The Dutch multidisciplinary guideline osteoporosis and fracture prevention, taking a local guideline to the international arena

Background: In 2018, a grant was provided for an evidence-based guideline on osteoporosis and fracture prevention based on 10 clinically relevant questions. Methods: A multidisciplinary working group was formed with delegates from Dutch scientific and professional societies, including representatives from the patient’s organization and the Dutch Institute for Medical Knowledge. The purpose was to obtain a broad consensus among all participating societies to facilitate the implementation of the updated guideline. Results: Novel recommendations in our guideline are as follows: - In patients with an indication for DXA of the lumbar spine and hips, there is also an indication for VFA. - Directly starting with anabolic drugs (teriparatide or romosozumab) in patients with a very high fracture risk; - Directly starting with zoledronic acid in patients 75 years and over with a hip fracture (independent of DXA); - Directly starting with parenteral drugs (denosumab, teriparatide, zoledronic acid) in glucocorticoid-induced osteoporosis with very high fracture risk; - A lifelong fracture risk management, including lifestyle, is indicated from the start of the first treatment. Conclusion: In our new multidisciplinary guideline osteoporosis and fracture prevention, we developed 5 “relatively new statements” that are all a crucial step forward in the optimization of diagnosis and treatment for fracture prevention. We also developed 5 flowcharts, and we suppose that this may be helpful for individual doctors and their patients in daily practice and may facilitate implementation.</p

Screening ethnically diverse human embryonic stem cells identifies a chromosome 20 minimal amplicon conferring growth advantage

The International Stem Cell Initiative analyzed 125 human embryonic stem (ES) cell lines and 11 induced pluripotent stem (iPS) cell lines, from 38 laboratories worldwide, for genetic changes occurring during culture. Most lines were analyzed at an early and late passage. Single-nucleotide polymorphism (SNP) analysis revealed that they included representatives of most major ethnic groups. Most lines remained karyotypically normal, but there was a progressive tendency to acquire changes on prolonged culture, commonly affecting chromosomes 1, 12, 17 and 20. DNA methylation patterns changed haphazardly with no link to time in culture. Structural variants, determined from the SNP arrays, also appeared sporadically. No common variants related to culture were observed on chromosomes 1, 12 and 17, but a minimal amplicon in chromosome 20q11.21, including three genes expressed in human ES cells, ID1, BCL2L1 and HM13, occurred in >20% of the lines. Of these genes, BCL2L1 is a strong candidate for driving culture adaptation of ES cells

A core outcome set for pre‐eclampsia research: an international consensus development study

Objective To develop a core outcome set for pre‐eclampsia. Design Consensus development study. Setting International. Population Two hundred and eight‐one healthcare professionals, 41 researchers and 110 patients, representing 56 countries, participated. Methods Modified Delphi method and Modified Nominal Group Technique. Results A long‐list of 116 potential core outcomes was developed by combining the outcomes reported in 79 pre‐eclampsia trials with those derived from thematic analysis of 30 in‐depth interviews of women with lived experience of pre‐eclampsia. Forty‐seven consensus outcomes were identified from the Delphi process following which 14 maternal and eight offspring core outcomes were agreed at the consensus development meeting. Maternal core outcomes: death, eclampsia, stroke, cortical blindness, retinal detachment, pulmonary oedema, acute kidney injury, liver haematoma or rupture, abruption, postpartum haemorrhage, raised liver enzymes, low platelets, admission to intensive care required, and intubation and ventilation. Offspring core outcomes: stillbirth, gestational age at delivery, birthweight, small‐for‐gestational‐age, neonatal mortality, seizures, admission to neonatal unit required and respiratory support. Conclusions The core outcome set for pre‐eclampsia should underpin future randomised trials and systematic reviews. Such implementation should ensure that future research holds the necessary reach and relevance to inform clinical practice, enhance women's care and improve the outcomes of pregnant women and their babies

Prediction of recurrence of hypertensive disorders of pregnancy in the term period, a retrospective cohort study

