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).

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.

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.

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.

Anticoagulation in pregnancy and the puerperium.

For the management of acute thrombotic events in pregnancy therapeutic doses of low molecular weight heparins (LMWH) may be used, unless the shorter half-life of intravenous unfractionated heparin (UH) and predictable reversibility by protamine are important. Treatment should be continued up until delivery and into the puerperium. Pregnant women who have had an acute thrombotic event should be delivered by a specialist team. In the case of recent thrombosis, delivery should be planned and the time during which anticoagulation therapy is ceased around the time of delivery should be minimised. Therapeutic doses of LMWH contraindicate the use of regional anaesthesia, and a switch to intravenous UH before delivery may allow greater flexibility in this regard. Prophylactic doses of LMWH can be used to reduce the risk of recurrent thromboembolic events in pregnancy. The regimen used will depend on the previous history, the family history and the presence of risk factors, including the genetic and acquired causes of thrombophilia. Women with mechanical heart valves are at high risk during pregnancy and require therapeutic anticoagulation throughout pregnancy under the direction of experienced specialists. Low-dose aspirin can reduce the risk of recurrent pre-eclampsia by about 15%, but the role of UH and LMWH in the prevention of recurrent miscarriage or obstetric complications associated with uteroplacental insufficiency is still uncertain.

Effects of lipoproteins from pre-eclamptic women on umbilical endothelial cell 6-oxo-prostaglandin f1alpha and endothelin 1 synthesis, and nitric oxide synthase 3 mRNA expression.

In order to evaluate whether lipid abnormalities may contribute to endothelial dysfunction in pre-eclampsia, the present study examined the in vitro effects of very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL), isolated from women with pre-eclampsia and matched controls, on the endothelial synthesis of 6-oxo-prostaglandin F(1alpha) (6-oxo-PGF(1alpha); a metabolite of prostacyclin) and endothelin 1, and on the expression of nitric oxide synthase 3 (NOS3) mRNA. VLDL, LDL and HDL cholesterol were isolated from 20 pre-eclamptic and 20 age- and gestation-matched normal pregnant women. The lipoproteins (50 microgram/ml) and lipoprotein-free control plasma were incubated for 1, 3 and 6 h at 37 degrees C with a human umbilical endothelial cell line. The synthesis of 6-oxo-PGF(1alpha) and endothelin 1, and NOS3 mRNA expression, were measured at each time point. VLDL from pre-eclamptic women stimulated endothelial cell 6-oxo-PGF(1alpha) synthesis to a lesser extent than that from normal pregnant women (P<0.05). LDL from women with pre-eclampsia also stimulated 6-oxo-PGF(1alpha) synthesis to a lesser extent than LDL from normal pregnant women, but the effect was less sustained. The effect of HDL from women with pre-eclampsia on 6-oxo-PGF(1alpha) synthesis was similar to that of HDL from normal pregnant women. The pre-incubation levels of lipid peroxides in VLDL and LDL were not different between the normal pregnant and pre-eclamptic women, and cannot account for the decrease in 6-oxo-PGF(1alpha) synthesis. VLDL, LDL and HDL from women with pre-eclampsia did not affect endothelial cell synthesis of endothelin 1 or expression of NOS3 mRNA differently from lipoproteins from normal pregnant women. This study suggests that VLDL, and to a lesser extent LDL, from women with pre-eclampsia could potentially contribute to the reduced systemic 6-oxo-PGF(1alpha) synthesis observed in the pre-eclamptic syndrome.

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.

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.

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?

Neutrophil CD11B expression and neutrophil activation in pre-eclampsia.

1. Neutrophil activation was examined in 22 women with pre-eclampsia and 22 age- and gestation-matched control subjects using whole-blood flow cytometry to assess basal and platelet-activating factor stimulated CD11b and CD18. 2. Basal neutrophil CD11b expression was significantly increased in women with pre-eclampsia compared with normal pregnancy before delivery. A similar non-significant trend for CD18 was also observed. 3. Before delivery, neutrophil CD11b expression increased in a dose-dependent fashion after platelet-activating factor stimulation, with the differences between the groups maintained. A similar dose-dependent increase in CD18 expression was observed after platelet-activating factor. 4. There were no between-group differences in expression of either CD11b or CD18 at either 6 weeks or 6 months post partum, either before or after platelet-activating factor stimulation. 5. Neutrophil CD11b was positively correlated with plasma uric acid (r = 0.44, P = 0.04) in women with pre-eclampsia, suggesting that the extent of neutrophil activation correlates with disease severity. 6. An increase in basal neutrophil CD11b expression in women with pre-eclampsia is likely to be an index of neutrophil activation in vivo. Neutrophil release of free radicals and proteases may then help perpetuate a vicious cycle of endothelial and vascular dysfunction in the placental and systemic circulations. The cause of this activation is not known but could involve platelet activation, increased production of endothelin-1 or release of cytokines. Further studies will be required to elucidate the consequences of neutrophil activation in pre-eclampsia.

