Peroperative administration of tranexamic acid in sleeve gastrectomy to reduce hemorrhage: a double-blind randomized controlled trial.

INTRODUCTION: In metabolic surgery, hemorrhage is the most common major complication. This study investigated whether peroperative administration of tranexamic acid (TXA) reduced the risk of hemorrhage in patients undergoing laparoscopic sleeve gastrectomy (SG). METHODS: In this double-blind randomized controlled trial, patients undergoing primary SG in a high-volume bariatric hospital were randomized (1:1) to receive 1500-mg TXA or placebo peroperatively. Primary outcome measure was peroperative staple line reinforcement using hemostatic clips. Secondary outcome measures were peroperative fibrin sealant use and blood loss, postoperative hemoglobin, heart rate, pain, major and minor complications, length of hospital stay (LOS), side effects of TXA (i.e., venous thrombotic event (VTE)) and mortality. RESULTS: In total, 101 patients were analyzed and received TXA (n = 49) or placebo (n = 52). There was no statistically significant difference in hemostatic clip devices used in both groups (69% versus 83%, p = 0.161). TXA administration showed significant positive changes in hemoglobin levels (millimoles per Liter; 0.55 versus 0.80, p = 0.013), in heart rate (beats per minute; -4.6 versus 2.5; p = 0.013), in minor complications (Clavien-Dindo ≤ 2, 2.0% versus 17.3%, p = 0.016), and in mean LOS (hours; 30.8 versus 36.7, p = 0.013). One patient in the placebo-group underwent radiological intervention for postoperative hemorrhage. No VTE or mortality was reported. CONCLUSION: This study did not demonstrate a statistically significant difference in use of hemostatic clip devices and major complications after peroperative administration of TXA. However, TXA seems to have positive effects on clinical parameters, minor complications, and LOS in patients undergoing SG, without increasing the risk of VTE. Larger studies are needed to investigate the effect of TXA on postoperative major complications.

Using ethnographic film in tackling podoconiosis.

BACKGROUND: Ethiopia has one of the worst podoconiosis rates in the world, affecting >1.5 million patients. We present our ethnographic film 'Tigist, the story of a girl with podoconiosis' and its potential use in tackling podoconiosis. METHODS: We conducted visual ethnography, consisting of video-recorded participant observations and interviews with seven patients, three healthcare workers and two podoconiosis experts. RESULTS: We acquired video recordings of social moments, the state of podoconiosis patients' bodies and minds, their emotions and the impact of poverty. CONCLUSIONS: Our film allows for an intensified understanding of patients' daily experiences with podoconiosis, potentially impacting care, awareness and medical teaching programs.

Effects of standard v. very long Roux limb Roux-en-Y gastric bypass on nutrient status: a 1-year follow-up report from the Dutch Common Channel Trial (DUCATI) Study.

Laparoscopic Roux-en-Y gastric bypass (RYGB) is considered the 'gold standard' for surgical treatment of morbid obesity. It is hypothesised that reducing the length of the common limb positively affects the magnitude and preservation of weight loss but may also impose a risk of malnutrition. The aim of this study was to compare patients' nutrient and vitamin deficiencies in standard RYGB with a very long Roux limb RYGB (VLRL-RYGB). This study was part of the multicentre randomised controlled trial (Dutch Common Channel Trial), including 444 patients undergoing an RYGB or a VLRL-RYGB. Laboratory results, use of multivitamin supplements and reoperations were collected at baseline and 1 year postoperative. Primary outcome measure was nutrient deficiency after 1 year postoperative. Secondary outcome measure was the reoperation rate due to malabsorption. In total, 227 patients underwent RYGB and 196 patients underwent VLRL-RYGB. Most common deficiencies at 1 year postoperative were ferritin (17·2-18·2 %), Fe (23·4-35·6 %), K (7·4-15·2 %), vitamin B12 (9·0-9·9 %) and vitamin D (22·7-34·5 %). Patients undergoing VLRL-RYGB had slightly but significantly lower levels of Ca, Fe and vitamin D compared with those undergoing RYGB at 1 year postoperative, but significantly higher levels of folic acid and Na. Reoperation rates due to malabsorption were not significantly different between RYGB (2/227, 0·9 %) and VLRL-RYGB (7/196, 3·6 %) (P = 0·088). We concluded that patients undergoing VLRL-RYGB had significantly lower levels of Ca, Fe and vitamin D compared with those undergoing RYGB at 1 year postoperative, but higher levels of folic acid and Na. Reoperation rates did not differ. Close monitoring on nutrient deficiencies should be performed in patients undergoing VLRL-RYGB.

