Chatarina Löfqvist - Academia.edu (original) (raw)
Papers by Chatarina Löfqvist
Neonatology
Introduction: Thrombocytopenia has been identified as an independent risk factor for retinopathy ... more 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 included. Infants were classified as having no/mild ROP or severe ROP. Serum levels of vascular endothelial growth factor A, platelet-derived growth factor BB, and brain-derived neurotrophic factor were measured in serum samples collected from birth until postmenstrual age (PMA) 40 weeks. Platelet counts were obtained from samples taken for clinical indication. Results: Postnatal platelet counts and serum concentrations of the 3 growth factors followed the same postnatal pattern, with lower levels in infants developing severe ROP at PMA 32 and 36 weeks (p < 0.05–0.001). With adjustment for GA, low platelet counts and low serum concentra...
JAMA Network Open
IMPORTANCE Supplementing preterm infants with long-chain polyunsaturated fatty acids (LC-PUFA) ha... more IMPORTANCE Supplementing preterm infants with long-chain polyunsaturated fatty acids (LC-PUFA) has been inconsistent in reducing the severity and incidence of retinopathy of prematurity (ROP). Furthermore, few studies have measured the long-term serum lipid levels after supplementation. OBJECTIVE To assess whether ROP severity is associated with serum levels of LC-PUFA, especially docosahexaenoic acid (DHA) and arachidonic acid (AA), during the first 28 postnatal days. DESIGN, SETTING, AND PARTICIPANTS This cohort study analyzed the Mega Donna Mega study, a randomized clinical trial that provided enteral fatty acid supplementation at 3 neonatal intensive care units in Sweden. Infants included in this cohort study were born at a gestational age of less than 28
JAMA Pediatrics
IMPORTANCE Lack of arachidonic acid (AA) and docosahexaenoic acid (DHA) after extremely preterm b... more 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, SETTING, AND PARTICIPANTS The Mega Donna Mega trial, a randomized clinical trial, was a multicenter study performed at 3 university hospitals in Sweden from December 15, 2016, to December 15, 2019. The screening pediatric ophthalmologists were masked to patient groupings. A total of 209 infants born at less than 27 weeks' gestation were tested for eligibility, and 206 infants were included. Efficacy analyses were performed on as-randomized groups on the intention-to-treat population and on the per-protocol population using as-treated groups. Statistical analyses were performed from February to April 2020. INTERVENTIONS Infants received either supplementation with an enteral oil providing AA (100 mg/kg/d) and DHA (50 mg/kg/d) (AA:DHA group) or no supplementation within 3 days after birth until 40 weeks' postmenstrual age. MAIN OUTCOMES AND MEASURES The primary outcome was severe ROP (stage 3 and/or type 1). The secondary outcomes were AA and DHA serum levels and rates of other complications of preterm birth. RESULTS A total of 101 infants (58 boys [57.4%]; mean [SD] gestational age, 25.5 [1.5] weeks) were included in the AA:DHA group, and 105 infants (59 boys [56.2%]; mean [SD] gestational age, 25.5 [1.4] weeks) were included in the control group. Treatment with AA and DHA reduced severe ROP compared with the standard of care (16 of 101 [15.8%] in the AA:DHA group vs 35 of 105 [33.3%] in the control group; adjusted relative risk, 0.50 [95% CI, 0.28-0.91]; P = .02). The AA:DHA group had significantly higher fractions of AA and DHA in serum phospholipids compared with controls (overall mean difference in AA:DHA group, 0.82 mol% [95% CI, 0.46-1.18 mol%]; P < .001; overall mean difference in control group, 0.13 mol% [95% CI, 0.01-0.24 mol%]; P = .03). There were no significant differences between the AA:DHA group and the control group in the rates of bronchopulmonary dysplasia (48 of 101 [47.5%] vs 48 of 105 [45.7%]) and of any grade of intraventricular hemorrhage (43 of 101 [42.6%] vs 42 of 105 [40.0%]). In the AA:DHA group and control group, respectively, sepsis occurred in 42 of 101 infants (41.6%) and 53 of 105 infants (50.5%), serious adverse events occurred in 26 of 101 infants (25.7%) and 26 of 105 infants (24.8%), and 16 of 101 infants (15.8%) and 13 of 106 infants (12.3%) died. CONCLUSIONS AND RELEVANCE This study found that, compared with standard of care, enteral AA:DHA supplementation lowered the risk of severe ROP by 50% and showed overall higher serum levels of both AA and DHA. Enteral lipid supplementation with AA:DHA is a novel preventive strategy to decrease severe ROP in extremely preterm infants.
