Fetal Hemoglobin Synthesis Determined by -mRNA/ -mRNA -mRNA Quantitation in Infants at Risk for Sudden Infant Death Syndrome Being Monitored at Home for Apnea

Objective. Fetal hemoglobin (HbF) levels in the hemolysates obtained from infants who died from sudden infant death syndrome (SIDS) are reported to be markedly increased compared with controls. This finding could have been explained by increased HbF synthesis caused by episodes of hypoxemia in the SIDS infants. A prospective study in a group of infants being monitored at home after an apparent life-threatening event (ALTE) and considered at increased risk for SIDS was conducted with an improved ribonuclease protection assay. The ribonuclease protection assay allowed for the quantitation of [ /( )]-globin mRNAs, which has a highly significant correlation with the levels of HbF synthesis. Methods. Thirty-five infants who were admitted for an ALTE were included in the study. All infants were at home under surveillance with a cardiorespiratory monitor and followed in an apnea clinic with monthly appointments. Seventy-three blood samples were obtained between 38 and 61 weeks of postconceptional age. For control purposes, a similar group of 37 normal infants (99 samples) whose HbF synthesis was previously determined were included. Results. Mean [ /( )]-globin mRNAs were increased in the ALTE group at 42 to 45 and 46 to 49 weeks of postconceptional age (mean: 55.2 17.4% and 33.9 14%) in comparison with HbF synthesis in controls (mean: 42.6 13.7% and 23.6 9.8%). Conclusions. The data obtained in this report from infants who were considered at risk for SIDS show that HbF synthesis is increased between 42 and 49 weeks of postconceptional age. Determining HbF synthesis as described in this study may have value as a marker for episodes of hypoxemia for certain infants who are at risk for SIDS. Pediatrics 2003;112:e285–e288. URL: http: //www.pediatrics.org/cgi/content/full/112/4/e285; sudden infant death syndrome, apparent life-threatening event, fetal hemoglobin. ABBREVIATIONS. SIDS, sudden infant death syndrome; ALTE, apparent life-threatening event; HbF, fetal hemoglobin; HbA, adult hemoglobin. Sudden infant death syndrome (SIDS) is defined as the death of an infant at 1 year of age for which a complete investigation did not reveal a cause of death. In developed countries, including Canada, the incidence of death by SIDS is approximately 0.5/1000 live births. Death occurs principally between the age of 2 and 4 months. Infants who have had 1 or more apparent life-threatening events (ALTEs) for which there was a need for resuscitation have a 7% to 10% risk of SIDS.1 The etiologic hypothesis that is frequently retained for SIDS is that there is an anomaly or a delay in maturation of the brainstem, where the cardiorespiratory centers are situated. This anomaly could cause repeated episodes of hypoxemia. Several markers of long-term hypoxemia have been described in SIDS victims, namely the retention of periadrenal fat, increases in smooth muscle about the small pulmonary arteries,2 and extramedullary hematopoiesis.3 Detailed neuropathology examination and specific studies that identified necrosis and apoptosis have also revealed evidence of previous episodes of severe hypoxemia/asphyxia in SIDS victims.4 It can be postulated that victims of SIDS have experienced recurrent episodes of hypoxemia before death. A study by Giulian et al5 and confirmed by others6–9 showed that fetal hemoglobin (HbF) levels in the hemolysates obtained from infants who died from SIDS were markedly increased compared with controls. This finding could have been explained by increased HbF levels caused by unsuspected episodes of hypoxemia in the SIDS infants. The differences in HbF levels were most marked in children who were older than 50 weeks postconceptional age (ie, the period of peak incidence for SIDS). A subsequent report by Zielke et al10 failed to confirm the findings of Giulian et al.5 They used 3 different assays for the determination of HbF and reported no significant differences in levels of HbF in postmortem blood samples of 67 infants who died of SIDS compared with 102 controls. However, a comprehensive study by Fagan and Walker6 showed elevated levels of HbF in blood samples of 106 full-term SIDS cases compared with 425 full-term control cases of known gestational ages. From the *Division of Neonatology, Department of Pediatrics, University of Montreal, Ste-Justine Hospital and Research Center, Montreal, Quebec, Canada; ‡Respiratory Medicine Division, Montreal Children’s Hospital, Montreal, Quebec, Canada; §Pulmonary Research Unit, Department of Pediatrics, Université de Sherbrooke, Québec, Quebec, Canada; and Department of Epidemiology and Biostatistics and Occupational Health, McGill University, Ste-Justine Hospital and Research Center, Montreal, Quebec, Canada. The results of this study were presented at a platform session at the Pediatric Academic Societies Annual Meeting; May 3, 2003; Seattle, WA. Received for publication Feb 21, 2003; accepted May 14, 2003. Reprint requests to (H.B.) Research Center, Hospital Sainte-Justine, 3175, Côte Ste-Catherine, Montreal, Quebec, H3T 1C5, Canada. E-mail: harry. [email protected] PEDIATRICS (ISSN 0031 4005). Copyright © 2003 by the American Acad-