A Single-Center Comparison of Extended and Restricted THROMBOPROPHYLAXIS with LMWH after Metabolic Surgery.

INTRODUCTION: Morbid obesity is an important risk factor for developing a venous thromboembolic events (VTE) after surgery. Fast-track protocols in metabolic surgery can lower the risk of VTE in the postoperative period by reducing the immobilization period. Administration of thromboprophylaxis can be a burden for patients. This study aims to compare extended to restricted thromboprophylaxis with low molecular weight heparin (LMWH) for patients undergoing metabolic surgery. METHODS: In this single center retrospective cohort study, data was collected from patients undergoing a primary Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) between 2014 and 2018. Patients operated in 2014-2017 received thromboprophylaxis for two weeks. In 2018, patients only received thromboprophylaxis during hospital admission. Patients already using anticoagulants were analyzed as a separate subgroup. The primary outcome measure was the rate of clinically significant VTEs within three months. Secondary outcome measures were postoperative hemorrhage and reoperations for hemorrhage. RESULTS: 3666 Patients underwent a primary RYGB or SG following the fast-track protocol. In total, two patients in the 2014-2017 cohort were diagnosed with VTE versus zero patients in the 2018 cohort. In the historic group, 34/2599 (1.3%) hemorrhages occurred and in the recent cohort 8/720 (1.1%). Postoperative hemorrhage rates did not differ between the two cohorts (multivariable analysis, p = 0.475). In the subgroup of patients using anticoagulants, 21/347(6.1%) patients developed a postoperative hemorrhage. Anticoagulant use was a significant predictor of postoperative hemorrhage (p < 0.001). CONCLUSION: Despite the restricted use of thromboprophylaxis administration since 2018, the rate of VTEs did not increase. This may be explained by quick mobilization and hospital discharge, as encouraged by the fast-track protocol. There was no significant difference in postoperative hemorrhage rates by thromboprophylaxis protocol. Short term use of thromboprophylaxis in metabolic surgery is safe in patients at low risk of VTE.

Total pregnancy loss after chorionic villus sampling and amniocentesis: a cohort study.

OBJECTIVES: To identify maternal-, operator- and procedure-related variables that affect procedure-related pregnancy loss after transcervical (TC) and transabdominal (TA) chorionic villus sampling (CVS) and amniocentesis and to estimate the rates of spontaneous and procedure-related loss in comparable subgroups of women. METHODS: This was a retrospective cohort study conducted at the University Medical Center Groningen and the Academic Medical Center, The Netherlands. Databases of both centers were searched to identify singleton pregnancies that had undergone a combined test and/or anomaly scan at around 20 weeks' gestation, or an invasive procedure (CVS and/or amniocentesis) between January 2001 and December 2011. Maternal characteristics, obstetric history, technical aspects of the invasive procedure, ultrasound examinations and fetal and neonatal outcomes were available for 29 201 cases. Women were categorized, according to the type of examination they had received, into the following five groups: first-trimester combined test (and 20-week anomaly scan); 20-week anomaly scan only; CVS; amniocentesis; amniocentesis after unsuccessful CVS. Rates of fetal loss were compared between groups. RESULTS: Variables significantly associated with a higher rate of fetal loss were, for CVS, repeat attempts during the procedure, use of TC cannula instead of biopsy forceps, gestational age at procedure ≥ 13 weeks and a pregnancy after assisted reproductive techniques, and, for amniocentesis, if indication was fetal anomaly or family history of anomalies and repeat attempts during the procedure. In women aged ≥ 36 years who did not undergo an invasive procedure, spontaneous fetal loss rate (FLR) after first-trimester combined test was 1.40%, whereas after CVS, FLR was 2.76% and 2.43% for a TC and TA approach, respectively. The additional risk of fetal loss with TC-CVS was therefore 1.36% (1 : 74), which varied according to the instrument used (0.27% for forceps and 3.12% for cannula), and with TA-CVS was 1.03% (1 : 97). In women aged ≥ 36 years who underwent a 20-week anomaly scan only, spontaneous FLR was 0.63%. In women who underwent amniocentesis solely because of advanced maternal age, FLR was 1.11%. The additional risk of fetal loss with amniocentesis was 0.48% (1 : 208). CONCLUSION: The total rate of procedure-related fetal loss after TA- and TC-CVS and amniocentesis appears lower than the risks on which women are currently counseled. There was a trend for a decrease in risk when the level of experience of the operator increased. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Evaluation of new laboratory tests to discriminate bacterial from nonbacterial chronic obstructive pulmonary disease exacerbations.

