What is Neonatal Abstinence Syndrome?

Definition of Neonatal abstinence syndrome is a group of drug withdrawal symptoms that occur in newborns due to their mother's drug abuse during pregnancy. There are two major types of NAS: the first type is caused by drug abuse by the mother during pregnancy, and the second is postnatal NAS secondary to discontinuation of medications such as morphine used for pain killers in the newborn.

Neonatal Abstinence Syndrome
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What are the causes of NAS? 

Opioids are the substances that most often cause NAS. Although amphetamines, antidepressants, benzodiazepines, and other psychotropic substances can also cause this syndrome. In addition to illegal opioids, therapy using opioid-derived drugs also has the risk of causing NAS.

What are the symptoms of neonatal abstinence syndrome?

The symptoms of NAS involve the central and autonomic nervous system, as well as the gastrointestinal system. Commonly, NAS is characterized by irritability, constant crying, tremors, appetite disturbances, vomiting, diarrhea, excessive sweating, disturbed sleep cycles, and sometimes accompanied by neonates' seizures.

What is the Pathophysiology of Neonatal Abstinence Syndrome (NAS)? 

Not all newborns by mothers who abuse opiates have Neonatal Abstinence Syndrome (NAS), and the pathophysiology is still not understood.

The opiate is water-soluble, lipophilic, has a low molecular weight,  so it can easily cross the placenta. Immature metabolic processes in the fetus cause the opiate's half-life to be longer. The interruption of opiate exposure after the baby is born will cause adenyl cyclase hyperactivity, which will trigger the release of various neurotransmitters.

In pregnant women taking antidepressants, NAS is caused by an increase in serotonin and noradrenaline. The use of benzodiazepines will cause an increase in GABA, which can cause withdrawal symptoms, while the amphetamine withdrawal symptom is a secondary result of a decrease in dopamine, serotonin, and other monoamines.

The severity of NAS symptoms is influenced by the substances/drug used, maternal factors (nutrition or stressors), metabolism by the placenta, genetic factors, infant factors (premature or infectious), and environmental factors (including initial treatment). 

Morbidity and Mortality of Neonatal Abstinence Syndrome (NAS)

Globally the number of pregnant women abusing substances is increasing so that the incidence of neonatal abstinence syndrome (NAS) has also increased, especially in developing countries. In the United States, the incidence of NAS has increased severalfold between 2004-2013. This incidence is equivalent to the United Kingdom, Canada, and Western Australia and shows incidence globally. However, reports on the incidence of NAS in Asian populations are still missing.

In addition to the risk of experiencing NAS, babies born to mothers who abuse substances are generally born prematurely and experience growth disorders. However, NAS's severity is usually lower in premature babies than in term infants due to shorter substance exposure. Moreover, immature metabolism causes imperfect substance clearance so that the concentration of substances in the blood is still relatively high when the baby is born and decreases slowly with maturation.

Although NAS is commonly not fatal, it can cause severe problems and cause extended maintenance. Infants with NAS can experience heart rhythm disturbances, respiration, muscle tone, temperature, and various other physiological responses due to the autonomic nerve's dysregulation and instability. These symptoms can last for several days or even months. Infants with NAS are also more likely to experience breathing problems, sepsis, and postnatal eating disorders.

A cohort study reported that the mortality rate before the age of 5 years in infants with Neonatal Abstinence Syndrome (NAS) was three times the mortality of infants without NAS. The proportion of infants with NAS rehospitalized in the first five years of life is also higher, especially in the first and second years.

Indications for hospitalization include infectious diseases, parasitic infestations, nervous system disorders, respiratory system disorders, digestive tract disorders, skin diseases, perinatal disorders, accidents, and poisoning. Even infants with NAS are reported to be 2.5 times more likely to be rehospitalized within 30 postnatal days.

Apart from that, mothers who abuse drugs have higher mortality and morbidity, which indirectly causes interference with the baby being born.

How to Treat Neonatal Abstinence Syndrome (NAS)

For prevention, mothers identified as having a high risk of substance abuse need to be screened, intervened and treated. Confirmation of neonatal abstinence syndrome (NAS) in infants can be done by urine or meconium examination to identify the causative agent.

Pregnant women who are addicted to substances can be treated with substitution with methadone or buprenorphine. Substitution therapy during pregnancy can reduce substance use and improve the outcome of babies born, although it does not reduce the incidence of NAS.

Nonpharmacologic therapy includes supportive efforts to calm the baby (music therapy and baby massage), reduce stimulation, and feed more frequently with high-calorie formulas.

Conditions to administrate Pharmacological therapy are:
  • Supportive therapy fails to treat symptoms.
  • Finnegan's score is still high. Finnegan's score consists of 3 components of assessment: central nervous system disorders, metabolic/vasomotor / respiration disorders, and gastrointestinal disorders. Scores are assessed every 2 -4 hours. Pharmacotherapy indications are a score of ≥ 8 three times in a row or  ≥ 12 2 times in a row.
  • Emergency signs such as seizures appear.
  • Dehydration due to vomiting or diarrhea.

To date, there are no standard guidelines for pharmacological therapy of NAS. Pharmacological therapy that can be given is by substitution therapy using morphine, methadone, or buprenorphine. Benzodiazepines or α-adrenergic receptor agonists can also be given to control symptoms.

Pharmacological therapy given is more supportive and symptomatic. If substitution therapy is given, it is necessary to think about decreasing the dose to ensure the baby no longer experiences withdrawal symptoms.

Infants with NAS need development and behavior monitoring. Monitoring includes feeding, weight, and sleep patterns. Scoring with the Finnegan scoring system can be a guide for starting, monitoring, and ending NAS treatment.

If the baby has a good sleep pattern, adequate nutrition, increased body weight, and a stable Finnegan score with minimal intervention, the baby can be discharged.

NAS is not a contraindication for breastfeeding, except if the mother uses street drugs, uses multiple drugs, or is infected with HIV, so it is recommended that mothers breastfeed their babies after discharge.

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