Factors that affect the presentation of neonatal abstinence syndrome

Maternal factors	Effects
Illicit substance use	Polysubstance use increases NAS severity.
Licit substance use (nicotine, psychotropic medications, OUD treatment medications, gabapentin)	Psychotropics can alter/increase NAS symptoms. OUD treatment medications can predispose the infant to NAS, but benefits of treatment outweigh risks. Gabapentin produces atypical NAS symptoms.
Poor maternal health and well-being during the pregnancy, which can be caused by: Poor medical/obstetric care Maternal stress ACEs Violence Poverty Stigma associated with substance use/abuse	Poor maternal health and well-being during pregnancy can affect the infant and alter/increase NAS symptoms. These factors can also alter the parent/caregiver's ability to respond appropriately to the infant, which can worsen NAS severity.
Breastfeeding	Breastfeeding can decrease the length of pharmacologic treatment needed for NAS and decrease the length of stay for infants with NAS.
Infant factors	Effects
Sex	Male sex increases risk for more severe NAS.
Gestational age	Preterm infants have less severe NAS expression.*
Fetal adaptation to poor maternal health and well-being during the pregnancy	How the fetus adapts to poor maternal health and well-being during the pregnancy can affect NAS symptoms.^¶
Genetics/epigenetics	Infants with particular genotypes (at OPRM1 and COMT gene sites) have less severe NAS expression. Hypermethylation at the same sites is associated with more severe NAS.
Environmental factors	Effects
Physical environment	NICU care can exacerbate NAS severity. Rooming-in can reduce NAS severity.
Caregiver (parent or medical staff) handling and communication	Inappropriate responses to infant cues or insensitive handling can exacerbate NAS expression.

This table summarizes factors affecting the expression of NAS in newborns. For additional details, refer to separate UpToDate content on prenatal substance exposure and NAS.

NAS: neonatal abstinence syndrome; OUD: opioid use disorder; ACEs: adverse childhood experiences; OPRM1: opioid receptor μ-1; COMT: catechol-O-methyltransferase; NICU: neonatal intensive care unit.

* Tools designed for NAS measurement are designed for term infants, so NAS may not be adequately assessed in preterm infants.

¶ Fetal adaptations to poor maternal health and well-being during pregnancy may not be evident until later in life, when the affected neurosystem matures.

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Factors that affect the presentation of neonatal abstinence syndrome