Similar adverse pregnancy outcome in native and nonnative dutch women with pregestational type 2 diabetes:a multicentre retrospective study

Objective. To assess the incidence of adverse pregnancy outcome in native and nonnative Dutch women with pregestational type 2 diabetes (T2D) in a multicenter study in The Netherlands. Methods. Maternal characteristics and pregnancy outcome were retrospectively reviewed and the influence of ethnicity on outcome was evaluated using independent t-test, Mann-Whitney U-test, and chi-square test. Results. 272 pregnant women (80 native and 192 non-native Dutch) with pregestational T2D were included. Overall outcome was unfavourable, with a perinatal mortality of 4.8%, major congenital malformations of 6.3%, preeclampsia of 11%, preterm birth of 19%, birth weight >90th percentile of 32%, and a Caesarean section rate of 42%. In nonnative Dutch women, the glycemic control was slightly poorer and the gestational age at booking somewhat later as compared to native Dutch women. However, there were no differences in incidence of preeclampsia/HELLP, preterm birth, perinatal mortality, macrosomia, and congenital malformations between those two groups. Conclusions. A high incidence of adverse pregnancy outcomes was found in women with pregestational T2D, although the outcome was comparable between native and non-native Dutch women. This suggests that easy access to and adequate participation in the local health care systems contribute to these comparable outcomes, offsetting potential disadvantages in the non-native group

Antenatal allopurinol for reduction of birth asphyxia induced brain damage (ALLO-Trial); a randomized double blind placebo controlled multicenter study

<p>Abstract</p> <p>Background</p> <p>Hypoxic-ischaemic encephalopathy is associated with development of cerebral palsy and cognitive disability later in life and is therefore one of the fundamental problems in perinatal medicine. The xanthine-oxidase inhibitor allopurinol reduces the formation of free radicals, thereby limiting the amount of hypoxia-reperfusion damage. In case of suspected intra-uterine hypoxia, both animal and human studies suggest that maternal administration of allopurinol immediately prior to delivery reduces hypoxic-ischaemic encephalopathy.</p> <p>Methods/Design</p> <p>The proposed trial is a randomized double blind placebo controlled multicenter study in pregnant women at term in whom the foetus is suspected of intra-uterine hypoxia.</p> <p>Allopurinol 500 mg IV or placebo will be administered antenatally to the pregnant woman when foetal hypoxia is suspected. Foetal distress is being diagnosed by the clinician as an abnormal or non-reassuring foetal heart rate trace, preferably accompanied by either significant ST-wave abnormalities (as detected by the STAN-monitor) or an abnormal foetal blood scalp sampling (pH < 7.20).</p> <p>Primary outcome measures are the amount of S100B (a marker for brain tissue damage) and the severity of oxidative stress (measured by isoprostane, neuroprostane, non protein bound iron and hypoxanthine), both measured in umbilical cord blood. Secondary outcome measures are neonatal mortality, serious composite neonatal morbidity and long-term neurological outcome. Furthermore pharmacokinetics and pharmacodynamics will be investigated.</p> <p>We expect an inclusion of 220 patients (110 per group) to be feasible in an inclusion period of two years. Given a suspected mean value of S100B of 1.05 ug/L (SD 0.37 ug/L) in the placebo group this trial has a power of 90% (alpha 0.05) to detect a mean value of S100B of 0.89 ug/L (SD 0.37 ug/L) in the 'allopurinol-treated' group (z-test_2-sided). Analysis will be by intention to treat and it allows for one interim analysis.</p> <p>Discussion</p> <p>In this trial we aim to answer the question whether antenatal allopurinol administration reduces hypoxic-ischaemic encephalopathy in neonates exposed to foetal hypoxia.</p> <p>Trial registration number</p> <p>Clinical Trials, protocol registration system: NCT00189007</p

An extended mtDNA phylogeography for the alpine newt illuminates the provenance of introduced populations

Many herpetofauna species have been introduced outside of their native range. MtDNA barcoding is regularly used to determine the provenance of such populations. The alpine newt has been introduced across the Netherlands, the United Kingdom and Ireland. However, geographical mtDNA structure across the natural range of the alpine newt is still incompletely understood and certain regions are severely undersampled. We collect mtDNA sequence data of over seven hundred individuals, from both the native and the introduced range. The main new insights from our extended mtDNA phylogeography are that 1) haplotypes from Spain do not form a reciprocally monophyletic clade, but are nested inside the mtDNA clade that covers western and eastern Europe; and 2) haplotypes from the northwest Balkans form a monophyletic clade together with those from the Southern Carpathians and Apuseni Mountains. We also home in on the regions where the distinct mtDNA clades meet in nature. We show that four out of the seven distinct mtDNA clades that comprise the alpine newt are implicated in the introductions in the Netherlands, United Kingdom and Ireland. In several introduced localities, two distinct mtDNA clades co-occur. As these mtDNA clades presumably represent cryptic species, we urge that the extent of genetic admixture between them is assessed from genome-wide nuclear DNA markers. We mobilized a large number of citizen scientists in this project to support the collection of DNA samples by skin swabbing and underscore the effectiveness of this sampling technique for mtDNA barcoding

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

An isolated crested newt population in Dutch coastal dunes: distribution relict or introduction?

