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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, respectively; 74.2% were mothers. Parents expressed high healthcare satisfaction. Following discharge from neonatal care, the satisfaction with the infant's treatment, support from personnel and being respected as a parent significantly declined but remained high. The criteria for suspected developmental deviation according to the screening test early symptomatic syndromes eliciting neurodevelopmental clinical examinations-questionnaire was fulfilled by 84.3%, 55.6% had suspected avoidant restrictive food intake disorder and 47.9% had visual perception problems. Parents experienced severe fatigue (48.6%) despite strong social support and family self-efficacy. Economic support was provided to 30.6%, and 37.9% of children were enrolled in habilitation services. CONCLUSION: This study highlighted the substantial challenges faced by parents of infants born before 24 weeks of gestation, including decreased satisfaction post-discharge, fatigue and concerns about children's well-being. The findings underscore the need for comprehensive family-centred support and long-term multi-professional follow-up centres.
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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, vascular endothelial growth factor, and platelet-derived growth factor (expressed as area under the curve [AUC] for serum samples from postnatal days 1, 7, 14, and 28) were utilized in a multivariable linear regression model. Brain volumes were determined by magnetic resonance imaging (MRI) at term equivalent age. RESULTS: In total, 49 infants (median [range] GA 25.4 [22.9-27.9] weeks) were included following MRI segmentation quality assessment and AUC calculation. IGF-1 levels were independently positively associated with the total brain (p < 0.001, ß = 0.90), white matter (p = 0.007, ß = 0.33), cortical gray matter (p = 0.002, ß = 0.43), deep gray matter (p = 0.008, ß = 0.05), and cerebellar (p = 0.006, ß = 0.08) volume adjusted for GA at birth and postmenstrual age at MRI. No associations were seen for other growth factors. CONCLUSIONS: Endogenous exposure to IGF-1 during the first 4 weeks of life was associated with total and regional brain volumes at term. Optimizing levels of IGF-1 might improve brain growth in extremely preterm infants. IMPACT: High serum levels of insulin-like growth factor (IGF)-1 during the first month of life were independently associated with increased total brain volume, white matter, gray matter, and cerebellar volume at term equivalent age in extremely preterm infants. IGF-1 is a critical regulator of neurodevelopment and postnatal levels are low in preterm infants. The effects of IGF-1 levels on brain development in extremely preterm infants are not fully understood. Optimizing levels of IGF-1 may benefit early brain growth in extremely preterm infants. The effects of systemically administered IGF-1/IGFBP3 in extremely preterm infants are now being investigated in a randomized controlled trial (Clinicaltrials.gov: NCT03253263).
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Lactente Extremamente Prematuro , Fator de Crescimento Insulin-Like I , Lactente , Humanos , Recém-Nascido , Fator de Crescimento Insulin-Like I/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Encéfalo , Substância Cinzenta/metabolismo , Idade Gestacional , Imageamento por Ressonância Magnética/métodosRESUMO
PURPOSE: Choline is an essential nutrient for fetal and infant growth and development. Parenteral nutrition used in neonatal care lack free choline but contain small amounts of lipid-bound choline in the form of phosphatidylcholine (PC). Here, we examined the longitudinal development of serum free choline and metabolically related compounds betaine and methionine in extremely preterm infants and how the concentrations were affected by the proportion of parenteral fluids the infants received during the first 28 postnatal days (PNDs). METHODS: This prospective study included 87 infants born at gestational age (GA) < 28 weeks. Infant serum samples were collected PND 1, 7, 14, and 28, and at postmenstrual age (PMA) 32, 36, and 40 weeks. The serum concentrations of free choline, betaine, and methionine were determined by 1H NMR spectroscopy. RESULTS: The median (25th-75th percentile) serum concentrations of free choline, betaine, and methionine were 33.7 (26.2-41.2), 71.2 (53.2-100.8), and 25.6 (16.4-35.3) µM, respectively, at PND 1. The choline concentration decreased rapidly between PND one and PND seven [18.4 (14.1-26.4) µM], and then increased over the next 90 days, though never reaching PND one levels. There was a negative correlation between a high intake of parenteral fluids and serum-free choline. CONCLUSION: Circulating free choline in extremely preterm infants is negatively affected by the proportion of parenteral fluids administered. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02760472, April 29, 2016, retrospectively registered.
