This Article Abstract Full Text (PDF) All Versions of this Article: 47/2/203    most recent 01.HYP.0000200042.64517.19v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Salas, S. P. Articles by Rosso, P. Search for Related Content PubMed PubMed Citation Articles by Salas, S. P. Articles by Rosso, P. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB ESTRADIOL PROGESTERONE Medline Plus Health Information High Risk Pregnancy Hormones Pregnancy Related Collections Other hypertension Clinical Studies

(Hypertension. 2006;47:203.)
© 2006 American Heart Association, Inc.

Original Articles

Time Course of Maternal Plasma Volume and Hormonal Changes in Women With Preeclampsia or Fetal Growth Restriction

From the Departments of Obstetrics and Gynecology (S.P.S.), Public Health (G.M.), and Pediatrics (P.R.) and Center for Medical Research (S.P.S., B.L.G., P.R.), School of Medicine Pontificia Universidad Católica de Chile, Sandiago, Chile.

Correspondence to Sofía P. Salas, Center for Medical Research, School of Medicine, Pontificia Universidad Católica de Chile, Marcoleta 391, Santiago, Chile. E-mail ssalas{at}med.puc.cl

	Abstract

Top Abstract Introduction Methods Results Discussion References

 
We tested the hypothesis that women with idiopathic fetal growth restriction (FGR) or preeclampsia (PE) have lower concentrations of some water-retaining hormones, such as aldosterone and estradiol, either preceding or concomitant with the onset of the reduced plasma volume described in these women. Plasma volume and serum concentrations of estradiol, progesterone, and aldosterone were measured serially at monthly intervals in 135 pregnant women from week 10 until term. Twenty-three developed idiopathic FGR, 17 had PE, and 95 remained normotensive and delivered normal-size infants (controls). Changes over time for each variable were studied using mixed models. Maternal age, parity, and weight/height at term were similar in all of the groups. Birth weight, body length, and ponderal index were lower in FGR and PE than in controls. Plasma volume increased throughout pregnancy in controls but was lower in FGR and PE from week 14 to 17 until term. Aldosterone values were lower in PE from week 26 to 29 onwards and in FGR after week 34. Progesterone concentrations were higher in PE than either control or FGR from week 18 to 21 until term. In contrast, FGR pregnancies had reduced progesterone and estradiol concentrations after week 34. Progesterone:estradiol ratio was significantly higher only in the PE group. In mothers with idiopathic FGR or PE, less expansion in plasma volume occurred before alterations in hormonal concentrations. We speculate that the early rise in progesterone may have a pathogenic role in the development of preeclampsia.

Key Words: blood • aldosterone • preeclampsia • estrogen

	Introduction

Top Abstract Introduction Methods Results Discussion References

 
Preeclampsia (PE) and fetal growth restriction (FGR) are frequent disorders of pregnancy and a leading cause of prenatal morbidity and mortality. In near-term pregnant women with either PE or FGR, we demonstrated lower plasma volume expansion, reduced cardiac output, and an increased total peripheral vascular resistance when compared with normotensive women who gave birth to normal-size infants.^1–3 Volume expansion during normal pregnancy seems to be secondary to renal and systemic vasodilatation that would activate the renin–angiotensin–aldosterone system that, in turn, would cause renal sodium and water retention.^4–6 Estrogen production may also have a role in plasma volume expansion by stimulating hepatic angiotensinogen synthesis.^5,7 According to this proposed pathway for volume expansion, in the present study we tested the hypothesis that women with PE or FGR would have lower serum aldosterone and estradiol concentrations either preceding or concomitant with the onset of the reduced plasma volume. We measured plasma volume and hormonal concentrations in initially healthy pregnant women from weeks 10 to 13 until near term. After delivery, we compared the time course of these changes in control, FGR, and PE women.

