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

Abstract

Abstract-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 Ⅲ aldosterone Ⅲ preeclampsia Ⅲ estrogen P reeclampsia (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. MethodsParticipants 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 ...

Relationship of aldosterone synthase gene (C-344T) and mineralocorticoid receptor (S810L) polymorphisms with gestational hypertension

“…Our work confirms earlier observations stating that plasma aldosterone [5][6][7]26,28 and PRA levels 9,28,29 are lower, and progesterone levels 7 are higher in pregnancy-induced hypertension. Multiple regression analysis shows a negative correlation of both systolic and diastolic blood pressure with aldosterone and PRA, and a positive correlation with progesterone levels.…”

“…On the other hand, Schmider-Ross et al, 22 in 38 patients with pregnancy-induced hypertension, as well as Escher et al, 19 in 48 preeclamptic women, were not able to detect the MR L810 mutation. Although those studies were inconclusive, the earlier observation that progesterone levels were significantly elevated in preeclamptic women 7 prompted us to address the MR L810 mutation frequency in hypertensive women. Progesterone has a higher affinity for MR than aldosterone, but it confers solely a low agonistic mineralocorticoid activity.…”

“…On the other hand, progesterone values are elevated before the clinical onset of disease. 7 It has been shown that an excess of progesterone relative to estrogen antagonizes the stimulatory effects of estrogen on endothelium-dependent responses associated with NO production. 30 In accordance with the findings of Israel and Peceñ o, 28 the aldosterone/renin ratio is lower in our hypertensive group of women as compared with the normotensive group, meaning that the circulating renin-angiotensin-aldosterone system is suppressed in pregnancy-induced hypertension.…”

“…This low plasma volume expansion precedes aldosterone and estradiol diminution. [5][6][7] The renin-angiotensinaldosterone system and estrogens are considered primary modulators of plasma volume expansion during pregnancy. 8 Although plasma aldosterone concentration is reduced in hypertensive pregnant women, the aldosterone-renin ratio is twofold larger than in normal pregnancy, and it may be another manifestation of increased adrenal sensitivity to angiotensin II.…”

Le paradoxe cardiovasculaire de la grossesse

“…On a aussi attribué à une augmentation du volume sanguin, associée à un trouble de la gestion du sodium par le rein, la mobilisation d'inhibiteurs de la Na/K-ATPase (bufodiènolides) qui nuirait à l'invasion trophoblastique des artères spiralées [5]. Salas et al [6] ont suggéré que chez la femme l'expansion retardée ou lente du volume sanguin et l'élévation rapide de la production de progestérone (antagoniste de l'aldosté-rone ?) installeraient, avant le 2 e trimestre, les conditions propres à provoquer au 3 e trimestre l'apparition > Malgré l'accès plus généralisé aux soins préna-taux dans les pays développés, on connaît très peu les mécanismes qui régissent l'adaptation maternelle à l'état physiologique qu'est la grossesse.…”