Endothelin 1 and leptin in the pathophysiology of intrauterine growth restriction.

OBJECTIVES: To evaluate the relationship of endothelin 1 (ET-1) and leptin concentrations in women and newborns following a pregnancy complicated with intrauterine growth restriction (IUGR). METHODS: Twenty-five women with a pregnancy complicated with IUGR at 19 different gestational ages were matched with women with uncomplicated pregnancies. Blood samples from the umbilical artery and maternal peripheral venous circulation were collected at delivery, and ET-1 and leptin levels were determined from the blood samples. Data relating to obstetric complications (e.g., pregnancy-induced hypertension), delivery (e.g. mode, birth weight, signs of intrapartum fetal distress, and Apgar scores) were also recorded. RESULTS: Mean maternal ET-1 (13.4+/-6.2-9.9+/-2.9 pmol/l) and mean fetal ET-1 (14.5+/-4.2-11.7+/-3.1 pmol/l) concentrations were significantly higher when women had experienced pregnancies complicated with IUGR than when they had had normal pregnancies. Mean fetal leptin concentration was significantly lower in the study group (6.8+/-2.2 ng/ml) than in the control group (10.6+/-3.6 ng/ml (P<0.05). However, fetal leptin per kilogram of fetal weight was not significantly different in the study group (3.16+/-1.18 ng/ml) than in the control group (3.23+/-0.96 ng/ml) (P>0.05, paired t-test). However, a statistically significant correlation was observed between fetal leptin concentrations per kilogram of fetal weight and fetal endothelin concentrations in pregnancies complicated with IUGR (r=0.546; P<0.05). CONCLUSIONS: These results suggest the intertwined roles of ET-1 and leptin in the pathophysiology of IUGR. Further studies concerning interaction between these peptides in different pregnancy conditions may provide important information about the actions of ET-1 and leptin on fetal growth.     

Elevated amniotic fluid leptin levels in pregnant women who are destined to develop preeclampsia

OBJECTIVE: To analyze whether leptin levels of the amniotic fluid elevate during early pregnancy in women destined to develop preeclampsia and to evaluate the relationship between amniotic fluid leptin levels and gestational age, maternal body mass index, and fetal sex. STUDY DESIGN: Leptin levels of the amniotic fluid were compared in two groups of women, preeclamptic (n = 20) and normotensive pregnant (n = 40), matched for fetal sex, maternal body mass index at sampling, gravidity and fetal gestational age at sampling. Furthermore, amniotic leptin levels in 400 normotensive pregnant women were analyzed for their correlation with gestational age, maternal body mass index, and fetal sex. RESULTS: Median leptin concentrations were significantly higher (p < 0.001) in the women with preeclampsia (7.3+/-0.7 ng/ml) than in the normotensive pregnant women (4.1 +/- 0.3 ng/ml), independent of fetal sex. The leptin levels in the amniotic fluid decreased with advanced gestational age (r = 0.24, p < 0.001). Amniotic fluid leptin levels in the pregnant women carrying a female fetus (5.6+/-0.3ng/ml) were significantly higher than those carrying a male fetus (4.7+/-0.2 ng/ml) (p = 0.004). CONCLUSION: Higher amniotic fluid leptin levels were observed in the preeclamptic pregnant women, and they decreased as gestational age advanced. Furthermore, the women with a female fetus were noted to have higher amniotic fluid leptin levels.     

Elevated amniotic fluid leptin levels in early second trimester are associated with earlier delivery and lower birthweight in twin pregnancy

