Neonatal Abstinence Syndrome Clinical Presentation
- Author: Ashraf H Hamdan, MD, MBBCh, MSc, MRCP; Chief Editor: Ted Rosenkrantz, MD more...
History
When assessing potential neonatal abstinence syndrome (NAS), the most reliable method of determining the extent of drug use in pregnancy is maternal history as part of routine antenatal assessment, with a structured interview providing a greater yield than an informal interview.
The amount of information obtained from the mother about prenatal drug exposure widely varies and may not be reliable. How the mother is questioned and the specificity of the questions are the most important factors. Maternal interviews have been reported to be the least sensitive method of identifying drug use in pregnancy when compared with maternal hair and meconium drug testing. Maternal self-report was found to underestimate in utero drug exposure by as much as 44% when compared with data from meconium analyses.[17]
Despite concerted efforts by health care professionals to promote prenatal care, the mother may not have received such care and the delivery hospitalization may be the only opportunity to elicit information on the nature and extent of the infant's in utero exposure to drugs and alcohol. The mother's concern for her infant's health may encourage valid responses; conversely, fear of legal reprisals or loss of custody of the infant may cause the mother to deny drug use.
The Committee on Substance Abuse of the American Academy of Pediatrics recommends obtaining a comprehensive medical and psychological history that includes specific information regarding maternal drug use as part of every newborn evaluation.[18]
The relationship between maternal cocaine use and placental abruption is well established. Therefore, a perinatal history of abruption should alert the medical caretaker that prenatal exposure to cocaine is a possibility.
Physical
A thorough physical examination of the neonate should include accurate assessment of weight, length, and head circumference and a standardized assessment of gestational age. Special attention should be paid to signs of intrauterine growth retardation (IUGR), microcephaly, prematurity, congenital infection, and major and minor congenital malformations.
Infants are suspected of having neonatal abstinence syndrome if they exhibit any of the following signs:
- CNS dysfunction
- High-pitched cry
- Restlessness, with sleep duration less than 1-3 hours after feeding
- Hyperactive reflexes
- Jitteriness
- Tremors
- Hypertonia
- Myoclonic jerks
- Generalized convulsions
- Metabolic, vasomotor, and respiratory disturbances
- Sweating
- Fever
- Mottling
- Frequent yawning
- Sneezing (>3 times per interval)
- Nasal flaring
- Respiratory rate greater than 60 breaths per minute without retractions
- Apnea
- GI dysfunction
- Excessive (frantic) sucking or rooting
- Poor feeding
- Hyperphagia, usually associated with poor weight gain
- Regurgitation or projectile vomiting
- Loose or watery stools
- Alcohol-specific symptoms
- Withdrawal that presents within the first 24 hours of life is reported among infants with the dysmorphic features of fetal alcohol syndrome.
- Neonates also exhibit irritability, tremors, seizures, opisthotonus, and abdominal distention.
- Lysergic acid (LSD) symptoms
- The effect of LSD on the fetus is clouded by the high incidence of polydrug abuse.
- Withdrawal symptoms manifest as hypertonia, tremors, poor feeding, and abnormal feeding patterns.
- Other symptoms
- Nicotine may produce withdrawal symptoms in infants, including increased excitability and hypertonicity.
- Caffeine withdrawal includes feeding difficulties, vomiting, excessive crying, irritability, and poor sleep patterns. Onset of symptoms may occur as long as 5 days after birth and persist for weeks or months.
The timing of onset of the symptoms gives an indication of the maternal drug abuse. Withdrawal from high levels of maternal alcohol can occur within a day or 2 of birth. Heroin has a short half-life and withdrawal also occurs within 48–72 h of birth, whereas methadone withdrawal occurs at 7–14 days.
