Maternal cancer and congenital anomalies in children - a Danish nationwide cohort study

PLoS One. 2017 Mar 6;12(3):e0173355. doi: 10.1371/journal.pone.0173355. eCollection 2017.


Several studies on pregnancy-associated cancers have suggested an association with congenital anomalies in offspring. Previous studies have included maternal cancers diagnosed up to 2 years after pregnancy; however, long latency periods of some cancers mean that cancers diagnosed many years postpartum might have been present during pregnancy in a preclinical state. This paper considers the association between maternal cancers diagnosed from 2 years prior to pregnancy until the mother reaches 50 years of age, and congenital anomalies, as diagnosed at birth or within the first year of life. The current population-based study looks at associations of cancers in mothers with congenital anomalies in their children. Children were followed up from birth to diagnosis of a congenital anomaly, death, emigration or end of follow-up (whichever occurred first). A total of 56,016 children (2.6%) were considered exposed to a maternal cancer of any type; and they had a hazard ratio (HR) of 1.04 (95% confidence interval [CI]: 1.00, 1.09) compared with unexposed children. The greatest HR was seen among children whose mothers had been diagnosed with cancers before or during pregnancy (HR: 1.37, 95% CI: 1.07, 1.75). Similar results were seen when paternal cancers were used as a 'negative control'. Statistically significant associations were seen for some specific congenital anomalies of organ systems (congenital anomalies of the musculoskeletal system [HR: 1.13, 95% CI: 1.02, 1.25]) and for some specific types of maternal cancer (leukaemia [HR: 1.31, 95% CI: 1.01, 1.61], The results of the main analyses suggest a small increase in risk of congenital anomalies in offspring of mothers diagnosed with cancer from 2 years before pregnancy, until the mother reaches 50 years of age; with the greatest increase seen for exposure in the pre-pregnancy and pregnancy period. These results may reflect shared causes for some cancers and some congenital anomalies. The similar results seen for paternal cancers indicate that the cause may be genetic or related to the families' social and environmental conditions.

MeSH terms

  • Adult
  • Child
  • Cohort Studies
  • Congenital Abnormalities / epidemiology*
  • Congenital Abnormalities / etiology*
  • Denmark / epidemiology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasms / complications*
  • Pregnancy
  • Pregnancy Complications, Neoplastic*
  • Prenatal Exposure Delayed Effects*
  • Proportional Hazards Models
  • Registries
  • Risk
  • Young Adult

Grant support

The Novo Nordisk Foundation (, 12535), the Nordic Cancer Union (, 2013_129830, 2015_176673), the European Research Council (, ERC-2010-StG-260242-PROGEURO), Danish Council for Independent Research (, DFF-6110-00019), and Karen Elise Jensens Fond (, 2016). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.