INTRODUCTIONS: Discriminating bacterial from nonbacterial acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is difficult, causing antibiotics overuse and bacterial resistance. Sputum cultures are of limited use because results take time. In our hospital, only leukocyte concentration and CRP are laboratory parameters evaluated in AECOPD. We evaluated additional tests to discriminate bacterial vs. nonbacterial AECOPD: 5-part leukocyte differentiation (hematology analyzer), leukocyte differentiation using flow cytometry (Leukoflow, Cytodiff), Leuko64 kit, and procalcitonin. METHODS: Retrospectively, patients were classified as bacterial or nonbacterial AECOPD. ROC analyses tested how the additional tests discriminate these groups. RESULTS: Twenty-two AECOPD were classified as bacterial and 23 as nonbacterial. From the additional tests, basophil percentage (Cytodiff) has superior AUC (0.800). At a cutoff resulting in ≥90% sensitivity, neutrophil/lymphocyte ratio (AUC:0.755) and CD4-positive T cells (Leukoflow, AUC:0.747) have the highest specificity (57%). Both neutrophil mean volume and standard deviation (Cell Population Data, DxH800 hematology analyzer) had good combined sensitivity and specificity (AUC:0.846/0.804, 91% sensitivity, 69% specificity). Addition of leukocyte populations and procalcitonin to CRP in regression models (AUC: 0.907/0.876/0.890) increased specificity compared to CRP alone (71% or 73% vs. 39%). CONCLUSION: No additional test has sufficient accuracy on its own to predict bacterial AECOPD. Combining CRP with several parameters from the additional tests may improve this.

Perinatal outcomes in gestational diabetes in relation to ethnicity in the Netherlands.

BACKGROUND: The influence of ethnicity in women with gestational diabetes in relation to maternal, pregnancy and neonatal outcome is not well defined. AIM: To compare the perinatal outcome in women with gestational diabetes between different ethnic groups reflecting the multi-ethnic population in the Netherlands. METHODS: Patients with gestational diabetes (n = 388) who visited the multidisciplinary outpatient clinic for Diabetes Care and Obstetrics of the Sint Franciscus Gasthuis in Rotterdam between 2010 and 2013 were included. Ethnicity was distinguished into six groups: Moroccan (n = 100); Turkish (n = 43); Caucasian (n = 146); Suriname-Creole (n = 23); Suriname-Hindu (n = 32); and Miscellaneous (n = 44). RESULTS: Caucasians were the largest group with gestational diabetes (37.7%), followed by Moroccans (25.8%). Body mass index before pregnancy was highest in Surinamese-Creole women, followed by Turks and Moroccans (p < 0.001). Gravidity and parity were highest in Moroccans. Gravidity was lowest in Surinamese-Hindus and parity was lowest in Caucasians (p < 0.001). There was also a remarkable, significant difference in the mode of delivery between the ethnicities with the lowest number of normal deliveries in Caucasians and the highest in Moroccans (p = 0.03). Assisted delivery occurred most frequently in Caucasian women, although there was no difference in the frequency of caesarean sections. Birth weight was the only neonatal parameter showing significant differences between the ethnicities, with the highest birth weight for Moroccan children and the lowest for Surinamese children (3542 g vs. 3200; p = 0.001). CONCLUSION: This study did not show major differences in maternal or neonatal complications, however there are significant disparities in (percentile) birth weight and mode of delivery across the different ethnic groups.

