Combined Diffusion-Relaxometry MRI to Identify Dysfunction in the Human Placenta

Purpose: A combined diffusion-relaxometry MR acquisition and analysis pipeline for in-vivo human placenta, which allows for exploration of coupling between T2* and apparent diffusion coefficient (ADC) measurements in a sub 10 minute scan time. Methods: We present a novel acquisition combining a diffusion prepared spin-echo with subsequent gradient echoes. The placentas of 17 pregnant women were scanned in-vivo, including both healthy controls and participants with various pregnancy complications. We estimate the joint T2*-ADC spectra using an inverse Laplace transform. Results: T2*-ADC spectra demonstrate clear quantitative separation between normal and dysfunctional placentas. Conclusions: Combined T2*-diffusivity MRI is promising for assessing fetal and maternal health during pregnancy. The T2*-ADC spectrum potentially provides additional information on tissue microstructure, compared to measuring these two contrasts separately. The presented method is immediately applicable to the study of other organs

Prospective biomarkers in preterm preeclampsia: A review

Preterm pre-eclampsia (prior to 37 weeks’ gestation) remains a major cause of maternal and fetal morbidity and mortality particularly in low to middle income countries. Much research has focused on first and second trimester predictors of pre-eclampsia with the aim of allowing stratification of antenatal care and trialling of potential preventative and therapeutic agents. However, none have been shown to be of benefit in randomised controlled trials. In this literature review we critically evaluate predictive and diagnostic tests for preterm pre-eclampsia and discuss their clinical use and potential value in the management of preterm pre-eclampsia. We defined preterm pre-eclampsia as pre-eclampsia occurring prior to 37 weeks’ gestation. Substantial progress has been made in the development of predictive screening tests for preterm pre-eclampsia, but further research is needed prior to their introduction and integration into routine clinical practice. The performance of diagnostic tests mainly utilising angiogenic and anti-angiogenic factors for determining time to delivery in later pregnancy currently hold more promise than first trimester predictive tests, possible reflecting the heterogeneity of pre-eclampsia

A randomised controlled trial of blood pressure self-monitoring in the management of hypertensive pregnancy. OPTIMUM-BP:A feasibility trial

Objective: To assess the feasibility of a blood pressure self-monitoring intervention for managing pregnancy hypertension. Study design: OPTIMUM-BP was an unmasked randomised controlled trial comparing a self-monitoring of blood pressure (SMBP) intervention versus usual care for the management of pregnancy hypertension. Women with chronic (CH) or gestational hypertension (GH) from 4 UK centres were randomised (2:1) intervention to control. Self-monitoring involved daily home blood pressure (BP) measurements, with recording via study diary or telemonitoring. Clinicians were invited to use the home readings in clinical and antihypertensive titration decisions. Main outcomes: The primary outcomes were recruitment, retention, adherence and persistence with the intervention. Results: Women from four UK centres were randomised: 158/222 (71%) of those approached agreed, comprising: 86 women with chronic hypertension (55 SMBP, 31 control) and 72 with gestational hypertension (49 SMBP, 23 control) of whom outcome data were available from 154 (97%) and were included in the analysis. The median (IQR) number of days with home BP readings per week were 5.5 (3.1–6.5) for those with chronic hypertension and 6.1 (4.5–6.7) with gestational hypertension. Participants persisted with the intervention for 80% or more of their time from enrolment until delivery in 86% (43/50) and 76% (38/49) of those with chronic and gestational hypertension respectively. Recorded clinic and study BPs were similar for both groups. Conclusions: This is the first randomised investigation of BP self-monitoring for the management of pregnancy hypertension and indicates that a large RCT would be feasible.</p

Urinary congophilia in women with hypertensive disorders of pregnancy and preexisting proteinuria or hypertension.

