Background: Public attention is given to infants with socially high risks of child abuse and neglect, while clinical attention is provided to infants with a biologically high risk of diseases. However, few studies have systematically evaluated how biological or social factors cross over and affect cause-specific infant mortality.

Methods: We linked birth data with death data from the Japanese national vital statistics database for all infants born from 2003–2010. Using multivariate logistic regression, we examined the association between biological and social factors and infant mortality due to medical causes (internal causes), abuse (intentional external causes), and accidents (unintentional external causes).

Results: Of 8,941,501 births, 23,400 (0.26%) infants died by 1 year of age, with 21,884 (93.5%) due to internal causes, 175 (0.75%) due to intentional external causes, and 1,194 (5.1%) due to unintentional external causes. Infants with high social risk (teenage mothers, non-Japanese mothers, single mothers, unemployed household, four or more children in the household, or birth outside of health care facility) had higher risk of death by intentional, unintentional, and internal causes. Infant born with small for gestational age and preterm had higher risks of deaths by internal and unintentional causes, but not by intentional causes.

Conclusions: Both biological as well as social factors were associated with infant deaths due to internal and external causes. Interdisciplinary support from both public health and clinical-care professionals is needed for infants with high social or biological risk to prevent disease and injury.