Inherited susceptibility to miscarriage: a nested case-control study of 31565 women from an intergenerational cohort

Andrea M F Woolner; Edwin-Amalraj Raja; Siladitya Bhattacharya; Peter Danielian; Sohinee Bhattacharya

doi:10.1016/j.ajog.2019.08.013

Inherited susceptibility to miscarriage: a nested case-control study of 31565 women from an intergenerational cohort

Andrea M F Woolner^* (Corresponding Author), Edwin-Amalraj Raja, Siladitya Bhattacharya, Peter Danielian, Sohinee Bhattacharya

^*Corresponding author for this work

Aberdeen Royal Infirmary

Research output: Contribution to journal › Article › peer-review

13 Citations (Scopus)

5 Downloads (Pure)

Abstract

Background

Miscarriage can be a devastating outcome for couples and most miscarriages are unexplained. Many adverse obstetric outcomes are thought to be inherited such as pre-eclampsia, preterm birth and growth restriction. It is possible these conditions could share similar pathophysiological mechanisms with miscarriage such as endothelial dysfunction. Therefore, it was hypothesised that there could be a susceptibility to miscarriage transmitted from mother to daughter.

Objective

This study aimed to investigate the association between a maternal history of miscarriage and the risk of miscarriage in daughters.

Study design

A case-control study nested within an intergenerational cohort was conducted. Mother-daughter pairs were identified from the intergenerational cohort within the Aberdeen Maternity and Neonatal Databank (AMND), United Kingdom. A mother’s history of miscarriage was the exposure. The primary outcome was miscarriage in daughters. There were 31, 565 mother-daughter pairs eligible for inclusion. A population average model using Generalised Estimating Equations (GEE) with robust standard errors was used to estimate odds of a mother’s history of miscarriage in daughters with a miscarriage 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

Daughters who miscarried had 11% greater odds of being born to mothers with a history of miscarriage (adjusted Odds Ratio (aOR) 1.11; 95% Confidence Intervals (95% CI) 1.01 to 1.22). Daughters with recurrent miscarriage (two or more) were also more likely to be born to a mother with a history of miscarriage (aOR 1.25; 95%CI 1.04 to 1.49).

Conclusions

There may be an inherited predisposition to miscarriage transmitted from mothers to daughters. Future research should investigate genetic or familial environmental factors which may predispose women to miscarriage.

Original language	English
Pages (from-to)	168.e1-168.e8
Number of pages	8
Journal	American Journal of Obstetrics and Gynecology
Volume	222
Issue number	2
Early online date	19 Aug 2019
DOIs	https://doi.org/10.1016/j.ajog.2019.08.013
Publication status	Published - Feb 2020

Bibliographical note

Funding

There was no external funding received for this study. Internal funding was sought for the costs of AMND data management fees from the Fetal and Perinatal endowment fund, NHS Grampian, Aberdeen, U.K.

Acknowledgements

Thank you to the Aberdeen Maternity and Neonatal Databank data management team for their efforts in extracting the data and to Dr Gordon Prescott, Medical Statistician at the University of Aberdeen, for providing statistical advice.

Keywords

Familial
family history
inheritance
inherited predisposition
intergenerational
miscarriage
mother-daughter pairs
recurrent miscarriage
hereditary
familial
POPULATION
GENERALIZED ESTIMATING EQUATIONS
RISK-FACTORS
ENDOTHELIAL DYSFUNCTION
PREECLAMPSIA
PREGNANCY LOSS
PERINATAL OUTCOMES
RECURRENT SPONTANEOUS-ABORTIONS
CARDIOVASCULAR-DISEASE
2ND PREGNANCY

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.ajog.2019.08.013Licence: Unspecified

Accepted Manuscript
© 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
Accepted author manuscript, 288 KBLicence: CC BY-NC-ND

Cite this

Inherited susceptibility to miscarriage: a nested case-control study of 31565 women from an intergenerational cohort. / Woolner, Andrea M F (Corresponding Author); Raja, Edwin-Amalraj ; Bhattacharya, Siladitya et al.
In: American Journal of Obstetrics and Gynecology, Vol. 222, No. 2, 02.2020, p. 168.e1-168.e8.

