BMJ 2001;323:1213-1217 ( 24 November )

Papers

Long term mortality of mothers and fathers after pre-eclampsia: population based cohort study

Henrik U Irgens, medical student,  Lars Reisæter, medical student,  Lorentz M Irgens, professor,  Rolv T Lie, professor. 

Medical Birth Registry of Norway, Locus for Registry Based Epidemiology, Department of Public Health and Primary Health Care, University of Bergen, Haukeland Hospital, N5021 Bergen, Norway

Correspondence to: L M Irgens lorentz.irgens{at}mfr.uib.no

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


© BMJ 2001
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?

Relevant Articles

Prepregnancy cardiovascular risk factors as predictors of pre-eclampsia: population based cohort study
Elisabeth Balstad Magnussen, Lars Johan Vatten, Tom Ivar Lund-Nilsen, Kjell Åsmund Salvesen, George Davey Smith, and Pål Richard Romundstad
BMJ 2007 335: 978. [Abstract] [Full Text] [PDF]

Pre-eclampsia increases long term risk of death from cardiovascular causes
BMJ 2001 323: 0. [Full Text]

This article has been cited by other articles:

  • Sugulle, M., Dechend, R., Herse, F., Weedon-Fekjaer, M. S., Johnsen, G. M., Brosnihan, K. B., Anton, L., Luft, F. C., Wollert, K. C., Kempf, T., Staff, A. C. (2009). Circulating and Placental Growth-Differentiation Factor 15 in Preeclampsia and in Pregnancy Complicated by Diabetes Mellitus. Hypertension 54: 106-112 [Abstract] [Full text]  
  • Wang, A., Rana, S., Karumanchi, S. A. (2009). Preeclampsia: The Role of Angiogenic Factors in Its Pathogenesis. Physiology 24: 147-158 [Abstract] [Full text]  
  • Escher, G., Cristiano, M., Causevic, M., Baumann, M., Frey, F. J., Surbek, D., Mohaupt, M. G. (2009). High aldosterone-to-renin variants of CYP11B2 and pregnancy outcome. Nephrol Dial Transplant 24: 1870-1875 [Abstract] [Full text]  
  • Lykke, J. A., Langhoff-Roos, J., Sibai, B. M., Funai, E. F., Triche, E. W., Paidas, M. J. (2009). Hypertensive Pregnancy Disorders and Subsequent Cardiovascular Morbidity and Type 2 Diabetes Mellitus in the Mother. Hypertension 53: 944-951 [Abstract] [Full text]  
  • Topal, A. E., Eren, M. N. (2009). Acute ventricular rupture due to myocardial infarction during postpartum period. ICVTS 8: 565-567 [Abstract] [Full text]  
  • Basaran, A. (2009). Pregnancy-induced Hyperlipoproteinemia: Review of the Literature. Reproductive Sciences 16: 431-437 [Abstract]  
  • Poon, L. C.Y., Kametas, N. A., Maiz, N., Akolekar, R., Nicolaides, K. H. (2009). First-Trimester Prediction of Hypertensive Disorders in Pregnancy. Hypertension 53: 812-818 [Abstract] [Full text]  
  • Kajantie, E., Eriksson, J. G., Osmond, C., Thornburg, K., Barker, D. J.P. (2009). Pre-Eclampsia Is Associated With Increased Risk of Stroke in the Adult Offspring: The Helsinki Birth Cohort Study. Stroke 40: 1176-1180 [Abstract] [Full text]  
  • Valdes, G., Quezada, F., Marchant, E., von Schultzendorff, A., Moran, S., Padilla, O., Martinez, A. (2009). Association of Remote Hypertension in Pregnancy With Coronary Artery Disease: A Case-Control Study. Hypertension 53: 733-738 [Abstract] [Full text]  
  • Champagne, K., Schwartzman, K., Opatrny, L., Barriga, P., Morin, L., Mallozzi, A., Benjamin, A., Kimoff, R. J. (2009). Obstructive sleep apnoea and its association with gestational hypertension. Eur Respir J 33: 559-565 [Abstract] [Full text]  
  • Fitzpatrick, E., Johnson, M.P., Dyer, T.D., Forrest, S., Elliott, K., Blangero, J., Brennecke, S.P., Moses, E.K. (2009). Genetic association of the activin A receptor gene (ACVR2A) and pre-eclampsia. Mol Hum Reprod 15: 195-204 [Abstract] [Full text]  
