Haplotypes of the surfactant protein genes A and D as susceptibility factors for the development of respiratory distress syndrome

AIMS: Polymorphisms of genes are transmitted together in haplotypes, which can be used in the study of the development of complex diseases such as respiratory distress syndrome (RDS). The surfactant proteins (SPs) play important roles in lung function, and genetic variants of these proteins have been linked with lung diseases, including RDS. To determine whether haplotypes of SP-A and SP-D are transmitted disproportionately from parents to offspring with RDS, we hypothesized that previously unstudied genetic haplotypes of these SP genes are associated with the development of RDS. METHODS: DNA was collected from 132 families of neonates with RDS. Genotyping was performed, and haplotype transmission from parent to offspring was determined by transmission disequilibrium test. RESULTS: The two-marker SP-D/SP-A haplotype DA160_A/SP-A2 1A(1) is protective against the development of RDS (p = 0.035). Four three- and four-marker haplotypes containing one or both loci from the significant two-marker haplotype are also protective against the development of RDS. CONCLUSIONS: These data identify protective haplotypes against RDS and support findings related to SP genetic differences in children who develop RDS. Study of haplotypes in complex diseases with both genetic and environmental risk factors may lead to better understanding of these types of diseases.     

毛细支气管炎患儿血清肺表面活性蛋白A和D的检测及临床意义

目的：探讨血清肺表面活性蛋白A（SP-A）和D（SP-D）在不同程度毛细支气管炎患儿中的变化及其临床意义。方法：将70例毛细支气管炎患儿依据临床症状分为毛细支气管炎急性期组（42例）和恢复期组（28例）,另选取26例同期因非感染性疾病住院的小儿外科术前患儿为对照组;同时依据症状严重程度将急性期毛细支气管炎患儿分为重症组（12例）和轻症组（30例）。采用竞争性ELISA法定量测定各组血清SP-A和SP-D水平变化。结果：毛细支气管炎急性期组患儿血清SP-A和SP-D水平显著高于恢复期组和对照组（均P<0.01）,且恢复期组与对照组比较,血清SP-A和SP-D仍维持在较高水平（P<0.01）;重症组患儿血清SP-A和SP-D水平明显高于轻症组（P<0.01）。结论：毛细支气管炎患儿急性期血清SP-A和SP-D水平明显增高,且随病情加重而增高;临床症状缓解后,血清SP-A和SP-D水平仍然维持在较高水平。     

The sudden infant death syndrome gene: does it exist?