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Colina , Lactente Extremamente Prematuro , Betaína , Humanos , Lactente , Recém-Nascido , Nutrição Parenteral , Estudos ProspectivosRESUMO
AIM: Extrauterine growth restriction is common among extremely preterm infants. We explored whether intake of unpasteurised maternal milk (MM) and pasteurised donor milk (DM) was associated with longitudinal growth outcomes and neonatal morbidities in extremely preterm infants. METHODS: Observational study of 90 preterm infants born between 2013 and 2015 in Gothenburg, Sweden. Data were prospectively collected on nutritional and breast milk intakes during the first 28 days. RESULTS: Ninety infants (39 girls and 51 boys) with a median gestational age of 25.3 (22.7-27.9) weeks were evaluated. MM intake (mL/kg/d) correlated positively with almost all z-scores for weight, length and head circumference at 28 postnatal days and at postmenstrual age (PMA) 32 and 36 weeks. After multivariable adjustment, MM intake and weight z-score at 28 postnatal days and at PMA 32 and 36 weeks remained significantly associated. Infants consuming ≥80% MM had more favourable weight z-scores at PMA 32 and 36 weeks. Intake of DM did not correlate with any growth outcomes. Infants without retinopathy of prematurity had a significantly higher intake of MM (mL/kg/d). CONCLUSION: Unpasteurised MM was positively associated with longitudinal growth outcomes. Motivating mothers to provide their infants with their own milk after preterm birth should be emphasised.
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Leite Humano , Nascimento Prematuro , Animais , Cefalometria , Feminino , Humanos , Lactente , Fenômenos Fisiológicos da Nutrição do Lactente , Lactente Extremamente Prematuro , Recém-Nascido , Masculino , Gravidez , Suécia/epidemiologiaRESUMO
AIM: This study evaluated poor weight gain as a risk factor for infants who required treatment for retinopathy of prematurity (ROP), by comparing those born before and after the implementation of higher oxygen saturation (SpO2 ) targets at the Queen Silvia Children's Hospital, Gothenburg, Sweden. METHODS: We compared infants born at less than 31 weeks, who were screened and, or, treated for ROP: 127 in 2011-2012 when SpO2 targets were 88-92% and 142 in 2015-2016 when they were 91-95%. The subjects were reviewed for birth characteristics, weekly weight and ROP treatment. Data were analysed using the weight, insulin-like growth factor 1, neonatal, ROP (WINROP) prediction tool. RESULTS: The 2011-2012 infants who needed ROP treatment (12.6%) had significantly poorer postnatal weight gain than those who did not, but this was not seen in the treated (17.6%) and nontreated ROP groups in 2015-2016. WINROP sensitivity decreased from 87.5% in 2011-12 to 48% in 2015-2016. CONCLUSION: After the SpO2 target range was increased from 88-92% to 91-95%, postnatal weight gain was no longer a significant risk factor and WINROP lost its ability to predict ROP requiring treatment. Risk factors clearly change as neonatal care develops.
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Oxigênio/sangue , Retinopatia da Prematuridade/epidemiologia , Aumento de Peso , Desenvolvimento Infantil , Feminino , Humanos , Lactente Extremamente Prematuro , Recém-Nascido , Masculino , Retinopatia da Prematuridade/sangue , Estudos Retrospectivos , Medição de Risco , Suécia/epidemiologiaRESUMO
AIM: Our aim was to perform an in-depth analysis of the composition of fatty acids in milk from mothers delivering extremely preterm babies. We investigated longitudinal changes in milk fatty acid profiles and the relationship between several types of fatty acids, including omega-3 and omega-6. METHODS: Milk samples were collected at three stages of lactation from 78 mothers who delivered at less than 28 weeks of pregnancy at the Sahlgrenska University Hospital, Gothenburg, Sweden, from April 2013 to September 2015. Fatty acid composition was analysed by gas chromatography-mass spectrometry. RESULTS: A reduction in long-chain polyunsaturated fatty acids (LCPUFAs) was observed during the lactation period. The concentrations of arachidonic acid and docosahexaenoic acid declined from medians of 0.34 to 0.22 mol% and 0.29 to 0.15 mol%, respectively, between postnatal day 7 and a postmenstrual age of 40 weeks. Strong correlations were found between the intermediates of several classes of fatty acids, including omega-3, omega-6 and omega-9. CONCLUSION: A rapid reduction in LCPUFA content in the mother's milk during the lactation period emphasises the importance of fatty acid supplementation to infants born extremely preterm, at least during the period corresponding to the third trimester, when rapid development of the brain and adipose tissue requires high levels of LCPUFAs.