BACKGROUND: Congophilia indicates the presence of amyloid protein, which is an aggregate of misfolded proteins, that is implicated in the pathophysiologic condition of preeclampsia. Recently, urinary congophilia has been proposed as a test for the diagnosis and prediction of preeclampsia. OBJECTIVES: The purpose of this study was to determine whether urine congophilia is present in a cohort of women with preeclampsia and in pregnant and nonpregnant women with renal disease. STUDY DESIGN: With the use of a preeclampsia, chronic hypertension, renal disease, and systemic lupus erythematosus cohort, we analyzed urine samples from healthy pregnant control subjects (n = 31) and pregnant women with preeclampsia (n = 23), gestational hypertension (n = 10), chronic hypertension (n = 14), chronic kidney disease; n = 28), chronic kidney disease with superimposed preeclampsia (n = 5), and chronic hypertension and superimposed preeclampsia (n = 12). Samples from nonpregnant control subjects (n = 10) and nonpregnant women with either systemic lupus erythematosus with (n = 25) and without (n = 14) lupus nephritis were analyzed. For each sample, protein concentration was standardized before it was mixed with Congo Red, spotted to nitrocellulose membrane, and rinsed with methanol. The optical density of the residual Congo Red stain was determined; Congo red stain retention was calculated, and groups were compared with the use of the Mann-Whitney test or Kruskal-Wallis analysis of Variance test, as appropriate. RESULTS: Congophilia was increased in urine from women with preeclampsia (median Congo red stain retention, 47%; interquartile range, 22-68%) compared with healthy pregnant control subjects (Congo red stain retention: 16%; interquartile range, 13-21%; P = .002), women with gestational hypertension (Congo red stain retention, 20%; interquartile range, 13-27%; P = .008), or women with chronic hypertension (Congo red stain retention, 17%; interquartile range, 12-28%; P = .01). There were no differences in Congo red retention between pregnant women with chronic hypertension and normal pregnant control subjects (Congo red stain retention, 17% [interquartile range, 12-28%] vs 16% [interquartile range, 13-21%], respectively; P = .72). Congophilia was present in pregnant women with chronic kidney disease (Congo red stain retention, 32%; interquartile range, 14-57%), being similar to values found in women with preeclampsia (P = .22) and for women with chronic kidney disease and superimposed preeclampsia (Congo red stain retention, 57%; [interquartile range, 29-71%; P = .18). Nonpregnant women with lupus nephritis had higher congophilia levels compared with nonpregnant female control subjects (Congo red stain retention, 38% [interquartile range, 17-73%] vs 9% [7-11%], respectively; P < .001) and nonpregnant women with systemic lupus erythematosus without nephritis (Congo red stain retention, 38% [interquartile range, 17-73%] vs 13% [interquartile range, 11-17%], respectively; P = .001). A significant positive correlation was observed between congophilia and protein:creatinine ratio (Spearman rank correlations, 0.702; 95% confidence interval, 0.618-0.770; P < .001). CONCLUSION: This study confirms that women with preeclampsia and chronic kidney disease without preeclampsia have elevated urine congophilia levels compared with healthy pregnant women. Nonpregnant women with lupus nephritis also have elevated urine congophilia levels compared with healthy control subjects. An elevated Congo Red stain retention may not be able to differentiate between these conditions; further research is required to explore the use of congophilia in clinical practice.National Institute for Health ResearchThis is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.ajog.2016.04.04

Association between maternal micronutrient status, oxidative stress and common genetic variants in antioxidant enzymes at 15 weeks’ gestation in nulliparous women who subsequently develop pre-eclampsia

Aims: Pre-eclampsia is a pregnancy-specific condition affecting 2-7% of women and a leading cause of perinatal and maternal morbidity and mortality. Deficiencies of specific micronutrient antioxidant activities associated with copper, selenium, zinc and manganese, have previously been linked to pre-eclampsia at time of disease. Our aims were to investigate whether maternal plasma micronutrient concentrations and related antioxidant enzyme activities are altered prior to pre-eclampsia onset and to examine the dependence on genetic variations in these antioxidant enzymes. Methods: Pre-disease plasma samples (15+1 weeks’ gestation) were obtained from women enrolled in the international SCreening fOr Pregnancy Endpoints (SCOPE) study who subsequently developed pre-eclampsia (n=244), and age- and BMI-matched normotensive controls (n=472). Micronutrient concentrations were measured by inductively coupled plasma mass spectrometry; associated antioxidant enzyme activities, selenoprotein-P, caeruloplasmin concentrations and activities, antioxidant capacity and markers of oxidative stress were measured by colorimetric assays. Sixty four tagSNPs within genes encoding the antioxidant enzymes and selenoprotein-P were genotyped using allele-specific competitive PCR. Results: Plasma copper and caeruloplasmin concentrations were modestly, but significantly elevated in women who subsequently developed pre-eclampsia (both P<0.001) compared to controls (median [IQR], copper: 1957.4 [1787, 2177.5] vs. 1850.0 [1663.5, 2051.5] µg/L; caeruloplasmin: 2.5[1.4, 3.2] vs. 2.2[1.2, 3.0] µg/ml). There were no differences in other micronutrients or enzymes between groups. No relationship was observed between genotype for single nucleotide polymorphisms (SNPs) and antioxidant enzyme activity. Conclusions: This analysis of a prospective cohort study reports maternal micronutrient concentrations in combination with associated antioxidant enzymes and SNPs in their encoding genes in women at 15 weeks’ gestation that subsequently developed pre-eclampsia. The modest elevation in copper may contribute to oxidative stress, later in pregnancy, in those women that go on to develop pre-eclampsia. The lack of evidence to support the hypothesis that functional SNPs influence antioxidant enzyme activity in pregnant women argues against a role for these genes in the aetiology of pre-eclampsia