An antenatal prediction model for adverse birth outcomes in an urban population: The contribution of medical and non-medical risks.

OBJECTIVES: in the Netherlands the perinatal mortality rate is high compared to other European countries. Around eighty percent of perinatal mortality cases is preceded by being small for gestational age (SGA), preterm birth and/or having a low Apgar-score at 5 minutes after birth. Current risk detection in pregnancy focusses primarily on medical risks. However, non-medical risk factors may be relevant too. Both non-medical and medical risk factors are incorporated in the Rotterdam Reproductive Risk Reduction (R4U) scorecard. We investigated the associations between R4U risk factors and preterm birth, SGA and a low Apgar score. DESIGN: a prospective cohort study under routine practice conditions. SETTING: six midwifery practices and two hospitals in Rotterdam, the Netherlands. PARTICIPANTS: 836 pregnant women. INTERVENTIONS: the R4U scorecard was filled out at the booking visit. MEASUREMENTS: after birth, the follow-up data on pregnancy outcomes were collected. Multivariate logistic regression was used to fit models for the prediction of any adverse outcome (preterm birth, SGA and/or a low Apgar score), stratified for ethnicity and socio-economic status (SES). FINDINGS: factors predicting any adverse outcome for Western women were smoking during the first trimester and over-the-counter medication. For non-Western women risk factors were teenage pregnancy, advanced maternal age and an obstetric history of SGA. Risk factors for high SES women were low family income, no daily intake of vegetables and a history of preterm birth. For low SES women risk factors appeared to be low family income, non-Western ethnicity, smoking during the first trimester and a history of SGA. KEY CONCLUSIONS: the presence of both medical and non-medical risk factors early in pregnancy predict the occurrence of adverse outcomes at birth. Furthermore the risk profiles for adverse outcomes differed according to SES and ethnicity. IMPLICATIONS FOR PRACTICE: to optimise effective risk selection, both medical and non-medical risk factors should be taken into account in midwifery and obstetric care at the booking visit.

Adherence to cardiovascular prevention strategies in patients with rheumatoid arthritis.

OBJECTIVES: Patients with rheumatoid arthritis (RA) have a high risk of cardiovascular disease (CVD). Recent national and international guidelines suggest strict treatment of CVD risk factors in RA. The aim of this study was to evaluate the self-reported adherence to CV prevention strategies in patients with RA. METHOD: RA patients visiting an outpatient clinic for strict CVD risk management received a validated questionnaire to evaluate adherence to CV prevention strategies. Strict treatment targets were defined and lifestyle recommendations were given following a prespecified protocol. CVD risk was assessed using the SCORE algorithm. RESULTS: In total, 111 questionnaires were returned (response rate of 82%). A high 10-year CVD risk (≥ 20%) was present in 53%, but only 3% thought they had an increased CVD risk. A total of 53% of patients reported that they 'follow the doctors' suggestions exactly' and 75% reported finding it 'easy to follow the suggestions'. Of the 69% of patients who were prescribed lipid- and/or blood pressure-lowering drugs, 90% reported taking all prescribed tablets. The advice to follow a diet was given to 42%, of whom 68% said they followed the advised diet. Physical exercise was advised to 67%, of whom 62% said they performed specific physical exercise on at least 3 days a week. The adherence to lifestyle recommendations was not significantly different across the CVD risk groups. CONCLUSIONS: RA patients tend to underestimate their CVD risk. The self-reported adherence of RA patients to CVD risk management was high concerning pharmaceutical interventions and moderate in the case of lifestyle interventions.

Vitamin D3 mediated effects on postprandial leukocyte activation and arterial stiffness in men and women.

