Format

Send to

Choose Destination
Cancer Causes Control. 2017 Jun;28(6):599-624. doi: 10.1007/s10552-017-0890-2. Epub 2017 Apr 11.

Maternal fetal loss history and increased acute leukemia subtype risk in subsequent offspring: a systematic review and meta-analysis.

Author information

1
Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, University of Athens, 75 Mikras Asias Str, 11527, Athens, Greece.
2
Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
3
Department of Women's and Children׳s Health, Karolinska Institutet and Karolinska University Hospital, 17176, Stockholm, Sweden.
4
Division of Pediatric Epidemiology and Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
5
First Department of Obstetrics and Gynecology of the University of Athens, Alexandra Hospital, Athens, Greece.
6
First Department of Pediatrics, University of Athens, Medical School, Aghia Sophia Children's Hospital, Athens, Greece.
7
Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, University of Athens, 75 Mikras Asias Str, 11527, Athens, Greece. epetrid@med.uoa.gr.

Abstract

PURPOSE:

History of fetal loss including miscarriage and stillbirth has been inconsistently associated with childhood (0-14 years) leukemia in subsequent offspring. A quantitative synthesis of the inconclusive literature by leukemia subtype was therefore conducted.

METHODS:

Eligible studies (N = 32) were identified through the screening of over 3500 publications. Random-effects meta-analyses were conducted on the association of miscarriage/stillbirth history with overall (AL; 18,868 cases/35,685 controls), acute lymphoblastic (ALL; 16,150 cases/38,655 controls), and myeloid (AML; 3042 cases/32,997 controls) leukemia. Sensitivity and subgroup analyses by age and ALL subtype, as well as meta-regression were undertaken.

RESULTS:

Fetal loss history was associated with increased AL risk [Odds Ratio (OR) 1.10, 95% Confidence Intervals (CI) 1.04-1.18]. The positive association was seen for ALL (OR 1.12, 95%CI 1.05-1.19) and for AML (OR 1.13, 95%CI 0.91-1.41); for the latter the OR increased in sensitivity analyses. Notably, stillbirth history was significantly linked to ALL risk (OR 1.33, 95%CI 1.02-1.74), but not AML. By contrast, the association of ALL and AML with previous miscarriage reached marginal significance. The association of miscarriage history was strongest in infant ALL (OR 2.34, 95%CI 1.19-4.60).

CONCLUSIONS:

In this meta-analysis involving >50,000 children, we found noteworthy associations by indices of fetal loss, age at diagnosis, and leukemia type; namely, of stillbirth with ALL and miscarriage history with infant ALL. Elucidation of plausible underlying mechanisms may provide insight into leukemia pathogenesis and indicate monitoring interventions prior to and during pregnancy.

KEYWORDS:

Childhood acute lymphoblastic leukemia; Childhood acute myeloid leukemia; Meta-analysis; Meta-regression; Miscarriage; Stillbirth

PMID:
28401353
DOI:
10.1007/s10552-017-0890-2
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center