The German case-control scene investigation study on SIDS: epidemiological approach and main results.

The present study, which was part of the German SIDS Study (GeSID), enrolled sudden infant death syndrome (SIDS) cases and population controls and obtained objective scene data via specifically trained observers shortly after discovery of each dead infant. Infants who had died suddenly and unexpectedly at ages between 8 and 365 days were enrolled in five regions of Germany between November 1998 and October 2001. Shortly after discovery of each dead infant, a specially trained doctor of legal medicine visited the bereaved family at home. Data were obtained by measurements and observations. Dead infants underwent a standardised autopsy, additional information being obtained by standardised parent interviews. Investigation of the sleep environment and wake-up scene in matched controls followed the same protocol. A total of 52 SIDS cases and 154 controls were enrolled, 58% were boys, and median age of cases vs. controls was 126 vs. 129 days. Risk factors in the sleeping environment were pillow use (adjusted OR 4.3; 95%CI 1.6-11.6), heavy duvets (OR 4.4; 1.5-13.3), soft underlay (OR 3.0; 1.1-8.7), face covered by bedding (OR 15.8; 2.5-102.1) and entire body covered by bedding (OR 35.5; 5.5-228.3). Using a standardised protocol, including objective measurements of the sleep environment and a case-control design, this study was able to confirm many risk factors for SIDS.

Population data of Y-chromosomal STRs in Russian males of the Primorye region population.

Data of eight Y-chromosomal STRs, the so called "minimal core set", were obtained from 152 unrelated males of the Primorye region of Russia. The allelic frequencies correspond to other European populations. The background is a settlement of males from the European part of Russia, Ukraine and other states which were included in the former western part of the Soviet Union. On the other hand the distribution of the most frequent haplotypes differs to the Ukraine and Russian population. The most frequent haplotype was obtained five times in the population corresponding to 3.3%. The haplotype data reported here have been included into the Y-STR database maintained at the Institute of Legal Medicine, Humboldt-University, Berlin.

Molecular and cytogenetic characterization of a non-mosaic isodicentric Y chromosome in a patient with Klinefelter syndrome.

We report on an adult male with Klinefelter phenotype and an isodicentric Y chromosome (47,XX,+idic(Y)(q12)), a combination which has to the best of our knowledge not been reported before. The patient was hospitalized in forensic psychiatry because of repeated delinquency, aggressive, aberrant and inappropriate behavior, and borderline intelligence. Molecular cytogenetic studies (FISH) showed that the SRY gene was present on both ends of the idicY, while there was only one signal for the Yq subtelomere probe. Molecular investigations by multiplex PCR, using STS markers covering the short and long arm of the Y chromosome did not indicate a deletion of Y chromosomal material. Molecular investigations of STR markers located on Xp22.3 and Xq28 indicated paternal origin of the additional X chromosome and an error in paternal meiosis I. Results of FISH analysis and molecular investigations are compatible with a phenotype as described for individuals with a 48,XXYY karyotype and support the findings that isodicentric Y chromosomes are frequently accompanied by other sex chromosomal abnormalities.

A controlled study of the relationship between Bordetella pertussis infections and sudden unexpected deaths among German infants.

