SIDS Risk Up Fourfold in Siblings of SIDS Victims

Patrice Wendling

March 19, 2018

BARCELONA — The adjusted risk for sudden infant death syndrome (SIDS) is up to fourfold higher among siblings of SIDS infants than in the general population, a nationwide study shows.

"This study provides strong support for genetic testing of SIDS probands with indication for prevention of future SIDS in affected families,” study author Charlotte Glinge, MD, PhD student, Copenhagen University Hospital, Rigshospitalet, Denmark, said during a young investigator awards session at the European Heart Rhythm Association (EHRA) 2018 meeting.

Dr Charlotte Glinge

She suggested that the cause of SIDS is best explained by a triple-risk model that consists of exogenous stressors, such as prone sleeping and smoking exposure; a critical development period for the infant; and an underlying vulnerability, such as genetic susceptibility. This model would suggest an aggregation of SIDS in families, but previous studies have been mostly on smaller selected cases and not in the general population.

To address this issue, the investigators used five nationwide Danish registries to examine data for all 2,516,785 Danish children younger  than 1 year of age born between 1978 and 2015. Of these, there were 1535 SIDS victims, 1455 SIDS victims with siblings, and 2373 siblings of SIDS victims.

Sibling sex and mother’s age (median, 29 years) were similar in both groups; however, siblings of SIDS infants were significantly more likely than the general population to live in households with low income (35% vs 23%) and to have mothers with only basic school education (51% vs 22%), which might be expected, Glinge said.

SIDS occurred in only 8 of the 2373 siblings of SIDS probands and in 1535 of the 2.5 million controls, with 90% of deaths occurring within the first 9 months of life (median, 3 months).

The standardized incidence rate of SIDS among siblings of SIDS probands was 4.06 after adjustment for sex, age, and calendar year (95% CI, 2.08 - 8.11) and 3.51 after further adjustment for mother’s age and education (95% CI, 1.75 - 7.01).

"Although we cannot in this study distinguish between genetic and environmental risk factors, the fact that in a country like Denmark where we have been working hard to reduce the SIDS rate with public health campaigns we can still see a family aggregation of SIDS points to a genetic component of SIDS,” Glinge said. "In addition, we know that in 5 to 15 percent of SIDS cases we can identify a genetic mutation related to inherited cardiac disorders that might have contributed to the arrhythmic sudden death.”

She said siblings who survive the first year of life could still be at high risk for sudden death and that genetic and clinical follow-up with electrocardiography and echocardiography is warranted for families with a SIDS infant. While ECG screening of all infants is controversial, this targeted screening is cost beneficial, even with the few number of sibling deaths.

Glinge told theheart.org | Medscape Cardiology that genetic testing is recommended in the EHRA and Heart Rhythm Society guidelines and is offered to families of SIDS cases in Denmark. Notably, the incidence of SIDS in Denmark is 0.1 per 1000 births but 0.5 per 1000 births in the United States, a rate that remains relatively unchanged in recent years after declining in the 1990s.

"We believe that all parents should be asked about a family history of sudden cardiac death, and that parents and siblings should be offered cardiology tests to provide the best chance to identify a cardiac condition. However, we know that management of a surviving family member requires a multidisciplinary team,” she said.

Vincent Probst, MD, Centre Hospitalier Universitaire de Nantes, France, who served as a judge for the session, told theheart.org | Medscape Cardiology that information on SIDS siblings is limited and that these results are valuable in terms of clinical practice.

"It's important because after the occurrence of SIDS, the first question a parent will ask to the physician is, 'What happened to my child?' and second, 'Is there a risk for my other children?'" he said.

Despite the small number of SIDS cases among siblings, Probst agreed that these families should be evaluated for cardiac pathologies and that it's necessary to perform genetic analyses, especially if SIDS occurs very early in life. Families with low income and education levels also should be counseled on ways to reduce the risk for SIDS, such as infant sleeping position and smoking avoidance, but the emphasis there has to be "on the population as a whole and not specifically after the occurrence of SIDS.”

The work was supported by a grant from the Novo Nordisk Foundation and the H2020 Program of the EU ESCAPE-NET project. Glinge was funded by Copenhagen University Hospital. Probst reported having no relevant financial relationships.

European Heart Rhythm Association (EHRA) 2018. Presentation 518. Presented March 19, 2018.

Follow Patrice Wendling on Twitter: @pwendl. For more from theheart.org | Medscape Cardiology, follow us on Twitter and Facebook.

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