Prevention of venous thromboembolism in patients admitted to Australian hospitals: summary of National Health and Medical Research Council clinical practice guideline.

Each year in Australia, about 1 in 1000 people develop a first episode of venous thromboembolism (VTE), which approximates to about 20,000 cases. More than half of these episodes occur during or soon after a hospital admission, which makes them potentially preventable. This paper summarises recommendations from the National Health and Medical Research Council's 'Clinical Practice Guideline for the Prevention of Venous Thromboembolism in Patients Admitted to Australian Hospitals' and describes the way these recommendations were developed. The guideline has two aims: to provide advice on VTE prevention to Australian clinicians and to support implementation of effective programmes for VTE prevention in Australian hospitals by offering evidence-based recommendations which local hospital guidelines can be based on. Methods for preventing VTE are pharmacological and/or mechanical, and they require appropriate timing, dosing and duration and also need to be accompanied by good clinical care, such as promoting mobility and hydration whilst in hospital. With some procedures or injuries, the risk of VTE is sufficiently high to require that all patients receive an effective form of prophylaxis unless this is contraindicated; in other clinical settings, the need for prophylaxis requires individual assessment. For optimal VTE prevention, all patients admitted to hospital should have early and formal assessments of: (i) their intrinsic VTE risk and the risks related to their medical conditions; (ii) the added VTE risks resulting from surgery or trauma; (iii) bleeding risks that would contraindicate pharmacological prophylaxis; (iv) any contraindications to mechanical prophylaxis, culminating in (v) a decision about prophylaxis (pharmacological and/or mechanical, or none). The most appropriate form of prophylaxis will depend on the type of surgery, medical condition and patient characteristics. Recommendations for various clinical circumstances are provided as summary tables with relevance to orthopaedic surgical procedures, other types of surgery and medical inpatients. In addition, the tables indicate the grades of supporting evidence for the recommendations (these range from Grade A which can be trusted to guide practice, to Grade D where there is more uncertainty; Good Practice Points are consensus-based expert opinions).

PIERS proteinuria: relationship with adverse maternal and perinatal outcome.

OBJECTIVE: To examine the ability of three different proteinuria assessment methods (urinary dipstick, spot urine protein:creatinine ratio [Pr/Cr], and 24-hour urine collection) to predict adverse pregnancy outcomes. METHODS: We performed a prospective multicentre cohort study, PIERS (Preeclampsia Integrated Estimate of RiSk), in seven academic tertiary maternity centres practising expectant management of preeclampsia remote from term in Canada, New Zealand, and Australia. Eligible women were those admitted with preeclampsia who had at least one antenatal proteinuria assessment by urinary dipstick, spot urine Pr/Cr ratio, and/or 24-hour urine collection. Proteinuria assessment was done either visually at the bedside (by dipstick) or by hospital clinical laboratories for spot urine Pr/Cr and 24-hour urine collection. We calculated receiver operating characteristic area under the curve (95% CI) for each proteinuria method and each of the combined adverse maternal outcomes (within 48 hours) or adverse perinatal outcomes (at any time). Models with AUC ≥ 0.70 were considered of interest. Analyses were run for all women who had each type of proteinuria assessment and for a cohort of women ("ALL measures") who had all three proteinuria assessments. RESULTS: More women were proteinuric by urinary dipstick (≥ 2+, 61.4%) than by spot urine Pr/Cr (≥ 30 g/mol, 50.4%) or 24-hour urine collection (≥ 0.3g/d, 34.7%). Each proteinuria measure evaluated had some discriminative power, and dipstick proteinuria (categorical) performed as well as other methods. No single method was predictive of adverse perinatal outcome. CONCLUSION: The measured amount of proteinuria should not be used in isolation for decision-making in women with preeclampsia. Dipstick proteinuria performs as well as other methods of assessing proteinuria for prediction of adverse events.

