title: Maternal smoking during pregnancy and risk for childhood leukemia: a nationwide case-control study in Greece and meta-analysis.
abstract: BACKGROUND
  Maternal smoking during pregnancy has been often implicated in the development of childhood leukemia with ambiguous results. Hence, we conducted a meta-analysis aiming to summarize current evidence and quantify any tentative impact.
  
  
  METHODS
  We retrieved one cohort (553 leukemias compared to 1,440,542 children), 20 case-control studies and also analyzed the updated Greek case-control dataset with unpublished data, yielding in total 11,092 cases and 25,221 controls.
  
  
  RESULTS
  Odds ratios reported in the studies included ranged from 0.70 to 2.20 for acute lymphocytic (ALL) and from 0.60 to 2.17 for acute myelocytic leukemia (AML). The combined effect regarding the association of maternal smoking (any vs. no) and leukemia risk was 1.03 for ALL (95% CI = 0.95-1.12, random effects model) and 0.99 for AML (95% CI = 0.90-1.09, fixed effects model). The results remained unchanged when sensitivity analyses were undertaken of studies reporting same maternal smoking periods, those focusing only on childhood leukemia deaths or investigations which did not clearly define AML subtype.
  
  
  CONCLUSIONS
  The findings of the meta-analysis challenge the limits of traditional epidemiology to provide sound inferences when point estimates of constituent studies range around the null. In particular, this study provides no support to a hypothesis linking maternal smoking during pregnancy with subsequent development of main childhood leukemia subtypes. Further investigations employing molecular and genetic epidemiology, however, might be needed in the hope to reveal even minimal risks pertaining individuals with specific susceptibility to tobacco compounds who sustain high environmental exposures prenatally or postnatally.
authors: Department of Hygiene, Epidemiology and Medical Statistics, National and Kapodistrian University of Athens, Medical School, 75 M. Asias Str., Goudi, Athens, Greece.
authors: Alexandra
authors: A
authors: Klimentopoulou
authors: Constantine N
authors: CN
authors: Antonopoulos
authors: Charalampia
authors: C
authors: Papadopoulou
authors: Prodromos
authors: P
authors: Kanavidis
authors: Aristomenis-Dimitrios
authors: AD
authors: Tourvas
authors: Sofia
authors: S
authors: Polychronopoulou
authors: Margarita
authors: M
authors: Baka
authors: Fani
authors: F
authors: Athanasiadou-Piperopoulou
authors: Maria
authors: M
authors: Kalmanti
authors: Vassiliki
authors: V
authors: Sidi
authors: Maria
authors: M
authors: Moschovi
authors: Eleni Th
authors: ET
authors: Petridou
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D006115:Greece / Q000453:epidemiology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015470:Leukemia, Myeloid, Acute / Q000453:epidemiology / Q000209:etiology*; D008297:Male; D016555:Matched-Pair Analysis; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology / Q000209:etiology*; D012306:Risk; D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology