AbstractsOne of the most striking features of the sudden infant death syndrome (SIDS) is its age-related pattern. The incidence of SIDS peaks at 2 to 4 months after delivery, and it is rare after 9 months. Research into specific mechanisms frequently suggests an association between SIDS and cardiopulmonary deficiences, defective central respiratory control, or both.This study was undertaken to determine whether levels of fetal hemoglobin (hemoglobin F) are elevated in patients with SIDS, as compared with the levels in age-matched controls. By eliminating (at autopsy) known clinical conditions associated with sustained elevations in hemoglobin F apparent in older infants (i.e., older than 1 month), such as sickle cell disease, hereditary persistence of fetal hemoglobin, thalassemia, hypoplastic anemia, leukemia, and trisomy 13, the authors found that hemoglobin F was substantially increased in the majority of patients with SIDS.Blood samples were collected at autopsies during a 5-year period (1981–1986). Control samples were collected from normal living infants. In all cases of death from SIDS or other known causes, complete autopsies were performed. The percentage of hemoglobin F (relative to hemoglobin A) was determined by hemoglobin-subunit analysis with a high-voltage vertical-slab isoelectric focusing procedure.Known relative amounts of hemoglobin F and hemoglobin A were compared for their relative proportions of γ-and β-globin chains, as measured with the isoelectric focusing protocol. The data showed good linearity (r= 0.9917) between the proportion of γ-globin chain and the total hemoglobin F between 0 and 97.5 per cent. The use of subunit analysis of denatured samples eliminated the problems associated with heterogenicity in the charge of the heme ring in native hemoglobiin tetramers.The results of an analysis of a representative gel are shown in Figure 1.Lane Acontains a hemoglobin A and hemoglobin S standard with both the β and βs(sickle) isoforms, whereas B and C contain mixed hemoglobin F and hemoglobin A standards. The standards served as internal controls, withlane Bcontaining a high proportion of hemoglobin F (85 per cent), andlane Ca low proportion (10 per cent).Lanes 1 to 4demonstrate the globin profiles of living controls, matched for the postconceptional ages of 51 and 63 weeks (lanes 1 and 3) with infants with SIDS(lanes 2 and 4). The hemoglobin F levels were substantially higher in the blood from patients with SIDS than in the blood from controls at both 51 and 63 weeks of postconceptional age. TheGγ/Aγ ratios were calculated from den-sitometric scans. Previous studies have shown that the ratio is normally 3:1 at birth and approximately 2:3 at 6 months of age. The control samples had normalGγ/Aγ ratios for their respective ages. Although the patients with SIDS had normal ratios for the percentage of hemoglobin F present, these ratios were elevated for their postconceptional ages.The percentage of hemoglobin F in the SIDS and control groups was plotted against increasing postconceptional age. All samples in both groups were from infants born at least 2 weeks before the sample was taken. Ten infants in the control group had been born 4 to 14 weeks prematurely. The mean (± 2 SD) value for the normal decline in hemoglobin F with increasing age was derived from 432 different determinations of the percentage of hemoglobin F by means of alkali denaturation,59Fe labeling, and globin analysis. The authors assumed a term delivery to be one that occurred at least 39 weeks after conception.The data on the infants with SIDS and the controls are summarized in Table 1, according to age group (less than 50 weeks, below the midpoint of the normal steep decline in hemoglobin F, and more than 50 weeks) and in the total population (39–75 weeks). The hemoglobin F levels in each of the populations with SIDS were significantly elevated as compared with those in the controls and the published normal ranges, particularly those after 50 weeks of postconceptional age.