Objectives: To assess the recurrence risk of term hypertensive disease of pregnancy and to determine which potential risk factors are predictive of recurrence. Study design: We performed a retrospective cohort study in two secondary and one tertiary care hospitals in the Netherlands. We identified women with a hypertensive disorder in the index pregnancy and delivery after 37 weeks of gestation between January 2000 and December 2002. Data were extracted from medical files and women were approached for additional information on subsequent pregnancies. Adverse outcome was defined as recurrence of a hypertensive disorder in the next subsequent pregnancy. Main outcome measures: The absolute risk of recurrence and a prediction model containing demographic and clinical factors predictive of recurrence. Results: We identified 638 women for potential inclusion, of whom 503 could be contacted. Of these women, 312 (62%) had a subsequent pregnancy. Hypertensive disorders recurred in 120 (38%, 95% CI 33-44) women, of whom 15 (5%, 95% CI 3-7) delivered preterm. Women undergoing recurrence were more at risk to develop chronic hypertension after pregnancy (35% versus 16%, OR 2.8, 95% CI 1.5-5.3). Body mass index, non-White European origin, chronic hypertension, maximum diastolic blood pressure, no use of anticonvulsive medication and interpregnancy interval were predictors for recurrence. Conclusions: Women with hypertensive disorders and term delivery have a substantial chance of recurrence, but a small risk of preterm delivery. A number of predictors for recurrence could be identified and women with a recurrence more often developed chronic hypertension. (C) 2014 International Society for the Study of Hypertension in Pregnancy Published by Elsevier B. V. All rights reserve

Cerebrovascular, cardiovascular and renal hypertensive disease after hypertensive disorders of pregnancy

Strong associations have been established in nationwide registry studies between hypertensive disorders of pregnancy (HDP) and later vascular morbidities and mortality. The aim of this case-control study is to examine the interdependent relationships of different predictive factors for vascular disease and HDP, because they are not clearly elucidated due to lack of detail in registries. We assembled three different case groups of women who had cerebrovascular, cardiovascular, or hypertensive kidney disease before the age of 55. The control group consisted of age-matched women who underwent hysterectomy for benign reasons. We assessed the occurrence of HDP in previous pregnancies. The strength of the association with vascular morbidities was tested with multivariable logistic regression in comparison with classic vascular risk factors. In all case groups, previous HDP occurred more frequent than in the control group. In logistic regression analysis, previous HDP were the strongest predictor in the cerebrovascular group (OR 4.2; 95% confidence interval [CI] 1.6-11.0). In the cardiovascular group and the kidney failure group a similar association was found, however, this was not statistically significant (OR 4.4 (95% CI 0.82-4) and 2.9 (95% CI 0.61-14), respectively). Previous hypertensive disorders of pregnancy are a strong predictor for later vascular morbidity. This is partially mediated through the presence of classic vascular risk factors, but our data suggest it is also an independent predicto

Herhaling hypertensieve aandoening tijdens zwangerschap*

To assess the recurrence risk of late preterm hypertensive disease of pregnancy and to determine whether potential risk factors are predictive. Retrospective cohort study. Our study cohort included 425 women with a pregnancy-related hypertensive disorder who had delivered between 34 and 37 weeks of gestation at three different academic and three tertiary care hospitals in the Netherlands during the 2000-2002 period. Data were collected from medical files and by telephone interviews with the women. An adverse outcome was defined as the recurrence of a hypertensive disorder during the subsequent pregnancy. We also designed a prediction model containing demographic and clinical factors predictive for an adverse outcome. Of the 425 women who met the inclusion criteria, 351 could be contacted, of whom 189 (54%) had had a subsequent pregnancy. Pregnancy-related hypertensive disorders had recurred in 96 (51%; 95% CI: 43-58) women. Seventeen women (9%; 95% CI: 5-14) had delivered again before the 37th week. Pre-existing hypertension and maternal age were the strongest predictors for recurrence. Women who had experienced a recurrence had a 9-fold chance of developing chronic hypertension (37 vs. 6%; OR 8.7; 95% CI: 3.3-23). Women with hypertensive disorders and late preterm deliveries have a 50% chance of recurrence of the disorder and a 9% chance of recurrent premature delivery. Women with pre-existing hypertension or who are older are prone to recurrence. Women with a recurrent hypertensive disorder during a subsequent pregnancy often later develop chronic hypertensio