Growth Hormone & IGF Research
Acta Paediatrica
Preterm infants are at increased risk of extrauterine growth restriction, which at least in part ... more Preterm infants are at increased risk of extrauterine growth restriction, which at least in part is caused by very high extrauterine nutritional needs. 1 In addition, the inability to assimilate sufficient nutrition due to feeding intolerance secondary to immaturity and neonatal morbidities is especially common in extremely preterm infants. The result is significant energy and protein deficits, primarily in the early postnatal period. 2 Most extremely preterm neonates suffer from growth restriction that can persist into childhood. 3
The Journal of Clinical Endocrinology & Metabolism
Context Little is known about the individual response of glucose-regulating factors to administra... more 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 insulin because of hyperglycemia. Design Prospective longitudinal cohort study. Setting Two university hospitals in Sweden between December 2015 and September 2016. Patients and Intervention Serum samples were obtained from nine extremely preterm infants, gestational age between 22 (+3) and 26 (+5) weeks (+ days), with hyperglycemia (plasma-glucose…
JCI insight, Jan 4, 2018
Retinopathy of prematurity (ROP) is characterized by abnormal retinal neovascularization in respo... more Retinopathy of prematurity (ROP) is characterized by abnormal retinal neovascularization in response to vessel loss. Platelets regulate angiogenesis and may influence ROP progression. In preterm infants, we assessed ROP and correlated with longitudinal postnatal platelet counts (n = 202). Any episode of thrombocytopenia (<100 × 109/l) at ≥30 weeks postmenstrual age (at onset of ROP) was independently associated with severe ROP, requiring treatment. Infants with severe ROP also had a lower weekly median platelet count compared with infants with less severe ROP. In a mouse oxygen-induced retinopathy model of ROP, platelet counts were lower at P17 (peak neovascularization) versus controls. Platelet transfusions at P15 and P16 suppressed neovascularization, and platelet depletion increased neovascularization. Platelet transfusion decreased retinal of vascular endothelial growth factor A (VEGFA) mRNA and protein expression; platelet depletion increased retinal VEGFA mRNA and protein e...
JPEN. Journal of parenteral and enteral nutrition, Jan 21, 2018
Infants born prematurely are at risk of a deficiency in ω-6 and ω-3 long-chain polyunsaturated fa... more Infants born prematurely are at risk of a deficiency in ω-6 and ω-3 long-chain polyunsaturated fatty acids (LC-PUFAs) arachidonic acid (AA) and docosahexaenoic acid (DHA). We investigated how fatty acids from breast milk and parenteral lipid emulsions shape serum LC-PUFA profiles in extremely preterm infants during early perinatal life. Ninety infants born < 28 weeks gestational age were randomized to receive parenteral lipids with or without the ω-3 LC-PUFAs eicosapentaenoic acid (EPA) and DHA (SMOFlipid: Fresenius Kabi, Uppsala, Sweden, or Clinoleic: Baxter Medical AB, Kista, Sweden, respectively). The fatty acid composition of infant serum phospholipids was determined from birth to postmenstrual age 40 weeks, and in mother's milk total lipids on postnatal day 7. Enteral and parenteral intake of LC-PUFAs was correlated with levels in infant serum. Infants administered parenteral ω-3 LC-PUFAs received 4.4 and 19.3 times more DHA and EPA, respectively, over the first 2 weeks ...