	Methods

Top Abstract Introduction Methods Results Discussion References

 
Participants were women attending 2 prenatal clinics of the Southeastern Health Service of Santiago, Chile (Alejandro del Río and La Granja). These women belonged to a low-income population and were of either European or mixed European and American Indian ancestry, reflecting the general patient population of these clinics. Participants received iron supplementation and standard prenatal care and delivered at the Sótero del Río Hospital, which is affiliated with the Universidad Católica School of Medicine. The Institutional Review Boards of the Southeastern Health Service and the Universidad Católica approved study procedures. Written informed consent was obtained before enrollment. All of the procedures followed the ethical standards for human experimentation established by the Declaration of Helsinki.

Inclusion criteria were a reliable gestational age, a body mass index between 21 and 24 at 10 to 13 weeks and between 25.5 and 28 at term, singleton fetuses, and absence of either chronic medical conditions or obstetric complications. Only women who denied using drugs, alcohol, or tobacco were invited to participate in the study.

Maternal height and unclothed weight were measured at the first prenatal visit (10 to 13 weeks) and then at monthly intervals until weeks 34 to 37 of gestation. Blood pressure was measured in seated subjects after a 30-minute rest with a mercury sphygmomanometer; the disappearance of sound (phase V) was used for the diastolic reading.⁸ Blood samples for plasma volume, hematocrit, estradiol, progesterone, and aldosterone determinations were obtained at each prenatal visit between 9:00 AM and 12:00 PM. Plasma volume was measured by the Evan’s Blue dye dilution technique, as described previously.^2,3,9 The remaining sera were aliquoted and stored at –70°C for hormone measurements. Serum estradiol, progesterone, and aldosterone concentrations were measured by radioimmunoassay, with the use of commercial kits (Diagnostic Products Corporation). Between- and within-assay coefficients of variability were <10% for each of these determinations.

Newborns were examined within 12 hours of birth to make anthropometric measurements and to rule out congenital infections and anomalies. Adequacy of birth weight for gestational age was evaluated using a Chilean prenatal growth standard that includes corrections for newborn gender, maternal parity, and height.¹⁰ This same chart was used in our previous studies.^1–3 Group assignment was made after delivery as follows: (1) controls: mothers who remained normotensive, had uncomplicated pregnancies, and delivered infants with a body weight and ponderal index above the tenth percentile for gestational age (n=95); (2) FGR: women who were normotensive throughout pregnancy and without pregnancy complications but who delivered infants with a birth weight below the tenth percentile (n=23); and (3) PE: women who developed hypertension after week 20 and who were normotensive at 6 weeks postpartum. Hypertension was defined based on blood pressure readings >140/90 mm Hg on 2 occasions 6 hour apart, plus proteinuria >0.3 g/ 24 hours.¹¹

Statistical Analysis
For time-independent factors, such as anthropometric values, we compared differences in the group means by a 1-way ANOVA followed by a Fisher’s protected least-significant difference test to determine pair-wise differences among group means (Stat View II, Abacus Concepts Inc). Statistical significance was accepted at a level of P<0.05. Linear¹² and nonlinear¹³ mixed-effects models were used to evaluate subject-specific and group average curves for the time-dependent changes. Based on the descriptive analyses, we established for each variable a parametric curve best fitting the changes occurring as pregnancy progressed. An overall comparison between the 3 study groups was done by testing the parameters of the curves using a Wald-type test. Comparisons among the 3 study groups at different gestational age intervals were performed by using the area under the curve with a Wald test. The S-PLUS statistical software MathSoft (Version 3.3, MathSoft, Inc) was used for these statistical analyses.

	Results

Top Abstract Introduction Methods Results Discussion References

 
No significant differences in maternal age, parity, height, and weight at term were observed among groups (Table 1). Gestational age at delivery was lower in PE mothers than in control or FGR mothers. Neonates from the FGR and PE groups had lower birth weight, body length, ponderal index, and head circumference than controls (Table 1). There was no difference in the male:female newborn ratios (controls, 51:44; FGR, 14:9; PE, 5:12; ² test, P=0.120).

