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

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Abstract

Background
Previous evidence suggests that placental dysfunction including pre-eclampsia is inherited from mother to daughter, but heritability of stillbirth has never been investigated.

Objective
To investigate if there is an inherited predisposition to stillbirth transmitted from mother to daughter.

Study Design
We carried out a nested case-control study within the intergenerational cohort held in the Aberdeen Maternity and Neonatal Databank (AMND). All mothers who had at least one daughter in Aberdeen, United Kingdom between 1949 and 2000 were included. Mother – daughter pairs were linked using the Scottish Community Health Index (CHI) number. The main exposure was mother’s history of stillbirth. The primary outcome was stillbirth in any of the daughter’s pregnancies. A population average model using Generalised Estimating Equations (GEE) with robust standard errors was used to estimate odds of a mother’s history of stillbirth in daughters with a stillbirth compared to daughters with only livebirths. This method accounted for clustering of daughters within mothers and multi-adjusted analyses were performed to include confounders at the daughter’s pregnancy level.

Results
Among the daughters, 384 had a history of one or more stillbirths (cases) while 26,404 only ever had livebirths (controls). We found no statistically significant association between mothers’ history of stillbirth (adjusted Odds Ratio (aOR) 0.63; 95% CI 0.24-1.63) or miscarriage (aOR 1.01; 95% CI 0.71-1.42) and stillbirth in daughters.

Conclusions
This is the first study to investigate an inherited predisposition to stillbirth. There was no evidence of an inherited predisposition to stillbirth transmitted from mother to daughter.
Original languageEnglish
Pages (from-to)393.e1-393.e7
Number of pages7
JournalAmerican Journal of Obstetrics and Gynecology
Volume220
Issue number4
Early online date23 Jan 2019
DOIs
Publication statusPublished - Apr 2019

Fingerprint

Stillbirth
Odds Ratio
Pregnancy
Spontaneous Abortion
Pre-Eclampsia
Cluster Analysis
Case-Control Studies
Databases

Keywords

  • Stillbirth
  • intrauterine death
  • mother-daughter pairs
  • family history
  • familial
  • intergenerational
  • intrauterine
  • stillbirth
  • generalized estimating equations
  • patterns
  • death
  • generations
  • growth
  • recurrence
  • fetal
  • birth

ASJC Scopus subject areas

  • Obstetrics and Gynaecology

Cite this

@article{b459d609235a410aaeebc6ed2e35aece,
title = "Inherited predisposition to stillbirth: an intergenerational analysis of 26,788 mother-daughter pairs",
abstract = "BackgroundPrevious evidence suggests that placental dysfunction including pre-eclampsia is inherited from mother to daughter, but heritability of stillbirth has never been investigated.ObjectiveTo investigate if there is an inherited predisposition to stillbirth transmitted from mother to daughter.Study DesignWe carried out a nested case-control study within the intergenerational cohort held in the Aberdeen Maternity and Neonatal Databank (AMND). All mothers who had at least one daughter in Aberdeen, United Kingdom between 1949 and 2000 were included. Mother – daughter pairs were linked using the Scottish Community Health Index (CHI) number. The main exposure was mother’s history of stillbirth. The primary outcome was stillbirth in any of the daughter’s pregnancies. A population average model using Generalised Estimating Equations (GEE) with robust standard errors was used to estimate odds of a mother’s history of stillbirth in daughters with a stillbirth compared to daughters with only livebirths. This method accounted for clustering of daughters within mothers and multi-adjusted analyses were performed to include confounders at the daughter’s pregnancy level.ResultsAmong the daughters, 384 had a history of one or more stillbirths (cases) while 26,404 only ever had livebirths (controls). We found no statistically significant association between mothers’ history of stillbirth (adjusted Odds Ratio (aOR) 0.63; 95{\%} CI 0.24-1.63) or miscarriage (aOR 1.01; 95{\%} CI 0.71-1.42) and stillbirth in daughters.ConclusionsThis is the first study to investigate an inherited predisposition to stillbirth. There was no evidence of an inherited predisposition to stillbirth transmitted from mother to daughter.",
keywords = "Stillbirth, intrauterine death, mother-daughter pairs, family history, familial, intergenerational, intrauterine, stillbirth, generalized estimating equations, patterns, death, generations, growth, recurrence, fetal, birth",
author = "Woolner, {Andrea M. F.} and Raja, {Edwin Amalraj} and Siladitya Bhattacharya and Peter Danielian and Sohinee Bhattacharya",
note = "Internal funding was received for the costs of data extraction from the Aberdeen Maternity and Neonatal Databank from the Fetal and Perinatal NHS Grampian endowment fund, NHS Grampian, Aberdeen, UK. No external funding was received.",
year = "2019",
month = "4",
doi = "10.1016/j.ajog.2019.01.215",
language = "English",
volume = "220",
pages = "393.e1--393.e7",
journal = "American Journal of Obstetrics and Gynecology",
issn = "0002-9378",
publisher = "Mosby/Elsevier,",
number = "4",

}

TY - JOUR

T1 - Inherited predisposition to stillbirth

T2 - an intergenerational analysis of 26,788 mother-daughter pairs

AU - Woolner, Andrea M. F.

