. Author manuscript; available in PMC: 2020 Nov 2.

Published in final edited form as: Pediatr Clin North Am. 2019 Apr;66(2):353–367. doi: 10.1016/j.pcl.2018.12.006

Table 1.

Maternal, infant, and/or environmental factors that can alter infant neonatal abstinence syndrome expression

Maternal Factors

Illicit substance use: heroin, cocaine, marijuana	In general, polysubstance exposure alters NAS expression by increasing its severity, or causes neurobehavioral signs consistent with a withdrawal phenomenon.¹⁰

Licit substance use/misuse: oxycodone, benzodiazepines, gabapentin, nicotine	Oxycodone and benzodiazepines increase NAS expression.^11–13
	Gabapentin produces an atypical NAS display.¹⁴
	Cigarette smoking can increase NAS severity.^15,16

Licit medications: psychotropics, OUD treatment medications (eg, methadone, buprenorphine)	Psychotropic exposure can alter or increase NAS display.¹⁷
	OUD treatment medications can predispose the exposed infant to NAS, but benefits associated with maternal comprehensive treatment that includes medications for OUD are paramount for the dyad.

Genetics/epigenetics	Infants with particular genotypes (SNPs) at the OPRM1 and COMT gene sites had less severe NAS expression.¹⁸
	Hypermethylation at the same sites was associated with more severe NAS, consistent with gene silencing.¹⁹

Breastfeeding	Can reduce NAS severity.²⁰

Infant factors

Sex	Male infants have been reported to have more severe NAS expression.^21,22

Gestational age	Preterm infants have less severe expression of NAS (notably, NAS measurement tools were designed for term infants. As such, NAS may not be adequately assessed in preterm infants).²³

Fetal programming	The fetus adapts to an unfavorable intrauterine environment by altering ANS set points. These changes can be adaptive in utero and maladaptive ex utero and may be expressed as NAS.²² Alterations from these changes may not be evident until the affected neurosystem matures, potentially later in life.²⁴

Environmental factors

Physical environment	NICU care can exacerbate NAS severity, while maternal rooming-in can reduce NAS severity.^25,26

Caregiver (parent or medical staff) handling and communication	Misinterpretation of or inappropriate responses to infant cues or insensitive handling can exacerbate NAS expression.²⁷

Abbreviations: ANS, autonomic nervous system; NICU, newborn intensive care unit; OUD, opioid use disorder; SNP, single nucleotide polymorphism.