Objective To quantify the association between prophylactic radiologic interventions and perioperative blood loss in women with risk factors for placenta accreta spectrum disorder (PAS)Methods We... Show moreObjective To quantify the association between prophylactic radiologic interventions and perioperative blood loss in women with risk factors for placenta accreta spectrum disorder (PAS)Methods We conducted a retrospective nationwide cohort study of women with risk factors for placenta accreta spectrum disorder who underwent planned cesarean section in 69 Dutch hospitals between 2008 and 2013. All women had two risk factors for PAS: placenta previa/anterior low-lying placenta and a history of cesarean section(s). Women with and without ultrasonographic signs of PAS were studied as two separate groups. We compared the total blood loss of women with prophylactic radiologic interventions, defined as preoperative placement of balloon catheters or sheaths in the internal iliac or uterine arteries, with that of a control group consisting of women without prophylactic radiologic interventions using multivariable regression. We evaluated maternal morbidity by the number of red blood cell (RBC) units transfused within 24 h following childbirth (categories: 0, 1-3, >4), duration of hospital admission, and need for intensive care unit (ICU) admission.Results A total of 350 women with placenta previa/anterior low-lying placenta and history of cesarean section(s) were included: 289 with normal ultrasonography, of whom 21 received prophylactic radiologic intervention, and 61 had abnormal ultrasonography, of whom 22 received prophylactic intervention. Among women with normal ultrasonography without prophylactic intervention (n = 268), the median blood loss was 725 mL (interquartile range (IQR) 500-1500) vs. 1000 mL (IQR 550-1750) in women with intervention (n = 21); the adjusted difference in blood loss was 9 mL (95% confidence interval (CI) -315-513), p = .97). Among women with abnormal ultrasonography, those without prophylactic intervention (n = 39) had a median blood loss of 2500 mL (IQR 1200-5000) vs. 1750 mL (IQR 775-4000) in women with intervention (n = 22); the adjusted difference in blood loss was -1141 mL (95% CI -1694- -219, p = .02). Results of outcomes on maternal morbidity were comparable among women with and without prophylactic intervention.Conclusion These findings suggest that prophylactic radiologic interventions prior to planned cesarean section may help to limit perioperative blood loss in women with clear signs of placenta accreta spectrum disorder on ultrasonography, but there was no evidence of a difference within the subgroup without such ultrasonographic signs. The use of these interventions should be discussed in a multidisciplinary shared decision-making process, including discussions of potential benefits and possible complications.Trial registration Netherlands Trial Registry, https://onderzoekmetmensen.nl/en/trial/28238, identifier NL4210 (NTR4363) Show less
Tweel, M.M. van den; Munckhof, E.H.A. van den; Zanden, M. van der; Molijn, A.C.; Lith, J.M.M. van; Cessie, S. le; Boers, K.E. 2023
PurposeThis study investigates the role of bacterial vaginosis (BV) on pregnancy rates during various fertility treatments. BV is known to influence several obstetric outcomes, such as preterm... Show morePurposeThis study investigates the role of bacterial vaginosis (BV) on pregnancy rates during various fertility treatments. BV is known to influence several obstetric outcomes, such as preterm delivery and endometritis. Only few studies investigated the effect of BV in subfertile women, and studies found a negative effect on fecundity especially in the in vitro fertilisation population.MethodsObservational prospective study, 76 couples attending a fertility clinic in the Netherlands between July 2019 and June 2022, undergoing a total of 133 attempts of intra uterine insemination, in vitro fertilization or intra cytoplasmatic sperm injection. Vaginal samples taken at oocyte retrieval or insemination were analysed on qPCR BV and 16S rRNA gene microbiota analysis of V1-V2 region. Logistic regression with a Generalized Estimated Equations analysis was used to account for multiple observations per couples.ResultsA total of 26% of the 133 samples tested positive for BV. No significant differences were observed in ongoing pregnancy or live birth rates based on BV status (OR 0.50 (0.16-1.59), aOR 0.32 (0.09-1.23)) or microbiome community state type. There was a tendency of more miscarriages based on positive BV status (OR 4.22 (1.10-16.21), aOR 4.28 (0.65-28.11)) or community state type group III and IV. On baseline qPCR positive participants had significantly higher body mass index and smoked more often. Odds ratios were adjusted for smoking status, body mass index, and socioeconomic status.ConclusionBacterial vaginosis does not significantly impact ongoing pregnancy rates but could affect miscarriage rates. Show less
Wind, M.; Akker-van Marle, M.E. van den; Ballieux, B.E.P.B.; Cobbaert, C.M.; Rabelink, T.J.; Lith, J.M.M. van; ... ; Sueters, M. 2022
