The association of beta-2 adrenoceptor genotype with short-cervix mediated preterm birth

A case-control study

R. Miller, R. Smiley, E. A. Thom, W. A. Grobman, J. D. Iams, B. M. Mercer, George Saade, A. T. Tita, U. M. Reddy, D. J. Rouse, Y. Sorokin, S. C. Blackwell, M. S. Esplin, J. E. Tolosa, S. N. Caritis

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Objective To determine whether β<inf>2</inf>-adrenoceptor (β<inf>2</inf>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. β<inf>2</inf>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 β<inf>2</inf>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 β<inf>2</inf>AR genotype do not appear to involve a short cervix pathway.

Original languageEnglish (US)
Pages (from-to)1387-1394
Number of pages8
JournalBJOG: An International Journal of Obstetrics and Gynaecology
Volume122
Issue number10
DOIs
StatePublished - Sep 1 2015

Fingerprint

Premature Birth
Cervix Uteri
Adrenergic Receptors
Case-Control Studies
Genotype
Second Pregnancy Trimester
National Institute of Child Health and Human Development (U.S.)
Pregnancy Outcome
Randomized Controlled Trials
Mothers
Medicine
Outcome Assessment (Health Care)
Amino Acids
Control Groups
Population

Keywords

  • Beta-2 adrenoceptor
  • genotype
  • short cervix

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

The association of beta-2 adrenoceptor genotype with short-cervix mediated preterm birth : A case-control study. / Miller, R.; Smiley, R.; Thom, E. A.; Grobman, W. A.; Iams, J. D.; Mercer, B. M.; Saade, George; Tita, A. T.; Reddy, U. M.; Rouse, D. J.; Sorokin, Y.; Blackwell, S. C.; Esplin, M. S.; Tolosa, J. E.; Caritis, S. N.

In: BJOG: An International Journal of Obstetrics and Gynaecology, Vol. 122, No. 10, 01.09.2015, p. 1387-1394.

Research output: Contribution to journalArticle

Miller, R, Smiley, R, Thom, EA, Grobman, WA, Iams, JD, Mercer, BM, Saade, G, Tita, AT, Reddy, UM, Rouse, DJ, Sorokin, Y, Blackwell, SC, Esplin, MS, Tolosa, JE & Caritis, SN 2015, 'The association of beta-2 adrenoceptor genotype with short-cervix mediated preterm birth: A case-control study', BJOG: An International Journal of Obstetrics and Gynaecology, vol. 122, no. 10, pp. 1387-1394. https://doi.org/10.1111/1471-0528.13243
Miller, R. ; Smiley, R. ; Thom, E. A. ; Grobman, W. A. ; Iams, J. D. ; Mercer, B. M. ; Saade, George ; Tita, A. T. ; Reddy, U. M. ; Rouse, D. J. ; Sorokin, Y. ; Blackwell, S. C. ; Esplin, M. S. ; Tolosa, J. E. ; Caritis, S. N. / The association of beta-2 adrenoceptor genotype with short-cervix mediated preterm birth : A case-control study. In: BJOG: An International Journal of Obstetrics and Gynaecology. 2015 ; Vol. 122, No. 10. pp. 1387-1394.
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abstract = "Objective To determine whether β2-adrenoceptor (β2AR) 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. β2AR 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 β2AR 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 β2AR genotype do not appear to involve a short cervix pathway.",
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T1 - The association of beta-2 adrenoceptor genotype with short-cervix mediated preterm birth

T2 - A case-control study

AU - Miller, R.

AU - Smiley, R.

AU - Thom, E. A.

AU - Grobman, W. A.

AU - Iams, J. D.

AU - Mercer, B. M.

AU - Saade, George

AU - Tita, A. T.

AU - Reddy, U. M.

AU - Rouse, D. J.

AU - Sorokin, Y.

AU - Blackwell, S. C.

AU - Esplin, M. S.

AU - Tolosa, J. E.

AU - Caritis, S. N.

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N2 - Objective To determine whether β2-adrenoceptor (β2AR) 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. β2AR 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 β2AR 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 β2AR genotype do not appear to involve a short cervix pathway.

AB - Objective To determine whether β2-adrenoceptor (β2AR) 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. β2AR 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 β2AR 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 β2AR genotype do not appear to involve a short cervix pathway.

KW - Beta-2 adrenoceptor

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