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The association between birth order and childhood brain tumors

a systematic review and meta-analysis

Nguyen, Mai V.a,,*; Tran, Mo T.a,,*; Tran, Chi TDua; Tran, Quang H.a; Tuonga, Thuy TVa; Phung, Lam N.a; Vu, Huyen X.a; Le, Linh C.b; Boffetta, Paoloc,,†; Luu, Hung N.d,,e,,f,,†

European Journal of Cancer Prevention: November 2019 - Volume 28 - Issue 6 - p 551–561
doi: 10.1097/CEJ.0000000000000490
Research Papers: Pediatric Cancer

The incidence of childhood brain tumors (CBT) has increased worldwide, likely resulting from the improvements of early diagnostics. We conducted a systematic review and meta-analysis to clarify the association between birth order and CBT. We followed established guidelines to systematically search Ovid Medline, PubMed, and the Cochrane Library for English language studies, published before March 2018. Quality assessment was performed using the Newcastle–Ottawa Scale. Meta-analysis provided pooled risk estimates and their 95% confidence intervals (CIs) for birth order and CBT. We identified 16 case–control studies with a total sample of 32 439 cases and 166 144 controls and three prospective cohort studies (i.e. 4515 incident cases of CBTs among 5 281 558 participants). Compared with first birth order, the meta-odds ratio for second birth order in case–control studies was 1.04 (95% CI: 1.01–1.07), that for third birth order was 0.98 (95% CI: 0.90–1.06), and that for fourth order was 0.85 (95% CI: 0.78–0.92). The meta-hazard ratio for second or higher birth order compared with first birth order in cohort studies was 1.00 (95% CI: 0.96–1.05). We found no association between birth order and CBT in both case–control and cohort study designs; the small association observed for fourth birth order deserves further consideration.

aVietnam Colorectal Cancer and Research Program

bVinUniversity Project, Health Sciences, Vinmec Healthcare System, Hanoi, Vietnam

cTisch Cancer Institute, Icahn School of Medicine, Mount Sinai School of Medicine, New York, New York

dDepartment of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Comprehensive Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee

eDepartment of Epidemiology, University of Pittsburgh Graduate School of Public Health

fCurrently at the Division of Cancer Control and Population Sciences, University of Pittsburgh Hillman Cancer Center, Pittsburgh, Pennsylvania, USA

* Mai V. Nguyen and Mo T. Tran contributed equally to the writing of this article.

† Paolo Boffetta and Hung N. Luu contributed equally to this work as senior authors.

Received 16 May 2018 Accepted 6 July 2018

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Correspondence to Hung N. Luu, MD, PhD, Division of Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute-UPCI, UPMC Cancer Pavilion, 5150 Centre Avenue, Suite 4C, Room 466 Pittsburgh, PA 15232, USA Tel: + 1 412 623 3386; fax: +1 412 623 3303; e-mail:

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