Background: This study investigated the clinical value of adding the sFlt-1/PlGF ratio to the spot urine protein/creatinine ratio (PCr) in women with suspected pre-eclampsia. Methods: This was a... Show moreBackground: This study investigated the clinical value of adding the sFlt-1/PlGF ratio to the spot urine protein/creatinine ratio (PCr) in women with suspected pre-eclampsia. Methods: This was a prospective cohort study performed in a tertiary referral centre. Based on the combination of PCr (< 30) and sFlt-1/PlGF (& LE;38) results, four groups were described: a double negative result, group A-/-; a negative PCr and positive sFlt-1/PlGF, group B-/+; a positive PCr and negative sFlt-1/PlGF, group C+/-; and a double positive result, group D+/+. The primary outcome was the proportion of false negatives of the combined tests in comparison with PCr alone in the first week after baseline. Secondary, a cost analysis comparing the costs and savings of adding the sFlt-1/PlGF ratio was performed for different follow-up scenarios. Results: A total of 199 women were included. Pre-eclampsia in the first week was observed in 2 women (2%) in group A-/-, 12 (26%) in group B-/+, 4 (27%) in group C+/-, and 12 (92%) in group D+/+. The proportion of false negatives of 8.2% [95% CI 4.9-13.3] with the PCr alone was significantly reduced to 1.6% [0.4-5.7] by adding a negative sFlt-1/PlGF ratio. Furthermore, the addition of the sFlt-1/PlGF ratio to the spot urine PCr, with telemonitoring of women at risk, could result in a reduction of 41% admissions and 36% outpatient visits, leading to a cost reduction of euro46,- per patient. Conclusions: Implementation of the sFlt-1/PlGF ratio in addition to the spot urine PCr, may lead to improved selection of women at low risk and a reduction of hospital care for women with suspected pre-eclampsia. Show less
Wind, M.; Akker-van Marle, M.E. van den; Ballieux, B.E.P.B.; Cobbaert, C.M.; Rabelink, T.J.; Lith, J.M.M. van; ... ; Sueters, M. 2022
BackgroundThis study investigated the clinical value of adding the sFlt-1/PlGF ratio to the spot urine protein/creatinine ratio (PCr) in women with suspected pre-eclampsia.MethodsThis was a... Show moreBackgroundThis study investigated the clinical value of adding the sFlt-1/PlGF ratio to the spot urine protein/creatinine ratio (PCr) in women with suspected pre-eclampsia.MethodsThis was a prospective cohort study performed in a tertiary referral centre. Based on the combination of PCr (< 30) and sFlt-1/PlGF (≤38) results, four groups were described: a double negative result, group A−/−; a negative PCr and positive sFlt-1/PlGF, group B−/+; a positive PCr and negative sFlt-1/PlGF, group C+/−; and a double positive result, group D+/+. The primary outcome was the proportion of false negatives of the combined tests in comparison with PCr alone in the first week after baseline. Secondary, a cost analysis comparing the costs and savings of adding the sFlt-1/PlGF ratio was performed for different follow-up scenarios.ResultsA total of 199 women were included. Pre-eclampsia in the first week was observed in 2 women (2%) in group A−/−, 12 (26%) in group B−/+, 4 (27%) in group C+/−, and 12 (92%) in group D+/+. The proportion of false negatives of 8.2% [95% CI 4.9–13.3] with the PCr alone was significantly reduced to 1.6% [0.4–5.7] by adding a negative sFlt-1/PlGF ratio. Furthermore, the addition of the sFlt-1/PlGF ratio to the spot urine PCr, with telemonitoring of women at risk, could result in a reduction of 41% admissions and 36% outpatient visits, leading to a cost reduction of €46,- per patient.ConclusionsImplementation of the sFlt-1/PlGF ratio in addition to the spot urine PCr, may lead to improved selection of women at low risk and a reduction of hospital care for women with suspected pre-eclampsia. Show less
Youssef, A.; Hoorn, M.L. van der; Eekelen, R. van; Geloven, N. van; Wely, M. van; Smits, M.A.J.; ... ; Lashley, E. 2022
Introduction: Recurrent pregnancy loss (RPL) is defined as the loss of two or more conceptions before 24 weeks gestation. Despite extensive diagnostic workup, in only 25%-40% an underlying cause is... Show moreIntroduction: Recurrent pregnancy loss (RPL) is defined as the loss of two or more conceptions before 24 weeks gestation. Despite extensive diagnostic workup, in only 25%-40% an underlying cause is identified. Several factors may increase the risk for miscarriage, but the chance of a successful pregnancy is still high. Prognostic counselling plays a significant role in supportive care. The main limitation in current prediction models is the lack of a sufficiently large cohort, adjustment for relevant risk factors, and separation between cumulative live birth rate and the success chance in the next conception. In this project, we aim to make an individualised prognosis for the future chance of pregnancy success, which could lead to improved well-being and the ability managing reproductive choices. Methods and analysis: In this multicentre study, we will include both a prospective and a retrospective cohort of at least 931 and 1000 couples with RPL, respectively. Couples who have visited one of the three participating university hospitals in the Netherlands for intake are eligible for the study participation, with a follow-up duration of 5 years. General medical and obstetric history and reports of pregnancies after the initial consultation will be collected. Multiple imputation will be performed to cope for missing data. A Cox proportional hazards model for time to pregnancy will be developed to estimate the cumulative chance of a live birth within 3 years after intake. To dynamically estimate the chance of an ongoing pregnancy, given the outcome of earlier pregnancies after intake, a logistic regression model will be developed. Ethics and dissemination: The Medical Ethical Research Committee of the Leiden University Medical Center approved this study protocol (N22.025). There are no risks or burden associated with this study. Participant written informed consent is required for both cohorts. Findings will be published in peer-reviewed journals and presentations at international conferences. Show less
