Signs due to hyperactivity of stomach and intestines:
Poor feeding and sucking reflex
Vomiting
Diarrhea
Signs due to hyperactivity of autonomous nervous system:
Fever
Sweating
Yawning, stuffy nose, and sneezing
Fast breathing

Causes
The drugs involved can include opioids, selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitor (SNRIs), tricyclic antidepressants (TCAs), ethanol, and benzodiazepines. Opioids may be more likely to cause NAS than other substances due to an increase in its usage. Exposure to heroin and methadone claimed to be correlated with a 60 to 80% occurrence of neonatal withdrawal, whereas buprenorphine has been associated with a lower risk. Neonatal abstinence syndrome does not happen in prenatal cocaine exposure. Prematurity and exposure to other drugs may instead be the cause of symptoms.The main mechanistic pathway of prescribed and illicit substance-induced NAS is the hyperactivity of the central and autonomic nervous system and gastrointestinal tract There are several potential mechanisms and pathways that have been proposed, which includes the interaction between the neurotransmitters and lack of adequate expression of opioid receptors. However, the main pathophysiology of this syndrome remains unknown. Most of the opioid induced NAS are due to opioid exposure during pregnancy for pain relief, misuse, or abuse of prescribed opioids or other medication-assisted treatment of opioid use disorder. Diagnosis
The presence of withdrawal in the neonate can be confirmed by taking a detailed medical history from the mother.
Both TIMP and MTIMP have been reported to inhibit glutamine-5-phosphoribosylpyrophosphate amidotransferase, the first enzyme unique to the de novo pathway for purine ribonucleotide synthesis. Experiments indicate that radiolabeled mercaptopurine may be recovered from the DNA in the form of deoxythioguanosine. Some mercaptopurine is converted to nucleotide derivatives of 6-thioguanine (6-TG) by the sequential actions of inosinate (IMP) dehydrogenase and xanthylate (XMP) aminase, converting TIMP to thioguanylic acid (TGMP). Animal tumors that are resistant to mercaptopurine often have lost the ability to convert mercaptopurine to TIMP. However, it is clear that resistance to mercaptopurine may be acquired by other means as well, particularly in human leukemias. It is not known exactly which of any one or more of the biochemical effects of mercaptopurine and its metabolites are directly or predominantly responsible for cell death.6-MP ribonucleotide inhibits purine nucleotide synthesis and metabolism by inhibiting an enzyme called phosphoribosyl pyrophosphate amidotransferase (PRPP amidotransferase). Since this enzyme is the rate limiting factor for purine synthesis, this alters the synthesis and function of RNA and DNA. Mercaptopurine interferes with nucleotide interconversion and glycoprotein synthesis. Pharmacogenetics
The enzyme thiopurine S-methyltransferase (TPMT) is responsible, in part, for the inactivation of 6-mercaptopurine. TPMT catalyzes the methylation of 6-mercaptopurine into the inactive metabolite 6-methylmercaptopurine – this methylation prevents mercaptopurine from further conversion into active, cytotoxic thioguanine nucleotide (TGN) metabolites.