Review and Theme Article
Risk and Protective Factors for Childhood Asthma: What Is the Evidence?

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To summarize the principal findings on risk and protective factors for childhood asthma, we retrieved systematic reviews on these topics in children (aged 1 to 18 years), up to January 2016, through MEDLINE, EMBASE, CINAHL, SCOPUS, and CDSR. A total of 227 studies were searched from databases. Among those, 41 systematic reviews (SRs) were included: 9 focused on prenatal factors, 5 on perinatal factors, and 27 on postnatal factors. Of these 41 SRs, 83% had good methodological quality, as determined by the Assess Systematic Reviews tool. After reviewing all evidence, parental asthma, prenatal environmental tobacco smoke, and prematurity (particularly very preterm birth) are well-established risk factors for childhood asthma. Current findings do suggest mild-to-moderate causal effects of certain modifiable behaviors or exposures during pregnancy (maternal weight gain or obesity, maternal use of antibiotics or paracetamol, and maternal stress), the perinatal period (birth by Caesarean delivery), or postnatal life (severe respiratory syncytial virus infection, overweight or obesity, indoor exposure to mold or fungi, and outdoor air pollution) on childhood asthma, but this suggestive evidence must be confirmed in interventional studies or (if interventions are not feasible) well-designed prospective studies.

Section snippets

Data extraction and assessment of risk of bias

Titles, abstracts, and citations for studies meeting the inclusion criteria outlined above were independently analyzed by 3 authors (J.A.C-R, C.E.R-M, and E.F.). Full texts of all studies were then evaluated for eligibility, and the methodological quality of the eligible systematic reviews was assessed using the AMSTAR (Assess Systematic Reviews) tool.3 The AMSTAR tool has a maximum of 11 points; a systematic review assigned 8 or more points is deemed of good quality. Disagreements between the

Parental asthma

A meta-analysis of 33 studies showed that children with maternal asthma (defined as self-reported physician-diagnosed asthma or as self-reported ever asthma) had approximately 3-fold greater odds of asthma than those without maternal asthma, with no significant heterogeneity.4 Moreover, children with paternal asthma had 2.4 times higher odds of asthma than those without paternal asthma, with no significant heterogeneity. Compared with paternal asthma, maternal asthma was associated with

Birth by Caesarean section

In a meta-analysis of 23 studies,14 birth by Caesarean section was significantly associated with 22% excess odds of asthma (aged 1 to 28 years), with moderate heterogeneity across studies. Restricting the analysis to childhood asthma (ascertained before age 18 years) yielded similar results (OR = 1.20), with reduced heterogeneity across studies.

Preterm delivery

In a meta-analysis of 19 studies including predominantly children, Jaakkola et al15 reported that prematurity (a gestational age < 37 weeks) was

Bacillus Calmette-Guérin (BCG) vaccination

El-Zein et al19 performed a meta-analysis of 16 studies of BCG vaccination and asthma with a total of 67,179 participants. In this analysis, BCG vaccination was significantly associated with a 14% reduction in the odds of asthma, with no heterogeneity across studies. However, only 1 prospective study was included in this meta-analysis.

Breastfeeding

In a meta-analysis of 12 studies including 8183 subjects,20 exclusive breastfeeding during the first 3 months of life was associated with 30% reduced odds of

Discussion

A systematic review or meta-analysis is ultimately dependent on the underlying quality of the primary studies included in the analysis. Limitations include the design of the original studies (eg, observational or cross-sectional), the covariates included in the original analyses (eg, different studies may have adjusted for different confounders), and unknown sources of bias that may have been inadvertently included in the primary studies. The degree of heterogeneity between studies is also

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    This work was supported by grant #1141195 from Fondecyt-Chile, to J. A. Castro-Rodriguez. J. C. Celedón contribution was supported by grants HL079966 and HL117191 from the US National Institutes of Health (NIH), and by The Heinz Endowments. E. Forno contribution was supported by grant HL125666 from the US NIH.

    Conflicts of interest: J. A. Castro-Rodriguez has received research support from Fondo Nacional de Desarrollo Científico y Tecnológico, Chile (No. 1141195). E. Forno has received research support from National Heart, Lung, and Blood Institute (Grant HL125666). C. E. Rodriguez-Martinez has received travel support from Pfizer and AstraZeneca. J. C. Celedón declares no relevant conflicts of interest.

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