Fosse, N.A. du; Lashley, E.E.L.O.; Anholts, J.D.H.; Beelen, E. van; Cessie, S. le; Lith, J.M.M. van; ... ; Hoorn, M.L.P. van der 2022
Background: Seminal plasma contains signaling molecules capable of modulating the maternal immune environment to support implantation and pregnancy. Prior studies indicated that seminal plasma... Show moreBackground: Seminal plasma contains signaling molecules capable of modulating the maternal immune environment to support implantation and pregnancy. Prior studies indicated that seminal plasma induces changes in gene transcription of maternal immune cells. Reduced immune suppressive capacity may lead to pregnancy loss. The aim of this study was to investigate the immunomodulating effects of seminal plasma on T cells and monocytes in the context of recurrent pregnancy loss (RPL).Methods: Female T cells and monocytes were incubated with seminal plasma of 20 males in unexplained RPL couples (RPL males) and of 11 males whose partners had ongoing pregnancies (control males). The effect of seminal plasma on messenger RNA (mRNA) expression of immune cells was measured. Levels of mRNA expression were related to key signaling molecules present in the seminal plasma. Agglomerative hierarchical cluster analysis was performed on seminal plasma expression profiles and on mRNA expression profiles. Results: Expression of CD25 and anti-inflammatory IL-10 by female T cells was significantly lower after stimulation with seminal plasma of RPL males compared to control males. Female monocytes treated with seminal plasma of RPL males showed an immune activation signature of relatively elevated HLA-DR expression. Expression of these T cell and monocyte components was particularly correlated with the amounts of TGF-beta and VEGF in the seminal plasma. Conclusion: Our findings indicate that seminal plasma has immunomodulating properties on female immune cells compatible with the induction of a more regulatory phenotype, which may be impaired in cases of unexplained RPL. Show less
Background CenteringPregnancy (CP), a model of group antenatal care, was implemented in 2012 in the Netherlands to improve perinatal health; CP is associated with improved pregnancy outcomes.... Show moreBackground CenteringPregnancy (CP), a model of group antenatal care, was implemented in 2012 in the Netherlands to improve perinatal health; CP is associated with improved pregnancy outcomes. However, motivating women to participate in CP can be difficult. As such, we explored the characteristics associated with CP uptake and attendance and then investigated whether participation differs between health care facilities. In addition, we examined the reasons why women may decline participation and the reasons for higher or lower attendance rates. Methods Data from a stepped-wedge cluster randomized controlled trial were used. Univariate and multivariate logistic regression models were used to determine associations among women's health behavior, sociodemographic and psychosocial characteristics, health care facilities, and participation and attendance in CP. Results A total of 2562 women were included in the study, and the average participation rate was 31.6% per health care facility (range of 10%-53%). Nulliparous women, women 30 years old, and women reporting average or high levels of stress were more likely to participate in CP. Participation was less likely for women who had stopped smoking before prenatal intake, or who scored below average on lifestyle/pregnancy knowledge. For those participating in CP, 87% attended seven or more out of the 10 sessions, and no significant differences were found in women's characteristics when compared for higher or lower attendance rates. After the initial uptake, group attendance rates remained high. Conclusion A more comprehensive understanding of the variation in participation rate between health care facilities is required, in order to develop effective strategies to improve the recruitment of women, especially those with less knowledge and understanding of health issues and smoking habits. Show less
Fosse, N.A. du; Hoorn, M.L.P. van der; Koning, R. de; Mulders, A.G.M.G.J.; Lith, J.M.M. van; Cessie, S. le; Lashley, E.E.L.O. 2022
Objective: To identify, besides maternal age and the number of previous pregnancy losses, additional characteristics of couples with unexplained recurrent pregnancy loss (RPL) that improve the... Show moreObjective: To identify, besides maternal age and the number of previous pregnancy losses, additional characteristics of couples with unexplained recurrent pregnancy loss (RPL) that improve the prediction of an ongoing pregnancy.Design: Hospital-based cohort study in couples who visited specialized RPL units of two academic centers between 2012 and 2020.Setting: Two academic centers in the Netherlands.Patients: Clinical data from 526 couples with unexplained RPL were used in this study.Intervention(s): None.Main Outcome Measures: The final model to estimate the chance of a subsequent ongoing pregnancy was determined using a backward selection process and internally validated using bootstrapping. Model performance was assessed in terms of calibration and discrimination (area under the receiver operating characteristic curve).Results: Subsequent ongoing pregnancy was achieved in 345 of 526 couples (66%). The number of previous pregnancy losses, maternal age, paternal age, maternal body mass index, paternal body mass index, maternal smoking status, and previous in vitro fertilization/intracytoplasmic sperm injection treatment were predictive of the outcome. The optimism-corrected area under the receiver operating characteristic curve was 0.63 compared with 0.57 when using only the number of previous pregnancy losses and maternal age.Conclusions: The identification of additional predictors of a subsequent ongoing pregnancy after RPL, including male characteristics, is significant for both clinicians and couples with RPL. At the same time, we showed that the predictive ability of the current model is still limited and more research is warranted to develop a model that can be used in clinical practice. (C) 2021 by American Society for Reproductive Medicine. Show less
