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Brenda Eskenazi, PhD; Laura Fenster, MPH, PhD;
Stephen Sidney, MD, MPH
risk factors for preeclampsia remain un¬ clear, however, and thus preeclampsia has been called a "disease of theories."6 With the exception of nulliparity (ap¬ proximately 75% of women with pre¬ eclampsia are nulliparous)7 and a previ¬ ous history of preeclampsia in multípa¬ ras,8 few other risk factors are univer¬ it has been suggested that the risk fac¬ tors for and causes of preeclampsia in nulliparas and multíparas may be differ¬ ent,9"" few have examined these differences. Some researchers have speculated that preeclampsia is a disease of the upper class,12 others more recently be¬ lieve it is a disease of the impover¬ ished,613 and still others think all social classes are at equal risk.14 It has been difficult to determine the exact role of socioeconomic status, since most stud¬ ies have not separated out the contribu¬ tions of socioeconomic status-related variables such as race, employment sta¬ tus, and nutritional status. Nor have these studies controlled for or excluded women with preexisting diseases that may be related to preeclampsia, such as essential hypertension, cardiovascular disease, and diabetes, and that may be more prevalent in groups with lower socioeconomic status. Black women have been observed to be at greater risk for developing pre¬ eclampsia. Chesley et al9 caution that this increased risk of preeclampsia may be due to the higher prevalence of pre¬ existing hypertension in black women. Nevertheless, the Collaborative Peri¬ natal Project15 found a higher incidence of both preeclampsia and eclampsia in black women compared with white women whether or not they had preex¬ isting hypertensive disease. Extremes of age are also postulated as risks for preeclampsia16; however, the effect of age may be confounded by other factors. For example, younger women are more likely to be primigrávi¬ das, and older women are more likely to have essential hypertension.'
Setting.\p=m-\Womenwho gave birth at Northern California Kaiser Permanente Medical Centers in 1984 and 1985. Participants.\p=m-\Preeclampticcases (n =139) were determined from discharge diagnosis of severe preeclampsia and by confirmation of blood pressures and proteinuria from medical records. Controls (n 132) were randomly selected women who had no discharge diagnosis of any hypertensive disorder of pregnancy and who had no evidence of hypertension or proteinuria from medical record review. Main Variables Examined.\p=m-\Medicalrecords were abstracted for information regarding maternal age, race, previous pregnancy history, family medical history, socioeconomic status, employment during pregnancy, body mass, and smoking and alcohol consumption. Results.\p=m-\Multiplelogistic regression analyses confirmed that case patients were more likely than control patients to be nulliparous (adjusted odds ratio [OR], 5.4; 95% confidence interval [CI], 2.8 to 10.3) and that preeclampsia in a previous pregnancy greatly increased the risk in a subsequent one (adjusted OR, 10.8; 95% CI, 1.2 to 29.1). However, regardless of parity, preeclamptic women were also more likely to be of high body mass (adjusted OR, 2.7; 95% CI, 1.2 to 6.2), to work during pregnancy (adjusted OR, 2.1; 95% CI, 1.1 to 4.4), and to have a
Objective.\p=m-\Todetermine, in a multivariate analysis, risk factors for preeclampsia that could be observed early in pregnancy and to establish whether these risk factors are different for nulliparas and multiparas. Design.\p=m-\Acase-control study of preeclampsia.
sally agreed on. Furthermore, although
family history of hypertension (adjusted OR, 1.7; 95% CI, 0.92 to 3.2). Having a previous history of a spontaneous abortion was protective but only in multiparous women (adjusted OR for multiparas, 0.09; 95% CI, 0.02 to 0.48). In contrast, being black was a significant risk for preeclampsia but only in nulliparous women (adjusted OR for nulliparas, 12.3; 95% CI, 1.6 to 100.8). Conclusions.\p=m-\Thereare a number of risk factors for preeclampsia that may be determined early in a woman's pregnancy. Multiparas and nulliparas share certain risk factors but not others. A cohort investigation is needed to determine the ability of these risk factors to predict who develops preeclampsia.
