds Cigarette smoking Desai et al 2015 We don t really know! Recommendations based on use of cocaine during pregnancy Cocaine isn t an opioid! AAP recommends screening in: Absent, late or inadequate prenatal care < 5 visits History of drug abuse Unexplained history of late fetal demise Precipitous delivery Hudak and Tan

5 Placental abruption Hypertensive episodes Severe mood swings Cerebrovascular accidents MI Repeated spontaneous abortions Open CPS cases Women identified by OB as at risk Hudak and Tan 2012 These authors recommend additional groups: Teen pregnancy History of pain syndrome Use of multiple medical providers Positive tox screens during previous pregnancy Clark and Rohan

6 Should be a protocol or guideline to decrease bias Screen should be either from cord or meconium Meconium has a long turn around time ~1 week Unless infant is sick or requires treatment for NAS, is home by 1 week of age If sent to Mayo (from CHI), cord screen turn around is ~48 hrs Choices are urine, meconium, or umbilical cord Should screen mom and baby Meconium is gold standard Collection and testing can be delayed and information from screen is time sensitive Umbilical cord is equivalent in accuracy to meconium Turn around time as fast as 48hours Montgomery et al 2006 Montgomery et al 2008 Marin et al

7 Symptoms in 55 94% of exposed neonates Central nervous system hyperirritability Excessive crying Increased muscle tone Tremors Sleep disturbance Respiratory Distress Gastrointestinal dysfunction Poor feeding Vomiting Diarrhea Autonomic Symptoms Sweating Sneezing Mottling NAS signs and symptoms also described in neonates with prenatal exposure to alcohol, benzodiazepines, and barbituates May require treatment Similar presentation can also be seen in neonates with prenatal exposure to crack/cocaine, marijuana and to SSRIs Do NOT require treatment 7

8 Currently use Finnegan scoring system Most widely used scoring form Validated for methadone exposure May be some differences in onset of symptoms as well as specific symptoms and scores between different opioids Little is truly known about this in neonates Neonates exposed to methadone More likely to have no symptoms compared to buprenorphine exposed Higher scores in hyperactive moro, tremors, failure to thrive and excessive irritability Neonates exposed to buprenorphine More likely to have nasal stuffiness, sneezing and loose stools compared to methadone exposed 8

9 Considered gold standard for NAS scoring 21 Items for 31 possible points Grouped into categories: CNS distubances, metabolic; vasomotor and respiratory disturbances; GI disturbances Modified Finnegan Unclear what the modifications were and all subsequent publications use this form MOTHER NAS scale Used in MOTHER trial and several other clinical trials Similar to Finnegan, few changes Not as widely used Novel approach, simplified assessment Non pharmacologic interventions were first line Fewer infants required pharmacologic treatment 45% reduction in ESC vs Finnegan However, Finnegan scores not used for treatment decisions Same results by another author in secondary analysis 12% in ESC vs 62% with Finnegan Wachman et al 2018 Grossman et al

10 There is a simplified Finnegan tool that uses only 10 items For all but 2 of the categories, it is dichotomous and a score is simply given no choice between different levels of severity of symptoms Correlated well with current Finnegan tool Thousands of observations in 2 institutions Pomar et al

11 Quiet environment Swaddling Pacifier Use Parent presence Breastfeeding Rooming in No good, RCT on these interventions Wachman et al 2018 Maternal cigarette use Increased medication requirement May increase length of stay Maternal SSRI use Higher peak NAS scores 11

12 Alcohol use May have similar presentation to NAS but this is controversial and low incidence of pregnant women reporting alcohol use Cocaine use Conflicting evidence Benzodiazepine use May prolong neonatal stay and duration of treatment Non breastfeeding Dyads Very little opioid is expressed in BM, but infants who are breast feeding have less need for medication intervention and shorter LOS Generally recommended that if mom is in treatment and not using illicit substances, breastfeeding is encouraged 12

13 AAP (2012) recommends guidelines for the following: Screening for maternal substance use Nonpharmacologic treatment of infants with NAS Scoring signs of NAS Breastfeeding and NAS Pharmacologic management of NAS Duration of observation of exposed infants Hudak and Tan 2012 Although AAP Guidelines (2012) recommended every nursery have a standardized protocol Less than 70% of NICU fellowship programs surveyed had this Hudak and Tan

14 Having a treatment and weaning protocol decreases treatment duration AND length of hospital stay This has so many benefits, only one of which is cost! Multiple studies have shown a decrease in LOS and treatment days when protocol used Minimum of 3 fewer days hospitalized As many as 10 fewer days hospitalized Not surprising as guidelines/protocols are helpful in management of many illnesses Patrick et al 2016 Hall et al 2015 Asti et al 2015 All articles refer to the video training by Karen D Apolito, PhD Reduce variability between individual scoring Standard described to start opioid treatment is: Finnegan scores 8 on 3 consecutive scores or Finnegan scores 12 on 2 consecutive scores All studies showed shortened treatment courses and shorter LOS when protocol was used 14

