The impact of prior preeclampsia on the risk of superimposed preeclampsia and other adverse...

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Research www.AJOG.org

OBSTETRICS

The impact of prior preeclampsia on the risk of superimposedpreeclampsia and other adverse pregnancy outcomesin patients with chronic hypertensionBaha 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

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OBJECTIVE: We sought to compare the rates of superimposed pre-clampsia and adverse outcomes in women with chronic hypertensionith or without prior preeclampsia.

STUDY DESIGN: We conducted secondary analysis of 369 women withchronic hypertension (104 with prior preeclampsia) enrolled at 12-19weeks as part of a multisite trial of antioxidants to prevent preeclampsia(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 of

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(1.0% vs 3.1%), perinatal death (6.7% vs 8.7%), and small for gesta-tional age (18.4% vs 14.3%) were similar between groups, but pretermdelivery �37 weeks was higher in the prior preeclampsia group (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-clampsia does not increase the rate of superimposed preeclampsia,ut is associated with an increased rate of delivery at �37 weeks.

ey words: adverse pregnancy outcome, chronic hypertension,
uperimposed preeclampsia superimposed preeclampsia (17.3% vs 17.7%), abruptio placentae
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 pregnancy
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Chronic hypertension is a relativelycommon 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

From the University of Cincinnati College ofSpinnato); Universidade Federal de Pernamband de Barros Santos), Universidade EstadualCecatti), Universidade Estadual Paulista, BotuFederal do Rio Grande do Sul, Hospital de ClíRamos), Brazil; RTI International, Research Tand the Eunice Kennedy Shriver National InstiBethesda, MD (Dr Moss).

Presented at the 25th Annual Meeting of the SoFeb. 1-6, 2010.

Received June 24, 2010; revised Aug. 16, 2010

Reprints: Baha M. Sibai, MD, 231 Albert Sabin [email protected].

This effort was supported by Grants nos. 1 U01Eunice Kennedy Shriver National Institute of Chiand Melinda Gates Foundation.

hildbearing at an older age and the epi-emic of obesity and type 2 diabetesorldwide, it is expected that the preva-

ence of chronic hypertension in preg-ancy will continue to increase.2

There are numerous studies describ-ing an increased rate of preeclampsia inwomen with chronic hypertension.1-8 Inddition, the findings of these studies

icine, Cincinnati, OH (Drs Sibai and, Hospital das Clínicas, Recife (Drs FreireCampinas, Campinas (Drs Pinto e Silva andu (Drs Rudge and Costa), and Universidadeas, Porto Alegre (Drs Martins-Costa andngle Park, NC (Dr Koch and Ms Moore);e of Child Health and Human Development,

y for Maternal-Fetal Medicine, San Diego, CA,

cepted Nov. 5, 2010.

, Cincinnati, OH 45267-0526.

40565 and U01 HD44036 cosponsored by theealth and Human Development and the Bill

g.2010.11.027

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mphasize that the development of su-erimposed preeclampsia is associatedith high rates of adverse pregnancyutcomes.1-8 In women without chronic

hypertension, the risk of preeclampsia isincreased with a history of preeclampsia,advanced maternal age, and increasedBMI,9 whereas it is reduced in those whosmoke 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 andhere are no data evaluating the impactf prior preeclampsia on adverse preg-ancy outcome in women with chronicypertension.We performed a secondary analysis of

69 women with chronic hypertensionnrolled as part of a trial of antioxidantso prevent preeclampsia.11 The primary

outcome for this analysis, the develop-ment of superimposed preeclampsia,

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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.

MATERIALS AND METHODSThe multicenter clinical trial was con-ducted as a protocol within the NationalInstitute of Child Health and HumanDevelopment (NICHD) Global Networkfor Women’s and Children’s Health Re-earch.11 The primary clinical centerRecife) and 3 additional clinical sitesCampinas, Botucatu, and Porto Alegre)re major teaching hospitals that serve a

FIGUREFlow chart for enrolled patients

n

Prior PE

n = 104

Vitamins C & E

(n = 49)

Placebo (n = 55)

Delivery ≥20 wks

n = 103

Completed fo

n = 36

Enrolled with chro

n = 3

Sibai. Impact of prior preeclampsia in chronic hypertension. A

rimarily urban low-income population i

1.e2 American Journal of Obstetrics & Gynecology

n Brazil. The study protocol was ap-roved by the NICHD and the institu-ional review boards at the University ofincinnati, each participating site, and

he data coordinating center.

