Plugging membranes after fetoscopy in congenital diaphragmatic hernia: early cost-effectiveness analysis.

OBJECTIVES: Fetal endoscopic tracheal occlusion (FETO) improves neonatal survival of fetuses with congenital diaphragmatic hernia (CDH). However, FETO also increases the risk of preterm prelabor rupture of membranes (PPROM) and preterm delivery (PTD), as fetal membrane defects after fetoscopy do not heal. To solve this issue, an advanced sealing plug for closing the membrane defect is being developed. Using early-stage health economic modeling, we aimed to estimate the potential value of this innovative plug in terms of costs and effects, and to determine the properties required for it to become cost-effective. METHODS: Early-stage health economic modeling was applied to the case of performing FETO in women with a singleton pregnancy whose fetus is diagnosed prenatally with CDH. We simulated a cohort of patients using a state-transition model over a 45-year time horizon. In our best-case-scenario analysis, we compared the current-care strategy with the perfect-plug strategy, which reduces the risk of PPROM and PTD by 100%, to determine the maximum quality-adjusted life years (QALYs) gained and costs saved. Using threshold analysis, we determined the minimum percentage reduction in the risk of PPROM and PTD required for the plug to be considered cost-effective. The impact of model parameters on outcome was investigated using a sensitivity analysis. RESULTS: Our model indicated that a perfect-plug strategy would yield on average an additional 1.94 QALYs at a cost decrease of €2554 per patient. These values were influenced strongly by the percentage of cases with early PTD (27-34 weeks). Threshold analysis showed that, for €500 per plug, the plug strategy needs a minimum percentage reduction of 1.83% in the risk of PPROM and PTD (i.e. reduction in the risk from 47.50% to 46.63% for PPROM and from 71.50% to 70.19% for PTD) to be cost-effective. CONCLUSIONS: Our model-based approach showed clear potential of the plug strategy when applied in the context of FETO for CDH fetuses, as only a minor reduction in the risk of PPROM and PTD is needed for the plug to be cost-effective. Its value is expected to be even higher when used in conditions associated with a higher rate of early PTD. Continued investment in research and development of the plug strategy appears to provide value for money. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Impact of body mass index on markers of vascular health in normotensive women with history of pre-eclampsia.

OBJECTIVE: Obesity and pre-eclampsia (PE) are both associated with vascular dysfunction, which translates into an increased risk for cardiovascular disease in later life. The aim of this study was to investigate whether there is an interaction between body mass index (BMI) and a history of PE in their effects on vascular health. METHODS: This was an observational case-control study of 30 women with a history of PE who were compared with 31 age- and BMI-matched controls who had an uncomplicated pregnancy. Flow-mediated dilation (FMD), carotid intima-media thickness (cIMT) and carotid distensibility (CD) were measured 6-12 months postpartum. To evaluate the impact of physical fitness, maximum oxygen uptake capacity was assessed using a standardized maximum exhaustion cycling test using breath-by-breath analysis. To specify further BMI subgroups, metabolic syndrome constituents were assessed in all individuals. RESULTS: Formerly pre-eclamptic women had significantly lower FMD (5.1 ± 2.1% vs 9.4 ± 3.4%; P < 0.01), higher cIMT (0.59 ± 0.09 vs 0.49 ± 0.07 µm; P < 0.01) and lower CD (1.54 ± 0.37%/10 mmHg vs 1.80 ± 0.39%/10 mmHg; P < 0.01) compared with controls. In our study, population BMI correlated negatively with FMD (P = 0.04) but not with cIMT or CD. BMI and PE did not exhibit an interaction effect on these vascular parameters. Physical fitness was lower in women with a history of PE and in women with higher BMI. Constituents of the metabolic syndrome, including insulin, homeostasis model assessment for insulin resistance (HOMA-ir), triglyceride, microalbuminuria and systolic and diastolic blood pressure, were significantly higher in formerly pre-eclamptic women. BMI affected glucose metabolism but not lipids or blood pressure. BMI and PE positively interacted in their effect on insulin (P = 0.04) and HOMA-ir (P = 0.02). CONCLUSIONS: Both BMI and a history of PE have negative effects on endothelial function, insulin resistance and physical fitness. In formerly pre-eclamptic women, the effect of BMI on insulin resistance was particularly high, suggesting a synergistic effect. Additionally, independently of BMI, a history of PE was associated with reduced FMD and CD and increased cIMT and blood pressure. Recognizing the cardiovascular risk profile is important for informing patients and encouraging targeted lifestyle modifications. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Cardiac output and peripheral vascular resistance during normotensive and hypertensive pregnancy - a systematic review and meta-analysis.