OBJECTIVE: To explore the possibility of using early second trimester amniotic fluid leptin levels as a predictor of pregnancy outcome in twin pregnancy. STUDY DESIGN: Amniotic fluid leptin levels from 18 twin-pregnant women in early second trimester were analyzed for their correlation with gestational age at delivery and fetal birthweight. Leptin levels in 16 amniotic fluid samples collected from small for gestational age (SGA) twin pregnancies were compared with those in 20 amniotic fluid samples collected from non-SGA twin pregnancies. RESULTS: A significant correlation was observed between amniotic fluid leptin levels and gestational age at delivery (r = 0.71, p < 0.001) as well as fetal birthweight (r = 0.72, p < 0.001). There was also a significant correlation between gestational age at delivery and fetal birthweight (r = 0.92, p < 0.001). The average gestational age at delivery was 30.4 +/- 1.4 weeks in the SGA group, with a mean birthweight of 1552 +/- 200 g at delivery. For the non-SGA group, the values were 37.3 +/- 0.5 weeks and 2759 +/- 115 g ( p < 0.001), respectively. Amniotic fluid leptin levels were found to be significantly higher ( p < 0.001) for women in the SGA group (11.4 +/- 1.5 ng/mL) than for those in the non-SGA group (5.4 +/- 0.5 ng/mL). CONCLUSION: Higher amniotic fluid leptin levels in early second trimester were associated with both lower gestational age at delivery and lower birthweight. Our results suggest that amniotic fluid leptin levels in early second trimester may be a good marker for the prediction of perinatal complications in twin pregnancy.     

Leptin as a possible marker of augmented metabolic risk during pregnancy

AIM: Leptin is a proteic hormone, isolated in 1994, mainly synthetized in the white adipose tissue. Aim of this study was to compare leptin concentrations in normal pregnancies with those measured in pregnancies complicated by gestational diabetes or gestational hypertension or pre-eclampsia. METHODS: We enrolled 48 pregnant women: 18 with uncomplicated pregnancy, 11 with gestational diabetes, 19 with gestational hypertension or pre-eclampsia. Leptin concentrations were measured in maternal serum at enrollment, together with insulin and cortisol, at delivery and in the immediate postpartum. At delivery serum leptin was calculated in the cord blood too. RESULTS: Fasting plasma leptin and insulin were higher in the group of patients with gestational hypertension, than in the other groups. Third-trimester maternal leptin concentrations correlated significantly with insulin levels in the group of women with gestational diabetes and in the group with gestational hypertension or pre-eclampsia, but not in the women with an uncomplicated pregnancy. CONCLUSIONS: Leptin concentrations in pregnancies complicated by hypertensive disorders are significantly higher than in normal pregnancies. The increased leptin concentrations are independent of associated proteinuria, as women with simple gestational hypertension and preeclampsia showed comparable third-trimester leptin concentrations. In both women with gestational diabetes and women with hypertensive disorders, serum leptin correlated closely with serum insulin, suggesting that the association between leptin and insulin resistance is preserved in pregnancy. Whatever the reasons for an increased maternal leptin production in pregnancies complicated by hypertension, maternal leptin homeostasis does not seem to influence foetal serum leptin concentrations, which seems to be mainly related to birth weight.     

Maternal plasma leptin levels and their relationship to insulin and glucose in gestational-onset diabetes

To investigate the changes in leptin levels and the relationship between this substance and insulin and glucose in pregnant women with gestational-onset diabetes, we measured plasma leptin levels in the maternal peripheral vein of 17 healthy and 17 diabetic women at 29 and 33 weeks of gestation. We also correlated maternal plasma leptin levels in diabetic women with fasting plasma insulin levels and plasma glucose levels obtained 1 h after oral administration of 50 g of glucose. Maternal serum leptin levels in women with gestational diabetes (mean +/- SD 16.52 +/- 5.07 ng/ml, range 10.84-27.4 ng/ml) were significantly higher (p < 0.001) than those found in uncomplicated pregnancies (10.61 +/- 1.47 ng/ml, range 7.28-13.4 ng/ml). A positive correlation was found between maternal serum leptin levels and glycosylated haemoglobin values in diabetic pregnant women (r = 0.94, p < 0.001). A positive correlation was also found between maternal leptin concentrations and fasting serum insulin levels, as well as between leptin concentrations and plasma glucose levels obtained 1 h after the administration of 50 g of glucose in women with gestational diabetes (r = 0.84, p < 0.001, and r = 0.92, p < 0.001, respectively). We conclude that leptin levels are elevated in pregnant women with gestational diabetes, and its metabolism depends on insulin levels and the severity of diabetes.     