JAMA ophthalmology, 2018
Mice with oxygen-induced retinopathy fed matched diets except for ω-3 long-chain polyunsaturated ... more Mice with oxygen-induced retinopathy fed matched diets except for ω-3 long-chain polyunsaturated fatty acids (LC-PUFAs) vs ω-6 LC-PUFAs demonstrate relative antiangiogenic and neuroprotective associations of ω-3 LC-PUFAs. However, supplementing preterm infants with LC-PUFAs has been inconsistent in reducing major preterm morbidities. However, few studies measured serum lipid levels after supplementation. To examine the associated risk of retinopathy of prematurity (ROP) from the levels of circulating ω-3 and ω-6 LC-PUFAs. This longitudinal clinical study was a further analysis of serum lipid levels from a randomized controlled trial cohort of 90 infants born at gestational age (GA) less than 28 weeks. From April 4, 2013, to September 22, 2015, cord blood samples, followed by venous blood samples, were obtained at birth and at 1, 7, 14, and 28 days after birth and then at postmenstrual age (PMA) 32, 36, and 40 weeks at the neonatal intensive care unit at Sahlgrenska University Hospit...
Acta paediatrica (Oslo, Norway : 1992), Jan 14, 2018
Our aim was to perform an in-depth analysis of the composition of fatty acids in milk from mother... more 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. 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. 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...
Current pharmaceutical design, Jan 2, 2017
Insulin-like growth factor 1 (IGF-1) is a mitogenic hormone involved in many processes such as gr... more Insulin-like growth factor 1 (IGF-1) is a mitogenic hormone involved in many processes such as growth, metabolism, angiogenesis and differentiation. After very preterm birth, energy demands increase while maternal supplies of nutrients and other factors are lost and the infant may become dependent on parenteral nutrition for weeks. Low postnatal IGF-1 concentrations in preterm infants are associated with poor weight gain, retinopathy of prematurity (ROP) and other morbidities. We will describe the process by which we aim to develop supplementation with recombinant human (rh) IGF-1 and its binding protein rhIGFBP-3 as a possible therapy to promote growth and maturation and reduce morbidities in extremely preterm infants. In order to calculate a dose of IGF-1 tolerated by neonates, a pharmacokinetic study of transfusion with fresh frozen plasma was performed, which provided a relatively low dose of IGF-1, (on average 1.4 μg/kg), that increased serum IGF-1 to levels close to those obse...
Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society, Jan 27, 2017
Retinopathy of prematurity (ROP) is a multifactorial disease linked to low insulin-like growth fa... more Retinopathy of prematurity (ROP) is a multifactorial disease linked to low insulin-like growth factor (IGF)-I levels and perhaps to postnatal inflammation. Here, we investigated the longitudinal postnatal serum concentrations of pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α in relation to IGF-I levels and ROP. The study cohort included 52 infants born before 31 gestational weeks. The infants were screened for ROP and classified as non-ROP (n=33), non-proliferative ROP (stages 1 and 2; n=10), or proliferative ROP (stage 3, all treated for ROP; n=9). Blood samples were collected at birth, 24h after birth, and then weekly until at least 36weeks postmenstrual age (PMA) (i.e., up to 13weeks after birth). Circulating levels of IL-6 and TNF-α were evaluated in relation to circulating IGF-I levels and ROP. IL-6 levels negatively correlated with IGF-I levels between 5 and 8weeks after birth, (p<0.01 to p<0.05). At birth, the IL-6 and TNF-α levels were ...
Investigative Opthalmology & Visual Science
Adiponectin mediates dietary omega-3 long-chain polyunsaturated fatty acid protection against cho... more Adiponectin mediates dietary omega-3 long-chain polyunsaturated fatty acid protection against choroidal neovascularization in mice.
Growth Hormone & IGF Research, 2016
Retinopathy of prematurity is a potentially blinding disease, which is associated with low neonat... more Retinopathy of prematurity is a potentially blinding disease, which is associated with low neonatal IGF-I serum concentrations and poor growth. In severe cases impaired retinal vessel growth is followed by pathologic neovascularization, which may lead to retinal detachment. IGF-I may promote growth even in catabolic states. Treating preterm infants with recombinant human (rh) IGF-I to concentrations normally found during gestation has been suggested to have a preventative effect on ROP. A recent phase 2 study treating infants (gestational age between 23weeks+0days and 27weeks +6days) with rhIGF-I/IGF binding protein-3 until 30 postmenstrual weeks showed no effect on ROP but a 53% reduction in severe bronchopulmonary dysplasia and 44% reduction in severe intraventricular hemorrhage. Oxygen is a major risk factor for ROP and during the phase 2 study oxygen saturation targets were increased to 90-95%, due to national guidelines, which might have affected ROP rate and severity making increased IGF-I a weaker preventative factor for ROP.