Preterm infants are at lower risk of drug withdrawal with less severe courses. Infants born at less than 35 weeks’ gestation whose mothers received methadone maintenance had significantly lower total and CNS abstinence scores than did term infants of mothers receiving similar methadone dosages.[19] In a more recent study, lower gestational age correlated with a lower risk of neonatal withdrawal.[20] The apparent decreased severity of signs in preterm infants may relate to developmental immaturity of the CNS, differences in total drug exposure, or lower fat deposits of drug.[21]
Different scoring systems have been developed for assessing the severity of neonatal abstinence syndrome, such as those by Finnegan, Ostrea, Lipsitz, Rivers, and the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS).[22, 23, 24] These are based on opiate withdrawal and may not be entirely appropriate for the infant exposed to cocaine or other drugs.
The most widely used system is the Finnegan scoring system, in both its original and modified forms. A neonatal abstinence syndrome scoring form is shown below.
Neonatal abstinence syndrome scoring form. The Finnegan scale assesses 21 of the most common signs of neonatal drug withdrawal syndrome and is scored on the basis of pathological significance and severity of the adverse symptoms, which sometimes requires pharmacological treatment. Despite the number of items that can be scored, it is nevertheless a relatively easy and reliable system to use once staff have been adequately trained. However, the potential for bias and subjectivity may affect the scores, and the thresholds for treatment reported in the literature vary. This scale can also be used to assess the resolution of signs and symptoms after initiating treatment.
To obtain a daily average score, measurements are performed every 4 hours until the patient is stable. If 3 consecutive scores are equal to or greater than 8, treatment for withdrawal is started. The decision to commence treatment can depend on factors other than this score alone, including the reported exposure, the age of the infant, consideration of comorbidities that might influence the score, whether an inpatient or outpatient strategy is used, and the experience of the clinician making treatment decisions.
The infant is best cared for in a unit with experienced personnel who can recognize problems, perform constant evaluations, and institute the necessary interventions.
Causes
Current resurgence in heroin use is associated with the introduction of a cheap, smokeable form that is comparable to crack cocaine, only more potent. Cocaine's current popularity is related to increased availability and the presence of newer, cheaper forms.
Depression is common in reproductive age women, and continued pharmacologic treatment of depression during pregnancy may be necessary to prevent relapse. Neonates who are exposed to antidepressant medications during gestation are at increased risk to have neonatal abstinence syndrome.
Chana S, Anand K. Can we use methadone for Analgesia in neonates?. Arch Dis Child Fetal Neonatal Ed. 2001;85:79-81. [Medline]. [Full Text].
Franck LS, Vilardi J, Durand D, Powers R. Opioid withdrawal in neonates after continuous infusions of morphine or fentanyl during extracorporeal membrane oxygenation. Am J Crit Care. Sep 1998;7(5):364-9. [Medline].
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. [Medline].
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. [Medline].
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. [Medline].
Wouldes TA, Woodward LJ. Maternal methadone dose during pregnancy and infant clinical outcome. Neurotoxicol Teratol. Jan 25 2010;[Medline].
BJ Cleary, M Eogan, MP O'Connell, T Fahey, PJ Gallagher, T Clarke, et al. Methadone and Perinatal Outcomes – a Prospective Cohort Study. Addiction. [Medline].
Law KL, Stroud LR, LaGasse LL, et al. Smoking during pregnancy and newborn neurobehavior. Pediatrics. Jun 2003;111(6 Pt 1):1318-23. [Medline]. [Full Text].
Haddad PM, Pal BR, Clarke P, Wieck A, Sridhiran S. Neonatal symptoms following maternal paroxetine treatment: serotonin toxicity or paroxetine discontinuation syndrome?. J Psychopharmacol. Sep 2005;19(5):554-7. [Medline].
Substance Abuse and Mental Health Services Administration. Results from the 2010 National Survey on Drug Use and Health: Summary of National Findings. US Department of Health and Human Services; September 2011. [Full Text].
SAMHSA. Substance Use among Women During Pregnancy and Following Childbirth. Rockville, MD: Substance Abuse and Mental Health Services Administration; May 21, 2009. [Full Text].
Cairns PA. Drug misuse: Conception into childhood. Current Paediatrics. December 2001;11(6):475-9.
Prentice S. Substance misuse in pregnancy. Obstetrics, Gynaecology & Reproductive Med. September 2007;17:272-7.
