The Reduced Uterine Perfusion Pressure as a model for preeclampsia and fetal growth restriction in murine: a systematic review and meta-analysis.

BACKGROUND: The Reduced Uterine Perfusion Pressure (RUPP) model is frequently used to study preeclampsia and fetal growth restriction. An improved understanding of influential factors might improve reproducibility and reduce animal use considering the variability in RUPP phenotype. METHOD: We performed a systematic review and meta-analysis by searching Medline and Embase (until 03-28-2023) for RUPP studies in murine. Primary outcomes included: maternal blood pressure (BP) or proteinuria, fetal weight or crown-rump-length, fetal reabsorptions, or anti-angiogenic factors. We aimed to identify influential factors by meta-regression analysis. RESULTS: We included 155 studies. Our meta-analysis showed that the RUPP procedure results in significantly higher BP (MD 24.1 mmHg; [22.6;25.7]; n=148), proteinuria (SMD 2.3; [0.9; 3.8]; n=28), fetal reabsorptions (MD 50.4%; [45.5; 55.2]; n=42), circulating soluble FMS-like tyrosine kinase-1 (sFlt-1) (SMD 2.6; [1.7; 3.4]; n=34), and lower fetal weight (MD -0.4 g; [-0.47; -0.34]; n=113. The heterogeneity (variability between studies) in primary outcomes appeared ≥90%. Our meta-regression identified influential factors in the method and time point of BP measurement, randomization in fetal weight, and type of control group in sFlt-1. DISCUSSION: The RUPP is a robust model considering the evident differences in maternal and fetal outcomes. The high heterogeneity reflects the observed variability in phenotype. Due to underreporting, we observed reporting bias and a high risk of bias. We recommend standardizing study design by optimal time point and method chosen for readout measures to limit the variability. This contributes to improved reproducibility and thereby eventually improves the translational value of the RUPP model.

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.NEW & NOTEWORTHY Our meta-analysis revealed echocardiographic differences between fetal growth-restricted and control offspring in humans during the neonatal period: a reduced left ventricular mass and interventricular septum thickness, reduced mitral annular peak velocity, and mitral lateral early diastolic velocity. We were unable to pool echocardiographic parameters in animal studies and human adults because of an insufficient number of studies per individual outcome. The few studies on myocardial strain analysis showed small preclinical changes in FGR offspring.

Reassuring pregnancy outcomes in women with mild COL4A3-5-related disease (Alport syndrome) and genetic type of disease can aid personalized counseling.

Individualized pre-pregnancy counseling and antenatal care for women with chronic kidney disease (CKD) require disease-specific data. Here, we investigated pregnancy outcomes and long-term kidney function in women with COL4A3-5 related disease (Alport Syndrome, (AS)) in a large multicenter cohort. The ALPART-network (mAternaL and fetal PregnAncy outcomes of women with AlpoRT syndrome), an international collaboration of 17 centers, retrospectively investigated COL4A3-5 related disease pregnancies after the 20th week. Outcomes were stratified per inheritance pattern (X-Linked AS (XLAS)), Autosomal Dominant AS (ADAS), or Autosomal Recessive AS (ARAS)). The influence of pregnancy on estimated glomerular filtration rate (eGFR)-slope was assessed in 192 pregnancies encompassing 116 women (121 with XLAS, 47 with ADAS, and 12 with ARAS). Median eGFR pre-pregnancy was over 90ml/min/1.73m2. Neonatal outcomes were favorable: 100% live births, median gestational age 39.0 weeks and mean birth weight 3135 grams. Gestational hypertension occurred during 23% of pregnancies (reference: 'general' CKD G1-G2 pregnancies incidence is 4-20%) and preeclampsia in 20%. The mean eGFR declined after pregnancy but remained within normal range (over 90ml/min/1.73m2). Pregnancy did not significantly affect eGFR-slope (pre-pregnancy ß=-1.030, post-pregnancy ß=-1.349). ARAS-pregnancies demonstrated less favorable outcomes (early preterm birth incidence 3/11 (27%)). ARAS was a significant independent predictor for lower birth weight and shorter duration of pregnancy, next to the classic predictors (pre-pregnancy kidney function, proteinuria, and chronic hypertension) though missing proteinuria values and the small ARAS-sample hindered analysis. This is the largest study to date on AS and pregnancy with reassuring results for mild AS, though inheritance patterns could be considered in counseling next to classic risk factors. Thus, our findings support personalized reproductive care and highlight the importance of investigating kidney disease-specific pregnancy outcomes.