  • Vikse, B. E., Irgens, L. M., Leivestad, T., Skjaerven, R., Iversen, B. M. (2008). Preeclampsia and the Risk of End-Stage Renal Disease. NEJM 359: 800-809 [Abstract] [Full text]  
  • Craici, I., Wagner, S., Garovic, V. D. (2008). Review: Preeclampsia and future cardiovascular risk: formal risk factor or failed stress test?. Ther Adv Cardiovasc Dis 2: 249-259 [Abstract]  
  • Lampinen, K. H., Ronnback, M., Groop, P.-H., Kaaja, R. J. (2008). A Relationship Between Insulin Sensitivity and Vasodilation in Women With a History of Preeclamptic Pregnancy. Hypertension 52: 394-401 [Abstract] [Full text]  
  • Roberts, J. M., Catov, J. M. (2008). Preeclampsia More Than 1 Disease: Or Is It?. Hypertension 51: 989-990 [Full text]  
  • LaMarca, B. D., Gilbert, J., Granger, J. P. (2008). Recent Progress Toward the Understanding of the Pathophysiology of Hypertension During Preeclampsia. Hypertension 51: 982-988 [Full text]  
  • Rasmussen, S., Irgens, L. M. (2008). History of Fetal Growth Restriction Is More Strongly Associated With Severe Rather Than Milder Pregnancy-Induced Hypertension. Hypertension 51: 1231-1238 [Abstract] [Full text]  
  • Berends, A. L., de Groot, C. J.M., Sijbrands, E. J., Sie, M. P.S., Benneheij, S. H., Pal, R., Heydanus, R., Oostra, B. A., van Duijn, C. M., Steegers, E. A.P. (2008). Shared Constitutional Risks for Maternal Vascular-Related Pregnancy Complications and Future Cardiovascular Disease. Hypertension 51: 1034-1041 [Abstract] [Full text]  
  • Hladunewich, M. A., Myers, B. D., Derby, G. C., Blouch, K. L., Druzin, M. L., Deen, W. M., Naimark, D. M., Lafayette, R. A. (2008). Course of preeclamptic glomerular injury after delivery. Am. J. Physiol. Renal Physiol. 294: F614-F620 [Abstract] [Full text]  
  • Gilbert, J. S., Ryan, M. J., LaMarca, B. B., Sedeek, M., Murphy, S. R., Granger, J. P. (2008). Pathophysiology of hypertension during preeclampsia: linking placental ischemia with endothelial dysfunction. Am. J. Physiol. Heart Circ. Physiol. 294: H541-H550 [Abstract] [Full text]  
  • Vatten, L. J, Nilsen, T. I L, Juul, A., Jeansson, S., Jenum, P. A, Eskild, A. (2008). Changes in circulating level of IGF-I and IGF-binding protein-1 from the first to second trimester as predictors of preeclampsia. Eur J Endocrinol 158: 101-105 [Abstract] [Full text]  
  • Vikse, B. E., Irgens, L. M., Leivestad, T., Hallan, S., Iversen, B. M. (2008). Low Birth Weight Increases Risk for End-Stage Renal Disease. J. Am. Soc. Nephrol. 19: 151-157 [Abstract] [Full text]  
  • Ness, R. B., Catov, J. (2007). Invited Commentary: Timing and Types of Cardiovascular Risk Factors in Relation to Offspring Birth Weight. Am J Epidemiol 166: 1365-1367 [Abstract] [Full text]  
  • Catov, J. M., Bodnar, L. M., Ness, R. B., Barron, S. J., Roberts, J. M. (2007). Inflammation and Dyslipidemia Related to Risk of Spontaneous Preterm Birth. Am J Epidemiol 166: 1312-1319 [Abstract] [Full text]  
  • Magnussen, E. B., Vatten, L. J., Lund-Nilsen, T. I., Salvesen, K. A., Smith, G. D., Romundstad, P. R. (2007). Prepregnancy cardiovascular risk factors as predictors of pre-eclampsia: population based cohort study. BMJ 335: 978-978 [Abstract] [Full text]  
  • Ilekis, J. V., Reddy, U. M., Roberts, J. M. (2007). Review Article: Preeclampsia A Pressing Problem: An Executive Summary of a National Institute of Child Health and Human Development Workshop. Reproductive Sciences 14: 508-523 [Abstract]  
