Maternal blood pressure in pregnancy, birth weight, and perinatal mortality in first births: prospective study
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《英国医生杂志》
1 Academic Department of Obstetrics and Gynaecology, Imperial College London, Faculty of Medicine, Chelsea and Westminster Hospital, London SW10 9NH, 2 Department of Epidemiology and Public Health, Imperial College London, Faculty of Medicine, London W2 1PG
Correspondence to: P Steer p.steer@imperial.ac.uk
Abstract
Hypertensive disorders in pregnancy are a leading cause of maternal and perinatal mortality in the developed world1 2 and have been extensively studied. Few studies, however, have reported fetal outcomes at lower blood pressures. In long term follow up studies, lower blood pressure (down to at least 115 mm Hg systolic and 75 mm Hg diastolic pressures) was associated with a lower risk of vascular and all cause mortality.3 Low blood pressure has also been associated with symptoms, including unexplained tiredness, chronic fatigue syndrome, and recurrent syncope.4-7 It is particularly common in underweight women with a low muscle mass.8 We hypothesised that the association of a low maternal weight with an increased risk of a low birthweight baby and poor infant survival9 might be due in part to low blood pressure leading to poor placental perfusion. Three small studies reported that low maternal blood pressure in pregnancy is associated with low birth weight and an increased risk of small for gestational age babies.10-12 Another study reported an increased risk of perinatal mortality.13 Since 1988, prospective data have been collected on all pregnancies booked into 15 of the 17 maternity units in the North West Thames region of London using the St Mary's Maternity Information System. We used this database to investigate the association between blood pressure in pregnancy and fetal outcome (birth weight and perinatal mortality) in women without pre-existing hypertension or proteinuria.
Materials and methods
We identified 210 814 first singleton births of babies weighing more than 200 g among women with no hypertension before 20 weeks' gestation and with no proteinuria, delivering between 24 and 43 weeks' gestation. The mean (SD) birth weight of the babies was 3282 g (545 g), and there were 1335 perinatal deaths. Recorded mean diastolic blood pressure at booking fell by an average of 0.23 mm Hg per year from 67.9 mm Hg in 1988 to 65.2 mm Hg in 2000. Table 1 shows the mean highest diastolic blood pressures during pregnancy and perinatal death rates for selected variables. We found statistically significant differences between groups for blood pressure by age at booking for antenatal checks; weeks of gestation at booking; mother's body mass index, ethnic group, Carstairs' score, and smoking status; birth weight, and year of birth. We also found statistically significant differences between groups for perinatal mortality for all variables except year of birth. Overall, there were 46 perinatal deaths in women excluded from the analysis with a history of hypertension and 58 perinatal deaths for those with proteinuria (including all cases of pre-eclampsia). In 10 of these women there was a history of hypertension and proteinuria; thus 94 perinatal deaths occurred in the excluded group; 93.4% of all perinatal deaths (1335 of 1429 deaths) therefore occurred in women without a history of hypertension and who did not develop pre-eclampsia.
Table 1 Mean highest diastolic blood pressure in mothers during pregnancy and perinatal death rates for selected variables in cohort of 210 814 first singleton births in North West Thames region, London*
Figure 1 shows diastolic blood pressures at booking for antenatal checks and weeks of gestation among 169 249 women when both were recorded. Substantial numbers of women had their first antenatal check at all gestations from eight to 40 weeks, thus providing cross sectional data on blood pressures through pregnancy. Mean diastolic blood pressure was 66.6 mm Hg in the first trimester and 66.3 mm Hg in the second trimester. It was progressively higher after 34 weeks' gestation, reaching 68.4 mm Hg by 40 weeks' gestation or more. This was after adjustment for the mother's ethnic group, smoking status, height and weight, calendar year, age at booking, and Carstairs' score; similar changes were also observed in the unadjusted data.
Before 34 weeks' gestation there was no substantial correlation between highest blood pressure in pregnancy and birth weight (data not shown). At 34 weeks' gestation or more, however, there was an inverted U shaped relation between birth weight and blood pressure, with a maximum birth weight at around 80 mm Hg (fig 2). When birth weight was adjusted for maternal height and weight, the relation remained similar but shifted slightly towards lower blood pressures. The relation of birth weight with blood pressure could not be explained by confounding by gestational age; analysis of the Z scores of birth weights (by gestational age) showed the same relation (data not shown). To account for the effects of obstetric interventions on relation between highest antenatal blood pressure and birth weight, we reanalysed the data only for women with spontaneous onset of labour at term (37-42 weeks' gestation). We found no material change in the results (data not shown).
