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PubMed2005

Recurrence of pre-eclampsia across generations: exploring fetal and maternal genetic components in a population based cohort.

OBJECTIVES: To assess the impact on risk of pre-eclampsia of genes that work through the mother, and genes of paternal origin that work through the fetus. DESIGN: Population based cohort study. SETTING: Registry data from Norway. PARTICIPANTS: Linked generational data from the medical birth registry of Norway (1967-2003): 438,597 mother-offspring units and 286,945 father-offspring units. MAIN OUTCOME MEASURES: Pre-eclampsia in the second generation. RESULTS: The daughters of women who had pre-eclampsia during pregnancy had more than twice the risk of pre-eclampsia themselves (odds ratio 2.2, 95% confidence interval 2.0 to 2.4) compared with other women. Men born after a pregnancy complicated by pre-eclampsia had a moderately increased risk of fathering a pre-eclamptic pregnancy (1.5, 1.3 to 1.7). Sisters of affected men or women, who were themselves born after pregnancies not complicated by pre-eclampsia, also had an increased risk (2.0, 1.7 to 2.3). Women and men born after pre-eclamptic pregnancies were more likely to trigger severe pre-eclampsia in their own (or their partner's) pregnancy (3.0, 2.4 to 3.7, for mothers and 1.9, 1.4 to 2.5, for fathers). CONCLUSIONS: Maternal genes and fetal genes from either the mother or father may trigger pre-eclampsia. The maternal association is stronger than the fetal association. The familial association predicts more severe pre-eclampsia.

Birth Order↗
PubMed2001

The relation between pre-eclampsia at term and neonatal encephalopathy.

OBJECTIVES: To determine whether pre-eclampsia, hypothesised to be an inflammatory condition, is associated with fever in term labour, and confirm and examine the reported association of pre-eclampsia at term with neonatal encephalopathy. DESIGN: Prospective cohort study. SETTING: A Dublin teaching hospital. PARTICIPANTS: 6163 women in labour with singleton pregnancies at term at low risk for intrapartum hypoxia, recruited to a randomised trial examining the effect of admission cardiotocography on neonatal outcome. RESULTS: Pre-eclampsia was associated with maternal fever > 37.5 degrees in labour (odds ratio (OR) 3.39, 95% confidence interval (CI) 2.1 to 5.4); this was independent of obstetric intervention (adjusted OR 2.07, 95% CI 1.24 to 3.47). Pre-eclampsia was associated with neonatal encephalopathy (OR 25.5, 95% CI 8.4 to 74.7); this too was independent of obstetric intervention (adjusted OR 18.5, 95% CI 5.9 to 58.1). Cord arterial pH values were significantly lower in pre-eclamptics (7.20 v 7.24), although severe cord acidaemia was not significantly more common (OR 2.91, 95% CI 0.7 to 9.9). The association of pre-eclampsia with encephalopathy was independent of maternal fever (adjusted OR 16.5, 95% CI 5.1 to 54) and cord acidaemia (adjusted OR 13.5, 95% CI 3.2 to 56.7). CONCLUSIONS: The association of pre-eclampsia with maternal fever at term supports the hypothesis that pre-eclampsia is an inflammatory condition. The association of pre-eclampsia with neonatal encephalopathy is independent of obstetric intervention and cannot be explained by either acidaemia or maternal fever. A systemic inflammatory response in the fetus, perhaps secondary to oxidative stress, could explain the link between maternal pre-eclampsia and neonatal encephalopathy, and this may occur through cerebral vasoconstriction.

Blood Gas Analysis↗
PubMed2006

Risk indicators of pre-eclampsia in north Jordan: is dental caries involved?

