
David LeyLund University | LU · Department of Paediatrics
David Ley
Professor
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219
Publications
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Introduction
Skills and Expertise
Publications
Publications (219)
Aim
To analyse the challenges faced by parents of extremely preterm infants born before 24 weeks of gestation and the potential buffering effect of perceived resources on the family's health continuum.
Methods
The qualitative data were obtained from 70 parents of 70 infants born before 24 weeks of gestation, through open‐ended questions in a surve...
Background
Two risk factors for severe retinopathy of prematurity (ROP) in extremely preterm infants are thrombocytopenia and low levels of arachidonic acid (AA) and docosahexaenoic acid (DHA). To date, these risk factors have not been linked.
Method
Infants born < 28 weeks gestational age (GA) from 2016 to 2019 were randomized to postnatal entera...
Objective
To evaluate if postnatal treatment with betamethasone in extremely preterm infants was associated with neurodevelopmental impairment (NDI) at 6.5 years of age.
Design
Prospective cohort study.
Setting
Extremely Preterm Infants in Sweden Study (gestational age <27 weeks, born 2004–2007).
Patients
428 children born extremely preterm were...
Reduced serum level of insulin-like growth factor 1 (IGF-1), a major regulator of perinatal development, in extremely preterm infants has been shown to be associated with neurodevelopmental impairment. To clarify the mechanism of IGF-1 transport at the blood-cerebrospinal fluid (CSF) barrier of the immature brain, we combined studies of in vivo pre...
Aim
To evaluate if increased survival and new ventilation strategies were accompanied by a changed incidence of bronchopulmonary dysplasia (BPD) in Sweden over a decade.
Methods
Data from two Swedish population-based studies of live-born infants with gestational ages (GA) 22–26 weeks, born during 2004–2007 (n=702) and 2014–2016 (n=885), were compa...
Objective
To investigate the relationship between the fraction of fetal haemoglobin (HbF(%)) and oxygen requirement as determined by the fraction of inspired oxygen (FiO 2 ) and alveolar–arterial gradient (A–a gradient). Increased alveolar exposure to oxygen may explain the association between decreased HbF(%) and the development of bronchopulmonar...
Background:
Neurofilament light chain (NfL) is known for indicating adult brain injury, but the role of NfL in extremely preterm infants is less studied. This study examines the relationship between NfL and neurovascular morbidities in these infants.
Methods:
A secondary analysis of the Mega Donna Mega trial was conducted on preterm infants <28...
Aim
We evaluated the increased centralisation of extremely preterm (EPT) births in Sweden in relation to the changes in mortality and morbidity.
Methods
Population‐based data covering Swedish live births from 22 + 0 to 26 + 6 weeks of gestation during 2004–2007 and 2014–2016 were analysed for associations between time‐period, birth within (inborn)...
Aim
To assess experience of care, well‐being of parents and children's development in a cohort of extremely premature infants born <24 weeks of gestation in Sweden from 2007 to 2018.
Methods
A survey based on multiple questionnaires answered by 124/349 (35.5%) parents.
Results
The median age of parents and children was 43 and 9 years, respectivel...
Background & aim: Clinical trials supplementing the long-chain polyunsaturated fatty acids (LCPUFAs) docosahexaenoic acid (DHA) and arachidonic acid (AA) to preterm infants have shown positive effects on inflammation-related morbidities, but the molecular mechanisms underlying these effects are not fully elucidated. This study aimed to determine as...
Insulin-like growth factor-1 (IGF-1) is essential for normal brain development and regulates processes of vascular maturation. The pathogenesis of intraventricular hemorrhage (IVH) relates to the fragility of the immature capillaries in the germinal matrix, and its inability to resist fluctuations in cerebral blood flow. In this work, using differe...
Objective
To investigate potential risk factors behind the increased incidence of necrotising enterocolitis (NEC) in Swedish extremely preterm infants.
