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PubMed2006

Brief overview of maternal triglycerides as a risk factor for pre-eclampsia.

BACKGROUND: Features of the metabolic syndrome-maternal obesity, diabetes mellitus and chronic hypertension-are risk factors for pre-eclampsia. OBJECTIVES: To determine the risk of pre-eclampsia in the presence of maternal hypertriglyceridemia, another major element of the metabolic syndrome. SEARCH STRATEGY: Two investigators independently searched PubMed and Embase databases from 1980 to December 2004 for relevant studies. The terms preeclampsia, eclampsia, pregnancy-induced hypertension or toxemia were combined with dyslipidemia, hyperlipidemia, hypertriglyceridemia, lipids, cholesterol, triglycerides (TG) or lipoprotein. SELECTION CRITERIA: We included case-control and cohort studies published in English that included at least 20 women with pre-eclampsia and that sampled serum or plasma TG at any time before, during or after pregnancy. DATA COLLECTION AND ANALYSIS: Mean maternal TG concentrations were compared between cases and controls within each study. The odds ratio of pre-eclampsia was calculated by comparing the risk of pre-eclampsia among women in each higher TG concentration category with that in the lowest reference category. MAIN RESULTS: A total of 19 case-control and 3 prospective cohort studies were included. In 14 studies, the mean TG concentration was significantly higher among pre-eclamptic cases than among unaffected controls; in seven other studies, there was a nonsignificant trend in the same direction. The risk of pre-eclampsia typically doubled with each increasing TG category. In the four studies that adjusted for potential confounders, such as maternal age, parity and body mass index, there was about a four-fold higher risk of pre-eclampsia in the highest relative to the lowest TG category. AUTHOR'S CONCLUSIONS: There exists a consistent positive association between elevated maternal TG and the risk of pre-eclampsia. Given that maternal hypertriglyceridemia is a common feature of the metabolic syndrome, interventional studies are needed to determine whether pre-pregnancy weight reduction and dietary modification can lower the risk of pre-eclampsia.

Biomarkers↗
PubMed1994

Eclampsia in the United Kingdom.

OBJECTIVES: To measure the incidence of eclampsia, establish how often it is preceded by signs of pre-eclampsia, document the morbidity associated with eclampsia, and determine the maternal case fatality rates. DESIGN: A prospective, descriptive study of every case of eclampsia in the United Kingdom in 1992. Information was collected from reviews of hospital case notes and questionnaires to general practitioners. SETTING: All 279 hospitals in the United Kingdom with a consultant obstetric unit. RESULTS: Obstetricians and midwives notified 582 possible cases, and 383 were confirmed as eclampsia. The national incidence of eclampsia was 4.9/10,000 maternities (95% confidence interval 4.5 to 5.4). Most convulsions occurred despite antenatal care (70%) and within one week of the woman's last visit to a doctor or midwife (85%). Three quarters of first seizures occurred in hospital, of which 38% developed before both proteinuria and hypertension had been documented. Forty four per cent of cases occurred postpartum, more than a third (38%) antepartum, and the remainder (18%) intrapartum. Nearly one in 50 women (1.8%) died, and 35% of all women had at least one major complication. The rate of stillbirths and neonatal deaths was 22.2/1000 and 34.1/1000, respectively. Preterm eclampsia occurred more commonly antepartum and was associated with more maternal complications and fetuses that were small for gestational age, as well as with higher rates of stillbirth and neonatal mortality. Antepartum eclampsia, which was more likely to occur preterm, was associated with a higher rate of maternal complications and a higher neonatal mortality. Both factors (gestational prematurity and antepartum occurrence) contributed independently to the severity of the outcome. CONCLUSION: Eclampsia occurs in nearly one in 2000 maternities in the United Kingdom and is associated with high maternal morbidity and fatality in cases. It may present unheralded by warning signs. Preterm and antenatal eclampsia seem to be particularly severe.

Adolescent↗
PubMed2000

Hypertension and its relation to renal function 10 years after pregnancy complicated by pre-eclampsia and pregnancy induced hypertension.