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.

Counselling on Conceiving: Attitudes and Factors Influencing Advice of Professionals in Transplantation.

Pregnancy after kidney transplantation (KT) conveys risks of adverse pregnancy outcomes (APO). Little is known about performance of pre-pregnancy counselling after KT. This study investigated perceptions of risk, attitudes towards pregnancy and factors influencing advice given at pre-pregnancy counselling after KT. A web-based vignette survey was conducted among nephrologists and gynaecologists between March 2020 and March 2021, consisting of five vignettes containing known risk factors for APO and general questions on pre-pregnancy counselling after KT. Per vignette, attitudes towards pregnancy and estimation of outcomes were examined. In total 52 nephrologists and 25 gynaecologists participated, 56% from university hospitals. One third had no experience with pregnancy after KT. All gave positive pregnancy advice in the vignette with ideal circumstances (V1), versus 83% in V2 (proteinuria), 81% in V3 (hypertension), 71% in V4 (eGFR 40 ml/min/1.73 m2). Only 2% was positive in V5 (worst-case scenario). Chance of preeclampsia was underestimated by 89% in V1. 63% and 98% overestimated risk for graft loss in V4 and V5. Professionals often incorrectly estimated risk of APO after KT. As experience with pregnancy after KT was limited among professionals, patients should be referred to specialised centres for multidisciplinary pre-pregnancy counselling to build experience and increase consistency in given advice.

OPtimal TIming of antenatal COrticosteroid administration in pregnancies complicated by early-onset fetal growth REstriction (OPTICORE): study protocol of a multicentre, retrospective cohort study.

INTRODUCTION: Early-onset fetal growth restriction (FGR) requires timely, often preterm, delivery to prevent fetal hypoxia causing stillbirth or neurologic impairment. Antenatal corticosteroids (CCS) administration reduces neonatal morbidity and mortality following preterm birth, most effectively when administered within 1 week preceding delivery. Optimal timing of CCS administration is challenging in early-onset FGR, as the exact onset and course of fetal hypoxia are unpredictable. International guidelines do not provide a directive on this topic. In the Netherlands, two timing strategies are commonly practiced: administration of CCS when the umbilical artery shows (A) a pulsatility index above the 95thh centile and (B) absent or reversed end-diastolic velocity (a more progressed disease state). This study aims to (1) use practice variation to compare CCS timing strategies in early-onset FGR on fetal and neonatal outcomes and (2) develop a dynamic tool to predict the time interval in days until delivery, as a novel timing strategy for antenatal CCS in early-onset FGR. METHODS AND ANALYSIS: A multicentre, retrospective cohort study will be performed including pregnancies complicated by early-onset FGR in six tertiary hospitals in the Netherlands in the period between 2012 and 2021 (estimated sample size n=1800). Main exclusion criteria are multiple pregnancies and fetal congenital or genetic abnormalities. Routinely collected data will be extracted from medical charts. Primary outcome for the comparison of the two CCS timing strategies is a composite of perinatal, neonatal and in-hospital mortality. Secondary outcomes include the COSGROVE core outcome set for FGR. A multivariable, mixed-effects model will be used to compare timing strategies on study outcomes. Primary outcome for the dynamic prediction tool is 'days until birth'. ETHICS AND DISSEMINATION: The need for ethical approval was waived by the Ethics Committee (University Medical Center Utrecht). Results will be published in open-access, peer-reviewed journals and disseminated by presentations at scientific conferences. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT05606497.

Optimizing cardiovascular risk assessment and registration in a developing cardiovascular learning health care system: Women benefit most.

