Non-preeclamptic Pregnant Women Research Articles

Association of TNFSF11 rs2200287 and TNFSF11 rs2148072 gene polymorphisms in preeclampsia.

Various cytokines released by white blood cells like lymphocytes are linked to the immune system during pregnancy. The polymorphism of the TNFSF11 (rs2200287 and rs2148072) gene is related to the preeclampsia of pregnancy. This study was a prospective study involving 304 pregnant women with preeclampsia (n=152) and controls (non-preeclamptic pregnant women) (n=152). To investigate the rs2200287 and rs2148072 SNP's of TNFSF11 gene polymorphism by using the PCR-RFLP techniques. A significantly different genotype distribution of TNFSF11 (rs2200287 and rs2148072) polymorphisms were observed between the two groups, with the G allele of variant rs2200287 was highly significant in the preeclamptic group (P=0.000; .5814; OR=.5814; 95% CI=.4211-.8012). And the C allele of variant rs2148072 was also highly significant in the preeclamptic group (P=0.000; OR=.5076; 95% CI, .362-.71) in this study. The outcomes of the present study indicate that there was an association in TNFSF 11 (rs2200287 and rs2148072) gene polymorphism with preeclampsia compared to non-preeclampsia women.

Magnitude of H. pylori and Its Association with Preeclampsia Among Pregnant Women in Ethiopia: A Case Control Study.

BackgroundHelicobacter pylori infections are associated with many complications of pregnancy including preeclampsia. It has been suggested that H. pylori infection could contribute to the etiopathogenesis of preeclampsia by inducing a pro-inflammatory state.ObjectiveTo assess the magnitude of H. pylori infection and its association with preeclamptic and non-preeclamptic pregnant women attending antenatal care in Ethiopia.MethodsHospital-based case control study was conducted among clinically diagnosed preeclamptic and non-preeclamptic pregnant women. Stool samples were collected for H. pylori antigen test from study participants. The collected data were analyzed using statistical methods in SPSS version 23. Simple descriptive statistics were used to present the socio-demographic and clinical characteristics of the study subjects. Association between clinical variables, preeclampsia and H. pylori infection was performed with multivariate logistic regression. A p-value of <0.05 at 95% confidence level was considered as statistically significant in all the analyses.ResultsA total of 93 cases and 186 controls were included in this study. The overall prevalence of H. pylori infection in all study participants was 38.9% (16/272). The prevalence of H. pylori infection was higher in cases than controls, 54.3% (50/92) vs 31.1% (56/180), respectively. The mean age was 29.01 (SD±4.93) years in cases and 30.37 (SD± 6.2) years in control group. A positive association was found between H. pylori infection and preeclampsia (OR: 2.45; 95% CI: 2.41–4.10).ConclusionH. pylori infection has been found to be associated with preeclamptic pregnant women. In this study, the prevalence of H. pylori infection was higher in cases than in controls. Age group, educational status, occupational status and body mass index were significantly associated with preeclamptic women with H. pylori. The association of H. pylori with preeclampsia needs to be further explored.

Serum Vasostatin-1 Level is Increased in Women with Preeclampsia.

To evaluate the serum vasostatin-1 levels in preeclamptic and non-preeclamptic pregnant women. Thirty consecutive women with mild preeclampsia and sixty consecutive women with severe preeclampsia were compared with ninety gestational age-matched (±1 week) non-preeclamptic pregnant women with an appropriate-for-gestational-age (AGA) fetus. Mean serum vasostatin-1 was significantly higher in women with preeclampsia than gestational age-matched controls. Mean serum vasostatin-1 was significantly higher in the mild preeclampsia group compared to its gestational age-matched control group, and in the severe preeclampsia group compared to its gestational age-matched control group. There was no significant difference in mean serum vasostatin-1 levels between the mild and severe preeclampsia groups, and in severe early- and severe late-onset preeclampsia groups. Serum vasostatin-1 had positive correlations with systolic and diastolic blood pressure. Serum vasostatin-1 was significantly higher in women with preeclampsia compared to those of the gestational age-matched controls. There was no significant difference in mean serum vasostatin-1 levels between the mild and severe preeclampsia groups and severe early- and severe late-onset preeclampsia groups.

To compare serum Vitamin D status in pre-eclamptic and non-preeclamptic pregnant women in labour: A tertiary care centre study of Northern India

Background: Pre-eclampsia and eclampsia have remained a major global public health threat in contributing significantly to maternal and perinatal morbidity and mortality. Based on the inverse relationship between serum 1,25(OH)2D3 levels and plasma renin activity found previously, it is speculated that 1,25(OH)2D3 might be a negative endocrine regulator of renin production in vivo. During pregnancy, vitamin D may play a role in implantation and placental function potentially due to angiogenic, immunomodulatory, and antiinflammatory effects. Vitamin D deficiency can affect the health of both mother and fetus by increasing the production of inflammatory cytokines and stimulating the activity of T-regulating cells. Vitamin D is emerging as a promising agent for pre-eclampsia prevention. Aims and objectives: The objective of this study is to compare the vitamin D levels in pre-eclamptic and healthy non-pre-eclamptic pregnant women in labor and find out the relationship between vitamin D levels and pre-eclampsia. Methodology: The present cross-sectional study was carried out on pregnant women with pre-eclampsia in labor. For each case with pre-eclampsia, one uncomplicated, normotensive pregnant woman in labor was taken as control. On admission to the labor room detailed history, physical examination followed by thorough obstetrics and systemic examination was done. Required investigations were done including vitamin D and calcium levels. Maternal and fetal condition was monitored during labor/cesarean section, mode of delivery, maternal and fetal outcomes were recorded. After delivery, 2cc of cord blood was collected in a serum tube and sent for vitamin D levels. Data was collected and analyzed statistically using Epi-info version 7.1. Results: It was observed that the patients in both groups were comparable with respect to demographic and obstetrics characteristics except for significantly high BP in group I. Vitamin D deficiency (i.e. &lt; 20 ng/ml) was significantly more in group I as compared to group II and the difference was highly significant (p &lt; 0.0001). Similarly, the mean maternal calcium levels were significantly lower in group I in comparison to group II (p &lt; 0.0001) i.e. the mean maternal calcium level in group I and group II were 8.03 ± 0.94 and 9.19 ± 0.67 respectively. It was also observed that the level of 25-OH-D in neonates of preeclamptic women was significantly lower than for those of the normal pregnant women (p &lt; 0.0001). Conclusion: Vitamin D deficiency is highly prevalent in all parts of the world. Pregnant women and neonates are highly vulnerable to vitamin D deficiency. Preeclampsia is indeed associated with lower vitamin D levels and the pathophysiology of pre-eclampsia involves vitamin D and calcium metabolism through their role in immunomodulation, angiogenesis and anti-inflammatory effects. From the present study, it was observed that vitamin D and calcium levels were significantly lowered in women with pre-eclampsia as compared to those of the normotensive pregnant women. So early detection of vitamin D and calcium deficiencies may be helpful in preventing occurrence of PET and its complications.

Incremental prognostic value of global left atrial peak strain in women with new-onset gestational hypertension.

