23 Pulmonary Hypertension Associated with Bronchopulmonary Dysplasia and Neurodevelopmental Outcomes: A Systematic Review and Meta-Analysis

Abstract Primary Subject area Neonatal-Perinatal Medicine Background Pulmonary Hypertension (PH) is estimated to occur in 1 in 4 infants with Bronchopulmonary Dysplasia (BPD). The impact of PH in infants with BPD on their neurodevelopmental (ND) outcomes is uncertain. Objectives This systematic review aims to evaluate whether PH in infants with BPD is associated with ND delay. Design/Methods A systematic literature search was performed to identify studies that reported ND outcomes of infants with BPD (based on NIH definition) and PH (based on echocardiographic findings of PH at 36 weeks PMA). The primary outcome was ND delay in infants with pulmonary hypertension associated with BPD compared with BPD alone. Standardized developmental tests evaluated ND outcomes at 18-24 months corrected age (CA) and three years of age. Quality assessment of the studies was done using the Newcastle-Ottawa Quality Assessment for Cohort studies. Results Three retrospective cohort studies met the inclusion criteria. Two studies reported ND outcomes based on Bayley Scales of Infant and Toddler Development-III Edition in cognitive, language, and motor domains at 18-24 months CA (Table 1 and Figure 1). One study reported outcomes at 3 years, including overall developmental delay (Kyoto Scale of Psychological Development [KSPD] scores < 70) and cerebral palsy. The quality of all 3 studies was rated between good, fair, and poor. Pooled data from the 2 studies reporting outcomes at 18-24 months showed no difference between the 2 infant groups for Bayley cognitive score < 85 (Odds ratio [OR]: 3.78; 95% CI 0.87-16.52), Bayley language score < 85 (OR: 1.19; 95% CI0.57-2.49), and Bayley motor score < 85 (OR: 2.04; 95% CI 0.89-4.67). At 3 years of age, children in the BPD-PH group had an increased risk of developmental delay (DQ < 70 in all areas) compared with the BPD group (OR: 4.37; 95% CI 1.16-16.46), but no difference in the risk of cerebral palsy (OR: 0.57; 95%0.03-12.39). Conclusion PH in BPD is not associated with a developmental delay compared to BPD alone at 18-24 months CA. However, a single study showed infants in BPD-PH had delayed development at 3 years of age. A large prospective cohort study with longer multidisciplinary follow-up is required to confirm this.

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Gender-Related Differences in Hypertrophic Cardiomyopathy: A Systematic Review and Meta-Analysis

Pulse ◽

10.1159/000517618 ◽

2021 ◽

Vol 9 (1-2) ◽

pp. 38-46

Author(s):

Angkawipa Trongtorsak ◽

Natchaya Polpichai ◽

Sittinun Thangjui ◽

Jakrin Kewcharoen ◽

Ratdanai Yodsuwan ◽

...

Keyword(s):

Systematic Review ◽

Hypertrophic Cardiomyopathy ◽

Cohort Studies ◽

Meta Analysis ◽

Phenotypic Expression ◽

Female Gender ◽

Increased Risk ◽

All Cause Mortality ◽

The Impact ◽

Related Mortality

Background: Gender-related differences in phenotypic expression and outcomes have been established in many cardiac conditions; however, the impact of gender in hypertrophic cardiomyopathy (HCM) remains unclear. We conducted a systematic review and meta-analysis to assess the differences in clinical outcomes between female and male HCM patients. Methods: We searched MEDLINE and EMBASE from inception to October 2020. Included were cohort studies that compared outcomes of interest including all-cause mortality, HCM-related mortality, and worsening heart failure (HF) or HF hospitalization between male and female. Data from each study were combined using the random effects model to calculate pooled odds ratio (OR) with 95% confidence interval (CI). Results: Eleven retrospective cohort studies with a total of 9,427 patients (3,719 females) were included. Female gender was significantly associated with an increased risk of all-cause mortality (pooled OR = 1.63, 95% CI: 1.26–2.10, p ≤ 0.001), HCM-related mortality (pooled OR = 1.47, 95% CI: 1.08–2.01, p = 0.015), and worsening HF or HF hospitalization (pooled OR = 2.05, 95% CI: 1.76–2.39, p ≤ 0.001). Conclusions: Female gender was associated with a worse prognosis in HCM. These findings suggest the need for improved care in women including early identification of disease and more possible aggressive management. Moreover, gender-based strategy may benefit in HCM patients.

