Family History of Hypertension, Heart Disease, and Stroke Among Women Who Develop Hypertension in Pregnancy Roberta B. Ness, MD, MPH, Nina Markovic, PhD, Debra Bass, MS, Gail Harger, MS, and James M. Roberts, MD OBJECTIVE: To assess familial cardiovascular risk factors in women developing hypertension in pregnancy. METHODS: Of 2211 women delivering live births after enrollment in a pregnancy cohort study, 85 (3.8%) developed preeclampsia (antepartum systolic blood pressure greater than 140 or diastolic blood pressure greater than 90 plus proteinuria) and 142 (6.4%) developed transient hypertension of pregnancy (antepartum blood pressure elevation without proteinuria). At a mean of 10.2 weeks’ gestation, women were asked about first-degree family members with heart disease or stroke, hypertension, diabetes, renal disease, or any of these, which defined familial cardiovascular risk. RESULTS: After adjustment for age and body size, having two or more family members, versus no family members, with cardiovascular risk imparted a 1.9-fold (95% confidence interval [CI] 1.1, 3.2) elevated risk for developing preeclampsia and a 1.7-fold (95% CI 1.1, 2.6) risk for developing transient hypertension of pregnancy. Having two or more family members with hypertension also imparted a significant, two-fold elevation in risk of preeclampsia and transient hypertension of pregnancy, and having two or more family members with heart disease or stroke imparted a 3.2-fold (95% CI 1.4, 7.7) elevation in the risk for preeclampsia. CONCLUSION: A strong family history of aggregate cardiovascular risk increased the likelihood for developing preeclampsia and transient hypertension of pregnancy. These findings support the theory that a preexisting tendency to cardiovascular risk, and particularly hypertension, increases a women’s susceptibility to developing hypertenFrom the University of Pittsburgh and Magee-Womens Research Institute, Pittsburgh, Pennsylvania. Supported by grants P01 HD30367 from the National Institutes of Child Health and Disease and 5MO1 RR00056 from the National Institute of Research Resources. The authors thank Cindy Schatzman, RN, and Jennifer Eicher, BS, for Pregnancy Exposures and Preeclampsia Prevention study leadership, coordination, and data collection; and Dr. Richard Day for statistical consultation.
1366
sion in pregnancy. (Obstet Gynecol 2003;102:1366 –71. © 2003 by The American College of Obstetricians and Gynecologists.)
Hypertension in pregnancy, comprising preeclampsia and transient hypertension of pregnancy, is associated with increased rates of hypertension and coronary heart disease later in life.1– 6 Whether preeclampsia and transient hypertension of pregnancy initiate vascular changes that later become clinically evident or whether a predisposition to cardiovascular disease increases the risk of developing hypertension in pregnancy is not clear. Evidence for the latter explanation includes the fact that women who are overweight or have a personal history of hypertension before becoming pregnant are more likely to develop preeclampsia and transient hypertension of pregnancy.7–11 Women who develop preeclampsia also have antepartum and intrapartum evidence of hyperlipidemia,12–15 glucose intolerance,16 –19 elevated blood pressure,20 and renal dysfunction,21–23 whereas metabolic aberrations are not consistently found among women with transient hypertension of pregnancy.9,24 One way to distinguish between these two notions— that predisposition to cardiovascular disease is linked to hypertension in pregnancy and that these pregnancy conditions cause cardiovascular damage—is to assess the relationship between preeclampsia and family history. Family history represents the shared genetic or environmental influences that women carry into their pregnancies. Several previous studies have demonstrated that preeclampsia is more common among the mothers, sisters, and monozygotic twins of women who develop preeclampsia.25–29 To the best of our knowledge, however, only a handful of retrospective studies have assessed the relationship between family history of cardiovascular risk (hypertension and diabetes) and preeclampsia,7,30,31 and none have examined family history in relation to transient hypertension of pregnancy.