BACKGROUND: In-depth insight into haemodynamic changes during normotensive pregnancy may help identify women at risk for gestational hypertensive complications. OBJECTIVES: To determine the magnitude of changes in cardiac output and its determinants stroke volume and heart rate, and total peripheral vascular resistance during singleton normotensive and hypertensive pregnancies. SEARCH STRATEGY: PubMed (NCBI) and Embase (Ovid) databases were searched from their inception up to November 2019. SELECTION CRITERIA: Studies reporting original measurements of haemodynamic parameters during pregnancy together with a non-pregnant reference measurement. Studies including women using antihypertensive medication were excluded. DATA COLLECTION AND ANALYSIS: Pooled mean differences between pregnant and non-pregnant women, and absolute values of haemodynamic parameters were calculated for predefined gestational intervals using a random-effects model in normotensive and hypertensive pregnancy. Meta-regression analysis was used to analyse group differences in adjustments and absolute values during pregnancy. MAIN RESULTS: In normotensive pregnancies, cardiac output increased from the first weeks on, reaching its highest level early in the third trimester (mean difference, 1.41 l·min1 ; 95% CI 1.18-1.63 l·min). In parallel, vascular resistance decreased progressively until its nadir in the early third trimester (mean difference, -331 dyn·sec-1 ·cm-5 ; 95% CI -384 to -277 dyn·sec-1 ·cm-5 ) and then increased slightly at term. In hypertensive pregnancies, the initial cardiac output increase was higher and vascular resistance did not change throughout gestation compared with reference values. CONCLUSIONS: Hemodynamic changes in women who eventually develop hypertensive complications are substantially different. Serial monitoring and plotting against developed normograms can identify women at risk and may allow timely intervention. TWEETABLE ABSTRACT: Monitoring haemodynamic changes in pregnancy helps identify women at risk for hypertensive complications.

Venous and autonomic function in formerly pre-eclamptic women and controls matched for body mass index.

OBJECTIVE: Prepregnancy reduced plasma volume (PV) increases the risk of subsequent pre-eclamptic pregnancy. Reduced PV is thought to reflect venous reserve capacity, especially when venous vasculature is constricted and sympathetic tone is elevated. As obesity might affect these variables, and is associated with pre-eclampsia, increased body weight may underlie these observations. The aim of this study was to determine whether the relationship between reduced venous reserve and pre-eclampsia is independent of body mass index (BMI). METHODS: This was an observational case-control study in which venous reserve capacity in 30 formerly pre-eclamptic, but currently non-pregnant, women divided equally into three groups based on BMI (BMI 19.5-24.9, 25.0-29.9 or ≥ 30.0 kg/m2 ), was compared with that in 30 healthy parous, non-pregnant controls. Cases and controls were matched for BMI, age and parity. Venous reserve capacity was quantified by assessing PV and venous compliance (VeC). The autonomic nervous system regulating venous capacitance was evaluated using heart rate (HR) variability analysis, with the women in a resting supine position and during positive head-up tilt (HUT). RESULTS: Compared with controls, formerly pre-eclamptic women had, when in a resting supine position, lower PV (1339 ± 79 vs 1547 ± 139 mL/m2 (P < 0.0001)), lower VeC (0.04 ± 0.02 vs 0.07 ± 0.02 mL/dL/mmHg (P < 0.0001)), higher sympathetic tone (1.9 ± 1.1 vs 1.2 ± 0.7 (P = 0.002)) and lower baroreceptor sensitivity (BRS; 8.7 ± 3.8 vs 19.0 ± 1.7 ms/mmHg (P < 0.0001)). During HUT, women with a history of pre-eclampsia had less modulatory capacity over VeC and BRS, while HR and sympathetic tone remained consistently higher. CONCLUSIONS: Women with a history of pre-eclampsia had reduced venous reserve capacity compared with that in BMI-matched controls. This is reflected by lower PV and VeC, with the autonomic balance being shifted towards sympathetic dominance and lower BRS. This suggests that underlying reduced venous reserve, but not BMI, relates to pre-eclampsia. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Maternal kidney function during pregnancy: systematic review and meta-analysis.