SubjectsWe enrolled women seeking prenatalcare who were 120/7–196/7 weeks preg-

ant and diagnosed with nonproteinurichronic hypertension or a history of pre-clampsia in their most recent preg-ancy that progressed �20 weeks’ gesta-

ion. Chronic hypertension was defineds the presence of hypertension prior toregnancy or �20 weeks’ gestation. Foromen receiving antihypertensive med-

17 withdrew or lost to follow-up

No prior PE

n = 265

Vitamins C & E

(n = 136)

Placebo (n = 129)

Delivery ≥20 wks

n = 258

w-up

hypertension

Obstet Gynecol 2010.

cations at time of enrollment, the pres- o

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nce of sustained hypertension �20eeks’ gestation was not mandated. A di-

gnosis of prior preeclampsia was basedn review of the medical record for therevious pregnancy by the researcheam. In the absence of medical records,he diagnosis was according to the bestudgment of the research team. This re-uired that the team confirm that theatients’ reported events of their preg-ancies are highly consistent with a diag-osis of prior preeclampsia. Exclusionriteria were planned delivery elsewhere,ultifetal gestation, allergy to vitamin C

r vitamin E, requirement for aspirin ornticoagulant medication, 24-hour uri-ary protein �300 mg, prepregnancyiabetes mellitus, known fetal anomaly

ncompatible with life, or prior partici-ation 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 ofascorbic 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 containedexcipients only and were externally iden-tical to the active drug. Participants wereinstructed to ingest 2 gel caps daily fromenrollment until delivery or until the di-agnosis of preeclampsia. Study partici-pants were discouraged from the use ofantioxidant vitamins, calcium supple-ments, and chronic use of aspirin. Thewomen were followed up at routine pre-natal visits, typically every 4 weeks until26-28 weeks of gestation, every 2-3 weeksuntil 36 weeks of gestation, and thenweekly until delivery or the onset ofpreeclampsia.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-

ocytopenia (platelet count �100 �03/mm3), elevated liver enzymes (as-artate aminotransferase or alanine ami-otransferase �70 IU/L), or pulmonarydema. Women were followed uphrough the 14th day postpartum for the

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In this analysis we compared the ratesof superimposed preeclampsia and otheradverse outcomes such as perinataldeaths, abruptio placentae, preterm de-livery at �37 weeks and �34 weeks,small for gestational age (SGA), and neo-natal respiratory distress syndrome, be-tween women with and without a his-tory of preeclampsia. We also analyzedother known risk factors that mayinfluence 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 virtuallyidentical 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, our sample size had a power of 61%to detect a difference in the rate of super-imposed preeclampsia. Statistical com-parisons were stratified by site usingCochran-Mantel-Haenszel general asso-ciation �2 statistics13 for categorical vari-ables and analysis of variance for contin-uous variables. Analyses that adjustedfor additional covariates used logistic re-gression models.14 Data were analyzedusing software (SAS/STAT, version9.1.3; SAS Institute Inc, 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 � �

.05 without adjustment for multiple
omparisons. s
RESULTS

Subjects were enrolled in the antioxidanttrial from July 2, 2003, through May 15,2006. Of the 739 women enrolled, 369had chronic hypertension; 104 had a his-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 the

emographics and clinical characteris-ics of the 369 subjects according to pres-nce or absence of history of preeclamp-

TABLE 1Baseline characteristics by history

Prior

Characteristic Yes,

Maternal age at enrollment, ya 30.6..........................................................................................................

�35 72 (..........................................................................................................

�35 32 (...................................................................................................................

Prepregnancy BMI, kg/M2a 29.8..........................................................................................................

�25 27 (..........................................................................................................

25-29 33 (..........................................................................................................

�30 41 (...................................................................................................................

GA at enrollment, wka 15.4...................................................................................................................

Primigravida 0 (...................................................................................................................

SBP at enrollment, mm Hga 126.6..........................................................................................................

�130 53 (..........................................................................................................

130-140 17 (..........................................................................................................

�140 34 (...................................................................................................................

DBP at enrollment, mm Hga 79.8..........................................................................................................

�80 37 (..........................................................................................................

80-90 33 (..........................................................................................................

�90 34 (...................................................................................................................

Duration of hypertension, ya 4.8...................................................................................................................

Antihypertensive medicationsb 60 (...................................................................................................................