Decreased maternal serum leptin in pregnancies complicated by preeclampsia

OBJECTIVE: To determine whether circulating levels of leptin differed between women with preeclampsia and women who had an uncomplicated pregnancy. METHODS: Maternal and umbilical venous plasma leptin concentrations obtained at delivery were compared in 36 pairs of women with either preeclampsia or normal pregnancy, matched 1:1 for prepregnancy body mass index and fetal gestational age at delivery. RESULTS: Prepregnancy body mass index was 21.1 +/- 2.1 kg/m2 in either study group (range 17.6-25.3 kg/m2 and 17.7-25.3 kg/m2 in the normal and preeclamptic group, respectively). Mean fetal gestational age at delivery was 40.1 +/- 1.3 weeks and 40.1 +/- 1.2 weeks in the normal and preeclamptic group, respectively. Median leptin concentrations were significantly lower (P <.0001) in women with preeclampsia (8.3 ng/mL, range 3.5-20.0 ng/mL) than in normal pregnant women (20.2 ng/mL, range 6.0-63.7 ng/mL). Median umbilical venous leptin was not significantly different between groups (preeclampsia 11.8 ng/mL, range 2.0-37.2 ng/mL; normal 7.6 ng/mL, range 1.6-24.3 ng/mL; P = .377). Umbilical venous leptin levels correlated positively with birth weight in both groups (preeclampsia rho = 0.501, P = .002; normal rho = 0.517, P = .001), whereas no correlations were found between maternal and fetal hormone concentrations. Maternal leptin concentrations did not correlate with birth weight. CONCLUSION: Our data suggest that the correlation between umbilical venous leptin concentration and birth weight is independent of the presence of preeclampsia. Given the inconsistency in literature concerning circulating leptin levels in preeclampsia, further studies should investigate the regulatory systems of leptin in preeclampsia.     

Predictive value of increased plasma levels of fibronectin in gestational hypertension

Blood pressure, proteinuria, and plasma fibronectin and plasminogen activator inhibitor-1 levels were measured in 120 apparently healthy normotensive primigravid women during the first, second, and third trimesters of pregnancy and 2 days post partum. Thirty-two women developed hypertension (diastolic blood pressure greater than or equal to 90 mm Hg) that in 17 women was associated with proteinuria (greater than 0.3 gm/day). Fibronectin levels were 83% +/- 22% of normal (mean +/- SD) during the first trimester and 75% +/- 20% at term in the healthy women but increased from 94% +/- 36% to 187% +/- 36% in the women who developed gestational hypertension (with or without proteinuria) (p less than 0.0001). Plasminogen activator inhibitor-1 levels increased from 26 +/- 19 ng/ml to 110 +/- 86 ng/ml in healthy women and from 32 +/- 35 ng/ml to 290 +/- 90 ng/ml in hypertensive women (p less than 0.001). Increased levels of fibronectin at 25 to 36 weeks of pregnancy (greater than or equal to mean + 2 SD of the healthy women, or greater than 140%) were found in 31 of the 32 women with gestational hypertension with or without proteinuria and in 5 of the 88 healthy women (sensitivity 96%, specificity 94%). Fibronectin levels increased 3.6 +/- 1.9 weeks earlier than the onset of hypertension and/or proteinuria. Increased levels of plasminogen activator inhibitor-1 at 25 to 32 weeks (greater than or equal to 280 ng/ml) were found in 16 of the 32 women who developed gestational hypertension with or without proteinuria and in 4 of the 88 healthy women (sensitivity 50%, specificity 95%). We conclude that increased fibronectin levels are the best predictor of gestational hypertension with or without proteinuria and that its level in plasma increases several weeks before the development of hypertension.     

