The association of beta-2 adrenoceptor genotype with short-cervix mediated preterm birth: a case-control study.

ABSTRACT

OBJECTIVE: To determine whether ß2 -adrenoceptor (ß2 AR) genotype is associated with shortening of the cervix or with preterm birth (PTB) risk among women with a short cervix in the second trimester. DESIGN: A case-control ancillary study to a multicentre randomised controlled trial. SETTING: Fourteen participating centres of the Maternal-Fetal Medicine Units Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. POPULATION Four hundred thirty-nine women, including 315 with short cervix and 124 with normal cervical length. METHODS: Nulliparous women with cervical length <30 mm upon a 16-22-week transvaginal sonogram and controls frequency-matched for race/ethnicity with cervical lengths ≥40 mm were studied. ß2 AR genotype was determined at positions encoding for amino acid residues 16 and 27. MAIN OUTCOME MEASURES: Genotype distributions were compared between case and control groups. Within the short cervix group, pregnancy outcomes were compared by genotype, with a primary outcome of PTB <37 weeks. RESULTS: Genotype data were available at position 16 for 433 women and at position 27 for 437. Using a recessive model testing for association between short cervix and genotype, and adjusted for ethnicity, there was no statistical difference between cases and controls for Arg16 homozygosity (OR 0.7, 95% CI 0.4-1.3) or Gln27 homozygosity (OR 0.9, 95% CI 0.3-2.7). Among cases, Arg16 homozygosity was not associated with protection from PTB or spontaneous PTB. Gln27 homozygosity was not associated with PTB risk, although sample size was limited. CONCLUSIONS: ß2 AR genotype does not seem to be associated with short cervical length or with PTB following the second-trimester identification of a short cervix. Influences on PTB associated with ß2 AR genotype do not appear to involve a short cervix pathway.