Prenatal exposure to smoking and alcohol increases the risk for Sudden Infant Death Syndrome (SIDS). Physiological changes associated with these exposures are not well studied. Full-term infants were tested within the first 3 days of life. We hypothesized that maternal alcohol consumption and/or smoking during pregnancy would alter autonomic nervous system function. Newborns whose mothers smoked during pregnancy had lower beat-to-beat heart rate variability in quiet sleep. Infants whose mothers consumed alcohol had lower global heart rate variability, but only in active sleep. Unexposed infants demonstrated increases in heart rate with head-up tilt and decreases in heart rate with head-down tilt, but smoking and alcohol-exposed infants showed no significant responses. These results indicate that autonomic function is altered by prenatal exposure to alcohol and smoking. Such markers may provide early identification of infants at greatest risk for SIDS.

Sudden infant death syndrome (SIDS) is characterized by a sleep-related death in a seemingly healthy infant. Previously, we reported abnormalities in the serotonergic (5-HT) system of the medulla in SIDS cases in 2 independent datasets, including in the Northern Plains American Indians. The medullary 5-HT system is composed of 5-HT neurons in the raphé, extra-raphé, and arcuate nucleus at the ventral surface. This system is thought to modulate respiratory and autonomic function, and thus abnormalities within it could potentially lead to imbalances in sympathetic and parasympathetic tone. We report the case of a full-term American Indian boy who died of SIDS at 2 postnatal weeks, and who had subtle respiratory and autonomic dysfunction measured prospectively on the second postnatal day. Cardiorespiratory assessment of heart rate variability suggested that the ratio of parasympathetic to sympathetic tone was higher than normal in active sleep and lower than normal in quiet sleep in this case. At autopsy, arcuate nucleus hypoplasia and 5-HT receptor-binding abnormalities in the arcuate nucleus and other components of the medullary 5-HT system were found. This case suggests that medullary 5-HT system abnormalities may be able to be identified by such physiological tests before death. Replication of these findings in a large population may lead to the development of predictive cardiorespiratory assessment tools for future screening to identify infants with medullary 5-HT abnormalities and SIDS risk.

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