Table 2 shows the curve fit formulas and coefficient values for mean blood pressure, plasma volume, aldosterone, progesterone, and estradiol. We consider that 2 curves are significantly different at all of the gestational time points when the coefficients of the models are significantly different. The best-fit model for mean blood pressure was quadratic (Figure 1 A; Table 2). When the coefficients of the fitted model for the 3 groups were compared using Wald test, significant differences were found among the 3 groups (²=15.6 with 6 degrees of freedom; P=0.016). During the first trimester, blood pressure was similar in all of the groups; this variable exhibited a moderate decline during the second trimester in all of the groups and increased in the third trimester in women who developed PE (Figure 1A; Table 3). The best-fit model for plasma volume was a logistic curve (Figure 1B; Table 2). When the coefficients of the fitted model were compared, significant differences were found among the 3 groups (²=72.4 with 8 degrees of freedom; P<0.001). Plasma volume increased progressively from early pregnancy until 34 to 37 weeks in controls, when the highest mean value was observed. In the FGR and PE groups, plasma volume was significantly lower than in controls by weeks 14 to 17 of pregnancy and remained lower than controls throughout pregnancy (Figure 1B; Table 3). The best-fit models for aldosterone and progesterone were quadratic, whereas for estradiol it was linear (Figure 2; Table 2). When the coefficients of the fitted model for the 3 groups were compared using Wald test, a difference of borderline significance was found for aldosterone (P=0.054), and significant differences were found for progesterone (P<0.001) and estradiol (P<0.005). During the first half of pregnancy, aldosterone values increased similarly in all of the groups. As of weeks 22 to 25 of gestation, values continued to increase in controls but remained rather constant in FGR and PE groups (Figure 2A). Aldosterone concentrations were significantly lower in PE than in controls by weeks 26 to 29 (Table 3) and after week 34 in FGR mothers (536±50 versus 439±46 pg/mL; P<0.05). Progesterone values were higher in PE than in control or FGR mothers from weeks 18 to 21 of pregnancy onward and were lower in FGR than in controls by weeks 30 to 33. Serum estradiol concentrations were similar in all of the groups until week 34; thereafter, estradiol values were lower in FGR and PE mothers when compared with controls (Figure 2; Table 3). The best-fit model for the progesterone: estradiol ratio was quadratic (data not shown). The progesterone:estradiol ratio fell in the 3 groups until weeks 18 to 21; thereafter, values remained rather constant in control and FGR mothers but were statistically significantly higher in the PE group (Table 3). Table 3 shows a summary of the gestational age at first occurrence of significant intergroup differences in some selected parameters, according to the area under the curve using a Wald test.

View larger version (19K): [in this window] [in a new window]   Figure 1. Curve fit and observed mean values for mean blood pressure (A) and plasma volume (B) values throughout pregnancy in control, FGR, or PE groups.

View larger version (14K): [in this window] [in a new window]   Figure 2. Curve fit and observed mean values for serum aldosterone (A), progesterone (B), and estradiol (C) concentrations throughout pregnancy in control, FGR, or PE groups.

In the PE group, 9 newborns were normal size (3194±96 g), and 8 had FGR (2312±203 g). Comparison between these 2 subgroups of PE mothers indicated that, near term, PE mothers with normal-size infants had a significantly higher plasma volume than those with FGR (3102±107 versus 2733±93 mL; P<0.020). However, we observed no significant differences in estradiol (18.5±1.7 versus 17.3±2.0 ng/mL), progesterone (265±26.7 versus 266±30 ng/mL), or aldosterone (368±73 versus 249±31 pg/mL) in preeclamptic women with normal-size or FGR newborns, respectively.