Since 2015 we organized a uniform, structured collection of a fixed set of cardiovascular risk factors according the (inter)national guidelines on cardiovascular risk management. We evaluated the current state of a developing cardiovascular towards learning healthcare system-the Utrecht Cardiovascular Cohort Cardiovascular Risk Management (UCC-CVRM)-and its potential effect on guideline adherence in cardiovascular risk management. We conducted a before-after study comparing data from patients included in UCC-CVRM (2015-2018) and patients treated in our center before UCC-CVRM (2013-2015) who would have been eligible for UCC-CVRM using the Utrecht Patient Oriented Database (UPOD). Proportions of cardiovascular risk factor measurement before and after UCC-CVRM initiation were compared, as were proportions of patients that required (change of) blood pressure, lipid, or blood glucose lowering treatment. We estimated the likelihood to miss patients with hypertension, dyslipidemia, and elevated HbA1c before UCC-CVRM for the whole cohort and stratified for sex. In the present study, patients included up to October 2018 (n = 1904) were matched with 7195 UPOD patients with similar age, sex, department of referral and diagnose description. Completeness of risk factor measurement increased, ranging from 0% -77% before to 82%-94% after UCC-CVRM initiation. Before UCC-CVRM, we found more unmeasured risk factors in women compared to men. This sex-gap resolved in UCC-CVRM. The likelihood to miss hypertension, dyslipidemia, and elevated HbA1c was reduced by 67%, 75% and 90%, respectively, after UCC-CVRM initiation. A finding more pronounced in women compared to men. In conclusion, a systematic registration of the cardiovascular risk profile substantially improves guideline adherent assessment and decreases the risk of missing patients with elevated levels with an indication for treatment. The sex-gap disappeared after UCC-CVRM initiation. Thus, an LHS approach contributes to a more inclusive insight into quality of care and prevention of cardiovascular disease (progression).

Cohort profile: the Utrecht Cardiovascular Cohort-Second Manifestations of Arterial Disease (UCC-SMART) Study-an ongoing prospective cohort study of patients at high cardiovascular risk in the Netherlands.

PURPOSE: The Utrecht Cardiovascular Cohort-Second Manifestations of Arterial Disease (UCC-SMART) Study is an ongoing prospective single-centre cohort study with the aim to assess important determinants and the prognosis of cardiovascular disease progression. This article provides an update of the rationale, design, included patients, measurements and findings from the start in 1996 to date. PARTICIPANTS: The UCC-SMART Study includes patients aged 18-90 years referred to the University Medical Center Utrecht, the Netherlands, for management of cardiovascular disease (CVD) or severe cardiovascular risk factors. Since September 1996, a total of 14 830 patients have been included. Upon inclusion, patients undergo a standardised screening programme, including questionnaires, vital signs, laboratory measurements, an ECG, vascular ultrasound of carotid arteries and aorta, ankle-brachial index and ultrasound measurements of adipose tissue, kidney size and intima-media thickness. Outcomes of interest are collected through annual questionnaires and adjudicated by an endpoint committee. FINDINGS TO DATE: By May 2022, the included patients contributed to a total follow-up time of over 134 000 person-years. During follow-up, 2259 patients suffered a vascular endpoint (including non-fatal myocardial infarction, non-fatal stroke and vascular death) and 2794 all-cause deaths, 943 incident cases of diabetes and 2139 incident cases of cancer were observed up until January 2020. The UCC-SMART cohort contributed to over 350 articles published in peer-reviewed journals, including prediction models recommended by the 2021 European Society of Cardiology CVD prevention guidelines. FUTURE PLANS: The UCC-SMART Study guarantees an infrastructure for research in patients at high cardiovascular risk. The cohort will continue to include about 600 patients yearly and follow-up will be ongoing to ensure an up-to-date cohort in accordance with current healthcare and scientific knowledge. In the near future, UCC-SMART will be enriched by echocardiography, and a food frequency questionnaire at baseline enabling the assessment of associations between nutrition and CVD and diabetes.

