Postal recruitment for genetic studies of preterm birth: A feasibility study

Oonagh E Keag; Lee Murphy; Aoibheann Bradley; Naomi Deakin; Sonia Whyte; Jane E Norman; Sarah J Stock

doi:10.12688/wellcomeopenres.15207.2

Postal recruitment for genetic studies of preterm birth: A feasibility study

Wellcome Open Res. 2020 Jun 30:5:26. doi: 10.12688/wellcomeopenres.15207.2. eCollection 2020.

Authors

Oonagh E Keag¹, Lee Murphy², Aoibheann Bradley³, Naomi Deakin⁴, Sonia Whyte⁵, Jane E Norman⁶, Sarah J Stock^{1

7}

Affiliations

¹ Simpson Centre for Reproductive Health, Royal Infirmary of Edinburgh, Edinburgh, EH16 4SA, UK.
² Edinburgh Clinical Research Facility, Western General Hospital, Edinburgh, EH4 2XU, UK.
³ Queen Margaret Hospital, Dunfermline, KY12 0SU, UK.
⁴ Department of Clinical Neurosciences, University of Cambridge, Cambridge, CB2 0QQ, UK.
⁵ MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, EH16 4TJ, UK.
⁶ Faculty of Health Sciences, University of Bristol, Bristol, BS8 1UD, UK.
⁷ Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, EH16 4UX, UK.

Abstract

Background: Preterm birth (PTB) represents the leading cause of neonatal death. Large-scale genetic studies are necessary to determine genetic influences on PTB risk, but prospective cohort studies are expensive and time-consuming. We investigated the feasibility of retrospective recruitment of post-partum women for efficient collection of genetic samples, with self-collected saliva for DNA extraction from themselves and their babies, alongside self-recollection of pregnancy and birth details to phenotype PTB. Methods: 708 women who had participated in the OPPTIMUM trial (a randomised trial of progesterone pessaries to prevent PTB [ISRCTN14568373]) and consented to further contact were invited to provide self-collected saliva from themselves and their babies. DNA was extracted from Oragene OG-500 (adults) and OG-575 (babies) saliva kits and the yield measured by Qubit. Samples were analysed using a panel of Taqman single nucleotide polymorphism (SNP) assays. A questionnaire designed to meet the minimum data set required for phenotyping PTB was included. Questionnaire responses were transcribed and analysed for concordance with prospective trial data using Cohen's kappa ( k). Results: Recruitment rate was 162/708 (23%) for self-collected saliva samples and 157/708 (22%) for questionnaire responses. 161 samples from the mother provided DNA with median yield 59.0µg (0.4-148.9µg). 156 samples were successfully genotyped (96.9%). 136 baby samples had a median yield 11.5µg (0.1-102.7µg); two samples failed DNA extraction. 131 baby samples (96.3%) were successfully genotyped. Concordance between self-recalled birth details and prospective birth details was excellent ( k>0.75) in 4 out of 10 key fields for phenotyping PTB (mode of delivery, labour onset, ethnicity and maternal age at birth). Conclusion: This feasibility study demonstrates that self-collected DNA samples from mothers and babies were sufficient for genetic analysis but yields were variable. Self-recollection of pregnancy and birth details was inadequate for accurately phenotyping PTB, highlighting the need for alternative strategies for investigating genetic links with PTB.

Keywords: DNA; fetal membranes; obstetric labour; phenotype; premature; premature birth; premature rupture; surveys and questionnaires.

Associated data

figshare/10.6084/m9.figshare.7887083

Abstract

Associated data

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