Left atrial strain and strain rate parameters, measured by bidimensional-speckle tracking echocardiography, have been proposed as predictors of atrial fibrillation, stroke, congestive heart failure and cardiovascular death. However, they have not yet been tested in hypertensive disorders of pregnancy. The aim of this study was to assess the prognostic role of global left atrial peak strain (GLAPS) in a population of pregnant women with new-onset hypertension in a medium-term follow-up. Twenty-seven consecutive women with new-onset hypertension after 20 weeks pregnancy and 23 age-matched, race-matched and gestational week-matched consecutive normotensive pregnant women were enrolled in this prospective study. All participants underwent a complete echocardiographic study with bidimensional-speckle tracking echocardiography and carotid examination. At 1-year follow-up, we evaluated the occurrence of persistent hypertension. In comparison with normotensive women, those hypertensive had a higher burden of cardiovascular risk factors, similar left atrial volume indexed (P = 0.14), but severely impaired left atrial strain (P < 0.0001) and strain rate values (P < 0.0001). At 1-year follow-up, persistent hypertension was documented in 59.3% of patients. At the univariate Cox analysis, the variables associated with the occurrence of the investigated outcome in all hypertensive pregnancies were SBP (hazard ratio 1.04, P = 0.04), DBP (hazard ratio 1.11, P = 0.01), mean arterial pressure (hazard ratio 1.09, P = 0.01) values and the GLAPS value (hazard ratio 0.85, P = 0.0019). The latter was significantly associated with the investigated outcome both in preeclamptic (hazard ratio 0.84, P = 0.02) and nonpreeclamptic pregnant women (hazard ratio 0.83, P = 0.04). The receiver operating characteristics curve analysis highlighted that a GLAPS value of 23.5% or less predicted persistent hypertension with sensitivity of 100% and specificity of 90.90%. In hypertensive pregnant women a GLAPS value of 23.5% or less reveals a greater severity of atrial cardiomyopathy and might predict postpregnancy persistent hypertension.

Impact of HOTAIR variants on preeclampsia susceptibility based on blood and placenta and in silico analysis.

HOX transcript antisense RNA (HOTAIR) as a lncRNA involves in epigenetic regulation of various genes. Several studies have been suggested the effects of HOTAIR polymorphisms on different diseases. The aim of the present study was to evaluate the effect of maternal and placental HOTAIR polymorphisms on risk of preeclampsia (PE). The maternal blood of 203 preeclamptic and 202 nonpreeclamptic pregnant women as well as the placentas of 87 of preeclamptic and 95 nonpreeclamptic pregnant women were genotyped for HOTAIR polymorphisms. There was no association between maternal and placental HOTAIR polymorphisms (rs12826786, rs920778, and rs1899663) and PE risk. However, the maternal rs4759314AG and dominant model genotypes were associated with increased risk of PE. The maternal and placental HOTAIR rs10783618 polymorphism was associated with PE risk in recessive and allelic models. Haplotype analysis showed that, the maternal CTGAT and CCTAT and placental CTGAT haplotypes were significantly higher and maternal CTGAC, TCTAT, and TTGAT and placental CTGAC haplotypes were significantly lower in PE women. In silico analysis revealed that HOTAIR rs1899663 had a main effect on the secondary structure of mRNA, however, HOTAIR rs4759314 variant had potential alteration of splicing. In conclusion, the maternal and placental HOTAIR rs10783618 polymorphism might increase PE susceptibility. © 2019 IUBMB Life, 71(9):1367-1381, 2019.

Relationship between serum zinc levels and preeclampsia at the University Teaching Hospital, Lusaka, Zambia

&#x0D; Background: Preeclampsia is one of the common conditions in the pregnant mothers in Zambia. This condition has been shown in some studies to be associated with increased oxidative stress. This study aimed at evaluating the association of zinc, an important cofactor in the antioxidant metalloproteins in the aetiology of preeclampsia&#x0D; Methods: A comparative cross-sectional study design was employed on conveniently sampled 41 preeclamptic and 57 non-preeclamptic pregnant women over a four month period at the University Teaching Hospital in Lusaka, Zambia. Serum samples from participants were analysed for Zinc concentration by Atomic Absorption Spectrometry.&#x0D; Results: There was no significant difference in the mean serum Zinc levels between the preeclamptic and the nonpreeclamptic pregnant women.&#x0D; Conclusion: Based on our findings serum zinc level is not associated with the occurrence of preeclampsia .&#x0D;

Transorbital Ultrasonographic Measurement of the Optic Nerve Sheath Diameter in Preeclampsia [24J