Postprandial inflammation is considered to be pro-atherogenic. Vitamin D can reduce inflammation and arterial stiffness. We hypothesized that vitamin D3 improves postprandial arterial elasticity by the modulation of leukocyte activation. Healthy volunteers underwent two oral fat-loading tests (OFLTs). The augmentation index (AIx) and flow cytometric quantification of leukocyte activation markers were measured. After the first OFLT, 100 000 IU of vitamin D3 was administered and a second OFLT was carried out 7 days later. Six men and six women were included. A favorable reduction in AIx was found after vitamin D3 supplementation (P=0.042) in both genders. After vitamin D3, exclusively in women a reduction in the area under the postprandial curve for monocytes CD11b and CD35 by 10.5% (P=0.016) and 12.5% (P=0.04) and neutrophil CD11b by 17.0% (P=0.014) was observed. In conclusion, vitamin D3 probably increased postprandial arterial elasticity in men and women, but reduced postprandial leukocyte activation exclusively in women.

Quantitative ultrasound of the heel as triage test to measure bone mineral density compared with dual energy X-ray absorptiometry in men with prostate cancer commencing with androgen deprivation therapy.

OBJECTIVE: Androgen deprivation therapy (ADT) puts patients at an increased risk of developing osteoporosis. Assessment of bone mineral density (BMD) is most commonly performed by dual energy X-ray absorptiometry (DXA). Alternative ways of estimating BMD, such as quantitative ultrasound (QUS) measurement of the heel, are explored as DXA is expensive, non-portable and uses ionising radiation. We therefore investigated the diagnostic value of QUS as compared with DXA in patients commencing ADT. METHODS: In this cross-sectional study of 60 patients with prostate cancer who were about to start ADT, BMD was measured with DXA and QUS. The fracture risk score, as implemented by the Dutch National Osteoporosis Guideline, was also measured. RESULTS: No significant correlations were found between the separate DXA T scores and worst DXA T score, and the QUS T scores. Correlations between DXA T scores/QUS scores and fracture risk score were also non-significant. If QUS had been used as a screening tool, with a threshold of T ≤ -0.5 to perform DXA, then relevant osteopenia/osteoporosis (worst DXA T score ≤ -2.0) would have been missed in 1/18 (5.6%) patients. The negative predictive value is 0.95. Using QUS as a screening test prior to DXA and a QUS threshold T score ≤ -0.5 would avoid 21 (35%) DXA scans at the cost of missing one (5.6%) case. CONCLUSION: QUS testing cannot replace DXA scans fully as a diagnostic test. However, QUS can be incorporated as triage test prior to DXA to reduce the need for unnecessary DXA scans and the associated costs.

Intra-operator and inter-operator reliability of manual and semiautomated measurement of fetal nuchal translucency: a cross sectional study.

OBJECTIVE: The goal of this study was to examine the intra-operator and inter-operator differences of the manual and semiautomated nuchal translucency (NT) measurements and to evaluate if these differences alter women's risk status. METHODS: A cross sectional study was performed. Two operators obtained manual and semiautomated NT measurements of 153 NT images. The maximal acceptable difference in NT measurements within and between operators was 0.15 mm. Intra and inter-operator differences were analyzed by the paired Student's t-test and homogeneity of variances by the Levene's test. Intra-operator and inter-operator agreement were quantified with Bland and Altman's limits of agreement, and changes in women's risk status were tested with the binomial test. RESULTS: Intra-operator agreement was high for each of the measurement methods. Operator 1 had lower SDS for manual measurements. Conversely, operator 2 had lower SDS of the differences for semiautomated measurements, although the SD never reached the same level as operator 1. Inter-operator agreement was highest for the semiautomated measurements. Changes in risk status occurred between the manual and inner-middle method resulting in different clinical policies in up to 1 out of 20 cases. CONCLUSION: Well-trained operators do not seem to benefit from the use of the semiautomated measurement methods.

Decreased excitability of the distal motor nerve of young patients with type 1 diabetes mellitus.