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Ácidos Graxos/análise , Leite Humano/química , Adolescente , Adulto , Ácidos Graxos/biossíntese , Feminino , Humanos , Lactente Extremamente Prematuro , Recém-Nascido , Pessoa de Meia-Idade , Gravidez , Adulto JovemRESUMO
Neovascular eye diseases are a major cause of blindness including retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration in which new vessel formation is driven by hypoxia or metabolic abnormalities affecting the fuel supply. White-adipose-tissue derived adipokines such as adiponectin modulate metabolic responses. Increasing evidence shows that lack of adiponectin may result in retinal neovascularization. Activation of the adiponectin pathway may in turn restore energy metabolism, to suppress the drive for compensatory but ultimately pathological neovessels of retinopathy. In this review, we will summarize our current knowledge of the role of adiponectin in eye diseases of premature infants, diabetic patients as well as the elderly. Further investigations in this field are likely to lead to new preventative approaches for these diseases.
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Adiponectina/metabolismo , Retinopatia Diabética/metabolismo , Metabolismo Energético , Neovascularização Retiniana/metabolismo , Idoso , Idoso de 80 Anos ou mais , Animais , Retinopatia Diabética/patologia , Humanos , Lactente , Recém-Nascido , Neovascularização Retiniana/patologiaRESUMO
BACKGROUND: The role of vascular endothelial growth factor (VEGF) in the pathogenesis of retinopathy of prematurity (ROP) has been clearly established. However, little is known about temporal changes in circulating VEGF concentrations in the preterm infant. The objective was to determine the longitudinal serum concentrations of VEGF in relation to ROP. METHODS: This study included 52 infants born at <31 wk gestational age (non-ROP n = 33, nonproliferative ROP n = 10, treated for ROP n = 9). VEGF concentrations were analyzed in blood samples collected at birth, at 3 d postnatal age, and then weekly until at least a gestational age of 35 wk. RESULTS: VEGF concentrations at birth did not differ between groups, independent of later ROP status. In contrast, VEGF serum concentrations were significantly higher at first detection of ROP in infants who were later treated for ROP compared to infants without ROP. At the time of laser therapy, serum VEGF concentrations did not differ between groups. CONCLUSION: Circulatory concentrations of VEGF, in infants who later developed severe ROP, were elevated at the time when ROP first was detected but not at the time when current treatment most often occurred. This supports the need for further studies of circulating VEGF in relation to the timing of ROP treatment.
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Recém-Nascido Prematuro/sangue , Retinopatia da Prematuridade/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Comorbidade , Feminino , Sangue Fetal/química , Idade Gestacional , Humanos , Recém-Nascido , Doenças do Recém-Nascido/sangue , Terapia a Laser , Masculino , Projetos Piloto , Estudos Prospectivos , Retinopatia da Prematuridade/cirurgiaRESUMO
UNLABELLED: Poor postnatal growth after preterm birth does not match the normal rapid growth in utero and is associated with preterm morbidities. Insulin-like growth factor 1 (IGF-1) axis is the major hormonal mediator of growth in utero, and levels of IGF-1 are often very low after preterm birth. We reviewed the role of IGF-1 in foetal development and the corresponding preterm perinatal period to highlight the potential clinical importance of IGF-1 deficiency in preterm morbidities. CONCLUSION: There is a rationale for clinical trials to evaluate the potential benefits of IGF-1 replacement in very preterm infants.
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Desenvolvimento Fetal , Recém-Nascido Prematuro/crescimento & desenvolvimento , Fator de Crescimento Insulin-Like I/fisiologia , Animais , Terapia de Reposição Hormonal , Humanos , Recém-Nascido , Recém-Nascido Prematuro/sangueRESUMO
The neonatal period of very preterm infants is often characterized by a difficult adjustment to extrauterine life, with an inadequate nutrient supply and insufficient levels of growth factors, resulting in poor growth and a high morbidity rate. Long-term multisystem complications include cognitive, behavioral, and motor dysfunction as a result of brain damage as well as visual and hearing deficits and metabolic disorders that persist into adulthood. Insulinlike growth factor 1 (IGF-1) is a major regulator of fetal growth and development of most organs especially the central nervous system including the retina. Glucose metabolism in the developing brain is controlled by IGF-1 which also stimulates differentiation and prevents apoptosis. Serum concentrations of IGF-1 decrease to very low levels after very preterm birth and remain low for most of the perinatal development. Strong correlations have been found between low neonatal serum concentrations of IGF-1 and poor brain and retinal growth as well as poor general growth with multiorgan morbidities, such as intraventricular hemorrhage, retinopathy of prematurity, bronchopulmonary dysplasia, and necrotizing enterocolitis. Experimental and clinical studies indicate that early supplementation with IGF-1 can improve growth in catabolic states and reduce brain injury after hypoxic/ischemic events. A multicenter phase II study is currently underway to determine whether intravenous replacement of human recombinant IGF-1 up to normal intrauterine serum concentrations can improve growth and development and reduce prematurity-associated morbidities.
