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

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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 languageEnglish
Pages (from-to)168.e1-168.e8
Number of pages8
JournalAmerican Journal of Obstetrics and Gynecology
Volume222
Issue number2
Early online date19 Aug 2019
DOIs
Publication statusPublished - Feb 2020

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

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