Early-onset fetal growth restriction:A systematic review on mortality and morbidity

Introduction: Severe early-onset fetal growth restriction is an obstetric condition with significant risks of perinatal mortality, major and minor neonatal morbidity, and long-term health sequelae. The prognosis of a fetus is influenced by the extent of prematurity and fetal weight. Clinical care is individually adjusted. In literature, survival rates vary and studies often only include live-born neonates with missing rates of antenatal death. This systematic review aims to summarize the literature on mortality and morbidity. Material and methods: A broad literature search was conducted in OVID MEDLINE from 2000 to 26 April 2019 to identify studies on fetal growth restriction and perinatal death. Studies were excluded when all included children were born before 2000 because (neonatal) health care has considerably improved since this period. Studies were included that described fetal growth restriction diagnosed before 32 weeks of gestation and antenatal mortality and neonatal mortality and/or morbidity as outcome. Quality of evidence was rated with the GRADE instrument. Results: Of the 2604 publications identified, 25 studies, reporting 2895 pregnancies, were included in the systematic review. Overall risk of bias in most studies was judged as low. The quality of evidence was generally rated as very low to moderate, except for 3 large well-designed randomized controlled trials. When combining all data on mortality, in 355 of 2895 pregnancies (12%) the fetus died antenatally, 192 died in the neonatal period (8% of live-born neonates) and 2347 (81% of all pregnancies) children survived. Of the neonatal morbidities recorded, respiratory distress syndrome (34% of the live-born neonates), retinopathy of prematurity (13%) and sepsis (30%) were most common. Of 476 children that underwent neurodevelopmental assessment, 58 (12% of surviving children, 9% of all pregnancies) suffered from cognitive impairment and/or cerebral palsy. Conclusions: When combining the data of 25 included studies, survival in fetal growth restriction pregnancies, diagnosed before 32 weeks of gestation, was 81%. Neurodevelopmental impairment was assessed in a minority of surviving children. Individual prognostic counseling on the basis of these results is hampered by differences in patient and pregnancy characteristics within the included patient groups

Recurrent pregnancy loss : diagnostic workup after two or three pregnancy losses? A systematic review of the literature and meta-analysis

BACKGROUND Recurrent pregnancy loss (RPL) occurs in 1–3% of all couples trying to conceive. No consensus exists regarding when to perform testing for risk factors in couples with RPL. Some guidelines recommend testing if a patient has had two pregnancy losses whereas others advise to test after three losses. OBJECTIVE AND RATIONALE The aim of this systematic review was to evaluate the current evidence on the prevalence of abnormal test results for RPL amongst patients with two versus three or more pregnancy losses. We also aimed to contribute to the debate regarding whether the investigations for RPL should take place after two or three or more pregnancy losses. SEARCH METHODS Relevant studies were identified by a systematic search in OVID Medline and EMBASE from inception to March 2019. A search for RPL was combined with a broad search for terms indicative of number of pregnancy losses, screening/testing for pregnancy loss or the prevalence of known risk factors. Meta-analyses were performed in case of adequate clinical and statistical homogeneity. The quality of the studies was assessed using the Newcastle-Ottawa scale. OUTCOMES From a total of 1985 identified publications, 21 were included in this systematic review and 19 were suitable for meta-analyses. For uterine abnormalities (seven studies, odds ratio (OR) 1.00, 95% CI 0.79–1.27, I2 = 0%) and for antiphospholipid syndrome (three studies, OR 1.04, 95% CI 0.86–1.25, I2 = 0%) we found low quality evidence for a lack of a difference in prevalence of abnormal test results between couples with two versus three or more pregnancy losses. We found insufficient evidence of a difference in prevalence of abnormal test results between couples with two versus three or more pregnancy losses for chromosomal abnormalities (10 studies, OR 0.78, 95% CI 0.55–1.10), inherited thrombophilia (five studies) and thyroid disorders (two studies, OR 0.52, 95% CI: 0.06–4.56). WIDER IMPLICATIONS A difference in prevalence in uterine abnormalities and antiphospholipid syndrome is unlikely in women with two versus three pregnancy losses. We cannot exclude a difference in prevalence of chromosomal abnormalities, inherited thrombophilia and thyroid disorders following testing after two versus three pregnancy losses. The results of this systematic review may support investigations after two pregnancy losses in couples with RPL, but it should be stressed that additional studies of the prognostic value of test results used in the RPL population are urgently needed. An evidenced-based treatment is not currently available in the majority of cases when abnormal test results are present

Hypothalamic-pituitary-adrenal axis and autonomic nervous system reactivity in children prenatally exposed to maternal depression:A systematic review of prospective studies