BACKGROUND: Sudden infant death syndrome (SIDS) is in a difficult position between the legal and medical systems. In the United Kingdom, prosecutors have for years applied the simple rule that 1 unexpected death in a family is a tragedy, 2 are suspicious, and 3 are murder. However, it seems that the pendulum has now swung to the opposite extreme; mutations or polymorphisms with unclear biological significance are accepted in court as possible causes of death. This development makes research on genetic predisposing factors for SIDS increasingly important, from the standpoint of the legal protection of infants. The genetic component of sudden infant death can be divided into 2 categories, ie (1) mutations that give rise to genetic disorders that constitute the cause of death by themselves and (2) polymorphisms that might predispose infants to death in critical situations. Distinguishing between these 2 categories is essential, and cases in which a mutation causing a lethal genetic disorder is identified should be diagnosed not as SIDS but as explained death. GENETIC ALTERATIONS THAT MAY CAUSE SUDDEN INFANT DEATH: Deficiencies in fatty acid metabolism have been extensively studied in cases of SIDS, and by far the most well-investigated mutation is the A985G mutation in the medium-chain acyl-CoA dehydrogenase (MCAD) gene, which is the most prevalent mutation causing MCAD deficiency. However, <1% of sudden infant death cases investigated have this mutation, and findings of biochemical profiles seen in specific fatty acid oxidation disorders in a number of such cases emphasize the importance of investigating fatty acid oxidation disorders other than MCAD deficiency. Severe acute hypoglycemia may cause sudden death among infants, but only rare novel polymorphisms have been found when key proteins involved in the regulation of blood glucose levels are investigated in cases of SIDS. The long QT syndrome (LQTS) is another inherited condition proposed as the cause of death in some cases of sudden infant death. The LQTS is caused by mutations in genes encoding cardiac ion channels, and mutations in the genes KVLQT1 and SCNA5 have been identified in cases initially diagnosed as SIDS, in addition to several polymorphisms in these 2 genes and in the HERG gene. In addition, genetic risk factors for thrombosis were investigated in a small number of SIDS cases; the study concluded that venous thrombosis is not a major cause of sudden infant death. GENE POLYMORPHISMS THAT MAY PREDISPOSE INFANTS TO SUDDEN INFANT DEATH UNDER CERTAIN CIRCUMSTANCES: Many SIDS victims have an activated immune system, which may indicate that they are vulnerable to simple infections. One reason for such vulnerability may be partial deletions of the complement component 4 gene. In cases of SIDS, an association between slight infections before death and partial deletions of the complement component 4 gene has been identified, which may indicate that this combination represents increased risk of sudden infant death. There have been a few studies investigating HLA-DR genotypes and SIDS, but no association has been demonstrated. The most common polymorphisms in the interleukin-10 (IL-10) gene promoter have been investigated in SIDS cases, and the ATA/ATA genotype has been reported to be associated with both SIDS and infectious death. The findings may indicate that, in a given situation, an infant with an unfavorable IL-10 genotype may exhibit aberrant IL-10 production, and they confirm the assumption that genes involved in the immune system are of importance with respect to sudden unexpected infant death. Another gene that has been investigated is the serotonin transporter gene, and an association between the long alleles of this gene and SIDS has been demonstrated. Serotonin influences a broad range of physiologic systems, as well as the interactions between the immune and nervous systems, and findings of decreased serotonergic binding in parts of the brainstem, together with the findings in the serotonin transporter gene, may indicate that serotonin plays a regulatory role in SIDS. It has also been speculated that inadequate thermal regulation is involved in SIDS, but investigations of genes encoding heat-shock proteins and genes encoding proteins involved in lipolysis from brown adipose tissue have not found evidence of linkages between common polymorphisms in these genes and SIDS. A number of human diseases are attributable to mutations in mitochondrial DNA (mtDNA), and there are several reasons to think that mtDNA mutations also are involved in SIDS. Both a higher substitution frequency and a different substitution pattern in the HVR-I region of mtDNA have been reported in SIDS cases, compared with control cases. A number of coding region mtDNA mutations have also been reported, but many are found only in 1 or a few SIDS cases, and, to date, no predominant mtDNA mutation has been found to be associated with SIDS. CONCLUSIONS: All mutations giving rise to metabolic disorders known to be associated with life-threatening events are possible candidates for genes involved in cases of sudden infant death, either as a cause of death or as a predisposing factor. It is necessary to distinguish between lethal mutations leading to diseases such as MCAD and LQTS, and polymorphisms (for instance, in the IL-10 gene and mtDNA) that are normal gene variants but might be suboptimal in critical situations and thus predispose infants to sudden infant death. It is unlikely that one mutation or polymorphism is the predisposing factor in all SIDS cases. However, it is likely that there are "SIDS genes" operating as a polygenic inheritance predisposing infants to sudden infant death, in combination with environmental risk factors. For genetically predisposed infants, a combination of, for instance, a slight infection, a prone sleeping position, and a warm environment may trigger a vicious circle with a death mechanism, including hyperthermia, irregular breathing, hypoxemia, and defective autoresuscitation, eventually leading to severe hypoxia, coma, and death.     

The G protein beta3 subunit 825C allele is associated with sudden infant death due to infection

AIM: To investigate the Gbeta3 subunit C825T polymorphism with regard to sudden unexpected infant death. The reported association between the Gbeta3s protein and increased immune cell function in humans makes this polymorphism highly interesting both with regard to sudden infant death syndrome (SIDS) and deleterious infectious disease. METHODS: The cases investigated in the present study consist of 250 SIDS cases, 38 cases of sudden unexpected infant death due to infection and 99 living infant controls. Typing of the C825T polymorphism was performed by real-time PCR with allele-specific probes and melting curve analyses. RESULTS: The cases of infectious death have a higher percentage of both the C allele (p=0.037 compared to the SIDS cases, p=0.022 compared to the controls) and the CC genotype (p=0.05 compared to the SIDS cases, p=0.016 compared to the controls). There were no differences between SIDS cases and controls. CONCLUSION: The observed association between the 825C allele and infectious death may indicate that the presence of the 825T allele exerts a protective effect towards serious infection, possibly through enhanced G protein signalling. The C allele, on the other hand, appears to represent a disadvantage in this regard.     