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
This longitudinal study demonstrated that pregnant mothers who subsequently develop PE or idiopathic FGR have lower plasma volume by the beginning of the second trimester of gestation. Lower plasma volume anteceded changes in estradiol or aldosterone concentrations. Additionally, the present data indicate that mothers who develop PE have elevated progesterone values before the clinical onset of the disease.

We have reported previously that near-term pregnant women with PE or FGR have reduced plasma volume that is caused by a limited expansion and not by a reduced prepregnancy plasma volume.^2,3 Newborns in the FGR group had a reduced ponderal index, suggesting the presence of an asymmetrical type of growth restriction. The clinical onset of this type of FGR has been established at weeks 27 to 30 of gestation.^14,15 In the present study, we demonstrated that the reduced volume expansion occurred by weeks 14 to 17 of pregnancy, before the clinical onset of either disease, thus confirming previous findings.^16–19 Using transvaginal Doppler ultrasound of the uteroplacental circulation, it was observed that women who developed complications of pregnancy, such as PE, premature delivery, or FGR, exhibited differences in uterine and umbilical artery Doppler blood flow indices as early as 12 to 16 weeks, when compared with women with uneventful pregnancy outcome.²⁰ This similarity suggests a possible causal relationship between reduced plasma volume and abnormal uteroplacental blood flow. In addition, a recent study demonstrated an enhanced microvascular response preceding the clinical onset of PE by several weeks,²¹ suggesting that alteration in vascular tone is an early event, at least in PE.

The events that lead to plasma volume expansion, although incompletely understood, are most likely triggered by a primary fall in systemic vascular tone. In turn, this would lead to a compensatory activation of volume-restoring mechanisms, such as renal vasodilatation and activation of the renin–angiotensin–aldosterone system, both of which occur before full placentation.^4,5,22 Placental estrogen may also play a role in volume expansion through hepatic stimulation of angiotensinogen synthesis²³ and by activation of NO synthase activity.²⁴ For these reasons, changes in the renin–angiotensin–aldosterone system and in estrogen concentrations are considered primary modulators of plasma volume expansion during pregnancy.

If this proposed pathway for plasma volume regulation is correct, we could expect that women who develop FGR or PE would have lower serum aldosterone and estradiol concentrations either preceding or concomitant with the onset of the reduced plasma volume. In contrast, the present study indicates that aldosterone and estradiol concentrations in PE and FGR mothers were within the range of values observed in controls at the time when inadequate volume expansion was detected and were altered afterward. Thus, other factors not explored in the present study may contribute to the inadequate volume expansion observed in these pregnancies, including changes in atrial natriuretic peptide, relaxin, and NO, among others.⁶ Because in the present study all 3 of the groups had acceptable body mass index and similar weight at term, this confounding variable can be ruled out as a possible explanation.²⁵

There were distinct differences in estradiol and progesterone concentrations among control, FGR, and PE mothers. The relative fall in estradiol concentrations observed in FGR and PE pregnancies during late gestation might reflect an altered metabolic function of the fetoplacental unit, most likely caused by the reduced uteroplacental blood flow described in these pregnancies.²⁶ Thus, the lower estradiol concentration seems to be a consequence rather than a cause of the reduced plasma volume expansion. Progesterone concentrations were increased in PE mothers starting at the second trimester and were reduced in FGR mothers. In addition, around midpregnancy, the progesterone:estradiol ratio was elevated in PE but not in FGR mothers. We are fully aware that a limitation of the present study is the lack of consideration for hormonal circadian rhythms. Some changes in the dynamics (eg, circadian amplitude and/or phase) may have taken place and could not have been assessed with the design used. This is particularly relevant for progesterone, a hormone that has a known circadian rhythm with highest values between 2:00 PM and 8:00 PM and 8:00 PM and 2:00 AM.²⁷ We intended to counteract this possible confounding variable by obtaining samples in the morning, at a time of the day when progesterone values are not increased. Other investigators have observed that circulating progesterone concentrations are increased in hypertensive women who subsequently develop PE²⁸ and in normotensive women around week 27, before the development of PE.²⁹ Several lines of evidence suggest that these changes might have a role in the development of PE. Placental progesterone production is elevated by 50% in PE,³⁰ and this excess of progesterone inhibits the production of the vasodilator prostacyclin by normal placentas to a rate characteristic of PE.³¹ It has been shown that the messenger RNA expression level of the progesterone receptor is elevated in placentas from women with PE, without changes in estradiol receptors,³² suggesting a functional progesterone predominance in PE. The possible role of estrogen and progesterone in endothelium-dependent relaxations has been evaluated in vitro using coronary arteries obtained from ovariectomized female dogs supplemented with hormones. In this model, it was shown that an excess of progesterone relative to estradiol antagonizes the stimulatory effects of estrogen on endothelium-dependent responses associated with the production of NO.³³ Taken altogether, these data suggest that elevated progesterone relative to estradiol can impair vasodilatation. Therefore, it is tempting to speculate that higher progesterone concentration might have a causal role in both vasospasm and in the imbalance between thromboxane and prostacyclin described in PE.^34,35 Although several authors, including us, have postulated that PE and FGR share a common pathophysiological mechanism, these distinct differences do not support this idea.