Depression is a common condition affecting up to 20% of all pregnant women, and is associated with subsequent developmental and behavioral problems in children, such as conduct disorder and ADHD. One proposed mechanism underlying these associations is modification of the fetal hypothalamic pituitary adrenal (HPA)-axis and the autonomic nervous system (ANS), resulting in altered responses to stress. This review examined the evidence regarding altered HPA-axis and ANS reactivity in children prenatally exposed to high maternal depressive symptoms. A systematic search was conducted in the electronic databases MEDLINE, EMBASE and PsycINFO, for studies published till 25 July 2017. A total of 13 studies comprising 2271 mother-infant dyads were included. None of the studies were suitable for meta-analysis. Risk of bias assessment showed low risk for four studies. Only three studies described an independent association between exposure to high maternal prenatal depressive symptoms and altered stress reactivity in children. There is limited evidence of an independent association between prenatal exposure to maternal depression and altered HPA or ANS reactivity in children

Neonatal pulmonary hypertension after severe early-onset fetal growth restriction:post hoc reflections on the Dutch STRIDER study

The aim was to reflect on the unexpected finding of persistent pulmonary hypertension of the neonate (PPHN) and pulmonary hypertension in infants born within the Dutch STRIDER trial, its definition and possible pathophysiological mechanisms. The trial randomly assigned pregnant women with severe early-onset fetal growth restriction to sildenafil 25 mg three times a day versus placebo. Sildenafil use did not reduce perinatal mortality and morbidity, but did result in a higher rate of neonatal pulmonary hypertension (PH). The current paper reflects on the used definition, prevalence, and possible pathophysiology of the data on pulmonary hypertension. Twenty infants were diagnosed with pulmonary hypertension (12% of 163 live born infants). Of these, 16 infants had PPHN shortly after birth, and four had pulmonary hypertension associated with sepsis or bronchopulmonary dysplasia. Four infants with PPHN in the early neonatal period subsequently developed pulmonary hypertension associated with bronchopulmonary dysplasia in later life. Infants with pulmonary hypertension were at lower gestational age at delivery, had a lower birth weight and a higher rate of neonatal co-morbidity. The infants in the sildenafil group showed a significant increase in pulmonary hypertension compared to the placebo group (relative risk 3.67; 95% confidence interval 1.28 to 10.51, P = 0.02). Conclusion: Pulmonary hypertension occurred more frequent among infants of mothers allocated to antenatal sildenafil compared with placebo. A possible pathophysiological mechanism could be a “rebound” vasoconstriction after cessation of sildenafil. Additional studies and data are necessary to understand the mechanism of action. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00431-021-04355-x

Vasopressors and Inotropes in Acute Myocardial Infarction Related Cardiogenic Shock: A Systematic Review and Meta-Analysis

Vasopressors and inotropes are routinely used in acute myocardial infarction (AMI) related cardiogenic shock (CS) to improve hemodynamics. We aimed to investigate the effect of routinely used vasopressor and inotropes on mortality in AMI related CS. A systematic search of MEDLINE, EMBASE and CENTRAL was performed up to 20 February 2019. Randomized and observational studies reporting mortality of AMI related CS patients were included. At least one group should have received the vasopressor/inotrope compared with a control group not exposed to the vasopressor/inotrope. Exclusion criteria were case reports, correspondence and studies including only post-cardiac surgery patients. In total, 19 studies (6 RCTs) were included, comprising 2478 CS patients. The overall quality of evidence was graded low. Treatment with adrenaline, noradrenaline, vasopressin, milrinone, levosimendan, dobutamine or dopamine was not associated with a difference in mortality between therapy and control group. We found a trend toward better outcome with levosimendan, compared with control (RR 0.69, 95% CI 0.47–1.00). In conclusion, we found insufficient evidence that routinely used vasopressors and inotropes are associated with reduced mortality in patients with AMI related CS. Considering the limited evidence, this study emphasizes the need for randomized trials with appropriate endpoints and methodology

European position paper on rhinosinusitis and nasal polyps 2020

The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise . The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included

European Position Paper on Rhinosinusitis and Nasal Polyps 2020

The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise. The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included.Peer reviewe

Otoacoustic emissions versus audiometry in monitoring hearing loss after long-term noise exposure - a systematic review

Objectives The objective of this systematic review was to compare otoacoustic emissions (OAE) with audiometry in their effectiveness to monitor effects of long-term noise exposure on hearing. Methods We conducted a systematic search of MEDLINE, Embase and the non-MEDLINE subset of PubMed up to March 2016 to identify longitudinal studies on effects of noise exposure on hearing as determined by both audiometry and OAE. Results This review comprised 13 articles, with 30-350 subjects in the longitudinal analysis. A meta-analysis could not be performed because the studies were very heterogeneous in terms of measurement paradigms, follow-up time, age of included subjects, inclusion of data points, outcome parameters and method of analysis. Overall there seemed to be small changes in both audiometry and OAE over time. Individual shifts were detected by both methods but a congruent pattern could not be observed. Some studies found that initial abnormal or low-level emissions might predict future hearing loss but at the cost of low specificity due to a high number of false positives. Other studies could not find such predictive value. Conclusions The reported heterogeneity in the studies calls for more uniformity in including, reporting and analyzing longitudinal data for audiometry and OAE. For the overall results, both methods showed small changes from baseline towards a deterioration in hearing. OAE could not reliably detect threshold shifts at individual level. With respect to the predictive value of OAE, the evidence was not conclusive and studies were not in agreement. The reported predictors had low specificity