Ch. 9.5: Neonatal Exposure to Opioids

In this chapter, we look at what is known about prenatal exposure to opioids and a common result: neonatal withdrawal syndrome (NWS) at birth. While the emphasis here is on outcomes for the baby, it is important to recognize that opioid misuse/OUD greatly amplifies the risk of maternal health complications and death—representing “a leading cause of pregnancy-related deaths in the U.S.” (Sanjanwala & Harper, 2019, p. 192). Furthermore, opioid misuse during pregnancy often leads to mothers losing child custody, and parents using opioids are less likely to retain child custody than parents using other substances (Hall et al., 2016). Evidence suggests that medication-assisted treatment (MAT) for opioid use disorder increased the odds of parents retaining child custody (Hall et al., 2016).

Prenatal Opioid Exposure

As the explosion of prescription opioid drug misuse developed, the rate of maternal opiate use during pregnancy increased dramatically. In the U.S., the rate of mothers experiencing opioid use disorder at the time of hospital delivery in 2014 increased by more than 4 times compared to the 1999 rate—and OUD statistics do not fully describe opioid misuse during pregnancy (Haight et al., 2018). Opioid misuse/OUD during pregnancy contributes to a multitude of poor infant outcomes: stillbirth, preterm birth, low birth weight, neonatal withdrawal syndrome, and sudden infant death syndrome (Kandall, et al., 1993; Sanjanwala & Harper, 2019). The problem stems from opioids passing to the developing fetus’s brain and body organs through the placenta, then interacting with the baby’s opioid (mu-)receptors which resemble the adult pattern of distribution in the spinal cord by about 24 weeks (Ray & Wadhwa, 1999). Like an adult, the fetus can develop tolerance to the drug and withdrawal symptoms when the drug is no longer available with placenta separation from the mother at birth.

Each time a pregnant mother experiences withdrawal it places stress on the fetus and jeopardizes the pregnancy. For this reason, opioids with longer half-life (such as methadone) deliver a more even dose over 24 hours, reducing the mother’s withdrawal episodes, and improving outcomes for the pregnancy compared to a drug like heroin which has a relatively short half-life and multiple experiences of withdrawal daily (Reber et al., in press). The presence and severity of NWS is unpredictable, even with controlled dosing guidelines for methadone management: “some babies exposed to relatively low doses may experience severe NWS while other babies exposed to even higher doses may not” (Reber et al., in press).

Neonatal Withdrawal Syndrome

Previously called neonatal abstinence syndrome (NAS), the currently preferred term is neonatal withdrawal syndrome (NWS). The shift in terminology from abstinence to withdrawal more accurately described the infant’s experience of abruptly transitioning from the prenatal environment involving opioid exposure to the post-birth opioid withdrawal experience. As the rate of maternal opioid misuse during pregnancy has grown, so too has the rate at which NWS occurs 7.3 per 1,000 live births in 2017 compared to 1.5 in 1999 (Reber et al., in press; https://hcup-us.ahrq.gov/faststats/NASMap?setting=IP).  The rate also varies by geographical trends in opioid prescribing and OUD; for example, NWS ranges from fewer than 1 per 1,000 births in the District of Columbia to almost 50 per 1,000 in Vermont (Ko et al., 2016).

Withdrawal symptoms may appear up to 5 days following birth; symptoms following heroin exposure (4-24 hours) is typically more rapid than for methadone (24-48 hours) or buprenorphine (48-72 hours), due to the different half-lives and pharmacokinetic actions of these different substances (Reber et al., in press). Babies prenatally exposed to opioids may exhibit difficulty with breathing, meconium aspiration complications, feeding, sepsis (systemic infection), gastrointestinal symptoms (diarrhea leading to dehydration), moderating autonomic nervous system functions (e.g., managing body temperature, sweating), poor sleep, irritability, fussiness, jitteriness, seizures, and even death (Reber et al., in press; Sanjanwala & Harper, 2019). Their symptoms make these babies more difficult to care for and contribute to later developmental and health complications, as well as child maltreatment risks; long-term outcome effects of chronic exposure during prenatal development are unclear from the literature, in part because it is difficult to separate the impact of confounding, co-occurring, and post-birth risk and vulnerability factors and social determinants of health (Reber et al., in press). Initial newborn hospitalization is typically as long as 20 days for babies affected by NWS, resulting in tremendous direct medical costs across the nation estimated at $500 million to $1.5 billion annually (Reber et al., in press).

Screening for possible maternal opioid use/OUD is an important aspect of early detection and intervention during pregnancy and for infants born following prenatal opioid exposure—whether the opioid use was the result of following healthcare provider prescribing protocols, prescription drug misuse, methadone as MAT, or illicit substance use (e.g., heroin). All babies deemed at risk should be carefully screened and monitored throughout the first 3- to 5-day period (Reber et al., in press). Other psychoactive substances (polydrug use) can also affect the timing, degree, and outcomes of opioid withdrawal in newborns (Reber et al., in press). Treatment typically involves medically managed, step-wise withdrawal protocols using opioid medications (morphine, methadone, buprenorphine) to gradually wean the infant from all substances. However, if symptoms are not severe, supportive interventions and medical management of symptoms may suffice without escalation to pharmacologic treatment (Reber et al., in press). Non-pharmacologic interventions include:

• skin-to-skin contact with mother (and other parent/caregiver);
• low-stimulation environment (light and noise), which may include music and/or massage therapy;
• reduce auto-stimulation with tight swaddling, timely response to hunger and discomfort cues, providing comforting positions like gentle swaying/rocking;
• attending to hydration and increased caloric needs, including involving multi-disciplinary teams to aid in feeding infants with dysregulated suck/swallow/breathe patterns and “sensitive stomach” formulas as a supplement to/replacement for breast milk which can carry opioids to the nursing infant (Reber et al., in press).

The benefits of additional family support services following the infant’s release from care have been demonstrated (Reber et al., in press).