Genetic polymorphisms and spontaneous preterm birth

Obstet Gynecol. 2007 Feb;109(2 Pt 1):384-91. doi: 10.1097/01.AOG.0000252712.62241.1a.


Objective: To examine whether selected genetic polymorphisms in the infant are associated with spontaneous preterm birth (less than 37 weeks) among children with or without later-diagnosed cerebral palsy.

Methods: Exploratory case-control study investigating the relationship of gestational age at delivery to 31 single nucleotide polymorphisms measured in newborn screening bloodspots. Among all 443 children with later-diagnosed cerebral palsy born to white women in South Australia in 1986-1999, 234 were born after spontaneous onset of labor, and 108 of these were preterm (gestational age less than 37 weeks). The comparison group was 549 infants born after spontaneous onset of labor, of whom 147 were preterm. Distributions of genotypic frequencies were examined in preterm compared with term infants with and without cerebral palsy. Genotyping was performed using a Taqman assay.

Results: In children without cerebral palsy, preterm birth after spontaneous onset of labor was more frequent in association with a variant of the beta2 adrenergic receptor gene (ADRB2 Q27E, P=.003), inducible nitric oxide synthase (iNOS or NOS2A, P=.042), or thrombomodulin (G127A, P=.006). Among children with cerebral palsy, preterm birth was associated with polymorphisms in genes for endothelial nitric oxide synthase (eNOS -922, P=.012), plasminogen activator inhibitor-2 (P=.015 and .019), and alpha adducin (ADD1, P=.047).

Conclusion: We confirm previous observations that variants of the beta adrenergic receptor and of nitric oxide synthase are associated with prematurity, and suggest that genetic variants of the placental antifibrinolytic plasminogen activator inhibitor-2, and thrombomodulin and alpha adducin may be contributors to risk of spontaneous preterm birth.

Level of evidence: II.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Cerebral Palsy / ethnology
  • Cerebral Palsy / genetics*
  • European Continental Ancestry Group / genetics*
  • Female
  • Gestational Age
  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Infant, Premature, Diseases / ethnology
  • Infant, Premature, Diseases / genetics*
  • Male
  • Polymorphism, Single Nucleotide / genetics*
  • Pregnancy
  • Premature Birth / genetics*
  • South Australia / epidemiology