BACKGROUND: Despite a huge body of published research, understanding the basic pathology that leads to pre-eclampsia is still incomplete. This study was conducted among women in north Jordan to determine factors associated with pre-eclampsia and to determine if dental caries was involved. METHODS: A case-control study was carried out among women who delivered at Princess Badea Teaching Hospital, Irbid, North Jordan, between September 1, 2004 and January 1, 2005. 115 women with pre-eclampsia and 230 normotensive controls were included in the study. Information regarding participants' demographics, antenatal history and family history were collected through personal interviews. Several oral parameters were measured for each participant. RESULTS: In multivariate analysis, factors found to be associated with increased odds of pre-eclampsia were age > or =35 years (adjusted OR 2.20; 95% CI 1.08, 4.48), nulliparity (adjusted OR 2.73; 95% CI 1.38, 5.39), emotional stress during pregnancy (adjusted OR 4.22; 95% CI 1.79, 9.90), maternal history of pre-eclampsia (adjusted OR 16.04; 95% CI 5.82, 44.22), family history of cardiovascular diseases (adjusted OR 2.82; 95% CI 1.22, 6.51), family history of pre-eclampsia (adjusted OR 23.26; 95% CI 5.07, 106.78), twin births (adjusted OR 37.79; 95% CI 4.22, 338.51), and Body Mass Index (BMI). In comparison with women with pre-pregnancy BMI <25, adjusted OR were 1.97, 95% CI 1.02, 3.81 for women with BMI from 25 to 29.9, and 3.31, 95% CI 1.36, 8.03 for women with BMI > or =30. Mean decayed teeth surface was found to be associated with increased odds of pre-eclampsia (adjusted OR 1.14, 95% CI 1.03, 1.27). CONCLUSION: This study demonstrated no difference to reported risk indicators of pre-eclampsia in other populations, but adds that dental caries may have an association with increased odds of pre-eclampsia.

Adolescent↗
PubMed2002

The upper airway in pregnancy and pre-eclampsia.

Snoring is common in pregnancy, and snoring pregnant women have increased rates of pre-eclampsia. Patients with pre-eclampsia show upper airway narrowing during sleep. The present study aimed to compare upper airway dimensions in pregnant and nonpregnant women and in patients with pre-eclampsia. A total of 50 women in the third trimester of pregnancy and 37 women with pre-eclampsia were recruited consecutively from the antenatal service and matched with 50 nonpregnant women. Upper airway dimensions were measured using acoustic reflection. Comparisons were made by analysis of variance and Student-Newman-Keuls tests. Snoring was reported by 14% of nonpregnant women, 28% of pregnant women, and 75% of pre-eclamptic women (p < 0.001). When seated, pregnant women had wider upper airways than nonpregnant women (p < 0.02), but there was no difference when supine. Oropharyngeal junction area in the seated position was less (p < 0.01) in the women with pre-eclampsia (mean +/- SD: 0.9 +/- 0.1 cm2) than either nonpregnant (1.1 +/- 0.1 cm2) or pregnant women (1.3 +/- 0.1 cm2). Supine oropharyngeal junction area was less in the women with pre-eclampsia than in the nonpregnant women (0.8 +/- 0.1 versus 1.0 +/- 0.1 cm2; p = 0.01) but similar in women with pre-eclampsia and pregnant women (0.9 +/- 0.1 cm2; p > 0.3). The study showed that women with pre-eclampsia have upper airway narrowing in both upright and supine postures. These changes could contribute to the upper airway resistance episodes during sleep in patients with pre-eclampsia, which may further increase their blood pressure.

Adolescent↗
PubMed2002

Pregnancy-associated and placental proteins in the placental tissue of normal pregnant women and patients with pre-eclampsia at term.

OBJECTIVE: Pre-eclampsia is a placental disease of unknown cause. Maternal circulating concentrations of a number of protein markers are altered (mainly increased) in pre-eclampsia in comparison with controls of matched gestational age. Inhibin A and activin A were found to be elevated even before the onset of the disease. The aim of this study was to compare the levels of inhibin A, activin A: follistatin ratio, leptin, pregnancy-associated plasma protein-A (PAPP-A), human placental lactogen (HPL), placenta growth factor (PLGF) and pregnancy-specific beta1-glycoprotein (SP1) in placental extracts of normal pregnant women and pre-eclampsia patients at term. METHODS: Placental tissue from normal pregnancies (n=14) and patients with pre-eclampsia (n=13) were collected at term (> or =37 weeks of gestation) and stored at -80 degrees C. The frozen tissue pieces were homogenised and the above-mentioned proteins were measured by specific enzyme-linked immunosorbent assays. RESULTS: Placental contents of inhibin A and PAPP-A were significantly higher (P<0.05) in pre-eclampsia placental extracts compared with the controls. Activin A:follistatin ratio was higher (23) in pre-eclampsia extracts than in the controls (15). Leptin, PLGF, SP1 and HPL levels were not altered in the term pre-eclampsia placenta. Inhibin A and PAPP-A contents were increased in the placental extracts of pre-eclampsia patients. CONCLUSION: Our data suggest that the placenta, possibly by a compensatory mechanism, is at least in part responsible for the altered serum levels observed in pre-eclampsia.