Fosse, N.A. du; Lashley, E.E.L.O.; Treurniet, T.T.; Lith, J.M.M. van; Cessie, S. le; Boosman, H.; Hoorn, M.L.P. van der 2021
Background International guidelines recommend to offer supportive care during a next pregnancy to couples affected by recurrent pregnancy loss (RPL). In previous research, several options for... Show moreBackground International guidelines recommend to offer supportive care during a next pregnancy to couples affected by recurrent pregnancy loss (RPL). In previous research, several options for supportive care have been identified and women's preferences have been quantified. Although it is known that RPL impacts the mental health of both partners, male preferences for supportive care have hardly been explored. Methods A cross-sectional study was conducted in couples who visited a specialized RPL clinic in the Netherlands between November 2018 and December 2019. Both members of the couples received a questionnaire that quantified their preferences for supportive care in a next pregnancy and they were asked to complete this independently from each other. Preferences for each supportive care option were analysed on a group level (by gender) and on a couple level, by comparing preferences of both partners. Results Ninety-two questionnaires (completed by 46 couples) were analysed. The overall need for supportive care indicated on a scale from 1 to 10 was 6.8 for men and 7.9 for women (P = 0.002). Both genders preferred to regularly see the same doctor with knowledge of their obstetric history, to make a plan for the first trimester and to have frequent ultrasound examinations. A lower proportion of men preferred a doctor that shows understanding (80% of men vs. 100% of women, P = 0.004) and a doctor that informs on wellbeing (72% vs. 100%, P = <= 0.000). Fewer men preferred support from friends (48% vs. 74%, P = 0.017). Thirty-seven percent of men requested more involvement of the male partner at the outpatient clinic, compared to 70% of women (P = 0.007). In 28% of couples, partners had opposing preferences regarding peer support. Conclusions While both women and men affected by RPL are in need of supportive care, their preferences may differ. Current supportive care services may not entirely address the needs of men. Health care professionals should focus on both partners and development of novel supportive care programs with specific attention for men should be considered. Show less
Fosse, N.A. du; Lashley, E.E.L.O.; Beelen, E. van; Meuleman, T.; Cessie, S. le; Lith, J.M.M. van; ... ; Hoorn, M.L.P. van der 2021
Background: Seminal plasma contains a wide range of cytokines, chemokines and growth factors. Part of these signalling molecules assist in inducing a state of active maternal immune tolerance... Show moreBackground: Seminal plasma contains a wide range of cytokines, chemokines and growth factors. Part of these signalling molecules assist in inducing a state of active maternal immune tolerance towards the fetus. Disbalances in seminal plasma content may contribute to pregnancy loss. This study investigated cytokine expression profiles in seminal plasma of male partners of couples with unexplained recurrent pregnancy loss (RPL) and the association with clinical and lifestyle characteristics, including smoking, alcohol consumption and body mass index (BMI). Methods: In the seminal plasma of 52 men who visited a specialised RPL clinic the levels of 25 pre-selected cytokines, chemokines and growth factors were measured by Bio-Plex assay or ELISA. Two-way hierarchical cluster analysis was performed. Identified patient clusters were compared on clinical and lifestyle characteristics. Results: Two distinct cytokine expression profiles in the seminal plasma were revealed by cluster analysis. Patient cluster I showed relatively higher levels of pro-inflammatory cytokines, including IL-1 alpha, IL-1 beta, IL-6, IL-8, IL-12, IL-18 and TNF-alpha, compared to Patient cluster II. Men belonging to Patient cluster I were significantly older and had significantly more lifestyle risk factors compared to men in Patient cluster II. Conclusion: Cluster analysis suggested the existence of a less favourable pro-inflammatory cytokine expression profile, being present in part of men affected by RPL and associated with advanced male age and lifestyle risk factors. These findings may serve as a starting point for further research into underlying mechanisms and ultimately lead to novel diagnostic and therapeutic approaches for couples with RPL. Show less
Ramler, P.I.; Gillissen, A.; Henriquez, D.D.C.A.; Caram-Deelder, C.; Markovski, A.A.; Maat, M.P.M. de; ... ; Bom, J.G. van der 2021