INTRODUCTION: Preeclampsia is ranked as the second leading cause of maternal mortality worldwide, mostly due to acute cerebral complications. The objective of this study is to estimate the frequency of increased intracranial pressure (ICP) using transorbital ultrasound among pregnant women with and without preeclampsia. METHODS: Between September and October 2014, a cross-sectional study was conducted in a tertiary care hospital in Recife, Brazil. Ultrasonographic measurements of the optic nerve sheath diameter (ONSD), using a 10–12 MHz ultrasound linear probe, were performed in two groups: preeclamptic patients and non-preeclamptic pregnant women. Fisher's exact test was used to compare categorical data established to detect increased intracranial pressure between groups. RESULTS: A total of 33 cases were included in the study: 18 women with and 15 without preeclampsia with a mean (SD) age of 27.7 (7.4) and 23.3 (7.2) years respectively. The most frequent severe features in the patients with preeclampsia were: BP ≥160/110 mm Hg (100%), headache (22.2%) and focal neurologic signs (22.2%). Signs of elevated ICP were found in 27.7% of preeclamptic women, whereas none of the healthy ones had the ONSD measurement above 5 mm (value associated to detect ICP >20 cm H2O with a sensitivity of 88% and specificity of 93%). There was a statistically significant relation between increased ICP and preeclampsia (P<.05). CONCLUSION: Ultrasonographic measurement of the ONSD is a promising tool for the assessment of increased ICP and risk stratification in patients with preeclampsia. Further studies are necessary to substantiate the value of this non-invasive technique considering the possible neurologic complications in preeclampsia.

Vitamin D Status in Preeclamptic and Non-preeclamptic Pregnant Women: A Case-Control Study in the North West of Iran.

Background: There are few studies on the vitamin D status in preeclamptic women. The objective of this case-control study was to determine vitamin D status, in preeclamptic women and compare it with that of healthy pregnant controls. Methods: Forty preeclamptic women, aged 18 to 45yr and forty age- and pregnancy weight-matched healthy controls participated in the study. Serum 25-hydroxy vitamin D (25(OH)D) levels were measured and its levels of <10, 10-30, 30-90 and >90 nanogram per milliliter (ng/ml) were considered as vitamin D deficiency, insufficiency, sufficiency, and toxicity, respectively. Results: Sixty and forty percent of preeclamptic women were vitamin D deficient and insufficient, while in the control group they were 10% and 90%, respectively. No significant difference was found in the median intake of vitamin D between preeclamptic and non preeclamptic women (1.45 and 1.20µg/day respectively), but serum 25(OH)D concentration was significantly lower in preeclamptic cases compared to controls (10.09 ± 6.66 and 15.73 ± 5.85ng /ml respectively, P= 0.002) . Conclusion: Vitamin D deficiency is common among preeclamptic and non-preeclamptic pregnant women in the north-west of Iran. Preeclampsia can cause decreasing of serum level of 25(OH)D.

Influence of preeclampsia and gestational obesity in maternal and newborn levels of vitamin D.

BackgroundIn recent years, a high prevalence of vitamin D deficiency amongst pregnant women and newborns has been observed throughout several regions of the world, especially in the presence of preeclampsia (PE) or obesity (OB). The aim of this study was to investigate whether nonobese and obese preeclamptic pregnant women and their newborns have low 25(OH)D compared with nonobese and obese nonpreeclamptic pregnant women; and to verify whether the maternal level of this vitamin correlates with the newborns’ level.MethodsThis is a cross-sectional study conducted with 179 pregnant women recruited immediately before delivery, divided into four groups: PE+/OB−; PE+/OB+; PE−/OB+; and PE−/OB−, with gestational age ≥ 34 weeks. Maternal peripheral blood and newborns umbilical cord blood were collected and 25(OH)D levels were measured by chemiluminescence (LIAISON®).ResultsInfants born to preeclamptic mothers had a lower median 25(OH)D level than those born to nonpreeclamptic mothers (p < 0.01). Obese pregnant women and their newborns had higher frequencies of 25(OH)D deficiency, but the difference with respect to nonobese pregnant women and their newborns was not significant. The vitamin D status of preeclamptic obese women was not worse than that of their nonobese counterparts. Newborns and maternal 25(OH)D levels were significantly correlated (p = 0.01). Obesity weakened this correlation.ConclusionsPreeclamptic women and their newborns presented higher frequencies of 25(OH)D deficiency, but 25(OH)D levels were not significantly influenced by obesity. Obese pregnant women transferred less 25(OH)D to their fetuses.