15 Morphine Methadone Buprenorphine Clonidine? Phenobarbitol? Randomized Control Trial 31 patients randomized to methadone or morphine 47 mothers of eligible infants declined to participate (60%) Those treated with methadone had decreased length of treatment 14 days vs 21 days (p = 0.008) Brown et al

16 Retrospective chart review 26 neonates included 13 in each group Weaning protocol for morphine, but no protocol for weaning methadone!! Morphine group had decreased hospital days days vs days Difficult to draw any conclusions about treatment Young et al patients randomized to phenobarbital vs morphine as first line No difference in mean treatment days 3.3% of infants treated with morphine required adjuvant treatment 6.6% of infants treated with phenobarbital required adjuvant treatment Nayeri et al

17 117 infants randomized to methadone vs morphine Sample size of 184 was needed for 80% power to detect a difference Used alcohol free methadone, not used commercially We use solution with 8% alcohol, standard is 15% Primary outcome was LOS No statistically significant differences between drugs, but trends in decreased LOS and LOT with methadone Planning for follow up at months Davis et al 2018 Retrospective review of buprenorphine vs methadone 201 infants included 38 treated with buprenorphine Fewer days of treatment 9.4 vs 14 days Shorter LOS 16.3 vs 20.7 days Hall et al 2014 had 15 pts tx with buprenorphine data not analyzed because of small # 10 days tx, 16 days hospitalization Hall et al 2014 Hall et al

18 Additional RCT enrolled 13 patients in each arm Buprenoprhine vs neonatal opium solution No difference between groups We do not use neonatal opium solution Kraft et al 2008 Things to consider Ceiling effect on respiratory depression Partial mu agonist Longer half life than morphine Compounded with 30% alcohol solution Very small volumes required for dosing ~0.2ml Very few studies looking at buprenorphine in neonates Seemingly safe in pregnancy with no additional adverse neonatal outcomes?? Increased risk of CHD compared to methadone Kraft et al 2008 Jones et al

19 Clonidine Longer LOS vs phenobarbital No neurodevelopmental concerns Study underway using clonidine as first line tx Phenobarbital Neurodevelopment concerns Length of treatment greater Decreased length of treatment when clonidine added vs placebo 80 babies in study 11 days of treatment vs 15 days of treatment Opioid used = diluted tincture of opium Decreased length of treatment with clonidine or phenobarbital compared to pretrial of morphine alone 34 infants per group 4.6 day treatment of morphine in phenobarbital group Phenobarbital continued for 1 8 months after discharge Streetz et al

20 Small study looked at clonidine vs morphine as monotherapy RCT included 31 infants Developmental outcomes at 1 year showed no difference 42.7 ±17.8 days in morphine vs 32 ±20.4 days in clonidine (p=0.02) Streetz et al 2016 Rooming in for at risk infants Prospective cohort study out of Canada Infants at risk of NAS who roomed in had decreased risk of opioid treatment and decreased LOS 20/24 infants in NICU group required treatment 3/20 infants in rooming in group required treatment Median LOS 24 days vs 5 days! Likely effect of treatment vs no treatment McKnight

21 Likely increased risk of CHD Possible increased risk of neural tube defects Lower birth weight Increased risk of preterm delivery Yazdy et al 2015 Increased maternal risks Pre eclampsia Third trimester bleeding Fetal malpresentation Pre term labor Increased risk of meconium aspiration Increased risk of microcephaly Increased neonatal mortality Increased risk of SIDS Tsai and Doan

22 Retrospective study looking at infants treated for NAS vs control 87 patients included Infants with prenatal exposure, but who didn t require neonatal treatment were excluded Children with NAS requiring treatment scored lower in cognitive, language and motor subscales (1 standard deviation below mean) Those who lived with foster or adoptive families at time of evaluation scored significantly higher in the cognitive subscore than those in care of mother 26% of families reported issues with sleep and behavior 40% of children required EI LOS, GA and BW not correlated with Bayley scores Merhar et al 2018 School aged kids who were prenatally exposed to opioids had worse developmental outcomes 72 exposed 58 controls Even when controlling for SES, GA, birth weight and stable foster/adoptive family vs birth parents At 8.5 yo, still had significantly worse outcomes Lower IQ (WISC) p<0.001 Nygaard et al

23 Incidence of NAS is increasing Protocol to guide screening of pregnant women and infants is necessary Protocol for weaning opiates decreases time needed for treatment and LOS Prenatal exposure to opiates has long term neurodevelopmental risks 23