Design
Registry data from two population-based national cohorts were studied. NEC diagnoses (Bell stage ≥II) were validated against hospital records.
Patients
All liveborn infants <27 weeks of ges...
Left ventricular shape alterations predict cardiovascular outcomes and have been observed in children born preterm and after fetal growth restriction (FGR). The aim was to investigate whether left ventricular shape is altered in adolescents born very preterm and if FGR has an additive effect. Adolescents born very preterm due to verified early-onse...
Insulin-like growth factor-1 (IGF-1) is essential for normal brain development and regulates essential processes of vascular maturation and stabilization. Importantly, preterm birth is associated with reduced serum levels of IGF-1 as compared to in utero levels. Using a preterm rabbit pup model, we investigated the uptake of systemic recombinant hu...
Background
Germinal matrix hemorrhage and intraventricular hemorrhage (GMH‐IVH) may contribute to neonatal morbidity and mortality and result in long‐term neurodevelopmental sequelae. Appropriate pain and sedation management in ventilated preterm infants may decrease the risk of GMH‐IVH; however, it might be associated with harms.
Objectives
To su...
Neonates with critical congenital heart defects undergoing open-heart surgery on cardiopulmonary bypass circulation are at risk for white matter brain injury. This article reports on pre- and postoperative plasma concentrations of brain injury markers glial fibrillary acidic protein (GFAP), neurofilament light (NfL) and Tau, and their respective as...
Background
Preterm birth is the leading cause of neonatal mortality and morbidity. Early diagnosis and interventions are critical to improving the clinical outcomes of extremely premature infants. Blood protein profiling during the first months of life in preterm infants can shed light on the role of early extrauterine development and provide an in...
Background:
We investigated ophthalmological outcomes at 2.5 years of corrected age in children born extremely preterm (EPT) to evaluate the effects of postnatal enteral supplementation with ω-3 and ω-6 long-chain polyunsaturated fatty acids.
Methods:
In the Mega Donna Mega clinical trial, EPT infants born at less than 28 weeks of gestation were...
Objective
To explore associations between perinatal activity and survival in infants born at 22 and 23 weeks of gestation in Sweden.
Design/Setting
Data on all births at 22 and 23 weeks’ gestational age (GA) were prospectively collected in 2004–2007 (T1) or obtained from national registers in 2014–2016 (T2) and 2017–2019 (T3). Infants were assigne...
Objective
Blood cell populations, including red blood cells (RBC) unique to the extremely preterm (EPT) infant, are potentially lost due to frequent clinical blood sampling during neonatal intensive care. Currently, neonatal RBC population heterogeneity is not described by measurement of total haemoglobin or haematocrit. We therefore aimed to descr...
Objective
To quantify the risks of mortality, morbidity and postnatal characteristics associated with extreme preterm fetal growth restriction (EP-FGR).
Design
The EVERREST (Do e s v ascular endothelial growth factor gene therapy saf e ly imp r ove outcome in seve r e e arly-onset fetal growth re st riction?) prospective multicentre study of women...
Background and aim:
Preterm infants risk deficits of long-chain polyunsaturated fatty acids (LCPUFAs) that may contribute to morbidities and hamper neurodevelopment. We aimed to determine longitudinal serum fatty acid profiles in preterm infants and how the profiles are affected by enteral and parenteral lipid sources.
Methods:
Cohort study analyzi...
Very preterm infants show low levels of insulin-like growth factor-1 (IGF-1), which is associated with postnatal growth restriction and poor neurologic outcomes. It remains unknown whether supplemental IGF-1 may stimulate neurodevelopment in preterm neonates. Using cesarean-delivered preterm pigs as a model of preterm infants, we investigated the e...
Children born before 24 gestational weeks had high neonatal morbidity and a majority had one or more neurodevelopmental disorders in addition to somatic diagnoses in childhood. Active Swedish perinatal care of infants with gestational age <24 weeks has resulted in a survival rate of more than 50 percent. Resuscitation of these immature infants is c...