OBJECTIVE: To assess the development of hypertension and its relation to renal function 10 years after pregnancy complicated by pre-eclampsia and pregnancy induced hypertension. METHODS: Women with pre-eclampsia (n=47), pregnancy induced hypertension (n=54) or normotensive (n=46) during 1988 were reviewed at King Hussein Medical Center, Amman, Jordan, for the development of hypertension and renal disorder. Their renal function was reviewed by measuring blood levels of urea, uric acid, creatinine, calcium and albumin. Urine was examined for microalbuminuria. RESULTS: Women with pre-eclampsia and pregnancy induced hypertension had a higher risk of developing hypertension 10 years later compared to the control group, (23% for pre-eclampsia, and 39% for pregnancy induced hypertension vs. 3% for control). Albumin corrected calcium levels were significantly higher in patients with history of pre-eclampsia (2.41 mmol/l) and pregnancy induced hypertension (2.42 mmol/l) vs. control (2.33 mmol/l) as well as a significant difference in microalbuminuria levels (23% in pre-eclampsia, and 16% in pregnancy induced hypertension vs. 3% in control). Serum urea, creatinine and uric acid levels were not significantly affected (4.4 mmol/l in pre-eclampsia, 4.7 mmol/l in pregnancy induced hypertension and 4.6 mmol/l in control for urea, 76.0 mmol/l in pre-eclampsia, 74.0 mmol/l in pregnancy induced hypertension and 77.0 mmol/l in control for creatinine and 252.0 mmol/l in pre-eclampsia, 250.0 in pregnancy induced hypertension and 248 mmol/l in control for uric acid). CONCLUSION: The risk of development of chronic hypertension 10 years after pregnancy complicated by pre-eclampsia and pregnancy induced hypertension is increased and this is closely related to residual renal disorder.

Adult↗
PubMed2001

Hypertensive retinopathy and pre-eclampsia.

The aim of the study was to determine the relationship between hypertensive retinopathy and the severity of pre-eclampsia. Forty women with pre-eclampsia, mean age 29.1 (+/- 7.4; range, 19-44) years, were retrospectively analyzed. They were treated at the Department of Obstetrics and Gynecology of the Clinical Hospital Split, from January 1997 to December 1999. The mean age of gestation was 36.0 +/- 2.8 weeks (range, 28-39). Pre-eclampsia was classified according to Goecke. Based on the ophthalmoscopic fundus examinations the patients were divided into four groups, according to Keith-Wagner classification system of grading retinal changes. Of 40 analyzed women, 18 (45%) had ophthalmologically verified hypertensive retinopathy. Ten of them were classified as grade I, six as grade II and two as grade III. Twenty-two patients had mild pre-eclampsia, ten patients had moderate pre-eclampsia, and eight patients had severe pre-eclampsia. A statistically significant correlation (t-test) was found between the degree of hypertensive retinopathy and patient age, Apgar score, trophism, Goecke's index, proteinuria, systolic and diastolic pressure (P < 0.001) and edema (P = 0.01). The degree of hypertensive retinopathy was directly proportional with the severity of pre-eclampsia and significant correlation was found between them (r = 0.338, p = 0.033). These findings showed that the degree of hypertensive retinopathy in women with pre-eclampsia is a valid and reliable prognostic factor in determining the severity of the pre-eclampsia. Therefore, it can be concluded that the examination of the fundus is a valuable and necessary diagnostic procedure in pregnant women with pre-eclampsia.

Adult↗
PubMed2003

Levels of antibodies against cytomegalovirus and Chlamydophila pneumoniae are increased in early onset pre-eclampsia.