PREECLAMPSIA, a hypertensive dis¬ order of pregnancy, is a major contribu¬ tor to maternal mortality, premature birth, intrauterine growth retardation,
From the Programs of Maternal and Child Health and Epidemiology and The Northern California Occupational Health Center, School of Public Health, University of California, Berkeley (Dr Eskenazi); Reproductive Epidemiology Program, California Department of Health Services, Berkeley (Dr Fenster); and Division of Re-
and perinatal mortality. Low-dose aspi¬ rin has been found to be effective in preventing its development.1"1 Howev¬ er, the use of aspirin during pregnancy may not be without risk.5 Hence, it is
search, Kaiser Permanente Medical Center, Oakland, Calif (Dr Sidney). Reprint requests to 312 Earl Warren Hall, School of Public Health, University of California, Berkeley, CA
94720 (Dr Eskenazi).
important to identify women who are likely to be at high risk for developing preeclampsia and to identify them early in pregnancy so that they can benefit
from intervention. The
Downloaded From: http://jama.jamanetwork.com/ on 05/16/2012
urinary protein. sion. Without baseline blood pressure: MAP >105 Hg. or 2.21. and the woman and her partner's occupation. race.—Potential con¬ trols (n 260) were randomly selected from the discharge data tape from those women who had not received a dis¬ charge diagnosis of any hypertensive disorder of pregnancy (International Classification of Diseases. another 34 did not meet the urinary pro¬ tein criteria. with main effects forced into the model. and medical history shown in Table 1. the dis¬ charge diagnoses. especially if it ends later in gestation. In addition. 76 Job information was obtained from the prenatal history form usually com¬ pleted by the clinician at the first prena¬ tal visit. For example. To include as many wom¬ en as possible in the multivariate mod¬ els. A total of 139 cases remained (105 nulliparas.The relationship of body habitus and preeclampsia has been debated for al¬ most 200 years. and 14 others had a history of either diabetes or chronic hyperten¬ sion. history of toxemia (any pregnancy record prior to the in¬ dex pregnancy).22 Its effect is dose related and independent of body mass. information about the length of employment during pregnancy was not consistently provided on the medical chart and therefore was not abstracted.1819 Again. Job title and industry were coded using the Bureau of the Census codes. Control Group A. codes 642.10) by either the stepwise or the backward regression procedures were entered together as the main effects in the final model. race (any time). leaving a total of 132 controls (52 nulliparas. family history of hy¬ pertension (up to a year prior to the pregnancy). dummy variables for missing information were constructed for each of those variables with information missing on more than 35 women (ie. " Downloaded From: http://jama. urinary tract infection. Of the 260 eligible controls. or change in MAPt 220 mm Urinary protein (after 20 wks' gestation) urinary protein dipstick measurements} of 1 Hg 'Including during labor.10 on the univariate analysis were entered into both a stepwise and a backward multiple logistic regression model.jamanetwork.9). seizures). <300 mg of protein in all 24-h urine collections C No medical history of diabetes or chronic hypertension 1. discharge diagnoses of preeclampsia. Women who gave birth to twins were excluded from all multivari¬ ate modeling. Urinary protein 1. Ninth Revi¬ sion. and all measured blood pressures.18. Using a stepwise procedure. past and present medical and pregnancy history (diabetes. 2300 mg of protein in a 24-h urine collection C No history of diabetes or chronic hypertension II. tMAP indicates mean arterial pressure.17 whereas others claimed heavyset women are more vulnera¬ ble. Blood pressure 1. All dipstick measurements* <1 + after 20 wks. Blood pressure (at least 2 readings fulfilling criteria after 20 wks' gestation*) 1 With a recorded baseline blood pressure (before 20 wks' gestation): from baseline. weight were per¬ gain). Controls were also required to meet the blood pres¬ sure.26 The final model was rerun for those who had blood pres¬ sure measurements before 20 weeks' gestation. Case Selection. body mass. Information was obtained