Germinal matrix-intraventricular haemorrhage (GMH-IVH) and encephalopathy of prematurity (EoP) remain substantial issues in neonatal intensive care units worldwide. Current therapies to prevent or treat these conditions are limited. Stem cell-based therapies offer a potential therapeutic approach to repair, restore, or regenerate injured brain tiss...
An increasing number of long-term follow-up studies of growth-restricted infants has been published during the recent years. This chapter reviews implications of abnormal fetal blood flow in fetal growth restriction (FGR) on postnatal development. The majority of follow-up studies has focused on examining relationships between absent or reverse end...
Preterm birth is the leading cause of neonatal mortality and morbidity. Early diagnosis and interventions are critical to improve the clinical outcomes of extremely premature infants. Here, we have investigated the blood protein profiles during the first months of life in preterm infants to shed light on the role of early extrauterine development....
Background
Preterm birth and fetal growth restriction (FGR) are associated with structural and functional kidney changes, increasing long-term risk for chronic kidney disease and hypertension. However, recent studies in preterm children are conflicting, indicating structural changes but normal kidney function. This study therefore assessed kidney s...
Background
Although preterm birth predisposes for cardiovascular disease, recent studies in children indicate normal blood pressure and arterial stiffness. This prospective cohort study therefore assessed blood pressure and arterial stiffness in adolescents born very preterm due to verified fetal growth restriction (FGR).
Methods
Adolescents (14 (...
Exposure to circulating cell-free hemoglobin is a ubiquitous feature of open-heart surgery on cardiopulmonary bypass circulation. This study aims to determine the origins and dynamics of circulating cell-free hemoglobin and its major scavenger proteins haptoglobin and hemopexin during neonatal cardiopulmonary bypass. Forty neonates with an isolated...
Background
Growth factors important for normal brain development are low in preterm infants. This study investigated the link between growth factors and preterm brain volumes at term.
Material/methods
Infants born <28 weeks gestational age (GA) were included. Endogenous levels of insulin-like growth factor (IGF)−1, brain-derived growth factor, vas...
Background
Intraventricular hemorrhage causes significant lifelong mortality and morbidity, especially in preterm born infants. Progress in finding an effective therapy is stymied by a lack of preterm animal models with long-term follow-up. This study addresses this unmet need, using an established model of preterm rabbit IVH and analyzing outcomes...
Objective
To determine if plasma transfusions with male donor plasma to very preterm infants affect circulatory levels of sex steroids.
Design and patients
Retrospective multicentre cohort study in 19 infants born at gestational age <29 weeks requiring plasma transfusion during their first week of life.
Setting
Three neonatal intensive care units...
This study assesses rates of extremely preterm births (22-26 weeks’ gestation) and their outcomes by hospital level of care among all births registered in Sweden from 2014 to 2019.
Objectives:
To determine the costs directly or indirectly related to bronchopulmonary dysplasia (BPD) in preterm infants. The secondary objective was to stratify the costs based on gestational age and/or birth weight.
Design:
Systematic literature review.
Setting:
PubMed and Scopus were searched on 3 February 2020. Studies were selected based...
Following preterm birth, serum levels of insulin-like growth factor 1 (IGF-1) decrease compared to corresponding in utero levels. A recent clinical trial indicated that supplementation with recombinant human (rh) IGF-1/rhIGF-binding protein 3 (rhIGF-1/rhIGFBP-3) prevents severe intraventricular hemorrhage (IVH) in extremely preterm infants. In a pr...
Importance
Circulating levels of neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) are important in the course of brain injury in adults, but longitudinal postnatal circulating levels in preterm infants have not been investigated.
Objectives
To examine postnatal longitudinal serum levels of NfL and GFAP in preterm infants during...
Introduction:
Thrombocytopenia has been identified as an independent risk factor for retinopathy of prematurity (ROP), although underlying mechanisms are unknown. In this study, the association of platelet count and serum platelet-derived factors with ROP was investigated.
