title: Can drug effects explain the recent temporal increase in atonic postpartum haemorrhage?
abstract: BACKGROUND
  Rates of postpartum haemorrhage and atonic postpartum haemorrhage have increased in several high-income countries. We carried out a study to examine if drug use in pregnancy, or drug and other interactions, explained this increase in postpartum haemorrhage.
  
  
  METHODS
  The linked administrative and hospital databases of the Québec Pregnancy Cohort were used to define a cohort of pregnant women in Québec, Canada, from 1998 to 2009 (n = 138,704). Case-control studies on any postpartum haemorrhage and atonic postpartum haemorrhage were carried out within this population, with up to five controls randomly selected for each case after matching on index date and hospital of delivery (incidence density sampling). Conditional logistic regression was used to estimate the effects of drug use on postpartum haemorrhage and atonic postpartum haemorrhage.
  
  
  RESULTS
  There was an unexpected non-linear, declining temporal pattern in postpartum haemorrhage and atonic postpartum haemorrhage between 1998 and 2009. Use of antidepressants (mainly selective serotonin reuptake inhibitors) was associated with higher rates of postpartum haemorrhage [adjusted rate ratio (aRR) 1.48, 95% confidence interval (CI) 1.23, 1.77] and atonic postpartum haemorrhage [aRR 1.40, 95% CI 1.13, 1.74]. Thrombocytopenia was also associated with higher rates of postpartum haemorrhage [aRR 1.52, 95% CI 1.16, 2.00]. There were no statistically significant drug interactions. Adjustment for maternal factors and drug use had little effect on temporal trends in postpartum haemorrhage and atonic postpartum haemorrhage.
  
  
  CONCLUSIONS
  Although antidepressant use and thrombocytopenia were associated with higher rates of atonic postpartum haemorrhage, antidepressant and other drug use did not explain temporal trends in postpartum haemorrhage.
authors.affiliation: Department of Obstetrics and Gynaecology, School of Population and Public Health, Children's and Women's Hospital and Health Centre of British Columbia, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: K S
authors.initials: KS
authors.lastname: Joseph
authors.forename: Odile
authors.initials: O
authors.lastname: Sheehy
authors.forename: Azar
authors.initials: A
authors.lastname: Mehrabadi
authors.forename: Marcelo L
authors.initials: ML
authors.lastname: Urquia
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Hutcheon
authors.forename: Michael
authors.initials: M
authors.lastname: Kramer
authors.forename: Anick
authors.initials: A
authors.lastname: Bérard
mesh_terms: D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D000928:Antidepressive Agents / Q000009:adverse effects*; D001008:Anxiety Disorders / Q000188:drug therapy*; D016022:Case-Control Studies; D015897:Comorbidity; D005260:Female; D006633:Histamine Antagonists / Q000009:adverse effects*; D006801:Humans; D007231:Infant, Newborn; D016015:Logistic Models; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects*; D006473:Postpartum Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology* / Q000503:physiopathology; D011247:Pregnancy; D011792:Quebec / Q000453:epidemiology; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects*; D014593:Uterine Inertia
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000928:Antidepressive Agents; D006633:Histamine Antagonists; D010975:Platelet Aggregation Inhibitors; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Atonic postpartum hemorrhage; etiology; selective serotonin reuptake inhibitors; temporal trends; thrombocytopenia
references.citation: BJOG. 2013 Jun;120(7):853-62
references.pmid: 23464351
references.citation: Am J Med. 2000 Dec 15;109(9):727-33
references.pmid: 11137489
references.citation: BJOG. 2007 Jun;114(6):751-9
references.pmid: 17516968
references.citation: Obstet Gynecol. 2011 Sep;118(3):561-8
references.pmid: 21860284
references.citation: CNS Drugs. 2009;23(6):493-509
references.pmid: 19480468
references.citation: J Obstet Gynaecol Can. 2014 Jan;36(1):21-33
references.pmid: 24444284
references.citation: BMC Pregnancy Childbirth. 2009 Nov 27;9:55
references.pmid: 19943928
references.citation: Am J Obstet Gynecol. 1995 May;172(5):1553-7
references.pmid: 7755070
references.citation: Am J Epidemiol. 1976 Feb;103(2):226-35
references.pmid: 1251836
references.citation: Br J Obstet Gynaecol. 1998 Mar;105(3):293-9
references.pmid: 9532989
references.citation: Int J Gynaecol Obstet. 2007 Sep;98(3):237-43
references.pmid: 17482190
references.citation: Am J Obstet Gynecol. 2007 Jun;196(6):544.e1-5
references.pmid: 17547888
references.citation: BJOG. 2012 Feb;119(3):306-14
references.pmid: 22168794
references.citation: Am J Respir Crit Care Med. 2007 May 15;175(10):991-7
references.pmid: 17272783
references.citation: Am J Public Health. 1998 Jan;88(1):15-9
references.pmid: 9584027
references.citation: J Clin Epidemiol. 1989;42(6):491-6; discussion 497-8
references.pmid: 2661728
references.citation: J Obstet Gynaecol Can. 2011 Aug;33(8):810-9
references.pmid: 21846436
references.citation: Anesth Analg. 2010 May 1;110(5):1368-73
references.pmid: 20237047
references.citation: BMJ. 2013 Aug 21;347:f4877
references.pmid: 23965506
references.citation: Acta Obstet Gynecol Scand. 2010 Oct;89(10):1248-55
references.pmid: 20809871
references.citation: J Chronic Dis. 1985;38(7):543-48
references.pmid: 4008595
references.citation: Am J Obstet Gynecol. 2010 Apr;202(4):353.e1-6
references.pmid: 20350642
references.citation: Can J Clin Pharmacol. 2009 Summer;16(2):e360-9
references.pmid: 19553702
references.citation: J Neurosurg. 2014 Jun;120(6):1358-63
references.pmid: 24506245
references.citation: IARC Sci Publ. 1980;(32):5-338
references.pmid: 7216345
references.citation: J Clin Psychopharmacol. 2008 Dec;28(6):714-6
references.pmid: 19011450
references.citation: Drugs Aging. 2011 May 1;28(5):345-67
references.pmid: 21542658
references.citation: Obstet Gynecol. 1998 Sep;92(3):435-40
references.pmid: 9721785
references.citation: Ann Epidemiol. 2001 Jan;11(1):7-12
references.pmid: 11164114
references.citation: CMAJ. 2011 Nov 8;183(16):1835-43
references.pmid: 21948719
references.citation: Cochrane Database Syst Rev. 2007 Apr 18;(2):CD004659
references.pmid: 17443552
references.citation: J Clin Psychopharmacol. 2008 Apr;28(2):230-4
references.pmid: 18344737
references.citation: Am J Obstet Gynecol. 2011 Jan;204(1):56.e1-6
references.pmid: 21047614
references.citation: Pharmacoepidemiol Drug Saf. 2008 Apr;17(4):345-53
references.pmid: 18271060
references.citation: PLoS One. 2014 Apr 04;9(4):e93870
references.pmid: 24705674
references.citation: J Clin Psychiatry. 2010 Dec;71(12):1565-75
references.pmid: 21190637
references.citation: Pharmacoepidemiol Drug Saf. 2013 Sep;22(9):1013-8
references.pmid: 23893932
references.citation: Am J Obstet Gynecol. 2013 Nov;209(5):449.e1-7
references.pmid: 23871950