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The impact of prior preeclampsia on the risk of superimposed preeclampsia and other adverse pregnancy outcomes in patients with chronic hypertension

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The impact of prior preeclampsia on the risk of superimposed preeclampsia and other adverse pregnancy outcomes in patients with chronic hypertension
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  OBSTETRICS The impact of prior preeclampsia on the risk of superimposedpreeclampsia and other adverse pregnancy outcomesin patients with chronic hypertension Baha M. Sibai, MD; Matthew A. Koch, MD, PhD; Salvio Freire, MD; Joao Luiz Pinto e Silva, MD;Marilza Vieira Cunha Rudge, MD; Sérgio Martins-Costa, MD; Janet Moore, MS; Cleide de Barros Santos, MD;Jose Guilherme Cecatti, MD; Roberto Costa, MD; José Geraldo Ramos, MD; Nancy Moss, PhD; Joseph A. Spinnato II, MD OBJECTIVE:  We sought to compare the rates of superimposed pre-eclampsia and adverse outcomes in women with chronic hypertensionwith or without prior preeclampsia. STUDYDESIGN:  We conducted secondary analysis of 369 women withchronic hypertension (104 with prior preeclampsia) enrolled at 12-19weeksaspartofamultisitetrialofantioxidantstopreventpreeclampsia(no reduction was found). Outcome measures were rates of superim-posed preeclampsia and other adverse perinatal outcomes. RESULTS:  Prepregnancy body mass index, blood pressure, and smok-ing status at enrollment were similar between groups. The rates ofsuperimposed preeclampsia (17.3% vs 17.7%), abruptio placentae(1.0% vs 3.1%), perinatal death (6.7% vs 8.7%), and small for gesta-tionalage(18.4%vs14.3%)weresimilarbetweengroups,butpretermdelivery  37weekswashigherinthepriorpreeclampsiagroup(36.9%vs 27.1%; adjusted risk ratio, 1.46; 95% confidence interval, 1.05–2.03; P   .032). CONCLUSION:  In women with chronic hypertension, a history of pre-eclampsia does not increase the rate of superimposed preeclampsia,but is associated with an increased rate of delivery at  37 weeks. Key words:  adverse pregnancy outcome, chronic hypertension,superimposed preeclampsia Cite this article as: Sibai BM, Koch MA, Freire S, et al. The impact of prior preeclampsia on the risk of superimposed preeclampsia and other adverse pregnancyoutcomes in patients with chronic hypertension. Am J Obstet Gynecol 2010;204:x.ex-x.ex. C hronic hypertension is a relatively common disorder occurring in ap-proximately 1-5% of pregnant women. 1 The incidence depends on the woman’sage, body mass index (BMI), ethnic ori-gin, and the presence of associated med-ical disorders such as renal disease, dia-betes mellitus, and connective tissuedisease. 1 Because of the current trend of childbearing at an older age and the epi-demic of obesity and type 2 diabetesworldwide, it is expected that the preva-lence of chronic hypertension in preg-nancy will continue to increase. 2 There are numerous studies describ-ing an increased rate of preeclampsia inwomen with chronic hypertension. 1-8 Inaddition, the findings of these studiesemphasize that the development of su-perimposed preeclampsia is associatedwith high rates of adverse pregnancy outcomes. 1-8 In women without chronichypertension, the risk of preeclampsia isincreasedwithahistoryofpreeclampsia,advanced maternal age, and increasedBMI, 9 whereasitisreducedinthosewhosmoke during pregnancy. 10 Despite theextensive research on the rate of super-imposed preeclampsia and associatedadverse outcome related to superim-posed preeclampsia in women withchronic hypertension, there are limiteddata on risk factors for superimposedpreeclampsia in such women, 7,8 andthere are no data evaluating the impactof prior preeclampsia on adverse preg-nancy outcome in women with chronichypertension.We performed a secondary analysis of 369 women with chronic hypertensionenrolled as part of a trial of antioxidantsto prevent preeclampsia. 11 The primary outcome for this analysis, the develop-ment of superimposed preeclampsia,and other adverse pregnancy outcomes FromtheUniversityofCincinnatiCollegeofMedicine,Cincinnati,OH(DrsSibaiandSpinnato);UniversidadeFederaldePernambuco,HospitaldasClínicas,Recife(DrsFreireanddeBarrosSantos),UniversidadeEstadualdeCampinas,Campinas(DrsPintoeSilvaandCecatti),UniversidadeEstadualPaulista,Botucatu(DrsRudgeandCosta),andUniversidadeFederaldoRioGrandedoSul,HospitaldeClínicas,PortoAlegre(DrsMartins-CostaandRamos),Brazil;RTIInternational,ResearchTrianglePark,NC(DrKochandMsMoore);andthe EuniceKennedyShriver  NationalInstituteofChildHealthandHumanDevelopment,Bethesda,MD(DrMoss). Presentedatthe25thAnnualMeetingoftheSocietyforMaternal-FetalMedicine,SanDiego,CA,Feb.1-6,2010.ReceivedJune24,2010;revisedAug.16,2010;acceptedNov.5,2010.Reprints:BahaM.Sibai,MD,231AlbertSabinWay,Cincinnati,OH45267-0526.baha.sibai@uc.edu. ThiseffortwassupportedbyGrantsnos.1U01HD40565andU01HD44036cosponsoredbythe Eunice Kennedy Shriver  NationalInstituteofChildHealthandHumanDevelopmentandtheBillandMelindaGatesFoundation.0002-9378/$36.00 • © 2010 Published by Mosby, Inc. • doi: 10.1016/j.ajog.2010.11.027 Research  www. AJOG .org  MONTH 2010  American Journal of Obstetrics &  Gynecology  1.e1  were compared between women withand without prior preeclampsia in themost recent pregnancy lasting at least 20weeks. We also examined risk factorsfor development of superimposed pre-eclampsia in this population. M ATERIALS AND M ETHODS The multicenter clinical trial was con-ducted as a protocol within the NationalInstitute of Child Health and HumanDevelopment (NICHD) Global Network for Women’s and Children’s Health Re-search. 