Methods:
Data for 78 infants born at gestational age (GA) <28 weeks were...
Background
Germinal matrix intraventricular hemorrhage (GM-IVH) is associated with deposition of redox active cell-free hemoglobin (Hb), derived from hemorrhagic cerebrospinal fluid (CSF), in the cerebrum and cerebellum. In a recent study, using a preterm rabbit pup model of IVH, intraventricularly administered haptoglobin (Hp), a cell-free Hb scav...
Background:
Blood loss and adult blood transfusions are common during the neonatal period in preterm infants. The objective of the study was to clarify if degree of loss of fetal haemoglobin (HbF) was associated with later retinopathy of prematurity (ROP).
Methods:
Retrospective observational cohort study. In total, 452 infants born <30 gestatio...
Importance
Lack of arachidonic acid (AA) and docosahexaenoic acid (DHA) after extremely preterm birth may contribute to preterm morbidity, including retinopathy of prematurity (ROP).
Objective
To determine whether enteral supplementation with fatty acids from birth to 40 weeks’ postmenstrual age reduces ROP in extremely preterm infants.
Design, S...
Objective
To examine the prevalence of dysnatraemias among children admitted for paediatric surgery before and after a change from hypotonic to isotonic intravenous maintenance fluid therapy.
Design
Retrospective consecutive time series intervention study.
Setting
Paediatric surgery ward at the Children’s Hospital in Lund, during a 7-year period,...
Background: Postnatal insulin-like growth factor-1 (IGF-1) replacement with recombinant human (rh)IGF-1 and IGF binding protein-3 (rhIGF-1/rhIGFBP-3) is being studied as a potential treatment to reduce comorbidities of prematurity. We have recently reported on a phase II, multicenter, randomized, controlled trial comparing postnatal rhIGF-1/rhIGFBP...
Hyperglycemia, insulin insensitivity, and low IGF1 levels in extremely preterm infants are associated with an increased risk of retinopathy of prematurity (ROP), but the interactions are incompletely understood. In 117 extremely preterm infants, serum glucose levels and parenteral glucose intake were recoded daily in the first postnatal week. Serum...
Objective
Early decrease in fetal haemoglobin (HbF) is an indicator of loss of endogenous blood components that might have predictive value for development of bronchopulmonary dysplasia (BPD). The link between HbF and BPD has not been evaluated.
Design
Retrospective observational study.
Setting
Tertiary level neonatal intensive care unit, referra...
Background:
Hypoxic-ischaemic encephalopathy (HIE) is a leading cause of mortality and long-term neurological sequelae, affecting thousands of children worldwide. Current therapies to treat HIE are limited to cooling. Stem cell-based therapies offer a potential therapeutic approach to repair or regenerate injured brain tissue. These preclinical fi...
( JAMA . 2019;321(12):1188–1199)
Since 2004-2007, Sweden has created new recommendations, regulations and laws concerning extremely preterm births. In 2008, it became mandatory to register all stillbirths at 22 to 27 weeks’ gestational age to record statistics for all extremely preterm births. The withholding or withdrawal of advanced life support...
[This corrects the article DOI: 10.3389/fphys.2016.00330.].
Neonates born with critical congenital heart defects are at risk of diffuse white matter injuries and neurodevelopmental impairments. This study aimed to determine the impact of circulating cell-free hemoglobin and hyperoxia, both present during cardiopulmonary bypass circulation, on white matter brain development. Postnatal day 6 rat pups were inj...
Neonatal caffeine treatment might affect brain development. Long-term studies show conflicting results on brain-related outcomes. Herein we aimed to investigate the long-term effects of neonatal caffeine administration in a rabbit model of preterm birth.
Preterm (born day 29) and term (day 32) pups were raised by wet nurses and allocated to treatme...