Research output: Contribution to journal › Article › peer-review

@article{60fd0ddea7c346e58c9e38aa4eb1a745,

title = "Inherited susceptibility to miscarriage: a nested case-control study of 31565 women from an intergenerational cohort",

abstract = "BackgroundMiscarriage can be a devastating outcome for couples and most miscarriages are unexplained. Many adverse obstetric outcomes are thought to be inherited such as pre-eclampsia, preterm birth and growth restriction. It is possible these conditions could share similar pathophysiological mechanisms with miscarriage such as endothelial dysfunction. Therefore, it was hypothesised that there could be a susceptibility to miscarriage transmitted from mother to daughter.ObjectiveThis study aimed to investigate the association between a maternal history of miscarriage and the risk of miscarriage in daughters.Study designA case-control study nested within an intergenerational cohort was conducted. Mother-daughter pairs were identified from the intergenerational cohort within the Aberdeen Maternity and Neonatal Databank (AMND), United Kingdom. A mother{\textquoteright}s history of miscarriage was the exposure. The primary outcome was miscarriage in daughters. There were 31, 565 mother-daughter pairs eligible for inclusion. A population average model using Generalised Estimating Equations (GEE) with robust standard errors was used to estimate odds of a mother{\textquoteright}s history of miscarriage in daughters with a miscarriage 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{\textquoteright}s pregnancy level.ResultsDaughters who miscarried had 11% greater odds of being born to mothers with a history of miscarriage (adjusted Odds Ratio (aOR) 1.11; 95% Confidence Intervals (95% CI) 1.01 to 1.22). Daughters with recurrent miscarriage (two or more) were also more likely to be born to a mother with a history of miscarriage (aOR 1.25; 95%CI 1.04 to 1.49).ConclusionsThere may be an inherited predisposition to miscarriage transmitted from mothers to daughters. Future research should investigate genetic or familial environmental factors which may predispose women to miscarriage.",

keywords = "Familial, family history, inheritance, inherited predisposition, intergenerational, miscarriage, mother-daughter pairs, recurrent miscarriage, hereditary, familial, POPULATION, GENERALIZED ESTIMATING EQUATIONS, RISK-FACTORS, ENDOTHELIAL DYSFUNCTION, PREECLAMPSIA, PREGNANCY LOSS, PERINATAL OUTCOMES, RECURRENT SPONTANEOUS-ABORTIONS, CARDIOVASCULAR-DISEASE, 2ND PREGNANCY",

author = "Woolner, {Andrea M F} and Edwin-Amalraj Raja and Siladitya Bhattacharya and Peter Danielian and Sohinee Bhattacharya",

note = "Funding There was no external funding received for this study. Internal funding was sought for the costs of AMND data management fees from the Fetal and Perinatal endowment fund, NHS Grampian, Aberdeen, U.K. Acknowledgements Thank you to the Aberdeen Maternity and Neonatal Databank data management team for their efforts in extracting the data and to Dr Gordon Prescott, Medical Statistician at the University of Aberdeen, for providing statistical advice.",

year = "2020",

month = feb,

doi = "10.1016/j.ajog.2019.08.013",

language = "English",

volume = "222",

pages = "168.e1--168.e8",

journal = "American Journal of Obstetrics and Gynecology",

issn = "0002-9378",

publisher = "Mosby/Elsevier,",

number = "2",

}

TY - JOUR

T1 - Inherited susceptibility to miscarriage

T2 - a nested case-control study of 31565 women from an intergenerational cohort

AU - Woolner, Andrea M F

AU - Raja, Edwin-Amalraj

AU - Bhattacharya, Siladitya

AU - Danielian, Peter

AU - Bhattacharya, Sohinee

N1 - Funding There was no external funding received for this study. Internal funding was sought for the costs of AMND data management fees from the Fetal and Perinatal endowment fund, NHS Grampian, Aberdeen, U.K. Acknowledgements Thank you to the Aberdeen Maternity and Neonatal Databank data management team for their efforts in extracting the data and to Dr Gordon Prescott, Medical Statistician at the University of Aberdeen, for providing statistical advice.