Multiple Prior Live Births Are Associated With Cardiac Remodeling and Heart Failure Risk in Women.

OBJECTIVE: Greater parity has been associated with cardiovascular disease risk. We sought to find whether the effects on cardiac remodeling and heart failure risk are clear. METHODS: We examined the association of number of live births with echocardiographic measures of cardiac structure and function in participants of the Framingham Heart Study (FHS) using multivariable linear regression. We next examined the association of parity with incident heart failure with preserved (HFpEF) or reduced (HFrEF) ejection fraction using a Fine-Gray subdistribution hazards model in a pooled analysis of n = 12,635 participants in the FHS, the Cardiovascular Health Study, the Multi-Ethnic Study of Atherosclerosis, and Prevention of Renal and Vascular Endstage Disease. Secondary analyses included major cardiovascular disease, myocardia infarction and stroke. RESULTS: Among n = 3931 FHS participants (mean age 48 ± 13 years), higher numbers of live births were associated with worse left ventricular fractional shortening (multivariable ß -1.11 (0.31); P = 0.0005 in ≥ 5 live births vs nulliparous women) and worse cardiac mechanics, including global circumferential strain and longitudinal and radial dyssynchrony (P < 0.01 for all comparing ≥ 5 live births vs nulliparity). When examining HF subtypes, women with ≥ 5 live births were at higher risk of developing future HFrEF compared with nulliparous women (HR 1.93, 95% CI 1.19-3.12; P = 0.008); by contrast, a lower risk of HFpEF was observed (HR 0.58, 95% CI 0.37-0.91; P = 0.02). CONCLUSIONS: Greater numbers of live births are associated with worse cardiac structure and function. There was no association with overall HF, but a higher number of live births was associated with greater risk for incident HFrEF.

Statins in pre-eclampsia or fetal growth restriction: A systematic review and meta-analysis on maternal blood pressure and fetal growth across species.

BACKGROUND: Several human randomised controlled trials (RCTs) are investigating the effects of statins on pre-eclampsia (PE) and fetal growth restriction (FGR). This cross-species meta-analysis summarises the preclinical evidence of statin use for PE and FGR. OBJECTIVES: Evaluate the effects of statins on maternal blood pressure (MBP) and birthweight (BW) in pregnancies complicated by PE or FGR. SEARCH STRATEGY: PubMed and Embase.com were searched on 10 May 2022 using 'statins' and 'pregnancy'. SELECTION CRITERIA: We included RCTs and cohorts with matched control groups as well as animal studies. DATA COLLECTION AND ANALYSIS: The main outcomes were MBP in mmHg and BW in grams. The standardised mean difference (SMD) with a 95% confidence interval (CI) was calculated. Subgroup analyses on species, statin, dose, timing and route of administration were performed if subgroups included at least three studies. MAIN RESULTS: Our data included one human and 12 animal studies. Prenatal administration of statins significantly reduced MBP during pregnancy (SMD  -2.49 mmHg [95% CI -4.26 to -0.71], p = 0.01). There was no significant effect of statins on BW (SMD 0.69 [95% CI -0.65 to 2.03], p = 0.28). Our subgroup analyses showed no effect on MBP of different doses, species or route of administration. CONCLUSIONS: Our cross-species meta-analyses demonstrate that statins only reduce maternal blood pressure in rodent pregnancies complicated by pre-eclampsia or fetal growth restriction and have no effect on birthweight across species. The broad confidence intervals, inconsistent direction of the observed effects across the studies and large risk of bias lead us to conclude that a solid base for further human RCTs is lacking.

A nationwide Dutch cohort study shows relatively good pregnancy outcomes after kidney transplantation and finds risk factors for adverse outcomes.