Adult↗
PubMed1999

Is proteinuric pre-eclampsia a different disease in primigravida and multigravida?

This study aimed to identify if the clinical features of proteinuric pre-eclampsia or the biochemical markers of endothelial dysfunction associated with this syndrome are altered according to parity in a direction that would suggest a different pathophysiology. Groups of 27 primigravid and 35 multigravid women with pre-eclampsia (defined as blood pressure >140/90 mmHg and 2+ proteinuria) were studied ante-partum, and at 6 weeks and 6 months post-partum. Clinical markers of severity of pre-eclampsia, including blood pressure, markers of renal, hepatic and coagulatory function, and biochemical markers of endothelial dysfunction were measured. Fetal outcome was assessed by birthweight and birthweight percentile. Ante-partum systolic blood pressure was 10 mmHg higher in the primigravida, and this difference was independent of age and anti-hypertensive medication. Analysis of systolic blood pressure before and after delivery showed the primigravid women to have elevated systolic blood pressure over the whole time period (P<0.01). The primigravid women had more severe hepatic dysfunction, with elevated aspartate aminotransferase levels, but plasma creatinine, proteinuria, platelet counts and haematocrit were similar, indicating that renal and coagulatory function and plasma volume were affected to the same extent in the two groups and were independent of parity. Birthweight was similar in the two groups, and the percentage of infants weighing less than the 10th centile for gestation was also similar. Biochemical markers of endothelial dysfunction, assessed by measuring the urinary prostacyclin metabolite 2, 3-dinor-6-oxo-prostaglandin F(1alpha) and plasma endothelin 1, did not differ according to parity. There were no differences in a number of other biochemical markers of pre-eclampsia, including plasma albumin, uric acid, triacylglycerol, and total, low-density lipoprotein and high-density lipoprotein cholesterol. Basophil, monocyte and lymphocyte counts were elevated before delivery in primigravid women with pre-eclampsia. The differences in lymphocyte counts persisted post-partum. Further studies are required to clarify the role, if any, of monocytes, basophils and lymphocytes in the pathophysiology of pre-eclampsia. In conclusion, the elevated systolic blood pressure and raised aspartate aminotransferase levels observed in primigravida suggest a more severe form of pre-eclampsia. The lack of differences in birthweight and other biochemical and endothelial markers of severity of pre-eclampsia do not suggest a different pathophysiology; however, the persistently higher white cell counts in the primigravid pre-eclamptics are of interest, and might reflect differences in immune responses in the two groups. We suggest that studies of the pathophysiology of pre-eclampsia should include multigravida, as long as there is adequate post-partum follow-up to exclude underlying disease.

Adult↗
PubMed1999

Markers of tubular damage in pre-eclampsia.

BACKGROUND: The aaim of this study is to investigate the tubular damage markers in pre-eclampsia and in pregnancy induced hypertension (PIH). METHODS: This transversal study involved 111 women admitted to the Department of Obstetric and Gynaecology, University Hospital, Padua (Italy) and was conducted from the 24th week until delivery: 23 had normal pregnancies, 54 manifest pre-eclampsia, and 34 manifested pregnancy-induced hypertension (PIH) without superimposed pre-eclampsia. The following laboratory tests were performed: U-alpha 1 microglobulin, U-NAG, uric acid and microalbuminuria. The four groups were compared using the Mann-Whitney test and the Kruskall-Wallis test for multiple comparisons. A value of p < 0.05 was considered as statistically significant. RESULTS: As for the markers of tubular damage, the values for urinary NAG were significantly lower in the control group (0.97 U/mmol Creat) than in the pre-eclampsia group (2.89 U/mmol Creat), and the PIH group (2.12 U/mmol Creat) (p < 0.01). Values for urinary alpha 1-microglobulin were higher in the pre-eclampsia group (4.03 U/mmol Creat) than in the control (0.74 U/mmol Creat), and PIH groups (1.88 U/mmol Creat) (p < 0.01). As for the markers of glomerular damage, the values of microalbuminuria were higher in the pre-eclampsia group (134 micrograms/min) than in the control (9.4 micrograms/min), and PIH groups (10 micrograms/min), (p < 0.05). Uric acid, the marker of glomerular and tubular damage, was higher in the pre-eclampsia group (0.27 mmol/L) than in the control (0.20 mmol/L), and PIH groups (0.24 mmol/L), (p < 0.05). CONCLUSIONS: In pre-eclampsia there is a tubular and glomerular damage to point out by an increased urinary excretion of NAG. In pre-eclampsia, an increase of urinary alpha 1-microglobulin excretion may be considered to be partly due to the overloading of the tubule and partly due to a mixed glomerular and tubular lesion.