Background
Newborns, admitted to the Neonatal Intensive Care Unit (NICU), are exposed to a large number of medications, the majority of which are not labeled for use in infants, especially in preterm newborns, because clinical trials on their benefits and harms are lacking. There is a huge gap in knowledge on pharmacokinetic (PK) data in sick prete...
Germinal matrix–intraventricular hemorrhage (IVH) occurs in nearly half of infants born at less than 26 weeks’ gestation. Up to 50% of survivors with IVH develop cerebral palsy, cognitive deficits, behavioral disorders, posthemorrhagic ventricular dilatation, or a combination of these sequelae. After the initial bleeding and the primary brain injur...
Objective:
Steady state insulin-like growth factor-1 (IGF-1) levels vary significantly during continuous intravenous infusion of recombinant human insulin-like growth factor-1/recombinant human insulin-like growth factor binding protein-3 (rhIGF-1/rhIGFBP-3) in the first weeks of life in extremely preterm infants. We evaluated interleukin-6 (IL-6)...
The recently documented high survival of extremely preterm infants in Sweden is related to a high degree of centralization of pre- and postnatal care and to recently issued national consensus guidelines providing recommendations for perinatal care at 22-24 gestational weeks. The prevalence of major neonatal morbidity remains high and exceeded 60 %...
Background:
Germinal matrix-intraventricular haemorrhage (GMH-IVH) remains a substantial issue in neonatal intensive care units worldwide. Current therapies to prevent or treat GMH-IVH are limited. Stem cell-based therapies offer a potential therapeutic approach to repair, restore, and/or regenerate injured brain tissue. These preclinical findings...
Aim:
Studies indicate that reduced fetal haemoglobin levels are related to increased neonatal morbidity rates. This study investigated the relationships between sampling-related blood loss and adult blood transfusions administered during postnatal day 1-14 and the development of severe neonatal morbidities in extremely preterm infants born before...
(Abstracted from JAMA 2019;321(12):1188–1199)
The long-term health outcomes for preterm infants have improved over time, but infants born at extreme preterm gestational ages continue to present issues of optimal antenatal and postnatal management, resource allocation and costs, quality of care, and long-term health outcomes. To better understand va...
Background:
Germinal matrix intraventricular hemorrhage (GM-IVH) is associated with cerebro-cerebellar damage in very preterm infants, leading to neurodevelopmental impairment. Penetration, from the intraventricular space, of extravasated red blood cells and extracellular hemoglobin (Hb), to the periventricular parenchyma and the cerebellum has be...
Context
Little is known about the individual response of glucose-regulating factors to administration of exogenous insulin infusion in extremely preterm infants.
Objective
To evaluate longitudinal serum concentrations of insulin, C-peptide, and plasma glucose levels in a high frequency sampling regimen in extremely preterm infants treated with ins...
Importance
Since 2004-2007, national guidelines and recommendations have been developed for the management of extremely preterm births in Sweden. If and how more uniform management has affected infant survival is unknown.
Objective
To compare survival of extremely preterm infants born during 2004-2007 with survival of infants born during 2014-2016...
Objective:
To compare the effect of early and late intervention for posthemorrhagic ventricular dilatation on additional brain injury and ventricular volume using term-equivalent age-MRI.
Study design:
In the Early vs Late Ventricular Intervention Study (ELVIS) trial, 126 preterm infants ≤34 weeks of gestation with posthemorrhagic ventricular di...
We are grateful to Vliegenthart et al for their letter (1) commenting on our systematic review, which compared the use of high versus low dose caffeine in preterm infants (2). A clear definition of the inclusion criteria in a systematic review is an essential step to minimise the risk of intellectual bias. Vliegenthart et al state that pooling the...
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:To determine the efficacy and safety of stem cell-based interventions for the treatment of hypoxic-ischaemic encephalopathy (HIE) in newborn infants.
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
To determine the efficacy and safety of stem cell-based interventions for the prevention or treatment of germinal matrix-intraventricular haemorrhage (GM-IVH) in preterm infants.