OBJECTIVE: The origins of pre-eclampsia/eclampsia lie in a mismatch between feto-placental demands and utero-placental supply, a situation that also arises in normotensive intrauterine growth restriction (IUGR). Could reactivated chronic infection be both a trigger for these differential maternal responses to the same underlying pathology and a link between pre-eclampsia and its attendant lifelong risks of atherosclerosis? DESIGN: Nested case-control study. SETTING: Tertiary obstetric centre. POPULATION: Cases of pre-eclampsia, normotensive IUGR and controls. METHODS: A nested case-control study of serum from a population-based bank was performed. Seroprevalence and levels of anti-cytomegalovirus (CMV) and Chlamydophila pneumoniae immunoglobulin G (IgG) were compared (non-parametrically) between women with early onset pre-eclampsia (<34 weeks of gestation, n = 9), late onset pre-eclampsia (> or =34 + 0 weeks of gestation, n = 29), normotensive IUGR (birthweight less than third centile, n = 33) and matched normal pregnancy (n = 113, up to 2 per case). RESULTS: There was a significant difference in both anti-CMV and Chl. pneumoniae antibodies between groups (Kruskal-Wallis test, P < 0.05). Women with early onset pre-eclampsia had higher anti-CMV levels (median: 79, 95% confidence interval [95% CI] = 47, 164) than women with late onset pre-eclampsia (26 [95% CI = 22, 82], P < 0.05), normotensive IUGR (40 [95% CI = 31, 72], P < 0.05) and normal pregnancy (49 [95% CI = 45, 70], P < 0.05). Women with normotensive IUGR had significantly lower anti-Chl. pneumoniae antibodies (0.10 [95% CI = 0.08, 0.38]) than did normal pregnancy controls (0.21 [95% CI = 0.20, 0.28], P <0.05). CONCLUSIONS: The anti-CMV and anti-Chl. pneumoniae antibodies were higher in early onset pre-eclampsia than in late onset pre-eclampsia, normotensive IUGR and normal pregnancy. This may provide a pathophysiological link between pre-eclampsia and the known increased risk for subsequent atherosclerosis.

Adult↗
PubMed1989

Human chorionic gonadotropin and its subunits in pre-eclampsia.

The serum levels of hCG and its subunits were studied in 11 cases of pre-eclampsia (8 cases of severe pre-eclampsia and 3 cases of mild pre-eclampsia) and 72 normal pregnant women. The hCG (human chorionic gonadotropin) immunoactivity measured by H80 RIA (radioimmunoassay) and Sb6 RIA showed no significant difference between pre-eclampsia and normal pregnancy. This result suggests that no significant amount of free hCG-beta existed, since H80 RIA measured intact hCG but not hCG-beta, and Sb6 RIA measured both hCG and hCG-beta. Furthermore, from the result of elution behavior of gel HPLC (high performance liquid chromatography), hCG of pre-eclampsia and comparison of the Sb6 RIA/H80 RIA ratio between pre-eclampsia and normal pregnancy, it was evident that there was little amount of free hCG-beta secretion in pre-eclampsia as in normal pregnancy. However, the free hCG-alpha was significantly higher in severe pre-eclampsia, probably caused by placental dysfunction. In summary, free hCG-alpha is increased in pre-eclampsia, but its role as a marker of placental function in pre-eclampsia requires further investigation.

Chorionic Gonadotropin↗
PubMed1993

Community-based home-care program for the management of pre-eclampsia: an alternative.

OBJECTIVE: To evaluate the safety, acceptability and cost of a community-based home-care program for the management of mild pre-eclampsia. DESIGN: A descriptive study of outcomes between Apr. 1, 1985, and Dec. 31, 1989. SETTING: St. Boniface General Hospital, Winnipeg. PATIENTS: Urban Winnipeg residents between 27 and 40 weeks' gestation with mild pre-eclampsia who demonstrated acceptance and compliance with home-care management; 321 patients of 1330 were enrolled in the program. INTERVENTIONS: Bed rest at home with daily biochemical and biophysical follow-up protocol and weekly clinic visits; patient education; hospital admission for labour, induction, worsening pre-eclampsia or noncompliance with rest at home. OUTCOME MEASURES: Patterns of referral to the program; clinical, biochemical and biophysical profiles; incidence of severe complications; reduction in total hospital stay and cost analysis. RESULTS: As many women were referred from physicians' offices as were referred from the hospital's antepartum unit, the average gestational age at referral being 36 weeks. Most (205 [64%]) of the women were nulliparous. The average length of stay in the program was 11.5 days. The program's availability resulted in a reduction of 2 days (from 5.7 days to 3.7 days) on average in the length of hospital stay when analysed for all 1330 women with pre-eclampsia. Of the 321 patients in the program 137 (43%) were admitted to hospital for worsening pre-eclampsia; severe pre-eclampsia developed 4 days after admission in 9. No patient suffered eclampsia, disseminated intravascular coagulopathy, abruption or fetal loss related to pre-eclampsia while in the program. The estimated cost saving in the management of pre-eclampsia was over $700,000 over the study period. CONCLUSION: The community-based home-care program is a safe, feasible and less costly alternative to hospital admission in the management of mild pre-eclampsia.

