To the Editor: The study of brainstem abnormalities in sudden infant death syndrome (SIDS) by Dr Paterson and colleagues1 concluded that an abnormality of serotonin function in the brainstem is a specific cause of SIDS, but the authors did not address contrary evidence. The key issue is whether these abnormalities are a cause or an effect of hypoxia. Because the autopsies were not part of a prospective study, they cannot establish when changes in serotonin function occurred.
Paterson et al suggest that the serotonergic abnormalities arise in the fetal state as a developmental disorder involving delayed neuronal maturation, leaving the infant vulnerable to SIDS; this is one of the factors of their triple risk model that also includes an exogenous stressor and a critical development period. However, this suggestion conflicts with reports of normal respiratory physiology in neonates who were assessed prospectively and subsequently died of SIDS.2
Another difficulty for the theory of a fetal origin of SIDS is the distribution of age at death of infants with SIDS. If a vulnerability originated in the fetus, that infant by definition has a congenital defect. We have shown that the age at death in infants with a congenital defect is most frequently just after birth3 ; their mortality rate in the first 2 weeks is 14 times that for SIDS for that period and decreases monotonically toward 0. A similar age distribution was also seen in the age of death of infants from severe maternal anemia3 who, as a result, experienced hypoxia before birth. With SIDS deaths, in contrast, mortality is initially low and peaks between 2 and 3 months—the first month being relatively spared.3
In the cerebrospinal fluid of 53 infants with SIDS, Cann-Moisan et al4 found that the levels of metabolites of serotonin and other neurotransmitters were elevated compared with those of age-matched controls, indicating that these metabolites were released from brain tissues, presumably in an attempt at autoresuscitation. These authors also found similar levels of tryptophan in the spinal fluid of infants who had survived severe asphyxia.
The absence of gliosis in some infants with SIDS can be explained by the work of Del Bigio and Becker,5 who showed that the appearance of gliosis required an interval of 4 or more days after hypoxic injury.
We believe that the evidence presented by Paterson et al does not overcome the results of studies that point to hypoxia as the probable genesis of both gliosis and injury to the neurotransmitter systems. There is scant evidence that serotonin abnormalities in the fetus are a specific precursor of SIDS weeks after birth.
Financial Disclosures: None reported.
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
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