11 The primary clinical center(Recife) and 3 additional clinical sites(Campinas,Botucatu,andPortoAlegre)are major teaching hospitals that serve aprimarily urban low-income populationin Brazil. The study protocol was ap-proved by the NICHD and the institu-tional review boards at the University of Cincinnati, each participating site, andthe data coordinating center. Subjects We enrolled women seeking prenatalcare who were 12 0/7 –19 6/7 weeks preg-nantanddiagnosedwithnonproteinuricchronichypertensionorahistoryofpre-eclampsia in their most recent preg-nancy that progressed  20 weeks’ gesta-tion. Chronic hypertension was definedas the presence of hypertension prior topregnancy or  20 weeks’ gestation. Forwomen receiving antihypertensive med-ications at time of enrollment, the pres-ence of sustained hypertension   20weeks’gestationwasnotmandated.Adi-agnosis of prior preeclampsia was basedon review of the medical record for theprevious pregnancy by the researchteam. In the absence of medical records,the diagnosis was according to the best judgment of the research team. This re-quired that the team confirm that thepatients’ reported events of their preg-nanciesarehighlyconsistentwithadiag-nosis of prior preeclampsia. Exclusioncriteriawereplanneddeliveryelsewhere,multifetal gestation, allergy to vitamin Cor vitamin E, requirement for aspirin oranticoagulant medication, 24-hour uri-nary protein   300 mg, prepregnancy diabetes mellitus, known fetal anomaly incompatible with lif e, or prior partici-pation in the study. 11 Women were assigned randomly toreceive daily vitamin C 1000 mg and vi-tamin E 400 IU or placebo. Each activetreatment gel cap contained 500 mg of ascorbic acid, 100 IU of d-alpha tocoph-erol, 100 IU of d-alpha tocopherol ace-tate, and excipients (gelatin, soybean oil,glycerin, water lecithin, and caramelcolor). The placebo gel caps containedexcipientsonlyandwereexternallyiden-ticaltotheactivedrug.Participantswereinstructed to ingest 2 gel caps daily fromenrollment until delivery or until the di-agnosis of preeclampsia. Study partici-pants were discouraged from the use of antioxidant vitamins, calcium supple-ments, and chronic use of aspirin. Thewomen were followed up at routine pre-natal visits, typically every 4 weeks until26-28weeksofgestation,every2-3weeksuntil 36 weeks of gestation, and thenweekly until delivery or the onset of preeclampsia. 11 The primary outcome of the trial wasthe development of preeclampsia. Forwomen with chronic hypertension, (su-perimposed) preeclampsia was definedby onset of proteinuria (either 300 mg/24 hour or  2  by dipstick) or throm-bocytopenia (platelet count   100   10 3 /mm 3 ), elevated liver enzymes (as-partateaminotransferaseoralanineami-notransferase  70 IU/L), or pulmonary edema. Women were followed upthroughthe14thdaypostpartumfortheoccurrence of preeclampsia. 11 FIGURE Flow chart for enrolled patients  n = 17 withdrew or lost to follow-up Prior PE n = 104 Vitamins C & E (n = 49) Placebo n = 55 Delivery ≥20 wks n = 103  No prior PE n = 265 Vitamins C & E (n = 136) Placebo (n = 129) Delivery ≥20 wks n = 258 Completed follow-up n = 369 Enrolled with chronic hypertension n = 386 Sibai. Impact of prior preeclampsia in chronic hypertension. Am J Obstet Gynecol 2010. Research  Obstetrics  www.AJOG.org  1.e2  American Journal of Obstetrics &  Gynecology  MONTH 2010  In this analysis we compared the ratesofsuperimposedpreeclampsiaandotheradverse outcomes such as perinataldeaths, abruptio placentae, preterm de-livery at   37 weeks and   34 weeks,smallforgestationalage(SGA),andneo-natal respiratory distress syndrome, be-tween women with and without a his-tory of preeclampsia. We also analyzedother known risk factors that may influence the rate of superimposedpreeclampsia such as maternal age, du-ration of hypertension, use of antihy-pertensive medications, BMI, systolicand diastolic blood pressures at enroll-ment, and smoking during pregnancy.SGA was defined as a birth weight  10th percentile according to thegrowth tables of Alexander et al. 12 Ab-ruptio placentae was diagnosed ac-cording to clinical findings and/or pla-cental examination. 11 Because no differences were found inthe rates of superimposed preeclampsiaor other adverse outcomes between thetreatment groups in the trial, 11 the datawere pooled across treatment groups forthis analysis. Parallel analyses adjustingfor treatment group yielded virtually identical results and are not reported.Assuming a rate of superimposed pre-eclampsia of 15% in those without priorpreeclampsia, and 25% in those withprior preeclampsia with a 2-sided     0.05,oursamplesizehadapowerof61%todetectadifferenceintherateofsuper-imposed preeclampsia. Statistical com-parisons were stratified by site usingCochran-Mantel-Haenszel general asso-ciation   2 statistics 13 forcategoricalvari-ablesandanalysisofvarianceforcontin-uous variables. Analyses that adjustedforadditionalcovariatesusedlogisticre-gression models. 