Decreased serotonergic receptor binding in rhombic lip-derived regions of the medulla oblongata in the sudden infant death syndrome.

The sudden infant death syndrome (SIDS) is postulated to result from a failure of homeostatic responses to life-threatening challenges (e.g. asphyxia, hypercapnia) during sleep. The ventral medulla participates in sleep-related homeostatic responses, including chemoreception, arousal, airway reflex control, thermoregulation, respiratory drive, and blood pressure regulation, in part via serotonin and its receptors. The ventral medulla in humans contains the arcuate nucleus, in which we have shown isolated defects in muscarinic and kainate receptor binding in SIDS victims. We also have demonstrated that the arcuate nucleus is anatomically linked to the nucleus raphé obscurus, a medullary region with serotonergic neurons. We tested the hypothesis that serotonergic receptor binding is decreased in both the arcuate nucleus and nucleus raphé obscurus in SIDS victims. Using quantitative autoradiography, 3H-lysergic acid diethylamide (3H-LSD binding) to serotonergic receptors (5-HT1A-D and 5-HT2 subtypes) was measured blinded in 19 brainstem nuclei. Cases were classified as SIDS (n = 52), acute controls (infants who died suddenly and in whom a complete autopsy established a cause of death) (n = 15), or chronic cases with oxygenation disorders (n = 17). Serotonergic binding was significantly lowered in the SIDS victims compared with controls in the arcuate nucleus (SIDS, 6 +/- 1 fmol/mg tissue; acutes, 19 +/- 1; and chronics, 16 +/- 1; p = 0.0001) and n. raphé obscurus (SIDS, 28 +/- 3 fmol/mg tissue; acutes, 66 +/- 6; and chronics, 59 +/- 1; p = 0.0001). Binding, however, was also significantly lower (p < 0.05) in 4 other regions that are integral parts of the medullary raphé/serotonergic system, and/or are derived, like the arcuate nucleus and nucleus raphé obscurus, from the same embryonic anlage (rhombic lip). These data suggest that a larger neuronal network than the arcuate nucleus alone is involved in the pathogenesis of SIDS, that is, a network composed of inter-related serotonergic nuclei of the ventral medulla that are involved in homeostatic mechanisms, and/or are derived from a common embryonic anlage.

Brainstem 3H-nicotine receptor binding in the sudden infant death syndrome.

Maternal cigarette smoking during pregnancy has been shown to be a major risk factor for the sudden infant death syndrome (SIDS). We hypothesized that SIDS is associated with altered 3H-nicotine binding to nicotinic receptors in brainstem nuclei related to cardiorespiratory control and/or arousal. We analyzed 3H-nicotine binding in 14 regions in SIDS and control brainstems using quantitative tissue receptor autoradiography. Three groups were analyzed: SIDS (n = 42), acute controls (n = 15), and a chronic group with oxygenation disorders (n = 18). The arcuate nucleus, postulated to be important in cardiorespiratory control and abnormal in at least some SIDS victims, contained binding below the assay detection limits in all (SIDS and control) cases. We found no significant differences among the 3 groups in mean 3H-nicotine binding in the 14 brainstem sites analyzed. When a subset of the cases were stratified by the history of the presence or absence of maternal cigarette smoking during pregnancy, however, we found that there was no expected increase (upregulation) of nicotinic receptor binding in SIDS cases exposed to cigarette smoke in utero in 3 nuclei related to arousal or cardiorespiratory control. This finding raises the possibility that altered development of nicotinic receptors in brainstem cardiorespiratory and/or arousal circuits put at least some infants, i.e. those exposed to cigarette smoke in utero, at risk for SIDS, and underscores the need for further research into brainstem nicotinic receptors in SIDS in which detailed correlations with smoking history can be made.

Tritiated-naloxone binding to brainstem opioid receptors in the sudden infant death syndrome.

The sudden infant death syndrome (SIDS) is defined as the sudden death of an infant under 1 year of age that remains unexplained after a thorough case investigation, including a complete autopsy. We hypothesized that SIDS is associated with altered 3H - naloxone binding to opioid receptors in brainstem nuclei related to respiratory and autonomic control. We analyzed 3H - naloxone binding in 21 regions in SIDS and control brainstems using quantitative tissue receptor autoradiography. Three groups were analyzed: SIDS (n = 45); acute controls (n = 14); and a chronic group with oxygenation disorders (n = 15). Opioid binding was heavily concentrated in the caudal nucleus of the solitary tract, nucleus parabrachialis medialis, spinal trigeminal nucleus, inferior olive, and interpeduncular nucleus in all cases analyzed (n = 74). The arcuate nucleus on the ventral medullary surface contained negligible binding in all cases (n = 74), and therefore binding was not measurable at this site. We found no significant differences among the three groups in the age-adjusted mean 3H - naloxone binding in 21 brainstem sites analyzed. The only differences we have found to date between SIDS and acute controls are decreases in 3H - quinuclidinyl benzilate binding to muscarinic cholinergic receptors and in 3H - kainate binding to kainate receptors in the arcuate nucleus in alternate sections of this same data set. The present study suggests that there is not a defect in opioid receptor binding in cardiorespiratory nuclei in SIDS brainstems.

