Are substitutions in the first hypervariable region of the mitochondrial DNA displacement-loop in sudden infant death syndrome due to maternal inheritance?

AIM: To investigate whether all substitutions in the first hypervariable region (HVR1) in sudden infant death syndrome (SIDS) can be recovered along the maternal line of the family (inherited), or whether SIDS victims have new substitutions compared to maternal relatives (somatic mutations) that may be related to environmental factors. METHODS: Seventy-one SIDS/mother pairs, including 11 families with SIDS, mother and mother's relatives and/or SIDS siblings, were studied. The HVR1 sequence was recorded in the base-pair range 16056-16400. The recorded HVR1 sequence was compared with the Cambridge sequence, and differences were recorded as substitutions. The substitution pattern in the SIDS victims was compared with the pattern found in family members along the maternal line. RESULTS: All the substitutions found in SIDS victims could be traced in the maternal line of the family; in 5 cases this was observed through three generations, and in 3 cases through four generations. DISCUSSION: In patients with known mitochondrial (mt) DNA disease, a large number of sequence variants have been found in the D-loop region. Substitutions in the D-loop may be part of a haplotype with mutations elsewhere in the mtDNA. CONCLUSION: HVR1 substitutions in SIDS victims are hereditary and not due to somatic mutations.

Comparative epidemiology of sudden infant death syndrome and sudden intrauterine unexplained death.

BACKGROUND: Unexplained antepartum stillbirth and sudden infant death syndrome (SIDS) are major contributors to perinatal and infant mortality in the western world. A relation between them has been suggested. As an equivalent of SIDS, only cases validated by post mortem examination are diagnosed as sudden intrauterine unexplained death (SIUD). OBJECTIVE: To test the hypothesis that SIDS and SIUD have common risk factors. METHODS: Registration comprised all stillbirths in Oslo and all infant deaths in Oslo and the neighbouring county, Akershus, Norway during 1986-1995. Seventy six cases of SIUD and 78 of SIDS were found, along with 582 random controls surviving infancy, all singletons. Odds ratios were obtained by multiple logistic regression analysis. RESULTS: Whereas SIUD was associated with high maternal age, overweight/obesity, smoking, and low education, SIDS was associated with low maternal age, smoking, male sex, multiparity, proteinuria during pregnancy, and fundal height exceeding +2 SD. Thus the effects of maternal age were opposite in SIUD and SIDS (adjusted odds ratio 1.39 (95% confidence interval 1.17 to 1.66) per year, p < 0.0005). Heavy smoking, male sex, and a multiparous mother was less likely in SIUD than in SIDS (0.22 (0.06 to 0.83), 0.22 (0.07 to 0.78), and 0.03 (<0.01 to 0.17) respectively). Overweight/obesity and low fundal height were more common in SIUD than in SIDS (7.45 (1.49 to 37.3) and 13.8 (1.56 to 122) respectively). CONCLUSIONS: The differences in risk factors do not support the hypothesis that SIDS and SIUD have similar determinants in maternal or fetal characteristics detectable by basic antenatal care.

Fatal overdose of zopiclone in an elderly woman with bronchogenic carcinoma.

The death of a 72-year-old woman with respiratory debilitation due to bronchogenic carcinoma is described. She overdosed herself with probably 200 to 350 mg of zopiclone. Zopiclone, quantitated by HPLC in femoral postmortem blood, was found to be 1.9 mg/L (4.8 micromol/L). This level is higher than many other zopiclone fatalities reported. We report a case where only zopiclone was detected.

Changes in the epidemiological pattern of sudden infant death syndrome in southeast Norway, 1984-1998: implications for future prevention and research.

AIM: To look for changes in risk factors for sudden infant death syndrome (SIDS) after decrease and stabilisation of the SIDS rate. METHODS: Questionnaires were distributed to parents of 174 SIDS infants, dying between 1984 and 1998, and 375 age and sex matched controls in southeast Norway. RESULTS: The proportion of infants sleeping prone has decreased, along with the decrease in SIDS rate for the region during the periods studied, but over half of the SIDS victims are still found in the prone position. As the number of SIDS cases has decreased, additional risk factors have become more significant. Thus, after 1993, a significantly increased risk of SIDS is seen when the mother smokes during pregnancy. After 1993, young maternal age carries an increased risk. Maternal smoking and young maternal age are associated with each other. For SIDS victims, an increase in the number of infants found dead while co-sleeping is seen, and the age peak between 2 and 4 months and the winter peak have become less pronounced. CONCLUSION: Changes in risk factor profile following the decrease in SIDS rate in the early 1990s, as well as consistency of other factors, provides further clues to SIDS prevention and to the direction of further studies of death mechanisms.