14 Data were analyzedusing software (SAS/STAT, version9.1.3;SASInstituteInc,Cary,NC).ExactCochran-Mantel-Haenszel proceduresin software (StatXact, version 8; CytelInc, Cambridge, MA) were used whenbinary outcomes were sparse, yieldingodds ratios instead of risk ratios. Analy-ses were performed using 2-sided     0.05 without adjustment for multiplecomparisons. R  ESULTS Subjectswereenrolledintheantioxidanttrial from July 2, 2003, through May 15,2006. Of the 739 women enrolled, 369hadchronichypertension;104hadahis-tory of preeclampsia and 265 did not.The Figure is a flow chart describing thepatients enrolled according to their his-tory of preeclampsia as well as accordingto their treatment assignment. Amongthese patients, 52.6% were receiving an-tihypertensive therapy at onset of preg-nancy. The rate of superimposed pre-eclampsia was not reduced with the useof antioxidants. 11 Table 1 describes thedemographics and clinical characteris-ticsofthe369subjectsaccordingtopres-ence or absence of history of preeclamp-sia.Therewerenostatisticallysignificantdifferencesbetweenthe2groupsregard-ing any of the variables studied.After enrollment, 65 (17.6%) devel-oped superimposed preeclampsia. Table2 shows the association of some clinicalcharacteristicswiththeoccurrenceofsu-perimposed preeclampsia. Patients withsuperimposed preeclampsia were morelikely to have higher systolic and dia-stolic blood pressures at enrollment, ascompared to those without superim-posed preeclampsia. In contrast, the rateof superimposed preeclampsia was notaffected by maternal age, BMI, or smok-ing status during pregnancy.Table 3 compares pregnancy outcomebetweenthosewithandwithoutpriorpre-eclampsia.Theratesofsuperimposedpre-eclampsiawerenotdifferentbetweenthe2 TABLE 1 Baseline characteristics by history of preeclampsia Prior preeclampsiaCharacteristic Yes, n (%) (n  104) No, n (%) (n  265) Maternal age at enrollment, y a 30.6  6.3 30.7  6.3 .....................................................................................................................................................................................................................................  35 72 (69.2) 182 (68.7) .....................................................................................................................................................................................................................................  35 32 (30.8) 83 (31.3) .............................................................................................................................................................................................................................................. Prepregnancy BMI, kg/M 2a 29.8  7.7 30.9  7.4 .....................................................................................................................................................................................................................................  25 27 (26.7) 63 (23.9) ..................................................................................................................................................................................................................................... 25-29 33 (32.7) 64 (24.2) .....................................................................................................................................................................................................................................  30 41 (40.6) 137 (51.9) .............................................................................................................................................................................................................................................. GA at enrollment, wk  a 15.4  2.5 15.7  2.7 .............................................................................................................................................................................................................................................. Primigravida 0 (0.0) 68 (25.7) .............................................................................................................................................................................................................................................. SBP at enrollment, mm Hg a 126.6  14.9 129.9  16.5 .....................................................................................................................................................................................................................................  130 53 (51.0) 102 (38.5) ..................................................................................................................................................................................................................................... 