  • Callaway, L. K., McIntyre, H. D., O'Callaghan, M., Williams, G. M., Najman, J. M., Lawlor, D. A. (2007). The Association of Hypertensive Disorders of Pregnancy with Weight Gain over the Subsequent 21 Years: Findings from a Prospective Cohort Study. Am J Epidemiol 166: 421-428 [Abstract] [Full text]  
  • Klemmensen, A. K., Olsen, S. F., Osterdal, M. L., Tabor, A. (2007). Validity of Preeclampsia-related Diagnoses Recorded in a National Hospital Registry and in a Postpartum Interview of the Women. Am J Epidemiol 166: 117-124 [Abstract] [Full text]  
  • Irgens, L. M (2007). Commentary: On the clinical prediction of pre-eclampsia and its enigmatic aetiology. Int J Epidemiol 0: dym030v1-2 [Full text]  
  • Catov, J. M, Ness, R. B, Kip, K. E, Olsen, J. (2007). Risk of early or severe preeclampsia related to pre-existing conditions. Int J Epidemiol 36: 412-419 [Abstract] [Full text]  
  • Sabour, S., Franx, A., Rutten, A., Grobbee, D. E., Prokop, M., Bartelink, M.-L., van der Schouw, Y. T., Bots, M. L. (2007). High Blood Pressure in Pregnancy and Coronary Calcification. Hypertension 49: 813-817 [Abstract] [Full text]  
  • Rasmussen, S., Irgens, L. M. (2007). Pregnancy-Induced Hypertension in Women Who Were Born Small. Hypertension 49: 806-812 [Abstract] [Full text]  
  • Hubel, C. A., Wallukat, G., Wolf, M., Herse, F., Rajakumar, A., Roberts, J. M., Markovic, N., Thadhani, R., Luft, F. C., Dechend, R. (2007). Agonistic Angiotensin II Type 1 Receptor Autoantibodies in Postpartum Women With a History of Preeclampsia. Hypertension 49: 612-617 [Abstract] [Full text]  
  • Germain, A. M., Romanik, M. C., Guerra, I., Solari, S., Reyes, M. S., Johnson, R. J., Price, K., Karumanchi, S. A., Valdes, G. (2007). Endothelial Dysfunction: A Link Among Preeclampsia, Recurrent Pregnancy Loss, and Future Cardiovascular Events?. Hypertension 49: 90-95 [Abstract] [Full text]  
  • Roberts, J. M., Von Versen-Hoeynck, F. (2007). Maternal Fetal/Placental Interactions and Abnormal Pregnancy Outcomes. Hypertension 49: 15-16 [Full text]  
  • Brown, D. W., Dueker, N., Jamieson, D. J., Cole, J. W., Wozniak, M. A., Stern, B. J., Giles, W. H., Kittner, S. J. (2006). Preeclampsia and the Risk of Ischemic Stroke Among Young Women: Results From the Stroke Prevention in Young Women Study. Stroke 37: 1055-1059 [Abstract] [Full text]  
  • James, A. H., Jamison, M. G., Biswas, M. S., Brancazio, L. R., Swamy, G. K., Myers, E. R. (2006). Acute Myocardial Infarction in Pregnancy: A United States Population-Based Study. Circulation 113: 1564-1571 [Abstract] [Full text]  
  • Vikse, B. E., Irgens, L. M., Bostad, L., Iversen, B. M. (2006). Adverse Perinatal Outcome and Later Kidney Biopsy in the Mother. J. Am. Soc. Nephrol. 17: 837-845 [Abstract] [Full text]  
  • Pepine, C. J., Kerensky, R. A., Lambert, C. R., Smith, K. M., von Mering, G. O., Sopko, G., Bairey Merz, C. N. (2006). Some Thoughts on the Vasculopathy of Women With Ischemic Heart Disease. J Am Coll Cardiol 47: S30-S35 [Abstract] [Full text]  
  • Roberts, J. M., Gammill, H. S. (2005). Preeclampsia: Recent Insights. Hypertension 46: 1243-1249 [Abstract] [Full text]  
  • Kajantie, E., Kaaja, R., Ylikorkala, O., Andersson, S., Laivouri, H. (2005). Adiponectin Concentrations in Maternal Serum: Elevated in Preeclampsis But Unrelated to Insulin Sensitivity. Reproductive Sciences 12: 433-439 [Abstract]  
  • Freeman, D. J., McManus, F., Brown, E. A., Cherry, L., Norrie, J., Ramsay, J. E., Clark, P., Walker, I. D., Sattar, N., Greer, I. A. (2004). Short- and Long-Term Changes in Plasma Inflammatory Markers Associated With Preeclampsia. Hypertension 44: 708-714 [Abstract] [Full text]  