Perspectives
Three main conclusions may be drawn from the present study. First, it confirms previous findings that demonstrate that plasma volume either fails to increase or falls before the clinical onset of both PE and FGR. Second, the present data do not support the idea that estradiol and aldosterone are the most important modulators of plasma volume expansion during pregnancy, because plasma volume values were reduced in FGR and PE mothers 15 weeks before these hormones were altered. Third, high progesterone concentrations were observed early in pregnancy in women who later developed PE. We speculate that additional research in the mechanisms of progesterone metabolism during normal and abnormal pregnancy may provide a better understanding of the pathogenesis of PE.

	Acknowledgments

 
This study was supported by grants 91-0734 and 92-0657 from Fondo Nacional de Desarrollo Científico y Tecnológico, Chile.

Received April 29, 2005; first decision May 20, 2005; accepted December 5, 2005.

	References

Top Abstract Introduction Methods Results Discussion References

 
1. Rosso P, Donoso E, Braun S, Espinoza R, Fernández C, Salas SP. Maternal hemodynamic adjustments in idiopathic fetal growth retardation. Gynecol Obstet Invest. 1993; 35: 162–165.[CrossRef][Medline] [Order article via Infotrieve]

2. Salas SP, Rosso P, Espinoza R, Robert JA, Valdés G, Donoso E. Maternal plasma volume expansion and hormonal changes in women with idiopathic fetal growth retardation. Obstet Gynecol. 1993; 81: 1029–1033.[Medline] [Order article via Infotrieve]

3. Salas SP, Rosso P. Plasma volume, renal function, and hormonal levels in pregnant women with idiopathic fetal growth restriction or preeclampsia. Hypertens Pregnancy. 1998; 17: 69–79.

4. Chapman AB, Abraham WT, Zamudio S, Coffin C, Merouani A, Young D, Johnson A, Osorio F, Goldberg C, Moore LG, Dahms T, Schrier RW. Temporal relationships between hormonal and hemodynamic changes in early human pregnancy. Kidney Int. 1998; 54: 2056–2063.[CrossRef][Medline] [Order article via Infotrieve]

5. Schrier RW, Briner VA. Peripheral arterial vasodilation hypothesis of sodium and water retention in pregnancy: Implications for pathogenesis of preeclampsia-eclampsia. Obstet Gynecol. 1991; 77: 632–639.[Medline] [Order article via Infotrieve]

6. Conrad KP. Mechanisms of renal vasodilation and hyperfiltration during pregnancy. J Soc Gynecol Investig. 2004; 11: 438–448.[Abstract/Free Full Text]