pri¬ marily from the prenatal record forms. Those variables that were debated in the literature as important risk factors for preeclampsia or that produced a point estimate at a value <. and marital status (up to 3 months prior to the pregnancy). All statistical analyses formed using SAS 5. life-style habits (alcohol and tobacco). and the criteria for cases and controls. or 2. Variables that were selected (P<. religion. Some authors have con¬ Table 1. cases had to meet the criteria for blood pressure.0 to 642. We focus on those potential risk factors that can be determined early in pregnancy be¬ fore the usual time of diagnosis (after 28 weeks' gestation). Without baseline blood pressure: all blood pressures after 20 wks <MAP of 105 mm Hg B. urinary protein con¬ centrations. 34 multíparas). the medical chart for a defined time period preceding the pregnancy was searched. height and prepregnancy weight. We also determine whether these risk factors for pre¬ eclampsia differ in multiparous and in cluded that frail women are more sus¬ ceptible. 34 others failed to meet the urinary protein criteria. and medical his¬ tory criteria listed in Table 1. including per¬ tinent family medical history. Of the 263 eligible case patients who received did not meet the blood pressure criteria. toxemia. if certain information was not available in the pregnancy rec¬ ord. This information included height (recorded at any time after the age of 18 years). Ninth Revi¬ sion. With a baseline blood pressure: a change from baseline In MAP <20 mm Hg in any reading*. the significant interaction terms were de¬ termined (P<. a previously termi¬ nated pregnancy. Information ab¬ stracted included such sociodemographic characteristics as maternal age. prepregnancy weight (up to 3 months preceding the pregnan¬ cy). Two + or 1 B. urinary protein. mm Group reading of 22 + . 80 multíparas). + 2 (diastolic)]/3. cigarette smoking has been consistently demonstrated to pro¬ tect women against preeclampsia. Control Selection.22 Also. MAP [systolic = JNo more than one of these can occur during labor.—Cases were select¬ ed from the 263 women who received a discharge diagnosis of severe pre¬ women Procedure Information was abstracted from medical charts by a trained abstractor using a standard form.5 and 642.—Criteria for Inclusion In the Case and in the Control I Case Groups a protection against preeclampsia in a subsequent pregnancy. Chesley7 suggests that the association with heavier weight is an artifact of including women with essen¬ tial hypertension in studies of pre¬ eclampsia. Nevertheless. METHODS Participants Cases and controls were drawn from who delivered live births and stillbirths in 1984 and 1985 at the 10 hospitals that constitute Kaiser Per¬ manente of Northern California. chronic hyperten¬ heart disease. the WHO Study Group20 concludes that high prepregnancy body mass increases a wom¬ an's risk for preeclampsia.6). and 2. and one additional woman had a history of chronic hypertension. However.com/ on 05/16/2012 . 2. The control group was frequency matched to the = eclampsia or eclampsia (International Classification of Diseases. and weights during preg¬ nancy.10). In addi¬ tion.24 Social class (working class and non-working class or professional/manager) was esti¬ mated from the occupation of the wom¬ an and from her partner based on a scheme developed by Krieger. case group on the year of delivery and the Kaiser Permanente hospital where the delivery occurred. crude odds ra¬ tios (ORs) and 95% confidence intervals (CIs) were calculated. codes 642. Some attributes seem to protect women from developing preeclampsia. The abstractor was blinded to our hypotheses. which are similar across the Kaiser sys¬ tem. all one-way interaction terms with parity were in¬ cluded to determine if risk factors dif¬ fered between nulliparas and multípa¬ ras. nulliparous women.26 For comparison of cases and controls on categorical variables. may provide some A. al¬ cohol consumption. 93 failed to meet the blood pressure criteria.23 The present case-control study exam¬ ines the interrelationship of these po¬ tential risk factors as well as others in a multivariate statistical model. Confidence intervals for interaction terms were determined by the Wald method. marital status.