Acetylglucosaminidase↗
PubMed1998

Risk factors for preeclampsia-eclampsia among Zimbabwean women: recurrence risk and familial tendency towards hypertension.

We sought to estimate the risk of recurrence of preeclampsia-eclampsia among Zimbabwean women. Additionally, we sought to assess the extent to which family history of pregnancy-induced or chronic hypertension was predicative of the risk of developing preeclampsia-eclampsia. This hospital based case-control study was conducted at Harare Maternity Hospital, Harare Zimbabwe during the period June 1995 to April 1996. Study participants were 200 women with preeclampsia or eclampsia and 200 normotensive pregnant women serving as controls. Logistic regression procedures were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Among multiparous women, a history of any pregnancy-induced hypertension was associated with a 10.5-fold increase in risk of preeclampsia-eclampsia in a subsequent pregnancy (95% CI 4.7-23.5). Women who reported that their mother or sisters experienced pregnancy-induced hypertension were found to be at an increased risk of preeclampsia-eclampsia (OR = 2.3 and 2.6, respectively). A 2.3-fold excess risk of preeclampsia-eclampsia was associated with paturients' maternal history of chronic hypertension (95% CI 1.3-3.6). The corresponding relative risk of preeclampsia-eclampsia for women reporting to have a sister with chronic hypertension was 2.6 (95% CI 1.2-5.3). Zimbabwean women, like North American and European women, are at increased risk for the recurrence of preeclampsia-eclampsia. Findings from our study and those of others suggest a possible genetic component involved in the multifactorial aetiology of preeclampsia-eclampsia. The information provided here should be useful to clinicians involved in the management of patients with a prior history or family history of hypertension.

Journal Article↗
PubMed1996

Novel appearance of placental nuclear monoamine oxidase: biochemical and histochemical evidence for hyperserotonomic state in preeclampsia-eclampsia.

OBJECTIVE: The aim of this study was to explore the relevance of placental monoamine oxidase at the subcellular level in the etiology of the hyperserotonomic state in preeclampsia-eclampsia. STUDY DESIGN: The study was conducted on placentas from 20 normal pregnant women and 25 women with varied severity of preeclampsia-eclampsia. Placental serotonin and subcellular monoamine oxidase activity were determined. Histochemical localization of monoamine oxidase was done in placental sections and cell isolates. RESULTS: Placental serotonin increases with severity (rsystolic 0.84, rdiastolic 0.83) and monoamine oxidase decreases (rsystolic 0.86, rdiastolic 0.79). Placental monoamine oxidase showed marked changes in preeclampsia-eclampsia. Histochemical localization of monoamine oxidase showed diffused low activity evenly throughout the cytoplasm and nucleus of the syncytiotrophoblastic cells in preeclampsia-eclampsia; in contrast, normal placenta showed high activity in the cytoplasm without any activity in the nucleus of syncytiotrophoblastic cells. Detection of monoamine oxidase activity in nuclei of the placenta in preeclampsia-eclampsia is a novel finding. Monoamine oxidase activity at the subcellular level further strengthens this observation. A severity-dependent decrease was present in the nuclei of placentas with preeclampsia-eclampsia. The use of specific substrates and inhibitors revealed the presence of monoamine oxidase in mitochondria and nucleus. CONCLUSION: The study delineates an impaired catabolism of placental serotonin in preeclampsia-eclampsia. The novel appearance of monoamine oxidase in nuclei in proximity to its normal site and low activity resulting in a hyperserotonomic state may lead to preeclampsia-eclampsia.

Adult↗
PubMed2000

Significance of changes in lipid peroxides and antioxidant enzyme activities in pregnant women with preeclampsia and eclampsia.