VOL. 102, NO. 6, DECEMBER 2003 © 2003 by The American College of Obstetricians and Gynecologists. Published by Elsevier.
0029-7844/03/$30.00 doi:10.1016/j.obstetgynecol.2003.08.011
We asked women enrolled in a prospective observational study of hypertension in pregnancy about their first-degree family history of cardiovascular disease, including hypertension, heart disease, stroke, diabetes, and renal disease to determine whether family history predicted the onset of preeclampsia or transient hypertension of pregnancy. MATERIALS AND METHODS The Pregnancy Exposures and Preeclampsia Prevention study was approved by the Magee-Womens Hospital Institutional Review Board. Women planning to deliver at Magee were enrolled at their first prenatal visit from prenatal clinics and private practices from March 1997 to October 2001. All women aged 14 – 44 years and less than 20 weeks’ gestation who consented were eligible for participation. Of the 6444 women screened for possible enrollment, 2399 (37.2%) were ineligible because of maternal age, gestational age, planned delivery at another hospital, or not being pregnant. Early in the study, only nulliparous women were included. A total of 4045 women were eligible for participation. Of those eligible, 1154 (28.5%) did not agree to participate, and 2891 (71.5%) were enrolled. An additional 680 women were excluded from analysis because they delivered at another hospital (173), had a spontaneous abortion (194), had a pregnancy termination (63), were determined after enrollment to be ineligible (26), rescinded consent (94), had an ectopic or other adverse event (8), or were lost to follow-up (122). A total of 2211 women were involved in this analysis. No baseline demographic or family history characteristic differed significantly between enrolled women excluded and included in these analyses. All women entering the Pregnancy Exposures and Preeclampsia Prevention study underwent a standardized interview at their first prenatal visit (mean 10.2 weeks’ gestation) administered by trained, professional interviewers. Women were asked about the following diseases among first-degree family members: diabetes, hypertension, heart disease, stroke, and kidney disease. An aggregate category of cardiovascular risk was created, comprising a family history of any of these. For each disease, women were asked to recall the number of each type of relative experiencing that condition. Because a family history of heart disease and of stroke yielded similar results, and because of small cell sizes, these exposures were combined into a single category. Preeclampsia was defined as an elevation of blood pressure plus proteinuria. The blood pressure criteria consisted of a mean blood pressure on repeated prelabor measurements of greater than 140 systolic and/or greater than 90 diastolic. The proteinuria criteria were greater
VOL. 102, NO. 6, DECEMBER 2003
than 1⫹ on a catheterized, greater than 2⫹ on a voided, and greater than 300 mg on a 24-hour urine specimen, or a protein/creatinine ratio of 0.3. The same elevations in blood pressure in the absence of proteinuria defined transient hypertension of pregnancy. Covariate information was also obtained by interview, on maternal age, race (white versus nonwhite), education (less than high school, high school graduate, post– high-school attainment), gravidity and parity, smoking since the woman suspected she might be pregnant, recalled prenatal weight and height (combined into body mass index: weight/height2), prepregnancy