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      Risk of pre-eclampsia in first and subsequent pregnancies: prospective cohort study

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          Abstract

          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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          Most cited references12

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          Comparison of risk factors for preeclampsia and gestational hypertension in a population-based cohort study.

          The objective of this study was to evaluate and compare risk factor patterns in association with preeclampsia and gestational hypertension. The data were collected from The Swedish Medical Birth Register and include all nulliparas aged 34 years or less who gave birth at the University Hospital of Uppsala, Sweden, during 1987-1993. Of these 10,666 women, 4.4% developed gestational hypertension, and 5.2% developed preeclampsia. The following risk factors were significantly associated with increased risk of preeclampsia: type 1 diabetes (odds ratio = 5.58, 95% confidence interval 2.72-11.43), gestational diabetes (odds ratio = 3.11, 95% confidence interval 1.61-6.00), and twin birth (odds ratio = 4.17, 95% confidence interval 2.30-7.55). The positive associations between these variables and the risk of gestational hypertension were weaker and nonsignificant. Compared with underweight women (body mass index 29) had increased risks of both gestational hypertension (odds ratio = 4.85, 95% confidence interval 1.97-11.92) and preeclampsia (odds ratio = 5.19, 95% confidence interval 2.35-11.48). Significantly lower risks of preeclampsia and gestational hypertension were observed for women born outside Nordic countries and in association with maternal smoking and summer birth. The similarities in risk factor patterns may indicate similarities in the biologic mechanisms underlying the two conditions.
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            CLASP: a randomised trial of low-dose aspirin for the prevention and treatment of pre-eclampsia among 9364 pregnant women. CLASP (Collaborative Low-dose Aspirin Study in Pregnancy) Collaborative Group.

            (1994)
            Pre-eclampsia is a common and serious complication of pregnancy that affects both mother and child. Review of previous small trials of antiplatelet therapy, particularly low-dose aspirin, suggested reductions of about three-quarters in the incidence of pre-eclampsia and some avoidance of intrauterine growth retardation (IUGR), but larger trials have not confirmed these results. In our multicentre study 9364 women were randomly assigned 60 mg aspirin daily or matching placebo. 74% were entered for prophylaxis of pre-eclampsia, 12% for prophylaxis of IUGR, 12% for treatment of pre-eclampsia, and 3% for treatment of IUGR. Overall, the use of aspirin was associated with a reduction of only 12% in the incidence of proteinuric pre-eclampsia, which was not significant. Nor was there any significant effect on the incidence of IUGR or of stillbirth and neonatal death. Aspirin did, however, significantly reduce the likelihood of preterm delivery (19.7% aspirin vs 22.2% control; absolute reduction of 2.5 [SD 0.9] per 100 women treated; 2p = 0.003). There was a significant trend (p = 0.004) towards progressively greater reductions in proteinuric pre-eclampsia the more preterm the delivery. Aspirin was not associated with a significant increase in placental haemorrhages or in bleeding during preparation for epidural anaesthesia, but there was a slight increase in use of blood transfusion after delivery. Low-dose aspirin was generally safe for the fetus and newborn infant, with no evidence of an increased likelihood of bleeding. Our findings do not support routine prophylactic or therapeutic administration of antiplatelet therapy in pregnancy to all women at increased risk of pre-eclampsia or IUGR. Low-dose aspirin may be justified in women judged to be especially liable to early-onset pre-eclampsia severe enough to need very preterm delivery. In such women it seems appropriate to start low-dose aspirin prophylactically early in the second trimester.
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              The effects and mechanisms of primiparity on the risk of pre-eclampsia: a systematic review.

              Pre-eclampsia has been dubbed as 'a disease of primiparity'. However, the effects and mechanisms of the association of primiparity with pre-eclampsia have not been clearly defined. We conducted a systematic review of studies evaluating the effect of primiparity on the risk of pre-eclampsia, and studies (published between January 1966 and July 2005) on the mechanisms underlying such an association. A total of 26 original studies were identified and a meta-analysis carried out for the risk of pre-eclampsia among primiparous vs. multiparous women. Variably (1.4-5.5 times) higher risks of pre-eclampsia were observed in primiparous women in all studies, with a summary odds ratio (OR) of 2.42 [95% CI 2.16, 2.71]. The adjusted ORs were larger than crude ORs in all but one study after various adjustments. Except for abundant epidemiological evidence in support of the immune maladaptation theory, only four original studies examined the actual mechanisms of such primiparity-associated risk. Two (small) studies suggested differences in immunological responses in the aetiology of pre-eclampsia in primiparous vs. multiparous women. Two recent studies indicated that differences in angiogenic factor profile or reactivity to insulin resistance in early pregnancy may explain the elevated pre-eclampsia risk in first pregnancies. In conclusion, primiparity is associated with approximately 2.4-fold elevated risk of pre-eclampsia. Although immune maladaptation is generally considered as the basis to explain such an elevated risk, few data are available on immune maladaptation parameters in primiparous vs. multiparous pregnancies. Available data are insufficient to interpret the mechanisms of such primiparity-associated excess risk of pre-eclampsia.

                Author and article information

                Contributors
                Role: associate professor
                Role: doctoral student
                Role: professor
                Journal
                BMJ
                bmj
                BMJ : British Medical Journal
                BMJ Publishing Group Ltd.
                0959-8138
                1468-5833
                2009
                2009
                18 June 2009
                : 338
                : b2255
                Affiliations
                [1 ]Department of Epidemiology, Harvard School of Public Health, 677 Huntington Ave, Boston, MA 02115, USA
                [2 ]Department of Medical Epidemiology and Biostatistics and Clinical Epidemiology Unit, Department of Medicine, Karolinska Institute, S-171 77 Stockholm, Sweden
                Author notes
                Correspondence to: S Hernández-Díaz shernan@ 123456hsph.harvard.edu
                Article
                hers615849
                10.1136/bmj.b2255
                3269902
                19541696
                5e870f61-2409-4633-b641-441114512395
                © Hernández et al 2009

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 26 February 2009
                Categories
                Research
                Epidemiologic Studies
                Pregnancy
                Reproductive Medicine

                Medicine
                Medicine

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