The association of pregnancy complications/risk factors with the development of cancer in women: an umbrella review

BACKGROUND: Among women in the UK, over 186,000 new cancer diagnoses and around 78,000 cancer deaths occurred annually from 2017 to 2019. Evidence suggests that pregnancy complications are linked to mortality and morbidity risks in later life. This umbrella review aims to assess the association between pregnancy complications and cancer risk. It forms part of a series of studies exploring associations between pregnancy complications and long-term health conditions.

METHODS: MEDLINE, Embase, and Cochrane databases were searched from inception to April 2024. Key search terms encompassed 'cancer' and 'pregnancy complications' or 'pregnancy risk factors'. Screening data extraction and quality appraisal (AMSTAR 2) were completed by two independent reviewers. Data were synthesised narratively and quantitatively. Relative risks (RR)/odds ratio (OR)/hazard ratios (HR) with 95% confidence intervals were reported.

RESULTS: Of the 25 reviews assessed for methodological quality, 2 were rated high, 12 moderate, 9 low, and 2 critically low. After excluding 10 overlapping reviews and 2 critically low reviews, 13 reviews included reviews consisted of 170 primary studies. Associations between 7 pregnancy complications and 17 cancers are reported. Women with molar pregnancy had four-fold higher risk of developing gestational trophoblastic neoplasia [OR 4.72 (1.81-12.32)]. Miscarriage was associated with thyroid cancer [OR 1.29 (95% CI 1.15-1.44)], but not with breast or ovarian cancer. Pre-eclampsia was associated with a reduced risk of breast cancer [RR 0.89 (0.83-0.95)] and an almost twofold higher risk of ovarian cancer [RR 1.82 (1.16-2.85)]. Gestational diabetes mellitus was associated with a higher risk of thyroid cancer [RR 1.28 (1.16-1.42)], stomach cancer [RR 1.43 (1.02-2.00)], liver cancer [RR 1.27 (1.03-1.55)], and blood cancer [RR 1.48 (1.04-2.09)] but was not associated with other cancers studied. Preterm birth showed a very small association with breast cancer risk (OR 1.03, 95% CI 1.00-1.07). There was no significant association between caesarean section and cervical cancer or multiple births and breast cancer.

CONCLUSIONS: Some pregnancy complications were associated with selected cancer outcomes, although the evidence was heterogeneous and limited by potential bias, confounding, and inconsistent review quality.