Terminating pregnancy for severe hypertension when the fetus is considered non-viable: a retrospective cohort study

Objective: To investigate frequency and practise of termination of pregnancy for early-onset hypertensive disorders where the fetus is considered to be non-viable. Study design: Retrospective cohort study in all Dutch tertiary perinatal care centres (n = 10), between January 2000 and January 2014. All women who underwent termination of pregnancy, without fetal surveillance or intention to intervene for fetal reasons, for early-onset hypertensive disorders in pregnancy, were analyzed. Women eligible for this study were identified in the local delivery databases. Medical records were used to collect relevant data. Results: Between January 2000 and January 2014, 2,456,584 women delivered in The Netherlands, of which 238,448 (9.7%) in a tertiary care centre. A total of 161 pregnancy terminations (11-12 per year) for severe early-onset preeclampsia were identified, including 6 women with a twin pregnancy. Mean gestational age at termination was 172 days (GA 24(4/7)) +/- 9.4 days. In 70% of cases termination was performed at or shortly after 24 weeks' gestation. 74.5% of women developed HELLP syndrome (n = 96), eclampsia (n = 10) or needed admission to an ICU (n = 14). Birth weight was below 500 gin 64% of cases. In 69% of the cases the estimated fetal weight was within a 10% margin of the actual birth weight. Conclusion: Termination of pregnancy for early-onset hypertensive disorders without intervention for fetal indication occurs approximately 12 times per year in The Netherlands. More data are needed to investigate contemporary best practice regarding termination of pregnancy for early-onset hypertensive indications at the limits of fetal viability. Considering the frequency of maternal complications, termination of pregnancy and not expectant management should be considered for all women presenting with severe early onset hypertensive disorders at the limits of fetal viability. (C) 2016 The Author(s). Published by Elsevier Ireland Ltd

Maternal and neonatal outcomes in women with severe early onset pre-eclampsia before 26 weeks of gestation, a case series

OBJECTIVE: To describe the maternal and neonatal outcomes and prolongation of pregnancies with severe early onset pre-eclampsia before 26 weeks of gestation. DESIGN: Nationwide case series. SETTING: All Dutch tertiary perinatal care centres. POPULATION: All women diagnosed with severe pre-eclampsia who delivered between 22 and 26 weeks of gestation in a tertiary perinatal care centre in the Netherlands, between 2008 and 2014. METHODS: Women were identified through computerised hospital databases. Data were collected from medical records. MAIN OUTCOME MEASURES: Maternal complications [HELLP (haemolysis, elevated liver enzyme levels, and low platelet levels) syndrome, eclampsia, pulmonary oedema, cerebrovascular incidents, hepatic capsular rupture, placenta abruption, renal failure, and maternal death], neonatal survival and complications (intraventricular haemorrhage, retinopathy of prematurity, necrotising enterocolitis, bronchopulmonary dysplasia, and sepsis), and outcome of subsequent pregnancies (recurrent pre-eclampsia, premature delivery, and neonatal survival). RESULTS: We studied 133 women, delivering 140 children. Maternal complications occurred frequently (54%). Deterioration of HELLP syndrome during expectant care occurred in 48%, after 4 days. Median prolongation was 5 days (range: 0-25 days). Neonatal survival was poor (19%), and was worse (6.6%) if the mother was admitted before 24 weeks of gestation. Complications occurred frequently among survivors (84%). After active support, neonatal survival was comparable with the survival of spontaneous premature neonates (54%). Pre-eclampsia recurred in 31%, at a mean gestational age of 32 weeks and 6 days. CONCLUSIONS: Considering the limits of prolongation, women need to be counselled carefully, weighing the high risk for maternal complications versus limited neonatal survival and/or extreme prematurity and its sequelae. The positive prospects regarding maternal and neonatal outcome in future pregnancies can supplement counselling. TWEETABLE ABSTRACT: Severe early onset pre-eclampsia comes with high maternal complication rates and poor neonatal survival