Tumor Necrosis Factor-Alpha Polymorphism at Position -238 in Preeclampsia

Background:Preeclampsia is the most common serious disorder during pregnancy and studies show several immune-related processes in its pathophysiology. The role of cytokines and their expression remains controversial in this field. One of the cytokines of interest in recent studies has been TNF-α, which has been shown to have a higher level in maternal plasma of preeclamptic women.Objectives:This study was designed to evaluate the role of TNF-α polymorphism at position -238 in the risk of developing preeclampsia during pregnancy.Patients and Methods:One hundred fifty three preeclamptic cases and 140 healthy pregnant women were retrieved from two major hospitals of Mashhad, Iran. Methods a case-control study were designed. Anyone with a history of inflammatory disease, hypertension, or chronic kidney disease was excluded. DNA was extracted from peripheral blood leukocytes. Both groups were genotyped for the polymorphism of the TNF-α gene at position -238 by the RFLP method with Ava II enzyme. Allele and genotype frequencies were compared using one-way ANOVA and the Fisher’s exact test.Results:There were significant differences between the two groups in TNF-α genotype at position -238 (P < 0.001). In the preeclamptic group, the frequency of the AA genotype was higher (P < 0.001) and the frequency of the GG genotype was lower (P < 0.001). The overall prevalence of the A allele at position -238 was higher in preeclamptic cases (P < 0.001).Conclusion:In this study group, TNF-α -238 polymorphism was shown to be different in preeclamptic and non-preeclamptic pregnant women. The AA genotype and the A allele may carry an increased risk for developing of preeclampsia.

Increased MPV Is Not a Significant Predictor for Preeclampsia During Pregnancy

Preeclampsia, defined as the presence of hypertension and proteinuria, is usually related with maternal and neonatal adverse effects. However, the exact predictor of preeclampsia is still lacking. Even though there are some conflicting data, mean platelet value or MPV, that is, platelet ratio with or without Doppler velocimetry was determined as highly sensitive markers for preeclampsia. We aimed to investigate the utility of MPV in prediction of preeclampsia. Seventy-four preeclamptic pregnant women (21 in mild, 53 in severe preeclampsia groups) were included in the study. To assess the difference of MPV between preeclamptic, normal pregnant, and healthy control rather than mild and severe preeclamptic pregnant women, we included in the analysis 31 healthy pregnant women and 35 healthy nonpregnant women. Mean age of the preeclamptic patients was 25.3 (17-38) years. Platelet levels were higher in mild preeclampsia (group 1) than severe preeclampsia (group 2), whereas alanine aminotransferase (AST), hemoglobin, and hematocrit level was higher in group 2. MPV levels were found to be similar in groups 1 and 2, MPV level increased from healthy control to preeclamptic women (P = 0.003). MPV:platelet ratio was similar according to the severity of preeclampsia (P = 0.123). Doppler velocimetry did not add an additional benefit to predict preeclampsia or its severity. Our results showed that MPV level was higher in the pregnant than the control group. However, MPV did not differ both between mild and severe preeclampsia, and preeclampsia and non-preeclamptic pregnant women.