Maternal serum concentrations of CA-125 in second trimester pregnancy complicated by congenital fetal anomalies

OBJECTIVE: The purpose of the study was to determine the value of maternal serum CA-125 concentrations in pregnancies complicated by fetal anomalies with or without hydramnios. STUDY DESIGN: The study population (n=40) consisted of the following four groups of patients: (1) 10 women with abnormal maternal serum alpha fetal protein (MSAFP) in whom no fetal anomalies were observed; (2) 10 women in whom fetal anomalies were diagnosed in addition to abnormal MSAFP; (3) 10 women with fetal anomalies accompanied by hydramnios and abnormal MSAF, and (4) 10 women had normal MSAFP and were diagnosed with hydramnios without fetal anomaly. The control group consisted of 10 patients who were matched for gestational age with normal MSAFP and normal ultrasonographic examination. In all 50 cases MSAFP and maternal serum CA-125 levels were assessed. CA-125 was measured using OC 125 monoclonal antibody (IMX CA-125, Abott Lab. IL) and a value of >20 U/ml was defined as abnormal. RESULTS: Maternal serum CA-125 levels were significantly higher in the study group than in the control group, 19.8+/-15.9 U/ml and 9.9+/-4.0 U/ml (P=0.015). The difference was even greater when patients with malformed fetuses and hydramnios were compared to those with fetal anomalies and normal amount of amniotic fluid, 32.4+/-12.7 U/ml and 7.2+/-2.1 U/ml, respectively (P=0.0005). The maternal serum CA-125 levels in patients with hydramnios but without fetal anomalies were significantly lower when compared with those of the malformed fetuses and hydramnios, 9.8+/-2.3 U/ml and 32.4+/-12.7 U/ml, respectively (P=0.002). CONCLUSION: Maternal serum CA-125 is lacking in value for screening fetal structural anomalies as a significant increase in maternal serum CA-125 levels was found only in patients with fetal anomalies accompanied by hydramnios.     

Preeclampsia disrupts the normal physiology of leptin

This study was designed to examine the leptin levels of preeclamptic women and their offspring, to compare them with those of normal pregnant women and to search for a correlation between maternal and fetal plasma leptin levels and their anthropometric characteristics. Twenty-one preeclamptic women and their babies were enrolled into the study. Control group consisted of 21 normal pregnant women and their babies, whose birth weights, gestational ages, and genders match with those of babies born to preeclamptic women. Median maternal leptin concentrations of the preeclamptic group (15.3 ng/mL) were significantly higher ( p = 0.03) than the control group (10.4 ng/mL). However, fetal plasma leptin concentrations were not different ( p = 0.06) between the two groups. Fetal plasma leptin levels were correlated with birth weight, length, body mass index, gestational age, and fetal hematocrit levels in the control group. However, no correlation between leptin levels and these parameters was found in the preeclamptic group. Therefore, preeclampsia may be thought to disrupt normal leptin physiology.     

A comparative study of serum soluble vascular cell adhesion molecule-1 and soluble intercellular adhesion molecule-1 in preeclampsia.

OBJECTIVES: Maternal serum soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1) were evaluated in preeclampsia to investigate whether these molecules could be helpful with regard to this pregnancy complication. STUDY DESIGN: The study population was composed of 30 preeclamptic patients with a mean gestational age of 35.5 +/- 4.6 weeks and 20 age-matched and gestational age-matched normotensive uncomplicated pregnancies (controls). Blood samples from 7 of the 30 preeclamptic patients and 15 of the 20 controls in the second trimester were also analyzed. Data were analyzed by parametric methods. RESULTS: Significantly higher maternal serum sVCAM-1 levels were found in both groups of preeclamptic patients with and without fetal growth restriction (981 +/- 145 ng/ml; n = 13; p < 0.0005 and 846 +/- 84 ng/ml; p < 0.02, respectively) compared with controls (668 +/- 186 ng/ml). In contrast, no significant difference was found in maternal serum sICAM-1 levels between preeclamptic and normotensive pregnancies, or in both adhesion molecules (1) in the controls between second and third trimester samples and (2) in the second trimester between pregnant women who developed preeclampsia later and gestational age-matched controls. CONCLUSION: These findings show a selective significant elevation of maternal serum sVCAM-1 in preeclampsia, with the highest values in cases complicated with fetal growth restriction, perhaps reflecting its angiogenic function. Hence, sVCAM-1 could be helpful in the diagnosis of this fetal complication in preeclampsia.     

