eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Neonatology

Neonatal Abstinence Syndrome: Differential Diagnoses & Workup

Author: Ashraf H Hamdan, MB, BCh, MSc, MD, MRCP, Clinical Assistant Professor of Pediatrics, Vanderbilt University Medical Center; Neonatologist, Mid Tennessee Neonatology Associates.
Contributor Information and Disclosures

Updated: Jun 18, 2009

Differential Diagnoses

Hyperthyroidism
Hypocalcemia
Hypoglycemia
Sepsis

Other Problems to Be Considered

Hyperviscosity and intracranial hemorrhage should also be considered. Drug withdrawal should be considered as a diagnosis in infants in whom compatible signs develop. Physicians should be aware of other potential diagnoses that should be evaluated and treated, if confirmed.

Infants with signs and symptoms of neonatal abstinence syndrome (NAS) may have other conditions that result in abnormal behavior. The nonspecific nature of the clinical features of neonatal abstinence syndrome mean that some drug-exposed infants may have exaggerated scores when they are hungry or may have other conditions such as neonatal sepsis, hypoglycemia, hypocalcemia, hyperthyroidism, or subarachnoid hemorrhage. On the other hand, congenital hypothyroidism has been reported to mask the symptoms of neonatal abstinence syndrome. For that reason, assess the infant and consider whether symptoms are solely due to neonatal abstinence syndrome and whether other investigations are warranted.

Workup

Laboratory Studies

Early drug screening during pregnancy reveals the need for counseling in pregnant women with a history of drug abuse. The following studies may be necessary to prevent or diagnose cases of neonatal abstinence syndrome (NAS):

  • Radioimmunoassay and enzyme immunoassay
    • These are the most commonly used drug screens. Both are semiquantitative and highly sensitive, but enzyme immunoassay takes less time to perform and is less expensive.
    • These tests inform the clinician about the presence or absence of substance abuse, rather than quantifying the drug level, as in toxicology screens.
  • Blood tests: The usefulness of neonatal blood samples varies. Blood samples are of limited value because the window of detection is narrow because of the rapid effects of metabolism and the low concentrations of drugs present in blood.
  • Urine toxicology assays
    • Urine was traditionally the specimen of choice for neonatal drug testing, although collection is difficult. The adhesive for the collection bag causes skin irritation and frequently fails to adhere. Another disadvantage is the short detection window; urine provides maternal drug use data only for a few days prior to delivery.
    • Urine toxicology screening is useful for clinical and research purposes. Urinary excretion of metabolites may be detectable only for a few days (eg, benzoylecgonine) to a few weeks (eg, cannabinoids). One cannot expect to ascertain early pregnancy use or even relatively recent use if the metabolite concentration does not reach the detection threshold.
    • Urine is relatively easy to obtain, requires minimal preparation (provided samples are not contaminated by meconium or feces), and can be analyzed using numerous laboratory techniques. Although urine samples generally contain a higher drug concentration than serum samples, the detection of compounds depends on obtaining an appropriate sample as close as possible to birth and also depends on the timing of maternal drug ingestion prior to delivery.
    • These tests detect recent use of cocaine and its metabolites, amphetamines, marijuana, barbiturates, and opiates. Cocaine can be detected in urine 6-8 hours after use in the mother and as long as 48-72 hours after use in the newborn.
    • Detection of drugs depends on many variables, including individual drug metabolism, hydration status of the subject, route of administration, and frequency of ingestion.
    • No drugs are known to crossreact with the immunoassays for cocaine and marijuana. Several over-the-counter remedies and herbal preparations may contain ephedrine and phenylpropanolamine (recalled from US market), which can produce false-positive enzyme immunoassay test results for amphetamines. Therefore, confirmatory testing is required.
    • Immunoassay for opiates does not distinguish between codeine, morphine, or their glucuronide conjugates.
  • Meconium analysis
    • Meconium analysis is currently considered the best method for detecting drug exposure in pregnancy. It provides a wider window of detection of gestational exposure, presumably as remote as the second trimester, when drugs begin to accumulate in meconium (by direct deposition from the biliary tree or when the fetus ingests amniotic fluid).
    • Meconium analysis is reliable for detecting opioid and cocaine exposure after the first trimester and can be used to detect a range of other illicit and prescribed medications.
    • Meconium can be contaminated by infant urine, although only cocaine or opiate use within approximately 72 hours of birth is reflected.
    • False positive results occur if meconium is contaminated with urine, reflecting antepartum and perinatal exposure. Theoretically, lidocaine can cause a positive result, but a large amount is required. 
    • When a meconium sample is stored at room temperature, it decreases cocaine and cannabinoid levels by 25% per day.
  • Hair analysis
    • Neonatal hair testing can also identify prenatal drug exposure. Hair begins to form at approximately 6 months' gestation; a positive result indicates use during the last trimester. Hair testing is advantageous because the specimen can be collected at any point during the first 3 months of life, after which time infant hair replaces neonatal hair.14
    • This method is useful in detecting narcotics, marijuana, cocaine, and cocaine-alcohol metabolites, but the technique is expensive, is not widely available, and is limited by the procedures required to quantify the very small amounts of drug present. Obtaining an adequate sample may be difficult, and recent exposure might not be detected because hair growth is slow.
    • Analysis of 1.5 cm of maternal hair reveals the maternal drug use pattern during the previous 3 months. Drug metabolites can be detected in infant hair for 2-3 months after birth.