Birth weight in relation to rises in blood pressure during pregnancy depended on the blood pressure at booking (fig 3). A blood pressure of 70 mm Hg or more at booking was associated with the highest birth weights as long as the blood pressure rise during pregnancy did not exceed 10 mm Hg; with rises greater than this, birth weight fell sharply. If the blood pressure at booking was less than 70 mm Hg, birth weight rose as the rise became greater, but started to fall again if the rise exceeded 30 mm Hg.
Fig 3 Birth weight and rise in blood pressure after booking for antenatal checks, by blood pressure at booking and gestation between 34 and 43 weeks at delivery, among women without chronic hypertension and no proteinuria. Values adjusted for calendar year and women's ethnic group, smoking status, height, weight, age at booking, and Carstairs' deprivation score
Perinatal mortality showed a strong curvilinear association with highest diastolic blood pressure (fig 4). In particular, if linear quadratic models were fitted to the data, the quadratic term was highly statistically significantly different from zero and remained so even when we excluded women with highest diastolic pressures of less than 60 mm Hg. This relation largely disappeared if corrected for birth weight (fig 4). Of the 824 perinatal deaths contributing to this analysis, we estimated that 94.3 (11.4%) were attributable to women with blood pressure differing from the optimal blood pressure (82.7 mm Hg) predicted by the linear quadratic model; most (91.2%) of these excess perinatal deaths (86.1) occurred among women with lower blood pressures (table 2), mainly in the ranges 70-79 mm Hg (51.2 excess deaths) and 60-69 mm Hg (30.9 excess deaths; table 2). Perinatal mortality still exhibited a strong curvilinear association with highest diastolic blood pressure even when we included women with proteinuria or chronic hypertension (fig 5); in linear quadratic models, the quadratic term was still highly statistically significantly different from zero. In this larger group, 98.7 perinatal deaths (11.2%) were attributable to mothers with blood pressure differing from the optimal blood pressure (80.4 mm Hg) predicted by the linear quadratic model; most (70.1%) of these excess perinatal deaths (69.2) occurred among mothers with lower blood pressures (see table 2).
Table 2 Number of perinatal deaths, by blood pressure range, attributed to mother's highest blood pressure during antenatal check being more or less than optimal value predicted by linear quadratic model
Discussion
American College of Obstetricians and Gynecologists. Hypertension in pregnancy. ACOG, 1996.
Anon. Report on confidential enquiries into maternal deaths in the United Kingdom 1994-1996. London: Stationery Office, 1998.
Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2004;360: 1903-13.
Pilgrim JA, Stansfeld S, Marmot M. Low blood pressure, low mood? BMJ 1992;304: 75-8.
Rowe PC. Orthostatic intolerance and chronic fatigue syndrome: new light on an old problem. J Pediatr 2002;140: 387-9.
Streeten DH, Thomas D, Bell DS. The roles of orthostatic hypotension, orthostatic tachycardia, and subnormal erythrocyte volume in the pathogenesis of the chronic fatigue syndrome. Am J Med Sci 2000;320: 1-8.
Mathias CJ, Deguchi K, Schatz I. Observations on recurrent syncope and presyncope in 641 patients. Lancet 2001;357: 348-53.
Owens PE, Lyons SP, O'Brien ET. Arterial hypotension: prevalence of low blood pressure in the general population using ambulatory blood pressure monitoring. J Hum Hypertens 2000;14: 243-7.
Cogswell ME, Yip R. The influence of fetal and maternal factors on the distribution of birthweight. Sem Perinatol 1995;19: 222-40.
Grunberger W, Leodolter S, Parschalk O. Maternal hypotension: fetal outcome in treated and untreated cases. Gynecologic Obstetric Invest 1979;10: 32-8.
Margulies M, Voto LS, Fescina R, Lastra L, Lapidus AM, Schwarcz R. Arterial blood pressure standards during normal pregnancy and their relation with mother-fetus variables. Am J Obstet Gynecol 1987;156: 1105-9.
Ng PH, Walters WA. The effects of chronic maternal hypotension during pregnancy. Aust NZ J Obstet Gynaecol 1992;32: 14-6.