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Desenvolvimento Fetal , Recém-Nascido Prematuro/sangue , Recém-Nascido Prematuro/crescimento & desenvolvimento , Fator de Crescimento Insulin-Like I/metabolismo , Displasia Broncopulmonar/sangue , Hemorragia Cerebral/sangue , Enterocolite Necrosante/sangue , Feminino , Humanos , Recém-Nascido , Fator de Crescimento Insulin-Like I/análise , Gravidez , Retinopatia da Prematuridade/sangue , Cordão UmbilicalRESUMO
Many sight-threatening diseases have two critical phases, vessel loss followed by hypoxia-driven destructive neovascularization. These diseases include retinopathy of prematurity and diabetic retinopathy, leading causes of blindness in childhood and middle age affecting over 4 million people in the United States. We studied the influence of omega-3- and omega-6-polyunsaturated fatty acids (PUFAs) on vascular loss, vascular regrowth after injury, and hypoxia-induced pathological neovascularization in a mouse model of oxygen-induced retinopathy. We show that increasing omega-3-PUFA tissue levels by dietary or genetic means decreased the avascular area of the retina by increasing vessel regrowth after injury, thereby reducing the hypoxic stimulus for neovascularization. The bioactive omega-3-PUFA-derived mediators neuroprotectinD1, resolvinD1 and resolvinE1 also potently protected against neovascularization. The protective effect of omega-3-PUFAs and their bioactive metabolites was mediated, in part, through suppression of tumor necrosis factor-alpha. This inflammatory cytokine was found in a subset of microglia that was closely associated with retinal vessels. These findings indicate that increasing the sources of omega-3-PUFA or their bioactive products reduces pathological angiogenesis. Western diets are often deficient in omega-3-PUFA, and premature infants lack the important transfer from the mother to the infant of omega-3-PUFA that normally occurs in the third trimester of pregnancy. Supplementing omega-3-PUFA intake may be of benefit in preventing retinopathy.
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Ácidos Graxos Ômega-3/farmacologia , Neovascularização Patológica/induzido quimicamente , Vasos Retinianos/efeitos dos fármacos , Animais , Dieta , Gorduras na Dieta , Ácidos Graxos Ômega-6/farmacologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Doenças Retinianas/induzido quimicamente , Doenças Retinianas/tratamento farmacológicoRESUMO
AIM: Preterm children are at risk of developing increased blood pressure (BP). We evaluated possible associations between BP, early insulin-like growth factor-1 (IGF-1) and IGF-binding protein-1 (IGFBP-1) levels and retinopathy of prematurity (ROP) in preterm children. METHODS: The study included 32 infants: median gestational age 28.1 weeks (range 24.6-31.3) and birthweight standard deviation scores (SDS) (±SD) 1.0 ± 2.7. IGF-1 and IGFBP-1 at postnatal weeks 32.6-34.6 and ROP stages were established after birth. BP was measured at the age of 4 years. The ratio (IGF-1)(2)/IGFBP-1 was created to investigate the influence of both IGF-1 and IGFBP-1 to later BP. RESULTS: Diastolic BP correlated with IGFBP-1, inversely correlated with IGF-1 and IGF-1(2)/IGFBP-1 (r = -0.71, p < 0.0001) and positively correlated with catch-up growth velocity from lowest weight SDS to age 36.5 weeks (r = 0.48, p < 0.01), independent of gestational age. Children with moderate-to-severe ROP as neonates had higher mean arterial BP [78 (±95%CI 74-83) vs 71 (±95%CI 68-75) mm Hg, p < 0.05] adjusted for gestational age and birthweight SDS compared to children diagnosed with no to mild ROP. CONCLUSION: Low neonatal IGF-1(2)/IGFBP-1 and severe ROP were associated with higher BP in 4-year-old children born very preterm and may thus predict future cardiovascular morbidity.