Other Tests

  • A recent report has suggested that detecting drug exposure from umbilical cord tissue has similar sensitivity and specificity to meconium samples and may have some advantages over collection of meconium.15 Testing umbilical cord tissue enables analysis to occur immediately after birth, compared with meconium testing, which is delayed as long as 3 days prior to specimen availability. Umbilical cord is easily and noninvasively collected and may reflect a long window of drug detection; however, because few studies have examined cord tissue analysis to date, interpreting results is difficult.
  • Additional assessment of mothers who abuse drugs and their infants includes screening for hepatitis B and hepatitis C and sexually transmitted diseases, including human immunodeficiency virus (HIV) infection.

More on Neonatal Abstinence Syndrome

Overview: Neonatal Abstinence Syndrome
Differential Diagnoses & Workup: Neonatal Abstinence Syndrome
Treatment & Medication: Neonatal Abstinence Syndrome
Follow-up: Neonatal Abstinence Syndrome
Multimedia: Neonatal Abstinence Syndrome
References
[ CLOSE WINDOW ]

References

  1. 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.

  2. 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].

  3. 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].

  4. 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].

  5. Substance Use During Pregnancy: 2002 and 2003 Update. National survey on drug use and health; June 2, 2005. [Full Text].

  6. Chasnoff IJ. Prenatal substance exposure: maternal screening and neonatal identification and management. Neoreviews. 2003;4(9):e228-e235.

  7. Cairns PA. Drug misuse: Conception into childhood. Current Paediatrics. December 2001;11(6):475-9.

  8. Prentice S. Substance misuse in pregnancy. Obstetrics, Gynaecology & Reproductive Med. September 2007;17:272-7.

  9. 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].

  10. [Guideline] American Academy of Pediatrics Committee on Substance Abuse. Drug-exposed infants. Pediatr. Aug 1995;96(2 Pt 1):364-7. [Medline].

  11. Finnegan LP. Neonatal abstinence syndrome: assessment and pharmacolotherapy. In: Neonatal therapy: An update. New York, NY: Excerpta Medica; 1986:122-46.

  12. 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].

  13. 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].

  14. Gray T, Huestis M. Bioanalytical procedures for monitoring in utero drug exposure. Anal Bioanal Chem. Aug 2007;388(7):1455-65. [Medline].

  15. Kassima Z, Greenough A. Neonatal abstinence syndrome: Identification and management. Current Paediatrics. June 2006;16:172-5.

  16. 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].

  17. 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].

  18. [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].

  19. 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].

  20. [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].

  21. 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].

  22. Jaudes PK, Ekwo E, Van Voorhis J. Association of drug abuse and child abuse. Child Abuse Negl. Sep 1995;19(9):1065-75. [Medline].

  23. American Academy of Pediatrics. Pickering LK. The Red Book: 2006 Report of the Committee on Infectious Diseases. 27th. 2006.

  24. [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].

  25. Bahwere P, Haumont D, Delange F. Congenital hypothyroidism and neonatal withdrawal syndrome. Eur J Pediatr. Nov 1996;155(11):937-8. [Medline].

  26. Bauer CR. Perinatal effects of prenatal drug exposure. Neonatal aspects. Clin Perinatol. Mar 1999;26(1):87-106. [Medline].

  27. 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].

  28. Buchi KF. The drug-exposed infant in the well-baby nursery. Clin Perinatol. Jun 1998;25(2):335-50. [Medline].

  29. 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].

  30. Frank L. Assessment and management of opioid withdrawal in ill neonates. Neonatal Network. 1995;14:39-48. [Medline].

  31. Johnson K, Gerada C, Greenough A. Treatment of neonatal abstinence syndrome. Arch Dis Child Fetal Neonatal Ed. Jan 2003;88(1):F2-5. [Medline].

  32. 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].

  33. 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].

  34. Kandall SR. Treatment strategies for drug-exposed neonates. Clin Perinatol. Mar 1999;26(1):231-43. [Medline].

  35. Kuschel C. Managing drug withdrawal in the newborn infant. Semin Fetal Neonatal Med. Apr 2007;12(2):127-33. [Medline].

  36. McKim EM. Caffeine and its effects on pregnancy and the neonate. J Nurse Midwifery. Jul-Aug 1991;36(4):226-31. [Medline].

  37. [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].

  38. 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].

  39. Pierog S, Chandavasu O, Wexler I. Withdrawal symptoms in infants with the fetal alcohol syndrome. J Pediatr. Apr 1977;90(4):630-3. [Medline].

  40. 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].

  41. 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].

  42. 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].

  43. Umans JG, Szeto HH. Precipitated opiate abstinence in utero. Am J Obstet Gynecol. Feb 15 1985;151(4):441-4. [Medline].

  44. 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].

  45. 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].

  46. Young T E, Mangum B. CNS Drugs. In: Neofax: A manual of drugs used in neonatal care. ed. Montvale, New Jersey: Thomson Reuters healthcare; 2008:173-205.

  47. Zeskind PS, Stephens LE. Maternal selective serotonin reuptake inhibitor use during pregnancy and newborn neurobehavior. Pediatrics. Feb 2004;113(2):368-75. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

neonatal abstinence syndrome, neonatal withdrawal syndrome, NAS, prenatal NAS, postnatal NAS, maternal substance abuse, low birth weight, prematurity, intrauterine growth retardation, IUGR, hypoglycemia, hypocalcemia, sepsis, hypoxic encephalopathy, intracranial hemorrhage, jitteriness, neonatal adaptation syndrome, maternal drug use, pregnant drug use, placental abruption, fetal alcohol syndrome, maternal substance abuse, drug use in pregnancy, sudden infant death syndrome, SIDS, depression, fetal alcohol syndrome, treatment, diagnosis

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Ashraf H Hamdan, MB, BCh, MSc, MD, MRCP, Clinical Assistant Professor of Pediatrics, Vanderbilt University Medical Center; Neonatologist, Mid Tennessee Neonatology Associates.
Ashraf H Hamdan, MB, BCh, MSc, MD, MRCP is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

Medical Editor

Scott MacGilvray, MD, Clinical Associate Professor of Pediatrics, East Carolina University School of Medicine
Scott MacGilvray, MD is a member of the following medical societies: American Academy of Pediatrics and American Medical Association
Disclosure: MedImmune Speakers Bureau Honoraria Speaking and teaching

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Brian S Carter, MD, FAAP, Professor of Pediatrics (Neonatology), Vanderbilt University School of Medicine; Co-director, Pediatric Advance Comfort Team, Monroe Carell Jr Children's Hospital at Vanderbilt
Brian S Carter, MD, FAAP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Hospice and Palliative Medicine, American Academy of Pediatrics, American Society for Bioethics and Humanities, American Society of Law Medicine and Ethics, National Hospice and Palliative Care Organization, and Southern Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Carol L Wagner, MD, Professor of Pediatrics, Medical University of South Carolina
Carol L Wagner, MD is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American Medical Women's Association, American Public Health Association, American Society for Bone and Mineral Research, American Society for Clinical Nutrition, Massachusetts Medical Society, National Perinatal Association, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Chief Editor

Ted Rosenkrantz, MD, Professor, Departments of Pediatrics and Obstetrics/Gynecology, Division of Neonatal-Perinatal Medicine, University of Connecticut School of Medicine
Ted Rosenkrantz, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Pediatric Society, Connecticut State Medical Society, Eastern Society for Pediatric Research, and Society for Pediatric Research
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.