Friedman EA, Neff RK. Hypertension-hypotension in pregnancy. Correlation with fetal outcome. JAMA 1978;239: 2249-51.
Cleary R, Beard RW, Coles J, Devlin HB, Hopkins A, Roberts S, et al. The quality of routinely collected maternity data. Br J Obstet Gynaecol 1994;101: 1042-7.
MacGillivray I, Rose GA, Rowe B. Blood pressure survey in pregnancy. Clin Sci 1969;37: 395-407.
Davey DA, MacGillivray I. The classification and definition of the hypertensive disorders of pregnancy. Am J Obstet Gynecol 1988;158: 892-8.
De Swiet M. Blood pressure measurement in pregnancy. Br J Obstet Gynaecol 1991;98: 239-40.
Perry IJ, Wilkinson LS, Shinton RA, Beevers DG. Conflicting views on the measurement of blood pressure in pregnancy. Br J Obstet Gynaecol 1991;98: 241-3.
Johenning AR, Barron WM. Indirect blood pressure measurement in pregnancy: Korotkoff phase 4 versus phase 5. Am J Obstet Gynecol 1992;167: 577-80.
De Swiet M, Shennan A. Blood pressure measurement in pregnancy. Br J Obstet Gynaecol 1996;103: 862-3.
Shennan A, Gupta M, Halligan A, Taylor DJ, de Swiet M. Lack of reproducibility in pregnancy of Korotkoff phase IV as measured by mercury sphygmomanometry. Lancet 1996;347: 139-42.
Lenfant C. Working group report on high blood pressure in pregnancy. J Clin Hypertens (Greenwich) 2001;3: 75-88.
Steer PJ. The definition of pre-eclampsia. Br J Obstet Gynaecol 1999;106: 753-5.
Redman CW, Jefferies M. Revised definition of pre-eclampsia. Lancet 1988;1: 809-12.
Biswas A, Choolani MA, Anandakumar C, Arulkumaran S. Ambulatory blood pressure monitoring in pregnancy induced hypertension. Acta Obstet Gynecol Scand 1997;76: 829-33.
Helewa ME, Burrows RF, Smith J, Williams K, Brain P, Rabkin SW. Report of the Canadian Hypertension Society Consensus Conference: 1. Definitions, evaluation and classification of hypertensive disorders in pregnancy. CMAJ 1997;157: 715-25.
CESDI. Confidential enquiry into stillbirths and deaths in infancy. London: Maternal and Child Health Consortium, 1998. (5th Annual Report.)
Carstairs V, Morris R. Deprivation and health in Scotland. Aberdeen: Aberdeen University Press, 1991.
Davison AC, Hinkley DV. Bootstrap methods and their application. Cambridge: Cambridge University Press, 1997.
McCullagh P, Nelder JA. Generalized linear models, second edition London: Chapman and Hall, 1989.
Reiss RE, O'Shaughnessy RW, Quilligan TJ, Zuspan FP. Retrospective comparison of blood pressure course during preeclamptic and matched control pregnancies. Am J Obstet Gynecol 1987;156: 894-8.
Clapp JF, Seaward BL, Sleamaker RH, Hiser J. Maternal physiologic adaptations to early human pregnancy. Am J Obstet Gynecol 1988;159: 1456-60.
Halligan A, O'Brien E, O'Malley K, Mee F, Atkins N, Conroy R, et al. Twenty-four-hour ambulatory blood pressure measurement in a primigravid population. J Hypertens 1993;11: 869-73.
Brown MA, Robinson A, Bowyer L, Buddle ML, Martin A, Hargood JL, et al. Ambulatory blood pressure monitoring in pregnancy: what is normal? Am J Obstet Gynecol 1998;178: 836-42.
Moutquin JM, Rainville C, Giroux L, Raynauld P, Amyot G, Bilodeau R, et al. A prospective study of blood pressure in pregnancy: prediction of preeclampsia. Am J Obstet Gynecol 1985;151: 191-6.
Page EW, Christianson R. The impact of mean arterial pressure in the middle trimester upon the outcome of pregnancy. Am J Obstet Gynecol 1976;125: 740-6.
Easterling TR, Brateng D, Schmucker B, Brown Z, Millard SP. Prevention of preeclampsia: a randomized trial of atenolol in hyperdynamic patients before onset of hypertension. Obstet Gynecol 1999;93: 725-33.
