Barry N. Walters

The detection, investigation and management of hypertension in pregnancy: full consensus statement

Hypertension in pregnancy is associated with increased maternal and fetal morbidity and mortality I t is a common sign, reflecting a number of underlying disorders that may have different clinical outcomes. It is important that a woman with hypertension be diagnosed accurately so that the cause of the hypertension can be identified. She can then be informed about her likely clinical course and be managed appropriately. Hypertensive disorders in pregnancy are best managed with a multidisciplinary approach; the obstetrician should remain the doctor in charge and seek advice from other appropriate specialists (eg anaesthetists. neonatologists, physicians) where indicated. This document offers a framework for a team approach to the diagnosis, investigation and management of women with hypertension in pregnancy The recommendations are those of a multidisciplinary working party set up by the Australasian Society for the Study of Hypertension in Pregnancy to review and revise its previous guidelines for the detection, investigation and management of hypertension in pregnancy They are based on definitions and a classification system that reflect current knowledge. It is recommended that each obstetric unit develop its own management protocols.

Prediction of adverse maternal outcomes in pre-eclampsia: development and validation of the fullPIERS model

BACKGROUND Pre-eclampsia is a leading cause of maternal deaths. These deaths mainly result from eclampsia, uncontrolled hypertension, or systemic inflammation. We developed and validated the fullPIERS model with the aim of identifying the risk of fatal or life-threatening complications in women with pre-eclampsia within 48 h of hospital admission for the disorder. METHODS We developed and internally validated the fullPIERS model in a prospective, multicentre study in women who were admitted to tertiary obstetric centres with pre-eclampsia or who developed pre-eclampsia after admission. The outcome of interest was maternal mortality or other serious complications of pre-eclampsia. Routinely reported and informative variables were included in a stepwise backward elimination regression model to predict the adverse maternal outcome. We assessed performance using the area under the curve (AUC) of the receiver operating characteristic (ROC). Standard bootstrapping techniques were used to assess potential overfitting. FINDINGS 261 of 2023 women with pre-eclampsia had adverse outcomes at any time after hospital admission (106 [5%] within 48 h of admission). Predictors of adverse maternal outcome included gestational age, chest pain or dyspnoea, oxygen saturation, platelet count, and creatinine and aspartate transaminase concentrations. The fullPIERS model predicted adverse maternal outcomes within 48 h of study eligibility (AUC ROC 0·88, 95% CI 0·84-0·92). There was no significant overfitting. fullPIERS performed well (AUC ROC >0·7) up to 7 days after eligibility. INTERPRETATION The fullPIERS model identifies women at increased risk of adverse outcomes up to 7 days before complications arise and can thereby modify direct patient care (eg, timing of delivery, place of care), improve the design of clinical trials, and inform biomedical investigations related to pre-eclampsia. FUNDING Canadian Institutes of Health Research; UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development, and Research Training in Human Reproduction; Preeclampsia Foundation; International Federation of Obstetricians and Gynecologists; Michael Smith Foundation for Health Research; and Child and Family Research Institute.

Guidelines for the management of hypertensive disorders of pregnancy 2008

This is the Executive Summary of updated guidelines developed by the Society of Obstetric Medicine of Australia and New Zealand for the management of hypertensive diseases of pregnancy. They address a number of challenging areas including the definition of severe hypertension, the use of automated blood pressure monitors, the definition of non‐proteinuric pre‐eclampsia and measuring proteinuria. Controversial management issues are addressed such as the treatment of severe hypertension and other significant manifestations of pre‐eclampsia, the role of expectant management in pre‐eclampsia remote from term, thromboprophylaxis, appropriate fluid therapy, the role of prophylactic magnesium sulfate and anaesthetic issues for women with pre‐eclampsia. The guidelines stress the need for experienced team management for women with pre‐eclampsia and mandatory hospital protocols for treatment of hypertension and eclampsia. New areas addressed in the guidelines include recommended protocols for maternal and fetal investigation of women with hypertension, preconception management for women at risk of pre‐eclampsia, auditing outcomes in women with hypertensive diseases of pregnancy and long‐term screening for women with previous pre‐eclampsia.