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Pressão Sanguínea , Hipertensão/complicações , Recém-Nascido Prematuro/sangue , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Retinopatia da Prematuridade/complicações , Pré-Escolar , Feminino , Idade Gestacional , Crescimento , Humanos , Hipertensão/fisiopatologia , Recém-Nascido , Recém-Nascido Prematuro/fisiologia , Masculino , Retinopatia da Prematuridade/fisiopatologia , Índice de Gravidade de DoençaRESUMO
Topic: Retinopathy of prematurity (ROP) is a severe retinal vascular disorder affecting preterm infants, potentially leading to retinal detachment and blindness. This review aims to elucidate the relationship between systemic VEGF levels and ROP. Clinical Relevance: This systematic review aims to consolidate evidence from available studies to guide future research and inform clinical practice. In particular, the role of circulating VEGF-A levels in predicting ROP onset and progression, and evaluating the impact of anti-VEGF therapy on these levels, is crucial in ensuring efficacy and safety in patient care. Methods: Scopus and PubMed were searched to identify studies investigating circulating VEGF-gene products in ROP patients using immunologic assays. Two authors independently screened the literature and extracted data, employing a random-effects meta-analysis to compare VEGF levels as the ratio of means between ROP patients and controls before and after treatment, heterogeneity was reported by I2-statistics. Risks of bias and publication bias were assessed using Quality Assessment of Diagnostic Accuracy Studies-2 and funnel plots/Egger's tests, respectively. Results: Out of 941 papers, 54 were included, with 26 providing posttreatment data and 31 providing biomarker data. Findings show a significant decrease in VEGF-A levels in the first week after ROP treatment (ratio of means [95% confidence interval] 0.34 [0.25-0.45], I2 = 97%, 17 publications). Anti-VEGF therapy showed a significantly more pronounced decrease (0.31 [0.25-0.38], I2 = 40%, 7 publications) than laser treatment in the first week after treatment (0.77 [0.61-0.97], I2 = 42%, 2 publications, subgroup difference, P < 0.01), among studies with a low risk of bias. Serum samples demonstrated a more marked decrease in VEGF-A than plasma (subgroup difference P < 0.01). However, the use of blood VEGF-A concentration as a biomarker for ROP prediction has shown inconsistent trends. The risk of bias mainly stems from unclear patient selection and lack of sample timing or analytical method details. Conclusion: While anti-VEGF treatment significantly reduced blood VEGF-A levels in the first week post-ROP treatment, blood VEGF-A levels did not consistently predict ROP development. Heterogeneity in the results underscores the need for optimized analytical methods and emphasizes the importance of considering individual variation in VEGF-A concentrations independent of ROP diagnosis. Financial Disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article.
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BACKGROUND: To evaluate the relationships between postnatal change in circulatory insulin-like growth factor-I (IGF-I) concentrations, brain volumes, and developmental outcome at 2 y of age in very preterm infants. METHODS: IGF-I was measured weekly, and nutritional intake was calculated daily from birth until a postmenstrual age (PMA) of 35 wk. Individual ß coefficients for IGF-I, IGF-I(B), representing the rate of increase in IGF-I from birth until a PMA of 35 wk were calculated. Brain magnetic resonance imaging was performed at term age, with segmentation into total brain, cerebellar, gray matter, and unmyelinated white matter volume (UWMV). Developmental outcome was evaluated using Bayley Scales of Infant Development-II. RESULTS: Forty-nine infants, with mean gestational age (GA) of 26.0 wk, were evaluated at mean 24.6 mo corrected age. Higher IGF-I(B), UWMV, and cerebellar volume were associated with a decreased risk for a Mental Developmental Index (MDI) < 85 (odds ratio (95% confidence interval): 0.6 (0.4-0.9), 0.96 (0.94-0.99), and 0.78 (0.6-0.96), respectively). In multivariate analysis, higher IGF-I(B) and higher UWMV combined with female gender constituted the two models with the highest predictive value for MDI > 85. CONCLUSION: A higher rate of increase in circulating IGF-I is associated with a decreased risk for subnormal MDI at 2 y of corrected age. This relationship is in part dependent on brain volume at term age.
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Encéfalo/crescimento & desenvolvimento , Desenvolvimento Infantil/fisiologia , Lactente Extremamente Prematuro/crescimento & desenvolvimento , Fator de Crescimento Insulin-Like I/metabolismo , Pré-Escolar , Feminino , Humanos , Fenômenos Fisiológicos da Nutrição do Lactente , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Tamanho do Órgão , SuéciaRESUMO
BACKGROUND: In preterm infants, low levels of insulin-like growth factor-I (IGF-I) and IGF binding protein 3 (IGFBP-3) are associated with impaired brain growth and retinopathy of prematurity (ROP). Treatment with IGF-I/IGFBP-3 may be beneficial for brain development and may decrease the prevalence of ROP. METHODS: In a phase II pharmacokinetics and safety study, five infants (three girls) with a median (range) gestational age (GA) of 26 wk + 6 d (26 wk + 0 d to 27 wk + 2 d) and birth weight of 990 (900-1,212) g received continuous intravenous infusion of recombinant human (rh)IGF-I/rhIGFBP-3. Treatment was initiated during the first postnatal day and continued for a median (range) duration of 168 (47-168) h in dosages between 21 and 111 µg/kg/24 h. RESULTS: Treatment with rhIGF-I/rhIGFBP-3 was associated with higher serum IGF-I and IGFBP-3 concentrations (P < 0.001) than model-predicted endogenous levels. Of 74 IGF-I samples measured during study drug infusion, 37 (50%) were within the target range, 4 (5%) were above, and 33 (45%) were below. The predicted dose of rhIGF-I/rhIGFBP-3 required to establish circulating levels of IGF-I within the intrauterine range in a 1,000 g infant was 75-100 µg/kg/24 h. No hypoglycemia or other adverse effects were recorded. CONCLUSION: In this study, continuous intravenous infusion of rhIGF-I/rhIGFBP-3 was effective in increasing serum concentrations of IGF-I and IGFBP-3, and was found to be safe.