Isolated distribution patches may represent local remnants of a formerly wider range or could have originated by human-mediated expansion beyond the natural range. Distinguishing between these two scenarios is not always straightforward. Northern crested newts (Triturus cristatus) in the Dutch coastal dunes are disconnected from the main species range by over 40 kilometres and whether they have been present historically is unclear. We genotyped crested newts from throughout the Netherlands for an mtDNA marker to determine the provenance of the coastal dune population. Because a closely related species, the Italian crested newt (T. carnifex), has an introduction history in the Netherlands, we also screened eight nuclear DNA SNP markers diagnostic for T. cristatus vs. T. carnifex. The crested newts from the coastal dunes carry a single T. cristatus mtDNA haplotype that naturally occurs in the south, but not the east, of the Netherlands. Therefore, we cannot distinguish if the population represents a natural distribution relict or is derived from an introduction. We find no evidence of genetic admixture with T. carnifex in the coastal dunes, but such admixture is apparent at another Dutch locality (far removed from a previously known genetically admixed population). Our study illustrates how difficult it can be to determine the origin of isolated populations. </p

The conservation paradox of an introduced population of a threatened species: spadefoot toads in the coastal dunes of the Netherlands

   Species that are threatened in their native range, may actually prosper as introduced populations. To investigate how such introduced populations were established involves determining from where within the natural range the founder individuals originated. This can be accomplished through mtDNA barcoding. The common spadefoot toad (Pelobates fuscus) naturally occurs in the south and east of the Netherlands and has shown a rapid decline. Yet, a flourishing introduced population was recently discovered in the coastal dunes in the west of the country. We use mtDNA barcoding to determine the provenance of the introduced population. We sampled both native and introduced populations from the Netherlands and compared our sequences to haplotypes from across the entire distribution range. The mtDNA haplotypes found in the introduced population are distinct from those naturally occurring in the Netherlands and point towards an origin in the Pannonian Basin, on the boundary between Central and Southeastern Europe. Paradoxically, the thriving P. fuscus population in the Dutch coastal dunes should be considered a conservation risk to local biodiversity, even though within the native range in the Netherlands the species is severely threatened. Our study illustrates the complicated conservation questions associated with species that are both native and invasive.</p

The limits of mtDNA analysis for determining the provenance of invasive species: a midwife toad example

For most if not all European herpetofauna, range-wide mtDNA phylogeographies have been published. This facilitates establishing the provenance of introduced populations. However, precision is contingent on the spatial genetic structure across the range of the taxon under study and, in particular, from where within that range the introduction was sourced. In the Netherlands, the common midwife toad, Alytes obstetricans, only naturally occurs in the extreme southeast and is on the decline there. Yet, introduced populations thrive elsewhere in the country. We use mtDNA analysis to try to determine the origin of two introduced populations along the Dutch coast, in the city of The Hague and the dune area Meijendel. We compiled a database of hundreds of individuals from throughout the distribution range and added over 130 individuals from both native and introduced populations from the Netherlands, Belgium and Germany. The mtDNA haplotypes found in the introduced populations are associated with postglacial expansion. The main haplotype predominates in the natural range in the Netherlands, but also occurs much more widely across western Europe, north of the Pyrenees. A closely related haplotype, newly identified from The Hague, was not found in the native Netherlands range, suggesting an origin from abroad. The combination of low phylogeographic resolution and low sampling density in the postglacially colonized part of the range hampers our ability to determine the provenance of the introduced A. obstetricans populations. </p

The introduction of three cryptic tree frog species in the Dutch coastal dunes challenges conservation paradigms

Invasive species are considered one of the main drivers of the sixth mass extinction. Conservation solutions depend on whether a species is also indigenous to the country it invades (i.e., beyond its native range). In the case of invasive cryptic species, genetic tools are required to establish their identity. We illustrate these issues with the human-mediated colonization of the Dutch coastal dunes by Hyla tree frogs. Although previously assumed to concern the indigenous common tree frog H. arborea, European tree frogs comprise a complex of allopatric cryptic species, meaning the taxonomic identity of introduced Dutch populations warrants investigation. We sequence mtDNA for 164 individuals from native and introduced populations across the Netherlands and compare our dataset with hundreds of Hyla haplotypes previously barcoded in the Western Palearctic. Two of the dune populations carry an mtDNA haplotype of the native species H. arborea that occurs naturally elsewhere in the Netherlands. In contrast, mtDNA assigned to the eastern tree frog H. orientalis was detected in all three other dune populations. In one of these populations mtDNA of the Italian tree frog H. intermedia was also found. Not one, but three species of tree frogs have thus been introduced to the Dutch coastal dunes, only one of them being native to the Netherlands. This situation causes a conservation conundrum as some introduced populations are lawfully protected but could pose a threat to local biodiversity. Regarding the ‘true’ exotic tree frog species, all conservation options should be considered. </p