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Epidural-Related Fever and Maternal and Neonatal Morbidity: A Systematic Review and Meta-Analysis

Neonatology ◽

10.1159/000504805 ◽

2020 ◽

Vol 117 (3) ◽

pp. 259-270 ◽

Cited By ~ 3

Author(s):

Sophie Jansen ◽

Enrico Lopriore ◽

Christiana Naaktgeboren ◽

Marieke Sueters ◽

Jacqueline Limpens ◽

...

Keyword(s):

Systematic Review ◽

Cohort Studies ◽

Antibiotic Treatment ◽

Assessment Tool ◽

Meta Analysis ◽

Cochrane Library ◽

Increased Risk ◽

Observational Cohort ◽

Meta Analyses ◽

The Impact

Background: While epidural analgesia (EA) is associated with maternal fever during labor, the impact on the risk for maternal and/or neonatal sepsis is unknown. Objectives: The aim of this systematic review was to investigate the effect of epidural-related intrapartum fever on maternal and neonatal outcomes. Methods: OVID MEDLINE, OVID Embase, the Cochrane Library, Cochrane Controlled Register of Trials, and clinical trial registries were searched for randomized controlled trials (RCT) and observational cohort studies from inception to November 2018. A total of 761 studies were identified with 100 eligible for full-text review. Only articles investigating the relationship between EA and maternal fever during labor were eligible for inclusion. Study quality was assessed using the Cochrane’s Risk of Bias tool and National Institute of Health Quality Assessment Tool. Two meta-analyses – one each for the RCT and observational cohort groups – were performed using the random-effects model of Mantel-Haenszel to produce summary risk ratios (RR) with 95% CI. Results: Twelve RCTs and 16 observational cohort studies involving 579,157 parturients were included. RRs for maternal fever for the RCT and cohort analyses were 3.54 (95% CI 2.61–4.81) and 5.60 (95% CI 4.50–6.97), respectively. Meta-analyses of RR for maternal infection in both groups were infeasible given few occurrences. Meta-analysis of data from observational studies showed an increased risk for maternal antibiotic treatment in the epidural group (RR 2.60; 95% CI 1.31–5.17). For both analyses, neonates born to women with an epidural were not evaluated more often for suspected sepsis. Neither analysis reported an increased rate of neonatal bacteremia or neonatal antibiotic treatment after EA, although data precluded conclusiveness. Conclusion: EA increases the risk of intrapartum fever and maternal antibiotic treatment. However, a definite conclusion on whether EA increases the risk for a proven maternal and/or neonatal bacteremia cannot be drawn due to the low quality of data. Further research on whether epidural-related intrapartum fever is of infectious origin or not is therefore needed.

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The impact of placental pathology discordance in multiple gestation pregnancies on bronchopulmonary dysplasia-associated pulmonary hypertension

Pulmonary Circulation ◽

10.1177/2045894020910674 ◽

2020 ◽

Vol 10 (1) ◽

pp. 204589402091067

Author(s):

Andrew Franklin ◽

Sushmita Yallapragada ◽

Robert Birkett ◽

William Grobman ◽

Linda M. Ernst ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Bronchopulmonary Dysplasia ◽

