Neonatal Abstinence Syndrome: An Emerging Epidemic? March 11, 2013 Balaji Govindaswami, MD, MPH Chief Newborn Medicine, Director - NICU Santa Clara Valley Health and Hospital System, San Jose, CA Clinical Professor (Affiliated) of Pediatrics Neonatal and Developmental Medicine Stanford University School of Medicine, Palo Alto, CA
Conflicts All pharmacologic suggested treatments may be considered off-label drug use. Dr. Govindaswami receives NIH-funding from R01 HD070795-01A1 (PI Gary Peltz Stanford University) Ondansetron Study 2012-17 Our NICU receives Funding Support from First 5 of Santa Clara County and VMC Foundation. SCVMC NICU is part of the 2013 VON-NAS collaborative (Site PI: Priya Jegatheesan, MD)
From: Neonatal Abstinence Syndrome and Associated Health Care Expenditures: United States, 2000-2009 JAMA. 2012;307(18):1934-1940. doi:10.1001/jama.2012.3951 Figure Legend: NAS indicates neonatal abstinence syndrome. Error bars indicate 95% CI. P for trend <.001 over the study period. The unweighted sample sizes for rates of NAS and for all other US hospital births are 2920 and 784 191 in 2000; 3761 and 890 582 in 2003; 5200 and 1 000 203 in 2006; and 9674 and 1 113 123 in 2009; respectively. Date of download: 3/7/2013 Copyright 2012 American Medical Association. All rights reserved.
From: Neonatal Abstinence Syndrome and Associated Health Care Expenditures: United States, 2000-2009 JAMA. 2012;307(18):1934-1940. doi:10.1001/jama.2012.3951 Figure Legend: Date of download: 3/7/2013 Copyright 2012 American Medical Association. All rights reserved.
From: Neonatal Abstinence Syndrome and Associated Health Care Expenditures: United States, 2000-2009 JAMA. 2012;307(18):1934-1940. doi:10.1001/jama.2012.3951 Figure Legend: Date of download: 3/7/2013 Copyright 2012 American Medical Association. All rights reserved.
Suggested Reading [Best Evidence] [Guideline] Hudak ML, Tan RC. Neonatal Drug Withdrawal. Pediatrics. January 2012;129(2):e540-560. Neonatal Abstinence Syndrome Treatment & Management Ashraf H Hamdan, April, 2012 http://emedicine.medscape.com/article/9787 63-clinical#a0217
NAS Complex disorder Constellation of behavioral and physiological signs and symptoms Remarkably similar inspite of marked differences in causal agent Prenatal: Maternal exposure Postnatal: predominately Opiate
Substances frequently associated with NAS Opiates & Narcotics Heroin, Methadone Meperidine (Demerol) Oxycodone, Morphine Hydromorphone (Dilaudid) Butorphanol (Stadol) Pentazocine Propoxyphene (Darvon) Chlordiazepoxide Buprenorphine Other Barbiturates, SSRIs, Antihistamines THC, Cocaine Nicotine, Caffeine, Alcohol Meprobamate Phencyclidine (PCP) angeldust Ethchlorvynol (Placidyl) Glutethemide Benzodiazepines: Diazepam, Lorazepam, chlordiazepoxide (Librium)
Pathophysiology Addiction in both Mom and Baby Placental barrier varies with agent Lipophilic, low molecular wt drugs CNS Facilitated placental transfer Fetus immature kidneys, enzyme systems Disruption of transplacental transfer at birth results in subsequent withdrawal
Maternal exposure 3% of 4.1 million women of childbearing age who abuse drugs are believed to continue drug use during pregnancy Poor PNC, abruption, IV drug marks, skin, nutritional and dentition deficiencies History of use is unreliable and underestimates exposure when compared to maternal hair or when compared to infant meconium analysis (44% underestimated) 1 Thus, every newborn should have comprehensive maternal medical and psychological history including history of drug use 2 30-90% of exposed infants may exhibit NAS 1. Lester BM, ElSohly M, Wright LL, Smeriglio VL, Verter J, Bauer CR. The Maternal Lifestyle Study: drug use by meconium toxicology and maternal selfreport. Pediatrics. Feb 2001;107(2):309-17. [Medline] 2. (Guideline) American Academy of Pediatrics Committee on Substance Abuse. Drug-exposed infants. Pediatr. Aug 1995;96(2 Pt 1):364-7. [Medline]
NAS variable Drug Withdrawal Onset of symptoms Peak Symptoms as late as Heroin 24 48-72 ( in 50-80% infants exposed) Benzodiazepines Barbiturates 6 days Longer Longer 2 weeks Methadone 48 h or 7-10 days 4 weeks to 6 months for subacute signs
Infants Examination Maturity & Growth, IUGR, head growth Dysmorphic features, malformations, infection CNS, SERIAL EXAMINATION Metabolic, Cardio(vasomotor) Respiratory Gastrointestinal Specific to agent of exposure eg FAS Recognize co-morbidities
CNS dysfunction Irritable, High-pitched cry Restlessness, with sleep duration less than 1-3 hours after feeding Stiff, Hypertonia, Hyperactive reflexes Jittery, Tremulous, Myoclonic jerks Generalized convulsions
Metabolic, Respiratory, Vasomotor Sweating, fever, mottling Frequent yawning Sneezing (>3 times per interval) Nasal flaring Tachypnea, retractions Apnea
Gastro Intestinal Excessive (frantic) sucking or rooting Poor feeding and weight gain Hyperphagia also with poor weight gain Regurgitation or projectile vomiting Loose or watery stools
Treatment CURRENTLY UNSATISFACTORY! Supportive Non-pharmacological Pharmacological Investigational Dietary/ Nutrition / Breast milk Family Support / Intervention
Resources for families Drug Dependence and Abuse Narcotic Abuse Substance Abuse www.emedicinehealth.com
Recent Reviews/ References Irner TB, Teasdale TW, Nielsen T, Vedal S, Olofsson M. Substance use during pregnancy and postnatal outcomes. J Addict Dis. Jan 2012;31(1):19-28. Kandall RS. Improving Treatment for Drug-Exposed Infants Treatment Improvement Protocol (TIP) Series 5. Available at http://ncadi.samhsa.gov/govpubs/bkd110/default.aspx. Wouldes TA, Woodward LJ. Maternal methadone dose during pregnancy and infant clinical outcome. Neurotoxicol Teratol. Jan 25 2010. Dryden C, Young D, Hepburn M, Mactier H. Maternal methadone use in pregnancy: factors associated with the development of neonatal abstinence syndrome and implications for healthcare resources. BJOG. Apr 2009;116(5):665-71. Substance Abuse and Mental Health Services Administration Office of Applied Studies. 2003 National Survey on Drug Use & Health: Results. US Department of Health and Human Services. Available at http://www.drugabusestatistics.samhsa.gov/nhsda/2k3nsduh/2k3results.htm. Accessed December, 2007. Hytinantti T, Kahila H, Renlund M, Jarvenpaa AL, Halmesmaki E, Kivitie-Kallio S. Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero. Acta Paediatr. Aug 2008;97(8):1040-4. Lim S, Prasad MR, Samuels P, Gardner DK, Cordero L. High-dose methadone in pregnant women and its effect on duration of neonatal abstinence syndrome. Am J Obstet Gynecol. Jan 2009;200(1):70.e1-5. Hale TW. Pharmacology review: drug therapy and breastfeeding: antidepressants, antipsychotics, antimanics, and sedatives. NeoReviews. May 2004;e451 -e456.
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