130-140 17 (16.3) 64 (24.2) .....................................................................................................................................................................................................................................  140 34 (32.7) 99 (37.4) .............................................................................................................................................................................................................................................. DBP at enrollment, mm Hg a 79.8  13.8 81.2  12.8 .....................................................................................................................................................................................................................................  80 37 (35.6) 76 (28.7) ..................................................................................................................................................................................................................................... 80-90 33 (31.7) 95 (35.8) .....................................................................................................................................................................................................................................  90 34 (32.7) 94 (35.5) .............................................................................................................................................................................................................................................. Duration of hypertension, y a 4.8  4.4 4.5  4.8 ..............................................................................................................................................................................................................................................  Antihypertensive medications b 60 (57.7) 134 (50.6) .............................................................................................................................................................................................................................................. Smoking at enrollment 7 (6.7) 24 (9.1) .............................................................................................................................................................................................................................................. Smoking during pregnancy c 13 (12.5) 39 (14.7) .............................................................................................................................................................................................................................................. BMI  , body mass index;  DBP  , diastolic blood pressure;  GA , gestational age;  SBP  , systolic blood pressure. a Values are mean  SD;  b  At onset of pregnancy;  c  As assessed at enrollment. Sibai. Impact of prior preeclampsia in chronic hypertension. Am J Obstet Gynecol 2010.  www.AJOG.org   Obstetrics  Research MONTH 2010  American Journal of Obstetrics &  Gynecology  1.e3  groups. In addition, there were no signifi-cant differences between groups in allother adverse pregnancy outcomes exceptfor the rate of preterm delivery at   37weeks, which was higher in the previouspreeclampsia group (36.9% vs 27.1%; ad- justed risk ratio [aRR], 1.46; 95% confi-dence interval [CI], 1.05–2.03;  P   .032).The difference in preterm delivery wasmainly due to difference in delivery at34 0/6 –36 6/7 weeks (30.9% vs 18.3% of on-going pregnancies at 34 weeks; aRR, 1.95;95%CI,1.26–3.04; P   .0033).Thesedif-ferencesremainedsignificantafterexclud-ingprimigravidasfromthegroupwithoutpriorpreeclampsia.Afteradjustingforsiteand prepregnancy BMI (quadratic) usinglogistic regression the  P   value for all sub- jectswas.070,butthedifferenceremainedsignificant among women with ongoingpregnanciesat34weeks( P   .012). C OMMENT Theprincipalfindingsofthestudyare:(1)superimposed preeclampsia occurred in17.6% of women with chronic hyperten-sion; (2) the rate of superimposed pre-eclampsia was not different in those withprior preeclampsia (17.3%) and thosewithoutsuchahistory(17.7%);(3)therateofsuperimposedpreeclampsiawasdepen-dent on maternal systolic and diastolicblood pressure values   20 weeks’ gesta-tion, but not on maternal age, BMI, orsmoking status during pregnancy; and (4)womenwithpriorpreeclampsiahadasig-nificantlyhigherrateofpretermdeliveryat  37 weeks’ gestation (aRR, 1.46; 95% CI,1.05–2.03),butnosignificantdifferenceinrates of perinatal deaths, abruptio placen-tae, SGA infants, or delivery at  34 weeksascomparedtothosewithoutpriorsuper-imposedpreeclampsia.The overall rate of superimposed pre-eclampsia(17.6%)inthisstudyissimilarto that reported by 5 previous observa-tionalstudiesfromCanada(21%), 3 New Zealand (14%), 4 United States (25%), 7 Italy (28%), 5 and United Kingdom(22%). 