The Relationship between Maternal Plasma Leptin Levels and Fetal Growth Restriction

Leptin is a satiety hormone secreted from the adipose tissue and human placenta. We previously demonstrated that severe preeclampsia up-regulated leptin mRNA expression in the placenta and elevated maternal plasma leptin concentrations. Preeclampsia is frequently related to generation of small for gestational age (SGA) infant especially in cases with severe preeclampsia. However, it is still controversial whether the increase in maternal plasma leptin levels is associated with fetal growth restriction without complication of preeclampsia. Therefore, the aim of the present study was to explore the relationship between maternal plasma leptin levels and fetal growth in non-preeclamptic (n = 98) and preeclamptic (n = 40) women. In non-preeclamptic pregnant women, plasma leptin levels in SGA group (n = 11) were significantly higher than those in appropriate for gestational age (AGA) group (n = 87, P<0.05). In pregnant women with preeclampsia, likewise, plasma leptin levels in SGA group (n = 15) were significantly higher than those in AGA group (n = 25, P<0.05). In multiple linear regression analysis, maternal BMI, mean arterial blood pressure and Delta SD of neonatal body weight were significant factors for determining maternal plasma leptin levels in all population studied. Maternal BMI and Delta SD of neonatal body weight showed positive correlation with maternal plasma leptin levels when analysis was performed in non-preeclamptic subjects alone. In conclusion, maternal plasma leptin levels reflect, at least partly, deterioration in fetal growth.

Circadian Rhythm of Blood Pressure Challenges Office Values as the “Gold Standard” in the Diagnosis of Gestational Hypertension

Despite poor sensitivity and specificity, office blood pressure (BP) determinations are still the “gold standard” for diagnosing gestational hypertension. This prospective blind study evaluates the prognostic value of office values as compared with ambulatory monitoring in pregnancy. We analyzed 2175 BP series systematically sampled from 355 non-preeclamptic pregnant women for 48 h every 4 wks from the first hospital visit until delivery. Women were divided for comparative purposes into three groups: “detected” gestational hypertension, defined on the basis of casual clinical BP>140/90 mm Hg after 20 wks of gestation and hyperbaric index (area of BP excess above the upper limit of a time-specified tolerance interval adjusted for the circadian pattern of the reference population) consistently above the threshold for diagnosing hypertension in pregnancy; “undetected” gestational hypertension, women with office BP<140/90 mm Hg but hyperbaric index consistently above the threshold for diagnosis; and normotension, women with both office values and hyperbaric index below the respective thresholds for diagnosis. Small and insignificant differences in the 24 h mean BP between “detected” and “undetected” gestational hypertension is observed in all trimesters, in contrast with highly significant differences between these two groups and normotensive pregnancies. Normotensive women are characterized by highly significant lesser incidence by 60% in preterm delivery, 70% in intrauterine growth retardation, and 50% in delivery by cesarean section (P<0.001) compared with women with “detected” and “undetected” gestational hypertension (P>0.715). In pregnancy, the hyperbaric index is markedly superior to office BP measurements for diagnosis of what should be truly considered gestational hypertension, and for prediction of the outcome of pregnancy.

Neonatal and maternal serum levels of soluble ICAM-1 in preeclamptic and normal pregnancies.

The aim of this study is to determine whether circulating levels of sICAM-1 were changed in infants of preeclamptic mothers, and factors influencing these levels. Peripheral venous blood samples were obtained from preeclamptic and nonpreeclamptic pregnant women (control) and their babies in the first 2 hours post partum. The enzyme-linked immunoadsorbent assay (ELISA) technique was used to determine concentrations of sICAM-1. Compared with the control group, maternal and neonatal serum sICAM-1 levels were higher in the preeclamptic group. Neonatal levels were correlated with the maternal levels only, and there were no difference between premature and term babies and their mothers. In the control group, on the other hand, premature babies and their mothers had higher sICAM-1 levels than term babies and their mothers, with values close to those of premature group in the preeclamptic group. Neonatal sICAM-1 levels were correlated with gestational age, birth weight, and also with maternal levels. Linear regression analysis of these parameters, however, showed that only the gestational age was significant. The study suggests that perinatal sICAM-1 levels possibly are not independent from the maternal levels. High sICAM-1 levels in infants of preeclamptic mothers and premature babies might reflect the high maternal levels.