Gyarmathy VA, Giraudon I, Hedrich D, Montanari L, Guarita B, Wiessing L. Drug use and pregnancy - challenges for public health. Euro Surveill. Mar 5 2009;14(9):33-6. [Medline]. [Full Text].
Substance Use During Pregnancy: 2002 and 2003 Update. National survey on drug use and health; June 2, 2005. [Full Text].
Lester BM, ElSohly M, Wright LL, Smeriglio VL, Verter J, Bauer CR. The Maternal Lifestyle Study: drug use by meconium toxicology and maternal self-report. Pediatrics. Feb 2001;107(2):309-17. [Medline].
[Guideline] American Academy of Pediatrics Committee on Substance Abuse. Drug-exposed infants. Pediatr. Aug 1995;96(2 Pt 1):364-7. [Medline].
Doberczak TM, Kandall SR, Wilets I. Neonatal opiate abstinence syndrome in term and preterm infants. J Pediatr. Jun 1991;118(6):933-7. [Medline].
Liu AJ, Jones MP, Murray H, Cook CM, Nanan R. Perinatal risk factors for the neonatal abstinence syndrome in infants born to women on methadone maintenance therapy. Aust N Z J Obstet Gynaecol. Jun 2010;50(3):253-8. [Medline].
[Best Evidence] [Guideline] Hudak ML, Tan RC. Neonatal Drug Withdrawal. Pediatrics. January 2012;129(2):e540-560. [Medline]. [Full Text].
Finnegan LP. Neonatal abstinence syndrome: assessment and pharmacolotherapy. In: Neonatal therapy: An update. New York, NY: Excerpta Medica; 1986:122-46.
Ostrea EM, Ostrea AR, Simpson PM. Mortality within the first 2 years in infants exposed to cocaine, opiate, or cannabinoid during gestation. Pediatrics. Jul 1997;100(1):79-83. [Medline]. [Full Text].
Lester BM, Tronick EZ. History and description of the Neonatal Intensive Care Unit Network Neurobehavioral Scale. Pediatrics. Mar 2004;113(3 Pt 2):634-40. [Medline].
Chasnoff IJ. Prenatal substance exposure: maternal screening and neonatal identification and management. Neoreviews. 2003;4(9):e228-e235.
Gray T, Huestis M. Bioanalytical procedures for monitoring in utero drug exposure. Anal Bioanal Chem. Aug 2007;388(7):1455-65. [Medline].
van Huis M, van Kempen AA, Peelen M, Timmers M, Boer K, Smit BJ. Brain ultrasonography findings in neonates with exposure to cocaine during pregnancy. Pediatr Radiol. Mar 2009;39(3):232-8. [Medline].
Kassima Z, Greenough A. Neonatal abstinence syndrome: Identification and management. Current Paediatrics. June 2006;16:172-5.
Lainwala S, Brown ER, Weinschenk NP, Blackwell MT, Hagadorn JI. A retrospective study of length of hospital stay in infants treated for neonatal abstinence syndrome with methadone versus oral morphine preparations. Adv Neonatal Care. Oct 2005;5(5):265-72. [Medline].
Kraft WK, Gibson E, Dysart K, et al. Sublingual buprenorphine for treatment of neonatal abstinence syndrome: a randomized trial. Pediatrics. Sep 2008;122(3):e601-7. [Medline].
[Best Evidence] Agthe AG, Kim GR, Mathias KB, et al. Clonidine as an adjunct therapy to opioids for neonatal abstinence syndrome: a randomized, controlled trial. Pediatrics. May 2009;123(5):e849-56. [Medline].
Sarkar S, Donn SM. Management of neonatal abstinence syndrome in neonatal intensive care units: a national survey. J Perinatol. Jan 1 2006;26(1):15-7. [Medline].
[Guideline] American Academy of Pediatrics Committee on Drugs. Neonatal drug withdrawal. [published erratum appears in Pediatrics 1998 Sep;102(3 Pt 1):660]. Pediatrics. Jun 1998;101(6):1079-88. [Medline].