40 Age.00 0.4 26.0 15.00 0.7 4. Similarly.8 52 80 39.00 0.95 1.75 1.2 35 31.8 56.72 1 72-30. includes those women who had given birth previously. fOnly includes those women who had been pregnant previously.8 27.30-0. A larger proportion of case patients were of higher body mass and a smaller percentage were of lower body mass. — Pregnancy and Medical History of Preeclamptic Cases and Controls* Cases No.0 13.3 0.00 1. 35.1 2. kg <5. whereas none of the controls gave birth to twins.62 Table 3.14-5. % Controls No.03-2.5 69.39.6 13. therapeutic abortion.6 25.85 1.3 4.2 4.7 75 16 55 70. y <20 -35 Marital status Married or living with Not living as married Race White 13. 0.57 1.7 kg more prior to pregnancy (62.8 74.0to4.1. case patients were almost five times more likely than control pa¬ tients to be nulliparous and twice as likely to be primigravid.29-1.8 1.18-3.82 Employed during No Yes Woman's pregnancy 27 103 72 47 36.00 Gravidity 1 Previous No 60 79 history of SABt 63 79.4 -5.8) Weight gain by week 20.6 95.7 1.5 24.83 0.2 56.4 62. Six of the case pregnancies ended in twin births (two for multípa¬ ras.09). on average.87 jonly *SAB indicates spontaneous abortion. P= .85 Hispanic Asian Other Black 18 22 22 1.24-0.5 87 39 1.9)_ Mid (-18.8 20.9 73.95%CI.55 0.95 Previous history of TABt No Yes Week at 1 st s13 35 44 443 55.7 8.08 95% Confidence Interval 0. However. 14).64 1. renal disease. kg/m2 High (>25.jamanetwork.00 2. and to be employed.19 1 00 282-8.3 34 62 Yes 0. Case patients were more likely than control patients to be living apart from their partner.5).3 2. to be black.00 2.6 50.0 1.00 1.8 79. case patients were less likely to drink alco¬ hol.com/ on 05/16/2012 . As expected.09).00 1.2 69. 29% of the part¬ ners of both case and control patients had professional or managerial jobs.5 43. Although the pregnancies of case pa¬ tients ended approximately 4 weeks earlier than those of control patients (mean.4 17.6 82 60 22 1.00 5. however.4 60.12 0.45-1. a similar pro¬ portion in both groups had professional or managerial jobs (30% of cases vs 27% of controls).9 53.20) and more likely to be of high Controls No.4 103 82.47-1.85 49. About 65% of case patients and 48% of the control group neither drank alcohol nor smoked. but half the proportion of case patients in comparison with control pa¬ tients had a history of spontaneous abortion. Crude Odds Ratio 95% Confidence Interval Parity 0 Previous Pregnancy History 105 34 75. The case and control groups were comparable in their history of heart dis¬ ease.0 31. four for nulliparas).34 56 Habits 0. 13. 19 108 Crude Odds Ratio 1.3 kg. more than twice the proportion of case pa¬ tients in comparison with control pa¬ tients had a history of therapeutic abor¬ tion. S25. 0.6 Characteristic No. Downloaded From: http://jama. 1.92-2.7 25 20.3 5. case patients were less likely to be of low body mass (OR.6 1. Case patients weighed.5 16. 2. 95% CI.00 0. case 32 46 73 67.0 kg.4 63.85 occupation Working class Non-working class 73. for women who worked.8 vs 14.7 36 1.97-3.4 96.8) 78 associated with preeclampsia.8 0.7 kg vs 60.6 85.81-4. and case patients were less likely to smoke than control patients.6 36 74 25.81 Limited 0. Case patients averaged 27 years of age and were.0 6.11 to 1.63 Smoked cigarettes No Yes Drank alcohol No Yes Previous No Yes No 123 13 90.2 65.RESULTS Table 2—Sociodemographic Characteristics of Preeclamptic Cases and Controls Cases Sociodemographic Characteristics and Medical History Table 2 shows the demographic char¬ acteristics of cases and controls.00 2.24-1.48 63. Similarly.2 26.03 79.34 Low (<18.9 30.1 vs Singleton Twins 133 dispersion Prepregnancy Quetelet index.9. even among nonsmok¬ ers.92 1.5 15. Table 3 presents the pregnancy and medical history of cases and controls.16 0. and urinary tract pa¬ tients gained more weight on average during the course of their pregnancy (15.12-3.99 history of toxemia} Medical 29 8 History 74 77.03 Family history of hypertension Yes 57 43.3 75 69. Approximately 10% of the case pa¬ tients smoked during pregnancy.8 38. of infants bodymass(OR. P .9 20.9 1. 2. Smokers had lower body masses than nonsmokers and there were fewer smokers among the cases.1 14. and TAB.50 1. on average. This result is expected given the increase in edema = 39.9 1.25-3. with only about 20% consuming al¬ cohol during pregnancy.96 prenatal visit Present 102 37 Pregnancy 91 41 132 68.8 0.36 No.2 weeks). a year younger than control patients (P =. Among women who had been pregnant before.6 113 19 82 18 10 7.