This review addresses the general hypothesis that the pathogenesis of preeclampsia and eclampsia are related to an imbalance of increased oxidative stress and lipid peroxidation coupled with a deficiency of antioxidant protection. Accordingly, this study was initiated to assess total antioxidant status and free-radical activity in preeclampsia and eclampsia. The patients studied were 44 healthy pregnant women and 45 women with hypertension classified as having preeclampsia (n=27), and eclampsia (n=18). The serum levels of lipid peroxide were significantly increased (p<0.0001) and antioxidant enzyme activities (superoxide dismutase and glutathione levels) in erythrocytes were significantly decreased (p<0.0001) in women with preeclampsia and eclampsia compared with the controls. The groups of preeclampsia and eclampsia had similar values of catalase activities as the controls (p>0.05). There were no correlations between serum levels of lipid peroxide and antioxidant enzyme activities or systolic-diastolic blood pressure of pregnant women with preeclampsia and eclampsia. The mean systolic and diastolic blood pressure, the serum lactate dehydrogenase (LDH) and aspartate transaminase (AST) levels of preeclamptic and eclamptic women were high, whereas haemoglobin (Hb), Hematocrit (Htc) and platelet levels were lower than those of the control subjects (p<0.0001). There were no differences in mean gestational week, whereas the mean age of eclamptic women was lower than that of the other two groups (p<0.001). The serum levels of Alanine-transaminase (ALT) and urea in eclamptic women were significantly higher compared with the other two groups (p<0.0001), whereas creatinine levels were lower than those of the other two groups (p<0.05). Our findings give support to those few studies considering lipid peroxidation as an important factor in the pathogenesis of preeclampsia and eclampsia. Further studies are needed to clarify the relations between lipid peroxidation and antioxidative function and their pathophysiological significance in preeclampsia and eclampsia.

Adult↗
PubMed2006

Rest during pregnancy for preventing pre-eclampsia and its complications in women with normal blood pressure.

BACKGROUND: Women at risk of pre-eclampsia or gestational hypertension are sometimes advised to rest. Whether this, overall, does more good than harm is unclear. OBJECTIVES: To assess the effects of rest or advice to reduce physical activity during pregnancy for preventing pre-eclampsia and its complications in women with normal blood pressure. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group Trials Register (December 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3, 2005), and EMBASE (2002 to August 2005). SELECTION CRITERIA: Studies were included if they were randomised trials evaluating the effects of rest or advise to reduce physical activity for preventing pre-eclampsia and its complications in women with normal blood pressure. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion and extracted data. Data were double checked for accuracy. MAIN RESULTS: Two small trials (106 women) of uncertain quality were included. Both recruited women with a singleton pregnancy at moderate risk of pre-eclampsia from 28 to 32 weeks' gestation. There was a statistically significant reduction in the relative risk of pre-eclampsia with four to six hours rest per day (one trial, 32 women; relative risk (RR) 0.05, 95% confidence interval (CI) 0.00 to 0.83), but not of gestational hypertension (RR 0.25, 95% CI 0.03 to 2.00), compared to normal activity. Rest of 30 minutes per day plus nutritional supplementation was associated with a reduction in the risk of pre-eclampsia (one trial, 74 women; RR 0.13, 95% CI 0.03 to 0.51) and also of gestational hypertension (RR 0.15, 95% CI 0.04 to 0.63). The effect on caesarean section was unclear (RR 0.82, 95% CI 0.48 to 1.41). No other outcomes were reported. AUTHORS' CONCLUSIONS: Daily rest, with or without nutrient supplementation, may reduce the risk of pre-eclampsia for women with normal blood pressure, although the reported effect may reflect bias and/or random error rather than a true effect. There is no information about outcomes such as perinatal mortality and morbidity, maternal morbidity, women's views, adverse effects, and costs. Current evidence is insufficient to support recommending rest or reduced activity to women for preventing pre-eclampsia and its complications. Whether women rest during pregnancy should therefore be a matter of personal choice.

Bed Rest↗
PubMed2003

Randomized controlled trial using low-dose aspirin in the prevention of pre-eclampsia in women with abnormal uterine artery Doppler at 23 weeks' gestation.