Does a predisposition to the metabolic syndrome sensitize women to develop pre-eclampsia?

OBJECTIVE: This study aimed to identify those factors in the non-pregnant state that distinguished women who developed pre-eclampsia from those who had normotensive pregnancies. DESIGN AND SETTING: This was a retrospective analysis of anthropometry, blood pressure, biochemical and haematological variables in 62 women with pre-eclampsia and 84 normotensive pregnant women who took part in studies of the pathophysiology of pre-eclampsia. Pregnant volunteers were seen, after admission to hospital or in the outpatient clinic, and followed-up at 6 weeks and 6 months post-partum in the outpatient clinic or their home. Participants Proteinuric pre-eclampsia was defined as blood pressure > or = 140/90 mmHg with proteinuria of at least 300 mg/24 h after 20 weeks gestation, in women with no history of hypertension and whose blood pressure returned to normal levels by 6 months post-partum. Normotensive pregnancy was defined as blood pressure < 130/90 mmHg without proteinuria. MAIN OUTCOME MEASURES: The primary outcome measures were blood pressure, body mass index (BMI), triglycerides, total cholesterol, low density lipoprotein (LDL) and high density lipoprotein cholesterol and markers of severity of pre-eclampsia. RESULTS: Regardless of parity, women with pre-eclampsia had elevated BMI before, during and after pregnancy compared with women who had normotensive pregnancies. Triglycerides were significantly elevated in women who had pre-eclampsia both before and after delivery, while total and LDL cholesterol were elevated significantly at both visits after delivery. Systolic and diastolic blood pressure, which by definition were elevated antepartum in women with pre-eclampsia, remained higher at post-partum visits compared with women who had normotensive pregnancies. Women with pre-eclampsia reported a greatly increased frequency of both maternal hypertension and pre-eclampsia. Markers of severity of pre-eclampsia, which normalized by 6 months postpartum, included plasma creatinine, uric acid, albumin, endothelin 1 and urinary protein, 2,3, dinor-6-keto-PGF1alpha, blood platelet and neutrophil counts. CONCLUSION: The relative elevation of blood pressure, BMI and lipids in the non-pregnant state are features of the metabolic syndrome and may be important sensitizing factors contributing to the pathogenesis of pre-eclampsia. A familial predisposition to pre-eclampsia may operate partly through these mechanisms.

Association between the endothelin-1 gene Lys198Asn polymorphism blood pressure and plasma endothelin-1 levels in normal and pre-eclamptic pregnancy.

OBJECTIVE: This study examined the frequency of the Lys198Asn polymorphism in the endothelin-1 (ET-1) gene in women with pre-eclampsia and normal pregnancy; and its contribution to levels of plasma ET-1 and blood pressure. DESIGN AND METHODS: This was a retrospective study examining the frequency of the ET-1 Lys198Asn polymorphism in 72 proteinuric pre-eclamptics and 81 normal pregnant women. Height, weight, blood pressure and plasma ET-1 were measured antenatally and at 6 weeks post-partum. Using specific mutagenic primers, the frequency of the G/G (normal), G/T heterozygote and T/T (mutant) genotypes of the Lys198Asn polymorphism were examined. RESULTS: The polymorphism was not associated with pre-eclampsia. However, in the combined pregnant groups after correction for BMI and group, a significant effect of the T-allele (T/T,G/T) on systolic blood pressure was found (121 +/- 1.5 mmHg compared with 116 +/- 1.3 mmHg in the G/G homozygotes). A significant interaction was found between the T-allele and pregnancy in determining systolic blood pressure, so that the effect was no longer seen post-partum. Pregnant women with the T/T genotype had significantly elevated plasma ET-1 levels 5.8 pg/ml [confidence interval (CI) 3.7-9.1] compared with 3.1 pg/ml (CI 2.6-3.8) in the G/T heterozygotes and 3.6 pg/ml (CI 3.0-4.1) in the normal G/G homozygotes. CONCLUSION: The Lys198Asn polymorphism does not directly contribute to the incidence of pre-eclampsia. However, the association of the T-allele with raised blood pressure and the T/T genotype with increased plasma ET-1 levels suggest that this polymorphism may interact with other genes or environmental factors to sensitize pregnant women to develop pre-eclampsia.

