Addressing Drivers of Sudden Unexplained Infant Death Among Prenatally Substance-Exposed Infants

Sudden unexplained infant death (SUID) is a devastating outcome for any family. In the United States, rates of SUID declined markedly from 1990 to 2000 because of public health messaging promoting supine sleep positioning.¹ However, SUID rates have remained relatively unchanged between 2000 and 2020, with persistent racial and geographic disparities.¹ A meta-analysis of literature through 2020 identified an association between increased risk of sudden infant death and prenatal substance exposure (PSE).² Few studies, however, have been able to comprehensively investigate drivers of SUID among infants with PSE. In this issue of Pediatrics, Deutsch and colleagues’ investigation substantially adds to previous research by evaluating an array of factors known to be related to SUID, including bedsharing, supervisor impairment, social drivers of poor health, and family vulnerability among cases of sleep-related SUID among infants with and without PSE.³ Deutsch et al used the National Fatality Review-Case Reporting System, where local and state agencies completing infant mortality reviews submit data using a standardized reporting tool.⁴

Deutsch and colleagues identified 2010 cases of sleep-related SUID reported between 2015 and 2020 and found that 14% of reported sleep-related SUID deaths had PSE.³ Among all cases, half of the deaths involved bedsharing with an adult, with no differences between infants with and without PSE. Additionally, 19% of cases were reported to have an impaired supervisor and 50% of supervisors were asleep at the time of infant death, with higher proportions among infants with PSE than unexposed infants.³ Notably, among cases with data available indicating supervisor impairment, the majority of cases also involved bedsharing, with no difference between infants with and without PSE.³

The study is an important contribution to the relatively sparse literature around postnatal modifiable factors contributing to sleep-related SUID risk among infants, including those with PSE, yet also highlights the challenge of studying SUID (an extremely rare condition at a rate of 93 cases per 100 000 live births) and its risk factors.¹ For example, without inclusion of a non-SUID control group, caution is needed when interpreting the significance of the risk factors identified among infants with PSE. It is unclear whether the magnitude of the risk factors identified among infants with PSE are similar to the general population.

Additionally, the lack of a control group leaves unanswered an important question: Is prenatal substance exposure itself an independent risk factor for SUID after adjustment for other known confounders? Although previous literature supports such a link, our understanding of confounding factors has advanced. Deutsch identified that 71% of infants with PSE had nicotine exposure, compared with only 31% of unexposed infants. Prenatal and postnatal nicotine exposure significantly increases the risk of SUID.⁵ Although the exact mechanism is not fully understood, it is proposed that nicotine exposure impairs the brainstem’s protective response to respiratory insults.⁵ Thus, nicotine exposure may be a critical confounder of SUID risk among infants with PSE. To address issues of residual and unmeasured confounding in previous studies describing an association between SUID and PSE, population-level registries, including large numbers of births, detailed data on social and medical risk factors prenatally and postnatally, and data on SUID cases are needed. However, developing and maintaining such registries poses significant challenges.

Finally, the study findings should be interpreted considering the potential influence of missing data, both within data of cases available, as well as relative to the overall population of sleep-related SUID cases. The registry used by Deutsch et al is estimated to encompass ∽40% of SUID cases in the United States.⁴ However, the southeastern part of the United States, including regions of Appalachia hit hard by the opioid overdose epidemic, are not proportionally represented, potentially underestimating cases of SUID among those with PSE. Additionally, the key field the authors selected to indicate PSE “was the infant/fetus delivered drug exposed” does not delineate type of prenatal substance exposure. Without high-quality information about prenatal exposures, it is unclear as to what the PSE category actually reflects.

Overall, regardless of the underlying mechanism of SUID risk among infants with PSE, the findings by Deutsch et al highlight the importance of supporting caregivers of infants with PSE in SUID-reducing strategies including smoking cessation, breastfeeding, and safe sleep practices (supine positioning, room-sharing but not bedsharing, and avoidance of soft bedding or objects in the sleep space).⁶ There are numerous effective interventions that include educational messaging targeting attitudes and beliefs of new parents.⁶ However, interventions targeting the unique needs of caregivers with infants with PSE are lacking. Many of these caregivers experience competing priorities related to their own medical and psychiatric care, a lack of social support, and addressing their infants’ ongoing withdrawal symptoms, feeding difficulties and challenging temperaments.^7–10 Tailored, supportive, and nonpunitive interventions that address the deleterious influence of stigma toward pregnant and parenting people who use substances are needed to ensure the well-being of families affected by prenatal substance use.

Glossary

PSE

prenatal substance exposure

SUID

sudden unexplained infant death