Early Human Development, 2016
The retina is part of the central nervous system and both the retina as well as the brain can suf... more The retina is part of the central nervous system and both the retina as well as the brain can suffer from severe damage after very preterm birth. Retinopathy of prematurity is one of the major causes of blindness in these children and brain neuronal impairments including cognitive defects, cerebral palsy and intraventricular hemorrhage (IVH) are also complications of very preterm birth. Insulin-like growth factor 1 (IGF-1) acts to promote proliferation, maturation, growth and survival of neural cells. Low levels of circulating IGF-1 are associated with ROP and defects in the IGF-1 gene are associated with CNS disorders including learning deficits and brain growth restriction. Treatment of preterm infants with recombinant IGF-1 may potentially prevent ROP and CNS disorders. This review compares the role of IGF-1 in ROP and CNS disorders. A recent phase 2 study showed a positive effect of IGF-1 on the severity of IVH but no effect on ROP. A phase 3 trial is planned.
Biochimica et biophysica acta, 2016
Neovascular eye diseases are a major cause of blindness including retinopathy of prematurity, dia... more 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.
Neonatology, 2016
Retinopathy of prematurity (ROP), a potentially blinding disease, affects preterm infants. High l... more Retinopathy of prematurity (ROP), a potentially blinding disease, affects preterm infants. High levels of oxygen saturation are a well-known risk factor for ROP. To assess the frequency of ROP type 1 needing treatment after improved oxygen monitoring (2011) in a Mexican preterm population selected for WINROP analyses and to retrospectively revalidate WINROP, an online surveillance system identifying infants at risk of developing ROP type 1. Preterm infants born with birth weight (BW) &amp;amp;amp;amp;amp;lt;1,750 g and/or at gestational age (GA) ≤34 weeks, screened for ROP in 2012-2014 at the Hospital Civil de Guadalajara, Mexico were included (n = 151). Eighty-five infants with GA &amp;amp;amp;amp;amp;lt;32 weeks qualified for WINROP analyses. GA, BW, maximal ROP stage, ROP treatment and weekly weights were recorded. The results in the present study were compared to those of a previous WINROP study in the same hospital (2005-2010; n = 352). In the present WINROP cohort, 11.8% of the infants born at GA &amp;amp;amp;amp;amp;lt;32 weeks received treatment compared to 51.0% of the infants in the previous WINROP cohort. One infant (3%) born at GA ≥32 weeks received treatment during the present study period compared to 35.6% during the previous period. WINROP displayed 80.0% sensitivity in infants born at GA &amp;amp;amp;amp;amp;lt;32 weeks in the present study compared to 84.7% in the previous study. Uncontrolled oxygen supplementation is the major risk factor for severe ROP in infants born at GA ≥32 weeks. After improved oxygen monitoring, the frequency of ROP treatment was dramatically reduced at the Hospital Civil de Guadalajara, Mexico.
Neonatology
Introduction: Thrombocytopenia has been identified as an independent risk factor for retinopathy ... more 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 included. Infants were classified as having no/mild ROP or severe ROP. Serum levels of vascular endothelial growth factor A, platelet-derived growth factor BB, and brain-derived neurotrophic factor were measured in serum samples collected from birth until postmenstrual age (PMA) 40 weeks. Platelet counts were obtained from samples taken for clinical indication. Results: Postnatal platelet counts and serum concentrations of the 3 growth factors followed the same postnatal pattern, with lower levels in infants developing severe ROP at PMA 32 and 36 weeks (p < 0.05–0.001). With adjustment for GA, low platelet counts and low serum concentra...