Gestational Age ◽

Small For Gestational Age ◽

Chronic Hypertension ◽

Multiple Gestation ◽

Placental Pathology ◽

Angiogenic Growth Factors ◽

Increased Risk ◽

The Impact

Bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH) may either be concordant or discordant between multiple gestation births. Abnormal placental development, particularly maternal vascular malperfusion, may account for discordance in BPD-PH through fetal programming mechanisms. Maternal vascular malperfusion is a placental histologic lesion associated with intrauterine growth restriction and BPD-PH. We conducted a retrospective longitudinal cohort study of infants born <29 weeks gestation with available placental histology at Prentice Women's Hospital in Chicago from 2005–2012. The primary outcome was discordant BPD-PH associated with placental maternal vascular malperfusion. We secondarily assessed whether the risk of BPD-PH and placental lesions was different among infants of multiple (compared to singleton) gestations. The cohort consisted of 135 multiple gestation infants and 355 singletons. In a separate cohort of 39 singletons and 35 multiples, associations between 12 cytokines and angiogenic growth factors in cord blood plasma for biomarker discordance, maternal vascular malperfusion, and bronchopulmonary dysplasia were explored. Among multiples, discordant maternal vascular malperfusion was not associated with BPD-PH (OR = 1.9 (0.52, 6.9); p = 0.33) in infants exposed to placental maternal vascular malperfusion. However, singleton infants were more likely to develop BPD-PH (compared to multiples) after adjusting for mode of delivery, chorioamnionitis, chronic hypertension, placental abruption, small-for-gestational age birth weight, and gestational age (aOR = 2.7 (1.2, 5.8); p = 0.038). Singletons were more likely to be small-for-gestational age (11% vs 4%, p = 0.025) and have placental lesions compared to their multiple-gestation counterparts (96% vs 81%, p < 0.001), principally severe maternal vascular malperfusion (17% vs 4%, p < 0.001) and chronic inflammation (32% vs 11%, p < 0.001). Increased risk of BPD-PH in singleton pregnancies <29 weeks gestation compared to multiples may be related to increased frequency of these histologic lesions. Placental pathology in singleton and multiple gestation pregnancies may serve as an early biomarker to predict BPD-PH.

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Association of the dysfunctional placentation endotype of prematurity with bronchopulmonary dysplasia: a systematic review, meta-analysis and meta-regression

Thorax ◽

10.1136/thoraxjnl-2020-216485 ◽

2021 ◽

pp. thoraxjnl-2020-216485

Author(s):

Maria Pierro ◽

Eduardo Villamor-Martinez ◽

Elke van Westering-Kroon ◽

Maria Alvarez-Fuente ◽

Steven H Abman ◽

...

Keyword(s):

Systematic Review ◽

Pulmonary Hypertension ◽

Bronchopulmonary Dysplasia ◽

Vascular Dysfunction ◽

Meta Analysis ◽

Supplemental Oxygen ◽

Growth Restriction ◽

Increased Risk ◽

Postmenstrual Age ◽

Registration Number

BackgroundAntenatal pathological conditions are key in the pathogenesis of bronchopulmonary dysplasia (BPD). Pathophysiological pathways or endotypes leading to prematurity and perinatal lung injury can be clustered into two groups: infection and dysfunctional placentation, which include hypertensive disorders of pregnancy (HDP) and intrauterine growth restriction (IUGR). We conducted a systematic review of observational studies exploring the association between the dysfunctional placentation endotype and BPD.MethodsMEDLINE, Embase and Web of Science databases were searched up to February 2020 for studies reporting data on the diagnosis of HDP, IUGR or small for gestational age (SGA) and BPD risk. BPD was classified as BPD28 (supplemental oxygen on day 28), BPD36 (oxygen at 36 weeks postmenstrual age), severe BPD (≥ 30% oxygen or mechanical ventilation), BPD36/death and BPD-associated pulmonary hypertension.ResultsOf 6319 studies screened, 211 (347 963 infants) were included. Meta-analysis showed an association between SGA/IUGR and BPD36 (OR 1.56, 95% CI 1.37 to 1.79), severe BPD (OR 1.82, 95% CI 1.36 to 2.29) and BPD/death (OR 1.91, 95% CI 1.55 to 2.37). Exposure to HDP was not associated with BPD but was associated with decreased odds of BPD/death (OR 0.77, 95% CI 0.64 to 0.94). Both HDP (OR 1.41, 95% CI 1.10 to 1.80) and SGA/IUGR (OR 2.37, 95% CI 1.86 to 3.02) were associated with BPD-associated pulmonary hypertension.ConclusionWhen placental vascular dysfunction is accompanied by fetal growth restriction or being born SGA, it is associated with an increased risk of developing BPD and pulmonary hypertension. The placental dysfunction endotype of prematurity is strongly associated with the vascular phenotype of BPD.Prospero registration numberReview protocol was registered in PROSPERO database (ID=CRD42018086877).

