The effectiveness of decision aids for pregnancy related decision-making in women with pre-pregnancy morbidity; systematic review and meta-analysis.

INTRODUCTION: Women with pre-existing morbidity arising from medical conditions or previous caesarean section are at higher risk of adverse pregnancy outcomes compared to women without such morbidity. Women often face complex pregnancy-related decision-making that may be characterized by conflicting maternal and perinatal priorities. The aim of this systematic review and meta-analysis was to assess randomised controlled trials of decision aids to evaluate whether they are effective at reducing decisional conflict scores and to evaluate what type of decision aids are most effective for women with pre-existing morbidity in pregnancy. METHODS: We searched Medline (via Ovid), Embase (via Ovid), CINAHL (via EBSCO) from the earliest entries until September 2021. We selected randomised controlled trials comparing patient decision aids for women with pre-existing morbidity with usual clinical practice or a control intervention. Study characteristics and Jadad risk of bias was recorded. Meta-analysis by pre-existing morbidity type was performed using Stata 17 and the data was presented with a Forest Plot. Random effects models were used to calculate summary estimates if there was substantial clinical or statistical heterogeneity and post mean DCS scores were described in a sensitivity analysis and presented as a line graph, to improve clinical interpretation of results.. A narrative synthesis of the selected studies evaluated what type of decision aid works and for in what circumstances. RESULTS: Ten randomised controlled trials, which reported data from 4028 women, were included. Patient decision aids were evaluated in women with pre-existing morbidity who were undertaking pregnancy-related decision-making. Patient decision aids reduced decisional conflict scale scores by an additional - 3.7, 95% Confidence Interval - 5.9% to - 1.6%) compared to the control group. Women with pre-existing medical conditions were more conflicted at baseline and had greater reductions in decisional conflict scale score (mean difference vs. control group: - 6.6%; 95% CI - 9.8% to - 3.3%), in contrast to those with previous caesarean section (mean difference - 2.4%; 95% CI - 4.8% to - 0.1%). There was limited evidence on the effect of decision aids on health outcomes. Decision aids reduced unwanted variation in decision-making support across maternity settings. CONCLUSION: Patient decision aids are effective tools to support personalised care planning and informed decision-making in women with pre-existing morbidity. Women with pre-existing medical morbidity were more conflicted at baseline and were more likely to benefit from decision aids. Adoption of aids in this population may lead to improve adherence and health outcomes, warranting further research.

The impact of chronic kidney disease Stages 3-5 on pregnancy outcomes.

BACKGROUND: Contemporaneous data are required for women with chronic kidney disease (CKD) Stages 3-5 to inform pre-pregnancy counselling and institute appropriate antenatal surveillance. METHODS: A retrospective cohort study in women with CKD Stages 3-5 after 20 weeks' gestation was undertaken in six UK tertiary renal centres in the UK between 2003 and 2017. Factors predicting adverse outcomes and the impact of pregnancy in accelerating the need for renal replacement therapy (RRT) were assessed. RESULTS: There were 178 pregnancies in 159 women, including 43 women with renal transplants. The live birth rate was 98%, but 56% of babies were born preterm (before 37 weeks' gestation). Chronic hypertension was the strongest predictor of delivery before 34 weeks' gestation. Of 121 women with known pre-pregnancy hypertension status, the incidence of delivery before 34 weeks was 32% (31/96) in women with confirmed chronic hypertension compared with 0% (0/25) in normotensive women. The risk of delivery before 34 weeks doubled in women with chronic hypertension from 20% [95% confidence interval (CI) 9-36%] to 40% (95% CI 26-56%) if the gestational fall in serum creatinine was <10% of pre-pregnancy concentrations. Women with a urinary protein:creatinine ratio >100 mg/mmol prior to pregnancy or before 20 weeks' gestation had an increased risk for birthweight below the 10th centile (odds ratio 2.57, 95% CI 1.20-5.53). There was a measurable drop in estimated glomerular filtration rate (eGFR) between pre-pregnancy and post-partum values (4.5 mL/min/1.73 m2), which was greater than the annual decline in eGFR prior to pregnancy (1.8 mL/min/1.73 m2/year). The effect of pregnancy was, therefore, equivalent to 1.7, 2.1 and 4.9 years of pre-pregnancy renal disease in CKD Stages 3a, 3b and 4-5, respectively. The pregnancy-associated decline in renal function was greater in women with chronic hypertension and in those with a gestational fall in serum creatinine of <10% of pre-pregnancy concentrations. At 1 year post-partum, 46% (58/126) of women had lost ≥25% of their pre-pregnancy eGFR or required RRT. Most women with renal transplants had CKD Stage 3 and more stable renal function prior to pregnancy. Renal transplantation was not independently associated with adverse obstetric or renal outcomes. CONCLUSIONS: Contemporary pregnancies in women with CKD Stages 3-5 are complicated by preterm delivery, low birthweight and loss of maternal renal function. Chronic hypertension, pre- or early pregnancy proteinuria and a gestational fall in serum creatinine of <10% of pre-pregnancy values are more important predictors of adverse obstetric and renal outcome than CKD Stages 3-5. Pregnancy in women with CKD Stages 3-5 advances the need for dialysis or transplantation by 2.5 years.