Introduction To evaluate rotational fibrin-based thromboelastometry (ROTEM(R) FIBTEM) with amplitude of clot firmness at 5 min (A5) as an early point-of-care parameter for predicting progression to... Show moreIntroduction To evaluate rotational fibrin-based thromboelastometry (ROTEM(R) FIBTEM) with amplitude of clot firmness at 5 min (A5) as an early point-of-care parameter for predicting progression to severe postpartum hemorrhage, and compare its predictive value with that of fibrinogen.Material and methods Prospective cohort study in the Netherlands including women with 800-1500 ml of blood loss within 24 h following birth. Blood loss was quantitatively measured by weighing blood-soaked items and using a fluid collector bag in the operating room. Both FIBTEM A5 values and fibrinogen concentrations (Clauss method) were measured between 800 and 1500 ml of blood loss. Predictive accuracy of both biomarkers for the progression to severe postpartum hemorrhage was measured by area under the receiver operating curves (AUC). Severe postpartum hemorrhage was defined as a composite endpoint of (1) total blood loss >2000 ml, (2) transfusion of >= 4 packed cells, and/or (3) need for an invasive intervention to cease bleeding.Results Of the 391 women included, 72 (18%) developed severe postpartum hemorrhage. Median (IQR) volume of blood loss at blood sampling was 1100 ml (1000-1300) with a median (interquartile range [IQR]) fibrinogen concentration of 3.9 g/L (3.4-4.6) and FIBTEM A5 value of 17 mm (13-20). The AUC for progression to severe postpartum hemorrhage was 0.53 (95% confidence interval [CI] 0.46-0.61) for FIBTEM A5 and 0.58 (95% CI 0.50-0.65) for fibrinogen. Positive predictive values for progression to severe postpartum hemorrhage for FIBTEM A5 <= 12 mm was 22.5% (95% CI 14-33) and 50% (95% CI 25-75) for fibrinogen <= 2 g/L.Conclusions The predictive value of FIBTEM A5 compared to fibrinogen concentrations measured between 800 and 1500 ml of blood loss following childbirth was poor to discriminate between women with and without progression towards severe postpartum hemorrhage. Show less
Objectives Functional development of the fetal cardiac autonomic nervous system (cANS) plays a key role in fetal maturation and can be assessed through fetal heart rate variability (fHRV)-analysis,... Show moreObjectives Functional development of the fetal cardiac autonomic nervous system (cANS) plays a key role in fetal maturation and can be assessed through fetal heart rate variability (fHRV)-analysis, with each HRV parameter representing different aspects of cANS activity. Current available techniques, however, are unable to assess the fHRV parameters accurately throughout the whole pregnancy. This study aims to test the feasibility of color tissue Doppler imaging (cTDI) as a new ultrasound technique for HRV analysis. Secondly, we explored time trends of fHRV parameters using this technique.Methods 18 healthy singleton fetuses were examined sequentially every 8 weeks from 10 weeks GA onwards. From each examination, 3 cTDI recordings of the four-chamber view of 10 seconds were retrieved to determine accurate beat-to-beat intervals. The fHRV parameters SDNN, RMSSD, SDNN/RMSSD, and pNN10, each representing different functional aspects of the cANS, were measured, and time trends during pregnancy were explored using spline functions within a linear mixed-effects model.Results In total, 77% (95% Cl 66-87%) of examinations were feasible for fHRV analysis from the first trimester onwards, which is a great improvement compared to other techniques. The technique is able to determine different maturation rates of the fHRV parameters, showing that cANS function, presumably parasympathetic activity, establishes around 20 weeks GA and matures rapidly until 30 weeks GA.Conclusions This is the first study able to assess cANS function through fHRV analysis from the first trimester onwards. The use of cTDI to determine beat-to-beat intervals seems feasible in just 3 clips of 10 seconds, which holds promise for future clinical use in assessing fetal well-being. Show less
Wind, M.; Gaasbeek, A.G.A.; Oosten, L.E.M.; Rabelink, T.J.; Lith, J.M.M. van; Sueters, M.; Teng, Y.K.O. 2021
Therapeutic plasma exchange (TPE) is indicated as a treatment for a wide array of diseases, extensively addressed in the Guidelines of the American Society for Apheresis. In pregnancy, TPE is an... Show moreTherapeutic plasma exchange (TPE) is indicated as a treatment for a wide array of diseases, extensively addressed in the Guidelines of the American Society for Apheresis. In pregnancy, TPE is an uncommon event and application is largely based on extrapolation of efficacy and safety in a non-pregnant population. This review intends to describe the currently available experience of TPE in pregnancy to help clinicians recognise indications during pregnancy and to support current guideline recommendations with literature-based experiences. In order to identify the clinical indications for which TPE is applied in pregnant women, we performed a literature search including studies till November 2019, without a start date restriction. Data extraction included medical indication for TPE and safety of TPE in pregnant women. 279 studies were included for analysis. Nowadays, TPE is predominantly applied for thrombotic microangiopathies, lipid disorders and a variety of autoimmune diseases. The application of TPE during pregnancy remains largely empiric and relies on individual case reports in the absence of high-quality studies and definitive evidence-based guidelines. Safety profile of TPE during pregnancy appears to be comparable to application of TPE in non-pregnant patients. In conclusion, based on the limited evidence that we found in literature with a high risk of publication bias, TPE procedures can be used safely during pregnancy with the appropriate preparation and experience of a multidisciplinary team. (C) 2021 The Author(s). Published by Elsevier B.V. Show less