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Climate Change, Weather, Housing Precarity, and Homelessness: A Systematic Review of Reviews

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18115812 ◽

2021 ◽

Vol 18 (11) ◽

pp. 5812

Author(s):

Mariya Bezgrebelna ◽

Kwame McKenzie ◽

Samantha Wells ◽

Arun Ravindran ◽

Michael Kral ◽

...

Keyword(s):

Climate Change ◽

Systematic Review ◽

Natural Disasters ◽

Green Infrastructure ◽

Temperature Extremes ◽

Weather Extremes ◽

Positive Effects ◽

Increased Risk ◽

Review Of Reviews ◽

The Impact

This systematic review of reviews was conducted to examine housing precarity and homelessness in relation to climate change and weather extremes internationally. In a thematic analysis of 15 reviews (5 systematic and 10 non-systematic), the following themes emerged: risk factors for homelessness/housing precarity, temperature extremes, health concerns, structural factors, natural disasters, and housing. First, an increased risk of homelessness has been found for people who are vulnerably housed and populations in lower socio-economic positions due to energy insecurity and climate change-induced natural hazards. Second, homeless/vulnerably-housed populations are disproportionately exposed to climatic events (temperature extremes and natural disasters). Third, the physical and mental health of homeless/vulnerably-housed populations is projected to be impacted by weather extremes and climate change. Fourth, while green infrastructure may have positive effects for homeless/vulnerably-housed populations, housing remains a major concern in urban environments. Finally, structural changes must be implemented. Recommendations for addressing the impact of climate change on homelessness and housing precarity were generated, including interventions focusing on homelessness/housing precarity and reducing the effects of weather extremes, improved housing and urban planning, and further research on homelessness/housing precarity and climate change. To further enhance the impact of these initiatives, we suggest employing the Human Rights-Based Approach (HRBA).

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What is the impact of multimorbidity on the risk of hospitalisation in older adults? A systematic review study protocol

BMJ Open ◽

10.1136/bmjopen-2021-049974 ◽

2021 ◽

Vol 11 (6) ◽

pp. e049974

Author(s):

Luciana Pereira Rodrigues ◽

Andréa Toledo de Oliveira Rezende ◽

Letícia de Almeida Nogueira e Moura ◽

Bruno Pereira Nunes ◽

Matias Noll ◽

...

Keyword(s):

Systematic Review ◽

Older Adults ◽

Study Protocol ◽

Average Length ◽

Length Of Hospital Stay ◽

Case Control Studies ◽

Cross Sectional ◽

Increased Risk ◽

Review Study ◽

The Impact

IntroductionThe development of multiple coexisting chronic diseases (multimorbidity) is increasing globally, along with the percentage of older adults affected by it. Multimorbidity is associated with the concomitant use of multiple medications, a greater possibility of adverse effects, and increased risk of hospitalisation. Therefore, this systematic review study protocol aims to analyse the impact of multimorbidity on the occurrence of hospitalisation in older adults and assess whether this impact changes according to factors such as sex, age, institutionalisation and socioeconomic status. This study will also review the average length of hospital stay and the occurrence of hospital readmission.Methods and analysisA systematic review of the literature will be carried out using the PubMed, Embase and Scopus databases. The inclusion criteria will incorporate cross-sectional, cohort and case–control studies that analysed the association between multimorbidity (defined as the presence of ≥2 and/or ≥3 chronic conditions and complex multimorbidity) and hospitalisation (yes/no, days of hospitalisation and number of readmissions) in older adults (aged ≥60 years or >65 years). Effect measures will be quantified, including ORs, prevalence ratios, HRs and relative risk, along with their associated 95% CI. The overall aim of this study is to widen knowledge and to raise reflections about the association between multimorbidity and hospitalisation in older adults. Ultimately, its findings may contribute to improvements in public health policies resulting in cost reductions across healthcare systems.Ethics and disseminationEthical approval is not required. The results will be disseminated via submission for publication to a peer-reviewed journal when complete.PROSPERO registration numberCRD42021229328.

