Preventing cardiovascular disease after hypertensive disorders of pregnancy: Searching for the how and when

Background: Women with a history of a hypertensive disorder during pregnancy (HDP) have an increased risk of cardiovascular events. Guidelines recommend assessment of cardiovascular risk factors in these women later in life, but provide limited advice on how this follow-up should be organized. Design: Systematic review and meta-regression analysis. Methods: The aim of our study was to provide an overview of existing knowledge on the changes over time in three major modifiable components of cardiovascular risk assessment after HDP: blood pressure, glucose homeostasis and lipid levels. Data from 44 studies and up to 6904 women with a history of a HDP were compared with risk factor levels reported for women of corresponding age in the National Health And Nutrition Examination Survey, Estudio Epidemiólogico de la Insuficiencia Renal en España and Hong Kong cohorts (N = 27,803). Results: Compared with the reference cohort, women with a HDP presented with higher mean blood pressure. Hypertension was present in a higher rate among women with a previous HDP from 15 years postpartum onwards. At 15 years postpartum (±age 45), one in five women with a history of a HDP suffer from hypertension. No differences in glucose homeostasis parameters or lipid levels were observed. Conclusions: Based on our analysis, it is not possible to point out a time point to commence screening for cardiovascular risk factors in women after a HDP. We recommend redirection of future research towards the development of a stepwise approach identifying the women with the highest cardiovascular risk

Understanding changes in echocardiographic parameters at different ages following fetal growth restriction:a systematic review and meta-analysis

Fetal growth restriction (FGR) increases cardiovascular risk by cardiac remodeling and programming. This systematic review and meta-analysis across species examines the use of echocardiography in FGR offspring at different ages. PubMed and Embase.com were searched for animal and human studies reporting on echocardiographic parameters in placental insufficiency- induced FGR offspring. We included six animal and 49 human studies. Although unable to perform a meta-analysis of animal studies because of insufficient number of studies per individual outcome, all studies showed left ventricular dysfunction. Our meta-analyses of human studies revealed a reduced left ventricular mass, interventricular septum thickness, mitral annular peak velocity, and mitral lateral early diastolic velocity at neonatal age. No echocardiographic differences during childhood were observed, although the small age range and number of studies limited these analyses. Only two studies at adult age were performed. Meta-regression on other influential factors was not possible due to underreporting. The few studies on myocardial strain analysis showed small changes in global longitudinal strain in FGR offspring. The quality of the human studies was considered low and the risk of bias in animal studies was mostly unclear. Echocardiography may offer a noninvasive tool to detect early signs of cardiovascular predisposition following FGR. Clinical implementation yet faces multiple challenges including identification of the most optimal timing and the exact relation to long-term cardiovascular function in which echocardiography alone might be limited to reflect a child's vascular status. Future research should focus on myocardial strain analysis and the combination of other (non)imaging techniques for an improved risk estimation.</p

Understanding changes in echocardiographic parameters at different ages following fetal growth restriction:a systematic review and meta-analysis

Fetal growth restriction (FGR) increases cardiovascular risk by cardiac remodeling and programming. This systematic review and meta-analysis across species examines the use of echocardiography in FGR offspring at different ages. PubMed and Embase.com were searched for animal and human studies reporting on echocardiographic parameters in placental insufficiency- induced FGR offspring. We included six animal and 49 human studies. Although unable to perform a meta-analysis of animal studies because of insufficient number of studies per individual outcome, all studies showed left ventricular dysfunction. Our meta-analyses of human studies revealed a reduced left ventricular mass, interventricular septum thickness, mitral annular peak velocity, and mitral lateral early diastolic velocity at neonatal age. No echocardiographic differences during childhood were observed, although the small age range and number of studies limited these analyses. Only two studies at adult age were performed. Meta-regression on other influential factors was not possible due to underreporting. The few studies on myocardial strain analysis showed small changes in global longitudinal strain in FGR offspring. The quality of the human studies was considered low and the risk of bias in animal studies was mostly unclear. Echocardiography may offer a noninvasive tool to detect early signs of cardiovascular predisposition following FGR. Clinical implementation yet faces multiple challenges including identification of the most optimal timing and the exact relation to long-term cardiovascular function in which echocardiography alone might be limited to reflect a child's vascular status. Future research should focus on myocardial strain analysis and the combination of other (non)imaging techniques for an improved risk estimation.</p

Sodium Thiosulfate in the Pregnant Dahl Salt-Sensitive Rat, a Model of Preeclampsia

