Kate Bramham

Chronic hypertension and pregnancy outcomes: systematic review and meta-analysis

Objective To provide an accurate assessment of complications of pregnancy in women with chronic hypertension, including comparison with population pregnancy data (US) to inform pre-pregnancy and antenatal management strategies. Design Systematic review and meta-analysis. Data sources Embase, Medline, and Web of Science were searched without language restrictions, from first publication until June 2013; the bibliographies of relevant articles and reviews were hand searched for additional reports. Study selection Studies involving pregnant women with chronic hypertension, including retrospective and prospective cohorts, population studies, and appropriate arms of randomised controlled trials, were included. Data extraction Pooled incidence for each pregnancy outcome was reported and, for US studies, compared with US general population incidence from the National Vital Statistics Report (2006). Results 55 eligible studies were identified, encompassing 795 221 pregnancies. Women with chronic hypertension had high pooled incidences of superimposed pre-eclampsia (25.9%, 95% confidence interval 21.0% to 31.5 %), caesarean section (41.4%, 35.5% to 47.7%), preterm delivery <37 weeks’ gestation (28.1% (22.6 to 34.4%), birth weight <2500 g (16.9%, 13.1% to 21.5%), neonatal unit admission (20.5%, 15.7% to 26.4%), and perinatal death (4.0%, 2.9% to 5.4%). However, considerable heterogeneity existed in the reported incidence of all outcomes (τ2=0.286-0.766), with a substantial range of incidences in individual studies around these averages; additional meta-regression did not identify any influential demographic factors. The incidences (the meta-analysis average from US studies) of adverse outcomes in women with chronic hypertension were compared with women from the US national population dataset and showed higher risks in those with chronic hypertension: relative risks were 7.7 (95% confidence interval 5.7 to 10.1) for superimposed pre-eclampsia compared with pre-eclampsia, 1.3 (1.1 to 1.5) for caesarean section, 2.7 (1.9 to 3.6) for preterm delivery <37 weeks’ gestation, 2.7 (1.9 to 3.8) for birth weight <2500 g, 3.2 (2.2 to 4.4) for neonatal unit admission, and 4.2 (2.7 to 6.5) for perinatal death. Conclusions This systematic review, reporting meta-analysed data from studies of pregnant women with chronic hypertension, shows that adverse outcomes of pregnancy are common and emphasises a need for heightened antenatal surveillance. A consistent strategy to study women with chronic hypertension is needed, as previous study designs have been diverse. These findings should inform counselling and contribute to optimisation of maternal health, drug treatment, and pre-pregnancy management in women affected by chronic hypertension.

Pregnancy and renal outcomes in lupus nephritis: an update, and guide to management

Systemic lupus erythematosis (SLE) commonly affects women of child bearing-age, and advances in treatment have resulted in an increasing number of women with renal involvement becoming pregnant. Knowledge of the relationship of the condition with respect to fertility and pregnancy is important for all clinicians involved in the care of women with lupus nephritis because they have complicated pregnancies. Presentation of lupus nephritis can range from mild asymptomatic proteinuria to rapidly progressive renal failure and may occur before, during, or after pregnancy. The timing of diagnosis may influence pregnancy outcome. Pregnancy may also affect the course of lupus nephritis. All pregnancies in women with lupus nephritis should be planned, preferably after more than six-months of quiescent disease. Predictors of poor obstetric outcome include active disease at conception or early pregnancy, baseline poor renal function with Creatinine >100 μmol/L, proteinuria >0.5 g/24 hours, presence of concurrent antiphospholipid syndrome and hypertension. In this review the most recent studies of pregnancies in women with lupus nephritis are discussed and a practical approach to managing women prepregnancy, during pregnancy and post-partum is described

Pre-pregnancy counseling for women with chronic kidney disease.

Pre-pregnancy counseling should be available for all women with chronic kidney disease (CKD) so that conception occurs at the right time in the course of their disease and while they are on the right medications, with the aims of minimizing risks for both mother and fetus. Key areas to consider are the factors which are associated with worse prognosis and the influence of underlying kidney conditions and their treatment, in particular lupus nephritis, advanced renal impairment and transplantation. This experience-based review provides a guide to clinicians managing women with CKD, before and during their pregnancy.