OBJECTIVE: Pre-eclampsia, which is a major cause of perinatal and maternal morbidity and mortality, is thought to be due to impaired perfusion of the placenta. There is contradictory evidence that the administration of low-dose aspirin may provide effective prophylaxis against the subsequent development of pre-eclampsia. In this study we tested the hypothesis that in women identified as being at high-risk for pre-eclampsia, because of impaired flow in the uterine arteries, the prophylactic use of low-dose aspirin from 23 weeks of gestation can reduce the incidence of pre-eclampsia. METHODS: We used color and pulsed Doppler to measure the flow in the uterine arteries in 19,950 singleton pregnancies at 22-24 weeks of gestation. Those women exhibiting increased impedance were recruited into a randomized study of aspirin 150 mg per day or placebo. We compared the two groups for the incidence of pre-eclampsia and the other consequences of impaired placentation. RESULTS: The screening study identified 844 women (4.2%) as being at high risk of uteroplacental insufficiency. After exclusion and refusal, 560 women were randomly allocated to aspirin 150 mg or placebo per day until 36 weeks' gestation. There were no significant differences between the aspirin and placebo groups in either the incidence of pre-eclampsia (18% vs. 19%, P = 0.6) or pre-eclampsia requiring delivery below 34 weeks (6% vs. 8%, P = 0.36). Furthermore, the administration of aspirin did not significantly alter the incidence of preterm delivery (24% vs. 27%, P = 0.46), birth weight below the 5th centile (22% vs. 24%, P = 0.4), perinatal death (3% vs. 1%, P = 0.33) or placental abruption (4% vs. 2%, P = 0.12). CONCLUSION: In pregnancies with impaired placentation, as demonstrated by increased impedance to flow in the uterine arteries, the daily administration of 150 mg aspirin after 23 weeks of gestation does not prevent the subsequent development of pre-eclampsia.

Adult↗
PubMed2006

Prediction of pre-eclampsia by uterine artery Doppler ultrasonography and maternal serum pregnancy-associated plasma protein-A, free beta-human chorionic gonadotropin, activin A and inhibin A at 22 + 0 to 24 + 6 weeks' gestation.

OBJECTIVE: To investigate the potential value of combining uterine artery Doppler ultrasonography with the measurement of maternal serum pregnancy-associated plasma protein-A (PAPP-A), free beta-human chorionic gonadotropin (beta-hCG), activin A and inhibin A at 22 + 0 to 24 + 6 weeks' gestation, in the prediction of pregnancies that subsequently develop pre-eclampsia. METHODS: The maternal serum PAPP-A, free beta-hCG, activin A and inhibin A concentrations at 22 + 0 to 24 + 6 weeks' gestation were measured in samples obtained from women with singleton pregnancies who participated in a screening study for pre-eclampsia by transvaginal color flow Doppler measurement of the uterine artery pulsatility index (PI). A search was made of the database to identify those who subsequently developed pre-eclampsia (n = 24) and a group of controls with normal outcome (n = 144). Regression analysis was performed to establish any relationship between the biochemical markers themselves and between the biochemical markers and uterine artery mean PI. A multivariate Gaussian model combining various biochemical markers with uterine artery mean PI was developed using standard statistical modeling techniques and the performance of such models in discriminating cases with pre-eclampsia was evaluated by receiver-operating characteristics curve (ROC) analysis. RESULTS: In the pre-eclampsia group, compared to the controls, the uterine artery mean PI and the maternal serum levels of PAPP-A, free beta-hCG, activin A and inhibin A were significantly increased. The predicted detection rates of pre-eclampsia, for a false positive rate of 5%, was 50% by uterine artery mean PI, 5% by PAPP-A, 10% by free beta-hCG, 35% by inhibin A and 44% by activin A. Screening by a combination of uterine artery mean PI and maternal serum activin A and inhibin A could detect 75% and 92% of patients who subsequently developed pre-eclampsia, for false positive rates of 5% and 10%, respectively. CONCLUSION: Screening for pre-eclampsia by uterine artery PI at 22 + 0 to 24 + 6 weeks' gestation can be improved by measurement of activin A and inhibin A levels.

Activins↗
PubMed2003

The addition of activin A and inhibin A measurement to uterine artery Doppler velocimetry to improve the early prediction of pre-eclampsia.