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Encéfalo/crescimento & desenvolvimento , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/farmacocinética , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like I/farmacocinética , Retinopatia da Prematuridade/prevenção & controle , Encéfalo/metabolismo , Feminino , Humanos , Lactente Extremamente Prematuro , Recém-Nascido , Infusões Intravenosas , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/administração & dosagem , Fator de Crescimento Insulin-Like I/administração & dosagem , Masculino , SuéciaRESUMO
BACKGROUND/AIMS: Retinopathy of prematurity (ROP) is currently diagnosed through repeated eye examinations to find the low percentage of infants that fulfil treatment criteria to reduce vision loss. A prediction model for severe ROP requiring treatment that might sensitively and specifically identify infants that develop severe ROP, DIGIROP-Birth, was developed using birth characteristics. DIGIROP-Screen additionally incorporates first signs of ROP in different models over time. The aim was to validate DIGIROP-Birth, DIGIROP-Screen and their decision support tool on a contemporary Swedish cohort. METHODS: Data were retrieved from the Swedish national registry for ROP (2018-2019) and two Swedish regions (2020), including 1082 infants born at gestational age (GA) 24 to <31 weeks. The predictors were GA at birth, sex, standardised birth weight and age at the first sign of ROP. The outcome was ROP treatment. Sensitivity, specificity and area under the receiver operating characteristic curve (AUC) with 95% CI were described. RESULTS: For DIGIROP-Birth, the AUC was 0.93 (95% CI 0.90 to 0.95); for DIGIROP-Screen, it ranged between 0.93 and 0.97. The specificity was 49.9% (95% CI 46.7 to 53.0) and the sensitivity was 96.5% (95% CI 87.9 to 99.6) for the tool applied at birth. For DIGIROP-Screen, the cumulative specificity ranged between 50.0% and 78.7%. One infant with Beckwith-Wiedemann syndrome who fulfilled criteria for ROP treatment and had no missed/incomplete examinations was incorrectly flagged as not needing screening. CONCLUSIONS: DIGIROP-Birth and DIGIROP-Screen showed high predictive ability in a contemporary Swedish cohort. At birth, 50% of the infants born at 24 to <31 weeks of gestation were predicted to have low risk of severe ROP and could potentially be released from ROP screening examinations. All routinely screened treated infants, excluding those screened for clinical indications of severe illness, were correctly flagged as needing ROP screening.
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Retinopatia da Prematuridade , Recém-Nascido , Lactente , Humanos , Retinopatia da Prematuridade/diagnóstico , Retinopatia da Prematuridade/epidemiologia , Retinopatia da Prematuridade/terapia , Suécia/epidemiologia , Fatores de Risco , Recém-Nascido Prematuro , Peso ao Nascer , Idade Gestacional , Triagem Neonatal , Estudos RetrospectivosRESUMO
BACKGROUND & 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 analyzing fatty acid data from the Mega Donna Mega study, a randomized control trial with infants born <28 weeks of gestation (n = 204) receiving standard nutrition or daily enteral lipid supplementation with arachidonic acid (AA):docosahexaenoic acid (DHA) (100:50 mg/kg/day). Infants received an intravenous lipid emulsion containing olive oil:soybean oil (4:1). Infants were followed from birth to postmenstrual age 40 weeks. Levels of 31 different fatty acids from serum phospholipids were determined by GC-MS and reported in relative (mol%) and absolute concentration (µmol l-1) units. RESULTS: Higher parenteral lipid administration resulted in lower serum proportion of AA and DHA relative to other fatty acids during the first 13 weeks of life (p < 0.001 for the 25th vs the 75th percentile). The enteral AA:DHA supplement increased the target fatty acids with little impact on other fatty acids. The absolute concentration of total phospholipid fatty acids changed rapidly in the first weeks of life, peaking at day 3, median (Q1-Q3) 4452 (3645-5466) µmol l-1, and was positively correlated to the intake of parenteral lipids. Overall, infants displayed common fatty acid trajectories over the study period. However, remarkable differences in fatty acid patterns were observed depending on whether levels were expressed in relative or absolute units. For example, the relative levels of many LCPUFAs, including DHA and AA, declined rapidly after birth while their absolute concentrations increased in the first week of life. For DHA, absolute levels were significantly higher compared to cord blood from day 1 until postnatal week 16 (p < 0.001). For AA, absolute postnatal levels were lower compared to cord blood from week 4 throughout the study period (p < 0.05). CONCLUSIONS: Our data show that parenteral lipids aggravate the postnatal loss of LCPUFAs seen in preterm infants and that serum AA available for accretion is below that in utero. Further research is needed to establish optimal postnatal fatty acid supplementation and profiles in extremely preterm infants to promote development and long-term health. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov, identifier: NCT03201588.