Cost Savings↗
PubMed2002

Does consanguinity affect the severity of pre-eclampsia?

To determine whether consanguinity is more likely to be associated with severe forms of pre-eclampsia/eclampsia. Presuming a pure genetic contribution, we speculated that consanguineous marriages would increase the occurrence of severe forms of pre-eclampsia/eclampsia, through an expected increased chance for homozygosity to the putative gene. The study is a clinical case series on pre-eclamptic/eclamptic primiparae delivered at Princess Badea Teaching Hospital, which is a tertiary referral center. The internationally accepted definitions for hypertension, proteinuria, mild and severe pre-eclampsia were adopted. The study included 77 primiparae. The incidence of consanguinity in the studied sample was 38%. Of them, 28 (36.4%) had mild pre-eclampsia, 45 (58.4%) had severe pre-eclampsia and four (5.2%) had eclampsia. There was no statistically significant difference in the occurrence of severe pre-eclampsia/eclampsia between primiparae married to a first cousin or a relative other than a first cousin and primiparae married to a non-relative, odds ratio 1.1 (95% CI 0.33-3.87), P value 0.94, odds ratio 2.6 (95% CI 0.45-27.6), P value 0.30, respectively. Also, there was no statistically significant difference in occurrence of severe pre-eclampsia/eclampsia between primiparae whose parents are first cousins or relatives other than a first cousin and primiparae whose parents are non-relatives, odds ratio 1.3 (95% CI 0.36-4.72), P value 0.81, odds ratio 1.61 (95% CI 0.23-18.4), P value 0.70, respectively. Our study did not support a causal relationship between consanguinity and the occurrence of severe pre-eclampsia/eclampsia. The role of more complex genetic, immunologic, metabolic, hemostatic or, possibly yet, other unknown factors have to be explored.

Adolescent↗
PubMed2003

[Risk factors for eclampsia: a case-control study].

OBJECTIVE: Our purpose was to characterize the risk factors of eclampsia in women with preeclampsia. PATIENTS AND METHODS: A case-control study was conducted at Monastir hospital to investigate risk factors for eclampsia between 1st January 1995 and 30th June 2000. Cases were matched to preeclamptic controls on a 2:1 ratio. Univariate analysis was used to determine which of the independent variables were significantly different between the groups. Those with significant differences were then entered into multiple logistic regression analysis to determine the characteristics that were independently related to eclampsia. RESULT: A total of 41 cases of eclampsia were ascertained from deliveries. The ratio of eclampsia cases to number of deliveries over the study period was 1.87 per 1000. The first seizures occurred at home in 59% of the cases. Univariate analysis revealed statistical significance for the following variables associated with eclampsia: systolic hypertension > or =160 mmHg and diastolic > or =110 mmHg, headache, visual symptoms, vivid deep tendon reflexes, proteinuria >3+ or >3 g d(-1), uric acid concentration > or =350 micromol l(-1), serum creatinine concentration >100 micromol l(-1) and aminotransferase aspartate >30 IU l(-1). A history of abortion appears to be the protective factor against eclampsia. However, with subsequent multivariate analysis, only vivid deep tendon reflexes and elevated uric acid concentration remained significant. CONCLUSION: These data indicate a need for improved prenatal care and medical attention focused on prodroms of eclampsia as well as the detection of preeclampsia to reduce the incidence of eclampsia.

Adult↗
PubMed2000

Maternal pre-eclampsia/eclampsia and the risk of sudden infant death syndrome in offspring.