7. Longo LD. Maternal blood volume and cardiac output during pregnancy: a hypothesis of endocrinologic control. Am J Physiol. 1983; 245: R720–R729.[Medline] [Order article via Infotrieve]

8. López MC, Belizán JM, Villar J, Bergel E. The measurement of diastolic blood pressure during pregnancy: Which Korotkoff phase should be used. Am J Obstet Gynecol. 1994; 170: 574–578.[Medline] [Order article via Infotrieve]

9. Nielsen MH, Nielsen NC. Spectrophotometric determinations of Evans blue dye in plasma with individual correction for blank density in a modified Gaeblers method. Scand J Clin Invest. 1962; 14: 605–617.[Medline] [Order article via Infotrieve]

10. Juez G, Lucero E, Ventura-Juncá P, González LH, Tapia JL, Winter AE. Crecimiento intrauterino en recién nacidos chilenos de clase media. Rev Chil Pediatr. 1989; 60: 198–202.[Medline] [Order article via Infotrieve]

11. Roberts JM, Pearson GD, Cutler JA, Lindheimer MD. Summary of the NHLBI working group on research on hypertension during pregnancy. Hypertens Pregnancy. 2003; 22: 109–127.[CrossRef][Medline] [Order article via Infotrieve]

12. Laird NM, Ware JH. Random-effects models for longitudinal data. Biometrics. 1982; 38: 963–974.[CrossRef][Medline] [Order article via Infotrieve]

13. Lindstrom MJ, Bates DM. Nonlinear random effects models for repeated measures data. Biometrics. 1990; 46: 673–687.[CrossRef][Medline] [Order article via Infotrieve]

14. Villar J, Belizán JM. The timing factor in the pathopysiology of the intrauterine growth retardation syndrome. Obstet Gynecol Surv. 1982; 37: 499–506.[Medline] [Order article via Infotrieve]

15. Pearce JM, Campbell S. Intrauterine growth retardation. Birth defects original article series. 1985; 21: 109–130.[Medline] [Order article via Infotrieve]

16. Gallery EDM, Hunyor SN, Györy AZ. Plasma volume contraction: a significant factor in both pregnancy associated hypertension (preeclampsia) and chronic hypertension in pregnancy. Q J Med New Series. 1979; 48: 593–602.

17. Hays PM, Cruikshank DP, Dunn LJ. Plasma volume determination in normal and preeclamptic pregnancies. Am J Obstet Gynecol. 1985; 151: 958–966.[Medline] [Order article via Infotrieve]

18. Huisman A, Aarnoudse JG. Increased 2nd trimester hemoglobin concentration in pregnancies later complicated by hypertension and growth retardation. Early evidence of a reduced plasma volume. Acta Obstet Gynecol Scand. 1986; 65: 605–608.[Medline] [Order article via Infotrieve]

19. Duvekot JJ, Cheriex EC, Pieters FAA, Menheere PPCA, Schouten HJA, Peeters LLH. Maternal volume homeostasis in early pregnancy in relation to fetal growth restriction. Obstet Gynecol. 1995; 85: 361–367.[CrossRef][Medline] [Order article via Infotrieve]

20. Harrington K, Carpenter RG, Goldfrad C, Campbell S. Transvaginal Doppler ultrasound of the uteroplacental circulation in the early prediction of pre-eclampsia and intrauterine growth retardation. Br J Obstet Gynaecol. 1997; 104: 674–681.[Medline] [Order article via Infotrieve]

21. Khan F, Belch JJ, MacLeod M, Mires G. Changes in endothelial function precede the clinical disease in women in whom preeclampsia develops. Hypertension. 2005; 46: 1123–1128.[Abstract/Free Full Text]

22. Duvekot JJ, Cheriex EC, Pieters FAA, Menheere PPCA, Peeters LLH. Early pregnancy changes in hemodynamics and volume homeostasis are consecutive adjustments triggered by a primary fall in systemic vascular tone. Am J Obstet Gynecol. 1993; 169: 1382–1392.[Medline] [Order article via Infotrieve]