Tacrolimus is an effective treatment for lupus nephritis in pregnancy

Lupus nephritis during pregnancy increases morbidity and mortality for mother and baby. Flares are difficult to treat as many therapeutic options are teratogenic or fetotoxic. Steroids alone may be unable to control disease activity and are associated with higher rates of preterm delivery, sepsis and gestational diabetes. Reports of using tacrolimus to treat lupus nephritis in pregnancy are limited. We describe the pregnancies of nine women in whom tacrolimus was successfully used to treat lupus nephritis flare (six patients) or maintain stable disease (three patients). Introduction or dose escalation of oral steroids was avoided in five of the patients who developed active disease and steroid dose was rapidly reduced in the sixth patient. All women with disease flare attained partial or complete remission after starting tacrolimus. None of the women on maintenance treatment developed active disease. We propose tacrolimus as an effective adjuvant or alternative therapy to steroids for treating lupus nephritis flare or maintaining stable disease during pregnancy.

The non-invasive biopsy—will urinary proteomics make the renal tissue biopsy redundant?

Proteomics is a rapidly advancing technique which gives functional insight into gene expression in living organisms. Urine is an ideal medium for study as it is readily available, easily obtained and less complex than other bodily fluids. Considerable progress has been made over the last 5 years in the study of urinary proteomics as a diagnostic tool for renal disease. Advantages over the traditional renal biopsy include accessibility, safety, the possibility of serial sampling and the potential for non-invasive prognostic and diagnostic monitoring of disease and an individuals response to treatment. Urinary proteomics is now moving from a discovery phase in small studies to a validation phase in much larger numbers of patients with renal disease. Whilst there are still some limitations in methodology, which are assessed in this review, the possibility of urinary proteomics replacing the invasive tissue biopsy for diagnosis of renal disease is becoming an increasingly realistic option.

Postpartum management of hypertension

#### Summary points Hypertension in the postpartum period affects several groups of women, including those with previous chronic hypertension, gestational hypertension, pre-eclampsia, and eclampsia. In addition, pre-eclampsia may present for the first time in the postnatal period. Although the underlying causes and clinical presentation of these types of hypertension vary, patients can be investigated and treated in a similar manner. This review covers management of postpartum hypertension and its future consequences. Hypertension affects 6-10% of pregnancies,1 but few studies have reported the incidence of postpartum hypertension. This review is relevant to general practitioners, obstetricians, and specialists in secondary care who may see women with postpartum hypertension. #### Sources and selection criteria We searched PubMed (June 2012) for relevant articles on postpartum management of hypertension, pre-eclampsia, and eclampsia. The MeSH terms for the search included “postpartum”, “hypertension”, “pre-eclampsia”, and “eclampsia”, in addition to keyword variations. We obtained information from prospective randomised clinical trials, cohort studies, case series, systematic reviews, and meta-analyses. We also searched national and international guidelines for those including advice on postpartum management of hypertension and kidney disease. Generalised systemic vasodilation occurs during pregnancy; despite a 40-50% increase in cardiac output, mean arterial pressure drops by about 10 mm Hg to reach its lowest value by mid-pregnancy.2 During the last trimester, blood pressure gradually increases to …

Pregnancy Outcomes in Liver and Cardiothoracic Transplant Recipients: A UK National Cohort Study