diabetes, and prepregnancy hypertension. We first compared demographic and clinical features among women who developed preeclampsia, transient hypertension of pregnancy, or neither. Baseline differences between groups were analyzed with Fisher exact test for categoric variables and Student t test for continuous variables. The proportion of women reporting one family member and the proportion reporting two or more family members (representing a stronger family aggregation), as compared with none, with each type of cardiovascular risk, were then compared among women developing preeclampsia, women developing transient hypertension of pregnancy, and women with no hypertension in pregnancy. Odds ratios (with 95% confidence intervals [CIs]) were the measure of association. Because the small numbers of exposed women in some categories would not allow the addition of multiple covariates into multivariable models, we instead repeated analyses among more homogeneous groups. First, we excluded women with prepregnancy diabetes and prepregnancy hypertension. Next, we separately analyzed associations among women who were primiparous and those who were multiparous. Finally, logistic regression analyses were performed adjusting for age and body mass index and separately considering each family history variable as the main independent factor. RESULTS Among 2211 women followed throughout pregnancy, 85 (3.8%) developed preeclampsia, and 142 (6.4%) developed transient hypertension of pregnancy. Both women eventually affected by preeclampsia and women affected by transient hypertension of pregnancy were significantly heavier and more likely to have prepregnancy hypertension than women having normotensive pregnancies (Table 1). Women developing preeclampsia were also more likely to be older, have prepregnancy diabetes, and to deny smoking before conception. Women reporting two or more first-degree relatives with cardiovascular risk (hypertension, heart disease or
Ness et al
Family History and Preeclampsia
1367
Table 1. Demographic Characteristics for Study Women With Incident Preeclampsia or Transient Hypertension of Pregnancy Transient hypertension
Preeclampsia n Race/ethnicity White Black Other Education ⬍ high school High school graduate Post–high school Pre-pregnancy diabetes Pre-pregnancy hypertension Smoking since pregnant Age (y) BMI Week gestation at baseline interview Gravidity 1 pregnancy ⱖ2 pregnancies Parity No live births ⱖ1 live birth
85
142
Normotensive 1984
58 (68.2) 27 (31.8) 0 (0.0)
79 (55.6) 61 (43.0) 2 (1.4)
1246 (62.8) 696 (35.1) 42 (2.1)
12 (14.1) 37 (43.5) 36 (42.4) 4 (4.7)* 6 (7.1)* 17 (20.0)‡ 26.6 ⫾ 6.0‡ 27.8 ⫾ 6.0* 10.1 ⫾ 3.9
29 (20.4) 60 (42.3) 53 (37.3) 0 (0.0) 15 (10.6)† 42 (29.6) 25.3 ⫾ 6.3 28.5 ⫾ 8.0† 10.1 ⫾ 3.9
403 (20.3) 736 (37.1) 845 (42.6) 7 (0.4) 37 (1.9) 640 (32.3) 25.1 ⫾ 6.0 25.2 ⫾ 6.3 10.2 ⫾ 4.6
38 (44.7) 47 (55.3)
60 (42.3) 82 (57.7)
802 (40.4) 1182 (59.6)
54 (63.5) 31 (36.5)
82 (57.7) 60 (42.3)
1130 (57.0) 854 (43.0)
BMI ⫽ body mass index. Data are presented as n (%) or mean ⫾ standard deviation. * P ⱕ .001 for comparison of preeclampsia with control. † P ⱕ .001 for comparison of transient hypertension of pregnancy with control. ‡ P ⱕ .05 for comparison of preeclampsia with control.
