Nicotinic Receptors in the Brainstem Ascending Arousal System in SIDS With Analysis of Pre-natal Exposures to Maternal Smoking and Alcohol in High-Risk Populations of the Safe Passage Study.

Pre-natal exposures to nicotine and alcohol are known risk factors for sudden infant death syndrome (SIDS), the leading cause of post-neonatal infant mortality. Here, we present data on nicotinic receptor binding, as determined by 125I-epibatidine receptor autoradiography, in the brainstems of infants dying of SIDS and of other known causes of death collected from the Safe Passage Study, a prospective, multicenter study with clinical sites in Cape Town, South Africa and 5 United States sites, including 2 American Indian Reservations. We examined 15 pons and medulla regions related to cardiovascular control and arousal in infants dying of SIDS (n = 12) and infants dying from known causes (n = 20, 10 pre-discharge from time of birth, 10 post-discharge). Overall, there was a developmental decrease in 125I-epibatidine binding with increasing postconceptional age in 5 medullary sites [raphe obscurus, gigantocellularis, paragigantocellularis, centralis, and dorsal accessory olive (p = 0.0002-0.03)], three of which are nuclei containing serotonin cells. Comparing SIDS with post-discharge known cause of death (post-KCOD) controls, we found significant decreased binding in SIDS in the nucleus pontis oralis (p = 0.02), a critical component of the cholinergic ascending arousal system of the rostral pons (post-KCOD, 12.1 ± 0.9 fmol/mg and SIDS, 9.1 ± 0.78 fmol/mg). In addition, we found an effect of maternal smoking in SIDS (n = 11) combined with post-KCOD controls (n = 8) on the raphe obscurus (p = 0.01), gigantocellularis (p = 0.02), and the paragigantocellularis (p = 0.002), three medullary sites found in this study to have decreased binding with age and found in previous studies to have abnormal indices of serotonin neurotransmission in SIDS infants. At these sites, 125I-epibatidine binding increased with increasing cigarettes per week. We found no effect of maternal drinking on 125I-epibatidine binding at any site measured. Taken together, these data support changes in nicotinic receptor binding related to development, cause of death, and exposure to maternal cigarette smoking. These data present new evidence in a prospective study supporting the roles of developmental factors, as well as adverse exposure on nicotinic receptors, in serotonergic nuclei of the rostral medulla-a finding that highlights the interwoven and complex relationship between acetylcholine (via nicotinic receptors) and serotonergic neurotransmission in the medulla.

Gastroschisis, destructive brain lesions, and placental infarction in the second trimester suggest a vascular pathogenesis.

The cause and pathogenesis of gastroschisis are uncertain. We report the autopsy and placental pathology of a stillbirth at 20 gestational weeks, in which gastroschisis was accompanied by destructive lesions in the cerebral cortex and brainstem, as well as cardiac calcification, consistent with ischemic injury during the 2nd trimester. An important potential underlying mechanism explaining the fetal abnormalities is the presence of infarcts in the placenta, indicative at this gestational age of maternal vascular underperfusion. The association of gastroschisis with ischemic lesions in the brain, heart, and placenta in this case supports the concept that gastroschisis, at least in some instances, may result from vascular event(s) causing disruption of the fetal abdominal wall and resulting in the extrusion of the abdominal organs, as well as hypoxic-ischemic brain and cardiac injury.

Hippocampal asymmetry and sudden unexpected death in infancy: a case report.

The differential diagnosis of known entities associated with sudden unexpected death in infancy is ever expanding. Here we report the case of a 10-month-old infant boy whose clinical presentation mimicked that of the sudden infant death syndrome (SIDS). This presentation included the typical features of SIDS: sleep-related death; prone position upon discovery; and minor illness within 2 days of death. Nevertheless, neuropathologic examination revealed striking hippocampal asymmetry and microdysgenesis similar to that reported previously by us in toddlers with sleep-related sudden death. Hippocampal maldevelopment in the setting of sudden death in infants and toddlers is analogous to sudden unexpected death in epilepsy associated with temporal lobe pathology, and suggests a possible role for seizures in the terminal events leading to sudden death. This report serves to alert pediatric and forensic pathologists to hippocampal asymmetry and microdysgenesis in the differential diagnosis of sudden infant death mimicking SIDS.