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

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.