OBJECTIVE: The compound muscle action potential (CMAP) scan is a novel neurophysiological technique that appears more sensitive in detecting peripheral motor neuropathy than conventional methods. This study explores the value of the CMAP scan for the detection of subclinical diabetic peripheral motor neuropathy. METHODS: In this cross-sectional pilot study, CMAP scanning of the peroneal nerve was performed in (i) 13 well-controlled patients (8-25 yr old) with type 1 diabetes mellitus (T1DM) duration between 2.5 and 5 yr; (ii) 17 patients (10-25 yr old) with a duration of T1DM of at least 10 yr, poorly controlled and/or with microvascular complications and (iii) 13 adults with T1DM and established clinical diabetic peripheral neuropathy (DPN). Various CMAP scan variables, including measures of axonal excitability and axonal loss and reinnervation, were compared between patients and healthy controls. RESULTS: Axonal excitability was significantly decreased in the young patient groups as compared to their controls. The CMAP scan measures of axonal loss and reinnervation differed only between patients with clinical DPN and their controls. CONCLUSIONS: Motor nerve axonal excitability seems to be reduced early in T1DM, even in well-controlled young patients, and probably before (irreversible) axonal damage occurs. These changes can be measured by the CMAP scan, which makes this a promising tool for detecting nerve dysfunction in T1DM.

Determinants of the intention of preconception care use: lessons from a multi-ethnic urban population in the Netherlands.

OBJECTIVES: To investigate the determinants of the intention of preconception care use of women in a multi-ethnic urban population. METHODS: The ASE-model-a health behaviour model-was used as an explanatory framework. A representative sample was taken from the municipal population registers of two districts in Rotterdam, the Netherlands, 2009-2010. 3,225 women (aged 15-60 years) received a questionnaire, which was returned by 631: 133 Dutch, 157 Turkish and Moroccan, and 341 Surinamese and Antillean. Descriptive, univariate and multivariate analyses were performed. RESULTS: The multiple logistic analyses showed that intention to attend preconception care was significantly higher in women with a Turkish and Moroccan background (ß 1.02, P = 0.006), a higher maternal age (ß 0.04, P = 0.008) and a positive attitude (ß 0.50, P < 0.001). Having no relationship (ß -1.16, P = 0.004), multiparity with previous adverse perinatal outcome (ß -1.32, P = 0.001), a high educational level (ß -1.23, P = 0.03), having paid work (ß -0.72, P = 0.01) and experienced barriers level (ß -0.15, P = 0.003) were associated with less intention to use preconception care. CONCLUSIONS: Modifiable determinants as attitude and barriers can be addressed to enhance preconception care attendance.

An urban perinatal health programme of strategies to improve perinatal health.

Promotion of a healthy pregnancy is a top priority of the health care policy in many European countries. Perinatal mortality is an important indicator of the success of this policy. Recently, it was shown that the Netherlands has relatively high perinatal death rates when compared to other European countries. This is in particular true for large cities where perinatal mortality rates are 20-50% higher than elsewhere. Consequently in the Netherlands, there is heated debate on how to tackle these problems. Without the introduction of measures throughout the entire perinatal health care chain, pregnancy outcomes are difficult to improve. With the support of health care professionals, the City of Rotterdam and the Erasmus University Medical Centre have taken the initiative to develop an urban perinatal health programme called 'Ready for a Baby'. The main objective of this municipal 10-year programme is to improve perinatal health and to reduce perinatal mortality in all districts to at least the current national average of l0 per 1000. Key elements are the understanding of the mechanisms of the large health differences between women living in deprived and non-deprived urban areas. Risk guided care, orientation towards shared-care and improvement of collaborations between health care professionals shapes the interventions that are being developed. Major attention is given to the development of methods to improve risk-selection before and during pregnancy and methods to reach low-educated and immigrant groups.

Defective deacetylation of histone 4 K12 in human oocytes is associated with advanced maternal age and chromosome misalignment.