Von Dadelszen P, Ornstein MP, Bull SB, Logan AG, Koren G, Magee LA. Fall in mean arterial pressure and fetal growth restriction in pregnancy hypertension: a meta-analysis. Lancet 2000;355: 87-92.(Philip J Steer, professor)
Correspondence to: P Steer p.steer@imperial.ac.uk
Abstract
Hypertensive disorders in pregnancy are a leading cause of maternal and perinatal mortality in the developed world1 2 and have been extensively studied. Few studies, however, have reported fetal outcomes at lower blood pressures. In long term follow up studies, lower blood pressure (down to at least 115 mm Hg systolic and 75 mm Hg diastolic pressures) was associated with a lower risk of vascular and all cause mortality.3 Low blood pressure has also been associated with symptoms, including unexplained tiredness, chronic fatigue syndrome, and recurrent syncope.4-7 It is particularly common in underweight women with a low muscle mass.8 We hypothesised that the association of a low maternal weight with an increased risk of a low birthweight baby and poor infant survival9 might be due in part to low blood pressure leading to poor placental perfusion. Three small studies reported that low maternal blood pressure in pregnancy is associated with low birth weight and an increased risk of small for gestational age babies.10-12 Another study reported an increased risk of perinatal mortality.13 Since 1988, prospective data have been collected on all pregnancies booked into 15 of the 17 maternity units in the North West Thames region of London using the St Mary's Maternity Information System. We used this database to investigate the association between blood pressure in pregnancy and fetal outcome (birth weight and perinatal mortality) in women without pre-existing hypertension or proteinuria.
Materials and methods
We identified 210 814 first singleton births of babies weighing more than 200 g among women with no hypertension before 20 weeks' gestation and with no proteinuria, delivering between 24 and 43 weeks' gestation. The mean (SD) birth weight of the babies was 3282 g (545 g), and there were 1335 perinatal deaths. Recorded mean diastolic blood pressure at booking fell by an average of 0.23 mm Hg per year from 67.9 mm Hg in 1988 to 65.2 mm Hg in 2000. Table 1 shows the mean highest diastolic blood pressures during pregnancy and perinatal death rates for selected variables. We found statistically significant differences between groups for blood pressure by age at booking for antenatal checks; weeks of gestation at booking; mother's body mass index, ethnic group, Carstairs' score, and smoking status; birth weight, and year of birth. We also found statistically significant differences between groups for perinatal mortality for all variables except year of birth. Overall, there were 46 perinatal deaths in women excluded from the analysis with a history of hypertension and 58 perinatal deaths for those with proteinuria (including all cases of pre-eclampsia). In 10 of these women there was a history of hypertension and proteinuria; thus 94 perinatal deaths occurred in the excluded group; 93.4% of all perinatal deaths (1335 of 1429 deaths) therefore occurred in women without a history of hypertension and who did not develop pre-eclampsia.
Table 1 Mean highest diastolic blood pressure in mothers during pregnancy and perinatal death rates for selected variables in cohort of 210 814 first singleton births in North West Thames region, London*
Figure 1 shows diastolic blood pressures at booking for antenatal checks and weeks of gestation among 169 249 women when both were recorded. Substantial numbers of women had their first antenatal check at all gestations from eight to 40 weeks, thus providing cross sectional data on blood pressures through pregnancy. Mean diastolic blood pressure was 66.6 mm Hg in the first trimester and 66.3 mm Hg in the second trimester. It was progressively higher after 34 weeks' gestation, reaching 68.4 mm Hg by 40 weeks' gestation or more. This was after adjustment for the mother's ethnic group, smoking status, height and weight, calendar year, age at booking, and Carstairs' score; similar changes were also observed in the unadjusted data.
Before 34 weeks' gestation there was no substantial correlation between highest blood pressure in pregnancy and birth weight (data not shown). At 34 weeks' gestation or more, however, there was an inverted U shaped relation between birth weight and blood pressure, with a maximum birth weight at around 80 mm Hg (fig 2). When birth weight was adjusted for maternal height and weight, the relation remained similar but shifted slightly towards lower blood pressures. The relation of birth weight with blood pressure could not be explained by confounding by gestational age; analysis of the Z scores of birth weights (by gestational age) showed the same relation (data not shown). To account for the effects of obstetric interventions on relation between highest antenatal blood pressure and birth weight, we reanalysed the data only for women with spontaneous onset of labour at term (37-42 weeks' gestation). We found no material change in the results (data not shown).