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Ácidos Docosa-Hexaenoicos , Ácidos Graxos , Lactente , Recém-Nascido , Humanos , Ácido Araquidônico , Estudos de Coortes , Lactente Extremamente Prematuro , FosfolipídeosRESUMO
Importance: The prognostic impact of parenteral nutrition duration (PND) on retinopathy of prematurity (ROP) is not well studied. Safe prediction models can help optimize ROP screening by effectively discriminating high-risk from low-risk infants. Objective: To evaluate the prognostic value of PND on ROP; to update and validate the Digital ROP (DIGIROP) 2.0 birth into prescreen and screen prediction models to include all ROP-screened infants regardless of gestational age (GA) and incorporate PND; and to compare the DIGIROP model with the Weight, IGF-1, Neonatal, and ROP (WINROP) and Postnatal Growth and ROP (G-ROP) models. Design, Setting, and Participants: This retrospective study included 11â¯139 prematurely born infants from 2007 to 2020 from the Swedish National Registry for ROP. Extended Poisson and logistic models were applied. Data were analyzed from August 2022 to February 2023. Main Outcomes and Measures: Any ROP and ROP requiring treatment were studied in relation to PND. ROP treatment was the outcome in DIGIROP models. Sensitivity, specificity, area under the receiver operating characteristic curve, and adjusted OR (aOR) with 95% CI were the main measures. Internal and external validations were performed. Results: Of 11â¯139 screened infants, 5071 (45.5%) were girls, and the mean (SD) gestational age was 28.5 (2.4) weeks. ROP developed in 3179 infants (29%), treatment was given in 599 (5%), 7228 (65%) had PND less than 14 days, 2308 (21%) had PND for 14 days or more, and 1603 (14%) had unknown PND. PND was significantly correlated with ROP severity (Spearman r = 0.45; P < .001). Infants with 14 days or more of PND vs less than 14 days had faster progression from any ROP to ROP treatment (adjusted mean difference, -0.9 weeks; 95% CI, -1.5 to -0.3; P = .004). Infants with PND for 14 days or more vs less than 14 days had higher odds of any ROP (aOR, 1.84; 95% CI, 1.62-2.10; P < .001) and of severe ROP requiring treatment (aOR, 2.20; 95% CI, 1.73-2.80; P < .001). Among all 11â¯139 infants, the DIGIROP 2.0 models had 100% sensitivity (95% CI, 99.4-100). The specificity was 46.6% (95% CI, 45.6-47.5) for the prescreen model and 76.9% (95% CI, 76.1-77.7) for the screen model. G-ROP as well as the DIGIROP 2.0 prescreen and screen models showed 100% sensitivity on a validation subset (G-ROP: sensitivity, 100%; 95% CI, 93-100; DIGIROP prescreen: sensitivity, 100%; 95% CI, 93-100; DIGIROP screen: sensitivity, 100%; 95% CI, 93-100), whereas WINROP showed 89% sensitivity (95% CI, 77-96). Specificity for each prediction model was 29% (95% CI, 22-36) for G-ROP, 38% (95% CI, 32-46) for DIGIROP prescreen, 53% (95% CI, 46-60) for DIGIROP screen at 10 weeks, and 46% (95% CI, 39-53) for WINROP. Conclusion and Relevance: Based on more than 11â¯000 ROP-screened infants born in Sweden, PND of 14 days or more corresponded to a significantly higher risk of having any ROP and receiving ROP treatment. These findings provide evidence to support consideration of using the updated DIGIROP 2.0 models instead of the WINROP or G-ROP models in the management of ROP.