Cytokine gene polymorphisms and sudden infant death syndrome

Aim: Several studies indicate that the mucosal immune system is stimulated in cases of sudden infant death syndrome (SIDS), and our hypothesis is that this immune reaction is because of an unfavourable combination of functional polymorphisms in the cytokine genes. Methods: Thus, in this study, single nucleotide polymorphisms (SNPs) in the genes encoding IL‐6, IL‐8, IL‐12, IL‐13, IL‐16, IL‐18 and IFNγ were investigated in 148 SIDS cases, 56 borderline SIDS cases, 41 cases of infectious death and 131 controls. Results: Regarding genotype distribution, no differences between the investigated groups were found. However, in the SIDS group, the genotypes IL‐8 ?251AA/AT and IL‐8 ?781CT/TT were significantly more frequent in the SIDS cases found dead in a prone sleeping position, compared with SIDS cases found dead in other sleeping positions. In addition, there was an association between fever prior to death and the genotype IL‐13 +4464GG in the cases of infectious death. Conclusion: This study indicates that specific interleukin genotypes are a part of a genetic make up that make infants sleeping prone at risk for SIDS.     

LOCALIZATION AND FUNCTIONS OF SP-A AND SP-D AT MUCOSAL SURFACES

Pulmonary surfactant protein A (SP-A) and D (SP-D), members of the collectin family, are implicated in innate host defense of the lung. Collectins consist of a collagen-like domain and a carbohydrate recognition domain. SP-A and SP-D recognize and interact with glycoconjugates on the surface of microorganisms. They protect the lung by interacting with a wide variety of potential pathogens, including viruses, bacteria, and fungi. This may result in enhanced killing and/or clearance by phagocytes. Although most extensively studied in the lung, both SP-A and SP-D, or proteins closely resembling SP-A and SPD, are found in a number of other sites in the body and therefore may play a protective role at other sites than the lung. SP-A and SP-D protein and/or mRNA have been detected at various sites of the body: the respiratory tract, the gastrointestinal tract, the middle ear, and in the peritoneal cavity. The presence of SP-A and SP-D at these mucosal surfaces, in close contact with numerous potentially harmful microorganisms, supports a role for these "lung"-collectins in innate mucosal defense. SP-A and SP-D may be important molecules in a threefold innate defense, particularly in the neonatal period between maternally acquired immunity and a fully developed adaptive immune system; the time interval between first exposure to a pathogen and generation of specific antibodies; and states of impaired immune function.     

The brain‐derived neutrophic factor val66met polymorphism and sudden unexpected infant death

Aim: Findings of hypoxia prior to death and involvement of a dysregulation of the serotonergic network in sudden infant death syndrome (SIDS) may indicate that brain‐derived neutrophic factor (BDNF) also is of importance with regard to sudden unexpected infant death. Based on this, the purpose of this study was to investigate the BDNF val66met polymorphism in SIDS cases, cases of infectious death and controls. Methods: The polymorphism was investigated in 163 SIDS cases, 34 cases of infectious death and 121 controls, using real‐time PCR and fluorescence melting curve analysis. Results: There were no differences in val66met genotype distribution between neither the SIDS cases nor the cases of infectious death and controls (p = 0.95 and p = 0.52, respectively). Conclusion: The study indicates that the val66met polymorphism is not important for sudden unexpected infant death. However, several other SNPs in the BDNF gene, as well as in other genes involved in this pathway, including G‐protein, have to be investigated to fully exclude any involvement of BDNF in SIDS.     

The intrauterine expression of surfactant protein D in the terminal airways of human fetuses compared with surfactant protein A

We investigated the expression of surfactant protein (SP)-D in pulmonary epithelial cells, compared with the expression of SP-A. A total of 15 fetuses aborted at 8, 15, 19, 20, 21 and 23 weeks gestation and four premature babies who were stillborn or died after birth between May 1997 and October 2001 were included in this study. Fetuses showing any findings associated with preterm premature rupture of membranes or infection were excluded. We performed immunohistochemical examinations for SP-D and SP-A. SP-D was not detected by immunostaining at 8, 15 and 19 weeks gestation. At 21 weeks gestation, SP-D was weakly localized, in some cases (5/9), in the epithelial lining of both bronchioles and terminal airways. In contrast at 21 weeks gestation, SP-A was more markedly detected in the epithelial lining of both bronchioles and terminal airways in all cases but not detected in bronchioles and terminal airways at 8, 15 and 19 weeks gestation. CONCLUSION: the findings in this investigation suggests that the production of SP-D in fetal human lungs begins in the bronchiolar and terminal epithelium from about 21 weeks of gestation.     