To determine whether maternal exposure to pre-eclampsia/eclampsia during pregnancy increases the risk of sudden infant death syndrome (SIDS) in offspring, we conducted a population-based case-control study using the California linked birth and death certificate data. All infants who died of SIDS (ICD-9 code 798.0) during 1989-91 were identified as cases. More than 96% of the identified SIDS cases were diagnosed through autopsy. Ten controls who did not die from SIDS were randomly selected for each case from the birth certificate matched to the case on the year of birth. Among 2,029 cases and 21,037 controls included in the final analysis, mothers of 49 cases (2.4%) and 406 controls (1.9%) had a diagnosis of either pre-eclampsia or eclampsia noted on the birth certificate. After adjustment for maternal age, prenatal smoking, race/ethnicity, parity, maternal education, gestational age at the initial visit for prenatal care, infant year of birth and infant sex, maternal pre-eclampsia/ eclampsia during pregnancy was associated with a 50% increased risk of SIDS in the offspring (odds ratio = 1.5, 95% confidence interval 1.1, 2.0). Potential under-reporting of pre-eclampsia/eclampsia on the birth certificates was likely to be non-differential and is unlikely to explain the finding. Fetal hypoxia resulting from pre-eclampsia/ eclampsia or immunological aetiology affecting the risk of both pre-eclampsia/eclampsia and SIDS may explain the finding.

Adolescent↗
PubMed1998

A randomised controlled trial of intravenous magnesium sulphate versus placebo in the management of women with severe pre-eclampsia.

OBJECTIVE: To determine whether the administration of prophylactic intravenous magnesium sulphate reduces the occurrence of eclampsia in women with severe pre-eclampsia. DESIGN: Randomised controlled trial. SETTING: A tertiary referral obstetric unit. POPULATION: Eight hundred and twenty-two women with severe pre-eclampsia requiring termination of pregnancy by induction of labour or caesarean section. METHODS: The women were randomised to receive either placebo (saline) or magnesium sulphate intravenously. The investigators were blinded to the contents of the pre-mixed solutions. MAIN OUTCOME MEASURE: The occurrence of eclampsia in the two groups. RESULTS: The data of 699 women were evaluated. Fourteen were withdrawn after randomisation. The overall incidence of eclampsia was 1.8%. Of 345 women who received magnesium sulphate, one developed eclampsia (0.3%); in the placebo group, 11/340 women (3.2%) developed eclampsia (relative risk 0.09; 95% confidence interval 0.01-0.69; P = 0.003). CONCLUSION: The use of intravenous magnesium sulphate in the management of women with severe pre-eclampsia significantly reduced the development of eclampsia.

Abortion, Induced↗
PubMed2005

Outcomes of severe pre-eclampsia/eclampsia in Yorkshire 1999/2003.

OBJECTIVE: To establish the risk of serious complications from severe pre-eclampsia and eclampsia in a region using a common guideline for the management of these conditions. DESIGN: A five-year prospective study. SETTING: Sixteen maternity units in Yorkshire. POPULATION: All women managed with severe pre-eclampsia and eclampsia. METHODS: A common guideline was developed for the management of women with these conditions. A network of midwives prospectively collected outcome data. MAIN OUTCOME MEASURE: Incidence of the conditions and serious complication rates. RESULTS: A total of 210,631 women delivered in the 16 units between 1 January 1999 and 31 December 2003. One thousand eighty-seven women were diagnosed with severe pre-eclampsia or eclampsia (5.2/1000). One hundred and fifty-one women had serious complications including 82 women (39/10,000) having eclamptic seizures and 49 women (23/10,000) requiring ICU admission. There were no maternal deaths but 54 out of 1145 babies died before discharge, giving a mortality rate of 47.2/1000. Of the 82 cases of eclampsia, 45 occurred antenatally (55%), 18 before admission to the maternity unit. Eleven cases occurred in labour (13%), including 1 during a caesarean section, and 26 cases occurred following delivery (32%). Twenty-five women developed pulmonary oedema (2.3% of cases) and six women required renal dialysis (0.55% of cases). One hundred and sixty-five (15%) required no antihypertensive therapy and 489 (53%) of the remainder required only oral therapy. Two hundred and one (18.5%) required more than one drug. CONCLUSION: A regional guideline for severe pre-eclampsia and eclampsia can be developed and implemented. Its use may contribute to a low rate of serious complications.