Smoking at enrollment 7 (...................................................................................................................

Smoking during pregnancyc 13 (...................................................................................................................

BMI, body mass index; DBP, diastolic blood pressure; GA, gesa Values are mean � SD; b At onset of pregnancy; c As asses

Sibai. Impact of prior preeclampsia in chronic hypertensio

ia. There were no statistically significant e

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ifferences between the 2 groups regard-ng any of the variables studied.

After enrollment, 65 (17.6%) devel-ped superimposed preeclampsia. Tableshows the association of some clinical

haracteristics with the occurrence of su-erimposed preeclampsia. Patients withuperimposed preeclampsia were moreikely to have higher systolic and dia-tolic blood pressures at enrollment, asompared to those without superim-osed preeclampsia. In contrast, the ratef superimposed preeclampsia was notffected by maternal age, BMI, or smok-ng status during pregnancy.

Table 3 compares pregnancy outcomeetween those with and without prior pre-clampsia. The rates of superimposed pre-

preeclampsia

eclampsia

) (n � 104) No, n (%) (n � 265)

6.3 30.7 � 6.3..................................................................................................................

2) 182 (68.7)..................................................................................................................

8) 83 (31.3)..................................................................................................................

7.7 30.9 � 7.4..................................................................................................................

7) 63 (23.9)..................................................................................................................

7) 64 (24.2)..................................................................................................................

6) 137 (51.9)..................................................................................................................

2.5 15.7 � 2.7..................................................................................................................

) 68 (25.7)..................................................................................................................

14.9 129.9 � 16.5..................................................................................................................

0) 102 (38.5)..................................................................................................................

3) 64 (24.2)..................................................................................................................

7) 99 (37.4)..................................................................................................................

13.8 81.2 � 12.8..................................................................................................................

6) 76 (28.7)..................................................................................................................

7) 95 (35.8)..................................................................................................................

7) 94 (35.5)..................................................................................................................

4.4 4.5 � 4.8..................................................................................................................

7) 134 (50.6)..................................................................................................................

) 24 (9.1)..................................................................................................................

5) 39 (14.7)..................................................................................................................

nal age; SBP, systolic blood pressure.

at enrollment.

m J Obstet Gynecol 2010.

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�.........

69..........

30..........

�.........

26..........

32..........

40..........

�.........

0.0.........

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16..........

32..........

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31..........

32..........

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clampsia were not different between the 2


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groups. In addition, there were no signifi-cant differences between groups in allother adverse pregnancy outcomes exceptfor the rate of preterm delivery at �37

eeks, which was higher in the previousreeclampsia group (36.9% vs 27.1%; ad-

usted risk ratio [aRR], 1.46; 95% confi-ence interval [CI], 1.05–2.03; P � .032).he difference in preterm delivery wasainly due to difference in delivery at

40/6–366/7 weeks (30.9% vs 18.3% of on-going pregnancies at 34 weeks; aRR, 1.95;95% CI, 1.26–3.04; P � .0033). These dif-ferences remained significant after exclud-ing primigravidas from the group withoutprior preeclampsia. After adjusting for siteand prepregnancy BMI (quadratic) usinglogistic regression the P value for all sub-

TABLE 2Factors associated with developmepreeclampsia in chronic hypertens

Super

CharacteristicYes, n(n � 6

Maternal age at enrollment, yb 30.5..........................................................................................................

�35 48 (7..........................................................................................................

�35 17 (2...................................................................................................................

Prior preeclampsiac 18 (2...................................................................................................................

GA at enrollment, wkb 15.3...................................................................................................................

Prepregnancy BMI, kg/M2b 30.7..........................................................................................................

�25 17 (2..........................................................................................................

25-29 16 (2..........................................................................................................

�30 32 (4...................................................................................................................

SBP at enrollment, mm Hgb 132.2..........................................................................................................

�130 20 (3..........................................................................................................

130-140 15 (2..........................................................................................................

�140 30 (4...................................................................................................................

DBP at enrollment, mm Hgb 84.9..........................................................................................................

�80 9 (1..........................................................................................................

80-90 24 (3..........................................................................................................

�90 32 (4...................................................................................................................

Smoking at enrollment 6 (9...................................................................................................................

Smoking during pregnancyd 8 (1...................................................................................................................