Assuntos
Sistemas de Apoio a Decisões Clínicas , Retinopatia da Prematuridade , Recém-Nascido , Lactente , Feminino , Humanos , Masculino , Retinopatia da Prematuridade/diagnóstico , Retinopatia da Prematuridade/epidemiologia , Estudos Retrospectivos , Prognóstico , Fatores de Risco , Triagem Neonatal , Idade Gestacional , Nutrição Parenteral/efeitos adversosRESUMO
AIM: To characterize postnatal changes in serum insulin-like growth factor-1 (IGF-I) in relation to development of bronchopulmonary dysplasia (BPD) in very preterm infants. METHODS: Longitudinal study of 108 infants with mean (SD) gestational age (GA) 27.2 (2.2) weeks. Weekly serum samples of IGF-I were analysed from birth until postmenstrual age (PMA) 36 weeks. Multivariate models were developed to identify independent predictors of BPD. RESULTS: Postnatal mean IGF-I levels at postnatal day (PND) 3-21 were lower in infants with BPD compared with infants with no BPD (16 vs. 26 µg/L, p < 0.001). Longitudinal postnatal change in IGF-I levels (IGF-I regression coefficient (ß)), PNDs 3-21, was lower in infants with BPD compared with infants with no BPD (0.28 vs. 0.97, p = 0.002) and mean IGF-I during PMA 30-33 weeks was lower in infants with BPD as compared with infants without BPD (22 vs. 29 µg/L, p < 0.001). In a binomial multiple regression model, lower GA, male gender and lower mean serum IGF-I levels during PND 3-21 were the most predictive risk factors associated with BPD (r(2) = 0.634, p < 0.001). CONCLUSION: Lower IGF-I concentrations during the first weeks after very preterm birth are associated with later development of BPD.
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Displasia Broncopulmonar/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Proteínas de Transporte/sangue , Desenvolvimento Infantil , Feminino , Glicoproteínas/sangue , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Recém-Nascido Pequeno para a Idade Gestacional , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like II/metabolismo , Estudos Longitudinais , Masculino , Análise Multivariada , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Intraocular treatment with antibodies targeting vascular endothelial growth factor (anti-VEGF) inhibits pathological vessel growth in adults and preterm infants. Recently, concerns regarding the impact of anti-VEGF treatment on systemic VEGF levels in preterm infants have been raised. Earlier studies suggest that preanalytical and methodological parameters impact analytical VEGF concentrations, but we have not found a comprehensive systematic review covering preanalytical procedures and methods for VEGF measurements. OBJECTIVE: This review aimed to evaluate the most critical factors during sample collection, sample handling, and the analytical methods that influence VEGF levels and therefore should be considered when planning a prospective collection of samples to get reproducible, comparable results. MATERIAL AND METHODS: PubMed and Scopus databases were searched 2021/Nov/11. In addition, identification of records via other methods included reference, citation, and Google Scholar searches. Rayyan QCRI was used to handle duplicates and the selection process. Publications reporting preanalytical handling and/or methodological comparisons using human blood samples were included. Exclusion criteria were biological, environmental, genetic, or physiological factors affecting VEGF. The data extraction sheets included bias assessment using the QUADAS-2 tool, evaluating patient selection, index-test, reference standard, and flow and timing. Concentrations of VEGF and results from statistical comparisons of analytical methods and/or preanalytical sample handling and/or different sample systems were extracted. The publications covering preanalytical procedures were further categorized based on the stage of the preanalytical procedure. Meta-analysis was used to visualize VEGF concentrations among healthy individuals. The quality of evidence was rated according to GRADE. RESULTS: We identified 1596 publications, and, after the screening process, 43 were considered eligible for this systematic review. The risk of bias estimation was difficult for 2/4 domains due to non-reported information. Four critical steps in the preanalytical process that impacted VEGF quantification were identified: blood drawing and the handling before, during, and after centrifugation. Sub-categorization of those elements resulted in nine findings, rated from moderate to very low evidence grade. The choice of sample system was the most reported factor. VEGF levels (mean [95% CI]) in serum (n = 906, 20 publications), (252.5 [213.1-291.9] pg/mL), were approximated to ninefold higher than in plasma (n = 1122, 23 publications), (27.8 [23.6-32.1] pg/mL), based on summarized VEGF levels with meta-analysis. Notably, most reported plasma levels were below the calibration range of the used method. CONCLUSION: When measuring circulating VEGF levels, choice of sample system and sample handling are important factors to consider for ensuring high reproducibility and allowing study comparisons. Protocol: CRD42020192433.