23. Oelkers WK. Effects of estrogens and progestogens on the renin-aldosterone system and blood pressure. Steroids. 1996; 61: 166–171.[CrossRef][Medline] [Order article via Infotrieve]

24. Weiner CP, Lizasoain I, Baylis SA, Knowles RG, Charles IA, Moncada S. Induction of calcium-dependent nitric oxide synthases by sex hormones. Proc Natl Acad Sci. 1994; 91: 5212–5216.[Abstract/Free Full Text]

25. Rosso P, Donoso E, Braun S, Espinoza R, Salas SP. Hemodynamic changes in underweight pregnant women. Obstet Gynecol. 1992; 79: 908–912.[Medline] [Order article via Infotrieve]

26. Lunell NO, Nylund LE, Lewander R, Sarby B. Uteroplacental blood flow in pre-eclampsia measurements with indium 113m and a computer-linked gamma camera. Clin Exp Hypertens B. 1982; 1: 105–107.[Medline] [Order article via Infotrieve]

27. Magiakou MA, Mastorakos G, Rabin D, Margioris AN, Dubbert B, Calogero AE, Tsigos C, Munson PJ, Chrousos GP. The maternal hypothalamic-pituitary-adrenal axis in the third trimester of human pregnancy. Clin Endocrinol (Oxf). 1996; 44: 419–428.[CrossRef][Medline] [Order article via Infotrieve]

28. August P, Lenz T, Ales KL, Druzin ML, Edersheim TG, Hutson JM, Müller FB, Laragh JH, Sealy JE. Longitudinal study of the renin-angiotensin-aldosterone system in hypertensive pregnant women: Deviations related to the development of superimposed preeclampsia. Am J Obstet Gynecol. 1990; 163: 1612–1621.[Medline] [Order article via Infotrieve]

29. Tamimi R, Lagiou P, Vatten LJ, Mucci L, Trichopoulos D, Hellerstein S, Ekbom A, Adami HO, Hsieh CC. Pregnancy hormones, pre-eclampsia, and implications for breast cancer risk in the offspring. Cancer Epidemiol Biomark Prev. 2003; 12: 647–650.[Abstract/Free Full Text]

30. Walsh SW. Progesterone and estradiol production by normal and preeclamptic placentas. Obstet Gynecol. 1988; 71: 222–226.[Medline] [Order article via Infotrieve]

31. Walsh SW, Coulter S. Increased placental progesterone may cause decreased placental prostacyclin production in preeclampsia. Am J Obstet Gynecol. 1989; 161: 1586–1592.[Medline] [Order article via Infotrieve]

32. Faxén M, Nasiell J, Lunell N-O, Nisell H, Blanck A. Placental mRNA expression of the progesterone but not the estrogen receptor in pregnancies complicated by preeclampsia. Hypertens Pregnancy. 1998; 17: 241–249.

33. Miller VM, Vanhoutte PM. Progesterone and modulation of endothelium-dependent responses in canine coronary arteries. Am J Physiol. 1991; 261: R1022–R1027.[Medline] [Order article via Infotrieve]

34. Wallenburg HC. Prevention of hypertensive disorders in pregnancy. Clin Exp Hypertens Pregnancy. 1988; B7: 121–137.

35. Wang Y, Walsh SW, Guo J, Zhang J. The imbalance between thromboxane and prostacyclin in preeclampsia is associated with an imbalance between lipid peroxides and vitamin E in maternal blood. Am J Obstet Gynecol. 1991; 165: 1695–1700.[Medline] [Order article via Infotrieve]

This article has been cited by other articles:

				T. Van Mieghem, R. van Bree, E. Van Herck, J. Deprest, and J. Verhaeghe Insulin-like growth factor-II regulates maternal hemodynamic adaptation to pregnancy in rats Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2009; 297(5): R1615 - R1621. [Abstract] [Full Text] [PDF]