孕妇外周血中胎儿DNA水平检测在子痫前期诊断中的应用

目的探讨孕妇外周血中胎儿DNA水平检测在子痫前期诊断中的应用价值。方法选择30例子痫前期孕妇为子痫前期组(其中轻度18例,重度12例),另选择30例正常孕妇作为对照组,两组孕妇分别于孕20周、孕晚期(子痫前期组孕33周+3、对照组孕34周+3)、分娩后1、3、6 h取外周血,采用荧光定量PCR检测外周血中Y染色体上的性别决定基因(SRY基因)胎儿DNA水平(B超确定两组孕妇所妊娠的胎儿均为男性);放射免疫法检测两组孕妇孕晚期内皮素水平。结果(1)子痫前期组孕20周时的胎儿DNA水平为(316±61)copy/m l,其中轻度、重度患者分别为(266±79)、(396±91)copy/m l;对照组孕妇为(165±43)copy/m l,子痫前期组及轻度、重度患者明显高于对照组,两组比较,差异有统计学意义(P<0.01)。(2)子痫前期组孕晚期胎儿DNA水平为(970±413)copy/m l,其中轻度、重度患者分别为(758±357)、(1285±573)copy/m l,对照组孕妇为(319±99)copy/m l,子痫前期组及轻度、重度患者明显高于对照组,两组比较,差异有统计学意义(P<0.01)。(3)子痫前期组产后1、3、6 h胎儿DNA水平分别为(139±45)、(76±31)、(44±13)copy/m l,其中轻度患者分别为(102±42)、(57±25)、(36±12)copy/m l,重度患者分别为(209±51)、(97±40)、(52±17)copy/m l;对照组分别为(33±13)、(9±5)、0 copy/m l。子痫前期组及轻度、重度患者明显高于对照组,两组比较,差异有统计学意义(P<0.01)。(4)子痫前期组内皮素水平为(80±18)ng/L,其中轻度患者为(74±14)ng/L,重度患者为(89±32)ng/L;对照组为(50±11)ng/L,子痫前期组及轻度、重度患者明显高于对照组,两组比较,差异有统计学意义(P<0.01)。(5)子痫前期组胎儿DNA水平与内皮素水平呈正相关关系(r=0.748,P<0.01)。结论孕妇外周血胎儿DNA水平变化可以作为预测和诊断子痫前期发病与疾病程度的一个指标。     

Diabetic pregnancy associated with increased epidermal growth factor in cord serum at term

OBJECTIVE: Epidermal growth factor is a ubiquitous mitogen that also possesses insulin-like properties. Fetal mal-growth is associated with altered epidermal growth factor levels. Maternal diabetes is frequently complicated by macrosomia, but the effect of maternal diabetes on fetal epidermal growth factor levels is not known. We studied cord serum epidermal growth factor concentrations in pregnancies complicated by diabetes and in normal pregnancies. METHODS: Cord serum epidermal growth factor concentrations were measured at birth by a sandwich-type time-resolved immunofluorometric assay in 63 pregnancies complicated by insulin-dependent diabetes mellitus, in 25 pregnancies complicated by insulin-treated gestational diabetes, and in 56 normal pregnancies. RESULTS: Cord serum epidermal growth factor correlated positively with the duration of pregnancy in diabetic and normal pregnancies. In a subgroup of women at similar gestational ages (38-39 weeks), cord serum epidermal growth factor concentrations were higher in pregnancies complicated by insulin-dependent diabetes mellitus (962 +/- 211 ng/L, P =.047; n = 9) and in pregnancies complicated by gestational diabetes (1133 +/- 115 ng/L, P =.001; n = 9) than in controls (564 +/- 75 ng/L; n = 22). In multiple regression analysis, only umbilical artery hemoglobin in diabetic pregnancies and vaginal delivery in normal pregnancies were associated with cord serum epidermal growth factor. CONCLUSION: Epidermal growth factor concentrations are higher than normal in fetuses of diabetic mothers at term. Pregnancy complications, such as hypertensive disorders, fetal hypoxia and fetal malgrowth, may not explain the rise in epidermal growth factor levels. We hypothesize that the rise in epidermal growth factor levels is a metabolic response of the fetoplacental unit to diabetes-related hyperglycemia. LEVEL OF EVIDENCE: III     

Quantitative analysis of DNA levels in maternal plasma in normal and Down syndrome pregnancies