Aberrant production of hydrogen sulfide (H2S) has been linked to preeclampsia. We hypothesized that sodium thiosulfate (STS), a H2S donor, reduces hypertension and proteinuria, and diminishes fetal growth restriction in the Dahl salt-sensitive (S) rat, a spontaneous model of superimposed preeclampsia. In addition to a control group (n = 13), two groups received STS via drinking water at a dose of 2 g (n = 9) or 3 g per kg body weight per day (n = 8) from gestational day (GD) 10 to 20. Uterine artery resistance index was measured (GD18), urinary protein excretion rate was determined (GD19), and blood pressure and fetal outcomes were evaluated (GD20). At 2 g, STS had no effect on preeclamptic symptoms or fetal outcome. At 3 g, STS reduced maternal hypertension (121.8 ± 3.0 vs. 136.3 ± 2.9), but increased proteinuria (89 ± 15 vs. 56 ± 5 mg/24h), and relative kidney weight (0.86 ± 0.04 vs. 0.73 ± 0.02%). Fetal/placental weight ratio was reduced (3.83 ± 0.07 vs. 4.31 ± 0.08) without affecting litter size. No differences in uterine artery flow or renal histological damage were noted across treatment groups. While these data suggest a promising antihypertensive effect that could imply prolongation of preeclamptic pregnancies, the unfavorable effects on proteinuria, kidney weight, and fetal/placental weight ratio implies that clinical implementation of STS is contra-indicated until safety for mother and child can be verified.</p

SAFE@HOME: Digital health platform facilitating a new care path for women at increased risk of preeclampsia – A case-control study

Objective: In women at risk of developing preeclampsia, we evaluated the use of a digital health platform for telemonitoring blood pressure and symptoms combined with a minimal antenatal visit schedule. Study design: A case-control study for women with chronic hypertension, history of preeclampsia, or maternal cardiac or kidney disease. A care path was designed with reduced visits enhanced with a digital platform (SAFE@HOME) for daily blood pressure and symptom monitoring starting from 16 weeks of gestation. Homemeasurements were monitored in-hospital by obstetric professionals, taking actions upon alarming results. This prospective SAFE@HOME group was compared to a retrospective control group managed without self-monitoring. Main outcome measures: Primary: healthcare consumption (number of antenatal visits, ultrasounds, admissions and diagnostics), user experiences of the platform. Secondary: mate

Pregnancy in Advanced Kidney Disease:Clinical Practice Considerations on a Challenging Combination

Background:Thanks to the advances in care, pregnancy is now attainable for the majority of young female CKD patients, although it is still a high-risk endeavor. Clinical decision-making in these cases is impacted by a myriad of factors, making (pre)pregnancy counseling a complex process. The complexities, further impacted by limited data and unknown risks regarding outcome, can cause discussions when deciding on the best care for a specific patient. Objectives:In this article, we provide an overview of the considerations and dilemmas we encounter in preconception counseling and offer our perspective on how to deal with them in daily clinical practice. Methods:The main topics we discuss in our counseling are (1) the high risk of pregnancy complications, (2) the risk of permanent CKD deterioration due to pregnancy and subsequent decreased life expectancy, (3) appropriate changes in renal medication, and (4) assisted reproduction, genetic testing, and prenatal or preimplantation genetic diagnostics. Results and Conclusions:In our clinic, we openly address moral dilemmas arising in clinical practice in pregnancy and CKD, both within the physician team and with the patient. We do this by ensuring an interpretive physician-patient interaction and shared decision-making, deliberating in a multidisciplinary setting and, if needed, with input from an expert committee

