Human milk feeding and cognitive outcome in preterm infants: the role of infection and NEC reduction

BACKGROUND: Breast milk has been associated with lower risk of infection and necrotising enterocolitis (NEC) and improved long-term cognitive outcomes in preterm infants but, if unsupplemented, does not meet the nutritional requirements of preterm infants. METHODS: Preterm infants were randomised to receive a high nutrient intervention diet: preterm formula (PTF) or the standard diet: term formula (TF) or banked donor breast milk (BBM), either as their sole diet or as supplement to maternal breast milk (MBM). IQ tests were performed at ages 7, 15, 20, and 30 years. RESULTS: An increase in MBM and BBM intake was associated with a lower chance of neonatal infection/NEC. Neonatal infection/NEC was associated with lower Full Scale IQ (FSIQ) and Performance IQ (PIQ) score at ages 7 and 30 years. The relationship between higher intake of MBM and PIQ at age 7 years was partly mediated by neonatal infection/NEC. The intervention diet was associated with higher Verbal IQ (VIQ) scores compared to the standard diet. There was no evidence that these effects changed from childhood through to adulthood. CONCLUSIONS: Neonatal diet is an important modifiable factor that can affect long-term cognitive outcome through a 'human milk' factor, protecting against infection/NEC, and a 'nutrient content' factor. IMPACT: This is the first study to demonstrate the effects of neonatal infection/necrotising enterocolitis (NEC) on IQ in the same cohort in childhood and adulthood. Diet can be a key factor in long-term cognitive outcome in people born preterm by preventing neonatal infection/NEC and providing adequate nutrients. Human milk, whether MBM or BBM, is associated with a reduced risk of infection/NEC. A higher nutrient diet is associated with better cognitive outcome in childhood. Performance IQ is particularly vulnerable to the effects of infection/NEC and verbal IQ to the quantity of (macro)nutrients in the diet

Postpartum blood pressure self-management following hypertensive pregnancy: protocol of the Physician Optimised Post-partum Hypertension Treatment (POP-HT) trial.

INTRODUCTION: New-onset hypertension affects approximately 10% of pregnancies and is associated with a significant increase in risk of cardiovascular disease in later life, with blood pressure measured 6 weeks postpartum predictive of blood pressure 5-10 years later. A pilot trial has demonstrated that improved blood pressure control, achevied via self-management during the puerperium, was associated with lower blood pressure 3-4 years postpartum. Physician Optimised Post-partum Hypertension Treatment (POP-HT) will formally evaluate whether improved blood pressure control in the puerperium results in lower blood pressure at 6 months post partum, and improvements in cardiovascular and cerebrovascular phenotypes. METHODS AND ANALYSIS: POP-HT is an open-label, parallel arm, randomised controlled trial involving 200 women aged 18 years or over, with a diagnosis of pre-eclampsia or gestational hypertension, and requiring antihypertensive medication at discharge. Women are recruited by open recruitment and direct invitation around time of delivery and randomised 1:1 to, either an intervention comprising physician-optimised self-management of postpartum blood pressure or, usual care. Women in the intervention group upload blood pressure readings to a 'smartphone' app that provides algorithm-driven individualised medication-titration. Medication changes are approved by physicians, who review blood pressure readings remotely. Women in the control arm follow assessment and medication adjustment by their usual healthcare team. The primary outcome is 24-hour average ambulatory diastolic blood pressure at 6-9 months post partum. Secondary outcomes include: additional blood pressure parameters at baseline, week 1 and week 6; multimodal cardiovascular assessments (CMR and echocardiography); parameters derived from multiorgan MRI including brain and kidneys; peripheral macrovascular and microvascular measures; angiogenic profile measures taken from blood samples and levels of endothelial circulating and cellular biomarkers; and objective physical activity monitoring and exercise assessment. An additional 20 women will be recruited after a normotensive pregnancy as a comparator group for endothelial cellular biomarkers. ETHICS AND DISSEMINATION: IRAS PROJECT ID 273353. This trial has received a favourable opinion from the London-Surrey Research Ethics Committee and HRA (REC Reference 19/LO/1901). The investigator will ensure that this trial is conducted in accordance with the principles of the Declaration of Helsinki and follow good clinical practice guidelines. The investigators will be involved in reviewing drafts of the manuscripts, abstracts, press releases and any other publications arising from the study. Authors will acknowledge that the study was funded by the British Heart Foundation Clinical Research Training Fellowship (BHF Grant number FS/19/7/34148). Authorship will be determined in accordance with the ICMJE guidelines and other contributors will be acknowledged. TRIAL REGISTRATION NUMBER: NCT04273854

Cardiac Remodeling After Hypertensive Pregnancy Following Physician-Optimized Blood Pressure Self-Management: The POP-HT Randomized Clinical Trial Imaging Sub-study.

