Infant mortality: the contribution of genetic disorders

Wojcik, Monica H.; Schwartz, Talia S.; Thiele, Katri; Paterson, Heather; Stadelmaier, Rachel; Mullen, Thomas E.; VanNoy, Grace E.; Genetti, Casie A.; Madden, Jill A.; Gubbels, Cynthia S.; Yu, Timothy W.; Tan, Wen‐Hann; Agrawal, Pankaj B.

doi:10.1038/s41372-019-0451-5

Cited by 56 publications

(46 citation statements)

References 32 publications

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“…Informed consent was obtained via our Institutional Review Board-approved protocol. Trio exome sequencing was performed through the Broad Institute Center for Mendelian Genomics using methods as previously described (Wojcik et al 2019).…”

Section: Examples Of Monogenic Cause Of Congenital Anomalies From Ourmentioning

confidence: 99%

Deciphering congenital anomalies for the next generation

Wojcik

Agrawal

2020

Cold Spring Harb Mol Case Stud

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Congenital anomalies are common, with 2-3% of infants estimated to have at least one major congenital malformation and countless others with minor malformations of lesser cosmetic or medical importance. As congenital malformations are major drivers of morbidity and mortality, representing the leading cause of infant mortality in the United States, there is substantial interest in understanding the underlying etiologies-particularly if modifiable causes may be identified or pre-or postnatal treatments can be offered. Recent research has begun to reveal the spectrum of monogenic disorders that commonly result in birth defects, and newer approaches have revealed non-Mendelian genetic contributions including gene-environment interactions. Our experience suggests that increased efforts to sequence and analyze cases of perinatal death, as well as continued global collaboration, will be essential in understanding the genomic landscape of structural anomalies.

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Section: Examples Of Monogenic Cause Of Congenital Anomalies From Ourmentioning

confidence: 99%

Deciphering congenital anomalies for the next generation

Wojcik

Agrawal

2020

Cold Spring Harb Mol Case Stud

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“…Little, however, has yet been published with regard to the contribution of genetic diseases to infant mortality using this technology. In six published studies and the cohort reported herein a weighted average of 21% of infant deaths was attributable to single locus genetic diseases 25 , 28 , 45 , 63 – 65 . However, the range of attribution varied widely between studies (6%-86%), reflecting different experimental designs and inclusion and exclusion criteria.…”

Section: Discussionmentioning

confidence: 91%

“…In two studies, genome sequencing was performed post mortem 63 , 64 . One study had both ante and post mortem genomic sequencing 65 . While all included inpatient and community deaths, the inclusion criteria differed in each study (Table 4 ).…”

Section: Resultsmentioning

confidence: 99%

Measurement of genetic diseases as a cause of mortality in infants receiving whole genome sequencing

et al. 2020

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Understanding causes of infant mortality shapes public health policy and prioritizes diseases for investments in surveillance, intervention and medical research. Rapid genomic sequencing has created a novel opportunity to decrease infant mortality associated with treatable genetic diseases. Herein, we sought to measure the contribution of genetic diseases to mortality among infants by secondary analysis of babies enrolled in two clinical studies and a systematic literature review. Among 312 infants who had been admitted to an ICU at Rady Children’s Hospital between November 2015 and September 2018 and received rapid genomic sequencing, 30 (10%) died in infancy. Ten (33%) of the infants who died were diagnosed with 11 genetic diseases. The San Diego Study of Outcomes in Mothers and Infants platform identified differences between in-hospital and out-of-hospital causes of infant death. Similarly, in six published studies, 195 (21%) of 918 infant deaths were associated with genetic diseases by genomic sequencing. In 195 infant deaths associated with genetic diseases, locus heterogeneity was 70%. Treatment guidelines existed for 70% of the genetic diseases diagnosed, suggesting that rapid genomic sequencing has substantial potential to decrease infant mortality among infants in ICUs. Further studies are needed in larger, comprehensive, unbiased patient sets to determine the generalizability of these findings.

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“…Congenital anomalies and genetic conditions are noted in approximately 2–5% of pregnancies and are major causes of fetal demise and infant death. 1 , 2 Chromosomal microarray is recommended to evaluate for chromosomal abnormalities in fetuses with congenital anomalies, but 60–70% of fetuses remain without a genetic diagnosis after microarray, which can complicate counseling, prenatal management, and parental decision-making. 3 , 4 …”

Section: Introductionmentioning

confidence: 99%