Wind, M.; Gaasbeek, A.G.A.; Oosten, L.E.M.; Rabelink, T.J.; Lith, J.M.M. van; Sueters, M.; Teng, Y.K.O. 2021
Therapeutic plasma exchange (TPE) is indicated as a treatment for a wide array of diseases, extensively addressed in the Guidelines of the American Society for Apheresis. In pregnancy, TPE is an... Show moreTherapeutic plasma exchange (TPE) is indicated as a treatment for a wide array of diseases, extensively addressed in the Guidelines of the American Society for Apheresis. In pregnancy, TPE is an uncommon event and application is largely based on extrapolation of efficacy and safety in a non-pregnant population. This review intends to describe the currently available experience of TPE in pregnancy to help clinicians recognise indications during pregnancy and to support current guideline recommendations with literature-based experiences. In order to identify the clinical indications for which TPE is applied in pregnant women, we performed a literature search including studies till November 2019, without a start date restriction. Data extraction included medical indication for TPE and safety of TPE in pregnant women. 279 studies were included for analysis. Nowadays, TPE is predominantly applied for thrombotic microangiopathies, lipid disorders and a variety of autoimmune diseases. The application of TPE during pregnancy remains largely empiric and relies on individual case reports in the absence of high-quality studies and definitive evidence-based guidelines. Safety profile of TPE during pregnancy appears to be comparable to application of TPE in non-pregnant patients. In conclusion, based on the limited evidence that we found in literature with a high risk of publication bias, TPE procedures can be used safely during pregnancy with the appropriate preparation and experience of a multidisciplinary team. Show less
Wind, M.; Hendriks, M.; Brussel, B.T.J. van; Eikenboom, J.; Allaart, C.F.; Lamb, H.J.; ... ; Teng, Y.K.O. 2021
Objectives SLE and/or antiphospholipid syndrome (SLE/APS) are complex and rare systemic autoimmune diseases that predominantly affect women of childbearing age. Women with SLE/APS are at high risk... Show moreObjectives SLE and/or antiphospholipid syndrome (SLE/APS) are complex and rare systemic autoimmune diseases that predominantly affect women of childbearing age. Women with SLE/APS are at high risk of developing complications during pregnancy. Therefore, clinical practice guidelines recommend that patients with SLE/APS should receive multidisciplinary counselling before getting pregnant. We investigated the clinical effectiveness of implementing a multidisciplinary clinical pathway including prepregnancy counselling of patients with SLE/APS. Methods A clinical pathway with specific evaluation and prepregnancy counselling for patients with SLE/APS was developed and implemented in a tertiary, academic hospital setting. Patients were prospectively managed within the clinical pathway from 2014 onwards and compared with a retrospective cohort of patients that was not managed in a clinical pathway. Primary outcome was a combined outcome of disease flares for SLE and thromboembolic events for APS. Secondary outcomes were maternal and fetal pregnancy complications. Results Seventy-eight patients with 112 pregnancies were included in this study. The primary combined outcome was significantly lower in the pathway cohort (adjusted OR (aOR) 0.20 (95% CI 0.06 to 0.75)) which was predominantly determined by a fivefold risk reduction of SLE flares (aOR 0.22 (95% CI 0.04 to 1.09)). Maternal and fetal pregnancy complications were not different between the cohorts (respectively, aOR 0.91 (95% CI 0.38 to 2.17) and aOR 1.26 (95% CI 0.55 to 2.88)). Conclusions The outcomes of this study suggest that patients with SLE/APS with a pregnancy wish benefit from a multidisciplinary clinical pathway including prepregnancy counselling. Show less
Background and aim: To investigate whether neonates with prenatally detected congenital heart defects (CHD) demonstrate cerebral abnormalities on early preoperative cranial ultrasound (CUS),... Show moreBackground and aim: To investigate whether neonates with prenatally detected congenital heart defects (CHD) demonstrate cerebral abnormalities on early preoperative cranial ultrasound (CUS), compared to healthy neonates, and to measure brain structures to assess brain growth and development in both groups.Study design, subjects and outcome measures: Prospective cohort study with controls. Between September 2013 and May 2016 consecutive cases of prenatally detected severe isolated CHD were included. Neonatal CUS was performed shortly after birth, before surgery and in a healthy control group. Blinded images were reviewed for brain abnormalities and various measurements of intracranial structures were compared.Results: CUS was performed in 59 healthy controls and 50 CHD cases. Physiological CUS variants were present in 54% of controls and in 52% of CHD cases. Abnormalities requiring additional monitoring (both significant and minor) were identified in four controls (7%) and five CHD neonates (10%). Significant abnormalities were only identified in four CHD neonates (8%) and never in controls. A separate analysis of an additional 8 CHD neonates after endovascular intervention demonstrated arterial stroke in two cases that underwent balloon atrioseptostomy (BAS). Cerebral measurements were smaller in CHD neonates, except for the cerebrospinal fluid measurements, which were similar to the controls.Conclusions: The prevalence of significant preoperative CUS abnormalities in CHD cases was lower than previously reported, which may be partially caused by a guarding effect of a prenatal diagnosis. Arterial stroke occurred only in cases after BAS. As expected, neonates with CHD display slightly smaller head size and cerebral growth. Show less