stroke, diabetes, or renal disease) were significantly more likely than women without affected relatives to develop hypertension in pregnancy (Table 2). After adjustment for age and body mass index, having two or more affected relatives imparted a 1.9-fold excess risk of preeclampsia (95% CI 1.1, 3.2) and a 1.7-fold excess risk of transient hypertension of pregnancy (95% CI 1.1, 2.6). Adjusted relative risks were approximately 2 for the associations between having two or more family members with hypertension and preeclampsia or transient hypertension of pregnancy. Having two or more family members, as opposed to none, with heart disease or stroke was 3.2-fold more likely (95% CI 1.4, 7.7) among women developing preeclampsia and 1.9-fold more likely (95% CI 0.8, 4.5) among women developing transient hypertension of pregnancy. Neither a family history of diabetes nor a family history of renal disease elevated the risk of preeclampsia or transient hypertension of pregnancy. These relationships were not significantly affected by exclusion of women with prepregnancy diabetes and prepregnancy hypertension (data not shown). Among primiparous women developing preeclampsia, the associations between family history of cardiovascular risk, hypertension, and heart disease or stroke
1368
Ness et al
Family History and Preeclampsia
persisted (Table 3). However, in primiparous women developing transient hypertension of pregnancy, no familial risk was apparent. Among multiparous women, familial cardiovascular risk was associated with both preeclampsia and transient hypertension of pregnancy. DISCUSSION Women who developed preeclampsia or transient hypertension of pregnancy were significantly more likely to have two or more first-degree relatives with aggregate cardiovascular risk. In particular, they were more likely to have familial hypertension or familial heart disease or stroke. Although there is substantial epidemiologic evidence supporting links between hypertension in pregnancy and later cardiovascular risk,1– 6 the role for familial cardiovascular risk in predicting preeclampsia has been little examined. Eskanazi et al,7 in a case– control study based on medical record reviews, found that regardless of parity, preeclamptic women were more likely to have a family history of hypertension. More recently, Qiu et al30 found that a first-degree family history of hypertension and a family history of diabetes were associated with preeclampsia cases compared with normotensive con-
OBSTETRICS & GYNECOLOGY
Table 2. Number of First-Degree Relatives With Cardiovascular Risk Factors and Relative Risks of Developing Preeclampsia and Transient Hypertension of Pregnancy Preeclampsia
Normotensive
Adjusted RR* (95% CI)
Transient hypertension
Normotensive
Adjusted RR* (95% CI)
29 27 29
1046 491 447
1.0 1.9 (1.1, 3.2) 1.9 (1.1, 3.2)
61 32 49
1046 491 447
1.0 1.1 (0.7, 1.8) 1.7 (1.1, 2.6)
65 12 8
1638 303 43
1.0 0.9 (0.5, 1.7) 3.2 (1.4, 7.7)
111 24 7
1638 303 43
1.0 1.2 (0.7, 1.9) 1.9 (0.8, 4.5)
41 32 12
1273 584 127
1.0 1.5 (1.0, 2.5) 2.2 (1.1, 4.5)
79 46 17
1273 584 127
1.0 1.2 (0.8, 1.8) 2.0 (1.1, 3.6)
66 16 3
1690 265 29
1.0 1.3 (0.7, 2.3) 1.1 (0.3, 5.0)
111 26 5
1690 265 29
1.0 1.3 (0.9, 2.1) 1.5 (0.6, 4.2)
80 5 0
1918 64 2
1.0 1.4 (0.5, 3.9)
139 2 1
1918 64 2
1.0 0.4 (0.1, 1.7) 3.9 (0.3, 48.7)
Cardiovascular risk† None reported One reported Two or more reported Heart disease/stroke None reported One reported Two or more reported Hypertension None reported One reported Two or more reported Diabetes None reported One reported Two or more reported Renal disease None reported One reported Two or more reported
RR ⫽ relative risk; CI ⫽ confidence interval. * Adjusted for age and body mass index. † Includes cardiovascular disease, hypertension, diabetes, renal disease, and stroke.