OBJECTIVES: To review systematically current literature on kidney function changes during pregnancy, in order to estimate the extent of adaptation over the course of both healthy physiological and complicated singleton pregnancies, and to determine healthy pregnancy reference values. METHODS: PubMed (NCBI) and EMBASE (Ovid) electronic databases were searched, from inception to July 2017, for studies on kidney function during uncomplicated and complicated pregnancies. Included studies were required to report a non-pregnant reference value of kidney function (either in a non-pregnant control group or as a prepregnancy or postpartum measurement) and a pregnancy measurement at a predetermined and reported gestational age. Kidney function measures assessed were glomerular filtration rate (GFR) measured by inulin clearance, GFR measured by creatinine clearance and serum creatinine level. Pooled mean differences between pregnancy measurements and reference values were calculated for predefined intervals of gestational age in uncomplicated and complicated pregnancies using a random-effects model described by DerSimonian and Laird. RESULTS: Twenty-nine studies met the inclusion criteria and were included in the analysis. As early as the first trimester, GFR was increased by up to 40-50% in physiological pregnancy when compared with non-pregnant values. Inulin clearance in uncomplicated pregnancy was highest at 36-41 weeks, with a 55.6% (53.7; 95% CI, 44.7-62.6 mL/min) increase when compared with non-pregnant values, and creatinine clearance was highest at 15-21 weeks' gestation, with a 37.6% (36.6; 95% CI, 26.2-46.9 mL/min) increase. Decrease in serum creatinine level in uncomplicated pregnancy was most prominent at 15-21 weeks, with a 23.2% (-0.19; 95% CI, -0.23 to -0.15 mg/dL) decrease when compared with non-pregnant values. Eight studies reported on pregnancies complicated by a hypertensive disorder. Meta-regression analysis showed a significant difference in all kidney function parameters when comparing uncomplicated and hypertensive complicated pregnancies. CONCLUSIONS: In healthy pregnancy, GFR is increased as early as the first trimester, as compared with non-pregnant values, and the kidneys continue to function at a higher rate throughout gestation. In contrast, kidney function is decreased in hypertensive pregnancy. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Physiological adaptation of maternal plasma volume during pregnancy: a systematic review and meta-analysis.