One noteworthy exception is that more case patients than control pa¬ tients had family members with a histo¬ ry of chronic hypertension (OR. 10. As shown in Table 4.6to 49. none of the 11 women diagnosed as eclamptic had a previous history of sei¬ zures. and having high prepreg¬ nancy common Table 4—Multivariate Logistic Regression Model for Predicting Case-Control Status (n 235)* = Intervalf Nulliparous (1 ) vs Multiparous (0)_5J4_2. 2.infection. and we have includ¬ ed only women with evidence of both proteinuria and hypertension.7 0. low body mass is associated with a slightly reduced risk. Two control patients and one case pa¬ tient had gestational diabetes during the present pregnancy.8-10. For example. year of deliv¬ ery (1984 or 1985). maternal age. renal disease. 1. and working during pregnancy posed a risk.6. being black posed a substantial increased risk (OR. being nulliparous (OR. High body mass. having had a previous spontaneous abortion was highly procase probably underrepresented.8) remained strong.1 Worked during pregnancy (1) vs Unemployed (0) 2.4) and for being black in nulliparous women (OR.4 1.16) which was (1)vsNonblack(0)_2j>_0. history ofther¬ apeutic abortion. First. a similar finding was observed in a cohort study of women exposed to organic solvents. was doubtful and. 79% of whom worked Downloaded From: http://jama.1-4. Similarly. SAB indicates spontaneous abortion. For example. although women from a wide range of social classes use the Kaiser Perman¬ ente Medical Care Program for their health care. 10 criteria for inclusion in the model with the exception of low body mass (P= . and smoking was protective in both multiparous and nulliparous women. Chesley7 wrote that the increased susceptibility for preeclampsia of black women and of heavyset women. history of toxemia in a previous pregnancy. and smoking. there was limited dispersion when twin pregnancy was included. we found that being nul¬ liparous and having a previous history of preeclampsia greatly increased a woman's risk for preeclampsia.45). Klebanoff et al30 reported that the risk of preeclampsia was higher in a group of female residents (100% employed) than in a control group consisting of spouses of male residents.3 Black Variable Odds Ratio Adjusted 95% Confidence Body mass Low body mass (1) vs Medium (0)_043_0. in a separate analysis. 0. for preeclampsia (OR. parity.jamanetwork.18-1.7).09 0. Case patients were over five times (albeit nonsignificantly) more likely than control patients to have a history of seizures prior to pregnancy (OR.29 In that study. case patients were more likely to be black. Smoking tended to have a protective effect (OR.43). Preeclampsia in a previous preg¬ nancy produced a sixfold increased risk. Only two risk factors were found to operate differently in nulliparous and multiparous women (Table 5). Low mass was forced into this model to body mass (OR. working previous history of tective (OR. if found. does not appear to be related to socioeconomic status.2 Smoked (1)vs Not (0)_045_0.4).2-6. 95% CI. However.8 0. all wom¬ en with a history of essential hyperten¬ sion were excluded.6-100. family history of hypertension.20-3.28 Working during pregnancy has been implicated as a risk factor for pre¬ eclampsia in a variety of studies. heart disease. weight gain in the first 20 weeks of gestation.7).13-1. the multivariate models contained a sample of 235 women (115 cases and 120 controls).68 Adjusted Interval 1. 11. a diagnosis of preeclampsia in a previous pregnancy greatly increased the risk for being a body cases than in controls. Table 5—Variables Predicting Case-Control Status That Differ in Nulliparous and Multiparous Women 95% Confidence (n 235)* = Variable Race Black Black Odds Ratio* 12. week of gestation at first visit. For the most part. although not sig¬ nificantly. 0.1 1.2-29. a conclusion also drawn by the WHO Study Group.3). 