Mazurier E, Cambonie G, Barbotte E, Grare A, Pinzani V, Picaud JC. Comparison of chlorpromazine versus morphine hydrochloride for treatment of neonatal abstinence syndrome. Acta Paediatr. Oct 2008;97(10):1358-61. [Medline].
SAMHSA. The Drug Addiction Treatment Act of 2000 (DATA 2000). DHHS; 2000. [Full Text].
Kraft WK, Gibson E, Dysart K, Damle VS, Larusso JL, Greenspan JS. Sublingual buprenorphine for treatment of neonatal abstinence syndrome: a randomized trial. Pediatrics. Sep 2008;122(3):e601-7. [Medline].
[Guideline] Jansson LM, Choo R, Velez ML, Harrow C, Schroeder JR, Shakleya DM. Methadone maintenance and breastfeeding in the neonatal period. Pediatrics. Jan 2008;121(1):106-14. [Medline].
[Guideline] AAP. Transfer of drugs and other chemicals into human milk. Pediatrics. Sep 2001;108(3):776-89. [Medline].
Anthony BE, Bryan BL. Neonatal Abstinence Syndrome. NeoReviews. 2009;10(5):e222.
Hale TW. Pharmacology review: drug therapy and breastfeeding: antidepressants, antipsychotics, antimanics, and sedatives. NeoReviews. May 2004;e451 -e456.
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. [Medline].
Gray KA, Day NL, Leech S, Richardson GA. Prenatal marijuana exposure: effect on child depressive symptoms at ten years of age. Neurotoxicol Teratol. May-Jun 2005;27(3):439-48. [Medline].
Goldschmidt L, Day NL, Richardson GA. Effects of prenatal marijuana exposure on child behavior problems at age 10. Neurotoxicol Teratol. May-Jun 2000;22(3):325-36. [Medline].
Maternal Resource Center. Prenatal Substance Exposure. April 2008;Available from: National Abandoned Infants Assistance Resource Center. Accessed 2/20/2010. Available at http://aia.berkeley.edu/media/pdf/2008_perinatal_se.pdf.
Jaudes PK, Ekwo E, Van Voorhis J. Association of drug abuse and child abuse. Child Abuse Negl. Sep 1995;19(9):1065-75. [Medline].
Smith DK, Johnson AB, Pears KC, Fisher PA, DeGarmo DS. Child maltreatment and foster care: unpacking the effects of prenatal and postnatal parental substance use. Child Maltreat. May 2007;12(2):150-60. [Medline].
American Academy of Pediatrics. Pickering LK. The Red Book: 2006 Report of the Committee on Infectious Diseases. 27th. 2006.
[Guideline] American Academy of Pediatrics Committee on Fetus and Newborn. The initiation or withdrawal of treatment for high-risk newborns. Pediatrics. Aug 1995;96(2 Pt 1):362-3. [Medline].
Bahwere P, Haumont D, Delange F. Congenital hypothyroidism and neonatal withdrawal syndrome. Eur J Pediatr. Nov 1996;155(11):937-8. [Medline].
Bauer CR. Perinatal effects of prenatal drug exposure. Neonatal aspects. Clin Perinatol. Mar 1999;26(1):87-106. [Medline].
Boukydis CF, Lester BM. The NICU Network Neurobehavioral Scale. Clinical use with drug exposed infants and their mothers. Clin Perinatol. Mar 1999;26(1):213-30. [Medline].
Buchi KF. The drug-exposed infant in the well-baby nursery. Clin Perinatol. Jun 1998;25(2):335-50. [Medline].
Chasnoff IJ, Bussey ME, Savich R, Stack CM. Perinatal cerebral infarction and maternal cocaine use. J Pediatr. Mar 1986;108(3):456-9. [Medline].
Connolly WB Jr, Marshall AB. Drug addiction, pregnancy, and childbirth: legal issues for the medical and social services communities. Clin Perinatol. Mar 1991;18(1):147-86. [Medline].
Frank L. Assessment and management of opioid withdrawal in ill neonates. Neonatal Network. 1995;14:39-48. [Medline].
