title: Smoking in preeclamptic women is associated with higher birthweight for gestational age and lower soluble fms-like tyrosine kinase-1 levels: a nested case control study.
abstract: BACKGROUND
  Smoking paradoxically increases the risk of small-for-gestational-age (SGA) birth but protects against preeclampsia. Some studies have reported a "U-shaped" distribution of fetal growth in preeclamptic pregnancies, but reasons for this are unknown. We investigated whether cigarette smoking interacts with preeclampsia to affect fetal growth, and compared levels of soluble fms-like tyrosine kinase-1 (sFlt-1), a circulating anti-angiogenic protein, in preeclamptic smokers and non-smokers.
  
  
  METHODS
  From a multicenter cohort of 5337 pregnant women, we prospectively identified 113 women who developed preeclampsia (cases) and 443 controls. Smoking exposure was assessed by self-report and maternal hair nicotine levels. Fetal growth was assessed as z-score of birthweight for gestational age (BWGA). sFlt-1 was measured in plasma samples collected at the 24-26-week visit.
  
  
  RESULTS
  In linear regression, smoking and preeclampsia were each associated with lower BWGA z-scores (β = -0.29; p = 0.008, and β = -0.67; p < 0.0001), but positive interaction was observed between smoking and preeclampsia (β = +0.86; p = 0.0008) such that smoking decreased z-score by -0.29 in controls but increased it by +0.57 in preeclampsia cases. Results were robust to substituting log hair nicotine for self-reported smoking and after adjustment for confounding variables. Mean sFlt-1 levels were lower in cases with hair nicotine levels above vs. below the median (660.4 pg/ml vs. 903.5 pg/ml; p = 0.0054).
  
  
  CONCLUSIONS
  Maternal smoking seems to protect against preeclampsia-associated fetal growth restriction and may account, at least partly, for the U-shaped pattern of fetal growth described in preeclamptic pregnancies. Smoking may exert this effect by reducing levels of the anti-angiogenic protein sFlt-1.
authors.affiliation: Department of Medicine, McGill University, Montreal, Quebec, Canada. susan.kahn@mcgill.ca
authors.forename: Susan R
authors.initials: SR
authors.lastname: Kahn
authors.forename: Nisha D
authors.initials: ND
authors.lastname: Almeida
authors.forename: Helen
authors.initials: H
authors.lastname: McNamara
authors.forename: Gideon
authors.initials: G
authors.lastname: Koren
authors.forename: Jacques
authors.initials: J
authors.lastname: Genest
authors.forename: Mourad
authors.initials: M
authors.lastname: Dahhou
authors.forename: Robert W
authors.initials: RW
authors.lastname: Platt
authors.forename: Michael S
authors.initials: MS
authors.lastname: Kramer
mesh_terms: D000293:Adolescent; D000328:Adult; D001724:Birth Weight; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005317:Fetal Growth Retardation / Q000097:blood / Q000453:epidemiology* / Q000209:etiology; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D011225:Pre-Eclampsia / Q000097:blood / Q000453:epidemiology* / Q000209:etiology; D011247:Pregnancy; D011505:Protein-Tyrosine Kinases / Q000097:blood*; D011792:Quebec / Q000453:epidemiology; D012044:Regression Analysis; D012907:Smoking; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D011505:Protein-Tyrosine Kinases
references.citation: Am J Obstet Gynecol. 2000 Jul;183(1):148-55
references.pmid: 10920323
references.citation: Pharmacology. 1999 Feb;58(2):70-86
references.pmid: 9873232
references.citation: Pediatrics. 2001 Aug;108(2):E35
references.pmid: 11483845
references.citation: Paediatr Perinat Epidemiol. 2005 Jan;19(1):12-8
references.pmid: 15670103
references.citation: Br J Biomed Sci. 2000;57(3):207-13
references.pmid: 11050771
references.citation: Nicotine Tob Res. 2007 Oct;9(10):1005-13
references.pmid: 17852766
references.citation: Am J Hypertens. 2008 Aug;21(8):943-7
references.pmid: 18566591
references.citation: Am J Epidemiol. 2009 Jan 1;169(1):33-40
references.pmid: 19001134
references.citation: Lancet. 2005 Feb 26-Mar 4;365(9461):785-99
references.pmid: 15733721
references.citation: Am J Pathol. 2002 Apr;160(4):1405-23
references.pmid: 11943725
references.citation: JAMA. 1994 Feb 23;271(8):621-3
references.pmid: 8301796
references.citation: CMAJ. 1997 Sep 15;157(6):715-25
references.pmid: 9307560
references.citation: Am J Obstet Gynecol. 1995 Oct;173(4):1042-8
references.pmid: 7485291
references.citation: N Engl J Med. 2004 Feb 12;350(7):672-83
references.pmid: 14764923
references.citation: Med Hypotheses. 2005;64(1):17-27
references.pmid: 15533604
references.citation: Am J Obstet Gynecol. 2009 Feb;200(2):151.e1-9; discussion e1-5
references.pmid: 19070828
references.citation: Circulation. 2007 Apr 3;115(13):1789-97
references.pmid: 17389265
references.citation: Front Biosci. 2007 Jan 01;12:2471-83
references.pmid: 17127256
references.citation: Lancet. 2001 Jan 6;357(9249):53-6
references.pmid: 11197372
references.citation: Am J Epidemiol. 2008 Aug 15;168(4):427-33
references.pmid: 18558661
references.citation: Nicotine Tob Res. 2011 May;13(5):328-35
references.pmid: 21330286
references.citation: Hypertension. 2010 May;55(5):1254-9
references.pmid: 20231527
references.citation: Mol Med. 2007 Nov-Dec;13(11-12):576-83
references.pmid: 17878927
references.citation: BMJ. 2007 Nov 10;335(7627):978
references.pmid: 17975256
references.citation: Paediatr Perinat Epidemiol. 2004 May;18(3):186-91
references.pmid: 15130157
references.citation: Thorax. 2004 Aug;59(8):713-21
references.pmid: 15282395
references.citation: Am J Obstet Gynecol. 1999 Oct;181(4):1026-35
references.pmid: 10521771
references.citation: Obstet Gynecol. 1985 Jul;66(1):102-5
references.pmid: 3839296
references.citation: Paediatr Perinat Epidemiol. 2001 Jul;15 Suppl 2:104-23
references.pmid: 11520404