Birth weight in relation to rises in blood pressure during pregnancy depended on the blood pressure at booking (fig 3). A blood pressure of 70 mm Hg or more at booking was associated with the highest birth weights as long as the blood pressure rise during pregnancy did not exceed 10 mm Hg; with rises greater than this, birth weight fell sharply. If the blood pressure at booking was less than 70 mm Hg, birth weight rose as the rise became greater, but started to fall again if the rise exceeded 30 mm Hg.
Fig 3 Birth weight and rise in blood pressure after booking for antenatal checks, by blood pressure at booking and gestation between 34 and 43 weeks at delivery, among women without chronic hypertension and no proteinuria. Values adjusted for calendar year and women's ethnic group, smoking status, height, weight, age at booking, and Carstairs' deprivation score
Perinatal mortality showed a strong curvilinear association with highest diastolic blood pressure (fig 4). In particular, if linear quadratic models were fitted to the data, the quadratic term was highly statistically significantly different from zero and remained so even when we excluded women with highest diastolic pressures of less than 60 mm Hg. This relation largely disappeared if corrected for birth weight (fig 4). Of the 824 perinatal deaths contributing to this analysis, we estimated that 94.3 (11.4%) were attributable to women with blood pressure differing from the optimal blood pressure (82.7 mm Hg) predicted by the linear quadratic model; most (91.2%) of these excess perinatal deaths (86.1) occurred among women with lower blood pressures (table 2), mainly in the ranges 70-79 mm Hg (51.2 excess deaths) and 60-69 mm Hg (30.9 excess deaths; table 2). Perinatal mortality still exhibited a strong curvilinear association with highest diastolic blood pressure even when we included women with proteinuria or chronic hypertension (fig 5); in linear quadratic models, the quadratic term was still highly statistically significantly different from zero. In this larger group, 98.7 perinatal deaths (11.2%) were attributable to mothers with blood pressure differing from the optimal blood pressure (80.4 mm Hg) predicted by the linear quadratic model; most (70.1%) of these excess perinatal deaths (69.2) occurred among mothers with lower blood pressures (see table 2).
Table 2 Number of perinatal deaths, by blood pressure range, attributed to mother's highest blood pressure during antenatal check being more or less than optimal value predicted by linear quadratic model
Discussion
American College of Obstetricians and Gynecologists. Hypertension in pregnancy. ACOG, 1996.
Anon. Report on confidential enquiries into maternal deaths in the United Kingdom 1994-1996. London: Stationery Office, 1998.
Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2004;360: 1903-13.
Pilgrim JA, Stansfeld S, Marmot M. Low blood pressure, low mood? BMJ 1992;304: 75-8.
Rowe PC. Orthostatic intolerance and chronic fatigue syndrome: new light on an old problem. J Pediatr 2002;140: 387-9.
Streeten DH, Thomas D, Bell DS. The roles of orthostatic hypotension, orthostatic tachycardia, and subnormal erythrocyte volume in the pathogenesis of the chronic fatigue syndrome. Am J Med Sci 2000;320: 1-8.
Mathias CJ, Deguchi K, Schatz I. Observations on recurrent syncope and presyncope in 641 patients. Lancet 2001;357: 348-53.
Owens PE, Lyons SP, O'Brien ET. Arterial hypotension: prevalence of low blood pressure in the general population using ambulatory blood pressure monitoring. J Hum Hypertens 2000;14: 243-7.
Cogswell ME, Yip R. The influence of fetal and maternal factors on the distribution of birthweight. Sem Perinatol 1995;19: 222-40.
Grunberger W, Leodolter S, Parschalk O. Maternal hypotension: fetal outcome in treated and untreated cases. Gynecologic Obstetric Invest 1979;10: 32-8.
Margulies M, Voto LS, Fescina R, Lastra L, Lapidus AM, Schwarcz R. Arterial blood pressure standards during normal pregnancy and their relation with mother-fetus variables. Am J Obstet Gynecol 1987;156: 1105-9.
Ng PH, Walters WA. The effects of chronic maternal hypotension during pregnancy. Aust NZ J Obstet Gynaecol 1992;32: 14-6.
Friedman EA, Neff RK. Hypertension-hypotension in pregnancy. Correlation with fetal outcome. JAMA 1978;239: 2249-51.
Cleary R, Beard RW, Coles J, Devlin HB, Hopkins A, Roberts S, et al. The quality of routinely collected maternity data. Br J Obstet Gynaecol 1994;101: 1042-7.