BMI, body mass index; DBP, diastolic blood pressure; GA, gesa Cochran-Mantel-Haenszel method or analysis of variance, a

previous pregnancy progressing to at least 20 weeks of ges


ects was .070, but the difference remained


significant among women with ongoingpregnancies at 34 weeks (P � .012).

COMMENTThe principal findings of the study are: (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 thosewithout such a history (17.7%); (3) the rateof superimposed preeclampsia was depen-dent on maternal systolic and diastolicblood pressure values �20 weeks’ gesta-tion, but not on maternal age, BMI, orsmoking status during pregnancy; and (4)women with prior preeclampsia had a sig-nificantly higher rate of preterm delivery at

of superimposedduring pregnancy

osed preeclampsia

) No, n (%)(n � 304) P valuea

.7 30.8 � 6.4 .92..................................................................................................................

) 206 (67.8) .38..................................................................................................................

) 98 (32.2)..................................................................................................................

) 86 (28.3) .34..................................................................................................................

.6 15.7 � 2.7 .54..................................................................................................................

.2 30.6 � 7.6 .67..................................................................................................................

) 73 (24.3) .61..................................................................................................................

) 81 (27.0)..................................................................................................................

) 146 (48.6)..................................................................................................................

3.0 128.3 � 16.7 .035..................................................................................................................

) 135 (44.4) .0095..................................................................................................................

) 66 (21.7)..................................................................................................................

) 103 (33.9)..................................................................................................................

0.1 79.9 � 13.4 �.0011..................................................................................................................

) 104 (34.2) �.0001..................................................................................................................

) 104 (34.2)..................................................................................................................

) 96 (31.6)..................................................................................................................

25 (8.2) .90..................................................................................................................

) 44 (14.5) .62..................................................................................................................

nal age; SBP, systolic blood pressure.

ing for study site; b Values are mean � SD; c In most recent; d As assessed at enrollment.


�37 weeks’ gestation (aRR, 1.46; 95% CI,

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1.05–2.03), but no significant difference inrates of perinatal deaths, abruptio placen-tae, SGA infants, or delivery at �34 weeksas compared to those without prior super-imposed preeclampsia.

The overall rate of superimposed pre-eclampsia (17.6%) in this study is similarto that reported by 5 previous observa-tional studies from Canada (21%),3 New

ealand (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-ated with increased risk of superimposedpreeclampsia which, is inconsistent withthe results of 2 large observational stud-ies.7,8 The study by Sibai et al7 reportedthat women with prior preeclampsia hada 1.6-fold (95% CI, 1.1–2.3) higher rateof superimposed preeclampsia thanthose without this history, although thisstudy included women with renal diseaseand did not report data on BMI. Both ofthese latter factors could have affectedthe rate of superimposed preeclampsia.In addition, the study by Chappell et al8

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 arteryDoppler at 18-20 weeks, all of whichcould have influenced their results.However, our study had only 61% powerto detect differences in rate of superim-posed preeclampsia between groups.

It is well established that advanced ma-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 find

nly 2 reports7,8 that examined the rela-tionship between advanced maternal ageand 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 1eport that examined the relationshipetween smoking during pregnancy andisk of preeclampsia in chronic hyper-ension.8 Chappell et al8 found that

smoking is an independent risk factor for

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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 specificallydesigned to answer this question areneeded.

Why might advanced maternal age,increased BMI, a history of preeclamp-sia, and smoking during pregnancy notbe associated with risk of preeclampsia inwomen with chronic hypertension? 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 association

etween increased BMI and preeclamp-ia in normotensive women may be dueo insulin resistance in such women.9 Its possible that in women with chronicypertension (a state of preexisting mi-rovascular disease and endothelial dys-unction) the addition of insulin resis-ance will have minimal impact on theathophysiologic abnormalities leadingo preeclampsia.

Our study is the first to report on the

TABLE 3Pregnancy outcome in those with a

Pri

Outcome Yes

Superimposed preeclampsia 18...................................................................................................................

Abruptio placentae 1...................................................................................................................

Perinatal deaths 7...................................................................................................................

Preterm delivery..........................................................................................................

�37 wk 38..........................................................................................................

34-36 wk 29/..........................................................................................................

�34 wk 9...................................................................................................................

Small for gestational age 19...................................................................................................................

Respiratory distress syndromee 14...................................................................................................................