5.2 Family history of hypertension (1 ) vs None (0) 0.5 nulliparas vs nonblack nulliparas multíparas vs nonblack multíparas History of SAB Nulliparas with SAB vs nulliparas without SAB_089_0. case patients did not differ from control patients in their family medical history.9 0. smoking during pregnancy.92-3.3 0.com/ on 05/16/2012 .1 History of preeclampsia (1 ) vs No history (0) *Twin pregnancies were excluded from model. working (OR.1). we found that the risk for high body mass (OR. because all twins occurred in the case group.8 1.13-3. was probably due to including women with essential hypertension. employment in either a work¬ increased women's risk relative to un¬ employed women. at least for nulliparous women. Second.09). body during pregnancy. 3. 12. including only women who had a clear increase in blood pressure during the course of pregnancy (ie.97-6.7) in ing-class or professional/managerial job were more patient (OR.1). COMMENT As expected.02-0 48 Multíparas with SAB vs multíparas without SAB ^Multiple logistic regression model controlling for the main effects of parity. This result. Howev¬ er. alcohol con¬ sumption during pregnancy. The interaction of body mass and smoking proved nonsig¬ nificant. Working during pregnancy more than doubled the risk for preeclampsia. marital status. Also.74 History of spontaneous abortion (1) vs No history 10. and history of sponta¬ neous abortion. preeclampsia.8). had a base¬ line blood pressure measurement be¬ fore 20 weeks). as not¬ ed by some authors. fAII variables listed met the P<. Among nulliparas but not multíparas. maternal history of hypertension. wom¬ en who worked longer into their preg¬ nancy (with solvents) were most at risk. in regard to other risk factors that continue to be debated. 0. however. race. the extremes of income are illustrate the dose-response relation¬ ship of case status with increased body mass. 0. family history of hypertension.13-0. Multivariate Analysis Variables (as categorized in Tables 2 and 3) entered into the multiple regres¬ sion models included race.31 0. there was no difference in the proportion of part¬ ners of case patients and control pa¬ tients who held working-class and professional/managerial jobs.4 forced in. among women who had been pregnant before. Howev¬ er. employment status. hav¬ ing a family history of hypertension (OR. It is unlikely that the increased risk associ¬ ated with being black in nulliparous women and with high body mass found in the present study can be explained by essential hypertension. and among multíparas but not nulliparas.20 and. approximately equal proportions of cases as controls had a positive family history for diabe¬ tes. we found that case patients were more likely to be heavier prior to pregnancy.4 High body mass (1) vs Medium (0)_2/7_1. we repeated the final regression model presented in Ta¬ ble 4. mass. 5. 2. Because of missing data. history of spontaneous abortion. 1. and seizures. prepreg¬ nancy body mass as measured by the Quetelet index (weight/height2).
22:63-68. Paul En¬ glish. 15. Alcohol. The slight increased risk of women under 21 years old observed on univariate analyses disappeared when parity was controlled for. 33.155:1011-1016. Dekker GA. Am J Obstet Gynecol. J Obstet Gynaecol Br Commonw. How¬ ever. Moreover. The frequency of kidney and urinary tract diseases in a defined population. et al. 11. In: Creasy RK. the re¬ gression models predicting risk of pre¬ eclampsia were identical for nulliparous and multiparous women. Outcome of pregnancy in a national sample of resident physicians. 1985. Marianne Sadler. Sadovsky E. Krieger N. Wahlen T. In addi¬ tion. Frusca T. Epidemiology.com/ on 05/16/2012 .14:177\x=req-\ 188. on average. Eklampsien i Danmark i Aarene Copenhagen. 1972. 1982. we found that being black posed a signif¬ icant increased risk in both nulliparous and multiparous women. 21. 1976. Social factors in obstetrics. Clin Obstet Gynecol. Prywes R. Am J Obstet Gynecol. 4. MD. Duffus and MacGillivray34 found that the perinatal death rate due to preeclampsia was higher among infants of smokers than of nonsmokers. 1986. 1986. Barron SL. We also thank Debra Patterson for her editorial comments. MD. Irva Hertz-Picciotto. Baird D. Resnick R. Irene Tekawa. Hypertensive diseases of pregnancy and parity. 