Table 3. Number of First-Degree Relatives With Cardiovascular Risk Factors and Relative Risks of Developing Preeclampsia or Transient Hypertension of Pregnancy by Parity Primiparous
Cardiovascular risk† None reported One reported Two or more reported Heart disease/stroke None reported One reported Two or more reported Hypertension None reported One reported Two or more reported Diabetes None reported One reported Two or more reported Renal disease None reported One reported Two or more reported
Multiparous
Preeclampsia adjusted RR* (95% CI)
Transient hypertension adjusted RR* (95% CI)
Preeclampsia adjusted RR* (95% CI)
Transient hypertension adjusted RR* (95% CI)
1.0 1.9 (1.0, 3.7) 1.6 (0.8, 3.3)
1.0 0.8 (0.4, 1.4) 1.2 (0.7, 2.1)
1.0 1.8 (0.7, 4.4) 2.3 (0.9, 5.6)
1.0 2.2 (1.1, 4.7) 3.0 (1.5, 6.1)
1.0 0.6 (0.2, 1.6) 7.2 (2.3, 22.8)
1.0 1.4 (0.7, 2.6) 1.3 (0.2, 10.7)
1.0 1.3 (0.5, 3.2) 1.7 (0.4, 7.8)
1.0 1.0 (0.5, 2.0) 1.8 (0.7, 5.0)
1.0 1.1 (0.6, 2.0) 2.5 (1.1, 5.8)
1.0 1.1 (0.7, 1.9) 1.4 (0.6, 3.4)
1.0 2.6 (1.2, 5.8) 1.9 (0.5, 7.1)
1.0 1.5 (0.8, 2.7) 2.6 (1.2, 5.8)
1.0 1.3 (0.6, 2.6) 1.7 (0.4, 8.1)
1.0 1.1 (0.6, 2.0)
1.0 1.3 (0.5, 3.2)
1.0 1.7 (0.9, 3.3) 2.9 (0.9, 9.5)
1.0 1.6 (0.5, 5.4)
1.0
1.0 0.9 (0.1, 7.0)
1.0 1.0 (0.2, 4.6) 5.2 (0.3, 107.8)
Abbreviations as in Table 2. Relative risks were not calculated when comparison cells contained zero observations. * Adjusted for age and body mass index. † Includes cardiovascular disease, hypertension, diabetes, renal disease, and stroke.
VOL. 102, NO. 6, DECEMBER 2003
Ness et al
Family History and Preeclampsia
1369
trols identified at delivery. Finally, Kobashi et al,31 in examining a Glu298Asp variant of the endothelial nitric oxide synthase gene (NOS3) noted a two-fold elevation in the familial risk of hypertension among women with hypertension in pregnancy (three quarters of whom had preeclampsia). All studies were retrospective, examined a limited set of cardiovascular risk factors among family members, and did not consider transient hypertension of pregnancy. This study, therefore, replicates and extends the previous findings. Familial aggregation represents shared genetic or environmental commonalities in families, commonalities that would be carried by a woman into her pregnancy. Our data, providing evidence for family aggregation in cardiovascular risk, thus supports the idea that women entering pregnancy with an elevated risk for cardiovascular disease are more likely to develop preeclampsia. Previous observations suggest that blood pressures are higher and endothelial function is impaired, even early in the second trimester, among women bound to develop hypertension in pregnancy.20,24 A question raised by our results is whether the family history of heart disease or stroke associated with hypertension in pregnancy is entirely accounted for by (diagnosed or undiagnosed) hypertension running in the family. We found some evidence of an association between family history of renal disease and hypertension in pregnancy, although the number of women with affected relatives was small and the estimates therefore did not reach statistical significance. A renal pathology or hematuria is also more common among women with preeclampsia or eclampsia and transient hypertension of pregnancy than among women without these conditions.21–23 Strengths of our study are as follows. Intervieweradministered questionnaires were used to ask women about family history. With the use of such techniques, recall of first-degree family history for cardiovascular risk is excellent.32 Family history information was obtained at the first prenatal visit, before the onset of preeclampsia, and is thus unbiased by knowledge of pregnancy outcome. Preeclampsia and transient hypertension of pregnancy were determined by meticulous chart review for all women and characterized on the basis of antepartum blood pressure and urinary protein measurements, so as to avoid any interference from labor in these determinations. The greatest weakness in our analysis is the limited number of women with familial cardiovascular risk who developed preeclampsia or transient hypertension of pregnancy. This is not surprising, given their young age and thus the relative youth of their first-degree relatives. Nonetheless, the incidence of preeclampsia (3.8%) in this
1370
Ness et al
Family History and Preeclampsia
study is similar to that reported in other, recent studies.33 Furthermore, elimination of women refusing to participate in our study, if they differed both by exposure and outcome from those enrolled, might have biased our results. In summary, our data suggest that a first-degree family history of cardiovascular risk, particularly when present in two or more relatives, increases the risk of developing preeclampsia and transient hypertension of pregnancy. This finding supports the theory that preexisting cardiovascular risk, and particularly hypertension, increases a woman’s susceptibility to developing hypertension in pregnancy.
