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      Recurrence of Preeclampsia in Northern Tanzania: A Registry-Based Cohort Study

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          Abstract

          Objective

          Preeclampsia occurs in about 4 per cent of pregnancies worldwide, and may have particularly serious consequences for women in Africa. Studies in western countries have shown that women with preeclampsia in one pregnancy have a substantially increased risk of preeclampsia in subsequent pregnancies. We estimate the recurrence risks of preeclampsia in data from Northern Tanzania.

          Methods

          A prospective cohort study was designed using 19,811 women who delivered singleton infants at a hospital in Northern Tanzania between 2000and2008. A total of 3,909 women were recorded with subsequent deliveries in the hospital with follow up through 2010. Adjusted recurrence risks of preeclampsia were computed using regression models.

          Results

          The absolute recurrence risk of preeclampsia was25%, which was 9.2-fold (95% CI: 6.4 - 13.2) compared with the risk for women without prior preeclampsia. When there were signs that the preeclampsia in a previous pregnancy had been serious either because the baby was delivered preterm or had died in the perinatal period, the recurrence risk of preeclampsia was even higher. Women who had preeclampsia had increased risk of a series of adverse pregnancy outcomes in future pregnancies. These include perinatal death (RR= 4.3), a baby with low birth weight (RR= 3.5), or a preterm birth (RR= 2.5). These risks were only partly explained by recurrence of preeclampsia.

          Conclusions

          Preeclampsia in one pregnancy is a strong predictor for preeclampsia and other adverse pregnancy outcomes in subsequent pregnancies in Tanzania. Women with previous preeclampsia may benefit from close follow-up during their pregnancies.

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          Most cited references 18

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          The global impact of pre-eclampsia and eclampsia.

           Lelia Duley (2009)
          Over half a million women die each year from pregnancy related causes, 99% in low and middle income countries. In many low income countries, complications of pregnancy and childbirth are the leading cause of death amongst women of reproductive years. The Millennium Development Goals have placed maternal health at the core of the struggle against poverty and inequality, as a matter of human rights. Ten percent of women have high blood pressure during pregnancy, and preeclampsia complicates 2% to 8% of pregnancies. Preeclampsia can lead to problems in the liver, kidneys, brain and the clotting system. Risks for the baby include poor growth and prematurity. Although outcome is often good, preeclampsia can be devastating and life threatening. Overall, 10% to 15% of direct maternal deaths are associated with preeclampsia and eclampsia. Where maternal mortality is high, most of deaths are attributable to eclampsia, rather than preeclampsia. Perinatal mortality is high following preeclampsia, and even higher following eclampsia. In low and middle income countries many public hospitals have limited access to neonatal intensive care, and so the mortality and morbidity is likely to be considerably higher than in settings where such facilities are available. The only interventions shown to prevent preeclampsia are antiplatelet agents, primarily low dose aspirin, and calcium supplementation. Treatment is largely symptomatic. Antihypertensive drugs are mandatory for very high blood pressure. Plasma volume expansion, corticosteroids and antioxidant agents have been suggested for severe preeclampsia, but trials to date have not shown benefit. Optimal timing for delivery of women with severe preeclampsia before 32 to 34 weeks' gestation remains a dilemma. Magnesium sulfate can prevent and control eclamptic seizures. For preeclampsia, it more than halves the risk of eclampsia (number needed to treat 100, 95% confidence interval 50 to 100) and probably reduces the risk of maternal death. A quarter of women have side effects, primarily flushing. With clinical monitoring serious adverse effects are rare. Magnesium sulfate is the anticonvulsant of choice for treating eclampsia; more effective than diazepam, phenytoin, or lytic cocktail. Although it is a low cost effective treatment, magnesium sulfate is not available in all low and middle income countries; scaling up its use for eclampsia and severe preeclampsia will contribute to achieving the Millennium Development Goals.
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            Risk of pre-eclampsia in first and subsequent pregnancies: prospective cohort study