OBJECTIVE: To describe the physiological pattern of gestational plasma volume adjustments in normal singleton pregnancy and compare this with the pattern in pregnancies complicated by pregnancy-induced hypertension, pre-eclampsia or fetal growth restriction. METHODS: We performed a meta-analysis of the current literature on plasma volume adjustments during physiological and complicated pregnancies. Literature was retrieved from PubMed (NCBI) and EMBASE (Ovid) databases. Included studies reported both reference plasma volume measurements (non-pregnant, prepregnancy or postpartum) and measurements obtained during predetermined gestational ages. Mean differences bet ween the reference and pregnancy plasma volume measurements were calculated for predefined intervals of gestational age using a random-effects model described by DerSimonian and Laird. RESULTS: Thirty studies were included in the meta-analysis with publication dates ranging from 1934 to 2007. Plasma volume increased in the first weeks of pregnancy, with the steepest increase occurring during the second trimester. Plasma volume continued to increase in the third trimester with a pooled maximum increase of 1.13 L (95% CI, 1.07-1.19 L), an increase of 45.6% (95% CI, 43.0-48.1%) in physiological pregnancies compared with the reference value. The plasma volume expansion in gestational hypertensive and growth-restricted pregnancies was 0.80 L (95% CI, 0.59-1.02 L), an increase of 32.3% (95% CI, 23.6-41.1%) in the third trimester, a smaller increase than in physiological pregnancies (P < 0.0001). CONCLUSIONS: During physiological pregnancy, plasma volume increases by, on average, more than 1 L as compared with non-pregnant conditions. In pregnancies complicated by pregnancy-induced hypertension, pre-eclampsia or fetal growth restriction, plasma volume increase in the third trimester is 13.3% lower than in normal pregnancy. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Adaptación fisiológica del volumen del plasma materno durante el embarazo: una revisi\xF3n sistemática y metaanálisis RESUMEN OBJETIVO: Describir el patrón fisiológico de los cambios en el volumen del plasma gestacional en embarazos normales con feto único y compararlo con el patrón en los embarazos complicados por hipertensión gestacional, preeclampsia o restricción del crecimiento fetal. MÉTODOS: Se realizó un metaanálisis de la literatura actual sobre los cambios en el volumen de plasma durante embarazos complicados y fisiológicos. La literatura se obtuvo de las bases de datos PubMed (NCBI) y EMBASE (Ovid). Los estudios incluidos mencionaban tanto mediciones de referencia del volumen plasmático (no embarazada, antes del embarazo o después del parto) como mediciones tomadas a edades gestacionales predeterminadas. Se calcularon las medias de las diferencias entre las mediciones de referencia y las del embarazo para el volumen plasmático a intervalos predefinidos de la edad gestacional, utilizando un modelo de efectos aleatorios descrito por DerSimonian y Laird. RESULTADOS: En el metaanálisis se incluyeron treinta estudios con fechas de publicación entre 1934 y 2007. El volumen plasmático aumentó en las primeras semanas de embarazo y el mayor incremento se produjo durante el segundo trimestre. El volumen de plasma continuó aumentando en el tercer trimestre con un aumento combinado máximo de 1,13L (IC 95%, 1,7-1,19 L), lo que supone un aumento del 45,6% (IC 95%, 43,0-48,1%) en embarazos fisiológicas en comparación con el valor de referencia. El aumento del volumen plasmático en los embarazos con hipertensión y con crecimiento intrauterino restringido fue de 0,80L (IC 95%, 0,59-1,02 L), lo que supone un aumento del 32,3% (IC 95%, 23,6-41,1%) en el tercer trimestre, y un incremento menor que en los embarazos fisiológicos (P <0,0001). CONCLUSIONES: Durante el embarazo fisiológico el volumen de plasma aumenta, en promedio, más de 1L, en comparación con el de las no embarazadas. En los embarazos complicados por hipertensión gestacional, preeclampsia o restricción del crecimiento fetal, el aumento del volumen plasmático en el tercer trimestre es un 13,3% menor que en el embarazo normal. :meta : ,、。 : meta。PubMed(NCBI)EMBASE(Ovid)。(、)。DerSimonianLaird,。 : Meta30,19342007。,。,1.13 L(95% CI,1.07~1.19 L),,45.6%(95% CI,43.0%~48.1%)。0.80 L(95%CI,0.59~1.02 L),32.3%(95% CI,23.6%~41.1%),(P<0.0001)。 : ,,1 L。、,13.3%。.

Physiological adaptation of endothelial function to pregnancy: systematic review and meta-analysis.

OBJECTIVES: To establish reference values for flow-mediated dilatation (FMD) and brachial artery diameter (BAD) in pregnancy and to provide insight into the physiological and pathological course of endothelial adaptation throughout human singleton pregnancy. METHODS: A meta-analysis was performed following a systematic review of current literature on FMD, as a derivative for endothelial function, and BAD, throughout uncomplicated and complicated pregnancy. PubMed (NCBI) and EMBASE (Ovid) electronic databases were used for the literature search, which was performed from inception to 9 June 2016. To allow judgment of changes in comparison with the non-pregnant state, studies were required to report both non-pregnant mean reference of FMD (matched control group, prepregnancy or postpartum measurement) and mean FMD at a predetermined and reported gestational age. Pooled mean differences between the reference and pregnant FMD values were calculated for predefined intervals of gestational age. RESULTS: Fourteen studies that enrolled 1231 participants met the inclusion criteria. Publication dates ranged from 1999 to 2014. In uncomplicated pregnancy, FMD was increased in the second and third trimesters. Between 15 and 21 weeks of gestation, absolute FMD increased the most, by a mean (95% CI) of 1.89% (0.25-3.53%). This was a relative increase of 22.5% (3.0-42.0%) compared with the non-pregnant reference. BAD increased progressively, in a steady manner, by the second trimester but not significantly in the first half of the second trimester. We could not discern differences in FMD and BAD between complicated and uncomplicated pregnancies at 29-35 weeks' gestation, reported in the three studies that met our inclusion criteria. Despite the increase in FMD and BAD throughout gestation, both reference curves were characterized by wide 95% CIs. CONCLUSION: During healthy pregnancy, endothelium-dependent vasodilatation and BAD increase. Women with a complicated pregnancy had FMD values within the lower range when compared with those with uncomplicated pregnancy but, as a group, did not differ from each other. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Cardiac remodeling in normotensive pregnancy and in pregnancy complicated by hypertension: systematic review and meta-analysis.