Effect of Pregnancy on eGFR after Kidney Transplantation:A National Cohort Study

BACKGROUND: The effect of pregnancy on the course of estimated glomerular filtration rate (eGFR) is unknown in kidney transplant recipients (KTRs). METHODS: We conducted a nationwide multicenter cohort study in KTRs with pregnancy (>20 weeks) after kidney transplantation (KT). Annual eGFR's after KT until death or graft loss and additional eGFR's before each pregnancy were collected according to protocol. Changes in eGFR slope before and after each pregnancy were analyzed by generalized estimating equations (GEE) multilevel analysis adjusted for transplant vintage. RESULTS: We included 3194 eGFR measurements before and after pregnancy in 109 (55%) KTRs with 1, 78 (40%) with 2 and 10 (5%) with 3 pregnancies after KT. Median follow-up after first delivery post-KT was 14 years (IQR 18 years). Adjusted mean eGFR pre-pregnancy was 59 ml/min/1.73m2 (SEM 1.72; 95% CI 56-63), after first pregnancy 56 ml/min/1.73m2 (SEM 1.70; 95% CI 53-60), after second pregnancy 56 ml/min/1.73m2 (SEM 2.19; 95% CI 51-60) and after third pregnancy 55 ml/min/1.73m2 (SEM 8.63; 95% CI 38-72). Overall eGFR slope after first, second and third pregnancy was not significantly worse than pre-pregnancy (p = 0.28). However, adjusted mean eGFR after first pregnancy was 2.8 ml/min/1.73m (p = 0.08) lower than pre-pregnancy. CONCLUSIONS: First pregnancy has a small, but no significant, effect on eGFR slope in KTR. Midterm hyperfiltration, a marker for renal reserve capacity, was associated with better eGFR and death-censored graft survival. In this KTR cohort with long-term follow-up, no significant effect of pregnancy on kidney function was detected

Prenatal Use of Sildenafil in Fetal Growth Restriction and Its Effect on Neonatal Tissue Oxygenation-A Retrospective Analysis of Hemodynamic Data From Participants of the Dutch STRIDER Trial

Objective: Sildenafil is under investigation as a potential agent to improve uteroplacental perfusion in fetal growth restriction (FGR). However, the STRIDER RCT was halted after interim analysis due to futility and higher rates of persistent pulmonary hypertension and mortality in sildenafil-exposed neonates. This hypothesis-generating study within the Dutch STRIDER trial sought to understand what happened to these neonates by studying their regional tissue oxygen saturation (rSO2) within the first 72 h after birth. Methods: Pregnant women with FGR received 25 mg placebo or sildenafil thrice daily within the Dutch STRIDER trial. We retrospectively analyzed the cerebral and renal rSO2 monitored with near-infrared spectroscopy (NIRS) in a subset of neonates admitted to two participating neonatal intensive care units, in which NIRS is part of standard care. Secondarily, blood pressure and heart rate were analyzed to aid interpretation. Differences in oxygenation levels and interaction with time (slope) between placebo- and sildenafil-exposed groups were tested using mixed effects analyses with multiple comparisons tests. Results: Cerebral rSO2 levels were not different between treatment groups (79 vs. 77%; both n = 14) with comparable slopes. Sildenafil-exposed infants (n = 5) showed lower renal rSO2 than placebo-exposed infants (n = 6) during several time intervals on day one and two. At 69-72 h, however, the sildenafil group showed higher renal rSO2 than the placebo group. Initially, diastolic blood pressure was higher and heart rate lower in the sildenafil than the placebo group, which changed during day two. Conclusions: Although limited by sample size, our data suggest that prenatal sildenafil alters renal but not cerebral oxygenation in FGR neonates during the first 72 post-natal hours. The observed changes in renal oxygenation could reflect a vasoconstrictive rebound from sildenafil. Similar changes observed in accompanying vital parameters support this hypothesis

Long-Term Kidney and Maternal Outcomes After Pregnancy in Living Kidney Donors

For counseling it is important to know if pregnancy after Living Kidney Donation (LKD) affects long-term outcomes of the mono-kidney and the mother. Therefore, we performed a retrospective multicenter study in women ≤45 years who donated their kidney between 1981 and 2017. Data was collected via questionnaires and medical records. eGFR of women with post-LKD pregnancies were compared to women with pre-LKD pregnancies or nulliparous. eGFR before and after pregnancy were compared in women with post-LKD pregnancies. Pregnancy outcomes post-LKD were compared with pre-LKD pregnancy outcomes. 234 women (499 pregnancies) were included, of which 20 with pre- and post-LKD pregnancies (68) and 26 with only post-LKD pregnancies (59). Multilevel analysis demonstrated that eGFR was not different between women with and without post-LKD pregnancies (p = 0.23). Furthermore, eGFR was not different before and after post-LKD pregnancy (p = 0.13). More hypertensive disorders of pregnancy (HDP) occurred in post-LKD pregnancies (p = 0.002). Adverse fetal outcomes did not differ. We conclude that, despite a higher incidence of HDP, eGFR was not affected by post-LKD pregnancy. In line with previous studies, we found an increased risk for HDP after LKD without affecting fetal outcome. Therefore, a pregnancy wish alone should not be a reason to exclude women for LKD.</p