Changes in sleep position during infancy: a prospective longitudinal assessment.

CONTEXT: Prone sleeping by infants has been associated with an increased risk of sudden infant death syndrome. OBJECTIVE: To document the prevalence of and identify risk factors for prone sleeping during the first 6 months of life. DESIGN: Prospective cohort study. SETTING: Eastern Massachusetts and northwest Ohio. STUDY PARTICIPANTS: A total of 7796 mothers of infants weighing 2500 g or more at birth. MAIN OUTCOME MEASURES: Maternal and infant characteristics related to prone sleeping at 1 month and 3 months of age. RESULTS: Between 1 month and 3 months of age, prone sleeping increased from 18% to 29%. At 1 month, prone sleeping was associated with the following maternal characteristics: non-Hispanic black or Hispanic race/ethnicity, younger age, less education, and higher parity. At 3 months, switching from nonprone to prone position was associated with mother's race/ethnicity of non-Hispanic black (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.2-2.3) or Hispanic (OR, 1.5; 95% CI, 1.1-2.2); younger maternal age (compared with mothers >34 years: 18-24 years, OR, 1.6; 95% CI, 1.2-2.2; <18 years, OR, 2.2; 95% CI, 1.2-4.3); increasing parity (compared with 1 child: 2 children, OR, 1.5; 95% CI, 1.2-1.8; > or =3 children, OR, 1.7; 95% CI, 1.4-2.2); and infant sex (male sex, OR, 1.4; 95% CI, 1.2-1.7). CONCLUSIONS: If infant sleeping practices in the study communities are representative of practices throughout the United States, a substantial number of infants who slept nonprone at 1 month sleep prone at 3 months.

Decreased kainate receptor binding in the arcuate nucleus of the sudden infant death syndrome.

The human arcuate nucleus is postulated to be homologous to ventral medullary surface cells in animals that participate in ventilatory and blood pressure responses to hypercarbia and asphyxia. Recently, we reported a significant decrease in muscarinic cholinergic receptor binding in the arcuate nucleus in victims of the sudden infant death syndrome compared with control patients that died of acute causes. To test the specificity of the deficit to muscarinic cholinergic binding, we examined kainate binding in the arcuate nucleus in the same database. We assessed 3H-kainate binding to kainate receptors with tissue receptor autoradiography in 17 brainstem nuclei. Analysis of covariance was used to examine differences in binding by diagnosis, adjusted for postconceptional age (the covariate). Cases were classified as SIDS, 47; acute control, 15; and chronic group with oxygenation disorder, 17. (Acute controls are infants who died suddenly and unexpectedly and in whom a complete autopsy established a cause of death). The arcuate nucleus was the only region in which there was a significant difference in the age-adjusted mean kainate binding between the SIDS group (37+/-2 fmol/mg tissue) and both the acute controls (77+/-4 fmol/mg tissue) (p < 0.0001) and the chronic group (69+/-4 fmol/mg tissue) (p < 0.0001). There was a positive correlation between the density of muscarinic cholinergic and kainate binding in the SIDS cases only (R = 0.460; p = 0.003). The neurotransmitter deficit in the arcuate nucleus in SIDS victims involves more than one receptor type relevant to carbon dioxide and blood pressure responses at the ventral medullary surface.

A new educational approach for supporting the professional development of third-year medical students.

This paper describes a new course designed to support the professional development of third-year medical students. The course runs through the clinical clerkships, and has several additional features: it includes a multidisciplinary faculty; it is centrally based in the medical school; it addresses students' values and attitudes in addition to their knowledge and skills; and it makes use of small-group learning methods, and faculty, student, and group continuity during the year. The curriculum, which addresses ethical, social, and communicative issues in medicine, plus the evaluation of students and of the course, are described.

Decreased muscarinic receptor binding in the arcuate nucleus in sudden infant death syndrome.

Muscarinic cholinergic activity in the human arcuate nucleus at the ventral medullary surface is postulated to be involved in cardiopulmonary control. A significant decrease in [3H]quinuclidinyl benzilate binding to muscarinic receptors in the arcuate nucleus is now shown to occur in sudden infant death syndrome (SIDS) infants, compared to infants dying acutely of known causes. In infants with chronic oxygenation abnormalities, binding is low in other nuclei, as well as in the arcuate nucleus. The binding deficit in the arcuate nucleus of SIDS infants might contribute to a failure of responses to cardiopulmonary challenges during sleep.

