What is the pathophysiology of neonatal abstinence syndrome (NAS)?

Updated: Dec 20, 2017
  • Author: Ashraf H Hamdan, MD, MBBCh, MSc, MRCP, FAAP; Chief Editor: Santina A Zanelli, MD  more...
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Most illicit drugs cause an addiction in the mother and dependence in the infant. Dependence or tolerance in the latter is due to passage of the drugs across the placental barrier; this occurs in varying degrees, depending on the pharmacokinetic properties of the individual drugs. Substances that act on the central nervous system (CNS) are usually highly lipophilic and have relatively low molecular weight. These characteristics facilitate crossing from maternal to fetal circulation, with rapid equilibration of free drug between mother and fetus. Once drugs cross the placenta, they tend to accumulate in the fetus because of the immaturity of the renal function and the enzymes used for metabolism. Disruption of the transplacental passage of drugs at birth results in the development of a withdrawal syndrome.

Neonatal abstinence syndrome (NAS) is often a multisystem disorder that frequently involves the CNS, gastrointestinal (GI) system, autonomic system, and respiratory system. Manifestations of NAS depend on various factors, including the drug used, its dose, frequency of use, and the infant's own metabolism and excretion of the active compound or compounds. In addition, prenatal NAS depends on the infant's last intrauterine drug exposure and the mother's drug metabolism and excretion. Withdrawal is generally a function of the drug's half-life; the longer the half-life, the later the onset of withdrawal. A longer half-life is also associated with a decreased likelihood of NAS in the infant.

It has been suggested that brain-derived neurotrophic factor (BDNF) may have a neuromodulatory role during withdrawal after in utero opiate exposure. A study of 67 infants with NAS (n = 34) and without NAS (n = 33) noted significantly elevated levels of plasma BDNF in infants with NAS during the first 48 hours of birth compared to those without NAS. [8]

The specific effects of illicit substances are complex and depend on the type of substance, the frequency and duration of use, the dose, the route of substance intake, and the timing of substance exposure with respect to gestational period.

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