Formal retrospective case review and sudden infant death

A review of 24 consecutive sudden infant deaths was undertaken to evaluate the importance of the various stages in the postmortem assessment of such cases. Death in three cases was caused by obvious trauma. Of the remainder, 16 were attributed to sudden infant death syndrome (SIDS), 4 to accidental asphyxia (identified by death scene examination and/or formal case review) and 1 to a lingual thyroglossal duct cyst. Three (14%) of 21 deaths thought to be SIDS after postmortem examination were attributed to asphyxia following subsequent formal case review.     

Sudden infant death syndrome: case-control frequency differences at genes pertinent to early autonomic nervous system embryologic development

We have previously identified polymorphisms in the serotonin transporter gene promoter region and in intron 2 that were more common among sudden infant death syndrome (SIDS) cases compared with control subjects. To elucidate further the genetic profile that might increase an infant's vulnerability to SIDS, we focused on the recognized relationship between autonomic nervous system (ANS) dysregulation and SIDS. We therefore studied genes pertinent to early embryologic development of the ANS, including MASH1, BMP2, PHOX2a, PHOX2b, RET, ECE1, EDN1, TLX3, and EN1 in 92 probands with SIDS and 92 gender- and ethnicity-matched control subjects. Eleven protein-changing rare mutations were identified in 14 of 92 SIDS cases among the PHOX2a, RET, ECE1, TLX3, and EN1 genes. Only 1 of these mutations (TLX3) was identified in 2 of 92 control subjects. Black infants accounted for 10 of these mutations in SIDS cases and 2 control subjects. Four protein-changing common polymorphisms were identified in BMP2, RET, ECE1, and EDN1, but the allele frequency did not differ between SIDS cases and control subjects. However, among SIDS cases, the allele frequency for the BMP2 common polymorphism demonstrated ethnic differences; among control subjects, the allele frequency for the BMP2 and the ECE1 common polymorphisms also demonstrated ethnic differences. These data represent further refinement of the genetic profile that might place an infant at risk for SIDS.     

Contribution of Long-QT Syndrome Genetic Variants in Sudden Infant Death Syndrome

A cohort of 52 French unrelated infant cases who died unexpectedly before they reached 12 months of age was blindly investigated to better quantify the contribution of long-QT syndrome (LQTS) genetic variants in French cases of sudden infant death syndrome (SIDS). After a standardized autopsy protocol, a blinded molecular screening of the KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 genes was performed on each case. These postmortem investigations enabled us to reclassify 18 as non-SIDS cases, 32 as SIDS cases, and 2 as suspected SIDS cases. Among the 18 non-SIDS cases, no LQTS mutation was identified. In contrast, our results led to a possible explanation for the death of at least three infants in the SIDS cohort. Half of the LQTS gene variants identified were located on the SCN5A gene. This study confirms that LQTS mutations may represent one of the leading genetic causes of SIDS. If autopsy fails to provide an explanation for an unexplained infant death, medicolegal investigation should be extended with a molecular screening of major LQTS genes. Identification of more LQTS mutations in SIDS cases could provide new insights into the pathophysiology of SIDS and, consequently, reduce the number of unexplained sudden infant deaths.     

Vitreous humor hypoxanthine levels in SIDS and infectious death

Vege Å, Chen Y, Opdal SH, Saugstad OD, Rognum TO. Vitreous humor hypoxanthine levels in SIDS and infectious death. Acta Pæediatr 1994;83:634–9. Stockholm. ISSN 0803–5253
Hypoxanthine concentrations in vitreous humor were determined in 107 cases of sudden infant death syndrome (SIDS) and compared with levels in 4 cases of borderline SIDS, 26 cases of infectious death and 16 cases of sudden violent death. The hypoxanthine measurements were made using a high-pcrformance liquid chromatography method. The hypoxanthine levels were significantly (p<0.01) higher in SIDS than in violent deaths, while no significant difference was found between SIDS and infectious deaths. The present report demonstrates a similar distribution pattern of hypoxanthine levels in vitreous humor in SIDS and infectious death. We have previously described signs of immune stimulation both in peripheral organs and in the central nervous system in these conditions. This indicates that the death mechanism in SIDS has some similarities with infectious death.     