24 Asti L, Magers JS, Keels E et al. A quality improvement project ot reduce length of stay for neonatal abstinence syndrome. Pediatrics 2015; 135: e Brown MS, Hayes MJ and Thornton LM. Methadone versus morphine for treatment of neonatal abstinence syndrome: a prospective randomized clinical trial. Journal of Perinatology 2015; 35: Clark L and Rohan A. Identifying and assessing the substance exposed infant. MCN Am J Matern Child Nurs. 2015; 40 (2): Davis JM, Shenberger J, Terrin N et al. Comparison of safety and efficacy of methadone vs morphine for treatment of neonatal abstinence syndrome. JAMA Pediatrics (2018) e1 8. Desai RJ, Huybrechts KF, Hernandez Diaz S et al. Exposure to prescription opioid analgesics in utero and risk of neonatal abstinence syndrome: population based cohort study. BMJ 2015; 350: Grossman MR, Lipshaw MJ, Osborn RR and Berkwitt AK. A novel approach to assessing infants with neonatal abstinence syndrome. Hospital Pediatrics (2018) 8: 1 6. Hall ES, Wexelblatt SL, Crowley M et al. A multicenter cohort study of treatments and hospital outcomes in neonatal abstinence syndrome. Pediatrics 2014; 134: e Hall ES, Wexelblatt SL, Crowley M et al. Implementation of a neonatal abstinence syndrome weaning protocol: a multicenter cohort study. Pediatrics 2015; 136: e Hall ES, Isemann BT, Wexelblatt SL et al. A cohort comparison of buprenorphine versus methadone treatment for neonatal abstinence syndrome. J of Peds 2016; 170: Hudak ML and Tan RC. Neonatal drug withdrawal. Pediatrics 2012; 129: e Jones HE, Arria AM, Baewert A et al. Buprenorphine treatment of opioid dependent women: a comprehensive review. Addiction 2012; 107: Kaltenbach K and Jones HE. Neonatal abstinence syndrome: presentation and treatment considerations. J Addict Med 2016; 00:1 7. Kraft WK, Gibson E, Dysart K et al. Sublingual buprenorphine for treatment of neonatal abstinence syndrome. Pediatrics 2008; 122: e Marin SJ, Metcalf A & Krasowski. Detection of neonatal drug exposure using umbilical cord tissue and liquid chromatography time of flight mass spectrometry. Ther Drug Monit 2014; 36: McKnight S, Coo H, Davies G et al. Rooming in for infants at risk of neonatal abstinence syndrome. Am J Perinatol 2016; 33: Merhar SL, McAllister JM, Wedig Stevie KE et al. Retrospective review of neurodevelopmental outcomes in infants treated for neonatal abstinence syndrome. Journal of Perinatology (2018) 38: Montgomery DP, Plate CA, Jones M et al. Using umbilical cord tissue to detect fetal exposure to illicit drugs: a multicentered study in Utah and New Jersey. Journal of Perinatology 2008; 28: Montgomery D, Plate C, Alder SC et al. Testing for fetal exposure to illicit drugs using umbilical cord tissue vs meconium. Journal of Perinatology 2006; 26: Nayeri F, Sheikh M, Kalani M et al. Phenobarbital versus morphine in the management of neonatal abstinence syndrome, a randomized control trial. BMC Pediatrics (2015) 15: Nygaard E, Moe V, Slinning K and Walhovd KB. Longitudinal cognitive development of children born to mothers with opioid and polysubstance use. Pediatric Research 2015; 78: Patrick SW, Schumacher RE, Horbar JD et al. Improving care for neonatal abstinence syndrome. Pediatrics 2016; 137: 1 8. Pomar EG, Finnegan LP, Devlin L et al. Simplification of the Finnegan neonatal abstinence scoring system: retrospective study of two institutions in the USA. BMJ Open (2017) 7:e1 7. Streetz VN, Gildon BL, and Thompson DF. Role of clonidine in neonatal abstinence syndrome: a systematic review. Annals of Pharmacolotherapy 2016; 50: Tsai LC and Doan TJ. Breastfeeding among mothers on opioid maintenance treatment: a literature review. Journal of Human Lactation 2016; 1 9 Wachman EM, Schiff DM, & Silverstein M. Neonatal abstinence syndrom; advances in diagnosis and treatment. JAMA (2018) 13: Yazdy MM, Desai RJ and Brogly SB. Prescription opioids in pregnancy and birth outcomes: a review of the literature. J Pediatr Genet 2015: 4: Young ME, Hager SJ, and Spurlock D. Retrospective chart review comparing morphine and methadone in neonates treated for neonatal abstinence syndrome. Am J Health SystPharm 2015; 72: s