BACKGROUND:Unexplained stillbirth and the sudden infant death syndrome (SIDS)share some features.A raised maternal serum level of alpha-fetoprotein during the second trimester of pregnancy is a marker of placental dysfunction and a strong predictor o f the risk of unexplained stillbirth.It is unknown whether alpha -fetoprotein levels also predict the risk of SIDS.METHODS:We linked a prenatal -screening database for wo men in western Scot-land with databases of maternity,perinatal death,and birth and death certifications to assess t he association between second -trimester levels of maternal serum alpha -feto-protein and the subsequent risk of SI DS.RESULTS:A-mong 214,532women with singleton bi rths,there were114cases of SIDS(incidence,2.7per 10,000births a-mong women with alpha -fetoprotein l evels in the lowest quintile and 7.5per 10,000births am ong those with levels in the highest quintile).When the lowest quintile was used as a referent,the unadjusted odds ra tios for SIDS for the second through fifth quintiles were1.7(95percent confi-dence interval,0.8to 3.5),1.8(95percent confidence interval,0.9to 3.7),2.5(95percent confidence inter-val,1.3to 4.8),and 2.8(95percent confidence inter-val,1.4to 5.4),respectively(P for trend =0.001).The risk of SIDS varied inversely with th e birth -weight per-centile and the gestational age at delivery;after adjustment for these factors,the odds ratios fo r SIDS were 1.7(95percent confidence interval,0.8to3.5),1.7(95percent confidence interval,0.8to 3.5),2.2(95percent confi-dence interval,1.1to 4.4),and 2.2(95percent confi-dence interval,1.1to 4.3),respectively(P for trend =0.01).CONCLUSIONS:There is a direct asso ciation be-tween second -trimester maternal se rumalpha -fetoprotein levels and the risk of SIDS,which may be mediated in part through impaired fetal growth and pr eterm birth. BACKGROUND: Unexplained stillbirth and the sudden infant death syndrome (SIDS) share some features. A raised maternal serum level of alpha-fetoprotein during the second trimester of pregnancy is a marker of placental dysfunction and a strong predictor of the risk of unexplained stillbirth. It is unknown whether alpha -fetoprotein levels also predict the risk of SIDS. METHODS: We linked a prenatal-screening database for wo men in western Scot-land with databases of maternity, perinatal death, and birth and death certifications to assess t he association between second -trimester levels of maternal serum alpha-feto-protein and the subsequent risk of SI DS .RESULTS: A-mong 214,532 women with singleton births, there were 114 cases of SIDS (incidence, 2.7per 10,000 births a-mong women with alpha - fetoprotein l evels in the lowest quintile and 7.5per 10,000births am ong those with levels in the highest quintile) .When the lowest quintile was used as a referent, the unadjusted odds raiosios for SIDS for the second through fifth quintiles were 1.7 (95percent confi dence interval, 0.8 to 3.5), 1.8 (95percent confidence interval, 0.9 to 3.7), 2.5 (95percent confidence inter-val, 1.3 to 4.8), and 2.8 val, 1.4to 5.4), respectively (P for trend = 0.001). The risk of SIDS varied inversely with th e birth-weight per-centile and the gestational age at delivery; after adjustment for these factors, the odds ratios fo r SIDS 1.7 (95percent confidence interval, 0.8 to 3.5), 1.7 (95percent confidence interval, 0.8 to 3.5), 2.2 (95percent confi-dence interval, 1.1to 4.4), and 2.2 , respectively (P for trend = 0.01). CONCLUSIONS: There is a direct asso ciation be-tween second -trimester maternal se rumalpha -fetoprotein levels and the risk of SIDS, which may be mediated in part through impaired fetal growth and pr eterm birth .