The epidemiological characteristics of unexplained antepartum stillbirths.

All antepartum stillbirths weighing 1000 g or more born in Western Australia from 1980 to 1983 were categorised as 'unexplained' or 'explained' based on information from Perinatal Death Certificates. Using data from hospital and doctors' antenatal records a number of variables in each stillbirth category were compared by unconditional logistic regression. Significant differences were observed between the two groups in medical disorders and abnormalities of pregnancy, thus confirming our classification system. Compared with mothers of 'explained' antepartum stillbirths, mothers of unexplained antepartum stillbirths tended to have younger ages at delivery and had associated lower parity, more antenatal visits to the medical practitioner, fewer hospital admissions, a greater chance of having received care by a general practitioner than by a specialist obstetrician and were of more advanced gestation at the time of diagnosis. The results of this study indicate that the epidemiological characteristics of pregnancies resulting in unexplained antepartum stillbirths differ from those resulting in explained antepartum stillbirths. This suggests that unexplained antepartum stillbirths are not merely the result of inadequate obstetrical management but consist of a series of fetal disease states which are not currently amenable to detection.

PP030. Cardiovascular disease and risk in a pregnant woman's father as a risk factor for preeclampsia.

INTRODUCTION: In women experiencing their first pregnancy the assessment of risk of developing a hypertensive disorder of pregnancy (HDP) including preeclampsia is imprecise. Identification of women at higher than normal risk of developing preeclampsia may improve pregnancy management and lead to better outcomes. Previous studies, mostly retrospective, have indicated a possible link between cardiovascular history and risk of preeclampsia. OBJECTIVES: To evaluate the self-reported family history of cardiovascular disease and risk (CVD/R) during an antenatal interview as a means of screening for risk of developing preeclampsia or other HDP. METHODS: Nulliparous women were recruited prospectively in early pregnancy before diagnosis of any HDP. Women reported on their maternal characteristics and the history of cardiovascular health in themselves, their parents and siblings and the father of the baby and his parents and siblings. Cardiovascular health was assessed as cardiovascular risk (high blood pressure, high cholesterol and diabetes) and cardiovascular disease (heart attack, stroke, angina and any major vascular surgery). Pregnancy outcomes were recorded after delivery, the diagnoses of gestational hypertension, preeclampsia and superimposed preeclampsia being assigned according to the criteria defined by SOMANZ, 2008. A nominal logistic regression analysis was used to evaluate the effects of family history on risk of developing HDP while adjusting for clinical risk factors known at the time of recruitment. RESULTS: Nine hundred and ninety-seven women completed the study. Median gestational age at recruitment was 31.3weeks (Interquartile range [IQR] 24.4-35.9, range 5.6-39.1). Median age was 27.0years (IQR 23.0-32.0, range 16.0-45.0), median BMI was 28.6 (IQR 24.8-36.4, range 16.7-64.4) and 76.4% of the women did not smoke during the pregnancy. Preeclampsia was diagnosed in 12.6% of the women (103/997 preeclampsia, 23/997 superimposed) and 6.2% developed gestational hypertension (62/997). CVD/R was reported by 22.3% of mothers (including 1.7% of CVD alone) and in 9.3% of the partners (including 1.7% of CVD alone). Women reported CVD/R in 39.1% of their mothers (including 6.5% CVD alone) and in 42.2% (including 13.3% CVD alone) of their fathers. Women reported CVD/R in 30.3% (including 6.1% CVD alone) of the partners' mothers and in 38.9% (including 15.0% CVD alone) of the partners' fathers. Women who knew of CVD/R in their fathers had increased risk of preeclampsia (16.2% vs. 10.1%; Odds Ratio [OR]=.66 95% Confidence Interval [CI] 1.16-2.36, p=.005) that remained elevated after adjustments for maternal age, BMI, smoking in pregnancy and maternal CVD/R. No similar increase in risk of gestational hypertension was evident (7.4% vs. 5.4%; OR=1.31 95% CI0.81-2.10,p=0.272). CVD/R reported for any other family member did not significantly alter the woman's risk of developing preeclampsia or any other HDP. CONCLUSION: The presence of a history of CVD/R in the father of the pregnant woman indicated an increased risk of developing preeclampsia. The possibility of a similar association between CVD/R in other family members and HDP may exist however women in their first pregnancy may not have sufficient knowledge of family history. This lack of comprehensive information may limit the potential value of family history in determining the risk of preeclampsia and other hypertensive disorders in pregnancy.