Anticonvulsants↗
PubMed2002

Methyldopa versus no drug treatment in the management of mild pre-eclampsia.

OBJECTIVES: To evaluate the efficacy of methyldopa in the treatment of mild pre-eclampsia, to prevent its progress and to investigate its effect on the pregnancy outcomes. DESIGNS: Randomised clinical trial. SETTING: Wad Medani Hospital in the central Sudan. SUBJECTS: Seventy primigravidae with single, alive baby of 28-36 weeks gestational age suffering from true mild pre-eclampsia were enrolled. The patients were randomised in two groups, treatment group who received methyldopa 750-4000 mg/day (n=34) and a control group who received no treatment (n=36). All the (treatment and control) patients were drug followed as in-patients till the delivery, seen with their babies on the days 7, 42 after the delivery. MAIN OUTCOMES MEASURES: The outcomes examined were, rise of the diastolic blood pressure to 110 mm Hg or more, occurrence of imminent eclampsia or the eclampsia, if the maturity could be achieved, occurrence of intrauterine growth retardation, abruptio placentae, mode of delivery, birth weight, placental weight, perinatal death, Apgar score and referral of the babies to the pediatrician. RESULTS: Three out of 34 (8.8%) of the treatment group had a rise in the diastolic blood pressure of 110 mm Hg, 18/36 (50%) of the control had a rise in the diastolic blood pressure of 110 mmHg (p < 0.05). Three out of thirty four (8.8%) of the treatment group developed imminent eclampsia, while 10/36 (27.8) of the control group developed imminent eclampsia (p < 0.05). The maturity was achieved in 82.3% and 88.8% of the treatment and the control, respectively (p > 0.05). There were ten (14.2%) perinatal deaths, four of them in the treatment group, while six in the control (p > 0.05). There was no difference regarding birth weight, occurrence of intrauterine growth retardation, placental weight, mode of delivery, Apgar score, referral of the babies to the paediatrician. No patient developed eclampsia or abruptio placenta; there was no maternal death in both groups. CONCLUSION: Methyldopa can prevent the progress of the mild pre-eclampsia to severe pre-eclampsia, without affecting the maturity, birthweight or the neonatal outcomes.

Abruptio Placentae↗
PubMed2002

Mid-trimester triple test levels in early and late onset severe pre-eclampsia.

OBJECTIVE: To study whether the degree of elevation of mid-trimester triple test markers differs in patients with early versus late onset severe pre-eclampsia. METHODS: A retrospective study of the medical records of 102 patients with severe pre-eclampsia for whom mid-trimester triple test result data were available was made. None of these patients had fetuses with abnormal karyotype nor delivered infants with malformations. Pre-eclampsia was defined as early onset when it presented before 32 weeks' gestation. The levels of mid-trimester maternal serum alpha-fetoprotein (MSAFP), human chorionic gonadotrophin (hCG) and unconjugated oestriol (MSuE(3)) in patients with early and late onset severe pre-eclampsia were compared. RESULTS: Twenty-five patients had early onset and 77 patients had late onset severe pre-eclampsia. The two groups did not differ significantly with regard to age, weight, parity and severity of pre-eclampsia. The mean MSAFP in patients with early onset was significantly higher than in patients with late onset severe pre-eclampsia (1.46 MoM, SE 0.12 versus 1.16 MoM, SE 0.05; p=0.01). The mean hCG in the early onset group was also significantly higher than in the late onset group (1.71 MoM, SE 0.18 versus 1.21 MoM, SE 0.07; p=0.03). Mean MSuE(3) levels in patients with early onset were significantly lower than in patients with late onset severe pre-eclampsia (0.83 MoM, SE 0.05 versus 1.02 MoM, SE 0.03; p=0.04). CONCLUSIONS: Higher MSAFP and hCG, and lower MSuE(3), may be more significant markers of early rather than late onset severe pre-eclampsia.

Adult↗
PubMed2007

First-trimester maternal serum PP-13, PAPP-A and second-trimester uterine artery Doppler pulsatility index as markers of pre-eclampsia.