REFERENCES 1. Ness RB, Roberts JM. Epidemiology of hypertension. In: Lindheimer MD, Roberts JM, Cunningham FG, Chesley’s hypertensive disorders in pregnancy. 2nd ed. Stamford, Connecticut: Appleton & Lange, 1999:43– 65. 2. Chambers JC, Fusi L, Malik IS, Haskard DO, DwSwiet M, Kooner JS. Association of maternal endothelial dysfunction with preeclampsia. JAMA 2001;285:1607–12. 3. Smith GC, Pell JP, Walsh D. Pregnancy complications and maternal risk of ischaemic heart disease: A retrospective cohort study of 129,290 births. Lancet 2001;357:2002–6. 4. Hannaford P, Ferry S, Hirsch S. Cardiovascular sequelae of toxaemia of pregnancy. Heart 1997;77:154–8. 5. Jonsdottir LS, Arngrimsson R, Giersson RT, Geirsson RT, Sigvaldason H, Sigfusson N. Death rates from ischemic heart disease in women with a history of hypertension in pregnancy. Acta Obstet Gynecol Scand 1995;74: 772–6. 6. Nisell H, Lintu H, Lunell NO, Mollerstrom G, Pettersson E. Blood pressure and renal function seven years after pregnancy complicated by hypertension. Br J Obstet Gynaecol 1995;102:876–81. 7. Eskenazi B, Fenster L, Sidney S. A multivariate analysis of risk factors for preeclampsia. JAMA 1991;266:237–41. 8. Masse J, Forest JC, Moutquin JM, Marcoux S, Brideau NA, Belanger M. A prospective study of several potential biologic markers for early prediction of the development of preeclampsia. Am J Obstet Gynecol 1993;169:501–8. 9. Thadhani R, Stampfer MJ, Hunter DJ, Manson JE, Solomon CG, Curhan GC. High body mass index and hypercholesterolemia: Risk of hypertensive disorders of pregnancy. Obstet Gynecol 1999;94:543–50. 10. Ness RB, Roberts J. Heterogeneous causes constituting the single syndrome of preeclampsia: A hypothesis and its implications. Am J Obstet Gynecol 1996;175:1365–70. 11. Odegard RA, Vatten LJ, Nilssen ST, Salvesen KA, Austgulen R. Risk factors and clinical manifestations of preeclampsia. Br J Obstet Gynaecol 2000;107:1410–6.
OBSTETRICS & GYNECOLOGY
12. Lorentzen B, Endresen MJ, Clausen T, Henriksen T. Fasting serum free fatty acids and triglycerides are increased before 20 weeks of gestation in women who later develop preeclampsia. Hypertens Pregnancy 1994;12: 276–82. 13. Hubel CA, McLaughlin MK, Evans RW, Hauth BA, Sims CJ, Roberts JM. Fasting serum triglycerides free fatty acids, and malondialdehyde are increased in preeclampsia, are positively correlated, and decrease within 48 hours post partum. Am J Obstet Gynecol 1996;174:975–82. 14. Gratacos E, Casals E, Sanllehy C, Cararach V, Alonso PL, Fortuny A. Variation in lipid levels during pregnancy in women with different types of hypertension. Acta Obstet Gynecol Scand 1996;75:896–901. 15. Sattar N, Bendomir A, Berry C, Shepherd J, Greer IA, Packard CJ. Lipoprotein subfraction concentrations in preeclampsia: Pathogenic parallels to atherosclerosis. Obstet Gynecol 1997;89:403–8. 16. Berkowitz KM. Insulin resistance and preeclampsia. Clin Perinatol 1998;25:873–5. 17. Greco P, Loverro G, Selvaggi L. Does gestational diabetes represent an obstetrical risk factor? Gynecol Obstet Invest 1994;37:242–5. 