Inherited predisposition to stillbirth: an intergenerational analysis of 26,788 mother-daughter pairs

Woolner, Andrea; Raja, Edwin Amalraj; Bhattacharya, Siladitya; Danielian, Peter; Bhattacharya, Sohinee

doi:10.1016/j.ajog.2019.01.215

Cited by 5 publications

(11 citation statements)

References 28 publications

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“…They demonstrated an increased risk of miscarriage but not stillbirth in their intergenerational analysis. 14,29 This difference between our results and theirs may be due to several factors. First, an intergenerational link may have been missed in their work due to the relative rarity of fetal death [?…”

Section: Discussioncontrasting

confidence: 96%

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

Workalemahu

Pagé

Meeks

et al. 2022

Preprint

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Objective To determine if 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=9 404) 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 Standardized 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 and live-birth were estimated using logistic regression models. Results We identified 390 high-risk pedigrees with evidence for excess familial aggregation (FSIR≥2.00 and P-value<0.05). FDRs, SDRs and TDRs of affected parents had 1.14-fold (95% confidence interval [CI]: 1.04-1.26), 1.22-fold (95% CI: 1.11-1.33), and 1.15-fold (95% CI: 1.08-1.21) higher stillbirth odds compared to FDRs, SDRs and TDRs of unaffected parents, respectively. Parental sex-specific analyses showed male FDRs, SDRs and TDRs of affected fathers had 1.22-fold (95% CI: 1.02-1.47), 1.38-fold (95% CI: 1.17-1.62), 1.17-fold (95% CI: 1.05-1.30) higher stillbirth odds compared to those of unaffected fathers, respectively. FDRs, SDRs and TDRs of affected mothers had 1.12-fold (95% CI: 0.98-1.28), 1.09-fold (95% CI: 0.96-1.24), and 1.15-fold (95% CI: 1.06-1.24) higher stillbirth odds compared with those of unaffected mothers, respectively. Conclusions We provide evidence for familial aggregation of stillbirth. Our findings warrant investigation into genes associated with stillbirth and underscore the need to design large-scale studies to determine its genetic architecture.

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Section: Discussioncontrasting

confidence: 96%

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

Workalemahu

Pagé

Meeks

et al. 2022

Preprint

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“…The study of miscarriage included 31 565 mother‐daughter pairs and the study of stillbirth included 27 688 mother‐daughter pairs. They demonstrated an increased risk of miscarriage but not stillbirth in their intergenerational analysis 14,35 . This difference between our results and theirs may be due to several factors.…”

Section: Discussioncontrasting

confidence: 95%

“…Accordingly, data regarding early pregnancy loss have been mixed in regard to a heritable risk of spontaneous abortion or fetal death. 33,34 Recent studies by Woolner et al investigated familial risk of miscarriage 35 or stillbirth 14 in mother-daughter pairs. Both studies included mothers (pregnancies between 1949 and 2000) with at least one daughter (pregnancies between 1965 and 2016) in Aberdeen, UK.…”

Section: F I G U R E 2 Stillbirth Odds Among Relatives Of Parents Aff...mentioning

confidence: 99%

“…One study evaluated mother-daughter pairs and did not find an inherited predisposition for stillbirth. 14 Given that there are both maternal and paternal contributions to the fetal genotype, investigation into broader pedigrees may reveal important insights to understand the extent to which genes may affect stillbirth risk. 15 Thus, we sought to investigate whether stillbirth aggregates in families and, if so, to quantify the risk of stillbirth for parents with family history in extended pedigrees.…”

Section: Introductionmentioning

confidence: 99%

“…However, data regarding an inherited genetic risk for stillbirth are limited. One study evaluated mother‐daughter pairs and did not find an inherited predisposition for stillbirth 14 . Given that there are both maternal and paternal contributions to the fetal genotype, investigation into broader pedigrees may reveal important insights to understand the extent to which genes may affect stillbirth risk 15 .…”

Section: Introductionmentioning

confidence: 99%

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

Workalemahu

Pagé

Meeks

et al. 2022

BJOG

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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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Inherited susceptibility to miscarriage: a nested case-control study of 31,565 women from an intergenerational cohort

Woolner

Raja²,

Bhattacharya

et al. 2020

American Journal of Obstetrics and Gynecology

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Inherited predisposition to stillbirth: an intergenerational analysis of 26,788 mother-daughter pairs

Cited by 5 publications

References 28 publications

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

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

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

Inherited susceptibility to miscarriage: a nested case-control study of 31,565 women from an intergenerational cohort

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