1984. Uzan S. We did not demonstrate that age. 1955. the well-known risk of both of these agents to the fetus outweighs the slight benefit. 17. 34. An Introduction to the Practice of Midwifery. Pregnancy-related hypertension. Am J Obstet Gynecol.323:1040-1045. 1821. Chiang CL. and hypertension. Lehmann16 did not show a clear increase in the incidence of preeclamp¬ sia until after women reached the age of 45 years. Roberts JM. I: epidemiological studies of a total community. 35. Geneva. Holford T. Schiff E. Goldhaber MK. Davies AM. Klatsky AL.43:147-152. Weiskopf P. MPH. Donsimoni R. we included in our logistic model only those potential risk factors that could be known by the 20th week of gestation. Denmark: Busck. Bracken MB.during pregnancy. Philadelphia. 28. Women who work may et al31 found that increased leisure-time activity (of which working women pre¬ be more stressed and have different lev¬ els of physical activity than non working women. N Engl J Med. Siegelaub AB.52:183-185. 1989. Pa: WB Saunders Co. however. Gary Stew¬ art.124:446-456. 1968. MPH. Grady J. 1991. Am J Ind Med. perhaps because women with essential hypertension were excluded. Brisson J.321:351-356. 1989.4(suppl III):143-150. Pa: WB Saunders Co. 9.2:33-39. Sterk VV. Klatsky AL. 1990. 1980 Census 1961. Am J Epidemiol. cigarette smokers and light drinkers. Eskenazi B. New York. Nelson TR. 1982. than therapeutic abortions. Lancet. alcohol consumption was pro¬ tective.154:1044-1049. spontaneous abortion was significantly protective in both nulliparous and mul¬ tiparous women.159:1-5. Gregorini G. The effect of leisure time physical activity on the risk of preeclampsia and gestational hypertension. The incidence of preeclamptic toxaemia in smokers and nonsmokers. dex of Industries and Occupations. DrPH. Marcoux S. Golub M. N Engl J Med. 1968. Hopenhayn-Rich C. MPH. is a risk factor for preeclampsia. Pitfalls in diagnosis and management of preeclampsia. 30. eclampsia. 8. 13. for statistical consultation and ana¬ lyses and Robert Hosang. Cigarette smoking tended to protect against preeclampsia in this investiga¬ tion. Brisson J. Similarly. The relationship of eclampsia to the other toxemias of pregnancy. particularly women. Gordon M. as Chesley suggested. J Obstet Gynaecol Br Commonw. MPH. MD. on univariate analyses. Duffus GM. Annitto JE. 1933. The usefulness of low-dose aspirin therapy and other preventive measures depends on the clinician's ability to iden¬ tify women who are at high risk for preeclampsia early in their pregnancy. Exposure to organic solvents and hypertensive disorders of pregnancy. MacGillivray23 suggested 5. 1987. 29. J Epidemiol Community Health. Benigni A. World Health Organization Technical Report Series 758. 20. 1985. The differen¬ tial risk of these variables in the two groups may be related to the stringent criteria we used to define preeclamptic cases and controls. MPH. 1988. Palmgren B. Markovitz JW. Czaczkes JW. Proc R Soc Med. We did not have any patients above 41 years of age. Epidemiol Rev. 1989. Rhoads GG. et al. N Engl J Med. 12. Wallander B. ei¬ ther old or young. Fitzgibbon G. future investigations should include multíparas in studies of preeclampsia but examine their risks separately from those of primíparas.27:801-820. Rotmans P. Kidney Int. Cary. 1984:703-752. Barbara Abrams. Hooper K. Gleicher N. The increased risk at old¬ er age was not evident in this sample. Switzerland: World Health Organization. therefore. We also found that. further investigation is needed to determine the exact param¬ eters of work that might increase risk. The research was funded by a grant from the Kaiser Foundation Research Institute. MacGillivray I. This finding suggests that a history of spontaneous abortion may be protective and being black may be a risk in both nulliparous and multi¬ we to the = = parous women with less severe forms of preeclampsia than that used to define inclusion in this study. 1973. Fireman BH. Boler LR.130:950-957. J Epidemiol Community Health. Washington. 23. Maternal-Fetal Medicine. 