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Meta-Analysis
. 2020 Jan;42(1):32-40.
doi: 10.1097/MPH.0000000000001657.

Paternal Smoking Before Conception and During Pregnancy Is Associated With an Increased Risk of Childhood Acute Lymphoblastic Leukemia: A Systematic Review and Meta-Analysis of 17 Case-Control Studies

Yue Cao  1 , Jing Lu  2 , Jing Lu  3
Affiliations
Meta-Analysis

Paternal Smoking Before Conception and During Pregnancy Is Associated With an Increased Risk of Childhood Acute Lymphoblastic Leukemia: A Systematic Review and Meta-Analysis of 17 Case-Control Studies

Yue Cao et al. J Pediatr Hematol Oncol. 2020 Jan.

Abstract

Objective: Current evidence regarding the association between paternal smoking before conception or during pregnancy and the risk of childhood acute lymphoblastic leukemia (ALL) are inconsistent. We aimed to systematically summarize the current evidence regarding this potential association.

Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Meta-analysis of Observational Studies in Epidemiology (MOOSE), we systematically retrieved PubMed, Embase, Web of Science, and Scopus, screened relevant literature, and assessed the methodologic quality of the included studies. We calculated the pooled estimates using random-effects models. We assessed statistical heterogeneity by I values and χ tests for the Cochrane Q statistic. We further investigate the dose-response relation using 2-stage nonlinear models.

Results: A total of 17 case-control studies were identified, and the synthesized risk ratios (RRs) for smoking before conception (RR=1.15, 95% confidence interval: 1.04-1.27) and during pregnancy (RR=1.20, 95% confidence interval: 1.12-1.28) were both statistically significant. Moreover, the dose-response analysis showed a positive association as well.

Conclusion: Current evidence from observational studies suggests the association between paternal smoking before conception or during pregnancy and the increased risk of childhood ALL, which needs to be confirmed in prospective studies.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Flow chart for study identification and selection.
FIGURE 2
FIGURE 2
Overall meta-analysis stratified by the exposure time window. CI indicates confidence interval; RR, risk ratio.
FIGURE 3
FIGURE 3
Meta-analysis by synthesizing RRs of the highest smoking consumption. CI indicates confidence interval; cig/d, cigarette per day; PY, pack-year; RR, risk ratio.
FIGURE 4
FIGURE 4
A, Dose-response curve by restricted cubic spline model (smoking before conception). The solid line is the fitted line, dash lines are the lines for 95% confidence interval, and dot line is the reference line. B, Dose-response curve by restricted cubic spline model (smoking during pregnancy). The solid line is the fitted line, dash lines are the lines for 95% confidence interval, and dot line is the reference line. cig/d indicates cigarette per day; RR, risk ratio.
FIGURE 5
FIGURE 5
Funnel plots, Egger tests, and trim/fill adjusted effect measures stratified by time windows. CI indicates confidence interval; RR, risk ratio.
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