A term gestation, newborn female was delivered vaginally to a G2P2 female with a history of heroin addiction. She had been on methadone treatment for 11 months and was doing well in treatment. She had prenatal care and her screening tests were negative. The intrapartum history was non-contributory and at delivery her Apgar scores were 8 and 9. The family history showed poly-drug addiction in the distant past, with only heroin addiction recently. The mother was getting regular mental health treatment. The parents were not married but both were employed and had 2 children by previous relationships in the household. The father had alcohol and tobacco use and no history of other substance use or abuse.
The pertinent physical exam at 30 minutes of life revealed a normal appearing female. Her weight was 3180 grams (25%), length 53 cm (50%) and head circumference of 34.0 cm (50%). She had some molding of her head. Normal red reflexes bilaterally. Heart was regular rate and rhythm without murmur. Lungs were clear for age. She had a 3-vessel cord. Neurologically she had good tone and strength.
The diagnosis of a healthy female was made. The parents agreed to all routine neonatal care at birth and she was monitored using the Finnagan scoring system. The mother was already aware that a cord drug screen would be sent because of the drug use which eventually was negative for any drugs that were not expected. The family also met with the social worker who did not identify any additional specific needs. The patient’s clinical course over the next 7 days did show intermittent elevated Finnagan scores but none were elevated serially so that pharmacological treatment was not needed. The patient was discharged and followed by the local family physician.
Neonatal abstinence syndrome (NAS) occurs in the first few days of life and is a complex withdrawal syndrome. The newborn is abruptly cut-off from their exposure to licit or illicit drugs that the mother is chronically consuming and which were being transmitted through the placenta to the fetus. “NAS is a highly variable and severe condition; it may be associated with central and autonomic nervous system dysfunction … and gastrointestinal disorders.” It can cause significant morbidity but is rarely fatal.
Fetal exposure has been increasing in the United States. In 2011-12, almost 5.9% of pregnant women were identified as drug abusers with the highest proportion being in the adolescent age group (15-17 years, 18.3%). A variety of drugs can cause it including opioids, methamphetamines and psychotropic agents. Fetuses exposed to opioids can have prematurity, intrauterine growth restriction, low birth weight, congenital anomalies and NAS. Transplacental passage of opioids increases with increasing gestational age and can also pass into the breast milk. Maternal treatment for drug addition can include long-acting opioids and other medications such as methadone or buprenorphine. Neonates of mothers using buprenorphine usually have milder post-natal courses than those treated with methadone, which is thought to be due to combinations of environment, physiologic and genetic factors.
NAS has variable onset, presentation and severity. Early onset (within 48 hours) is common for heroin, morphine or anti-depressant exposure. Late onset (after 48 hours) is common for methadone or buprenorphine exposure.
Common symptoms include:
- Central nervous system excitement – irritability, inconsolable crying, jittery, tremors, hypertonicity, seizures
- Central nervous system depression – lethargy, poor suck
- Autonomic nervous system – diaphoresis, temperature instability particularly hyperthermia, mottling, frequent sneezing and yawning, poor sleep
Hyperphagia is common with poor weight gain because the infants have high caloric needs (up to 150-250 kcals/kg/day).
- Cardiac – tachycardia, hypertension
- Gastrointestinal – diarrhea, emesis, electrolyte abnormalities, dehydration
Treatment includes keeping the infant with the family as appropriate, in a quiet, low-light environment with gentle handling. Non-nutritive sucking and breastfeeding (if not contraindicated) can also help the infant. Small, frequent amounts of liquid nutrition often help the infant. The Finnegen scoring system is one system designed to be used for monitoring term infants. Patients are serially monitored and scored and can assist in determining if additional interventions are needed including more frequent monitoring, pharmacological initiation, duration and weaning. Pharmacological treatment extends the usual hospital stay significantly with a mean stay of around 3+ weeks.
According to the American Academy of Pediatrics, “An infant born to a mother on a low-dose prescription opiate with a short half-life (eg, hydrocodone; average half-life, 4 hours) may be safety discharged if there are no signs of withdrawal by 3 days of age, whereas an infant born to a mother on an opiate with a prolonged half-life (eg, methadone) should be observed for a minimum of 5-7 days.
Questions for Further Discussion
1. Under what conditions would breastfeeding be encouraged and discouraged in mothers using licit or illicit substances?
2. What is the protocol for pharmacological intervention in NAS at your institution?
3. In your local environment, what is the role of the Department of Human Services, Social work and similar services in the care of a family with a substance exposed infant?
4. What are the potential long-term problems of in-utero exposure to illicit substances?
- Symptom/Presentation: Health Maintenance and Disease Prevention
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Hudak ML, Tan RC, Drugs TCO, Newborn TC on FA. Neonatal Drug Withdrawal. Pediatrics. 2012;129(2):e540-e560. doi:10.1542/peds.2011-3212
Raffaeli G, Cavallaro G, Allegaert K, et al. Neonatal Abstinence Syndrome: Update on Diagnostic and Therapeutic Strategies. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy. 2017;37(7):814-823. doi:10.1002/phar.1954
Tran TH, Griffin BL, Stone RH, Vest KM, Todd TJ. Methadone, Buprenorphine, and Naltrexone for the Treatment of Opioid Use Disorder in Pregnant Women. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy. 2017;37(7):824-839. doi:10.1002/phar.1958
Isemann BT, Stoeckle EC, Taleghani AA, Mueller EW. Early Prediction Tool to Identify the Need for Pharmacotherapy in Infants at Risk of Neonatal Abstinence Syndrome – Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy. 2017;37(7):840-848. Accessed September 28, 2020. https://accpjournals-onlinelibrary-wiley-com.proxy.lib.uiowa.edu/doi/10.1002/phar.1948
Holmes AP, Schmidlin HN, Kurzum EN. Breastfeeding Considerations for Mothers of Infants with Neonatal Abstinence Syndrome. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy. 2017;37(7):861-869. PubMed. Accessed October 6, 2020. tps://pubmed.ncbi.nlm.nih.gov/28488805/
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa