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Title: An investigation of familial predisposition to pregnancy loss
Author: Woolner, Andrea M. F.
ISNI:       0000 0004 7961 2826
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2019
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Background: Most miscarriages and stillbirths are unexplained. Pregnancy complications including pre-eclampsia, preterm birth and fetal growth restriction exhibit familial predisposition. Given potentially shared pathophysiology with these conditions and intrauterine pregnancy loss, it was hypothesised that miscarriage, stillbirth or pregnancy loss as a whole could run in families. Methods: First, a systematic review and meta-analysis of observational studies was conducted to investigate the association of a family history of pregnancy loss and the outcome of pregnancy loss in women. Second, an intergenerational case-control study was carried out using routinely collected population-based data from an intergenerational cohort to determine if a familial risk of pregnancy loss was transmitted from mother to daughter. All deliveries between 1949 and 2016 in the Aberdeen Maternity and Neonatal Databank (AMND) were included. Odds ratios (OR) with 95% confidence intervals were calculated to determine any association between mother's and daughter's history of pregnancy loss, miscarriage, or stillbirth. A generalised estimating equations (GEE) model was used to account for clustering of daughters within mothers. Results: Twelve studies were included in the systematic review. Women who miscarried were twice as likely to have a family history of miscarriage (pooled unadjusted OR 2.20 (95%CI 1.41 - 3.43)). In the case-control study a smaller association was seen between mother's history of any pregnancy loss (adjusted OR 1.12 (95%CI 1.02 - 1.22)) or miscarriage (adjusted OR 1.11 (1.01 - 1.22)) and miscarriage in daughters. Daughters with recurrent miscarriage (two or more) were more likely to be born to a mother with a history of miscarriage (adjusted OR 1.25 (95%CI 1.04 - 1.49)). Conclusions: Women who miscarry are significantly more likely to have a family history of miscarriage. There is a familial predisposition to miscarriage passed from mothers to daughters. There was no evidence of familial transmission of stillbirth risk transmitted from mother to daughter.
Supervisor: Bhattacharya, Sohinee ; Bhattacharya, Siladitya ; Danielian, Peter ; Edwin-Amalraj, Raja Sponsor: University of Aberdeen
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Pregnancy ; Miscarriage ; Stillbirth