BACKGROUND: We investigated fetal and total DNA levels in maternal plasma in patients bearing fetuses affected with Down syndrome in comparison to controls carrying fetuses with normal karyotype. METHODS: DNA levels in maternal plasma were measured using real-time quantitative PCR using SRY and beta-globin genes as markers. Twenty-one pregnant women with a singleton fetus at a gestational age ranging from 15 to 19 weeks recruited before amniocentesis (carried out for reasons including material serum screening and advanced material age), and 16 pregnant women bearing fetuses affected with Down syndrome between 17 to 22 weeks of gestation were involved in the study. RESULTS: The specificity of the system reaches 100% (no Y signal was detected in 14 women pregnant with female fetuses) and the sensitivity 91.7% (SRY amplification in 22 of 24 examined samples). The median fetal DNA levels in women carrying Down syndrome (n=11) and the controls (n=13) were 23.3 (range 0-58.5) genome-equivalents/ml and 24.5 (range 0-47.5) genome-equivalents/ml of maternal plasma, respectively (P = 0.62). The total median DNA levels in pregnancies with Down syndrome and the controls were 10165 (range 615-65000) genome-equivalents/ml and 7330 (range 1300-36750) genome-equivalents/ml, respectively (P = 0.32). The fetal DNA proportion in maternal plasma was 0%-6 % (mean 0.8%) in women carrying Down syndrome and 0%-2.6 % (mean 0.7 %) in the controls, respectively (P=0.86). CONCLUSIONS: Our study revealed no difference in fetal DNA levels and fetal DNA: maternal DNA ratio between the patients carrying Down syndrome fetuses and the controls.     

Lipid peroxidation in women with gestational hypertension complicated by asymetric intrauterine growth retardation

OBJECTIVES: Hypertension in pregnancy is connected with increased rate of prematurity and perinatal morbility. 8-isoprostane and lipid peroxides are the oxidative stress indices, similar to the prostaglandins both connected with vessels restriction. DESIGN: The aim of the study was to find the correlation between concentration of lipid peroxides and 8-isoprostane and the blood pressure in pregnancy. MATERIALS AND METHODS: The study was done in Dep. of Obstetrics and Gynaecology Medical University in Lodz in 2002-2005. The study group consisted of 78 women with diagnosed hypertension in pregnancy, the control group of 50 healthy pregnant women at the same gestational age. Lipid peroxides and 8-isoprostane were measured in maternal blood. The Oxis Immunoassay for 8-epi prostaglandin and LPO 586 were used. The results were expressed in ng/ml and microM. RESULTS: The concentration of 8-isoprostane in women with hypertension was 0,0691 ng/ml, in women with hypertension and IUGR the value of 8-isoprostane was similar--0,0728 ng/ml. In women in normal pregnancy was lower--0,0541 ng/ml. Lipid peroxides and 8-isoprostane concentration in both hypertensive groups was higher than in group of normotensive pregnant women. CONCLUSIONS: In pregnancies complicated by hypertension the concentration of vasorestrictive lipid peroxidation products is higher than in normotensive women and the antioxidative treatment may be used to decrease lipid peroxidation process.     

The renin-aldosterone system during normal and hypertensive pregnancy

Gestational hypertension complicates approximately 5%–7% of pregnancies and it may be deleterious to both maternal and fetal health. Gestational hypertension is a multisystem disorder which always resolves itself after delivery; its primary pathology still remains incompletely clarified. The renin-aldosterone system is a major determinant of sodium balance in pregnancy. To evaluate the changes in renin and aldosterone levels during normal and hypertensive pregnancy we undertook this study. Plasma renin activity and aldosterone levels were measured in 71 pregnant (43 normotensive, 28 hypertensive) and 24 non-pregnant (12 normotensive, 12 hypertensive) women, aged 19–43 years (mean±SD 28±2.8). Women were allocated into the following five groups: Groups 1 and 2 consisted of 12 normotensive and 12 hypertensive non-pregnant women, respectively; group 3 consisted of 20 women (14 normotensive and 6 hypertensive) at 11–19 weeks of gestation; group 4 consisted of 24 women (14 normotensive and 10 hypertensive) at 20–29 weeks of gestation, and group 5 consisted of 27 women (15 normotensive and 12 hypertensive) at 30–37 weeks of gestation. Both plasma renin activity and aldosterone levels progressively increased during normotensive pregnancy and were higher compared to normotensive non-pregnant women. Among hypertensive pregnant women, plasma renin activity levels remained unchanged during the three trimesters of pregnancy and were higher compared to hypertensive non-pregnant women. Only during the third trimester did aldosterone levels significantly increase in hypertensive pregnant women, compared to hypertensive non-pregnant women. Despite stable renin levels, aldosterone levels increased significantly during the third trimester of hypertensive pregnancy. Thus, we conclude that aldosterone biology seems to be directly or indirectly involved in the etiology of gestational hypertension independently of renin levels. Received: 12 July 2000 / Accepted: 25 July 2000     