Sudden infant death syndrome: the nurse counselor's response to bereavement counseling.

The sudden, unexpected death of an infant affects all who come in contact with both the infant and the family. The professional who is providing bereavement support is often affected by this catastrophic family event. This article explores the significance of this effect in a population of sudden infant death syndrome (SIDS) nurse counselors in the Massachusetts SIDS program.

Dermatoglyphics in sudden infant death syndrome.

An analysis of digital and palmar dermatoglyphic patterns was conducted in 173 victims of the sudden infant death syndrome (SIDS). The results expose four dermatoglyphic regions with pattern frequencies differing from those in a control population. These are an excess of Sydney creases, hypothenar patterns, open fields (with fewer vestiges) in interdigital region IV, and arches on all digits (females only). These findings indicate a genetic or early intrauterine environmental influence in SIDS infants. An increased incidence of dysmorphism and anomalies including recognition of specific syndromes support this contention. One could speculate that these dermatoglyphic deviations reflect specific genotypes and/or phenotypes particularly vulnerable to postnatal challenges. Differences in multiple dermatoglyphic categories support the concept of heterogeneity of the SIDS population and multicausality of SIDS.

Delayed central nervous system myelination in the sudden infant death syndrome.

This study was designed to assess whether development of the central nervous system (CNS) is delayed in victims of the sudden infant death syndrome (SIDS). We selected the parameter of myelination because it is a continuously changing and readily accessible marker of CNS development in the SIDS age-range. We assessed myelination blindly in 61 SIDS and 89 autopsy controls. In 62 sites the degree of myelination was visually graded in myelin-stained histological sections on an ordinal scale of 0-4 using the inferior cerebellar peduncle as an internal standard of degree 3. Cases were stratified by postconceptional age at death and SIDS and controls were compared with respect to myelin degree at each site. Significantly delayed myelination (p less than 0.05) occurred in the SIDS group in 25 of the 62 sites examined. Hypomyelination affected fiber systems in which myelination is initiated before or after birth and which myelinate with different tempos and preferentially affect pyramidal and cerebellar (somatomotor) and prefrontal-temporal-limbic (visceromotor) systems. Hypomyelination was not associated with individual clinicopathologic variables in the SIDS group. Somatic growth and brain weight were significantly greater in SIDS than controls. Therefore, we suggest that SIDS is associated with a developmental CNS disorder. Although delayed CNS myelination most likely shares a common antecedent with sudden death and is not its cause, the role of somato- and viscero-motor systems in central cardiorespiratory control and arousal warrants further analysis in SIDS.

Supporting the SIDS family.

Pediatric health professionals are often uncomfortable following a sudden unexpected death in their practice. Anxiety and grief by the pediatrician can prevent the practitioner from using even the most basic grief counseling skills. However, the pediatrician, while deeply affected by the death, is in a unique position to meet the needs of parents and siblings. Often, the pediatrician is the only contact families have with the medical world. This report outlines the techniques we have used to support families during this period of loss. Alleviating guilt, by providing information in a sensitive manner, explaining autopsy results, providing guidance for surviving children, and understanding the effects of loss on a subsequent pregnancy are part of the role the pediatrician can assume. Parents have consistently reported how beneficial it was when pediatricians took the time to listen to their concerns and problems following a sudden and unexpected infant death.

The surviving child in the SIDS family.

Children grieve, often very deeply. The unexpected loss of an infant elicits grieving from all family members and alters forever the family structure. What is the long-term impact of the death of a child in the family on the surviving sibling? What happens to children surviving this family catastrophe when they themselves become parents? In this report we present two accounts by children in the home when their siblings died. It reminds us that the effects of a sudden and unexpected loss of a child in the family can be long-lasting and return to us in childrearing practices of the next generation.

Clinical heterogeneity associated with deletions in the long arm of chromosome 15: report of 3 new cases and their possible genetic significance.

Deletions, duplications, and rearrangements of the long arm of chromosome 15 are frequently associated with the clinical diagnosis of the Prader-Willi syndrome. However, a number of other clinical entities have also been associated with similar, if not identical, cytogenetic defects, arguing for clinical heterogeneity associated with abnormalities in this region of chromosome 15. We present 3 patients who all appear to have deletions in 15q11-15q12, such as described for many patients with Prader-Willi syndrome; however, none of these patients has classical clinical features of the Prader-Willi syndrome. The first patient is a child with Williams syndrome, the second, Angelman (Happy Puppet) syndrome, and the third is a child with hypotonia of infancy, obesity, and developmental delay, but who does not meet specific diagnostic criteria for the Prader-Willi syndrome. It is proposed that different molecular abnormalities involving specific points or segments along the long arm of chromosome 15 might account for the clinical diversity seen among these and other patients.