Urgent treatment of acute hypertension.

Acute severe elevation of the blood pressure is a life-threatening event which requires prompt and effective action. Comparative studies of the agents discussed are lacking. Also, hypertensive crises occur in diverse clinical settings and afflict a heterogeneous group of patients. No single drug is ideal in all situations and treatment must be chosen to suit the individual patient.

Treatment of severe pregnancy-associated hypertension with the calcium antagonist nifedipine.

The calcium antagonist, nifedipine, was given orally to 21 women with acute episodes of severe hypertension during pregnancy or in the puerperium. A rapid and significant fall in blood pressure by an average of 26/20 mmHg was seen at 20 min after administration. The hypotensive effect was not significantly enhanced in those women already taking medication to lower the blood pressure. The principal side effects were headache and cutaneous flushing. No adverse fetal effects were detected. This is the first study of the use of this drug to control hypertension in pregnancy. The apparent efficacy of nifedipine justifies its further investigation in controlled trials.

Acute fatty liver of pregnancy: clinical features and diagnosis.

Five cases of acute fatty liver of pregnancy are described. These are the only recognized cases of this disorder occurring in a 2 year period in Western Australia. Clinical and laboratory features are presented. There was no maternal death. Of the six babies, there were three intrauterine deaths, including the only set of twins. All the babies were male. Vomiting in the third trimester was the chief presenting feature in all cases, often accompanied by a systemic illness with malaise and tiredness. Extreme polydipsia was noted as a prominent symptom in all cases. The combination of moderately abnormal liver function tests, extreme leucocytosis with other blood film abnormalities, hypoglycaemia, impaired renal function, coagulopathy and gross elevation of uric acid level is regarded as highly suggestive of the diagnosis. Features of a preeclamptic illness were present in several cases. Three of the patients have since had uneventful pregnancies. The constellation of clinical and laboratory features is sufficiently characteristic to allow accurate clinical diagnosis in most cases of this disorder. The chances of both maternal and fetal survival are enhanced by early diagnosis allowing intervention in the form of prompt delivery of the infant.

Tetracycline and benign intracranial hypertension: report of five cases.

Benign intracranial hypertension occurred in four young women taking tetracycline for acne; two were also taking vitamin A. In a fifth case a 14-year-old boy developed papilloedema after taking a short course of tetracycline for bronchitis. All symptoms disappeared soon after stopping the drugs, though in two cases the papilloedema persisted for many months. Benign intracranial hypertension should be sought in any young woman complaining of headache during treatment with tetracycline. Moreover, young women given vitamin A and tetracycline in combination for acne may be at special risk and should be kept under surveillance.

Neonatal listeriosis: a summer outbreak.