8 On the other hand, we foundthat prior preeclampsia was not associ-atedwithincreasedriskofsuperimposedpreeclampsia which, is inconsistent withthe results of 2 large observational stud-ies. 7,8 The study by Sibai et al 7 reportedthatwomenwithpriorpreeclampsiahada 1.6-fold (95% CI, 1.1–2.3) higher rateof superimposed preeclampsia thanthose without this history, although thisstudyincludedwomenwithrenaldiseaseand did not report data on BMI. Both of these latter factors could have affectedthe rate of superimposed preeclampsia.In addition, the study by Chappell et al 8 reported 1.95-fold (95% CI, 1.25–3.04)increased risk of superimposed pre-eclampsia in women with prior pre-eclampsia. However, this study also in-cluded women with chronic renaldisease, diabetes, antiphospholipid syn-drome, and abnormal uterine artery Doppler at 18-20 weeks, all of whichcould have influenced their results.However,ourstudyhadonly61%powerto detect differences in rate of superim-posed preeclampsia between groups.Itiswellestablishedthatadvancedma-ternal age, increased BMI (increasedrisk), and smoking during pregnancy (reduced risk) are risk factors for pre-eclampsia in women without chronichypertension. 9,10 We were able to findonly 2 reports 7,8 that examined the rela-tionshipbetweenadvancedmaternalageand risk of preeclampsia in chronic hy-pertension. Similar to our findings, bothof these reports found no increasedrisk. 7,8 We were also able to find only 1report that examined the relationshipbetween smoking during pregnancy andrisk of preeclampsia in chronic hyper-tension. 8 Chappell et al 8 found thatsmokingisanindependentriskfactorforsuperimposed preeclampsia (adjusted TABLE 2 Factors associated with development of superimposedpreeclampsia in chronic hypertension during pregnancy Superimposed preeclampsiaCharacteristicYes, n (%)(n  65)No, n (%)(n  304)  P   value a Maternal age at enrollment, y b 30.5  5.7 30.8  6.4 .92 .....................................................................................................................................................................................................................................  35 48 (73.8) 206 (67.8) .38 .....................................................................................................................................................................................................................................  35 17 (26.2) 98 (32.2) .............................................................................................................................................................................................................................................. Prior preeclampsia c 18 (27.7) 86 (28.3) .34 .............................................................................................................................................................................................................................................. GA at enrollment, wk  b 15.3  2.6 15.7  2.7 .54 .............................................................................................................................................................................................................................................. Prepregnancy BMI, kg/M 2b 30.7  7.2 30.6  7.6 .67 .....................................................................................................................................................................................................................................  25 17 (26.2) 73 (24.3) .61 ..................................................................................................................................................................................................................................... 25-29 16 (24.6) 81 (27.0) .....................................................................................................................................................................................................................................  30 32 (49.2) 146 (48.6) .............................................................................................................................................................................................................................................. SBP at enrollment, mm Hg b 132.2  13.0 128.3  16.7 .035 .....................................................................................................................................................................................................................................  130 20 (30.8) 135 (44.4) .0095 ..................................................................................................................................................................................................................................... 130-140 15 (23.1) 66 (21.7) .....................................................................................................................................................................................................................................  