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

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.