Diagnostic accuracy of repeat placental growth factor measurements in women with suspected preeclampsia: A case series study.

INTRODUCTION: Preeclampsia affects about 3% of singleton pregnancies and is characterized by placental dysfunction. It is associated with significant maternal and perinatal morbidity and mortality. The diagnosis of preeclampsia remains a challenge, and the clinical course can develop for weeks before a diagnosis is confirmed. National guidelines have approved placental growth factor (PlGF) testing to rule out suspected preeclampsia, but the utility of repeated PlGF measurement is unknown. The aim of this case series analysis was to evaluate the test performance of repeated PlGF sampling in women presenting with suspected preeclampsia, and to describe relevant clinical outcomes. MATERIAL AND METHODS: Women who presented to maternity services with suspected preeclampsia between 20+0 and 36+6  weeks' gestation who underwent repeat PlGF sampling with a minimum test interval of 7 days were assessed. The outcomes were delivery for preeclampsia within 14 days of sampling, the proportion changing PlGF categories, and time to delivery. RESULTS: In total, 289 women with suspected preeclampsia undergoing repeat PlGF sampling were included. PlGF <100 pg/mL had a high sensitivity (87.5%, 95% confidence interval [CI] 67.6%-97.3%) and a negative predictive value (97.7%, 95% CI 93.5%-99.5%) at the initial test (receiver operating characteristic [ROC] area 0.79, 95% CI 0.68-0.89). Similar test performance was seen for PlGF <100 pg/mL when undertaken as a repeat test (sensitivity 90.7%, 95% CI 85.2%-95.9%, negative predictive value 92.2%, 95% CI 85.3-96.6%). Overall, 25.6% of women changed PlGF category between the first and second PlGF tests. For each PlGF category, determination of time to delivery was similar for first and second tests. CONCLUSIONS: Repeat PlGF measurement demonstrates high negative predictive value for determining preeclampsia requiring delivery in 14 days. Repeat testing may be clinically useful to risk stratify women with ongoing symptoms of disease. Confirmation of the impact of these findings is required in further studies.

Chronic hypertension in pregnancy: impact of ethnicity and superimposed preeclampsia on placental, endothelial, and renal biomarkers.