140 30 (46.2) 103 (33.9) .............................................................................................................................................................................................................................................. DBP at enrollment, mm Hg b 84.9  10.1 79.9  13.4   .0011 .....................................................................................................................................................................................................................................  80 9 (13.8) 104 (34.2)   .0001 ..................................................................................................................................................................................................................................... 80-90 24 (36.9) 104 (34.2) .....................................................................................................................................................................................................................................  90 32 (49.2) 96 (31.6) .............................................................................................................................................................................................................................................. Smoking at enrollment 6 (9.2) 25 (8.2) .90 .............................................................................................................................................................................................................................................. Smoking during pregnancy d 8 (12.3) 44 (14.5) .62 .............................................................................................................................................................................................................................................. BMI  , body mass index;  DBP  , diastolic blood pressure;  GA , gestational age;  SBP  , systolic blood pressure. a Cochran-Mantel-Haenszel method or analysis of variance, adjusting for study site;  b Values are mean  SD;  c In most recentprevious pregnancy progressing to at least 20 weeks of gestation;  d  As assessed at enrollment. Sibai.Impactofpriorpreeclampsiainchronichypertension.AmJObstetGynecol2010. Research  Obstetrics  www.AJOG.org  1.e4  American Journal of Obstetrics &  Gynecology  MONTH 2010  odds ratio, 1.79; 95% CI, 1.0–3.18) inwomen with chronic hypertension. Incontrast, we found no such association.Thus, more studies that are specifically designed to answer this question areneeded.Why might advanced maternal age,increased BMI, a history of preeclamp-sia, and smoking during pregnancy notbeassociatedwithriskofpreeclampsiainwomenwithchronichypertension?First,in normotensive nulliparous women, theassociation between advanced maternalage and preeclampsia is not a consistentfinding among various studies. Alterna-tively, the association may be due to theincreased rates of chronic hypertensionand/or gestational diabetes with ad-vanced maternal age (both of these arerisk factors for preeclampsia) in nullipa-rous women. 9 Second, the associationbetween increased BMI and preeclamp-sia in normotensive women may be dueto insulin resistance in such women. 9 Itis possible that in women with chronichypertension (a state of preexisting mi-crovascular disease and endothelial dys-function) the addition of insulin resis-tance will have minimal impact on thepathophysiologic abnormalities leadingto preeclampsia.Our study is the first to report on theimpactofahistoryofpreeclampsiaonad-versepregnancyoutcomesinwomenwithchronic hypertension. We found thatwomen who had prior preeclampsia hadno increase in major adverse pregnancy outcomes except for higher rates of pre-term delivery at   37 weeks’ gestation(mainly late preterm births). This higherrate occurred in the absence of increasedrate of superimposed preeclampsia insuch women, suggesting that prior pre-eclampsia is an independent risk factorfor late preterm delivery in women withchronic hypertension. This increased ratemay also be related to the fact that physi-cians were more aggressive in deliveringthepatientsbecauseofexacerbatedhyper-tension because of concern that they may bedevelopingpreeclampsia.Our study has a few limitations. Weincluded patients who received antioxi-dants or placebo from the srcinal trial;however, we found no differences in therates of superimposed preeclampsia orother adverse outcomes between thegroups in the trial, and analyses of thepooled data in this report gave nearly identical results when adjusted for treat-ment arm. Therefore, it is unlikely thatthis strategy could have influenced ourresults. Another limitation relates to thelack of statistical differences in rates of abruptio placentae, SGA infants, perina-tal deaths, and delivery at   34 weeks’gestation between those with and with-out prior preeclampsia. This may be dueto inadequate sample size, however, therates of these outcomes were all lower inthe prior preeclampsia group. Also, fordiagnosis of SGA, we used standardsfrom US populations that might notapply to Brazilian populations. In addi-tion, in women with prior delivery, wedid not collect data regarding previouspreterm delivery. Such history mighthave explained the increased rate of pre-term delivery in women with a history ofpreeclampsia.Finally,thisisasecond-ary analysis, performed without adjust-ment for multiple comparisons, and assuch, the results should be consideredexploratory.In summary, we did not find that ad-vanced maternal age, increased BMI,prior preeclampsia, and smoking duringpregnancy were associated with the de-velopment of superimposed preeclamp-siainwomenwithchronichypertension.In addition, prior preeclampsia may bean independent risk factor for late pre-term delivery in women with chronichypertension.  