OBJECTIVE: The aim of this systematic review and meta-analysis was to describe comprehensively the pattern of cardiac remodeling during normotensive human singleton pregnancy and to compare it with that of pregnancy complicated by hypertension. METHODS: We performed a meta-analysis of the current literature on cardiac remodeling during normotensive and complicated pregnancies. Literature was retrieved from PubMed (NCBI) and EMBASE (Ovid) databases. Included studies needed to report a reference measurement (matched non-pregnant control group, prepregnancy or postpartum) and measurements made during predetermined gestational-age intervals. Mean differences between reference and pregnancy data were calculated using the random-effects model described by DerSimonian and Laird. RESULTS: Forty-eight studies were included in the meta-analysis, with publication dates ranging from 1977 to 2016. During normotensive pregnancy, most geometric indices started to increase in the second trimester. Left ventricular mass (LVM) increased by 28.36 (95% CI, 19.73-37.00) g (24%), and relative wall thickness (RWT) increased by 0.03 (95% CI, 0.02-0.05) (10%) compared with those in the reference group. During hypertensive pregnancy, LVM and RWT increased more than during normotensive pregnancy (92 (95% CI, 75.46-108.54) g (95%) and 0.14 (95% CI, 0.09-0.19) (56%), respectively). CONCLUSIONS: During normotensive pregnancy, most cardiac geometric indices change from the second trimester onwards. Both LVM and RWT increase, by 20% and 10%, respectively, consistent with concentric rather than eccentric remodeling. Cardiac adaptation in hypertensive pregnancy deviates from that in healthy pregnancy by a greater change in LVM (95% increase from reference) and RWT (56% increase from reference). Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

The Cloud DX connected HealthKit Pulsewave in home blood pressure monitoring during pregnancy: A clinical evaluation and user experience study.

OBJECTIVE: Clinical evaluation and user experience of the Cloud DX connected HealthKit Pulsewave wrist cuff blood pressure monitor (CDXP) for home blood pressure monitoring during pregnancy. METHODS: In the first phase, an adjusted version of the European Society of Hypertension International Protocol Revision 2010 was used to compare the CDXP and Omron M6 Comfort to the gold standard, the aneroid manometer, In the second phase, we evaluated the performance of home blood pressure measurement (HMBPM) by the CDXP to standard hospital blood pressure measurement with the Welch Allyn 53000P. Additionally, patients filled out a questionnaire regarding user experience. RESULTS: In 34 pregnant patients the blood pressure measured by the CDXP did not differ from the aneroid manometer, while the Omron M6 Comfort measured the systolic blood pressure slightly higher (1.5 ± 5.8 mmHg (p = 0.04)) and diastolic blood pressure slightly lower (-2.8 ± 5.8 mmHg (p < 0.01)) as compared to the aneroid manometer. In 32 patients the systolic blood pressure of home blood pressure measurement with the CDXP was significantly lower than the single standard hospital measurements. The mean system usability scaled score was high (85%). Of all patients, 97% reported they liked the idea of home monitoring and would like to use it in the future. CONCLUSION: The CDXP measured blood pressure correctly, even slightly better than the Omron M6 Comfort and gives a better representation of the blood pressure during the day at home than a single hospital measurement. Pregnant patients are positive about HMBPM and find the CDXP easy to use.

Prediction of Maternal and Fetal Doravirine Exposure by Integrating Physiologically Based Pharmacokinetic Modeling and Human Placenta Perfusion Experiments.

BACKGROUND AND OBJECTIVE: Doravirine is currently not recommended for pregnant women living with human immunodeficiency virus because efficacy and safety data are lacking. This study aimed to predict maternal and fetal doravirine exposure by integrating human placenta perfusion experiments with pregnancy physiologically based pharmacokinetic (PBPK) modeling. METHODS: Ex vivo placenta perfusions were performed in a closed-closed configuration, in both maternal-to-fetal and fetal-to-maternal directions (n = 8). To derive intrinsic placental transfer parameters from perfusion data, we developed a mechanistic placenta model. Next, we developed a maternal and fetal full-body pregnancy PBPK model for doravirine in Simcyp, which was parameterized with the derived intrinsic placental transfer parameters to predict in vivo maternal and fetal doravirine exposure at 26, 32, and 40 weeks of pregnancy. The predicted total geometric mean (GM) trough plasma concentration (Ctrough) values were compared with the target (0.23 mg/L) derived from in vivo exposure-response analysis. RESULTS: A decrease of 55% in maternal doravirine area under the plasma concentration-time curve (AUC)0-24h was predicted in pregnant women at 40 weeks of pregnancy compared with nonpregnant women. At 26, 32, and 40 weeks of pregnancy, predicted maternal total doravirine GM Ctrough values were below the predefined efficacy target of 0.23 mg/L. Perfusion experiments showed that doravirine extensively crossed the placenta, and PBPK modeling predicted considerable fetal doravirine exposure. CONCLUSION: Substantially reduced maternal doravirine exposure was predicted during pregnancy, possibly resulting in impaired efficacy. Therapeutic drug and viral load monitoring are advised for pregnant women treated with doravirine. Considerable fetal doravirine exposure was predicted, highlighting the need for clinical fetal safety data.

Transfer of uremic solutes across the human term placenta: An ex vivo study in the dual-side perfused cotyledon.

INTRODUCTION: An increasing number of women becomes pregnant while suffering from chronic kidney disease (CKD). As a result of decreased renal function, uremic solutes circulate at high levels in the maternal circulation. This study aimed to acquire more knowledge about the placental transfer of uremic solutes across the human placenta. METHODS: Placental transfer was studied in healthy term placentas, via the ex vivo dual-side human cotyledon perfusion technique (closed-closed set-up for both maternal and fetal circulations). Uremic solute concentrations in maternal and fetal perfusates were measured via LC-MS/MS over 180 min of perfusion. RESULTS: We found that the studied compounds demonstrated different degrees of placental transfer. Fetal-to-maternal perfusate ratios at t = 180 min were for anthranilic acid 1.00 ± 0.02, indole-3-acetic acid 0.47 ± 0.08, hippuric acid 0.36 ± 0.18, l-arabinitol 0.33 ± 0.04, indoxyl sulfate 0.33 ± 0.11, neopterin 0.28 ± 0.14 and kynurenic acid 0.13 ± 0.03. All uremic solutes studied also emerged in the perfusates when cotyledons were perfused in the absence of uremic solute concentrations added to the maternal reservoir. For kynurenin these concentrations were so high, it complicated the calculation of a transfer ratio for the exogenously administered compound. DISCUSSION: After 180 min of exposure the extent of placental transfer differs substantially for the solutes studied, reflecting different transfer rates. Future studies should investigate to what extent specific uremic solutes reach the fetal circulation in vivo and how they may interfere with organ function and development of the unborn child.

A clinical evaluation of blood pressure measurement by iHealth BP5 in pregnancy.

OBJECTIVE: To evaluate the value of blood pressure measurement by the smartphone device iHealth BP5 in pregnant women in a clinical setting, as compared to the Omron M6 Comfort and aneroid manometer. MATERIALS AND METHODS: Women with a gestational age of thirty weeks or more who visited the outpatient clinic for routine visit were eligible for inclusion. For the clinical evaluation we used an adjusted form of the European Society of Hypertension International Protocol. We performed six blood pressure measurements per patient, divided over the iHealth BP5, Omron M6 Comfort and aneroid monitor. Statistical analysis consisted of repeated measurement ANOVA and Bland-Altman plots. RESULTS: We included 45 women. The mean blood pressure differences between all tested devices were less than ±5 mmHg. These differences did not relate to gestational age, BMI or arm circumference. Bland-Altman plots showed good agreement of both iHealth BP5 and Omron M6 Comfort, without any systematic effects, as compared to the aneroid manometer. CONCLUSION: The iHealth BP5 is as good as the frequently used Omron M6 Comfort and can be used for blood pressure measurement during pregnancy. CONDENSED ABSTRACT: In 45 women the mean blood pressure differences between the Omron M6 Comfort, iHealth BP5 and the aneroid manometer were less dan ±5 mmHg. These differences did not relate to gestational age, BMI or arm circumference. Bland-Altman plots showed good agreement of both iHealth BP5 and Omron M6 Comfort, without any systematic effects, as compared to the aneroid manometer. The iHealth BP5 is as good as the frequently used Omron M6 Comfort and can be used for blood pressure measurement during pregnancy.

