Copy number variants and placental abnormalities in stillborn fetuses: A secondary analysis of the Stillbirth Collaborative Research Network study

Workalemahu, Tsegaselassie; Dalton, Susan; Allshouse, Amanda A.; Carey, Andrew; Pagé, Jessica; Blue, Nathan R.; Thorsten, Vanessa; Goldenberg, Robert L.; Pınar, Halit; Reddy, Uma M.; Silver, Robert M.

doi:10.1111/1471-0528.17269

Cited by 2 publications

(1 citation statement)

References 49 publications

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“…8 Interpreting the pathogenicity of CNVs, however, remains challenging, 6 as limited studies link relevant clinical information to genetic observations in a structured way. Following our recent work on CNVs and placental abnormalities, 10 we used our multicentre setting of stillbirth population to determine specific CNVs associated with fetal structural malformations. We hypothesised that duplicated or deleted pathogenic CNVs in fetal/placental genes are associated with fetal structural malformations.…”

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confidence: 99%

Copy number variants and fetal structural abnormalities in stillborn fetuses: A secondary analysis of the Stillbirth Collaborative Research Network study

Workalemahu

Dalton

Son

et al. 2023

BJOG

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ObjectiveTo examine the association of placental and fetal DNA copy number variants (CNVs) with fetal structural malformations (FSMs) in stillborn fetuses.DesignA secondary analysis of stillbirth cases in the Stillbirth Collaborative Research Network (SCRN) study.SettingMulticenter, 59 hospitals in five geographic regions in the USA.Population388 stillbirth cases of the SCRN study (2006–2008).MethodsFetal structural malformations were grouped by anatomic system and specific malformation type (e.g. central nervous system, thoracic, cardiac, gastrointestinal, skeletal, umbilical cord and craniofacial defects). Single‐nucleotide polymorphism array detected CNVs of at least 500 kb. CNVs were classified into two groups: normal, defined as no CNVs >500 kb or benign CNVs, and abnormal, defined as pathogenic or variants of unknown clinical significance.Main outcome measuresThe proportions of abnormal CNVs and normal CNVs were compared between stillbirth cases with and without FSMs using the Wald Chi‐square test.ResultsThe proportion of stillbirth cases with any FSMs was higher among those with abnormal CNVs than among those with normal CNVs (47.5 versus 19.1%; P‐value <0.001). The most common organ system‐specific FSMs associated with abnormal CNVs were cardiac defects, followed by hydrops, craniofacial defects and skeletal defects. A pathogenic deletion of 1q21.1 involving 46 genes (e.g. CHD1L) and a duplication of 21q22.13 involving four genes (SIM2, CLDN14, CHAF1B, HLCS) were associated with a skeletal and cardiac defect, respectively.ConclusionSpecific CNVs involving several genes were associated with FSMs in stillborn fetuses. The findings warrant further investigation and may inform counselling and care surrounding pregnancies affected by FSMs at risk for stillbirth.

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Section: Introductionmentioning

confidence: 99%

Copy number variants and fetal structural abnormalities in stillborn fetuses: A secondary analysis of the Stillbirth Collaborative Research Network study

Workalemahu

Dalton

Son

et al. 2023

BJOG

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Familial aggregation of stillbirth: A pedigree analysis of a matched case–control study

Workalemahu

Pagé

Meeks

et al. 2022

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Objective: To determine whether stillbirth aggregates in families and quantify its familial risk using extended pedigrees. Design: State-wide matched case-control study. Setting: Utah, United States. Population: Stillbirth cases (n = 9404) and live birth controls (18 808) between 1978 and 2019.Methods: Using the Utah Population Database, a population-based genealogical resource linked with state fetal death and birth records, we identified high-risk pedigrees with excess familial aggregation of stillbirth using the Familial Standardised Incidence Ratio (FSIR). Stillbirth odds ratio (OR) for first-degree relatives (FDR), second-degree relatives (SDR) and third-degree relatives (TDR) of parents with a stillbirth (affected) and live birth (unaffected) were estimated using logistic regression models.Main outcome measures: Familial aggregation estimated using FSIR, and stillbirth OR estimated for FDR, SDR and TDR of affected and unaffected parents using logistic regression models. Results:We identified 390 high-risk pedigrees with evidence for excess familial aggregation (FSIR ≥2.00; P-value <0.05). FDRs, SDRs and TDRs of affected parents had

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Copy number variants and placental abnormalities in stillborn fetuses: A secondary analysis of the Stillbirth Collaborative Research Network study

Cited by 2 publications

References 49 publications

Copy number variants and fetal structural abnormalities in stillborn fetuses: A secondary analysis of the Stillbirth Collaborative Research Network study

Copy number variants and fetal structural abnormalities in stillborn fetuses: A secondary analysis of the Stillbirth Collaborative Research Network study

Familial aggregation of stillbirth: A pedigree analysis of a matched case–control study

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