OBJECTIVE: To evaluate whether measurement of maternal serum placental protein-13 (PP-13) and pregnancy-associated plasma protein-A (PAPP-A) at 11 + 0 to 13 + 6 weeks of gestation alone or in combination with second-trimester uterine artery pulsitility measured by Doppler velocimetry is useful in predicting those women who will develop pre-eclampsia METHODS: This was a nested case-control study of pre-eclampsia cases with controls matched for gestational age and storage time for the maternal serum. Samples were collected as part of a first-trimester prenatal chromosomal anomaly screening program and were routinely tested for PAPP-A. PP-13 was tested using an enzyme linked immunosorbent assay (ELISA) by an examiner who was blinded to pregnancy outcome. All patients also underwent uterine artery Doppler flow velocimetry to measure the mean pulsatility index (PI) at 22-24 weeks' gestation. RESULTS: There were 446 controls and 44 cases with early pre-eclampsia where delivery was induced prior to 35 weeks. In addition there were a further 44 cases with pre-eclampsia in which delivery was not induced before term. Median PP-13 levels for controls, all cases and early pre-eclampsia cases were 176.9, 121.9 and 111.7 pg/mL, with multiples of the median (MoMs) of 1.00, 0.69 and 0.63, respectively (P < 0.001). PAPP-A MoMs were 1.00, 0.89 (P = 0.076) and 0.89 (P = 0.042) and mean PIs were 1.0, 1.6 (P < 0.001) and 1.7 (P < 0.001) for controls, all cases and early cases, respectively. Receiver-operating characteristics (ROC) curve analysis for either all cases or early cases vs. controls yielded areas under the curve for PP-13, PAPP-A and PI respectively of 0.68 (95% CI, 0.61-0.74; P < 0.001), 0.56 (95% CI, 0.49-0.63; P = 0.076) and 0.79 (95% CI, 0.72-0.87; P < 0.001) for all cases and 0.71 (95% CI, 0.63-0.79; P < 0.001), 0.59 (95% CI, 0.51-0.68; P = 0.076) and 0.86 (95% CI, 0.77-0.94; P < 0.001) for early cases. At a specificity set to 0.80 the sensitivities were 0.50, 0.23 and 0.76 for PP-13, PAPP-A and PI in the early cases and 0.44, 0.24 and 0.73 in all cases. Combining PP-13 and PI using logistic regression analysis yielded an area under the curve of 0.84 (95% CI, 0.78-0.90; P < 0.001) and a sensitivity of 0.74 in all cases, and 0.90 (95% CI, 0.84-0.96; P < 0.001) and a sensitivity of 0.79 for early cases. PAPP-A with PI gave an area under the curve of 0.82 (95% CI, 0.76-0.90; P < 0.001) and a sensitivity of 0.76 in all cases. Combining PAPP-A with PP-13 and PI did not add significantly to the sensitivity. CONCLUSION: First-trimester PP-13 levels may be useful in predicting pre-eclampsia and early pre-eclampsia, and the accuracy of the method increases when coupled with second-trimester Doppler PI measurement. First-trimester PAPP-A provides some prediction for pre-eclamspia when combined with PI but does not add to the prediction of early pre-eclampsia when PP-13 and PI are used together. Further studies are required to establish the real value of PP-13 in first-trimester screening for pre-eclampsia.

Adult↗
PubMed2005

The Glu298Asp variant of the endothelial nitric oxide synthase gene is associated with an increased risk for abruptio placentae in pre-eclampsia.