Heier LA, Carpanzano CR, Mast J, Brill PW, Winchester P, Deck MD. Maternal cocaine abuse: the spectrum of radiologic abnormalities in the neonatal CNS. AJNR Am J Neuroradiol. Sep-Oct 1991;12(5):951-6. [Medline].
Johnson K, Gerada C, Greenough A. Treatment of neonatal abstinence syndrome. Arch Dis Child Fetal Neonatal Ed. Jan 2003;88(1):F2-5. [Medline].
Kallen B. Neonate characteristics after maternal use of antidepressants in late pregnancy. Arch Pediatr Adolesc Med. Apr 2004;158(4):312-6. [Medline]. [Full Text].
Kaltenbach K, Berghella V, Finnegan L. Opioid dependence during pregnancy. Effects and management. Obstet Gynecol Clin North Am. Mar 1998;25(1):139-51. [Medline].
Kandall RS. Improving Treatment for Drug-Exposed Infants Treatment Improvement Protocol (TIP) Series 5. Available at http://ncadi.samhsa.gov/govpubs/bkd110/default.aspx. Accessed February, 14 2010.
Kandall SR. Treatment strategies for drug-exposed neonates. Clin Perinatol. Mar 1999;26(1):231-43. [Medline].
Kuschel C. Managing drug withdrawal in the newborn infant. Semin Fetal Neonatal Med. Apr 2007;12(2):127-33. [Medline].
McKim EM. Caffeine and its effects on pregnancy and the neonate. J Nurse Midwifery. Jul-Aug 1991;36(4):226-31. [Medline].
[Best Evidence] Moses-Kolko EL, Bogen D, Perel J, Bregar A, Uhl K, Levin B. Neonatal signs after late in utero exposure to serotonin reuptake inhibitors: literature review and implications for clinical applications. JAMA. May 18 2005;293(19):2372-83. [Medline].
Oei J, Lui K. Management of the newborn infant affected by maternal opiates and other drugs of dependency. J Paediatr Child Health. Jan-Feb 2007;43(1-2):9-18. [Medline].
Pierog S, Chandavasu O, Wexler I. Withdrawal symptoms in infants with the fetal alcohol syndrome. J Pediatr. Apr 1977;90(4):630-3. [Medline].
SAMHSA. Special issues during pregnancy. Rockford, MD: DHHS; May 21, 2009. [Full Text].
Sanz EJ, De-las-Cuevas C, Kiuru A, et al. Selective serotonin reuptake inhibitors in pregnant women and neonatal withdrawal syndrome: a database analysis. Lancet. Feb 5-11 2005;365(9458):482-7. [Medline].
Ter Horst PG, Jansman FG, van Lingen RA, Smit JP, de Jong-van den Berg LT, Brouwers JR. Pharmacological aspects of neonatal antidepressant withdrawal. Obstet Gynecol Surv. Apr 2008;63(4):267-79. [Medline].
Theis JG, Selby P, Ikizler Y, Koren G. Current management of the neonatal abstinence syndrome: a critical analysis of the evidence. Biol Neonate. 1997;71(6):345-56. [Medline].
Umans JG, Szeto HH. Precipitated opiate abstinence in utero. Am J Obstet Gynecol. Feb 15 1985;151(4):441-4. [Medline].
Vance JC, Chant DC, Tudehope DI, et al. Infants born to narcotic dependent mothers: physical growth patterns in the first 12 months of life. J Paediatr Child Health. Dec 1997;33(6):504-8. [Medline].
Wagner CL, Katikaneni LD, Cox TH, Ryan RM. The impact of prenatal drug exposure on the neonate. Obstet Gynecol Clin North Am. Mar 1998;25(1):169-94. [Medline].
Young T E, Mangum B. CNS Drugs. In: Thomson Reuters clinical editorial staff. Neofax: A manual of drugs used in neonatal care. 22nd ed. Montvale, New Jersey: Thomson Reuters healthcare; 2009:187-214.
Zeskind PS, Stephens LE. Maternal selective serotonin reuptake inhibitor use during pregnancy and newborn neurobehavior. Pediatrics. Feb 2004;113(2):368-75. [Medline].