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.     

Autopsies of sudden infant death syndrome—classification and epidemiology

An enquiry into sudden infant death syndrome (SIDS) in 1987 furnished us with detailed epidemiological data for 281 cases that underwent a thorough post-mortem examination. This analysis uses these data to evaluate the role the autopsy plays in explaining sudden death. The cases were classified into three diagnostic groups: explained causes of death (group 1), unexplained deaths with anomalies (group 2), and no anomaly (group 3). These 281 cases show the three essential features that characterize SIDS: over-representation of males, increased deaths during the second and third months of life, and increased deaths during winter. The autopsy examination revealed that many of these deaths had a medical explanation. Almost half were assigned to group 1. At the time of autopsy, no precise pathology could be diagnosed for 147 deaths; of these, 140 showed histological anomalies. There were only seven sudden deaths for which no abnormal sign was evident at the autopsy. These results are compared with those of similar studies and discussed in connection with three factors: the initial selection of cases, the nature and degree of the investigations, and the possible interpretations of the symptoms uncovered.     

Has changing diagnostic preference been responsible for the recent fall in incidence of sudden infant death syndrome in South Australia?

Objective: An apparent decrease in deaths attributed to sudden infant death syndrome (SIDS) has been noted in a number of diverse geographical areas during the past several years. At the same time the definition of SIDS has been in a state of flux and some observers have raised the possibility that the fall in SIDS deaths is due to diagnostic transfer rather than to a genuine decrease in numbers. The present study was undertaken to investigate this possibility.
Methodology: All sudden and unexpected deaths in infants under 1 year of age in South Australia during a 10 year period from 1984 to 1993 were reviewed.
Results: The number of deaths due to SIDS fell from 40 in 1984 to 17 in 1993, with a maximum of 52 cases per year in 1987. In contrast, the number of cases of sudden death not due to SIDS remained under 10 per year. The overall infant death rate also fell, while the total number of births per year remained relatively unchanged.
Conclusions: The lack of major change in sudden infant death rates from other causes, combined with the fall in SIDS deaths, is not supportive of diagnostic transfer being a major determinant of the declining SIDS death rate. Therefore, other factors are likely to be responsible for the falling SIDS rate in this population.     

肺炎患儿支气管肺泡灌洗液中肺表面活性蛋白A和D表达及其与肺炎临床特征的相关性

目的 观察肺表面活性蛋白A、D(SP-A、SP-D)在肺炎患儿支气管肺泡灌洗液(BALF)中的表达,探讨SP-A、SP-D与肺炎患儿临床特征的相关性。方法 35例肺炎患儿纳入研究,对其肺泡灌洗液细胞进行分类计数,采用酶联免疫吸附试验(ELISA)检测患儿BALF中SP-A和SP-D水平。结果 患儿BALF中SP-D水平显著高于SP-A水平(Prs=-0.5255,P8mg/L)的患儿BALF中SP-D水平明显低于C反应蛋白正常的患儿(PPP>0.05)。结论 肺炎患儿BALF中SP-D的表达显著高于SP-A,与肺炎患儿的临床特征有一定相关性,作为一种保护性因子在调节免疫及炎症反应中发挥着比SP-A更重要的作用。     

TNF-alpha and IL-10 gene polymorphisms versus cardioimmunological responses in sudden infant death

We hypothesized that genetic variations of cytokines could contribute to the risk of developing a fatal immunological reaction in the heart of infants. Thus, tumor necrosis factor (TNF)-alpha and interleukin (IL)-10 gene polymorphisms versus induction of cardioimmunologxical responses in victims of sudden infant death syndrome (SIDS) were explored. We genotyped 35 infants (23 cases of SIDS and 12 infants with a known cause of death), and 100 healthy adult controls for IL-10 -1082 G/A, -592 C/A and TNF-alpha-238 G/A, -308 G/A. We found a higher frequency of the ATA haplotype and ATA/ATA genotype of IL-10 associated with SIDS (13%). The frequency of homozygote infants for IL-10 haplotypes in SIDS was higher (52%) than the control group (34%). All SIDS cases were homozygotice for the TNF-alpha-238 G allele and 20 infants were homozygous for the TNF-alpha-308 G allele in the same group. None of the infants with higher levels of infiltrated T-cells (n=8) was homozygous for IL-10 gene polymorphisms, whereas in contrast 3 cases of the 6 that displayed higher levels of cardiac mast cells were homozygous. In this study, the increased number of interstitial T-cells, mast cells, and macrophages in the myocardial interstitium demonstrated no correlation with the genotype for either cytokines.     

