Long term mortality of mothers and fathers after pre-eclampsia: population based cohort study Pre-eclampsia and cardiovascular disease later in life: who is at risk?

Abstract

Objective: To assess whether mothers and fathers have a higher long term risk of death, particularly from cardiovascular disease and cancer, after the mother has had pre-eclampsia. Design: Population based cohort study of registry data. Subjects: Mothers and fathers of all 626 272 births that were the mothers' first deliveries, recorded in the Norwegian medical birth registry from 1967 to 1992. Parents were divided into two cohorts based on whether the mother had pre-eclampsia during the pregnancy. Subjects were also stratified by whether the birth was term or preterm, given that pre-eclampsia might be more severe in preterm pregnancies. Main outcome measures: Total mortality and mortality from cardiovascular causes, cancer, and stroke from 1967 to 1992, from data from the Norwegian registry of causes of death. Results: Women who had pre-eclampsia had a 1.2-fold higher long term risk of death (95% confidence interval 1.02 to 1.37) than women who did not have pre-eclampsia. The risk in women with pre-eclampsia and a preterm delivery was 2.71-fold higher (1.99 to 3.68) than in women who did not have pre-eclampsia and whose pregnancies went to term. In particular, the risk of death from cardiovascular causes among women with pre-eclampsia and a preterm delivery was 8.12-fold higher (4.31 to 15.33). However, these women had a 0.36-fold (not significant) decreased risk of cancer. The long term risk of death was no higher among the fathers of the pre-eclamptic pregnancies than the fathers of pregnancies in which pre-eclampsia did not occur. Conclusions: Genetic factors that increase the risk of cardiovascular disease may also be linked to pre-eclampsia. A possible genetic contribution from fathers to the risk of pre-eclampsia was not reflected in increased risks of death from cardiovascular causes or cancer among fathers. What is already known on this topic Maternal and fetal genes (including those inherited from the father) may contribute to pre-eclampsia, which occurs in 3-5% of pregnancies One set of candidate genes for pre-eclampsia is the maternal genes for thrombophilia, which may increase the mother's risk of death from cardiovascular disease What this study adds Women who have pre-eclampsia during a pregnancy that ends in a preterm delivery have an eightfold higher risk of death from cardiovascular disease compared with women who do not have pre-eclampsia and whose pregnancy goes to term Fathers of pregnancies in which pre-eclampsia occurred have no increased risk of death from cardiovascular disease These results are compatible with maternal genes for thrombophilia having an effect on the risk of pre-eclampsia and of death from cardiovascular disease Objective: To assess whether mothers and fathers have a higher long term risk of death, particularly from cardiovascular disease and cancer, after the mother has had pre-eclampsia. Design: Population based cohort study of registry data. Subjects: Mothers and fathers of all 626 272 births that were the mothers' first deliveries, recorded in the Norwegian medical birth registry from 1967 to 1992. Parents were divided into two cohorts based on whether the mother had pre-eclampsia during the pregnancy. Subjects were also stratified by whether the birth was term or preterm, given that pre-eclampsia might be more severe in preterm pregnancies. Main outcome measures: Total mortality and mortality from cardiovascular causes, cancer, and stroke from 1967 to 1992, from data from the Norwegian registry of causes of death. Results: Women who had pre-eclampsia had a 1.2-fold higher long term risk of death (95% confidence interval 1.02 to 1.37) than women who did not have pre-eclampsia. The risk in women with pre-eclampsia and a preterm delivery was 2.71-fold higher (1.99 to 3.68) than in women who did not have pre-eclampsia and whose pregnancies went to term. In particular, the risk of death from cardiovascular causes among women with pre-eclampsia and a preterm delivery was 8.12-fold higher (4.31 to 15.33). However, these women had a 0.36-fold (not significant) decreased risk of cancer. The long term risk of death was no higher among the fathers of the pre-eclamptic pregnancies than the fathers of pregnancies in which pre-eclampsia did not occur. Conclusions: Genetic factors that increase the risk of cardiovascular disease may also be linked to pre-eclampsia. A possible genetic contribution from fathers to the risk of pre-eclampsia was not reflected in increased risks of death from cardiovascular causes or cancer among fathers. What is already known on this topic Maternal and fetal genes (including those inherited from the father) may contribute to pre-eclampsia, which occurs in 3-5% of pregnancies One set of candidate genes for pre-eclampsia is the maternal genes for thrombophilia, which may increase the mother's risk of death from cardiovascular disease What this study adds Women who have pre-eclampsia during a pregnancy that ends in a preterm delivery have an eightfold higher risk of death from cardiovascular disease compared with women who do not have pre-eclampsia and whose pregnancy goes to term Fathers of pregnancies in which pre-eclampsia occurred have no increased risk of death from cardiovascular disease These results are compatible with maternal genes for thrombophilia having an effect on the risk of pre-eclampsia and of death from cardiovascular disease