Black ethnicity is associated with worse pregnancy outcomes in women with chronic hypertension. Preexisting endothelial and renal dysfunction and poor placentation may contribute, but pathophysiological mechanisms underpinning increased risk are poorly understood. This cohort study aimed to investigate the relationship between ethnicity, superimposed preeclampsia, and longitudinal changes in markers of endothelial, renal, and placental dysfunction in women with chronic hypertension. Plasma concentrations of placental growth factor (PlGF), syndecan-1, renin, and aldosterone and urinary angiotensinogen-to-creatinine ratio (AGTCR), protein-to-creatinine ratio (PCR), and albumin-to-creatinine ratio (ACR) were quantified during pregnancy and postpartum in women with chronic hypertension. Comparisons of longitudinal biomarker concentrations were made using log-transformation and random effects logistic regression allowing for gestation. Of 117 women, superimposed preeclampsia was diagnosed in 21% ( n = 25), with 24% ( n = 6) having an additional diagnosis of diabetes. The cohort included 63 (54%) women who self-identified as being of black ethnicity. PlGF concentrations were 67% lower [95% confidence interval (CI) -79 to -48%] and AGTCR, PCR, and ACR were higher over gestation, in women with subsequent superimposed preeclampsia (compared with those without superimposed preeclampsia). PlGF <100 pg/ml at 20-23.9 wk of gestation predicted subsequent birth weight <3rd percentile with 88% sensitivity (95% CI 47-100%) and 83% specificity (95% CI 70-92%). Black women had 43% lower renin (95% CI -58 to -23%) and 41% lower aldosterone (95%CI -45 to -15%) concentrations over gestation. Changes in placental (PlGF) and renal (AGTCR/PCR/ACR) biomarkers predated adverse pregnancy outcome. Ethnic variation in the renin-angiotensin-aldosterone system exists in women with chronic hypertension in pregnancy and may be important in treatment selection.

Quantifying adherence to antihypertensive medication for chronic hypertension during pregnancy.

Estimates of adherence to antihypertensive treatment in pregnancy are limited; identifying non-adherence could facilitate intervention and optimise blood pressure control. This study aimed to evaluate adherence to antihypertensive treatment amongst pregnant women with chronic hypertension using high-performance liquid chromatography-tandem mass spectrometry instrumentation. Spot urine samples collected from women who were randomised to labetalol or nifedipine were assessed. Samples from 74 women were included; documented prescribing and urine metabolite detection were concordant in 88% (n = 65). Evidence of self-administration of alternative treatment was observed in 8% (n = 6). Measurement of urinary antihypertensive metabolites in pregnancy provides insight into treatment adherence.

Impact of Antihypertensive Treatment on Maternal and Perinatal Outcomes in Pregnancy Complicated by Chronic Hypertension: A Systematic Review and Meta-Analysis.

BACKGROUND: Chronic hypertension complicates around 3% of all pregnancies. There is evidence that treating severe hypertension reduces maternal morbidity. This study aimed to systematically review randomized controlled trials of antihypertensive agents treating chronic hypertension in pregnancy to determine the effect of this intervention. METHODS AND RESULTS: Medline (via OVID), Embase (via OVID) and the Cochrane Trials Register were searched from their earliest entries until November 30, 2016. All randomized controlled trials evaluating antihypertensive treatments for chronic hypertension in pregnancy were included. Data were extracted and analyzed in Stata (version 14.1). Fifteen randomized controlled trials (1166 women) were identified for meta-analysis. A clinically important reduction in the incidence of severe hypertension was seen with antihypertensive treatment versus no antihypertensive treatment/placebo (5 studies, 446 women; risk ratio 0.33, 95%CI 0.19-0.56; I2 0.0%). There was no difference in the incidence of superimposed pre-eclampsia (7 studies, 727 women; risk ratio 0.74, 95%CI 0.49-1.11; I2 28.1%), stillbirth/neonatal death (4 studies, 667 women; risk ratio 0.37, 95%CI 0.11-1.26; I2 0.0%), birth weight (7 studies, 802 women; weighted mean difference -60 g, 95%CI -200 to 80 g; I2 0.0%), or small for gestational age (4 studies, 369 women; risk ratio 1.01, 95%CI 0.53-1.94; I2 0.0%) with antihypertensive treatment versus no treatment/placebo. CONCLUSIONS: Antihypertensive treatment reduces the risk of severe hypertension in pregnant women with chronic hypertension. A considerable paucity of data exists to guide choice of antihypertensive agent. Adequately powered head-to-head randomized controlled trials of commonly used antihypertensive agents are required to inform prescribing.

Labetalol Versus Nifedipine as Antihypertensive Treatment for Chronic Hypertension in Pregnancy: A Randomized Controlled Trial.

