title: Interaction of maternal smoking and preterm birth on future risk of maternal cardiovascular disease: A population-based record linkage study.
abstract: BACKGROUND
  While associations of smoking and preterm birth (PTB) with maternal cardiovascular disease (CVD) risks have been established, it is unknown whether the coexistence of these two conditions could synergistically increase the risks.
  
  
  METHODS
  We linked birth records of 902,008 mothers with singleton infants during 1994-2011 in New South Wales, Australia to the mothers' subsequent CVD hospitalisation or death. Multiplicative interaction was tested through an interaction term in a multivariate Cox-proportional hazard regression model, while additive interaction was assessed by calculating the synergy index.
  
  
  RESULTS
  Relative to never-smokers with term babies, the CVD risk in ever-smokers with PTBs (hazard ratio (HR) 3.35, 95% confidence interval (CI) 2.96-3.80) was significantly greater than the sum of risks in ever-smokers with term babies (HR 2.10, 95% CI 1.96-2.24) and in never-smokers with PTBs (HR 1.73, 95% CI 1.55-1.93), indicating an additive interaction (synergy index = 1.29, 95% CI 1.05-1.58). In ever-smokers, the association was stronger for extremely PTB (HR 3.83, 95% CI 3.23-4.69) than moderately PTB (HR 3.18, 95% CI 2.76-3.66), and for ≥2 PTB (HR 4.47, 95% CI 3.39-5.88) than one PTB (HR 3.20, 95% CI 2.81-3.64).
  
  
  CONCLUSIONS
  Maternal smoking and PTB interact on the additive scale to synergistically increase maternal CVD risks. The interaction was dose-dependent according to both the severity and number of PTBs.
authors.affiliation: Clinical and Population Perinatal Health Research, University of Sydney at Royal North Shore Hospital, Australia ducanhnguyet@yahoo.com.
authors.forename: Anh D
authors.initials: AD
authors.lastname: Ngo
authors.affiliation: Clinical and Population Perinatal Health Research, University of Sydney at Royal North Shore Hospital, Australia.
authors.forename: Christine L
authors.initials: CL
authors.lastname: Roberts
authors.affiliation: Clinical and Population Perinatal Health Research, University of Sydney at Royal North Shore Hospital, Australia.
authors.forename: Jian S
authors.initials: JS
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Royal North Shore Hospital, Australia.
authors.forename: Gemma
authors.initials: G
authors.lastname: Figtree
mesh_terms: D000328:Adult; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000453:epidemiology* / Q000401:mortality; D015331:Cohort Studies; D005260:Female; D005865:Gestational Age; D015438:Health Behavior; D017052:Hospital Mortality; D006760:Hospitalization; D006801:Humans; D007234:Infant, Premature; D008425:Maternal Behavior; D008498:Medical Record Linkage; D009517:New South Wales / Q000453:epidemiology; D010298:Parity; D011247:Pregnancy; D047928:Premature Birth / Q000175:diagnosis / Q000453:epidemiology*; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology*; D013997:Time Factors; D055815:Young Adult
keywords: Cardiovascular disease; hospitalisation; interaction; international classification of disease; preterm birth; record linkage