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The rate of sudden unexpected infant deaths (SUID) increased during the COVID-19 pandemic, with a potential link to respiratory syncytial virus (RSV) hospitalizations, according to a national study.

Compared with the prepandemic period of March 2018 to December 2019, the risk of SUID increased by a relative 6% during the pandemic (intensity ratio [IR] 1.06, 95% CI 1.05-1.07), reported Catharine Paules, MD, of Penn State Health Milton S. Hershey Medical Center in Hershey, Pennsylvania, and colleagues in .

Looking at data on a monthly level, SUID cases were elevated above prepandemic levels from July 2020 through December 2020 and especially from June 2021 to December 2021, with relative increases ranging from 10% to 14%.

Sudden infant death syndrome (SIDS) cases also increased by 10% in 2021 over the prepandemic period, with a significant intensity ratio. The greatest increases occurred in July 2021 (IR 1.18, 95% CI 1.13-1.22) and August 2021 (IR 1.17, 95% CI 1.13-1.22).

is defined as sudden death of a child younger than 1 year of age where the cause of death is not clear prior to investigation. SIDS is an infant death that occurs during sleep and remains unexplained even after postmortem investigation. SIDS comprises more than one-third of SUID cases, while SUID also includes accidental suffocation in a sleeping environment and other deaths from unknown causes.

Notably, seasonal shifts in RSV hospitalizations during 2021 correlated with monthly changes in SUID in that same year, Paules and colleagues wrote.

Prepandemic hospitalization rates for influenza and RSV followed conventional seasonal patterns, but during 2020 when the COVID-19 pandemic began, the U.S. experienced historically low levels of influenza and RSV cases due to infection mitigation measures. As a result, there were few influenza or RSV-related hospitalizations during 2020.

However, as COVID-19 vaccines became available in 2021, pandemic precautions were lifted across the country. As schools and workplaces reopened during the second year of the pandemic, resurgences of seasonal respiratory viruses occurred at unexpected times and with increased severity. Hospitalizations due to RSV increased in 2021 from June to December -- occurring over several months outside the normal respiratory season.

"This resurgence was particularly extensive in infants and small children, who were increasingly susceptible due to a combination of waning maternal immunity and lack of individual exposure," the authors wrote.

"These findings suggest that the pronounced shift in SUID epidemiology during the second year of the COVID-19 pandemic may be associated with altered infectious disease transmission at the time," Paules and colleagues posited.

"We still don't know why infants die from SUID, but our findings suggest more research is needed regarding infectious contributors to SUID, such as RSV," co-author Emma Guare, of Penn State College of Medicine in Hershey, told MedPage Today. "There may be multiple risk factors that make infants more vulnerable to SUID, including environmental and genetic susceptibility, and an infection like RSV may amplify those factors," she explained, emphasizing that any theories remain hypothetical.

Of note, few influenza hospitalizations were described for 2020 or 2021, and COVID-19 hospitalizations were not clearly associated with monthly changes in rates of SUID.

"There are several ways that we can continue to protect babies and reduce the risk of SUID," Guare emphasized. "Primary care providers should continue to encourage interventions known to decrease the risk of SUID such as safe sleep environments, consistent prenatal care, breastfeeding, and immunizations. In addition, RSV- and other infection-prevention modalities should be discussed with new and expectant parents."

Compared with the prepandemic period of March 2018 to December 2019, SUID cases increased by 9% and SIDS increased by 10% in 2021. Cases of SUID increased from 94.2 to 102.7 per 100,000 live births across that period. SIDS increased from 35.2 to 39.8 per 100,000 live births.

The most recent CDC data reveals that rates of SUID , at 100.9 deaths per 100,000 live births.

The study used mortality data from death certificates across the U.S. with a single underlying cause of death. Paules and investigators analyzed cause-specific death rates and overall SUID rates. The primary outcome was the monthly difference in SUID rates during the pandemic versus before the pandemic; the secondary outcome was monthly differences in the rate of SIDS. CDC data were used to identify hospital rates for influenza, RSV, and COVID-19 per 100,000 live births.

Among identified SUID cases, 42% were female. Race and ethnicity data were only available between 2018 and 2020 but showed that 38.6% of cases occurred in Black infants, 56.5% occurred in white infants, 2.5% occurred in American Indian or Alaska Natives, and 2.4% were Asian.

Paules and colleagues noted that the data used in the study were limited by variations in state reporting and investigation practices of SUID cases. They were also unable to confirm causation between RSV cases and SUID data, nor could they assess the impact of potential confounders.

"Risk factors and protective factors for SUID may have changed in a more nuanced way during the pandemic," said Guare. "We found it interesting that there was variation in the rates of SUID and SIDS when looking at this more granular level and feel this warrants more investigation."

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