Risk factors for sudden intrauterine unexplained death: epidemiologic characteristics of singleton cases in Oslo, Norway, 1986-1995.

OBJECTIVE: The epidemiologic characteristics of unexplained stillbirths are largely unknown or unreliable. We define sudden intrauterine unexplained death as a death that occurs antepartum and results in a stillbirth for which there is no explanation despite postmortem examinations, and we present risk factors for this type of stillbirth in singleton gestations. STUDY DESIGN: Singleton antepartum stillbirths (n = 291) and live births (n = 582) in Oslo were included and compared with national data (n = 2025 and n = 575,572, respectively). Explained stillbirths (n = 165) and live births in Oslo served as controls for the cases of sudden intrauterine unexplained death (n = 76) in multiple logistic regression analyses. RESULTS: One fourth of stillbirths remain unexplained. The risk of sudden intrauterine unexplained death (1/1000) increased with gestational age, high maternal age, high cigarette use, low education, and overweight or obesity. Primiparity and previous stillbirths or spontaneous abortions were not associated with sudden intrauterine unexplained death. CONCLUSIONS: Risk factors for sudden intrauterine unexplained death are identifiable by basic antenatal care. Adding unexplored stillbirths to the unexplained ones conceals several risk factors and underlines the necessity of a definition that includes thorough postmortem examinations.

Is the use of dummy or carry-cot of importance for sudden infant death?

UNLABELLED: The study was undertaken to test the significance of dummy use and carry-cots for counts of sudden infant death (SID). Based on the impression that very few SID victims have a dummy (comforter, pacifier) in their mouth at the time of death, and that a high proportion of SID babies were found dead in a carry-cot (portable crib, pram), a case-control study was performed. Questionnaires were sent to 167 parents of SID victims and to 352 parents of live-infants matched for sex and time of birth. Questionnaires were returned by 121 parents of SID victims (73%) and 307 parents of controls (87%). Only 4 SID victims (3%) were found dead with a dummy in their mouth. A quarter of the controls always used a dummy, 24% during night-time and 23% during daytime between 0 and 2 months of age, whereas this was only true for 10% in the SID group, the odds ratios being 0.27 for night-time and 0.36 for daytime. This trend was also seen until 1 year of life. Of the SID victims, 48% were found dead in a carry-cot, 79% during the cold time of the year and two thirds outdoors. Most deaths occurred during the afternoon (12 pm-5 pm). In both SID and control groups daytime use of carry-cots was equally frequent. Approximately 40% in both groups slept in such a cot between 5-7 days a week during the daytime. CONCLUSION: The use of dummy could be a favourable factor in the prevention of SID. Because of the frequent use of carry-cots during the daytime both in the SID group and the control group, the high percentage of SID in such cots does not seem to be of significance. However the high frequency of deaths in outdoor placed carry-cots during the cold period of the year may give clues to understanding the death mechanism in SID.

[Crib death in the eastern regions of Norway 1984-1992. A survey of risk factors]. / Krybbedød i østlandsregionen 1984-92. En kartlegging av risikofaktorer.

Cot death is the most important cause of death during the first year of life after the newborn period in Norway. A case control study was performed by sending questionnaires to 188 cot death parents and 475 control parents with infants matched for age, sex and time of birth. 76% of the cot death parents and 79% of the control parents completed the questionnaires. The male/female ratio of the babies in both groups was 64/36. The age distribution showed a peak between two and four months. 65% succumbed during the winter months. During the winter 32% died outdoors. This was true for only 16% of those who died during summer. A higher proportion of the cot death cases than the controls were premature (more than eight weeks). 78% of the cot death victims usually slept prone, whereas this was true for only 50% of the controls (p < 0.01). 91% of the cot death victims were found dead in a prone position. When comparing live babies during the first three months of life, significantly more cot death mothers than control mothers had stopped breastfeeding. A larger proportion of the cot death victims than the controls had had apparent life threatening events (p < 0.01). Foam mattresses were equally frequent in both groups.