Sudden and unexpected death. The pediatrician's response.

When an infant dies suddenly and unexpectedly, the sense of loss and terrible grief may overwhelm not only the parents but also the physician. When that sudden death is due to a known cause, the concrete character of the event can be incorporated into the normal rationalization of mourning. However, when death is due to an unknown mechanism, as in the sudden infant death syndrome, feelings of inadequacy in caring for the child are reinforced. The essential need for support of these families is clear. For physicians, this kind of loss is disquieting and anxiety-provoking. Forty-seven physicians responded to a survey exploring the relationship between the physician and the family after the death of an infant, the feelings of the physician about the death and his or her own sense of loss, and the physician's need for personal support and educational preparation for such an event. While 41 of the physicians indicated they had discussed the death with the family, six had made no contact with the survivors. Thirty-six of the respondents indicated that their relationship with the family continued, and ten physicians stated that their relationship terminated after the death. Physicians characterized their initial responses to the death as frustration, sadness, shock, anger, guilt, regret, hurt, and inadequacy. Most of the physicians believed that they had "missed" something and feared they might be blamed for the death. The competence, sincerity, and sensitivity shown to families during this tragic experience can positively influence the family's mourning and recovery. The pediatrician can provide a rational voice and a medical understanding of tragedy without blame.

An hepatic metabolic profile in sudden infant death (SIDS).

Levels of 18 enzymes and metabolites were measured in liver obtained at autopsy from 41 infants, 28 of whom were found unexpectedly dead at home. Four infants had meningitis, 11 had pathologic findings not clearly sufficient to explain death (SUD), and 13 were considered totally unexplained pathologically (SIDS). The possible contributions of postmortem interval, age and diet to the results are reviewed. No characteristic metabolic profile was recognized amongst SUD and SIDS groups. It is speculated that the amount of glycogen found in liver may provide insight into premortal events and reflect the rapidity of the death mechanism. Five individuals (20%) were suspected of having major metabolic abnormality including glycogenosis (1), urea cycle defect (1), and possibly abnormal levels of carnitine palmityl transferase (3).

Feeding induction in children who refuse to eat.

Seven chronically ill patients who refused to eat after prolonged hospitalizations were started on a feeding induction program that was based on behavior modification. Each of the children exhibited food aversions and was either dependent on central intravenous nutrition or received enteral feedings as the primary source of calories. An intervention program was initiated for six of the patients while they were hospitalized; the program was continued at home by the parents. All seven patients established consistent oral intake, and five were removed from supplemental feeding sources after implementation of the feeding induction programs.

Violence on television and imitative behavior: impact on parenting practices.

In the past 30 years, four federal government commissions have reported on the relationship between television violence and aggressive behavior. The latest report concluded categorically that there is a causal relationship between television violence and aggressive behavior. Two infants were seen at an emergency room as a direct consequence of their socially isolated single mothers seeing a particular made-for-television movie. In one case, the infant died as a possible result of a parent imitating an act of child abuse; in the other case, early medical intervention precluded possible tragedy. These cases illustrate another way in which children may be victimized by violence on television; namely, by parents imitating inappropriate parental behavior. The origins of imitative behavior are discussed with specific reference to the impact on vulnerable parents. The concept of media-influenced parenting behavior is presented and implications for physicians are discussed.

Unexpected death of an infant sibling.

When infants die suddenly and unexpectedly, family structures are abruptly altered. This loss and its subsequent changes affect remaining older siblings. New "big brother" and "big sister" roles are suddenly terminated, often in a catastrophic manner. Young surviving children are sometimes unable to understand the meaning of this event, its impact on the family, and their own role in what has occurred. In this study, 26 families that had sustained the sudden and unexpected death of an infant and that had surviving children were interviewed to obtain data about surviving siblings at least 10 months following the loss. Among the 26 families, there were 35 surviving siblings (ages 16 months to 6 years). The interview schedule sought information relevant to changes in patterns of sleep, toilet training, feeding habits, peer relationships, and parent-child interaction. Among these 35 surviving siblings, parents of 28 siblings (80%) perceived changes in their child's interaction with them, 24 siblings (69%) demonstrated changes in sleep patterns following the baby's death, and 13 siblings (37%) showed changes in social interaction. Regression in toilet training and changes in feeding patterns were infrequent and not areas of major concern for parents. These behavioral changes reflected both a continuum of adjustment by the child and a persistence of parental worries.