Placental disposition of the immunosuppressive drug tacrolimus in renal transplant recipients and in ex vivo perfused placental tissue.

Currently, tacrolimus is the most potent immunosuppressive agent for renal transplant recipients and is commonly prescribed during pregnancy. As data on placental exposure and transfer are limited, we studied tacrolimus placental handling in samples obtained from renal transplant recipients. We found transfer to venous umbilical cord blood, but particularly noted a strong placental accumulation. In patient samples, tissue concentrations in a range of 55-82 ng/g were found. More detailed ex vivo dual-side perfusions of term placentas from healthy women revealed a tissue-to-maternal perfusate concentration ratio of 113 ±â€¯49 (mean ±â€¯SEM), underlining the placental accumulation found in vivo. During the 3 h ex vivo perfusion interval no placental transfer to the fetal circulation was observed. In addition, we found a non-homogeneous distribution of tacrolimus across the perfused cotyledons. In conclusion, we observed extensive accumulation of tacrolimus in placental tissue. This warrants further studies into potential effects on placental function and immune cells of the placenta.

Impact of urometabolic evaluation on prevention of urolithiasis: a retrospective study.

OBJECTIVES: To obtain information on compliance to therapy and study its effect on recurrences. Over the past 20 years, a selective therapy protocol has been formed for prevention of urolithiasis recurrence. Many studies have been performed on the effectiveness of this therapy, but compliance has never been examined. METHODS: Data were abstracted from 177 medical records of patients who were seen at the outpatient clinic between 1985 and 1994. At that time, they were advised to follow a specific therapy regimen (high fluid intake, medication, and/or specific diet) on the basis of the outcome of a standardized metabolic evaluation. RESULTS: Thirty-six percent of the study population was still compliant to the prescribed therapy after a mean period of 5.3 years of follow-up. Therapy-compliant patients were older and had had more treatments, more lithiasis-related complaints, and more frequent follow-up visits. These characteristics suggest that patients' awareness of their disease might improve compliance. Survival analyses showed that patients can be classified into two groups characterized by the frequency of stone formation: a single stone episode versus frequent periods of stone formation. It appeared that the stone recurrence rate was twice as high among patients with a history of frequent stones compared with patients with a single stone episode, even though compliance to therapy seemed lower in the latter group. CONCLUSIONS: The usefulness of urometabolic evaluation and subsequent therapy advice seems questionable. Compliance to a life-long therapy is very low after a relatively short follow-up period. This study also suggests a prognostic classification based on stone rate.

Segregation analysis of plasma apolipoprotein B levels in familial combined hyperlipidemia.

Familial combined hyperlipidemia (FCH) is a heritable lipid disorder that is associated with an increased risk of premature cardiovascular disease. An elevated plasma apolipoprotein (apo) B concentration is reported to be a diagnostic feature of the disorder. Recently we demonstrated a strong relation between plasma apoB concentrations and the cholesterol concentration in VLDL plus LDL, both elevated in FCH families. Therefore, examination of the inheritance of elevated plasma apoB levels in FCH families may reveal important information about the mechanism responsible for the aggregation of elevated plasma lipids in FCH. This study included 663 Dutch family members in 40 families ascertained through FCH probands. Plasma apoB concentration correlated significantly with apoB-related cholesterol both in the probands and the relatives (r=.83 and r=.90, respectively). Adjustment for age, sex, body mass index, and smoking habits accounted for 35.7% of the variation in apoB levels, and there was strong familial aggregation in adjusted apoB levels in these families. Complex segregation analysis was performed to determine the mechanism of inheritance behind this familial aggregation. The aggregation of elevated apoB levels was best explained by a major gene effect inherited by a codominant mechanism. Estimated mean apoB levels for the three supposed genotypes AA, AB, and BB were 111.5, 126.7, and 165.7 mg/dL, respectively, with relative frequencies of 43.5%, 44.9%, and 11.6%, respectively. In conclusion, despite assumed metabolic and genetic heterogeneity of FCH, there is clear evidence for a single gene effect on apoB concentrations in families ascertained through FCH. Linkage studies based on this analysis may further clarify the molecular basis of the apoB regulation in these families.