Background: Hypertensive pregnancy disorders are associated with adverse cardiac remodeling, which can fail to reverse postpartum in some women. The Physician Optimized Postpartum Hypertension Treatment trial demonstrated improved blood pressure control, while the cardiovascular system recovers postpartum, associates with persistently reduced blood pressure. We now report the impact on cardiac remodeling. Methods: In this prospective, randomized, open-label, blinded endpoint trial, in a single UK hospital, 220 women were randomly assigned 1:1 to self-monitoring with research physician-optimized antihypertensive titration, or usual postnatal care from primary care physician and midwife. Participants were aged 18 years or over, with pre-eclampsia or gestational hypertension, requiring antihypertensives on hospital discharge postnatally. Pre-specified secondary cardiac imaging outcomes were recorded by echocardiography around delivery, and again at blood pressure primary outcome assessment, around nine months postpartum, when cardiovascular magnetic resonance was also performed. Results: 187 women (101 intervention; 86 usual care) underwent echocardiography at baseline and follow up, at a mean 258+/-14.6 days postpartum, of which 174 (93 intervention; 81 usual care) also had cardiovascular magnetic resonance at follow up. Relative wall thickness by echocardiography was 0.06 (95% CI0.07 to 0.05, P=<0.001) lower in the intervention group between baseline and follow up, and cardiovascular magnetic resonance at follow up demonstrated a lower left ventricular mass (-6.37g/m2 (95% CI -7.99 to -4.74, P<0.001), end diastolic volume (-3.87ml/m2, 95% CI -6.77 to -0.98, P=0.009) and end systolic volume (-3.25ml/m2, 95% CI 4.87 to -1.63, P <0.001) and higher left and right ventricular ejection fraction by 2.6% (95% CI 1.3 to 3.9, P<0.001) and 2.8% (95% CI 1.4 to 4.1, P<0.001) respectively. Echocardiography assessed left ventricular diastolic function demonstrated a mean difference in average E/E' of 0.52 (95% CI -0.97 to -0.07, P=0.024), and a reduction in left atrial volumes of -4.33ml/m2 (95% CI -5.52 to -3.21, P=<0.001) between baseline and follow up, when adjusted for baseline differences in measures. Conclusions: Short-term postnatal optimization of blood pressure control following hypertensive pregnancy, through self-monitoring and physician-guided antihypertensive titration, associates with long term changes in cardiovascular structure and function, in a pattern associated with more favorable cardiovascular outcomes

Machine learning augmented echocardiography for diastolic function assessment

&lt;jats:p&gt;Cardiac diastolic dysfunction is prevalent and is a diagnostic criterion for heart failure with preserved ejection fraction&#x2014;a burgeoning global health issue. As gold-standard invasive haemodynamic assessment of diastolic function is not routinely performed, clinical guidelines advise using echocardiography measures to determine the grade of diastolic function. However, the current process has suboptimal accuracy, regular indeterminate classifications and is susceptible to confounding from comorbidities. Advances in artificial intelligence in recent years have created revolutionary ways to evaluate and integrate large quantities of cardiology data. Imaging is an area of particular strength for the sub-field of machine-learning, with evidence that trained algorithms can accurately discern cardiac structures, reliably estimate chamber volumes, and output systolic function metrics from echocardiographic images. In this review, we present the emerging field of machine-learning based echocardiographic diastolic function assessment. We summarise how machine-learning has made use of diastolic parameters to accurately differentiate pathology, to identify novel phenotypes within diastolic disease, and to grade diastolic function. Perspectives are given about how these innovations could be used to augment clinical practice, whilst areas for future investigation are identified.&lt;/jats:p&gt

The preterm heart-brain axis in young adulthood: the impact of birth history and modifiable risk factors

People born preterm are at risk of developing both cardiac and brain abnormalities. We aimed to investigate whether cardiovascular physiology may directly affect brain structure in young adulthood and whether cardiac changes are associated with modifiable biomarkers. Forty-eight people born preterm, followed since birth, underwent cardiac MRI at age 25.1 ± 1.4 years and brain MRI at age 33.4 ± 1.0 years. Term born controls were recruited at both time points for comparison. Cardiac left and right ventricular stroke volume, left and right ventricular end diastolic volume and right ventricular ejection fraction were significantly different between preterm and term born controls and associated with subcortical brain volumes and fractional anisotropy in the corpus callosum in the preterm group. This suggests that cardiovascular abnormalities in young adults born preterm are associated with potentially adverse future brain health. Associations between left ventricular stroke volume indexed to body surface area and right putamen volumes, as well as left ventricular end diastolic length and left thalamus volumes, remained significant when adjusting for early life factors related to prematurity. Although no significant associations were found between modifiable biomarkers and cardiac physiology, this highlights that cardiovascular health interventions may also be important for brain health in preterm born adults

