To investigate the hypothesis that chronic fetal hypoxia contributes to the etiology of sudden infant death syndrome (SIDS), a possible interaction between the effect of maternal cigarette smoking and low hematocrit during pregnancy on the risk of SIDS was studied using the US Collaborative Perinatal Project cohort. The 193 SIDS cases identified in the cohort were analyzed with 1930 controls randomly selected from infants who survived the first year of life. After adjustment for maternal age, infants born to mothers who smoked 10 or more cigarettes per day and who were anemic (hematocrit less than 30%) during pregnancy were at a much higher risk of SIDS than infants born to mothers who did not smoke and were not anemic (odds ratio = 4.0; 95% confidence limits, 2.1 and 7.4). Smoking 10 or more cigarettes per day vs none increased the risk of SIDS by 70% among women with hematocrit at or above 30% but increased risk threefold among women with hematocrit below 30%. After adjustment for more potential confounders in a logistic regression model, the effect of smoking on SIDS continued to increase with lower levels of hematocrit during pregnancy. Birth weight accounted for very little of these associations. Low hematocrit was not a risk factor for SIDS among nonsmokers but became an important predictor among heavy smokers. These findings are in agreement with the hypothesis that chronic fetal hypoxia may predispose to SIDS, possibly by impairing the normal development of the fetal central nervous system.

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