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

Wellcome Open Research

article

Oonagh E. Keag¹  Lee Murphy²  Aoibheann Bradley³  Naomi Deakin⁴  Sonia Whyte⁵  Jane E. Norman⁶  Sarah J. Stock¹ 

[1] Simpson Centre for Reproductive Health, Royal Infirmary of Edinburgh;Edinburgh Clinical Research Facility, Western General Hospital;Queen Margaret Hospital;Department of Clinical Neurosciences, University of Cambridge;MRC Centre for Reproductive Health, University of Edinburgh;Faculty of Health Sciences, University of Bristol;Usher Institute of Population Health Sciences and Informatics, University of Edinburgh

关键词: premature birth;    fetal membranes;    premature rupture;    obstetric labour;    premature;    surveys and questionnaires;    phenotype;    DNA;   

DOI  :  10.12688/wellcomeopenres.15207.2

学科分类：内科医学

来源: Wellcome

【 摘 要 】

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 (k0.75) 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.

【 授权许可】

CC BY