				B. D. LaMarca, J. Gilbert, and J. P. Granger Recent Progress Toward the Understanding of the Pathophysiology of Hypertension During Preeclampsia Hypertension, April 1, 2008; 51(4): 982 - 988. [Full Text] [PDF]

				M. Vore and M. Leggas Progesterone Acts via Progesterone Receptors A and B to Regulate Breast Cancer Resistance Protein Expression Mol. Pharmacol., March 1, 2008; 73(3): 613 - 615. [Abstract] [Full Text] [PDF]

				G.-F. von Tempelhoff, L. Heilmann, L. Rudig, K. Pollow, G. Hommel, and J. Koscielny Mean Maternal Second-Trimester Hemoglobin Concentration and Outcome of Pregnancy: A Population-Based Study Clinical and Applied Thrombosis/Hemostasis, January 1, 2008; 14(1): 19 - 28. [Abstract] [PDF]

				S. Sena, I. R. Rasmussen, A. R. Wende, A. P. McQueen, H. A. Theobald, N. Wilde, R. O. Pereira, S. E. Litwin, J. P. Berger, and E. D. Abel Cardiac Hypertrophy Caused by Peroxisome Proliferator- Activated Receptor-{gamma} Agonist Treatment Occurs Independently of Changes in Myocardial Insulin Signaling Endocrinology, December 1, 2007; 148(12): 6047 - 6053. [Abstract] [Full Text] [PDF]

				S. P. Salas, A. Giacaman, W. Romero, P. Downey, E. Aranda, D. Mezzano, and C. P. Vio Pregnant Rats Treated With a Serotonin Precursor Have Reduced Fetal Weight and Lower Plasma Volume and Kallikrein Levels Hypertension, October 1, 2007; 50(4): 773 - 779. [Abstract] [Full Text] [PDF]

				J. M. Faupel-Badger, C.-C. Hsieh, R. Troisi, P. Lagiou, and N. Potischman Plasma Volume Expansion in Pregnancy: Implications for Biomarkers in Population Studies Cancer Epidemiol. Biomarkers Prev., September 1, 2007; 16(9): 1720 - 1723. [Abstract] [Full Text] [PDF]

				L. A. Mucci, P. W. Dickman, M. Lambe, H.-O. Adami, D. Trichopoulos, T. Riman, C.-c. Hsieh, and S. Cnattingius Gestational Age and Fetal Growth in Relation to Maternal Ovarian Cancer Risk in a Swedish Cohort Cancer Epidemiol. Biomarkers Prev., September 1, 2007; 16(9): 1828 - 1832. [Abstract] [Full Text] [PDF]

				J. Joyner, L. A. A. Neves, J. P. Granger, B. T. Alexander, D. C. Merrill, M. C. Chappell, C. M. Ferrario, W. P. Davis, and K. B. Brosnihan Temporal-spatial expression of ANG-(1-7) and angiotensin-converting enzyme 2 in the kidney of normal and hypertensive pregnant rats Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2007; 293(1): R169 - R177. [Abstract] [Full Text] [PDF]

				C. Wadsack, S. Tabano, A. Maier, U. Hiden, G. Alvino, V. Cozzi, M. Huttinger, W. J. Schneider, U. Lang, I. Cetin, et al. Intrauterine growth restriction is associated with alterations in placental lipoprotein receptors and maternal lipoprotein composition Am J Physiol Endocrinol Metab, February 1, 2007; 292(2): E476 - E484. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) All Versions of this Article: 47/2/203    most recent 01.HYP.0000200042.64517.19v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Salas, S. P. Articles by Rosso, P. Search for Related Content PubMed PubMed Citation Articles by Salas, S. P. Articles by Rosso, P. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB ESTRADIOL PROGESTERONE Medline Plus Health Information High Risk Pregnancy Hormones Pregnancy Related Collections Other hypertension Clinical Studies