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P070: Mixed effectiveness of emergency department diversion strategies: a systematic review

CJEM ◽

10.1017/cem.2017.272 ◽

2017 ◽

Vol 19 (S1) ◽

pp. S102

Author(s):

S.W. Kirkland ◽

A. Soleimani ◽

B.H. Rowe ◽

A.S. Newton

Keyword(s):

Systematic Review ◽

Health Care ◽

Emergency Department ◽

Health Care Services ◽

Grey Literature ◽

Study Data ◽

Care Utilization ◽

Alternative Source ◽

Increased Risk ◽

The Impact

Introduction: Diverting patients away from the emergency department (ED) has been proposed as a solution for reducing ED overcrowding. The objective of this systematic review is to examine the effectiveness of diversion strategies designed to either direct patients seeking care at an ED to an alternative source of care. Methods: Seven electronic databases and grey literature were searched. Randomized/controlled clinical trials and cohort studies assessing the effectiveness of pre-hospital and ED-based diversion interventions with a comparator were eligible for inclusion. Two reviewers independently screened the studies for relevance, inclusion, and risk of bias. Intervention effects are reported as proportions (%) or relative risks (RR) with 95% confidence intervals (CI). Methodological and clinical heterogeneity prohibited pooling of study data. Results: From 7,306 citations, ten studies were included. Seven studies evaluated a pre-hospital diversion strategy and three studies evaluated an ED-based diversion strategy. The impact of diversion on subsequent health services was mixed. One study of paramedic practitioners reported increased ED attendance within 7 days (11.9% vs. 9.5%; p=0.049) but no differences in return visits for similar conditions (75.2% vs. 72.1%; p=0.64). The use of paramedic practitioners was associated with an increased risk of subsequent contact with health care services (RR=1.21, 95% CI 1.06, 1.38), while the use of deferred care was associated with no increase in risk of subsequently seeking physician care (RR=1.09, 95% CI 0.23, 5.26). While two studies reported that diverted patients were at significantly reduced risk for hospitalization, two other studies reported no significant differences between diverted or standard care patients. Conclusion: The evidence regarding the impact of pre-hospital and ED-based diversion on ED utilization and subsequent health care utilization is mixed. Additional high-quality comparative effectiveness studies of diversion strategies are required prior to widespread implementation.

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Mechanical Ventilation in Preterm Infants: Neurosonographic and Developmental Studies

PEDIATRICS ◽

10.1542/peds.90.4.515 ◽

1992 ◽

Vol 90 (4) ◽

pp. 515-522 ◽

Cited By ~ 2

Author(s):

Leonard J. Graziani ◽

Alan R. Spitzer ◽

Donald G. Mitchell ◽

Daniel A. Merton ◽

Christian Stanley ◽

...

Keyword(s):

Mechanical Ventilation ◽

Early Childhood ◽

Cerebral Palsy ◽

Developmental Delay ◽

Preterm Infants ◽

Intracranial Hemorrhage ◽

Apgar Scores ◽

Mechanically Ventilated ◽

Increased Risk ◽

Grade Iii

Surviving preterm infants of less than 34 weeks' gestation who were selected on the basis of serial cranial ultrasonographic findings during their nursery course had repeated neurologic and developmental examinations during late infancy and early childhood that established the presence (n = 46) or absence (n = 205) of spastic forms of cerebral palsy. Of the 205 infants without cerebral palsy, 22 scored abnormally low on standardized developmental testing during early childhood. The need for mechanical ventilation beginning on the first day of life (n = 92) was significantly related to gestational age, birth weight, Apgar scores, patent ductus arteriosus, grade III/IV intracranial hemorrhage, large periventricular cysts, and the development of cerebral palsy. In the 192 mechanically ventilated infants, vaginal bleeding during the third trimester, low Apgar scores, and maximally low Pco2 values during the first 3 days of life were significantly related to large periventricular cysts (n = 41) and cerebral palsy (n = 43), but not to developmental delay in the absence of cerebral palsy (n = 18). The severity of intracranial hemorrhage in mechanically ventilated infants was significantly associated with gestational age and maximally low measurements of Pco2 and pH, but not with Apgar scores or maximally low measurements of Po2. Logistic regression analyses controlling for possible confounding variables disclosed that Pco2 values of less than 17 mm Hg during the first 3 days of life in mechanically ventilated infants were associated with a significantly increased risk of moderate to severe periventricular echodensity, large periventricular cysts, grade III/IV intracranial hemorrhage, and cerebral palsy. Neurosonographic abnormalities were highly predictive of cerebral palsy independent of Pco2 measurements. However, neither hypocarbia nor neurosonographic abnormalities were associated with a significantly increased risk of developmental delay in the absence of cerebral palsy. In this preterm infant population, therefore, the risk factors for developmental delay differed from those predictive of spastic forms of cerebral palsy. Of the 57 ventilated preterm infants who were exposed to a maximally low Pco2 of less than 20 mm Hg at least once during the first 3 days of life, 21 developed large periventricular cysts or cerebral palsy or both. Those results suggest that prenatal and neonatal factors including the need for mechanical ventilation beginning on the first day of life and marked hypocarbia during the first 3 postnatal days are associated with an increased risk of damage to the periventricular white matter of some preterm infants. However, a causal relationship between hypocarbia and brain damage in preterm infants remains unproven.