Serotonin transporter gene variation in sudden infant death syndrome

AIM: To investigate polymorphisms in the serotonin transporter (5-HTT) gene in cases of sudden infant death syndrome (SIDS) and controls, and further to elucidate a possible relationship between 5-HTT genotypes and external risk factors for SIDS. METHOD: The subjects investigated consist of 163 SIDS cases and 243 controls. Polymorphisms in both the promoter and intron 2 of the 5-HTT gene were investigated, and the genotypes were determined using polymerase chain reaction (PCR) and gel electrophoresis. RESULTS: In the promoter, there was a tendency for the L allele and L/L genotype to be found more often in the SIDS cases than in the controls (p=0.05 and p=0.07, respectively). Regarding the intron 2 polymorphism, there were no differences between the groups, and the SIDS cases were not found to have a higher frequency of either the L/L-12/12 genotype or the L-12 haplotype than the controls. When investigating possible correlations between genotype and risk factors for SIDS, there was a tendency towards different distribution of the promoter genotypes in cases found dead prone compared to cases found dead in other sleeping positions (p=0.06). CONCLUSION: Polymorphisms in the promoter of the 5-HTT gene may be of importance with regard to SIDS.     

Sudden unexpected child deaths: forensic autopsy results in cases of sudden deaths during a 5-year period

The aim of the present study was to determine the incidence of various causes of sudden unexpected child deaths (SUCD) and to assess the importance of an autopsy in predicting the likelihood of finding a cause of death. A retrospective analysis of autopsy findings in 97 cases of SUCD between the ages of 0--11 years was undertaken at the Council of Forensic Medicine, Ankara during a 5-year period (1995--2000). Cases were classified as explained causes (80.42 per cent) and sudden infant death syndrome (SIDS) (19.58 per cent). A total of 25.77 per cent of the deaths occurred in the neonatal period, 45.31 per cent of them in the first year of life and the remaining 28.86 per cent after 1 year of life. The causes of neonatal deaths were respiratory pathology (five cases), birth complications (four cases), gastrointestinal pathology (one case), homicide (10 cases), and SIDS (five cases). The incidence of SIDS in the newborn period was 33 per cent. The incidence of unexplained causes of deaths in the postneonatal period was 31 per cent and the causes of deaths were respiratory pathology (15 cases), aspiration (five cases), gastrointestinal pathology (four cases), SIDS (14 cases), and other causes (four cases). The study of an entire population provides more reliable data regarding causes of sudden unexpected child deaths than does the study of small groups and it is also recommended that in addition to a through evaluation, a detailed autopsy must be performed for each case in experienced centers.     

Do risk factors differ between explained sudden unexpected death in infancy and sudden infant death syndrome?

BACKGROUND: In Germany, 2910 infants died in 2004; for many infants the reason was clear, especially prematurity or congenital abnormalities. However, 394 babies die every year suddenly and unexpectedly. The cause may be immediately clear, but is often not obvious. AIMS: (1) To describe the causes of explained sudden unexpected death in infancy (SUDI) and (2) to compare risk factors for sudden infant death syndrome (SIDS) and explained SUDI. METHODS: A 3-year population-based case-control study in Germany, 1998-2001. RESULTS: 455 deaths, of which 51 (11.2%) were explained. Most of these deaths were due to respiratory or generalised infections. The risk factors for SIDS and explained SUDI were remarkably similar except for sleep position and breast feeding. Prone sleeping position is a major risk factor for SIDS (adjusted odds ratio (OR) 7.16, 95% confidence interval (CI) 3.85 to 13.31) but not for explained SUDI (adjusted OR 1.71, 95% CI 0.25 to 11.57). Not being breast fed in the first 2 weeks of life is a risk factor for SIDS (adjusted OR 2.37, 95% CI 1.46 to 3.84) but not for explained SUDI (adjusted OR 0.39, 95% CI 0.08 to 1.83). CONCLUSIONS: Prone sleeping position is a unique risk factor for SIDS. Socioeconomic disadvantage and maternal smoking are risk factors for both SIDS and explained SUDI, and provide an opportunity for targeted intervention.