BACKGROUND: Chromosome segregation errors during human oocyte meiosis are associated with low fertility in humans and the incidence of these errors increases with advancing maternal age. Studies of mitosis and meiosis suggest that defective remodeling of chromatin plays a causative role in aneuploidy. We analyzed the histone deacetylation pattern during the final stages of human oocyte maturation to investigate whether defective epigenetic regulation of chromatin remodeling in human oocytes is related to maternal age and leads to segregation errors. METHODS: Human surplus oocytes of different meiotic maturation stages [germinal vesicle (GV), metaphase (M)I and MII] were collected from standard IVF/ICSI treatments. Oocytes were analyzed for acetylation of different lysines of histone 4 (H4K5, H4K8, H4K12 and H4K16) and for α-tubulin. RESULTS: Human GV oocytes had an intense staining of the chromatin for all four histone 4 lysine acetylations. MI and MII stage oocytes showed either normal deacetylation or various amounts of defective histone deacetylation. Residual H4K12 acetylation was more frequently found in oocytes obtained from older women, with a significant correlation between defective deacetylation and maternal age (r = 0.185, P = 0.007). Eighty-eight percent of the oocytes with residual acetylation had misaligned chromosomes, whereas only 33% of the oocytes that showed correct deacetylated chromatin had misaligned chromosomes (P < 0.001). CONCLUSIONS: We conclude that defective deacetylation during human female meiosis increases with maternal age and is correlated with misaligned chromosomes. As chromosome misalignment predisposes to segregation errors, our data imply that defective regulation of histone deacetylation could be an important factor in age-related aneuploidy.

Individualized choice in prenatal diagnosis: the impact of karyotyping and standalone rapid aneuploidy detection on quality of life.

OBJECTIVE: To assess the reasons and perceptions of women who are offered a choice between karyotyping and standalone rapid aneuploidy detection (RAD) and to compare the impact of both tests on anxiety and health-related quality of life. METHODS: In this prospective comparative study, women undergoing amniocentesis on behalf of their age or for an increased Down syndrome risk were offered a choice between karyotyping (group 1, n = 68) and standalone RAD (group 2, n = 61). Follow-up was 9 weeks post amniocentesis. RESULTS: The most commonly cited reason for choosing karyotyping was obtaining as much information as possible, while for choosing standalone RAD, it was the short waiting time. Prenatal screening (OR 7.09), no knowledge of karyotyping (OR 4.2), and an intermediate perceived risk for chromosomal abnormalities (OR 3.6) were associated with choosing standalone RAD. There were no systematic differences in time of karyotyping and standalone RAD in terms of anxiety (P = 0.11), generic physical and mental health (P = 0.94, 0.52; P = 0.66, 0.07), personal perceived control (PPC; P = 0.69), and stress (P = 0.66). CONCLUSION: Offering a choice between karyotyping and standalone RAD does not influence anxiety, stress, PPC, or generic health. Individual choice in prenatal diagnosis meets individual needs and thereby could reduce anxiety and stress.

Aiming at multidisciplinary consensus: what should be detected in prenatal diagnosis?

OBJECTIVE: To determine expert consensus on which chromosomal abnormalities should and should not be detected in prenatal diagnosis, and for which abnormalities disagreement remains after structured discussion. METHODS: An expert panel of 24 prenatal experts (8 clinical cytogeneticists, 8 clinical geneticists and 8 obstetricians) rated 15 chromosomal abnormalities sampled from a nationwide study on rapid aneuploidy detection (RAD). In two individual anonymous rating rounds and one group meeting, the participants rated PRO or AGAINST detection and stated their main argument. The 15 chromosomal abnormalities were described in detail by a stylized vignette containing an obstetrical history, the indication for prenatal diagnosis and the range of possible outcomes of the chromosomal abnormality. Consensus was defined to be present if at least 80% of the experts agreed. RESULTS: Consensus was reached in 12 out of 15 cases. In ten cases, there was agreement PRO detection and in two cases experts agreed AGAINST detection. At the end of the third round, dissensus remained on three abnormalities. CONCLUSION: Experts largely agreed on detecting chromosomal abnormalities with severe consequences and AGAINST detection in case of irrelevant clinical consequences. For chromosomal abnormalities with mild or uncertain outcomes, dissensus remained. None of the currently available tests corresponds to these demands.