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Somatic growth and the risks of bronchopulmonary dysplasia and pulmonary hypertension: connecting epidemiology and physiology

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2018-0386 ◽

2019 ◽

Vol 97 (3) ◽

pp. 197-205 ◽

Cited By ~ 1

Author(s):

Mark A. Underwood ◽

Stephen Wedgwood ◽

Satyan Lakshminrusimha ◽

Robin H. Steinhorn

Keyword(s):

Pulmonary Hypertension ◽

Bronchopulmonary Dysplasia ◽

Somatic Growth ◽

Postnatal Growth ◽

Pulmonary Complications ◽

Growth Restriction ◽

Extreme Prematurity ◽

Poor Growth ◽

Increased Risk ◽

Poor Nutrition

In the premature infant, poor growth in utero (fetal growth restriction) and in the first weeks of life (postnatal growth restriction) are associated with increased risk for bronchopulmonary dysplasia and pulmonary hypertension. In this review, we summarize the epidemiologic data supporting these associations, present a novel rodent model of postnatal growth restriction, and review 5 promising mechanisms by which poor nutrition may affect the developing lung. These observations support the hypothesis that nutritional and (or) pharmacologic interventions early in life may be able to decrease risk of the pulmonary complications of extreme prematurity.

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Systematic review protocol exploring the impact of the COVID-19 pandemic on the wellbeing of general practitioners

10.1101/2021.08.05.21261627 ◽

2021 ◽

Author(s):

Laura Jefferson ◽

Su Golder ◽

Veronica Dale ◽

Holly Essex ◽

Elizabeth McHugh ◽

...

Keyword(s):

Mental Health ◽

Systematic Review ◽

Quality Assessment ◽

General Practitioners ◽

Systematic Reviews ◽

Assessment Tools ◽

Systematic Review Protocol ◽

Health And Wellbeing ◽

Review Protocol ◽

The Impact

Background Over recent years chronic stress and burnout have been reported by doctors working in general practice in the UK NHS and internationally. The COVID-19 pandemic has changed general practitioners working lives; adding potential pressures from avoiding infection and addressing pent-up demand for care, but also changing processes such as rapidly taking up remote consultations. To date, there has been a focus on exploring the impact of the pandemic on the wellbeing of hospital clinicians. No registered systematic reviews currently focus on exploring the impact of the pandemic on the mental health and wellbeing of general practitioners. Aims and objectives To synthesise the current international evidence base exploring the impact of COVID-19 on the mental health and wellbeing of general practitioners, and which factors are associated with their reported mental health and wellbeing during the pandemic. Methods In this paper we report a systematic review protocol, following PRISMA guidance. In our search strategy we will identify primary research studies or systematic reviews exploring the mental health and wellbeing of general practitioners during the COVID-19 pandemic in four databases (MEDLINE, Embase, PsychInfo and Medrxiv) and Google Scholar. We will hand-search reference lists and grey literature. Two reviewers will undertake all stages including study selection, data extraction and quality assessment, with arbitration by a third reviewer where necessary. We will use standardised quality assessment tools to ensure transparency and reduce bias in quality assessment. Depending on the quality of included studies, we may undertake a sensitivity analysis by excluding studies from narrative synthesis that are rated as low quality using the checklists. We will describe the findings across studies using narrative thematic data synthesis, and if sufficiently homogenous data are identified, we will pool quantitative findings through meta-analysis.

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