Data from randomized controlled trials to guide antihypertensive agent choice for chronic hypertension in pregnancy are limited; this study aimed to compare labetalol and nifedipine, additionally assessing the impact of ethnicity on treatment efficacy. Pregnant women with chronic hypertension (12+0-27+6 weeks' gestation) were enrolled at 4 UK centers (August 2014 to October 2015). Open-label first-line antihypertensive treatment was randomly assigned: labetalol- (200-1800 mg/d) or nifedipine-modified release (20-80 mg/d). Analysis included 112 women (98%) who completed the study (labetalol n=55, nifedipine n=57). Maximum blood pressure after randomization was 161/101 mm Hg with labetalol versus 163/105 mm Hg with nifedipine (mean difference systolic: 1.2 mm Hg [-4.9 to 7.2 mm Hg], diastolic: 3.3 mm Hg [-0.6 to 7.3 mm Hg]). Mean blood pressure was 134/84 mm Hg with labetalol and 134/85 mm Hg with nifedipine (mean difference systolic: 0.3 mm Hg [-2.8 to 3.4 mm Hg], and diastolic: -1.9 mm Hg [-4.1 to 0.3 mm Hg]). Nifedipine use was associated with a 7.4-mm Hg reduction (-14.4 to -0.4 mm Hg) in central aortic pressure, measured by pulse wave analysis. No difference in treatment effect was observed in black women (n=63), but a mean 4 mm Hg reduction (-6.6 to -0.8 mm Hg; P=0.015) in brachial diastolic blood pressure was observed with labetalol compared with nifedipine in non-black women (n=49). Labetalol and nifedipine control mean blood pressure to target in pregnant women with chronic hypertension. This study provides support for a larger definitive trial scrutinizing the benefits and side effects of first-line antihypertensive treatment. CLINICAL TRIAL REGISTRATION: URL: https://www.isrctn.com. Unique identifier: ISRCTN40973936.

A Multicenter Cohort Study of Histologic Findings and Long-Term Outcomes of Kidney Disease in Women Who Have Been Pregnant.

BACKGROUND AND OBJECTIVES: For many women pregnancy is the first contact with health services, thus providing an opportunity to identify renal disease. This study compares causes and long-term renal outcomes of biopsy-proven renal disease identified during pregnancy or within 1 year postpartum, with nonpregnant women. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Native renal biopsies (1997-2012), in women of childbearing age (16 to <50 years), from 21 hospitals were studied. The pregnancy-related diagnosis group included those women with abnormal urinalysis/raised creatinine identified during pregnancy or within 1 year postpartum. Pregnancy-related and control biopsies were matched for age and ethnicity (black versus nonblack). RESULTS: One hundred and seventy-three pregnancy-related biopsies (19 antenatal, 154 postpregnancy) were identified and matched with 1000 controls. FSGS was more common in pregnancy-related biopsies (32.4%) than controls (9.7%) (P<0.001) but there were no differences in Columbia classification. Women with a pregnancy-related diagnosis were younger (32.1 versus 34.2 years; P=0.004) and more likely to be black (26.0% versus 13.3%; P<0.001) than controls, although there were no differences in ethnicities in women with FSGS. The pregnancy-related group (excluding antenatal biopsies) was more likely to have a decline in Chronic Kidney Disease Epidemiology Collaboration eGFR in the follow-up period than the control group (odds ratio, 1.67; 95% confidence interval, 1.03 to 2.71; P=0.04), and this decline appeared to be more rapid (-1.33 versus -0.56 ml/min per 1.73 m2 per year, respectively; P=0.045). However, there were no differences between groups in those who required RRT or who died. CONCLUSIONS: Pregnancy is an opportunity to detect kidney disease. FSGS is more common in women who have been pregnant than in controls, and disease identified in pregnancy or within 1 year postpartum is more likely to show a subsequent decline in renal function. Further work is required to determine whether pregnancy initiates, exacerbates, or reveals renal disease.

The challenges of licensing drugs for use in pregnancy.

Most recommended obstetric therapeutic agents are not licensed for their purpose. There is a lack of funding for research and little development of new therapeutic agents for use in the treatment of pregnancy-related disorders. Current therapeutics used in maternal health and their licensing status are reviewed and suggestions for these shortfalls together with possible solutions considered.