  • Raijmakers, M. T. M., Dechend, R., Poston, L. (2004). Oxidative Stress and Preeclampsia: Rationale for Antioxidant Clinical Trials. Hypertension 44: 374-380 [Abstract] [Full text]  
  • Davison, J. M., Homuth, V., Jeyabalan, A., Conrad, K. P., Karumanchi, S. A., Quaggin, S., Dechend, R., Luft, F. C. (2004). New Aspects in the Pathophysiology of Preeclampsia. J. Am. Soc. Nephrol. 15: 2440-2448 [Abstract] [Full text]  
  • Taylor, A. (2004). Pre-eclampsia and the risk of cancer. BMJ 328: 909-910 [Full text]  
  • Paltiel, O., Friedlander, Y., Tiram, E., Barchana, M., Xue, X., Harlap, S. (2004). Cancer after pre-eclampsia: follow up of the Jerusalem perinatal study cohort. BMJ 328: 919- [Abstract] [Full text]  
  • Agatisa, P. K., Ness, R. B., Roberts, J. M., Costantino, J. P., Kuller, L. H., McLaughlin, M. K. (2004). Impairment of endothelial function in women with a history of preeclampsia: an indicator of cardiovascular risk. Am. J. Physiol. Heart Circ. Physiol. 286: H1389-H1393 [Abstract] [Full text]  
  • Pouta, A., Hartikainen, A.-L., Sovio, U., Gissler, M., Laitinen, J., McCarthy, M. I., Ruokonen, A., Elliott, P., Jarvelin, M.-R. (2004). Manifestations of Metabolic Syndrome After Hypertensive Pregnancy. Hypertension 43: 825-831 [Abstract] [Full text]  
  • Pell, J. P., Smith, G. C. S., Walsh, D. (2004). Pregnancy Complications and Subsequent Maternal Cerebrovascular Events: A Retrospective Cohort Study of 119,668 Births. Am J Epidemiol 159: 336-342 [Abstract] [Full text]  
  • Sattar, N., Ramsay, J., Crawford, L., Cheyne, H., Greer, I. A. (2003). Classic and Novel Risk Factor Parameters in Women With a History of Preeclampsia. Hypertension 42: 39-42 [Abstract] [Full text]  
  • Seely, E. W., Solomon, C. G. (2003). Insulin Resistance and Its Potential Role in Pregnancy-Induced Hypertension. J. Clin. Endocrinol. Metab. 88: 2393-2398 [Abstract] [Full text]  
  • Luft, F. C. (2003). Pre-eclampsia and the maternal cardiovascular risk. Nephrol Dial Transplant 18: 860-861 [Full text]  
  • Roberts, J. M., Balk, J. L., Bodnar, L. M., Belizan, J. M., Bergel, E., Martinez, A. (2003). Nutrient Involvement in Preeclampsia. J. Nutr. 133: 1684S-1692 [Abstract] [Full text]  
  • Wilson, B. J, Watson, M S., Prescott, G. J, Sunderland, S., Campbell, D. M, Hannaford, P., Smith, W C. S (2003). Hypertensive diseases of pregnancy and risk of hypertension and stroke in later life: results from cohort study. BMJ 326: 845-845 [Abstract] [Full text]  
  • Raijmakers, M T M, Roes, E M, te Morsche, R H M, Steegers, E A P, Peters, W H M (2003). Haptoglobin and its association with the HELLP syndrome. J. Med. Genet. 40: 214-216 [Full text]  
  • Ahmed, A. S. M. (2002). Pre-eclampsia: multisystem involvement and maternal risks. The Journal of the Royal Society for the Promotion of Health 122: 211-212  
  • van de Goot, F R W, Berge, R L t. (2002). Lamashtu, "she who erases", touched her stomach seven times to kill the child. J. Clin. Pathol. 55: 534-534 [Full text]  
  • (2002). Preeclampsia with Preterm Delivery Increases Risk for Cardiovascular Death. JWatch General 2002: 5-5 [Full text]  

Rapid Responses:

Read all Rapid Responses

Pre-eclampsia and remote cardiovascular problems
Marshall D Lindheimer
bmj.com, 2 Dec 2001 [Full text]
Insulin Resistance, Preeclampsia and Cardiovascular Disease
David SH Bell, et al.
bmj.com, 21 Dec 2001 [Full text]
Preeclampsia and Cancer Risk
Carolyn M. Salafia, MD MS, et al.
bmj.com, 9 Feb 2002 [Full text]
Access jobs at BMJ Careers
Whats new online at Student BMJ