Beta-endorphin in amniotic fluid in normal and hypertensive gestations: relationship with maternal blood pressure parameters.

beta-Endorphin (beta-E) immunoreactivity was measured in the amniotic compartment of 52 normotensive and 45 hypertensive gestations. All the fetuses of the normal group were healthy and showed appropriate intrauterine growth, whereas only suffering and growth-retarded fetuses were included in the pathological group. As expected, amniotic beta-E concentration was found to be significantly higher in hypertensive than in normotensive pregnancies (mean +/- SEM: 129.1 +/- 8.15 vs. 59.1 +/- 2.68 pg/ml; p < or = 0.005). A positive correlation between the hormone levels and the diastolic as well as the mean maternal blood pressure (r: 0.554; p < or = 0.05 and r: 0.525; p < or = 0.05, respectively) was present only in pregnancies complicated by hypertension. Furthermore, a negative correlation (r: -0.555; p < or = 0.05) linked amniotic beta-E and the pulse pressure in normal but not in complicated pregnancies. Unless beta-E in the amniotic compartment is also of amniochorial origin, our results suggest that the fetal endorphinergic tone is either activated by elevated diastolic and mean maternal pressure levels or lowered by increased pulse pressure values in normally elapsing pregnancies.     

Maternal serum nitric oxide levels associated with biochemical and clinical parameters in hypertension in pregnancy

OBJECTIVES: To measure maternal serum concentrations of total nitrites, as an index of nitric oxide synthesis, in normal and hypertensive pregnant women, and to examine the correlation between these concentrations and several variables of clinical interest. STUDY DESIGN: A total of 60 women in four different groups were studied: 10 normotensive pregnant women, 17 pregnant women with preeclampsia, 18 pregnant women with gestational hypertension and 15 pregnant women with chronic hypertension. Serum nitrite levels were determined using the Griess reaction after reduction with nitrate reductase. RESULTS: Serum nitrite levels were higher in preeclamptic women (34.11+/-14 micromol/l, P=0.04), lower in chronic hypertensive women (19.56+/-6.46 micromol/l, P=0.04) and similar in women with gestational hypertension (26.97+/-9.44 micromol/l) in comparison to the control group (25.37+/-7.24 micromol/l). Serum nitrite levels in preeclamptic women had significant positive correlations with hematocrit, fasting insulinemia, and apolipoprotein B and negative correlations with platelet count, serum phosphorus and glucose:insulin ratio. In pregnant women with chronic hypertension a negative correlation was found between serum nitrite levels and active partial thromboplastin time. In pregnant women with gestational hypertension, serum nitrite levels had negative correlations with birthweight and 24-h urine calcium, and positive correlations with mean corspuscular hemoglobin, 24-h urine sodium and maternal age. CONCLUSIONS: We suggest that in women with preeclampsia, a higher maternal nitric oxide level may act as a compensatory mechanism against hemoconcentration and platelet aggregation and that nitric oxide production may be related to some metabolic events. In women with gestational hypertension, higher serum nitrite levels may be related to clinical and biochemical findings common in preeclampsia. In chronic hypertension, a lower maternal nitric oxide level is related to the status of coagulation.     