Neonatal listeriosis, a condition associated with high morbidity and mortality, has been reported infrequently in Australia, with only seven isolated cases appearing in the literature. This paper describes 12 cases of neonatal listeriosis diagnosed in two Western Australian hospitals in the 22 months after January, 1978. These were the only cases diagnosed at these hospitals between 1970 and December, 1980. The early onset form of the disease was diagnosed in 11 infants, a group characterized by the frequent associations of low birthweight (mean, 1805 g; range, 1200 g to 2670 g), preterm delivery (gestational age: mean, 33 weeks; range, 28 weeks to 38 weeks), maternal fever at the onset of labour, meconium-stained liquor, low Apgar scores, respiratory distress and septicaemia. The delayed-onset form was diagnosed in one full-term infant (birth-weight, 3050 g) with probable meningitis at one week of age. The over-all mortality rate of 17% was low, perhaps as a result of the early institution of treatment and prompt transfer to a neonatal intensive care unit. Ten of the 12 cases presented during the hottest, driest period of the year. No other common epidemiological factor was identified.

alpha-Fetoprotein elevation and proteinuric pre-eclampsia.

In a retrospective study of pregnancy complicated by unexplained elevation of maternal serum alpha-fetoprotein (AFP), 60 patients were compared with 120 control subjects. Proteinuric pre-eclampsia occurred in 13% of the study patients compared with 1% of the control subjects. Primiparity, previous mid-trimester abortion and recurrent abortions were also significantly more common in the study group. It is proposed that an abnormality of the placenta predisposes to complications and that this abnormality is expressed early in pregnancy when the AFP level is first measured. This group of women is at high risk of adverse pregnancy outcome and requires careful monitoring.

Prophylaxis of thromboembolism in pregnancy: an alternative.

Twenty-six pregnancies in women who had one or more episodes of thromboembolism in the past were managed by a regimen in which routine antenatal prophylactic anticoagulation was not given, apart from during delivery which was covered with intravenous infusion of dextran 70. After delivery, these patients received either subcutaneous heparin for 6 weeks or subcutaneous heparin for 1 week, followed by 5 weeks of warfarin. One patient (4%) possibly developed an episode of thromboembolism in the antenatal period. There were no episodes of postnatal thromboembolism. There were two spontaneous mid-trimester abortions and no perinatal losses. There were no significant complications or reactions related to the use of dextran, heparin or warfarin.

Placental glycolysis and energy metabolism in preeclampsia.

We examined the possibility that in preeclampsia complicated by fetal growth retardation, placental energy state is low either because of impaired glycolysis or because of ischemia resulting from reduced maternal placental blood flow. Concentrations of pyruvate and lactate, but not of glycogen and glucose, were significantly low in placentas of mothers with severe preeclampsia, supporting previous indirect evidence of inhibited glycolysis. Nevertheless, direct measurements of adenine nucleotide concentrations did not indicate reduced placental energy level in the preeclamptic placentas. This along with a lack of change of the ratio of lactate/pyruvate concentration (an indication of the redox state of cytoplasmic reduced nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide) is also evidence against the hypothesis of general placental ischemia leading to energy deficiency. However, as glycolysis is an important source of precursors, particularly pyruvate, for synthesis of amino acids and lipids, these results suggest that there is a significant metabolic abnormality in placentas of mothers with severe preeclampsia.

Pain relief after episiotomy--a comparative study of suprofen and dihydrocodeine.

In a single-dose, randomized, double-blind study of 100 women, suprofen and dihydrocodeine were compared in the relief of pain after episiotomy. The drugs were equal in terms of analgesic efficacy, duration of analgesia and onset of action. Neither drug demonstrated any serious adverse effects.

Blood pressure in the puerperium.

Blood pressure was measured by random zero sphygmomanometer in the morning and afternoon for 5 days after normal delivery in a group of 136 previously normotensive women. The number of women studied each day varied from 32 to 125. The afternoon blood pressure was higher than the morning blood pressure (differences: 1.7 mmHg systolic, 2.6 mmHg diastolic; P less than 0.05). Both systolic and diastolic blood pressures rose for the first 4 days after delivery. The average rise over the whole period was about 6 mmHg systolic and 4 mmHg diastolic (P less than 0.05). A considerable number of previously normotensive women displayed elevations of blood pressure in the puerperium. Twelve per cent of all patients exceeded a diastolic blood pressure of 100 mmHg.