The detection, investigation and management of hypertension in pregnancy: executive summary

These are the recommendations of a multidisciplinary working party set up by the Australasian Society for the Study of Hypertension in Pregnancy to review and revise its previous guidelines for the detection, investigation and management of hypertension in pregnancy. They are based on definitions and a classification system that reflect current knowledge. It is recommended that each obstetric unit develop its own management protocols. The following summarises the contents of the consensus report. This may prove a useful “office guide” for clinicians but should still be interpreted in light of the full discussion within the body of this report.

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.

A randomised controlled trial of dietary energy restriction in the management of obese women with gestational diabetes

Summary: A randomised controlled trial was designed to determine the effect of moderate 30% maternal dietary energy restriction on the requirement for maternal insulin therapy and the incidence of macrosomia in gestational diabetes. Although the control group restricted their intake to a level similar to that of the intervention group (6845 kiloJoules (kJ) versus 6579 kJ), the resulting cohort could not identify any adverse effect of energy restriction in pregnancy. Energy restriction did not alter the frequency of insulin therapy (17.5% in the intervention group and 16.9% in the control group). Mean birth weight (3461 g in the intervention group and 3267 g in the control group) was not affected. There was a trend in the intervention group towards later gestational age at commencement of insulin therapy (33 weeks versus 31 weeks) and lower maximum daily insulin dose (23 units versus 60 units) which did not reach statistical significance. Energy restriction did not cause an increase in ketonemia.

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.

Recommendations for the diagnosis and treatment of deep venous thrombosis and pulmonary embolism in pregnancy and the postpartum period

Venous thromboembolism (VTE) in pregnancy and the postpartum is an important cause of maternal morbidity and mortality; yet, there are few robust data from clinical trials to inform an approach to diagnosis and management. Failure to investigate symptoms suggestive of pulmonary embolism (PE) is a consistent finding in maternal death enquiries, and clinical symptoms should not be relied on to exclude or diagnose VTE. In this consensus statement, we present our recommendations for the diagnosis and management of acute deep venous thrombosis (DVT) and PE. All women with suspected DVT in pregnancy should be investigated with whole leg compression ultrasonography. If the scan is negative and significant clinical suspicion remains, then further imaging for iliofemoral DVT maybe required. Imaging should be undertaken in all women with suspected PE, as the fetal radiation exposure with both ventilation/perfusion scans and CT pulmonary angiography is within safe limits. Low‐molecular‐weight heparin (LMWH) is the preferred therapy for acute VTE that occur during pregnancy. In observational cohort studies, using once‐daily regimens appears adequate, in particular with the LMWH tinzaparin; however, pharmacokinetic data support twice‐daily therapy with other LMWH and is recommended, at least initially, for PE or iliofemoral DVT in pregnancy. Treatment should continue for a minimum duration of six months, and until at least six weeks postpartum. Induction of labour or planned caesarean section maybe required to allow an appropriate transition to unfractionated heparin to avoid delivery in women in therapeutic doses of anticoagulation.

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)

Recommendations for the prevention of pregnancy-associated venous thromboembolism.

Pregnancy is a risk factor for venous thromboembolism (VTE), an important cause of maternal morbidity and mortality. Although there is a 4–5‐fold increased risk compared to that of nonpregnant women of the same age, the absolute risk is low at no more than two episodes of VTE per 1000 pregnancies. There is uncertainty about which women require thromboprophylaxis during pregnancy or postpartum because of a lack of data from appropriate clinical trials. For this reason, recommendations for prophylaxis should be made only after explaining the available evidence to the patient and taking into account her perception of the balance of risk and benefit in thromboprophylaxis. The aim of these recommendations is to provide clinicians with practical advice to assist in decisions regarding thromboprophylaxis in women considered to be at risk of VTE during pregnancy and the postpartum. The authors are clinicians from across New Zealand and Australia representing the fields of haematology, obstetric medicine, anaesthesiology, maternal–fetal medicine and obstetrics. Authors were invited to review the relevant literature and then worked collaboratively to devise recommendations and resolve areas of controversy. The recommendations contained herein were reached by consensus and represent the opinion of the panel. The absence of randomised clinical trials in this area limits the strength of evidence that can be used, and it is acknowledged that they represent level C evidence. The panel advocates for appropriate clinical studies to be carried out in this patient population to address the inadequacy of present evidence.