Foss, N.A. du; Hoorn, M.L.P. van der; Lith, J.M.M. van; Cessie, S. le; Lashley, E.E.L.O. 2020
BACKGROUND: Although spontaneous miscarriage is the most common complication of human pregnancy, potential contributing factors are not fully understood. Advanced maternal age has long been... Show moreBACKGROUND: Although spontaneous miscarriage is the most common complication of human pregnancy, potential contributing factors are not fully understood. Advanced maternal age has long been recognised as a major risk factor for miscarriage, being strongly related with fetal chromosomal abnormalities. The relation between paternal age and the risk of miscarriage is less evident, yet it is biologically plausible that an increasing number of genetic and epigenetic sperm abnormalities in older males may contribute to miscarriage. Previous meta-analyses showed associations between advanced paternal age and a broad spectrum of perinatal and paediatric outcomes. This is the first systematic review and meta-analysis on paternal age and spontaneous miscarriage.OBJECTIVE AND RATIONALE: The aim of this systematic review and meta-analysis is to evaluate the effect of paternal age on the risk of spontaneous miscarriage.SEARCH METHODS: PubMed, Embase and Cochrane databases were searched to identify relevant studies up to August 2019. The following free text and MeSH terms were used: paternal age, father's age, male age, husband's age, spontaneous abortion, spontaneous miscarriage, abortion, miscarriage, pregnancy loss, fetal loss and fetal death. PRISMA guidelines for systematic reviews and meta-analysis were followed. Original research articles in English language addressing the relation between paternal age and spontaneous miscarriage were included. Exclusion criteria were studies that solely focused on pregnancy outcomes following artificial reproductive technology (ART) and studies that did not adjust their effect estimates for at least maternal age. Risk of bias was qualitatively described for three domains: bias due to confounding, information bias and selection bias.OUTCOMES: The search resulted in 975 original articles. Ten studies met the inclusion criteria and were included in the qualitative synthesis. Nine of these studies were included in the quantitative synthesis (meta-analysis). Advanced paternal age was found to be associated with an increased risk of miscarriage. Pooled risk estimates for miscarriage for age categories 30-34, 35-39, 40-44 and >= 45 years of age were 1.04 (95% CI 0.90, 1.21), 1.15 (0.92, 1.43), 1.23 (1.06, 1.43) and 1.43 (1.13, 1.81) respectively (reference category 25-29 years). A second meta-analysis was performed for the subgroup of studies investigating first trimester miscarriage. This showed similar pooled risk estimates for the first three age categories and a slightly higher pooled risk estimate for age category >= 45 years (1.74; 95% CI 1.26, 2.41).WIDER IMPLICATIONS: Over the last decades, childbearing at later ages has become more common. It is known that frequencies of adverse reproductive outcomes, including spontaneous miscarriage, are higher in women with advanced age. We show that advanced paternal age is also associated with an increased risk of spontaneous miscarriage. Although the paternal age effect is less pronounced than that observed with advanced maternal age and residual confounding by maternal age cannot be excluded, it may have implications for preconception counselling of couples comprising an older aged male. Show less
Dijkhuizen, K.; Bustraan, J.; Bogaard, M.E.D. van den; Velthuis, S.I.; Lith, J.M.M. van; Driessen, E.W.; Beaufort, A.J. de 2020
Objectives Postgraduate trainee selection is a high-stakes process. While many studies focused on selection methods and psychometrics, little is known about the influence of selectors' personal... Show moreObjectives Postgraduate trainee selection is a high-stakes process. While many studies focused on selection methods and psychometrics, little is known about the influence of selectors' personal values and beliefs in the judgment and decision-making process. A better understanding of these factors is vital since selectors determine the future workforce. Methods We interviewed programme directors (PDs) from 11 specialties in one University Hospital. Thematic analysis was conducted with a combined approach of generic and in-vivo coding. Results PDs value excellence, 'fit' and personal characteristics. The content of these values are subject to personal interpretation and differ between PDs. PDs use various 'proxies' as alternative indicators of performance. They consider intuition, teamwork and autonomy important in judgement and decision-making. PDs find selection challenging and feel great accountability towards candidates and society. Conclusions Selectors criteria of judgement- and decision-making often remain implicit and focus on prior achievements and 'fit' with the current trainee-pool, possibly compromising the workforce's diversity. Implicit 'proxies' and intuitive decision-making may be an unwitting source of judgemental bias. 'Making the implicit explicit', by increasing awareness of personal values and beliefs and structuring the selection interview, may improve the quality of trainee selection. Show less
