Original articleFuture risk of cancer in women who have children with birth defects
Introduction
Cancer is the leading cause of death in women between 40 and 80 years of age [1]; but prevention remains a challenge. Many cancer risk factors appear when women are of reproductive age, with recent data suggesting that pregnancy outcomes such as preterm birth and macrosomia are associated with future cancer [2], [3]. However, risks associated with other reproductive outcomes receive limited attention. The lack of evidence is particularly prominent for birth defects. Birth defects occur in about 4% of newborns [4] and may involve genetic pathways that are similar to those in cancer. Some studies suggest that infants with congenital anomalies are at risk of cancer because of a genetic predisposition [5], [6]. Moreover, birth defects and cancer have common behavioral determinants such as smoking, alcohol, and suboptimal diet [4], [7]. The special care required for infants with birth defects may also impact maternal health and well-being [8], [9].
Whether having an infant with birth defects is linked with the risk of maternal cancer is poorly understood. A recent study of 455,250 women found that having an infant with a major congenital anomaly was associated with a higher risk of maternal death from cancer, compared with no anomaly [10]. However, the study could not assess cancer incidence. Another analysis of 795,607 women found no association overall, but women whose infants had heart or central nervous system defects had higher risks of respiratory and digestive cancers [11]. Many of the associations with specific birth defects disappeared when the study sample was increased to include a broader range of women [11]. A number of other studies provide inconsistent evidence of a link between specific birth defects and different maternal cancers [12], [13], [14], [15]. To clarify this relationship, we assessed whether having an infant with a birth defect was associated with the future risk of maternal cancer in a cohort of 1.2 million parous women.
Section snippets
Data
We used a retrospective cohort design to analyze women who delivered infants in hospitals of Quebec, Canada, between 1989 and 2016. We extracted data on all pregnant women and used encrypted health insurance numbers to follow up the women over time for future cancer hospitalizations. Follow-up extended up to 28 years after delivery and stopped when the woman was hospitalized for cancer, died, or the study ended on March 31, 2017. Data on the women were drawn from discharge abstracts in the
Results
In this study of 1,214,506 women comprising 19,251,851 person-years of follow-up, 117,508 had infants with birth defects and 36,050 developed cancer (Table 1). A total of 2,148,358 infants was born, of whom 5.7% had congenital anomalies. The average length of follow-up was 14.4 years for incident cancers. Cancer incidence was slightly lower for women whose infants had birth defects (1.74 per 1000 person-years) than for women whose infants had no defects (1.89 per 1000 person-years).
Women whose
Discussion
In this cohort of more than 1.2 million parous women, having an infant with birth defects was not associated with the overall risk of maternal cancer. Birth defects appeared to be associated with the future risk of leukemia and placental cancer, but there was no consistent association with other forms of cancer. Heart defects also tended to be more strongly associated with cancer, but again not consistently. Given the large sample size and absence of persistently elevated associations across
Conclusions
We did not find substantial evidence of an association between having an infant with a birth defect and the risk of early cancers in women. The associations we found for leukemia and placental cancer, and for heart defects with various cancers, may reflect type I error. However, we cannot rule out the possibility of an association with cancer much later in life. Mothers of children with birth defects may be reassured that birth defects are not markers of future risk of early-onset cancer in
Acknowledgments
This work was supported by grant PCC-156725 from the Canadian Institutes of Health Research, grant 6D02363004 from the Public Health Agency of Canada, and career award 34695 from the Fonds de recherche du Québec-Santé.
Authors' contribution: All authors have participated in conception and design or analysis and interpretation of the data; drafting the article or revising it critically for important intellectual content; and approval of the final version.
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The authors declare no potential conflicts of interest.