PY - 2020/2

Y1 - 2020/2

N2 - BackgroundMiscarriage can be a devastating outcome for couples and most miscarriages are unexplained. Many adverse obstetric outcomes are thought to be inherited such as pre-eclampsia, preterm birth and growth restriction. It is possible these conditions could share similar pathophysiological mechanisms with miscarriage such as endothelial dysfunction. Therefore, it was hypothesised that there could be a susceptibility to miscarriage transmitted from mother to daughter.ObjectiveThis study aimed to investigate the association between a maternal history of miscarriage and the risk of miscarriage in daughters.Study designA case-control study nested within an intergenerational cohort was conducted. Mother-daughter pairs were identified from the intergenerational cohort within the Aberdeen Maternity and Neonatal Databank (AMND), United Kingdom. A mother’s history of miscarriage was the exposure. The primary outcome was miscarriage in daughters. There were 31, 565 mother-daughter pairs eligible for inclusion. A population average model using Generalised Estimating Equations (GEE) with robust standard errors was used to estimate odds of a mother’s history of miscarriage in daughters with a miscarriage 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.ResultsDaughters who miscarried had 11% greater odds of being born to mothers with a history of miscarriage (adjusted Odds Ratio (aOR) 1.11; 95% Confidence Intervals (95% CI) 1.01 to 1.22). Daughters with recurrent miscarriage (two or more) were also more likely to be born to a mother with a history of miscarriage (aOR 1.25; 95%CI 1.04 to 1.49).ConclusionsThere may be an inherited predisposition to miscarriage transmitted from mothers to daughters. Future research should investigate genetic or familial environmental factors which may predispose women to miscarriage.

AB - BackgroundMiscarriage can be a devastating outcome for couples and most miscarriages are unexplained. Many adverse obstetric outcomes are thought to be inherited such as pre-eclampsia, preterm birth and growth restriction. It is possible these conditions could share similar pathophysiological mechanisms with miscarriage such as endothelial dysfunction. Therefore, it was hypothesised that there could be a susceptibility to miscarriage transmitted from mother to daughter.ObjectiveThis study aimed to investigate the association between a maternal history of miscarriage and the risk of miscarriage in daughters.Study designA case-control study nested within an intergenerational cohort was conducted. Mother-daughter pairs were identified from the intergenerational cohort within the Aberdeen Maternity and Neonatal Databank (AMND), United Kingdom. A mother’s history of miscarriage was the exposure. The primary outcome was miscarriage in daughters. There were 31, 565 mother-daughter pairs eligible for inclusion. A population average model using Generalised Estimating Equations (GEE) with robust standard errors was used to estimate odds of a mother’s history of miscarriage in daughters with a miscarriage 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.ResultsDaughters who miscarried had 11% greater odds of being born to mothers with a history of miscarriage (adjusted Odds Ratio (aOR) 1.11; 95% Confidence Intervals (95% CI) 1.01 to 1.22). Daughters with recurrent miscarriage (two or more) were also more likely to be born to a mother with a history of miscarriage (aOR 1.25; 95%CI 1.04 to 1.49).ConclusionsThere may be an inherited predisposition to miscarriage transmitted from mothers to daughters. Future research should investigate genetic or familial environmental factors which may predispose women to miscarriage.

KW - Familial

KW - family history

KW - inheritance

KW - inherited predisposition

KW - intergenerational

KW - miscarriage

KW - mother-daughter pairs

KW - recurrent miscarriage

KW - hereditary

KW - familial

KW - POPULATION

KW - GENERALIZED ESTIMATING EQUATIONS

KW - RISK-FACTORS

KW - ENDOTHELIAL DYSFUNCTION

KW - PREECLAMPSIA

KW - PREGNANCY LOSS

KW - PERINATAL OUTCOMES

KW - RECURRENT SPONTANEOUS-ABORTIONS

KW - CARDIOVASCULAR-DISEASE

KW - 2ND PREGNANCY

UR - http://www.mendeley.com/research/inherited-susceptibility-miscarriage-nested-casecontrol-study-31565-women-intergenerational-cohort

UR - http://www.scopus.com/inward/record.url?scp=85076011774&partnerID=8YFLogxK

U2 - 10.1016/j.ajog.2019.08.013

DO - 10.1016/j.ajog.2019.08.013

M3 - Article

C2 - 31437424

SN - 0002-9378

VL - 222

SP - 168.e1-168.e8

JO - American Journal of Obstetrics and Gynecology

JF - American Journal of Obstetrics and Gynecology

IS - 2

ER -

Inherited susceptibility to miscarriage: a nested case-control study of 31565 women from an intergenerational cohort

Abstract

Bibliographical note

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Aberdeen Maternity and Neonatal Databank

Siladitya Bhattacharya

Andrea Woolner

Cite this

Inherited susceptibility to miscarriage: a nested case-control study of 31565 women from an intergenerational cohort

Abstract

Bibliographical note

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Datasets

Aberdeen Maternity and Neonatal Databank

Profiles

Siladitya Bhattacharya

Andrea Woolner

Cite this