Maternal use of methadone and risk of sudden neonatal death.

AIM: To identify and describe infant deaths presenting suddenly and unexpectedly in whom there was a history of maternal methadone consumption or misuse of drugs during pregnancy. METHODS: Retrospective review of neonatal postmortem examinations between 2004 and 2011. RESULTS: A total of 138 autopsies were performed in infants up to 28 days. Thirty-two cases (23%) presented suddenly and unexpectedly. In 12 of 32 (37.5%), in whom the cause of death remained unexplained after a thorough postmortem, there was a history of methadone use and/or other drugs of abuse during pregnancy. Their mean age at death was 11 days (range 1-28 days). Multiple risk factors for sudden infant death syndrome were present in these 12 cases: smoking (10), prematurity (7), and inappropriate sleeping place (8). Five mothers were positive for hepatitis C. The history was inconsistent with the findings in only one case. CONCLUSION: An unexpectedly high proportion of infants dying suddenly and unexpectedly in the first month had a history of maternal substance misuse. All had multiple risk factors, for sudden infant death syndrome many avoidable. We would stress the need to emphasise the 'Safe Sleep' message with these families at every contact with health professionals.

Cardiac Genetic Investigation of Sudden Infant and Early Childhood Death: A Study From Victims to Families.

Background Sudden infant death syndrome (SIDS) is the leading cause of death up to age 1. Sudden unexplained death in childhood (SUDC) is similar but affects mostly toddlers aged 1 to 4. SUDC is rarer than SIDS, and although cardiogenetic testing (molecular autopsy) identifies an underlying cause in a fraction of SIDS, less is known about SUDC. Methods and Results Seventy-seven SIDS and 16 SUDC cases underwent molecular autopsy with 25 definitive-evidence arrhythmia-associated genes. In 18 cases, another 76 genes with varying degrees of evidence were analyzed. Parents were offered cascade screening. Double-blind review of clinical-genetic data established genotype-phenotype correlations. The yield of likely pathogenic variants in the 25 genes was higher in SUDC than in SIDS (18.8% [3/16] versus 2.6% [2/77], respectively; P=0.03), whereas novel/ultra-rare variants of uncertain significance were comparably represented. Rare variants of uncertain significance and likely benign variants were found only in SIDS. In cases with expanded analyses, likely pathogenic/likely benign variants stemmed only from definitive-evidence genes, whereas all other genes contributed only variants of uncertain significance. Among 24 parents screened, variant status and phenotype largely agreed, and 3 cases positively correlated for cardiac channelopathies. Genotype-phenotype correlations significantly aided variant adjudication. Conclusions Genetic yield is higher in SUDC than in SIDS although, in both, it is contributed only by definitive-evidence genes. SIDS/SUDC cascade family screening facilitates establishment or dismissal of a diagnosis through definitive variant adjudication indicating that anonymity is no longer justifiable. Channelopathies may underlie a relevant fraction of SUDC. Binary classifications of genetic causality (pathogenic versus benign) could not always be adequate.

Recurrent sudden unexpected death in infancy: a case series of sibling deaths.

OBJECTIVES: To determine the rate of sudden unexpected death in infancy (SUDI) for infants born after a previous SUDI in the same family, and to establish the causes of death and the frequency of child protection concerns in families with recurrent SUDI. DESIGN: Observational study using clinical case records. SETTING: The UK's Care of Next Infant (CONI) programme, which provides additional care to families who have experienced SUDI with their subsequent children. PATIENTS: Infants registered on CONI between January 2000 and December 2015. MAIN OUTCOME MEASURES: Cause of death, presence of modifiable risk factors for SUDI and child protection concerns. RESULTS: There were 6608 live-born infants registered in CONI with 29 deaths. 26 families had 2 deaths, and 3 families had 3 deaths. The SUDI rate for infants born after one SUDI is 3.93 (95% CI 2.7 to 5.8) per 1000 live births. Cause of death was unexplained for 19 first and 15 CONI deaths. Accidental asphyxia accounted for 2 first and 6 CONI deaths; medical causes for 3 first and 4 CONI deaths; and homicide for 2 first and 4 CONI deaths. 10 families had child protection concerns. CONCLUSIONS: The SUDI rate for siblings is 10 times higher than the current UK SUDI rate. Homicide presenting as recurrent SUDI is very rare. Many parents continued to smoke and exposed infants to hazardous co-sleeping situations, with these directly leading to or contributing to the death of six siblings. SUDI parents need support to improve parenting skills and reduce risk to subsequent infants.

