Defining the Newborn Blood Spot Screening Reference Interval for TSH: Impact of Ethnicity.

CONTEXT: There is variability in the congenital hypothyroidism (CH) newborn screening TSH cutoff across the United Kingdom. OBJECTIVE: To determine the influences of year, gender, and ethnicity on screening variability and examine whether there is an optimal operational TSH cutoff. DESIGN AND SETTING: Single center, retrospective population study using blood spot TSH cards received by the Great Ormond Street Hospital Screening Laboratory between 2006 and 2012. PATIENTS: A total of 824 588 newborn screening blood spot TSH cards. INTERVENTION: Blood spot TSH results were recorded with demographic data including the Ethnic Category Code. MAIN OUTCOME MEASURES: The proportions of samples exceeding different TSH cutoffs, ranked by ethnicity. RESULTS: The proportion of samples exceeding the TSH cutoff increased over time, with the cutoff at 4 mU/L, but not at 6 mU/L. There was a consistent trend with ethnicity, irrespective of cutoff, with the odds ratio of exceeding the TSH cutoff lowest (∼1.0) in White babies, higher in Pakistani and Bangladeshi (>2.0), and highest in Chinese (>3.5). CONCLUSIONS: The blood spot TSH screening data demonstrate a clear ranking according to ethnicity for differences in mean TSH. This suggests that there may be ethnic differences in thyroid physiology. Ethnic diversity within populations needs to be considered when establishing and interpreting screening TSH cutoffs.

Post-mortem interval and bacteriological culture yield in sudden unexpected death in infancy (SUDI).

It has been hypothesised that post-mortem translocation, the migration of micro-organisms from mucosal surfaces into the body after death, leads to microbial overgrowth in post-mortem samples, which is more frequently polymicrobial and which would be detected more frequently with increased post-mortem interval (PMI) from death to autopsy. This study aimed to evaluate the association between PMI and bacteriological yield in post-mortem examinations of sudden unexpected deaths in infancy (SUDI). A retrospective review of all microbiological findings from >500 SUDI autopsies (7-365 days of age) was performed as part of a larger review of >1500 paediatric autopsies over a 10-year period, 1996-2005. All autopsies were carried out in a single specialist centre by a small number of paediatric pathologists. For the 507 SUDI included in the analysis, there were 2079 samples collected for bacteriological culture. The median PMI was 2 days. The proportion of positive cultures decreased from 83% for samples taken within 24h of death, to 67% when taken five or more days after death (chi-square for linear trend=19.99, P<0.0001). Polymicrobial cultures decreased from 61% to 46% (chi-square for linear trend=12.88, P=0.0003), and cultures taken two or more days after death yielded significantly fewer isolates per sample than cultures taken less than 2 days after death (Mann-Whitney U-test, P=0.009). The findings of this study demonstrate that a PMI of several days' duration is neither associated with an increased frequency of positive cultures nor with an increased frequency of mixed-growth episodes as was hypothesised to occur with post-mortem translocation. Indeed, the opposite trend is observed, suggesting that a longer PMI may result in death of micro-organisms. However, these data do not allow assessment of the possibility of significant post-mortem translocation occurring within the first few hours after death. Whilst the interpretation of positive microbiological cultures in SUDI post-mortems remains difficult, a PMI of several days' duration is not associated with an increased risk of post-mortem translocation and routine microbiological sampling is recommended in all SUDI autopsies, even when there is a PMI of several days.

Sudden unexpected neonatal death in the first week of life: autopsy findings from a specialist centre.

OBJECTIVE: Sudden unexpected early neonatal death (SUEND) in the first week of life shares features with sudden unexpected death in infancy (SUDI) but is not included as SUDI, which is limited to post-perinatal deaths. The aim of this study was to review SUEND autopsies performed in a single specialist centre over a 10-year period, (1996-2005). METHODS: Retrospective analysis of >1500 consecutively performed paediatric autopsies performed by paediatric pathologists at one centre conducted according to a standard protocol including ancillary investigations. SUENDs were identified and autopsy findings reviewed. RESULTS: Of 1516 post-mortem examinations, 180 were first-week neonatal deaths, 55 (31%) presenting as SUEND. Thirty-two (58%) were explained following autopsy, whilst the remainder were unexplained; most deaths during sleep were associated with adult co-sleeping. Around 40% of explained deaths were associated with undiagnosed congenital abnormalities, mainly congenital heart disease. In addition, there were nine infection-related deaths and three deaths from unsuspected metabolic disease (fatty acid oxidation defects). CONCLUSION: There are distinct differences between SUEND and SUDI, with significantly more explained deaths in the former and a much greater proportion due to congenital abnormalities and metabolic disease.