AT(1) receptor agonistic antibodies from preeclamptic patients cause vascular cells to express tissue factor.

We recently described autoantibodies (angiotensin-1 receptor autoantibodies, AT(1)-AA) directed at the AT(1) receptor in the serum of preeclamptic patients, whose placentas are commonly infarcted and express tissue factor (TF). Mechanisms of how AT(1)-AA might contribute to preeclampsia are unknown. We tested the hypothesis that AT(1)-AA cause vascular smooth muscle cells (VSMC) to express TF. IgG from preeclamptic patients containing AT(1)-AA was purified with anti-human IgG columns. AT(1)-AA were separated from the IgG by ammonium sulfate precipitation. We transfected Chinese hamster ovary cells overexpressing the AT(1) receptor with TF promoter constructs coupled to a luciferase reporter gene. VSMC were obtained from human coronary arteries. Extracellular signal-related kinase activation was detected by an in-gel kinase assay. AP-1 activation was determined by electromobility shift assay. TF was measured by ELISA and detected by immunohistochemistry. Placentas from preeclamptic women stained strongly for TF, whereas control placentas showed far less staining. We proved AT(1)-AA specificity by coimmunoprecipitating the AT(1) receptor with AT(1)-AA but not with nonspecific IgG. Angiotensin (Ang) II and AT(1)-AA both activated extracellular signal-related kinase, AP-1, and the TF promoter transfected VSMC and Chinese hamster ovary cells, but only when the AP-1 binding site was present. We then demonstrated TF expression in VSMC exposed to either Ang II or AT(1)-AA. All these effects were blocked by losartan. Nonspecific IgG or IgG from nonpreeclamptic pregnant women had a negligible effect. We conclude that AT(1)-AA and Ang II both stimulate the AT(1) receptor and initiate a signaling cascade resulting in TF expression. These results show an action of AT(1)-AA on human cells that could contribute to the pathogenesis of preeclampsia.

Changes in platelet ATP secretion and aggregation during pregnancy and in preeclampsia.

Platelet secretion plays an important role in the aggregation of platelets. However, the quantitative relationship between platelet aggregation and secretion of ATP during pregnancy and in pre-eclampsia has yet to be clarified. This study is designed to determine whether platelet count, volume, aggregation, and the amount of secreted ATP change in healthy, nonpregnant women, nonpreeclamptic pregnant women, and preeclamptic pregnant women and whether beta-thromboglobulin (BTG) and platelet factor 4 (PF-4) concentrations alter in nonpreeclamptic and pre-eclamptic women. Peripheral blood was collected from 114 women. Nonpreeclamptic pregnant women were divided into four groups (gestational weeks 10, 20, 30, and 35). Platelet aggregation and ATP secretion were investigated with the use of a lumi-aggregometer. BTG and PF-4 concentrations in peripheral blood were determined in 12 pregnant and 11 preeclamptic women. The amount of secreted ATP upon induction by 5 microM ADP increased significantly (P < 0.05-0.01) with gestational age. On the other hand, the amount of secreted ATP induced by 5 microg/mL collagen reached the maximal value from gestational weeks 20 to 35 in nonpreeclamptic women. Significantly more platelet aggregation was induced by the ADP and collagen in nonpreeclamptic women in gestational weeks 20 and 30 than in the gestational weeks 10 or 35 (P < 0.05-0.005). The amount of secreted ATP and platelet count were significantly lower (P < 0.05) in preeclampsia than in normal pregnancy. The BTG and PF-4 concentrations were significantly higher (P < 0.05) in preeclampsia than in normal pregnancy. The sensitivity of platelets for ATP secretion may intensify with progression of pregnancy. In normal pregnancy, around gestational week 35, the platelets may exhibit weaker ability to aggregate but maintain the capacity to secrete ATP. In preeclampsia, secreted ATP decreased because platelets may be stimulated to undergo a partial secretion.