Quality of investigations into unexpected deaths of infants and young children in England after implementation of national child death review procedures in 2008: a retrospective assessment.

OBJECTIVES: In 2008, new statutory national procedures for responding to unexpected child deaths were introduced throughout England. There has, to date, been no national audit of these procedures. STUDY DESIGN: Families bereaved by the unexpected death of a child under 4 years of age since 2008 were invited to participate. Factors contributing to the death and investigations after the death were explored. Telephone interviews were conducted, and coroners' documents were obtained. The nature and quality of investigations was compared with the required procedures; information on each case was reviewed by a multiagency panel; and the death was categorised using the Avon clinicopathological classification. RESULTS: Data were obtained from 91 bereaved families (64 infant deaths and 27 children aged 1-3 years); 85 remained unexplained after postmortem examination. Documentation of multiagency assessments was poorly recorded. Most (88%) families received a home visit from the police, but few (37%) received joint visits by police and healthcare professionals. Postmortem examinations closely followed national guidance; 94% involved paediatric pathologists; 61% of families had a final meeting with a paediatrician to explain the investigation outcome. There was no improvement in frequency of home visits by health professionals or final meetings with paediatricians between 2008-2013 and 2014-2017 and no improvement in parental satisfaction with the process. CONCLUSIONS: Statutory procedures need to be followed more closely. The implementation of a national child mortality database from 2019 will allow continuing audit of the quality of investigations after unexpected child deaths. An important area amenable to improvement is increased involvement by paediatricians.

Adaptation of the Carter method to adjust lumbar spine bone mineral content for age and body size: application to children who were born preterm.

In adults, the Carter method allows the separation of the lumbar spine bone mineral content (BMC) into its constituents; bone volume (BV) and volumetric density (bone mineral apparent density [BMAD]). However, this method is not widely used in pediatric studies and does not account for the effects of body habitus on bone mass. The aims of this study were to modify the Carter method for use in children by developing an approach that adjusts separately for age and body height, and to test whether lumbar spine bone mass is normal in children born who were born preterm. Twenty-five preterm-born children were matched to a term-born child. Lumbar spine bone mass was measured using dual-energy X-ray absorptiometry. The BV and BMAD were calculated. Z-scores based on age and height were calculated. The preterm group had reduced absolute height, weight, BMC, BV, and BMAD, and reduced height, weight, and BMC for their age. The BMC was appropriate for height. The BV was appropriate for age. The BMAD was reduced for age but appropriate for height. In preterm children, the major abnormality at the lumbar spine is a decrease in volumetric density; however, this decrease is proportional with their reduced stature, and we speculate that there is no reduction in the strength of the lumbar spine.

Mortality of babies enrolled in a community-based support programme: CONI PLUS (Care of Next Infant Plus).

OBJECTIVE: To report mortality in babies enrolled on a community-based programme, Care of Next Infant Plus (CONI PLUS), which primarily supports parents anxious because of previous sudden unexpected death in infancy (SUDI) in their extended family or following an apparent life threatening event (ALTE) in their baby. DESIGN: Prospective observational study from 1996 to 2010 in the UK. RESULTS: Of 6487 babies enrolled, 37 died (5.7 per 1000). There were 2789 (43.0%) SUDI related babies of whom, six died suddenly and unexpectedly (2.15 per 1000). Four babies were sharing a sofa at night or a bed with parent(s) who smoked or had consumed alcohol. Of the 1882 (29.0%) babies enrolled following an ALTE, five died suddenly and unexpectedly (2.66 per 1000): four unexplained and one due to infection. None occurred while sharing a sleep surface, and at least three died during the day. The remaining 1816 (28%) babies were enrolled for other reasons. Seven died suddenly and unexpectedly (3.85 per 1000), two were unexplained and none associated with bed sharing. CONCLUSIONS: The number of SUDI deaths in babies enrolled on CONI PLUS is higher than expected from UK averages. Deaths in babies enrolled because of family history of SUDI were mostly associated with inappropriate sharing of a sleep surface at night and mostly outside the peak age range for sudden infant death. The opposite is true for those enrolled following an ALTE. The number of deaths is small but findings suggest a different mechanism for death in these two groups.