Pharmacogenomics of 17‐alpha hydroxyprogesterone caproate for recurrent preterm birth: a case–control study

• Published in: BJOG : an international journal of obstetrics and gynaecology 2018-02, Vol.125 (3), p.343-350
• Main Authors: Manuck, TA, Watkins, WS, Esplin, MS, Biggio, J, Bukowski, R, Parry, S, Zhan, H, Huang, H, Andrews, W, Saade, G, Sadovsky, Y, Reddy, UM, Ilekis, J, Yandell, M, Varner, MW, Jorde, LB
• Format: Article
• Language: English
• Subjects: 17‐Alpha hydroxyprogesterone caproate; Birth; Clinical outcomes; current preterm birth; Drug therapy; Genetic diversity; Genotypes; Gestational age; Pharmacogenomics; Pregnancy; Premature birth; spontaneous prematurity; Success
• ISSN: 1470-0328; 1471-0528
• DOI: 10.1111/1471-0528.14485

Objective To compare maternal genotypes between women with and without significant prolongation of pregnancy in the setting of 17‐alpha hydroxyprogesterone caproate (17‐P) administration for the prevention of recurrent preterm birth (PTB). Design Case–control. Setting Three tertiary‐care centres across the USA. Population Women (n = 99) with ≥ 1 prior singleton spontaneous PTB, receiving 17‐P. Methods Women were classified as having successful prolongation of pregnancy during the 17‐P treated pregnancy, in two ways: (1) Definition A: success/non‐success based on difference in gestational age at delivery between 17‐P‐treated and untreated pregnancies (success: delivered ≥ 3 weeks later with 17‐P) and (2) Definition B: success/non‐success based on reaching term (success: delivered at term with 17‐P). Main outcome measures To assess genetic variation, all women underwent whole exome sequencing. Between‐group sequence variation was analysed with the Variant Annotation, Analysis, and Search Tool (VAAST). Genes scored by VAAST with P