MacGillivray I, Rose GA, Rowe B. Blood pressure survey in pregnancy. Clin Sci 1969;37: 395-407.
Davey DA, MacGillivray I. The classification and definition of the hypertensive disorders of pregnancy. Am J Obstet Gynecol 1988;158: 892-8.
De Swiet M. Blood pressure measurement in pregnancy. Br J Obstet Gynaecol 1991;98: 239-40.
Perry IJ, Wilkinson LS, Shinton RA, Beevers DG. Conflicting views on the measurement of blood pressure in pregnancy. Br J Obstet Gynaecol 1991;98: 241-3.
Johenning AR, Barron WM. Indirect blood pressure measurement in pregnancy: Korotkoff phase 4 versus phase 5. Am J Obstet Gynecol 1992;167: 577-80.
De Swiet M, Shennan A. Blood pressure measurement in pregnancy. Br J Obstet Gynaecol 1996;103: 862-3.
Shennan A, Gupta M, Halligan A, Taylor DJ, de Swiet M. Lack of reproducibility in pregnancy of Korotkoff phase IV as measured by mercury sphygmomanometry. Lancet 1996;347: 139-42.
Lenfant C. Working group report on high blood pressure in pregnancy. J Clin Hypertens (Greenwich) 2001;3: 75-88.
Steer PJ. The definition of pre-eclampsia. Br J Obstet Gynaecol 1999;106: 753-5.
Redman CW, Jefferies M. Revised definition of pre-eclampsia. Lancet 1988;1: 809-12.
Biswas A, Choolani MA, Anandakumar C, Arulkumaran S. Ambulatory blood pressure monitoring in pregnancy induced hypertension. Acta Obstet Gynecol Scand 1997;76: 829-33.
Helewa ME, Burrows RF, Smith J, Williams K, Brain P, Rabkin SW. Report of the Canadian Hypertension Society Consensus Conference: 1. Definitions, evaluation and classification of hypertensive disorders in pregnancy. CMAJ 1997;157: 715-25.
CESDI. Confidential enquiry into stillbirths and deaths in infancy. London: Maternal and Child Health Consortium, 1998. (5th Annual Report.)
Carstairs V, Morris R. Deprivation and health in Scotland. Aberdeen: Aberdeen University Press, 1991.
Davison AC, Hinkley DV. Bootstrap methods and their application. Cambridge: Cambridge University Press, 1997.
McCullagh P, Nelder JA. Generalized linear models, second edition London: Chapman and Hall, 1989.
Reiss RE, O'Shaughnessy RW, Quilligan TJ, Zuspan FP. Retrospective comparison of blood pressure course during preeclamptic and matched control pregnancies. Am J Obstet Gynecol 1987;156: 894-8.
Clapp JF, Seaward BL, Sleamaker RH, Hiser J. Maternal physiologic adaptations to early human pregnancy. Am J Obstet Gynecol 1988;159: 1456-60.
Halligan A, O'Brien E, O'Malley K, Mee F, Atkins N, Conroy R, et al. Twenty-four-hour ambulatory blood pressure measurement in a primigravid population. J Hypertens 1993;11: 869-73.
Brown MA, Robinson A, Bowyer L, Buddle ML, Martin A, Hargood JL, et al. Ambulatory blood pressure monitoring in pregnancy: what is normal? Am J Obstet Gynecol 1998;178: 836-42.
Moutquin JM, Rainville C, Giroux L, Raynauld P, Amyot G, Bilodeau R, et al. A prospective study of blood pressure in pregnancy: prediction of preeclampsia. Am J Obstet Gynecol 1985;151: 191-6.
Page EW, Christianson R. The impact of mean arterial pressure in the middle trimester upon the outcome of pregnancy. Am J Obstet Gynecol 1976;125: 740-6.
Easterling TR, Brateng D, Schmucker B, Brown Z, Millard SP. Prevention of preeclampsia: a randomized trial of atenolol in hyperdynamic patients before onset of hypertension. Obstet Gynecol 1999;93: 725-33.
Von Dadelszen P, Ornstein MP, Bull SB, Logan AG, Koren G, Magee LA. Fall in mean arterial pressure and fetal growth restriction in pregnancy hypertension: a meta-analysis. Lancet 2000;355: 87-92.(Philip J Steer, professor)