Although numbers of pregnancy after kidney transplantation (KT) are rising, high risks of adverse pregnancy outcomes (APO) remain. Though important for pre-conception counselling and pregnancy monitoring, analyses of pregnancy outcomes after KT per pre-pregnancy estimated glomerular filtration rate-chronic kidney disease (eGFR-CKD)-categories have not been performed on a large scale before. To do this, we conducted a Dutch nationwide cohort study of consecutive singleton pregnancies over 20 weeks of gestation after KT. Outcomes were analyzed per pre-pregnancy eGFR-CKD category and a composite APO (cAPO) was established including birth weight under 2500 gram, preterm birth under 37 weeks, third trimester severe hypertension (systolic blood pressure over 160 and/or diastolic blood pressure over 110 mm Hg) and/or over 15% increase in serum creatinine during pregnancy. Risk factors for cAPO were analyzed in a multilevel model after multiple imputation of missing predictor values. In total, 288 pregnancies in 192 women were included. Total live birth was 93%, mean gestational age 35.6 weeks and mean birth weight 2383 gram. Independent risk factors for cAPO were pre-pregnancy eGFR, midterm percentage serum creatinine dip and midterm mean arterial pressure dip; odds ratio 0.98 (95% confidence interval 0.96-0.99), 0.95 (0.93-0.98) and 0.94 (0.90-0.98), respectively. The cAPO was a risk indicator for graft loss (hazard ratio 2.55, 1.09-5.96) but no significant risk factor on its own when considering pre-pregnancy eGFR (2.18, 0.92-5.13). This was the largest and most comprehensive study of pregnancy outcomes after KT, including pregnancies in women with poor kidney function, to facilitate individualized pre-pregnancy counselling based on pre-pregnancy graft function. Overall obstetric outcomes are good. The risk of adverse outcomes is mainly dependent on pre-pregnancy graft function and hemodynamic adaptation to pregnancy.

Menstrual problems in chronic immune thrombocytopenia: A monthly challenge - a cohort study and review.

Immune thrombocytopenia (ITP) may cause menstrual problems. This cross-sectional study assessed menstrual problems in premenopausal chronic ITP women by several questionnaires, including the pictorial bleeding assessment calendar (PBAC; score ≥100 indicates heavy menstrual bleeding [HMB]), and the menorrhagia multiattribute scale (MMAS). Spearman was used for assessing correlations. A literature review was performed in Pubmed. The cohort comprised 37 women (mean age 31 ± 9). A total of 29/37 (78%) had experienced clinical menstrual problems in the present or past. Of the 33 patients who returned the PBAC, 13 (39%) had a score of ≥100. The median MMAS score was 79 (IQR 60-95). The PBAC scores correlated with the MMAS. Both questionnaires were unrelated to the platelet count. Patients with a levonorgestrel intrauterine device (LNG-IUD) had lower PBAC scores than patients with other or no hormonal therapy. MMAS scores were correlated with fatigue. The review identified 14 papers. HMB occurred in 6%-55% at ITP diagnosis and 17%-79% during disease. Menstrual symptoms influenced the quality of life, particularly in patients with a low platelet count. This explorative study suggested that HMB is frequent in women with chronic ITP despite management and platelet counts >50 *109 /l. An LNG-IUD seemed to reduce blood loss significantly.

Corrigendum to "Maternal and Perinatal Outcome in Women with Systemic Lupus Erythematosus: A Retrospective Bicenter Cohort Study".

[This corrects the article DOI: 10.1155/2017/8245879.].

Chorioamnionitis Causes Kidney Inflammation, Podocyte Damage, and Pro-fibrotic Changes in Fetal Lambs.

