Effects of the neonatal intensive care environment on circadian health and development of preterm infants

The circadian system in mammals ensures adaptation to the light-dark cycle on Earth and imposes 24-h rhythmicity on metabolic, physiological and behavioral processes. The central circadian pacemaker is located in the brain and is entrained by environmental signals called Zeitgebers. From here, neural, humoral and systemic signals drive rhythms in peripheral clocks in nearly every mammalian tissue. During pregnancy, disruption of the complex interplay between the mother’s rhythmic signals and the fetal developing circadian system can lead to long-term health consequences in the offspring. When an infant is born very preterm, it loses the temporal signals received from the mother prematurely and becomes totally dependent on 24/7 care in the Neonatal Intensive Care Unit (NICU), where day/night rhythmicity is usually blurred. In this literature review, we provide an overview of the fetal and neonatal development of the circadian system, and short-term consequences of disruption of this process as occurs in the NICU environment. Moreover, we provide a theoretical and molecular framework of how this disruption could lead to later-life disease. Finally, we discuss studies that aim to improve health outcomes after preterm birth by studying the effects of enhancing rhythmicity in light and noise exposure.</p

Diagnostic and predictive value of Doppler ultrasound for evaluation of the brain circulation in preterm infants: a systematic review

INTRODUCTION: Very and extremely preterm infants frequently have brain injury-related long-term neurodevelopmental problems. Altered perfusion, for example, seen in the context of a hemodynamically significant patent ductus arteriosus (PDA), has been linked to injury of the immature brain. However, a direct relation with outcome has not been reviewed systematically. METHODS: A systematic review was conducted to provide an overview of the value of different cerebral arterial blood flow parameters assessed by Doppler ultrasound, in relation to brain injury, to predict long-term neurodevelopmental outcome in preterm infants. RESULTS: In total, 23 studies were included. Because of heterogeneity of studies, a meta-analysis of results was not possible. All included studies on resistance index (RI) showed significantly higher values in subjects with a hemodynamically significant PDA. However, absolute differences in RI values were small. Studies using Doppler parameters to predict brain injury and long-term neurodevelopmental outcome were inconsistent. DISCUSSION: There is no clear evidence to support the routine determination of RI or other Doppler parameters in the cerebral arteries to predict brain injury and long-term neurodevelopmental outcome in the preterm infant. However, there is evidence that elevated RI can point to the presence of a hemodynamically significant PDA

Atrial fibrillation progression risk factors and associated cardiovascular outcome in well-phenotyped patients:data from the AF-RISK study

Aims: Atrial fibrillation (AF) is a progressive disease, but identifying patients at risk for AF progression is challenging. We aimed to identify factors associated with AF progression. Methods and results: Atrial fibrillation progression was assessed in 392 patients with recent-onset paroxysmal or persistent AF included in the prospective, observational, multicentre identification of a risk profile to guide atrial fibrillation (AF-RISK) study. Progression of AF was assessed by Holter monitoring and 2-week event recorder at baseline and 1-year follow-up. AF progression was defined as: (i) doubling in AF burden at 1 year compared to baseline with a minimum AF burden of 10% in paroxysmal AF; or (ii) transition from paroxysmal to persistent or permanent AF; or (iii) persistent to permanent AF. Age was 60 ± 11 years, 62% were men, and 83% had paroxysmal AF. At 1 year, 52 (13%) had AF progression (11% in paroxysmal; 26% in persistent AF). Multivariable logistic regression showed that left atrial volume [odds ratio (OR) per 10 mL 1.251, 95% confidence interval (CI) 1.078-1.450; P < 0.001], N-terminal pro-B-type natriuretic peptide (NT-proBNP; OR per standard deviation increase 1.583, 95% CI 1.099-2.281; P = 0.014), and plasminogen activator inhibitor-1 (PAI-1; OR per standard deviation increase 0.660, 95% CI 0.472-0.921; P = 0.015) were associated with AF progression. In an additional follow-up of 1.9 (0.9-3.3) years patients with AF progression developed more cardiovascular events and all-cause mortality (12.4%/year vs. 2.3%/year, P < 0.001). Conclusion: Atrial fibrillation progression occurred in 13% of patients with recent-onset AF during 1-year follow-up. Left atrial volume, NT-proBNP, and PAI-1 were associated with AF progression. Patients with AF progression had a higher event rate. Trial registration number: Clinicaltrials.gov NCT01510210

The influence of progression of atrial fibrillation on quality of life: a report from the Euro Heart Survey.