特发性胎儿生长受限的病因研究

目的 通过研究胎儿生长受限(FGR)的相关因素,探讨特发性FGR的可能病因。方法63例孕期拟诊为FGR的孕妇,按新生儿出生体重分组,小于该孕龄平均体重第10百分位数的29例为研究组A;大于该孕龄平均体重第10百分位数的34例为研究组B。另选择25例分娩正常体重新生儿的孕妇为对照组。3组孕妇于孕期检测50 g葡萄糖负荷试验(50 g GCT)、75 g葡萄糖耐量试验(75 g OGTT)、瘦素、血红蛋白水平及红细胞压积、感染系列、抗心磷脂抗体(ACA)、脐动脉收缩期与舒张期(S/D)比值。于分娩时检测脐血瘦素、C肽、胰岛素水平及病毒系列、染色体。结果 (1)研究组A孕妇的空腹血糖和餐后3 h血糖分别为(3.8±0.6)mmol/L和(4.5±1.1)mmol/L,脐血瘦素、C肽、胰岛素水平分别为(7.3±5.2)ng/ml、(0.5±0.3)nmol/L、(2.3±1.3)mU/L,脐动脉S/D比值、母、儿巨细胞病毒(CMV)感染率、ACA-IgM阳性率及无症状菌尿症发生率分别为3.06、20.7％、24.1％、44.8％和62.1％。(2)研究组B孕妇的空腹血糖和餐后3 h血糖分别为(4.4±0.7)mmol/L和(4.6±1.1)mmol/L,脐血瘦素、C肽、胰岛素水平分别为(13.2±11.3)ng/ml、(0.7±0.4)nmol/L、(4.3±3.3)mU/L,脐动脉S/D比值、母、儿CMV感染率、ACA-IgM阳性率及无症状菌尿症发生率分别为2.63、2.9％、0、5.9％和44.1     

Treatment of premature labor in insulin-dependent diabetic women

This retrospective study was designed to analyze the safety and efficacy of beta-sympathomimetic agents used to treat premature labor in insulin-dependent diabetic women. The study evaluated 12 insulin-dependent diabetic women who experienced 15 pregnancies complicated by premature labor. A group of 30 insulin-dependent diabetic women who delivered at term served as matched controls. Treatment consisted of parenteral and oral administration of beta-sympathomimetic drugs (ritodrine and isoxsuprine). Premature labor was diagnosed, and tocolytic treatment was initiated at a mean gestational age of 31.5 +/- 0.9 weeks. The mean gestational age at the time of delivery was 35.8 +/- 0.5 weeks. Delivery was delayed in the study group by a mean of 30.5 +/- 6.6 days. No fetal or infant deaths occurred in the study group, and there was no difference between the two groups in the incidence of neonatal morbidity. No maternal complications occurred. There were no significant differences in hemoglobin A1 levels between the two groups at any period of gestation. Thus, beta-sympathomimetic drugs may be used safely to treat premature labor in patients with insulin-dependent diabetes, provided they are administered under strictly controlled clinical settings.     

妊娠晚期孕妇血清可溶性endoglin水平与子(癎)或子(癎)前期的关系

目的 探讨妊娠期高血压疾病(HDCP)患者血清可溶性endoglin(sEng)水平的变化及其与该疾病发生的关系.方法 采用酶联免疫吸附实验检测62例HDCP患者(包括妊娠期高血压20例,轻度子(癎)前期20例,重度子(癎)前期19例,子(癎)3例)和20例正常足月妊娠妇女血清sEng水平.结果 正常妊娠组、妊娠期高血压组、轻、重度子(癎)前期组和子(癎)组的血清sEng的浓度分别为(6.24±0.26)ng/ml、(6.56±0.29)ng/ml、(7.47±0.31)ng/ml、(8.71±0.37)ng/ml和(9.69±0.28)ng/ml.子(癎)前期组及子(癎)组与妊娠期高血压组及正常妊娠组比较,差异均有统计学意义(P均<0.01);重度子(癎)前期组水平高于轻度子(癎)前期组,子(癎)组高于重度子(癎)前期组(P均<0.01);妊娠期高血压与正常妊娠组相比差异无统计学意义(P>0.05).结论 sEng可能在HDCP的发生发展过程中起一定作用.