Background: Perinatal complications, such as prematurity and intrauterine growth restriction, are associated with increased risk of chronic kidney disease. Although often associated with reduced nephron endowment, there is also evidence of increased susceptibility for sclerotic changes and podocyte alterations. Preterm birth is frequently associated with chorioamnionitis, though studies regarding the effect of chorioamnionitis on the kidney are scarce. In this study, we aim to unravel the consequences of premature birth and/or perinatal inflammation on kidney development using an ovine model. Methods: In a preterm sheep model, chorioamnionitis was induced by intra-amniotic injection of lipopolysaccharide (LPS) at either 2, 8, or 15 days prior to delivery. Control animals received intra-amniotic injections of sterile saline. All lambs were surgically delivered at 125 days' gestation (full term is 150 days) and immediately euthanized for necropsy. Kidneys were harvested and processed for staining with myeloperoxidase (MPO), Wilms tumor-1 (WT1) and alpha-smooth muscle actine (aSMA). mRNA expression of tumor necrosis factor alpha (TNFA), Interleukin 10 (IL10), desmin (DES), Platelet derived growth factor beta (PDGFB), Platelet derived growth factor receptor beta (PDGFRB), synaptopodin (SYNPO), and transforming growth factor beta (TGFB) was measured using quantitative PCR. Results: Animals with extended (but not acute) LPS exposure had an inflammatory response in the kidney. MPO staining was significantly increased after 8 and 15 days (p = 0.003 and p = 0.008, respectively). Expression of TNFA (p = 0.016) and IL10 (p = 0.026) transcripts was increased, peaking on day 8 after LPS exposure. Glomerular aSMA and expression of TGFB was increased on day 8, suggesting pro-fibrotic mesangial activation, however, this was not confirmed with PDFGB or PDGFRB. The number of WT1 positive nuclei in the glomerulus, as well as expression of synaptopodin, decreased, indicating podocyte injury. Conclusion: We report that, in an ovine model of prematurity, LPS-induced chorioamnionitis leads to inflammation of the immature kidney. In addition, this process was associated with podocyte injury and there are markers to support pro-fibrotic changes to the glomerular mesangium. These data suggest a potential important role for antenatal inflammation in the development of preterm-associated kidney disease, which is frequent.

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 wk) after kidney transplantation (KT). Annual eGFRs after KT until death or graft loss and additional eGFRs before each pregnancy were collected according to protocol. Changes in eGFR slope before and after each pregnancy were analyzed by generalized estimating equations 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 y (interquartile range, 18 y). Adjusted mean eGFR prepregnancy was 59 mL/min/1.73 m2 (SEM [standard error of the mean] 1.72; 95% confidence interval [CI], 56-63), after the first pregnancy 56 mL/min/1.73 m2 (SEM 1.70; 95% CI, 53-60), after the second pregnancy 56 mL/min/1.73 m2 (SEM 2.19; 95% CI, 51-60), and after the third pregnancy 55 mL/min/1.73 m2 (SEM 8.63; 95% CI, 38-72). Overall eGFR slope after the first, second, and third pregnancies was not significantly worse than prepregnancy (P = 0.28). However, adjusted mean eGFR after the first pregnancy was 2.8 mL/min/1.73 m2 (P = 0.08) lower than prepregnancy. CONCLUSIONS: The first pregnancy has a small, but insignificant, effect on eGFR slope in KTRs. 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.

Cardiometabolic Profiles in Women with a History of Hypertensive and Normotensive Fetal Growth Restriction.

Background: The majority of evidence on associations between pregnancy complications and future maternal disease focuses on hypertensive (Ht) complications. We hypothesize that impaired cardiometabolic health after pregnancies complicated by severe fetal growth restriction (FGR) is independent of the co-occurrence of hypertension. Materials and Methods: In a prospective cohort of women with a pregnancy complicated by early FGR (delivery <34 weeks gestation), with or without concomitant hypertension, cardiometabolic risk factors were assessed after delivery. A population-based reference cohort was used for comparison, and analyses were adjusted for age, current body mass index (BMI), smoking habits, and hormonal contraceptive use. Results: Median time from delivery to assessment was 4 months in both the Ht (N = 115) and normotensive (Nt) (N = 42) FGR groups. Compared with the reference group (N = 380), in both FGR groups lipid profile and glucose homeostasis at assessment were unfavorable. Women with Ht-FGR had the least favorable cardiometabolic profile, with higher prevalence ratios (PRs) for diastolic blood pressure >85 mmHg (PR 4.0, 95% confidence interval [CI] 2.1-6.7), fasting glucose levels >5.6 mmol/L (PR 2.9, 95% CI 1.4-5.6), and total cholesterol levels >6.21 mmol/L (PR 4.5, 95% CI 1.9-8.8), compared with the reference group. Women with Nt-FGR more often had a BMI >30 kg/m2 (PR 2.5, 95% CI 1.2-4.7) and high-density lipoprotein-cholesterol levels <1.29 mmol/L (PR 2.4, 95% CI 1.4-3.5), compared with the reference group. Conclusions: Women with a history of FGR showed unfavorable short-term cardiometabolic profiles in comparison with a reference group, independent of the co-occurrence of hypertension. Therefore, women with a history of FGR may benefit from cardiovascular risk factor assessment and subsequent risk reduction strategies.

