Second-Trimester Maternal Serum Levels of Alpha-Fetoprotein and the Subsequent Risk of Sudden Infant Death Syndrome

Abstract

Because an elevated maternal serum level of alpha-fetoprotein (AFP) in the second trimester of pregnancy is evidence of placental function and strongly predicts unexplained stillbirth, a study was planned to determine whether second-trimester maternal AFP levels are associated with the future risk of sudden infant death syndrome (SIDS). Unexplained stillbirth and SIDS are known to have some characteristics in common. A prenatal screening database for women in western Scotland totalled 214,532 women having singleton births in the years 1991–2001. Deaths designated as being SIDS deaths occurred within the first year of life. The 114 deaths designated as SIDS made the incidence of such deaths 5.3 per 10,000 live births (95% confidence interval, 4.4–6.4). Women whose infants died of SIDS were younger and shorter than the others and had lower body mass indices. Their parity was higher and they were likelier to be socioeconomically deprived. The same mothers were more likely to smoke, more often delivered male infants, and had offspring of lower birth weight. Second-trimester AFP levels were higher in the SIDS mothers, and the risk of SIDS increased with increasing maternal serum AFP levels. The risk of SIDS correlated inversely with both birth weight and gestational age at birth. Although the association between AFP and SIDS was less marked after adjusting for these factors, it remained significant. Adjusting for maternal age, infant gender, parity, and smoking status by multivariate analysis did not substantially influence the association between AFP and the risk of SIDS. No significant interactions were found between maternal serum AFP and any maternal or obstetric characteristics. The risk of SIDS did not relate to maternal serum levels of human chorionic gonadotropin. These findings support a direct association between maternal serum AFP levels in midpregnancy and the subsequent risk of SIDS. An adverse intrauterine environment in early pregnancy, impairing fetal growth and disposing to preterm birth, may be a major determinant of the risk of SIDS.