CI, confidence interval.a In most recent prior pregnancy progressing to at least 20 we

study site; d Of ongoing pregnancies at 34 weeks of gestatio


mpact of a history of preeclampsia on ad- t

erse pregnancy outcomes in women withhronic hypertension. We found thatomen who had prior preeclampsia hado increase in major adverse pregnancyutcomes except for higher rates of pre-erm delivery at �37 weeks’ gestationmainly late preterm births). This higherate occurred in the absence of increasedate of superimposed preeclampsia inuch women, suggesting that prior pre-clampsia is an independent risk factoror late preterm delivery in women withhronic hypertension. This increased rateay also be related to the fact that physi-

ians were more aggressive in deliveringhe patients because of exacerbated hyper-ension because of concern that they maye developing preeclampsia.Our study has a few limitations. We

ncluded patients who received antioxi-ants or placebo from the original trial;owever, we found no differences in theates of superimposed preeclampsia orther adverse outcomes between theroups in the trial, and analyses of theooled data in this report gave nearly

dentical results when adjusted for treat-ent arm. Therefore, it is unlikely that

his strategy could have influenced ouresults. Another limitation relates to theack of statistical differences in rates ofbruptio placentae, SGA infants, perina-

without prior preeclampsia

reeclampsiaa

(%) (n � 104) No, n (%) (n � 265)

.3) 47 (17.7).........................................................................................................................

) 8 (3.1).........................................................................................................................

) 23 (8.7).........................................................................................................................

.........................................................................................................................

.9) 70 (27.1).........................................................................................................................

(30.9)d 42/237 (18.3)d.........................................................................................................................

) 28 (10.9).........................................................................................................................

.4) 34 (14.3).........................................................................................................................

.6) 32 (12.4).........................................................................................................................

f gestation; b Cochran-Mantel-Haenszel method, adjusting for stuDefinite or suspected.


al deaths, and delivery at �34 weeks’

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estation between those with and with-ut prior preeclampsia. This may be dueo inadequate sample size, however, theates of these outcomes were all lower inhe prior preeclampsia group. Also, foriagnosis of SGA, we used standards

rom US populations that might notpply to Brazilian populations. In addi-ion, in women with prior delivery, weid not collect data regarding previousreterm delivery. Such history mightave explained the increased rate of pre-erm delivery in women with a historyf preeclampsia. Finally, this is a second-ry analysis, performed without adjust-ent for multiple comparisons, and as

uch, the results should be consideredxploratory.

In summary, we did not find that ad-anced maternal age, increased BMI,rior preeclampsia, and smoking duringregnancy were associated with the de-elopment of superimposed preeclamp-ia in women with chronic hypertension.n addition, prior preeclampsia may ben independent risk factor for late pre-erm delivery in women with chronicypertension. f

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Adjusted riskratio (95% CI)b P valueb

1.28 (0.78–2.11) .34..................................................................................................................

0.44 (0.01–3.77)c .68c

..................................................................................................................

0.79 (0.33–1.88) .59..................................................................................................................

..................................................................................................................

1.46 (1.05–2.03) .032..................................................................................................................

1.95 (1.26–3.04) .0033..................................................................................................................

0.79 (0.39–1.60) .52..................................................................................................................

1.31 (0.76–2.25) .33..................................................................................................................

1.11 (0.64–1.93) .72..................................................................................................................

te; c Exact Cochran-Mantel-Haenszel procedure, adjusting for

nd

or p

, n

(17......... .........

(1.0......... .........

(6.7......... .........

......... .........

(36......... .........

94......... .........

(8.7......... .........

(18......... .........

(13......... .........

eks o dy sin; e

n. A

nancy. Obstet Gynecol 2002;100:369-77.



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modified by ischemic placental disease? Am JObstet Gynecol 2007;197:273.e1-7.7. Sibai BM, Lindheimer M, Hauth J, et al, forthe National Institute of Child Health and HumanDevelopment Network of Maternal-Fetal Medi-cine Units. Risk factors for preeclampsia,abruption placentae, and adverse neonatal out-comes among women with chronic hyperten-sion. N Engl J Med 1998;339:667-71.8. Chappell LC, Enye S, Seed P, Briley AL, Pos-ton L, Shennan AH. Adverse perinatal out-comes and risk factors for preeclampsia inwomen with chronic hypertension: a prospec-tive study. Hypertension 2008;51:1-8.9. Barton JR, Sibai BM. Prediction and preven-tion of recurrent preeclampsia. Obstet Gynecol
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The impact of prior preeclampsia on the risk of superimposed preeclampsia and other adverse...

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