Attempts to define a pre-eclampsia susceptibility profile have been hampered by the wide clinical spectrum of the condition and the complex genetics underlying it. Genes that modulate blood pressure, fluid homeostasis and placental vascular development have been considered plausible candidates. Among these are the angiotensinogen (AGT) gene variant Met235Threo, which has been associated with pre-eclampsia and the endothelial nitric oxide synthase (eNOS) polymorphism Glu298Asp, which has been associated with both pre-eclampsia and abruptio placentae, a condition that often co-exists with pre-eclampsia. The aim of this study was to investigate a potential association between these gene variants and pre-eclampsia with and without abruptio placentae in a South African patient group. Fifty primigravidas with early onset, severe pre-eclampsia, 50 women presenting primarily with abruptio placentae (whether associated with pre-eclampsia or not) and a control panel of 50 healthy pregnant women constituted the study groups. The Met235Threo and Glu298Asp variants were characterised by polymerase chain reaction and restriction enzyme analysis. No association was demonstrated between the M235T variant of the AGT gene and pre-eclampsia or abruptio placentae. In contrast, the combined frequency of the eNOS variant genotypes (GT and TT) was significantly higher in the abruptio placentae group (49%) than the control group (21%) (p=0.006). Furthermore, in the pre-eclampsia patients who subsequently developed abruptio placentae, the eNOS GT genotype emerged as a major risk factor for the development of abruptio placentae (p<0.0001). These data suggest that the presence of a Glu298Asp eNOS variant may pre-dispose a pre-eclamptic woman to develop abruptio placentae or that it is a marker for predisposition.

Abruptio Placentae↗
PubMed1998

Midtrimester urine human chorionic gonadotropin beta-subunit core fragment levels and the subsequent development of pre-eclampsia.

OBJECTIVE: Our purpose was to determine whether midtrimester maternal urine human chorionic gonadotropin beta-subunit core fragment predicts later pre-eclampsia. STUDY DESIGN: Urine beta-core fragment levels standardized to spot creatinine concentration and expressed as multiples of the median were prospectively determined in 347 midtrimester singleton pregnancies undergoing genetic amniocentesis. All women considered in the analysis were white and nonsmokers. Obstetric chart review was undertaken after delivery to identify cases in which pre-eclampsia developed. The risk of pre-eclampsia at different threshold levels of beta-core fragment of human chorionic gonadotropin was determined. RESULTS: The median maternal age was 36.0 years, with a median gestational age at urine collection of 16.0 weeks. The median level of the beta-core fragment of human chorionic gonadotropin was 1385.5 ng/mg of creatinine in those with pre-eclampsia, whereas that in those without pre-eclampsia was 1061.2 ng/mg. The difference was significant (Mann-Whitney U test, P = .03). A significant linear association was found between the beta-core fragment concentration and the risk of pre-eclampsia (Mantel-Haenszel test of linear association, P = .03). The relative risk and 95% confidence interval of subsequent pre-eclampsia increased from 2.07 (1.06 to 4.05) at beta-core fragment levels of human chorionic gonadotropin > or = 2.0 multiples of the median to 5.17 (1.95 to 13.7) at > or = 4.0 multiples of the median. CONCLUSION: Clinically normal patients with elevated midtrimester levels of urine beta-core fragment of human chorionic gonadotropin are at increased risk for the subsequent development of pre-eclampsia. The clinical value of this urine analyte as a marker for pre-eclampsia needs to be further investigated.

Adult↗
PubMed1998

Individually determined postpartum magnesium sulfate therapy with clinical parameters to safely and cost-effectively shorten treatment for pre-eclampsia.

OBJECTIVE: The purpose of this study was to investigate the safety of treating pre-eclampsia with magnesium sulfate, with clinical determinants used for drug discontinuation. STUDY DESIGN: One hundred sixty-eight patients were enrolled. After delivery, women with mild pre-eclampsia received a minimum of 6 hours of intravenous magnesium sulfate, whereas women with severe pre-eclampsia received a minimum of 12 hours. Magnesium sulfate was discontinued in the absence of clinical symptoms associated with spontaneous diuresis, minimal protein by urinary dipstick, and satisfaction of predetermined blood pressure criteria. RESULTS: Patients with mild pre-eclampsia required significantly less magnesium sulfate (mean 9.5 +/- 4.2 hours) than did those with severe pre-eclampsia alone (mean 16 +/- 5.9 hours); pre-eclampsia superimposed on chronic hypertension (mean 16 +/- 5.8 hours); or hemolysis, elevated liver enzyme, and low platelet count syndrome (mean 20 +/- 6.7 hours). With this protocol there was no eclampsia, and recovery room time was reduced by 50%. CONCLUSION: Individual determination of postpartum magnesium sulfate therapy for pre-eclampsia appears to be a safe approach that carries minimal risk of eclampsia.

Adolescent↗