Preeclampsia/eclampsia may increase risk of myelodysplastic and myeloproliferative diseases

A retrospective cohort study from French researchers suggests that preeclampsia or eclampsia, which may develop in as many as 5% of pregnancies, may increase a woman’s risk of developing certain cancers, while possibly reducing the risk for developing breast cancer.

The researchers, led by Chris Serrand, MD, of the Department of Biostatistics, Clinical Epidemiology, Public Health, and Innovation in Methodology, Centre Hospitalier Universitaire de Nîmes, Groupe Hospitalo–Universitaire Caremeau in Nîmes, France, looked at the experience of first pregnancy in a cohort of 4,322,970 women. They included women with and without preeclampsia/eclampsia in first pregnancy.

Just 1.1% (n=45,523) of the women developed the complication during first pregnancy, and after a maximum of 8 years follow-up, there was no significant difference in their overall incidence of cancer compared to women who were preeclampsia/eclampsia-free in first pregnancy.

But when they looked at adjusted hazard ratios (AHR) for individual types of cancer, they found “[P]reeclampsia/eclampsia was associated with an increase in the risk of myelodysplastic syndromes or myeloproliferative diseases (AHR, 2.43; 95% CI, 1.46-4.06) and kidney cancer (AHR, 2.19; 95% CI, 1.09-4.42) and a decrease in the risk of breast cancer (AHR, 0.79; 95% CI, 0.62-0.99) and cervical cancer (AHR, 0.75; 95% CI, 0.58-0.96).”

The results were published June 23, 2021, in JAMA Network Open.

This study by Serrand et al is not the first to suggest long-term health risks associated with preeclampsia/eclampsia. For example, premature mortality for women who develop hypertension (a hallmark symptom of preeclampsia) during pregnancy and vascular disease have been reported. Less clear, however, is the possibility of a link with cancer.

But Serrand and colleagues hypothesized that a number of factors “…suggest that there may be a change in the risk of some types of cancer after preeclampsia/eclampsia. First, preeclampsia/eclampsia induces hormonal surges and disorders that alter hormonal levels during pregnancy, which might be associated with the subsequent risk of hormone-dependent cancers. Second, a prevailing feature of preeclampsia/eclampsia is antiangiogenesis, which is essential to restricting tumor growth; thus, preeclampsia/eclampsia may be associated with a reduction in the risk of solid tumors in later life. Consistent with this hypothesis, a reduced risk of breast cancer among female individuals with a history of preeclampsia/eclampsia has been described, particularly among those who are premenopausal and those who have breast cancer associated with the ERB-B2 receptor tyrosine kinase 2 (ERBB2; formerly human epidermal growth factor receptor 2 [HER2]) gene. Another study reported an increased risk of endometrial cancer. The conclusions concerning the existence and direction of a possible association between preeclampsia/eclampsia and cancer are therefore heterogeneous, and cancer risk after preeclampsia/eclampsia could be different depending on the organ.”

The cohort studied were women ages 12 to 55 who had a first pregnancy during the period from Jan. 1, 2012 to Dec. 31, 2019. They used ICD-10 codes to identify preeclampsia/eclampsia diagnosis, as well as abruptio placenta, fetal growth restriction, and intrauterine fetal death.

Compared with women who didn’t develop preeclampsia, the women with preeclampsia/eclampsia during a first pregnancy had slightly higher rates of obesity, diabetes, hypertension, dyslipidemia, kidney failure, liver failure, respiratory disorders, stroke, myocardial infarction, and venous thromboembolism. Thus, taken as a whole, they were less healthy.

The cancer findings (all per 1,000 person years):

  • Overall incidence of cancer was 1.51 in the preeclampsia/eclampsia group versus 1.52 in controls.
  • Myelodysplastic or myeloproliferative disease, 0.08 versus 0.03, respectively.

Kidney cancer was rare but was “overrepresented in participants who had preeclampsia/eclampsia (AHR, 2.19; 95% CI, 1.09-4.42), and a decrease in breast cancer and cervical cancer after preeclampsia/eclampsia was observed, with AHRs of 0.79 (95% CI, 0.62-0.99) and 0.75 (95% CI, 0.58-0.96), respectively.”

The authors noted that the registry of pregnancies and cancers they used for the study was “almost exhaustive”, but the study was nonetheless limited by its retrospective cohort design and because it did not include information that could have contributed to cancer risk, such as genetic profiles, lifestyle habits, hormone treatments, and exposure to environmental carcinogens. Also, although cancer risk may be associated with the severity of placental disease, data on placental disease subtypes and severity was not available.

The authors concluded that the results reported “persisted when the spectrum of placental diseases was analyzed and suggest the presence of shared pathophysiological factors to be explored in the future.”

  1. French researchers who conducted a retrospective cohort study of more than 4 million women found that those who developed preeclampsia or eclampsia during their first pregnancy may have an increased risk for myelodysplastic syndromes as well as myeloproliferative diseases and kidney cancer, but a decreased risk of breast cancer.

  2. The findings suggest the presence of shared pathophysiological factors, which require further study.

Peggy Peck, Editor-in-Chief, BreakingMED™

This research was supported by internal funding from Nimes University Hospital.

Serrand had no disclosures.

Cat ID: 41

Topic ID: 83,41,730,6,111,22,468,835,935,127,410,41,192,925