OBJECTIVE: To evaluate whether the measurement of maternal serum activin A and inhibin A adds any clinically relevant information for the prediction of pre-eclampsia in women with altered uterine artery Doppler velocimetry at 24 weeks of gestation. METHODS: This was a prospective, controlled, hospital-based study involving 58 asymptomatic pregnant women at 24 weeks' gestation in whom a diastolic notch of the uterine artery waveform was noted at routine Doppler examination. Doppler assessment of the uterine artery waveform and measurement of maternal activin A and inhibin A serum levels by specific two-site enzyme immunoassays were performed. The cut-off points for defining 'high' serum activin A and inhibin A levels for prediction of pre-eclampsia were chosen by receiver-operating characteristics (ROC) curve analysis. The probability of developing pre-eclampsia was calculated for several combinations of results of hormone testing. RESULTS: Activin A and inhibin A levels were higher in patients who developed pre-eclampsia (n = 18; mean +/- standard error: 2.69 +/- 0.35 ng/mL and 131.2 +/- 22.7 pg/mL, respectively) than in those who did not present with pre-eclampsia at follow-up (n = 40; activin A: 1.79 +/- 0.18 ng/mL and inhibin A: 91.9 +/- 6.2 pg/mL; P < 0.05). Activin A at the cut-off value of 1.7 multiples of the median (MoM) achieved a sensitivity of 61% and a specificity of 89%, whereas inhibin A at the cut-off value of 1.8 MoM combined a sensitivity of 39% with a specificity of 92% for prediction of pre-eclampsia. The probability of pre-eclampsia was 31% in the whole study population, 86% if both activin A and inhibin A were elevated and 17% if both hormone markers were unaltered. CONCLUSION: The measurement of serum activin A and inhibin A levels may add significant prognostic information for predicting pre-eclampsia in pregnant women showing specific Doppler alterations in the late second trimester.

Activins↗
PubMed2007

Screening for pre-eclampsia and fetal growth restriction by uterine artery Doppler and PAPP-A at 11-14 weeks' gestation.

OBJECTIVE: To assess the role of maternal demographic characteristics, uterine artery Doppler velocimetry, maternal serum pregnancy-associated plasma protein-A (PAPP-A) and their combination in screening for pre-eclampsia and small-for-gestational age (SGA) fetuses at 11-14 weeks. METHODS: This was a prospective study of 878 consecutive women presenting for a routine prenatal ultrasound examination at 11-14 weeks. Pulsed wave Doppler was then used to obtain uterine artery flow velocity waveforms and the mean pulsatility index (PI) of the uterine arteries was calculated. Maternal serum samples for PAPP-A were assayed. Along with maternal history, these measurements were compared in their ability to predict adverse outcome, defined as pre-eclampsia and/or SGA and/or placental abruption. RESULTS: Mean uterine artery PI > or = 95(th) centile and PAPP-A < or = 10(th) centile each predicted 23% of the women that developed pre-eclampsia and 43% of cases of placental abruption. For SGA < or = 5(th) centile, mean uterine artery PI > or = 95(th) centile predicted 23% of cases and PAPP-A < or = 10(th) centile predicted 34%. Independent predictors for subsequent development of pre-eclampsia were increased mean uterine artery PI > or = 95(th) centile (OR, 2.76; 95% CI, 1.11-6.81) and maternal history of pre-eclampsia/hypertension (OR, 50.54; 95% CI, 10.52-242.73). The predicting factors for SGA < or = 5(th) centile were increased mean uterine artery PI > or = 95(th) centile (OR, 2.0; 95% CI, 1.07-3.74) and low PAPP-A (OR, 0.43; 95% CI, 0.20-0.93). Increased uterine artery PI was the only independent factor in the prediction of placental abruption (OR, 8.49; 95% CI, 2.78-25.94). The combination of uterine artery PI and maternal history of pre-eclampsia/hypertension was better than was using uterine artery Doppler alone in predicting pre-eclampsia. Similarly, for the prediction of SGA < or = 5(th) centile, combining uterine artery Doppler and maternal serum PAPP-A was better than was uterine artery Doppler alone. In both cases, the difference approached statistical significance. CONCLUSIONS: The combination of maternal history with abnormal uterine artery Doppler and low PAPP-A level at 11-14 weeks achieves better results than does either test alone in the prediction of pre-eclampsia and SGA.

Abruptio Placentae↗
PubMed1995

Magnesium sulfate as an anticonvulsant in eclampsia.

OBJECTIVE: To examine the efficacy of magnesium sulfate (MgSO4) as an anticonvulsant in eclampsia and imminent eclampsia. METHODS: Case records of 562 consecutive patients with eclampsia and 174 with imminent eclampsia treated at the Institute of Obstetrics and Gynaecology, Hyderabad, India, during the 3-year period from January 1987 to December 1989, were reviewed. Management consisted of: (1) MgSO4 to control convulsions; (2) sublingual nifedipine to control hypertension; and (3) delivery of the fetus. RESULTS: Convulsions were controlled in 95% of cases with the initial dose of magnesium and within half an hour in a further 2%. Cesarean section was performed mainly for obstetric indications. Depression of knee jerks was found to be the first sign of impending magnesium toxicity and with the precautions observed, magnesium toxicity was negligible. Maternal mortality was 2.4% (18 maternal deaths) and perinatal mortality 36% (247 perinatal deaths). Sixteen women with eclampsia (2.8%) and two with imminent eclampsia (1.1%) died. Of the 247 perinatal deaths, 61 were in the category of imminent eclampsia. There were 10 sets of twins. Cerebrovascular accident was the leading cause of maternal death. Fetal deaths and prematurity were important causes of perinatal loss. CONCLUSIONS: The control of convulsions is the most important aspect in the management of eclampsia, and MgSO4 is a very effective anticonvulsant.