OBJECTIVE: This was a prospective, controlled, multicenter study to investigate the relationship between Bordetella pertussis infections and sudden unexpected deaths among German infants. DESIGN: Between 1995 and 1997, all infants who died at 7 to 365 days of age and for whom autopsies were performed in 1 of 8 participating institutes of legal medicine were enrolled. During a standardized autopsy, nasopharyngeal specimens (NPSs) and tracheal specimens were obtained for polymerase chain reaction (PCR) assays to detect B pertussis. The oligonucleotide primers PTp1 and PTp2, which specifically amplify a 191-base pair DNA fragment of the pertussis toxin operon of B pertussis, were used. Two control subjects (matched according to residence, age, gender, and nationality) were enrolled for each case subject, via a network of pediatricians in private practice, and NPSs were obtained from those infants. Parents of case subjects and control subjects were asked to provide specific information on respiratory illnesses of the child, contact with a known case of pertussis, or close contact with a person with a cough illness during the 4 weeks before death or enrollment, as well as the child's pertussis immunization status. The pathologists performing the autopsies were unaware of the PCR results. RESULTS: Enrolled were 254 infants (66% male) with sudden unexpected deaths and 441 matched control subjects. Autopsies according to protocol were performed for 234 of the case subjects (92%); a diagnosis of sudden infant death syndrome (SIDS) was made for 76%. For the remaining subjects, causes of death were respiratory or other infections (14%), congenital anomalies or organ failures (4%), aspiration (2%), or accidents or traumatic events (4%). PCR results were positive for B pertussis for 12 case subjects (5.1%) (all with SIDS or respiratory infections) and 5.3% of control subjects. Of the 12 case subjects with positive PCR results, 10 (83%) were male. Questionnaires had been returned by the parents of 5 of the 12 infants. Three had experienced a respiratory illness (all with cough), beginning 7, 14, and 19 days before death. None had a known contact with a case of pertussis. Four of 15 control infants (27%) with positive PCR findings for B pertussis had a cough illness, indicating possible pertussis, and 2 of those 4 developed typical symptoms (whooping). Background information was received from 116 parents (46%) of case subjects and from parents of all control subjects. Upper respiratory tract infections within 4 weeks before death were reported for 53% of case subjects and 38% of control subjects. Also, fewer case subjects (33%) than control subjects (68%) had received age-adequate numbers of pertussis vaccine doses. CONCLUSIONS: The concept of infection as a factor in SIDS is supported by a number of observations, including the seasonal distribution of the occurrence of SIDS; the high incidence of concurrent upper respiratory tract infections among infants dying as a result of SIDS; the peak age at 3 to 4 months; nicotine use in a child's household, which predisposes children to respiratory infections such as otitis media; and the protective role of breastfeeding. A prominent role might be suspected for B pertussis, for several reasons. 1) B pertussis infections in infancy are frequently associated with apneic spells, which are occasionally life-threatening and, if leading to death, might be reported as SIDS. 2) Epidemiologic evidence from the United Kingdom, Sweden, and Norway indicates that SIDS is associated with B pertussis infection. 3) In a previously published study, we detected B pertussis DNA in the nasopharynx of 9 of 51 consecutive infants (18%) with sudden unexpected deaths. This is the first prospective, controlled study to investigate the possible etiologic role of B pertussis in SIDS. Clinically unrecognized B pertussis infections were relatively frequent (5.3%) among control infants during the course of our study. The rate of infection was similar or perhaps greater for control subjects, compared with case subjects (1.7%), when only NPS results were compared. This may seem surprising but is supported by other studies, in which asymptomatic infections or mild respiratory illnesses were observed among infants exposed to B pertussis. Careful autopsies, including histologic evaluations of organ specimens and use of PCR to detect B pertussis in NPSs and tracheal specimens, represented a strength of this study. Our general findings were as expected. The majority of cases were classified as SIDS. The second largest group included infants for whom respiratory infections were found. The findings of various other diagnoses, which in several instances would have been undiscovered otherwise, emphasize the need for autopsies after unexpected infant deaths. What is the significance of the identified B pertussis infections in 12 cases? Several pieces of evidence support the plausibility of a cause-and-effect relationship. Eight of the 12 case subjects died before 6 months of age, the typical age for death attributable to pertussis. In autopsies, 9 of the subjects were found to have signs of respiratory infections; for 2 infants, the autopsies suggested that death was attributable to a respiratory infection. One additional infant (data not shown) had brain edema (which could have been attributable to hypoxemia during pertussis). Lower rates of completed primary series or age-adequate numbers of pertussis vaccine doses among case subjects than among control subjects may indicate that immunization against pertussis protects children from death attributable to unrecognized B pertussis infection. Moreover, a recent study indicated that immunization with diphtheria-tetanus-pertussis vaccine induces antibodies that cross-react with pyrogenic staphylococcal toxins, which have been implicated in several cases of SIDS. Other microorganisms may be involved in the sudden death of infants, as suggested in this study by the higher rate of a history of concurrent upper respiratory tract infections among case subjects, compared with control subjects. Similarly, in a Scandinavian study, 48% of 244 SIDS case subjects, compared with 31% of 869 control subjects, exhibited symptoms of upper airway infection during the last week before death or interview, respectively. Because SIDS is a diagnosis of exclusion, every attempt should be made to identify a cause of death during autopsy. This should include the search for pathogenic microorganisms in the respiratory tract with the use of PCR and other sensitive tests. In conclusion, B pertussis infection was found for 12 of 234 infants (5.1%) with unexpected deaths, and the infections might have contributed to the deaths.