Objective Congenital heart defects (CHD) are still missed frequently in prenatal screening programs, which can result in severe morbidity or even death. The aim of this study was to evaluate the... Show moreObjective Congenital heart defects (CHD) are still missed frequently in prenatal screening programs, which can result in severe morbidity or even death. The aim of this study was to evaluate the quality of fetal heart images, obtained during the second-trimester standard anomaly scan (SAS) in cases of CHD, to explore factors associated with a missed prenatal diagnosis. Methods In this case-control study, all cases of a fetus born with isolated severe CHD in the Northwestern region of The Netherlands, between 2015 and 2016, were extracted from the PRECOR registry. Severe CHD was defined as need for surgical repair in the first year postpartum. Each cardiac view (four-chamber view (4CV), three-vessel (3V) view and left and right ventricular outflow tract (LVOT, RVOT) views) obtained during the SAS was scored for technical correctness on a scale of 0 to 5 by two fetal echocardiography experts, blinded to the diagnosis of CHD and whether it was detected prenatally. Quality parameters of the cardiac examination were compared between cases in which CHD was detected and those in which it was missed on the SAS. Regression analysis was used to assess the association of sonographer experience and of screening-center experience with the cardiac examination quality score.Results A total of 114 cases of isolated severe CHD at birth were analyzed, of which 58 (50.9%) were missed and 56 (49.1%) were detected on the SAS. The defects comprised transposition of the great arteries (17%), aortic coarctation (16%), tetralogy of Fallot (10%), atrioventricular septal defect (6%), aortic valve stenosis (5%), ventricular septal defect (18%) and other defects (28%). No differences were found in fetal position, obstetric history, maternal age or body mass index (BMI) or gestational age at examination between missed and detected cases. Ninety-two cases had available cardiac images from the SAS. Compared with the detected group, the missed group had significantly lower cardiac examination quality scores (adequate score (>= 12) in 32% vs 64%; P=0.002), rate of proper use of magnification (58% vs 84%; P=0.01) and quality scores for each individual cardiac plane (4CV (2.7 vs 3.9; P<0.001), 3V view (3.0 vs 3.8; P=0.02), LVOT view (1.9 vs 3.3; P<0.001) and RVOT view (1.9 vs 3.3; P<0.001)). In 49% of missed cases, the lack of detection was due to poor adaptational skills resulting in inadequate images in which the CHD was not clearly visible; in 31%, the images showed an abnormality (mainly septal defects and aortic arch anomalies) which had not been recognized at the time of the scan; and, in 20%, the cardiac planes had been obtained properly but showed normal anatomy. Multivariate regression analysis showed that the volume of SAS performed per year by each sonographer was associated significantly with quality score of the cardiac examination.Conclusions A lack of adaptational skills when performing the SAS, as opposed to circumstantial factors such as BMI or fetal position, appears to play an important role in failure to detect CHD prenatally. The quality of the cardiac views was inadequate significantly more often in undetected compared with detected cases. Despite adequate quality of the images, CHD was not recognized in 31% of cases. A high volume of SAS performed by each sonographer in a large ultrasound center contributes significantly to prenatal detection. In 20% of undetected cases, CHD was not visible even though the quality of the images was good. (c) 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology. Show less
Purpose Congenital heart defects (CHD) are associated with genetic syndromes. Rapid aneuploidy testing and chromosome microarray analysis (CMA) are standard care in fetal CHD. Many genetic... Show morePurpose Congenital heart defects (CHD) are associated with genetic syndromes. Rapid aneuploidy testing and chromosome microarray analysis (CMA) are standard care in fetal CHD. Many genetic syndromes remain undetected with these tests. This cohort study aims to estimate the frequency of causal genetic variants, in particular structural chromosome abnormalities and sequence variants, in fetuses with severe CHD at mid-gestation, to aid prenatal counselling. Methods Fetuses with severe CHD were extracted from the PRECOR registry (2012-2016). We evaluated pre- and postnatal genetic testing results retrospectively to estimate the frequency of genetic diagnoses in general, as well as for specific CHDs. Results 919 fetuses with severe CHD were identified. After exclusion of 211 cases with aneuploidy, a genetic diagnosis was found in 15.7% (111/708). These comprised copy number variants in 9.9% (70/708). In 4.5% (41/708) sequence variants were found that would have remained undetected with CMA. Interrupted aortic arch, pulmonary atresia with ventricular septal defect and atrioventricular septal defect were most commonly associated with a genetic diagnosis. Conclusion In case of normal CMA results, parents should be offered exome sequencing sequentially, if time allows for it, especially if the CHD is accompanied by other structural malformations due to the large variety in genetic syndromes. Show less
