Dataset Information

Exome sequencing in infants with congenital hearing impairment: a population-based cohort study.

ABSTRACT: Congenital hearing impairment (HI) is the most common sensory impairment and can be isolated or part of a syndrome. Diagnosis through newborn hearing screening and management through early intervention, hearing aids and cochlear implantation is well established in the Australian setting; however understanding the genetic basis of congenital HI has been missing. This population-derived cohort comprised infants with moderate-profound bilateral HI born in the 2016-2017 calendar years, detected through newborn hearing screening. Participants were recruited through an integrated paediatric, otolaryngology and genetics HI clinic and offered whole exome sequencing (WES) on a HiSeq4000 or NextSeq500 (Illumina) platform with a targeted average sequencing depth of 100x and chromosome microarray on the Illumina Infinium core exome-24v1.2 platform. Of those approached, 68% (106/156) consented to participate. The rate of genetic diagnosis was 56% (59/106), significantly higher than standard of care (GJB2/6 sequencing only), 21% (22/106). There were clinical implications for the 106 participants: 36% required no further screening, 9% had tailored screening initiated, 2% were offered treatment and 4% had informed care for a complex neurodevelopmental syndrome. WES in this cohort demonstrates the range of diagnoses associated with congenital HI and confirms the genetic heterogeneity of congenital HI. The high diagnostic yield and clinical implications emphasises the need for genomic sequencing to become standard of care.

SUBMITTER: Downie L

PROVIDER: S-EPMC7171096 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Exome sequencing in infants with congenital hearing impairment: a population-based cohort study.

Downie Lilian L Halliday Jane J Burt Rachel R Lunke Sebastian S Lynch Elly E Martyn Melissa M Poulakis Zeffie Z Gaff Clara C Sung Valerie V Wake Melissa M Hunter Matthew F MF Saunders Kerryn K Rose Elizabeth E Lewis Sharon S Jarmolowicz Anna A Phelan Dean D Rehm Heidi L HL Amor David J DJ

European journal of human genetics : EJHG 20191212 5

Congenital hearing impairment (HI) is the most common sensory impairment and can be isolated or part of a syndrome. Diagnosis through newborn hearing screening and management through early intervention, hearing aids and cochlear implantation is well established in the Australian setting; however understanding the genetic basis of congenital HI has been missing. This population-derived cohort comprised infants with moderate-profound bilateral HI born in the 2016-2017 calendar years, detected thro ...[more]

PMID: 31827275

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Project description:The purpose of this study is to evaluate the association between perinatal asphyxia, neonatal encephalopathy, and childhood hearing impairment. This is a population-based study including all Norwegian infants born ≥ 36 weeks gestation between 1999 and 2014 and alive at 2 years (n = 866,232). Data was linked from five national health registries with follow-up through 2019. Perinatal asphyxia was defined as need for neonatal intensive care unit (NICU) admission and an Apgar 5-min score of 4-6 (moderate) or 0-3 (severe). We coined infants with seizures and an Apgar 5-min score < 7 as neonatal encephalopathy with seizures. Infants who received therapeutic hypothermia were considered to have moderate-severe hypoxic-ischemic encephalopathy (HIE). The reference group for comparisons were non-admitted infants with Apgar 5-min score ≥ 7. We used logistic regression models and present data as adjusted odds ratios (aORs) with 95% confidence intervals (CI). The aOR for hearing impairment was increased in all infants admitted to NICU: moderate asphyxia aOR 2.2 (95% CI 1.7-2.9), severe asphyxia aOR 5.2 (95% CI 3.6-7.5), neonatal encephalopathy with seizures aOR 7.0 (95% CI 2.6-19.0), and moderate-severe HIE aOR 10.7 (95% CI 5.3-22.0). However, non-admitted infants with Apgar 5-min scores < 7 did not have increased OR of hearing impairment. The aOR for hearing impairment for individual Apgar 5-min scores in NICU infants increased with decreasing Apgar scores and was 13.6 (95% CI 5.9-31.3) when the score was 0. Conclusions: An Apgar 5-min score < 7 in combination with NICU admission is an independent risk factor for hearing impairment. Children with moderate-severe HIE had the highest risk for hearing impairment. What is Known: • Perinatal asphyxia and neonatal encephalopathy are associated with an increased risk of hearing impairment. • The strength of the association, and how other co-morbidities affect the risk of hearing impairment, is poorly defined. What is New: • Among neonates admitted to a neonatal intensive care unit (NICU), decreased Apgar 5-min scores, and increased severity of neonatal encephalopathy, were associated with a gradual rise in risk of hearing impairment. • Neonates with an Apgar 5-min score 7, but without NICU admission, did not have an increased risk of hearing impairment.

Project description:BackgroundHearing loss (HL) is a leading cause of disability worldwide, but its clinical consequences and population burden have been incompletely studied.MethodsWe did a retrospective population-based cohort study of 4,724,646 adults residing in Alberta between April 1, 2004 and March 31, 2019, of whom 152,766 (3.2%) had HL identified using administrative health data. We used administrative data to identify comorbidity and clinical outcomes, including death, myocardial infarction, stroke/transient ischemic attack, depression, dementia, placement in long-term care (LTC), hospitalization, emergency visits, pressure ulcers, adverse drug events and falls. We used Weibull survival models (binary outcomes) and negative binomial models (rate outcomes) to compare the likelihood of outcomes in those with vs without HL. We calculated population-attributable fractions to estimate the number of binary outcomes associated with HL.FindingsThe age-sex-standardized prevalence of all 31 comorbidities at baseline was higher among participants with HL than those without. Over median follow-up of 14.4 y and after adjustment for potential confounders at baseline, participants with HL had higher rates of days in hospital (rate ratio 1.65, 95% CI 1.39, 1.97), falls (RR 1.72, 95% CI 1.59, 1.86), adverse drug events (RR 1.40, 95% CI 1.35, 1.45), and emergency visits (RR 1.21, 95% CI 1.14, 1.28) compared to those without, and higher adjusted hazards of death, myocardial infarction, stroke/transient ischemic attack, depression, heart failure, dementia, pressure ulcers and LTC placement. The estimated number of people with HL who required new LTC placement annually in Canada was 15,631, of which 1023 were attributable to HL. Corresponding estimates for new dementia among people with HL were 14,959 and 4350, and for stroke/TIA the estimates were 11,582 and 2242.InterpretationHL is common, is often accompanied by substantial comorbidity, and is associated with significant increases in risk for a broad range of adverse clinical outcomes, some of which are potentially preventable. This high population health burden suggests that increased and coordinated investment is needed to improve the care of people with HL.FundingCanadian Institutes of Health Research; David Freeze chair in health services research.

Dataset Information

Exome sequencing in infants with congenital hearing impairment: a population-based cohort study.

Publications

Exome sequencing in infants with congenital hearing impairment: a population-based cohort study.

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