Adolescent↗
PubMed2003

Microvascular permeability is related to circulating levels of tumour necrosis factor-alpha in pre-eclampsia.

INTRODUCTION: The mechanism for the increased microvascular permeability which, underline many of the complications of pre-eclampsia, remain unexplained. It has been suggested that a factor present in the maternal circulation in pregnancies complicated by the disease may be responsible for increased microvascular permeability. In this study, we have investigated the relationship between filtration capacity (K(f)), an index of microvascular permeability, and maternal levels of VEGF, leptin and TNF-alpha, all of which are known permeability factors whose plasma levels are increased in pre-eclampsia. METHODS: We used a small cumulative pressure step venous congestion plethysmography protocol to compare K(f), an index of microvascular permeability, during the third trimester of 20 women with pre-eclampsia, 18 normal pregnant women and 18 non-pregnant female matched controls. Blood samples were obtained to measure plasma levels of VEGF, leptin, TNF-alpha plasma protein concentrations and full blood count. RESULTS: Microvascular filtration capacity (K(f)) was significantly increased in pre-eclampsia compared to the other groups (P<<0.0001, ANOVA). K(f) was also increased in the normal pregnant group when compared to the non-pregnant controls (P=0.02). Plasma levels of VEGF, leptin and TNF-alpha were significantly greater in pre-eclampsia compared to normal pregnancy and non-pregnant controls (P<0.0001, ANOVA, for all three analyses). Total plasma protein and albumin concentrations were significantly lower in the normal pregnant and pre-eclamptic groups, compared to the non-pregnant controls (P<0.0001, ANOVA). K(f) was significantly related to TNF-alpha in pre-eclampsia (r=0.53, P=0.018), and with VEGF in the non-pregnant controls (r=0.6, P=0.02). No significant relationship was observed between K(f) and VEGF, leptin and TNF-alpha during normal pregnancy. There was a significant inverse correlation between plasma albumin concentration and filtration capacity in the normal pregnant (r=-0.94, P<0.0001) and non-pregnant (r=-0.87, P<0.0001) groups but not in the women with pre-eclampsia (r=-0.18, P=0.8). CONCLUSIONS: These data show that that microvascular filtration capacity is significantly increased in pre-eclampsia, and correlates with circulating levels of TNF-alpha but not leptin or VEGF.

Adult↗
PubMed2001

Supplementary calcium in prevention of pre-eclampsia.

OBJECTIVE: To study the effect of calcium supplementation on reduction of pre-eclampsia in Iranian women at high risk of pre-eclampsia. METHODS: Thirty pregnant women at high risk of developing pre-eclampsia were randomized to 2 g of daily calcium and placebo. Subjects and investigators were blinded to treatment allocation. The inclusion criteria were positive rollover test, having at least one risk factor for pre-eclampsia, between 28 and 32 weeks of pregnancy, and blood pressure less than 140/90 (mm Hg). Exclusion criteria were having any chronic condition. Pre-eclampsia was defined as systolic/diastolic blood pressure over 140/90 plus proteinuria. All the subjects were followed up to delivery. RESULT: A sevenfold reduction in the occurrence of pre-eclamsia were seen among the calcium group compared with the placebo group (7 out of 15 developed pre-eclampsia in control group vs. 1 out of 15 in calcium group, P=0.014). No major effect on pregnancy induced hypertension was seen (66% in placebo and 76% in calcium group developed hypertension) but the onset of hypertension was delayed 3 weeks in the calcium group. A longer duration of pregnancy was seen in calcium than placebo (mean+/-S.D.=37+/-2 for calcium and 34+/-2 for placebo, P<0.05). Infants born to the calcium group, on average, were 552 g heavier than infants born to the placebo group, P<0.05. CONCLUSION: Calcium supplementation is beneficial for preventing pre-eclampsia among Iranian women at high risk of developing pre-eclampsia.

Adult↗