title: Combined adverse effects of maternal smoking and high body mass index on heart development in offspring: evidence for interaction?
abstract: OBJECTIVE
  To study the influence of a possible interaction between maternal smoking and high body mass index (BMI) on the occurrence of specific congenital heart anomalies (CHA) in offspring.
  
  
  METHODS
  Case-control study.
  
  
  METHODS
  Data from a population-based birth defects registry in the Netherlands.
  
  
  METHODS
  Cases were 797 children and fetuses born between 1997 and 2008 with isolated non-syndromic CHA. They were classified into five cardiac subgroups: septal defects (n=349), right ventricular outflow tract obstructive anomalies (n=126), left ventricular outflow tract obstructive anomalies (n=139), conotruncal defects (n=115) and other CHA (n=68). Controls were 322 children and fetuses with chromosomal anomalies without cardiac anomalies.
  
  
  METHODS
  Investigation of whether an interaction between maternal smoking and high BMI influences the occurrence of CHA in offspring by calculation of the synergy factors and 95% CIs.
  
  
  RESULTS
  As opposed to smoking or high BMI alone, the risk for CHA in the offspring of women with high BMI (≥25 kg/m(2)) who also smoked was significantly increased. The adjusted OR was 2.65 (95% CI 1.20 to 5.87) for all CHA, 2.60 (95% CI 1.05 to 6.47) for septal defects and 3.58 (95% CI 1.46 to 8.79) for outflow tract anomalies. The interaction between maternal high BMI and smoking contributed significantly to the occurrence of all offspring-CHA combined, and to the occurrence of all cardiac subgroup anomalies except right ventricular outflow tract obstructive anomalies.
  
  
  CONCLUSIONS
  Maternal overweight and smoking may have a synergistic adverse effect on the development of the fetal heart. Overweight women who wish to become pregnant should be strongly encouraged to stop smoking and to lose weight.
authors.affiliation: Eurocat Northern Netherlands, Department of Medical Genetics, University Medical Centre Groningen, PO Box 30001, 9700 RB Groningen, The Netherlands.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Baardman
authors.forename: Wilhelmina S
authors.initials: WS
authors.lastname: Kerstjens-Frederikse
authors.forename: Eva
authors.initials: E
authors.lastname: Corpeleijn
authors.forename: Hermien E K
authors.initials: HE
authors.lastname: de Walle
authors.forename: Robert M W
authors.initials: RM
authors.lastname: Hofstra
authors.forename: Rolf M F
authors.initials: RM
authors.lastname: Berger
authors.forename: Marian K
authors.initials: MK
authors.lastname: Bakker
mesh_terms: D000328:Adult; D015992:Body Mass Index; D016022:Case-Control Studies; D005260:Female; D006321:Heart / Q000196:embryology; D006330:Heart Defects, Congenital / Q000209:etiology*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D011247:Pregnancy; D012189:Retrospective Studies; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*