A case-control study of unexplained antepartum stillbirths.

OBJECTIVE: To ascertain factors that will identify women who are at increased risk of unexplained antepartum stillbirth. DESIGN: Matched case-control study. The cases and controls were initially analysed as a whole group and again after dichotomizing into those of low birthweight (< 2500 g) and those of normal birthweight (> or = 2500 g). SETTING: Western Australia 1980-1983. SUBJECTS: Unexplained antepartum stillbirths of > or = 1000 g birthweight (cases) and liveborn infants individually matched for year of birth, plurality, sex and birthweight of infant and race of mother (controls). RESULTS: The case pregnancies had more polyhydramnios (OR 10.83, 95% CI 2.41-48.69) and cord problems (OR 6.57 95% CI 1.36-31.75) than the controls but, paradoxically, other obstetric and medical complications were less common in the cases. The association with polyhydramnios persisted when the analysis was confined to those with low birthweight. With normal birthweight fetal distress was more frequent in the cases (OR 3.65 95% CI 1.36-9.80) but there were few other differences. CONCLUSIONS: The clinical and diagnostic systems currently in use are unable to identify many fetuses at risk of death. Decreases in the rate of unexplained antepartum stillbirths await the discovery of new preventable causes, or of innovations in clinical or laboratory aspects of obstetric care.

Plasma and urinary endothelin 1, prostacyclin metabolites and platelet consumption in pre-eclampsia and essential hypertensive pregnancy.

This study examined plasma and urinary endothelin 1 and urinary metabolites of prostacyclin and thromboxane, in women with pre-eclampsia and age and gestation matched controls. To determine if changes in endothelin 1 and urinary prostanoids in pre-eclampsia were due to hypertension per se, a comparison was made to a group of age and gestation matched pregnant uncomplicated essential hypertensive women. Measurements were taken prior to delivery, and at 6 weeks and 6 months post-partum, and were compared to a group of age matched non-pregnant controls. Plasma endothelin 1 was significantly elevated and the urinary metabolite of prostacyclin (2,3-dinor-6-keto-PGF1 alpha) was significantly suppressed in pre-eclamptic pregnancy, compared to normal pregnancy and essential hypertensive pregnancy. As the level of blood pressure was similar in the pre-eclamptic and essential hypertensive groups, these changes are not due to an increase in blood pressure per se. Urinary endothelin 1 was not different in the 3 pregnant groups prior to delivery but fell significantly after delivery. Urinary endothelin 1 was significantly lower in the essential hypertensive group at 6 weeks post-partum compared to pregnant controls with a similar trend at 6 months. Urinary 11-dehydro-TXB2 was elevated in pregnancy, but no further elevation was seen in women with pre-eclampsia. Platelet counts were lower, and circulating neutrophil counts higher in pre-eclampsia prior to delivery. A combination of increased plasma endothelin 1 and reduced tissue prostacyclin synthesis may contribute to hypertension, placental insufficiency, foetal growth retardation and renal dysfunction in pre-eclampsia.(ABSTRACT TRUNCATED AT 250 WORDS)

Withdrawal of nifedipine capsules: jeopardizing the treatment of acute severe hypertension in pregnancy? Australasian Society for the Study of Hypertension in Pregnancy.

Short-acting oral nifedipine has been withdrawn from the Australian market because of reports of its adverse effects after long-term treatment in non-pregnant patients with heart disease. This will have a major impact on the treatment of acutely hypertensive pregnant women, in whom the drug has proven to be safe, effective and easy to administer. Should pregnant women be forced to use less suitable agents, thus threatening their own and their babies' health?