            Objective To investigate whether pre-eclampsia is more common in first pregnancies solely because fewer affected women, who presumably have a higher risk of recurrence, go on to have subsequent pregnancies. Design Prospective cohort study. Setting Swedish Medical Birth Register. Participants 763 795 primiparous mothers who had their first births in Sweden, 1987-2004. Main outcome measures Pre-eclampsia. Results The risk of pre-eclampsia was 4.1% in the first pregnancy and 1.7% in later pregnancies overall. However, the risk was 14.7% in the second pregnancy for women who had had pre-eclampsia in their first pregnancy and 31.9% for women who had had pre-eclampsia in the previous two pregnancies. The risk for multiparous women without a history of pre-eclampsia was around 1%. The incidence of pre-eclampsia associated with delivery before 34 weeks’ gestation was 0.42% in primiparous women, 0.11% in multiparous women without a history of pre-eclampsia, and 6.8% and 12.5% in women who had had one or two previous pregnancies affected, respectively. The proportion of women who went on to have a further pregnancy was 4-5% lower after having a pregnancy with any pre-eclampsia but over 10% lower if pre-eclampsia was associated with very preterm delivery. The estimated risk of pre-eclampsia in parous women did not change with standardisation for pregnancy rates. Conclusions Having pre-eclampsia in one pregnancy is a poor predictor of subsequent pregnancy but a strong predictor for recurrence of pre-eclampsia in future gestations. The lower overall risk of pre-eclampsia among parous women was not explained by fewer conceptions among women who had had pre-eclampsia in a previous gestation. Early onset pre-eclampsia might be associated with a reduced likelihood of a future pregnancy and with more recurrences than late onset pre-eclampsia when there are further pregnancies. Findings are consistent with the existence of two distinct conditions: a severe recurrent early onset type affected by chronic factors, genetic or environmental, and a milder sporadic form affected by transient factors.
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              Fetal and maternal contributions to risk of pre-eclampsia: population based study.

              To use familial patterns of recurrence of pre-eclampsia to investigate whether paternal genes expressed in the fetus contribute to the mother's risk of pre-eclampsia and whether mother's susceptibility to pre-eclampsia is related to maternal inheritance by mitochondrial DNA. Linked data on pregnancies of different women who had children with the same father, and subsequently linked data on pregnancies of half sisters who either had same mother and different fathers or had same father and different mothers. Population based data from the Medical Birth Registry of Norway covering all births since 1967 (about 1.7 million) and the Norwegian Central Population Register. Relative risk of pre-eclampsia after a previous pre-eclamptic pregnancy in the family. Relative risks approximated by odds ratios. If a woman becomes pregnant by a man who has already fathered a pre-eclamptic pregnancy in a different woman her risk of developing pre-eclampsia is 1.8 (95% confidence interval 1.2 to 2.6). If the woman has a half sister who had pre-eclampsia and with whom she shares the same mother but different fathers the risk of pre-eclampsia is 1.6 (0.9 to 2.6). If the two sisters have the same father but different mothers the risk is 1.8 (1.01 to 2.9). Both the mother and the fetus contribute to the risk of pre-eclampsia, the contribution of the fetus being affected by paternal genes. Mitochondrial genes, which are transmitted by mothers, do not seem to contribute to the risk.
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                Author and article information

                Affiliations
                [1 ]Kilimanjaro Christian Medical University College, Moshi, Tanzania
                [2 ]Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
                [3 ]Centre for International Health, University of Bergen, Bergen, Norway
                [4 ]Norwegian Institute of Public Health, Oslo, Norway
                [5 ]Department of Obstetrics and Gynaecology, Kilimanjaro Christian Medical Centre, Moshi, Tanzania
                [6 ]Department of Pediatrics, Kilimanjaro Christian Medical Centre, Moshi, Tanzania
                Yale School of Public Health, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: MJM RTL. Performed the experiments: MJM RTL. Analyzed the data: MJM RTL. Contributed reagents/materials/analysis tools: MJM RTL. Wrote the manuscript: MJM AKD GM BTM JO RM RTL. Manuscript preparation and subsequent revisions: MJM Advice in designing the study and revision of the manuscript for important intellectual content: RTL. Reviewed the manuscript: AKD BTM JO RM. Responsible for the KCMC registry: GM.

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                1 November 2013
                : 8
                : 11
                PONE-D-13-21986
                10.1371/journal.pone.0079116
                3815128

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Funding
                The birth registry was supported by the Norwegian Council for Higher Education’s Program for Development Research or Nasjonalt program for Utvikling, Forskning og Utdanning (NUFU) and Quota scholarship scheme as part of MJM PhD training. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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                Research Article

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