f REFERENCES 1.  Sibai BM. Chronic hypertension in preg-nancy. Obstet Gynecol 2002;100:369-77. TABLE 3 Pregnancy outcome in those with and without prior preeclampsia Prior preeclampsia a Adjusted risk ratio (95% CI) b P   value b Outcome Yes, n (%) (n  104) No, n (%) (n  265) Superimposed preeclampsia 18 (17.3) 47 (17.7) 1.28 (0.78–2.11) .34 ................................................................................................................................................................................................................................................................................................................................................................................  Abruptio placentae 1 (1.0) 8 (3.1) 0.44 (0.01–3.77) c .68 c ................................................................................................................................................................................................................................................................................................................................................................................ Perinatal deaths 7 (6.7) 23 (8.7) 0.79 (0.33–1.88) .59 ................................................................................................................................................................................................................................................................................................................................................................................ Preterm delivery .......................................................................................................................................................................................................................................................................................................................................................................  37 wk 38 (36.9) 70 (27.1) 1.46 (1.05–2.03) .032 ....................................................................................................................................................................................................................................................................................................................................................................... 34-36 wk 29/94 (30.9) d 42/237 (18.3) d 1.95 (1.26–3.04) .0033 .......................................................................................................................................................................................................................................................................................................................................................................  34 wk 9 (8.7) 28 (10.9) 0.79 (0.39–1.60) .52 ................................................................................................................................................................................................................................................................................................................................................................................ Small for gestational age 19 (18.4) 34 (14.3) 1.31 (0.76–2.25) .33 ................................................................................................................................................................................................................................................................................................................................................................................ Respiratory distress syndrome e 14 (13.6) 32 (12.4) 1.11 (0.64–1.93) .72 ................................................................................................................................................................................................................................................................................................................................................................................ CI  , confidence interval. a In most recent prior pregnancy progressing to at least 20 weeks of gestation;  b Cochran-Mantel-Haenszel method, adjusting for study site;  c Exact Cochran-Mantel-Haenszel procedure, adjusting forstudy site;  d Of ongoing pregnancies at 34 weeks of gestation;  e Definite or suspected. Sibai. Impact of prior preeclampsia in chronic hypertension. Am J Obstet Gynecol 2010.  www.AJOG.org   Obstetrics  Research MONTH 2010  American Journal of Obstetrics &  Gynecology  1.e5
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