AU - Raja, Edwin Amalraj

AU - Bhattacharya, Siladitya

AU - Danielian, Peter

AU - Bhattacharya, Sohinee

N1 - Internal funding was received for the costs of data extraction from the Aberdeen Maternity and Neonatal Databank from the Fetal and Perinatal NHS Grampian endowment fund, NHS Grampian, Aberdeen, UK. No external funding was received.

PY - 2019/4

Y1 - 2019/4

N2 - BackgroundPrevious evidence suggests that placental dysfunction including pre-eclampsia is inherited from mother to daughter, but heritability of stillbirth has never been investigated.ObjectiveTo investigate if there is an inherited predisposition to stillbirth transmitted from mother to daughter.Study DesignWe carried out a nested case-control study within the intergenerational cohort held in the Aberdeen Maternity and Neonatal Databank (AMND). All mothers who had at least one daughter in Aberdeen, United Kingdom between 1949 and 2000 were included. Mother – daughter pairs were linked using the Scottish Community Health Index (CHI) number. The main exposure was mother’s history of stillbirth. The primary outcome was stillbirth in any of the daughter’s pregnancies. A population average model using Generalised Estimating Equations (GEE) with robust standard errors was used to estimate odds of a mother’s history of stillbirth in daughters with a stillbirth compared to daughters with only livebirths. This method accounted for clustering of daughters within mothers and multi-adjusted analyses were performed to include confounders at the daughter’s pregnancy level.ResultsAmong the daughters, 384 had a history of one or more stillbirths (cases) while 26,404 only ever had livebirths (controls). We found no statistically significant association between mothers’ history of stillbirth (adjusted Odds Ratio (aOR) 0.63; 95% CI 0.24-1.63) or miscarriage (aOR 1.01; 95% CI 0.71-1.42) and stillbirth in daughters.ConclusionsThis is the first study to investigate an inherited predisposition to stillbirth. There was no evidence of an inherited predisposition to stillbirth transmitted from mother to daughter.

AB - BackgroundPrevious evidence suggests that placental dysfunction including pre-eclampsia is inherited from mother to daughter, but heritability of stillbirth has never been investigated.ObjectiveTo investigate if there is an inherited predisposition to stillbirth transmitted from mother to daughter.Study DesignWe carried out a nested case-control study within the intergenerational cohort held in the Aberdeen Maternity and Neonatal Databank (AMND). All mothers who had at least one daughter in Aberdeen, United Kingdom between 1949 and 2000 were included. Mother – daughter pairs were linked using the Scottish Community Health Index (CHI) number. The main exposure was mother’s history of stillbirth. The primary outcome was stillbirth in any of the daughter’s pregnancies. A population average model using Generalised Estimating Equations (GEE) with robust standard errors was used to estimate odds of a mother’s history of stillbirth in daughters with a stillbirth compared to daughters with only livebirths. This method accounted for clustering of daughters within mothers and multi-adjusted analyses were performed to include confounders at the daughter’s pregnancy level.ResultsAmong the daughters, 384 had a history of one or more stillbirths (cases) while 26,404 only ever had livebirths (controls). We found no statistically significant association between mothers’ history of stillbirth (adjusted Odds Ratio (aOR) 0.63; 95% CI 0.24-1.63) or miscarriage (aOR 1.01; 95% CI 0.71-1.42) and stillbirth in daughters.ConclusionsThis is the first study to investigate an inherited predisposition to stillbirth. There was no evidence of an inherited predisposition to stillbirth transmitted from mother to daughter.

KW - Stillbirth

KW - intrauterine death

KW - mother-daughter pairs

KW - family history

KW - familial

KW - intergenerational

KW - intrauterine

KW - stillbirth

KW - generalized estimating equations

KW - patterns

KW - death

KW - generations

KW - growth

KW - recurrence

KW - fetal

KW - birth

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DO - 10.1016/j.ajog.2019.01.215

M3 - Article

VL - 220

SP - 393.e1-393.e7

JO - American Journal of Obstetrics and Gynecology

JF - American Journal of Obstetrics and Gynecology

SN - 0002-9378

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ER -