Introduction There are an increasing number of reports of pregnancy in transplant recipients but many questions remain regarding the effect of the transplant on pregnancy outcome, the pregnancy on the graft and the medication on the fetus. The majority of studies reporting outcomes in transplant recipients have focused on women with kidney transplants, and have included retrospective, voluntary registries or single centre studies. Methods The UK Obstetric Surveillance System (UKOSS) was used to prospectively identify all pregnant women with a liver or cardiothoracic transplant in the United Kingdom, between January 2007 and January 2012. Data were collected on demographics, transplant characteristics, immunosuppression regimens, antenatal care, maternal, graft and neonatal outcomes. In an exploratory analysis, we tested for associations between “poor fetal outcome” and medications used before or during pregnancy. Results and conclusions We report 62 pregnancies in 56 liver transplant recipients and 14 pregnancies in 14 cardiothoracic transplant recipients (including 10 heart, three lung and one heart-lung recipient). Liver transplant recipients, in comparison to cardiothoracic, had similar livebirth rates (92% vs. 87%) but better fetal outcomes (median gestational age 38 weeks vs. 35 weeks; median birthweight 2698 g vs. 2365 g), fewer caesarean deliveries (47% vs. 62%), fewer maternal intensive care (ICU) admissions (19% vs. 29%) and fewer neonatal ICU admissions (25% vs. 54%). Nine women (12%) were taking mycophenolate mofetil at conception, which was associated with adverse fetal outcomes. Pregnancy in transplant recipients may have successful outcomes, but complication rates are high, emphasising the role of pre-conception counselling and further research into the long-term effect on maternal and graft survival rates.

Pregnancy in pancreas–kidney transplant recipients: report of three cases and review of the literature

Seventy-three pregnancies in 43 women with SPK have now been described by the US National Transplantation Pregnancy Registry (NTPR) (established in 1991), which contains self-reported data from questionnaires and hospital records. These women have high rates of complications despite normoglycaemia and restoration of renal function. We describe the pregnancies of three SPK recipients in the UK managed in joint renal obstetric clinics and discuss the antenatal and postnatal complications specific to SPK transplants.

Reproductive health and pregnancy in women with chronic kidney disease

Chronic kidney disease (CKD) is associated with reduced fertility and an increased risk of adverse pregnancy outcomes. Rates of pre-eclampsia, fetal growth restriction and preterm delivery increase incrementally with the severity of CKD and proteinuria. Pre-pregnancy counselling can facilitate informed decision-making. Safe and effective contraception is required for women who wish to delay or avoid pregnancy. Pregnancy planning for women who wish to conceive involves appropriate substitution of known teratogens — including mycophenolate mofetil, angiotensin blockers and cyclophosphamide — and can aid optimization of disease control. However, pregnancy, which can occur in women with any stage of CKD, can exacerbate comorbidities such as anaemia, vitamin D deficiency and hypertension. Increased haemodialysis provision is associated with improved pregnancy outcomes for women on dialysis. Diagnosis of pre-eclampsia in women with CKD is complicated in patients with pre-existing hypertension and proteinuria but can be improved by the use of vasoactive biomarkers as well as placental and fetal Doppler ultrasound. Pregnancy data for newer drugs used in CKD are limited as pregnancy and CKD are common exclusion criteria for drug and intervention trials. Although prospective data may be available for older drugs, the use of most drugs in pregnancy is based on retrospective data and expert consensus.

PREGNANCY IN DIABETES AND KIDNEY DISEASE

SUMMARY With appropriate multi-disciplinary team care, most women with diabetic nephropathy will have successful pregnancy outcomes; however, pregnancy complications are increased compared to non-diabetic individuals, particularly in those with poor glycaemic control. Women with more severe renal impairment, especially those with hypertension and proteinuria at are highest risk of worse pregnancy outcomes and deterioration in pre-existing renal function. Pre-pregnancy counselling should be offered to all women with diabetes in order to optimise diabetic care, and inform women of potential complications. Pregnancy is an indicator of long-term health, and may indicate important issues for the future management of women with diabetic nephropathy.With appropriate multi-disciplinary team care, most women with diabetic nephropathy will have successful pregnancy outcomes; however, pregnancy complications are increased compared to non-diabetic individuals, particularly in those with poor glycaemic control. Women with more severe renal impairment, especially those with hypertension and proteinuria at are highest risk of worse pregnancy outcomes and deterioration in pre-existing renal function. Pre-pregnancy counselling should be offered to all women with diabetes in order to optimise diabetic care, and inform women of potential complications. Pregnancy is an indicator of long-term health, and may indicate important issues for the future management of women with diabetic nephropathy.