Association of systolic blood pressure elevation with disproportionate left ventricular remodeling in very preterm-born young adults

Importance: Preterm-born individuals have higher blood pressure with an increased risk of hypertension by young adulthood, as well as potentially adverse cardiac remodeling, even when normotensive. To what extent blood pressure elevation impacts left ventricular (LV) structure and function in adults born preterm is currently unknown. Objective: To investigate whether changes observed in LV structure and function in pretermborn adults make them more susceptible to cardiac remodeling in relation to blood pressure elevation. Design, Setting, and Participants: This cross-sectional cohort study included 468 adults aged 18 to 40 years. Of these, 200 were born preterm ( Main Outcomes and Measures: CMR measures of LV structure and function in response to systolic blood pressure elevation. Results: Normotensive and hypertensive preterm-born adults had higher LV mass index, reduced LV function, and smaller LV volumes compared to both term-born normotensive and hypertensive individuals (P<0.01). In regression analyses of systolic blood pressure with LV mass index and LV mass to end-diastolic volume ratio, there was a leftward shift in the slopes in preterm- compared to term-born adults. Compared to term-born adults, there was a 2.5-fold greater LV mass index per 1mmHg elevation in systolic blood pressure in very and extremely preterm-born adults ( Conclusions: Preterm-born adults have a unique LV structure and function that worsens with systolic blood pressure elevation. Additional primary prevention strategies specifically targeting cardiovascular risk reduction in this population may be warranted.</p

Association of preterm birth with myocardial fibrosis and diastolic dysfunction in young adulthood

Background Preterm birth affects about 10% of live births worldwide and is associated with cardiac alterations. Animal models of preterm birth suggest that left ventricular functional impairment may be due to an up-regulation of myocardial fibrosis. Objectives The aim of this study was to determine whether diffuse left ventricular fibrosis is evident in young adults born preterm. Methods One hundred one normotensive young adults born preterm (n = 47, mean gestational age 32.8 ± 3.2 weeks) and term (n = 54) were included from YACHT (Young Adult Cardiovascular Health sTudy). Left ventricular structure and function were quantified by cardiovascular magnetic resonance and echocardiography. Intravenous administration of a gadolinium-based contrast agent during cardiovascular magnetic resonance was used to quantify focal myocardial fibrosis on the basis of late gadolinium enhancement and, in combination with T1 mapping, to quantify diffuse myocardial fibrosis on the basis of assessment of myocardial extracellular volume fraction. Results Adults born preterm had smaller left ventricular end-diastolic and stroke volumes, with greater left ventricular mass and wall thickness (P < 0.001). In addition, longitudinal peak systolic strain and diastolic strain rate by both cardiovascular magnetic resonance and echocardiography, and E/A ratio measured by echocardiography, were lower in preterm-born compared to term-born adults (P < 0.05). Extracellular volume fraction was greater in preterm-born compared with term-born adults (27.81% ± 1.69% vs 25.48% ± 1.41%; P < 0.001) and was a significant mediator in the relationship between gestational age and both longitudinal peak diastolic strain rate and E/A ratio. Conclusions Preterm-born young adults have greater extracellular volume fraction in the left ventricle that is inversely related with gestational age and may underlie their diastolic functional impairments

Left atrial strain predicts cardiovascular response to exercise in young adults with suboptimal blood pressure

Aims To investigate the left ventricular response to exercise in young adults with hypertension, and identify whether this response can be predicted from changes in left atrial function at rest. Methods A total of 127 adults aged 18–40 years who completed clinical blood pressure assessment and echocardiography phenotyping at rest and during cardiopulmonary exercise testing, were included. Measurements were compared between participants with suboptimal blood pressure ≥120/80mm Hg (n = 68) and optimal blood pressure Results Participants with suboptimal blood pressure had higher left ventricular mass (p = 0.031) and reduced mitral E velocity (p = 0.02) at rest but no other cardiac differences. During exercise, their rise in left ventricular ejection fraction was reduced (p = 0.001) and they had higher left ventricular end diastolic and systolic volumes (p = 0.001 and p = 0.001, respectively). Resting cardiac size predicted left ventricular volumes during exercise but only left atrial booster pump function predicted the left ventricular ejection fraction response (urn:x-wiley:07422822:media:echo15149:echo15149-math-0001= .29, p = 0.011). This association persisted after adjustment for age, sex, body mass index, and mean arterial pressure. Conclusion Young adults with suboptimal blood pressure have a reduced left ventricular systolic response to exercise, which can be predicted by their left atrial booster pump function at rest. Echocardiographic measures of left atrial function may provide an early marker of functionally relevant, subclinical, cardiac remodelling in young adults with hypertension.</p