Maternal, Decidual, and Neonatal Lymphocyte Composition Is Affected in Pregnant Kidney Transplant Recipients.

Pregnancy after renal transplantation is associated with an increased risk of complications. While a delicately balanced uterine immune system is essential for a successful pregnancy, little is known about the uterine immune environment of pregnant kidney transplant recipients. Moreover, children born to kidney transplant recipients are exposed in utero to immunosuppressive drugs, with possible consequences for neonatal outcomes. Here, we defined the effects of kidney transplantation on the immune cell composition during pregnancy with a cohort of kidney transplant recipients as well as healthy controls with uncomplicated pregnancies. Maternal immune cells from peripheral blood were collected during pregnancy as well as from decidua and cord blood obtained after delivery. Multiparameter flow cytometry was used to identify and characterize populations of cells. While systemic immune cell frequencies were altered in kidney transplant patients, immune cell dynamics over the course of pregnancy were largely similar to healthy women. In the decidua of women with a kidney transplant, we observed a decreased frequency of HLA-DR+ Treg, particularly in those treated with tacrolimus versus those that were treated with azathioprine next to tacrolimus, or with azathioprine alone. In addition, both the innate and adaptive neonatal immune system of children born to kidney transplant recipients was significantly altered compared to neonates born from uncomplicated pregnancies. Overall, our findings indicate a significant and distinct impact on the maternal systemic, uterine, and neonatal immune cell composition in pregnant kidney transplant recipients, which could have important consequences for the incidence of pregnancy complications, treatment decisions, and the offspring's health.

Platelet count and indices as postpartum hemorrhage risk factors: a retrospective cohort study.

BACKGROUND: Severe postpartum hemorrhage (SPPH) is the leading cause of maternal mortality and morbidity worldwide. Platelet anomalies frequently occur during pregnancy. However, their role in the etiology of SPPH is largely unknown. OBJECTIVE: To study the relation between platelet parameters and SPPH. METHODS: This retrospective single-center cohort included deliveries between 2009 and 2017. SPPH was defined as ≥1000 ml blood loss within 24 h after delivery. Platelet parameters were measured within 72 h before delivery. Multiple imputation was performed for missing data. Odds ratios were adjusted (aORs) for maternal age, multiple gestation, macrosomia, induction of labor, preeclampsia, and hemolysis, elevated liver enzymes, and low platelets syndrome. RESULTS: A total of 23 205 deliveries were included. Of the 2402 (10.4%) women with thrombocytopenia (<150 × 109 /L), 10.3% developed SPPH, compared with 7.6% of women with a normal platelet count (aOR: 1.34, 95% CI: 1.14-1.59). Women with a platelet count of <50 × 109 /L were most at risk (aOR of 2.24 [1.01-4.94]) compared with the reference group with normal platelet counts; the aOR was 1.22 (0.77-1.93) for the 50-99 × 109 /L platelet count group and 1.31 (1.10-1.56) for the 100-149 × 109 /L platelet count group. Plateletcrit was associated with SPPH (aOR 1.15 [1.08-1.21] per 0.05% decrease), and, although rarely present, a platelet distribution width (PDW) ≥23% (n = 22) also increased the odds of SPPH (aOR 6.05 [2.29-16.20]). CONCLUSION: Different degrees of thrombocytopenia were independently associated with the occurrence of SPPH. Despite their relation to SPPH, plateletcrit and a PDW of ≥23% have limited additional value in addition to platelet count.