Plasma and urinary 8-iso-prostane as an indicator of lipid peroxidation in pre-eclampsia and normal pregnancy.

1. This study was designed to seek evidence for excessive lipid peroxidation in pre-eclamptic women using 8-iso-prostane as a novel bioactive marker of lipid peroxidation in vivo. Plasma free, total and urinary 8-iso-prostane were measured in 20 women with proteinuric pre-eclampsia, and compared with 18 age- and gestation-matched pregnant control subjects, before delivery and at 6 weeks post-partum. 2. Plasma free 8-iso-prostane was significantly elevated in the pre-eclamptic women compared with control subjects before delivery, and fell to control levels post-partum. Conversely, levels in women with normal pregnancy rose post-partum. 3. Total plasma 8-iso-prostane levels were not significantly elevated in pre-eclamptic women compared with control subjects during pregnancy, but fell significantly in the pre-eclamptic women post-partum, suggesting that they had relatively higher levels compared with their non-pregnant state. 4. Urinary 8-iso-prostane excretion was significantly lower in the pre-eclamptic women compared with control subjects during pregnancy, suggesting that renal clearance of 8-iso-prostane is impaired in pre-eclampsia. 5. Increased levels of plasma free 8-iso-prostane in pre-eclampsia could be due to an increase in lipid peroxidation, an increase in phospholipase A2 activity or a reduction in renal clearance of 8-iso-prostane, or a combination of all three. The potent direct and indirect vasoconstrictor actions of 8-iso-prostane may contribute to the pathogenesis of pre-eclampsia.

Elevated mid-trimester hCG and maternal lupus anticoagulant.

An association is described between women with lupus anticoagulant and abnormal prenatal serum screening results. Three cases of positive second-trimester serum screening for Down syndrome, with karyotypically normal fetuses, in women demonstrated to have lupus anticoagulant are presented. Serum screening positivity was principally due to a disproportionately elevated maternal serum human chorionic gonadotrophin (hCG) level. In each case, early, severe intrauterine growth restriction was documented, with only one fetus surviving the neonatal period. As maternal lupus anticoagulant may have a profoundly adverse effect on the course of pregnancy, we suggest that an elevated hCG level on prenatal screening prompt consideration of maternal lupus anticoagulant testing if ultrasonography demonstrates an otherwise normal singleton gestation and the fetal karyotype is normal.

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)

Neutrophil platelet-activating factor in normal and hypertensive pregnancy and in pregnancy-induced hypertension.

1. Platelet-activating factor is a phospholipid with potent vasodilator and platelet-activating properties. To test the hypothesis that a generalized change in cellular platelet-activating factor metabolism may be involved in the systemic vasodilatation of normal pregnancy or pregnancy-induced hypertension, we studied platelet-activating factor and eicosanoid synthesis in isolated leucocytes obtained from pregnant women before and after delivery compared with age-matched non-pregnant control subjects. Parallel observations were carried out in age- and gestation-matched women with uncomplicated hypertension in pregnancy and in women with pregnancy-induced hypertension and a further set of normotensive pregnant control subjects. 2. Leucocyte counts were higher in all pregnant groups compared with non-pregnant control subjects. Neutrophil production of platelet-activating factor and metabolites of prostacyclin, prostaglandin E2 and thromboxane in response to calcium ionophore stimulation were all lower in pregnant women compared with non-pregnant control subjects, but returned to similar levels 6 weeks post partum. There was no significant difference between essential hypertensive and normotensive groups. When women with pregnancy-induced hypertension were a priori sub-divided into those with or without proteinuria, subjects with proteinuria showed significantly lower levels of neutrophil platelet-activating factor synthesis. 3. Plasma levels of the platelet-activating factor metabolite (lyso-platelet-activating factor) were also lower in pregnancy, suggesting alterations in the activity of enzymes controlling synthesis or degradation of this phospholipid in pregnancy. In pregnancy-induced hypertension the levels of plasma lyso-platelet-activating factor were higher than in normal pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.