1988. The fetal life table revisited: spontaneous abortion rates in three Kaiser Permanente cohorts. Toxemia of pregnancy in Jerusalem.1:1070-1074.321:357-362. Alcohol and hypertension. of Population: Alphabetical In- 4(12):60-68. Del Grando A. Lancet. Am J Obstet Gynecol. 1980. The use of aspirin to prevent pregnancy-induced hypertension and lower the ratio of thromoboxane A2 to prostacyclin in relatively high-risk pregnancies. it does not appear that any previ¬ ous pregnancy provides protection. Colau JC. 3. 1918-1927.32. when applied the final multivariate model original sample of women who received a discharge diagnosis of severe preeclampsia or eclampsia (n 263) and the random sample of controls (n 260). Fabia J. Friedman GD.61:120-124.jamanetwork. Peleg E. Siegelaub AB. 6. Wallenburg HCS. Acta Obstet Gynecol Scand. 22. Having a previous history of sponta¬ neous abortion protected against pre¬ eclampsia in multiparous women. Downloaded From: http://jama.62:48-66. Friedman GD. 1922. 10. The epidemiology of human pregnancy.1:1-3. Toxemia and cigarette smoking during pregnancy.6:253-266. The remote prognosis of eclamptic women: sixth periodic report. 32. 2. Version 5. PhD. Hertz-Piccioto I. Effect of low-dose aspirin on fetal and maternal generation of thromboxane by platelets in women at risk for pregnancy-induced hypertension. These risk factors should be examined in a cohort study to determine the model's ability to predict who devel¬ ops preeclampsia. Hypertension in pregnancy and its consequences. Isr J Med Sci. New York. 1978. Beauphils M. 31.12:108\x=req-\ 148. MPH. Lancet.1:994-995. and James Roberts. Norusis M. Goldenberg M. 26. Hypertension. tobacco. A study by Marcoux sumably have less) protected against preeclampsia.38 Al¬ though tobacco and alcohol consumption may tend to protect against preeclamp¬ sia. Women and social class. Klebanoff M. An Introduction to Stochastic Processes and Their Applications. J Obstet Gynaecol Br Commonw. Niswander KR. Hiatt RA. Sibai BM. 19.1:840-842. SAS User's Guide. 1990. Cosgrove RA. Risk factors differ somewhat for nulliparas and multípa¬ ras. 1970. 25. for their review of and comments on the research. DC: US Bureau of the Census. Philadelphia. Shiono PH. El-Nazer A.68:557-569. NY: James Oram. We also acknowledge Linda Grand. We gratefully acknowledge the assistance of Bet¬ ty Wong and William Frank in abstracting and coding the data. Sibai BM. History and epidemiology of preeclampsia-eclampsia. 1991. 14. 1986. 24. in that having a previous therapeutic abortion did not protect against pre¬ that previous pregnancy. The Collaborative Perinatal Study of the National Institute of Neurological Diseases and Stroke: The Women and Their Pregnancies. eds. 1980. In a recent study of Kaiser patients. In: Perspectives in Hypertension 1982. Marcoux S.29:402-415. Chesley LC. A clinical study of preeclampsia. NC: SAS Institute. 27. 16. Severe 1989. Denman T. The Hypertensive Disorders of Pregnancy: Report of a WHO Study Group. References 1. 1949. Compr Ther.36 Except for being black and having a history of spontaneous abortion. Gonzalez-Ruiz A. MacGillivray I. Lancet. Prevention of pre-eclampsia by early antiplatelet therapy. The effect of cigarette smoking on the risk of preeclampsia and gestational hypertension. Lehmann K.45:35-42. NY: Robert E Krieger Publishing Co. In stud¬ ies of nonpregnant adults. 7. Low-dose aspirin prevents pregnancy\x=req-\ induced hypertension and pre-eclampsia in angiotensin-sensitive primigravidae. Fabia J. Therefore. Chesley LC. and Robert Sholtz. have been found to have lower blood pressures than abstainers. clinical¬ ly recognized spontaneous abortions oc¬ curred later in gestation. preeclampsia-eclampsia in young primigravid women: subsequent pregnancy outcome and remote prognosis. The risks and benefits of taking aspirin during pregnancy. Friedman GD. The apparent protective effect of alcohol may be associated with smok¬ ing since it was not found to be signifi¬ cant in the multivariate models. 18. For example. especially one that ended later in gestation. provided protection against preeclampsia.
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