18. Joffe GM, Esterlitz JR, Levine RJ, Clemens JD, Ewell MG, Sibai BM, et al. The relationship between abnormal glucose tolerance and hypertensive disorders of pregnancy in healthy nulliparous women. Calcium for Preeclampsia Prevention (CPEP) Study Group. Am J Obstet Gynecol 1998;179:1032–7. 19. Levy MT, Jacober SJ, Sowers JR. Hypertensive disorders of pregnancy in southwestern Navajo Indians. Arch Intern Med 1994;154:2181–3. 20. Caritis S, Sibai B, Hauth J, Lindheimer M, VanDorsten P, Klebanoff M, et al. Predictors of preeclampsia in women at high risk. Am J Obstet Gynecol 1998;179:946–51. 21. Fisher KA, Luger A, Spargo BH, Lindheimer MD. Hypertension in pregnancy: Clinical-pathological correlations and remote prognosis. Medicine 1981;60:267–76. 22. Murakami S, Saitoh M, Kubo T, Koyama T, Kobayashi M. Renal disease in women with severe preeclampsia or gestational proteinuria. Obstet Gynecol 2000;96:945–9. 23. Stehman-Breen C, Miller L, Fink J, Schwartz SM. Preeclampsia and premature labour among pregnant women with haematuria. Paediatr Perinatal Epidemiol 2000;14: 136–40.
VOL. 102, NO. 6, DECEMBER 2003
24. Wolf M, Sandler L, Jimenez-Kimble R, Shah A, Ecker JL, Thadhani R. Insulin resistance but not inflammation is associated with transient hypertension of pregnancy. Hypertension 2002;40:886–91. 25. Salonen Ros H, Lichtenstein P, Lipworth L, Cnattingius S. Genetic effects on the liability of developing pre-eclampsia and transient hypertension of pregnancy. Am J Med Genet 2000;91:256–60. 26. Chesley LC, Cooper DW. Genetics of hypertension in pregnancy: Possible single gene control of pre-eclampsia and eclampsia in the descendants of eclamptic women. Br J Obstet Gynaecol 1986;93:898–908. 27. Arngrimsson R, Bjornsson S, Geirsson RT, Bjornsson H, Walker JJ, Snaedal G. Genetic and familial predisposition to eclampsia and pre-eclampsia in a defined population. Br J Obstet Gynaecol 1990;97:762–9. 28. Humphries J. Occurrence of hypertensive toxemia of pregnancy in mother-daughter pairs. Johns Hopkins Hosp Bull 1960;107:271–7. 29. Cooper DW, Hill JA, Chesley LC, Bryans CI. Genetic control of susceptibility to eclampsia and miscarriage. Br J Obstet Gynaecol 1988;95:644–53. 30. Qui C, Williams MA, Leisenring WM, Sorensen TK, Frederick IO, Dempsey JC, et al. Family history of hypertension and type 2 diabetes in relation to preeclampsia risk. Hypertension 2003;41:408–13. 31. Kobashi G, Yamada H, Ohta K, Kato EH, Fujimoto S. Endothelial nitric oxide synthase gene (NOS3) variant and hypertension in pregnancy. 2001;103:241– 4. 32. Bensen JT, Liese AD, Rushing JT, Province M, Foslom AR, Rich SS, et al. Accuracy of proband reported family history: The NHLBI Family Heart Study (FHS). Genet Epidemiol 1999;17 Suppl:141–50. 33. Skjaerven R, Wilcox AJ, Lie RT. The interval between pregnancies and the risk of preeclampsia. N Engl J Med 2002;346:33–8. Address reprint requests to: Roberta B. Ness, MD, MPH, University of Pittsburgh, Graduate School of Public Health, Room A527 Crabtree Hall, 130 DeSoto Street, Pittsburgh, PA 15261; E-mail:
[email protected]. Received May 20, 2003. Received in revised form July 23, 2003. Accepted August 14, 2003.
Ness et al
Family History and Preeclampsia
1371