Aims: Progression of atrial fibrillation (AF) from paroxysmal to persistent forms is an active field of research. The influence of AF progression on health related quality of life (HRQoL) is currently unknown. We aimed to assess the influence of AF progression on HRQoL, and whether this association is mediated through symptoms, treatment, and major adverse events. Methods and results: In the Euro Heart Survey, 967 patients were included with paroxysmal AF who filled out EuroQoL-5D at baseline and at 1 year follow-up. Those who progressed (n = 132, 13.6%) developed more problems during follow-up than those who did not, on all EuroQoL-5D domains (increase in problems on mobility 20.5% vs. 11.4%; self-care 12.9% vs. 6.2%; usual activities 23.5% vs. 14.0%; pain/discomfort 20.5% vs. 13.7%; and anxiety/depression 22.7% vs. 15.7%; all P < 0.05), leading to a decrease in utility [baseline 0.744 ± 0.26, follow-up 0.674 ± 0.36; difference -0.07 (95% CI [-0.126,-0.013], P = 0.02)]. Multivariate analysis showed that the effect of progression on utility is mediated by a large effect of adverse events [stroke (-0.27 (95% CI [-0.43,-0.11]); P = 0.001], heart failure [-0.12 (95% CI [-0.20,-0.05]); P = 0.001], malignancy (-0.31 (95% CI [-0.56,-0.05]); P = 0.02] or implantation of an implantable cardiac defibrillator [-0.12 (95% CI [-0.23,-0.02]); P = 0.03)], as well as symptomatic AF [-0.04 (95% CI [-0.08,-0.01]); P = 0.008]. Conclusion: AF progression is associated with a decrease in HRQoL. However, multivariate analysis revealed that AF progression itself does not have a negative effect on HRQoL, but that this effect can be attributed to a minor effect of the associated symptoms and a major effect of associated adverse events

Increased plasma levels of NT-proBNP, Troponin T and GDF-15 are driven by persistent AF and associated comorbidities:Data from the AF-RISK study

Atrial fibrillation (AF) is a progressive disease, and early recognition and management may reflect an important strategy to reduce its disease burden. In this study, we evaluated plasma levels of three biomarkers - N-terminal pro-brain natriuretic peptide (NTproBNP), Troponin-T, and growth differentiation factor-15 (GDF-15) - in patients with paroxysmal AF (pAF) (≤7 days of continuous AF, n = 323) and persistent AF ((AF duration &gt; 7 days and &lt; 1 year, n = 84) using patients from AF RISK study (NCT01510210). In this AF-RISK sub-study, patients with persistent AF experienced more symptoms (higher European Heart Rhythm Association class (p &lt; 0.001)), had a higher comorbidity burden (p &lt; 0.001), and had more unfavorable echocardiographic parameters (p &lt; 0.001). All three biomarker levels were significantly higher in patients with persistent AF as compared to those with pAF (p &lt; 0.001). Multivariate linear regression analyses showed that age (beta-coefficient for NTproBNP: 0.21; GDF-15: 0.41; Troponin-T: 0.23) and CHA2DS2-VASc (beta-coefficient for NTproBNP: 0.20; GDF-15: 0.25; Troponin-T: 0.27) were determinants of all three biomarkers, and that persistent AF determined NTproBNP (beta-coefficient: 0.34), but not Troponin-T and GDF-15. More detailed analysis of CHA2DS2-VASc score showed that for all three biomarkers age, coronary artery disease and heart failure were determinants of plasma biomarkers levels, whereas sex determined NTproBNP and Troponin T, and hypertension determined NTproBNP and GDF15. Overall, this study therefore suggests that in AF, Troponin T and GDF15, and especially NTproBNP could be used to detect those patients with more persistent form of AF that may warrant more aggressive treatment of AF and concomitant comorbidities. Future studies, however, are essential to evaluate if more aggressive AF treatment and risk factor management will reduce disease progression and holds a novel therapeutic intervention to reduce the burden of AF.</p

Preterm white matter injury : ultrasound diagnosis and classification

White matter injury (WMI) is the most frequent form of preterm brain injury. Cranial ultrasound (CUS) remains the preferred modality for initial and sequential neuroimaging in preterm infants, and is reliable for the diagnosis of cystic periventricular leukomalacia. Although magnetic resonance imaging is superior to CUS in detecting the diffuse and more subtle forms of WMI that prevail in very premature infants surviving nowadays, recent improvement in the quality of neonatal CUS imaging has broadened the spectrum of preterm white matter abnormalities that can be detected with this technique. We propose a structured CUS assessment of WMI of prematurity that seeks to account for both cystic and non-cystic changes, as well as signs of white matter loss and impaired brain growth and maturation, at or near term equivalent age. This novel assessment system aims to improve disease description in both routine clinical practice and clinical research. Whether this systematic assessment will improve prediction of outcome in preterm infants with WMI still needs to be evaluated in prospective studies

Data quality in diffusion tensor imaging studies of the preterm brain: a systematic review

Background: To study early neurodevelopment in preterm infants, evaluation of brain maturation and injury is increasingly performed using diffusion tensor imaging, for which the reliability of underlying data is paramount. Objective: To review the literature to eva

State-of-the-art neonatal cerebral ultrasound: technique and reporting

In the past three decades, cerebral ultrasound (CUS) has become a trusted technique to study the neonatal brain. It is a relatively cheap, non-invasive, bedside neuroimaging method available in nearly every hospital. Traditionally, CUS was used to detect major abnormalities, such as intraventricular hemorrhage (IVH), periventricular hemorrhagic infarction, post-hemorrhagic ventricular dilatation, and (cystic) periventricular leukomalacia (cPVL). The use of different acoustic windows, such as the mastoid and posterior fontanel, and ongoing technological developments, allows for recognizing other lesion patterns (e.g., cerebellar hemorrhage, perforator stroke, developmental venous anomaly). The CUS technique is still being improved with the use of higher transducer frequencies (7.5-18\u2009MHz), 3D applications, advances in vascular imaging (e.g. ultrafast plane wave imaging), and improved B-mode image processing. Nevertheless, the helpfulness of CUS still highly depends on observer skills, knowledge, and experience. In this special article, we discuss how to perform a dedicated state-of-the-art neonatal CUS, and we provide suggestions for structured reporting and quality assessment