Sudden unexpected early neonatal deaths within the first week of life are associated with distinct features that diverge from sudden unexpected infant deaths that take place in the remainder of the first year of life, according to a retrospective analysis of CDC data.

Across all SUID and accidental suffocation cases recorded by the CDC from 2003 to 2013, lower live birth order, low birth weight, and married parents were risk factors for sudden unexpected early neonatal death, occurring within the first week of life, reported Tatiana Anderson, PhD, of Seattle Children's Research Institute, and colleagues.

By contrast, risk factors for deaths that occurred in the post-perinatal period (7-364 days) included higher live birth order, single mothers, younger mothers, or smoking in pregnancy, according to the study online in Pediatrics.

"A lot of theories in the literature suggest there is a whole continuum of underlying pathogenesis that contributes to sudden unexpected death through stillbirth and early childhood and perhaps some underlying complications during the neonatal period contributing to SUIDs," Anderson told MedPage Today. "We're not saying that's not a possibility, but our study suggests it isn't necessarily a continuum and the population of children that die in the first week is a very different population than the population of children that die after the first week."

More than 60% of deaths in the first month of life occur on the first day. This short time span, coupled with the emotional turmoil involved with sudden unexpected infant deaths, can lead to inconsistencies in terms of which infants receive birth certificates and are included in this dataset, wrote Richard Goldstein, MD, of Boston Children's Hospital, in an accompanying commentary.

"Research on SIDS and stillbirths suggests a biological continuum between fetal vulnerabilities and SIDS, not a disconnect," Goldstein wrote, adding that obstetric characteristics such as elevated ⍺ fetoprotein levels during pregnancy, brain abnormalities, and variants in cardiac arrhythmia genes are linked to both stillbirth and SIDS.

"Although [this study] may point to an area that requires new thinking, misclassification may exaggerate the differences within SUID and mask these commonalities," Goldstein noted. "In fact, [the] study's identification of birth order differences in the [two] populations may reflect the association between SIDS and less successful later pregnancies."

For this study, Anderson and colleagues included all SUID cases in the CDC Birth Cohort Linked Birth/Infant Death Data Set classified with ICD-10 codes for SIDS of an ill-defined or unknown cause, as well as accidental suffocation or strangulation in bed.

Overall, 37,624 cases were recorded, of which 3.3% occurred in the first week and 1.6% took place on day zero. The earlier deaths were mostly recorded as SIDS from an ill-defined or unknown cause (67%), with fewer categorized as SIDS (24%) and accidental suffocation in bed (9%). For the later deaths, more than half were classified as SIDS (55%), with a minority classified as SIDS of ill-defined or unknown cause (28%) or accidental suffocation (17%).

The ability of the model to discriminate between early and post-perinatal deaths was measured through an area under the curve of 77.3%, the investigators added.

Higher birth order was associated with post-perinatal SUID in a progressive fashion, a pattern that has been shown in prior studies and has also been linked to maternal age and lower socioeconomic status, the authors reported. However, the likelihood of an early death was lower for a mother's second versus first live birth, the team noted.

"It is currently unknown why the trends are opposite, but it is yet another clue that the underlying physiologic causes of death are different between these [two] groups," the researchers wrote.

For deaths occurring after 1 week of birth, children whose mothers were unmarried were at a higher risk for post-perinatal SUID (adjusted odds ratio 1.19, 95% CI 1.15-1.23, P<0.001), whereas the risk of early death was decreased (aOR 0.72, 95% CI 0.61-0.85, P<0.001), Anderson and co-authors reported. "This can possibly be explained by age because younger mothers (ages 15–24), who are more likely to be unmarried, also exhibited lower [sudden unexpected early neonatal death] rates."

There were two peaks of infant death rates that corresponded with birth weight. About one in five (19%) deaths occurring in the first week of life involved infants with birth weights below 500 grams and the second peak occurred among post-perinatal SUIDs at 3,000-3,499 grams.

"These [two] peaks exhibit different time functions in distinct periods of development likely indicating separate underlying causes of death," the authors noted.

Smoking was a risk factor regardless of timing of death, although the risk was higher in the post-perinatal period than in the early period. However, after adjustment, the risk of death within the first 48 hours was nonsignificant, although the risk sharply increased and peaked at day 21 (aOR 2.34, 95% CI 1.79-2.89, P<0.001), and then plateaued for the next 6 months.

The primary limitation of the study is that the data only extends to the point of birth, such that the authors did not have access to any environmental factors that may have affected death rates after birth, Anderson said. The process of classifying infant deaths is also subjective, and some coroners and medical examiners may have classified SUID deaths differently, she added.