JAMA Network Open
IMPORTANCE Supplementing preterm infants with long-chain polyunsaturated fatty acids (LC-PUFA) ha... more IMPORTANCE Supplementing preterm infants with long-chain polyunsaturated fatty acids (LC-PUFA) has been inconsistent in reducing the severity and incidence of retinopathy of prematurity (ROP). Furthermore, few studies have measured the long-term serum lipid levels after supplementation. OBJECTIVE To assess whether ROP severity is associated with serum levels of LC-PUFA, especially docosahexaenoic acid (DHA) and arachidonic acid (AA), during the first 28 postnatal days. DESIGN, SETTING, AND PARTICIPANTS This cohort study analyzed the Mega Donna Mega study, a randomized clinical trial that provided enteral fatty acid supplementation at 3 neonatal intensive care units in Sweden. Infants included in this cohort study were born at a gestational age of less than 28
JAMA Pediatrics
IMPORTANCE Lack of arachidonic acid (AA) and docosahexaenoic acid (DHA) after extremely preterm b... more 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, SETTING, AND PARTICIPANTS The Mega Donna Mega trial, a randomized clinical trial, was a multicenter study performed at 3 university hospitals in Sweden from December 15, 2016, to December 15, 2019. The screening pediatric ophthalmologists were masked to patient groupings. A total of 209 infants born at less than 27 weeks' gestation were tested for eligibility, and 206 infants were included. Efficacy analyses were performed on as-randomized groups on the intention-to-treat population and on the per-protocol population using as-treated groups. Statistical analyses were performed from February to April 2020. INTERVENTIONS Infants received either supplementation with an enteral oil providing AA (100 mg/kg/d) and DHA (50 mg/kg/d) (AA:DHA group) or no supplementation within 3 days after birth until 40 weeks' postmenstrual age. MAIN OUTCOMES AND MEASURES The primary outcome was severe ROP (stage 3 and/or type 1). The secondary outcomes were AA and DHA serum levels and rates of other complications of preterm birth. RESULTS A total of 101 infants (58 boys [57.4%]; mean [SD] gestational age, 25.5 [1.5] weeks) were included in the AA:DHA group, and 105 infants (59 boys [56.2%]; mean [SD] gestational age, 25.5 [1.4] weeks) were included in the control group. Treatment with AA and DHA reduced severe ROP compared with the standard of care (16 of 101 [15.8%] in the AA:DHA group vs 35 of 105 [33.3%] in the control group; adjusted relative risk, 0.50 [95% CI, 0.28-0.91]; P = .02). The AA:DHA group had significantly higher fractions of AA and DHA in serum phospholipids compared with controls (overall mean difference in AA:DHA group, 0.82 mol% [95% CI, 0.46-1.18 mol%]; P < .001; overall mean difference in control group, 0.13 mol% [95% CI, 0.01-0.24 mol%]; P = .03). There were no significant differences between the AA:DHA group and the control group in the rates of bronchopulmonary dysplasia (48 of 101 [47.5%] vs 48 of 105 [45.7%]) and of any grade of intraventricular hemorrhage (43 of 101 [42.6%] vs 42 of 105 [40.0%]). In the AA:DHA group and control group, respectively, sepsis occurred in 42 of 101 infants (41.6%) and 53 of 105 infants (50.5%), serious adverse events occurred in 26 of 101 infants (25.7%) and 26 of 105 infants (24.8%), and 16 of 101 infants (15.8%) and 13 of 106 infants (12.3%) died. CONCLUSIONS AND RELEVANCE This study found that, compared with standard of care, enteral AA:DHA supplementation lowered the risk of severe ROP by 50% and showed overall higher serum levels of both AA and DHA. Enteral lipid supplementation with AA:DHA is a novel preventive strategy to decrease severe ROP in extremely preterm infants.
Growth Hormone & IGF Research
Acta Paediatrica
Preterm infants are at increased risk of extrauterine growth restriction, which at least in part ... more Preterm infants are at increased risk of extrauterine growth restriction, which at least in part is caused by very high extrauterine nutritional needs. 1 In addition, the inability to assimilate sufficient nutrition due to feeding intolerance secondary to immaturity and neonatal morbidities is especially common in extremely preterm infants. The result is significant energy and protein deficits, primarily in the early postnatal period. 2 Most extremely preterm neonates suffer from growth restriction that can persist into childhood. 3
The Journal of Clinical Endocrinology & Metabolism
Context Little is known about the individual response of glucose-regulating factors to administra... more 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 insulin because of hyperglycemia. Design Prospective longitudinal cohort study. Setting Two university hospitals in Sweden between December 2015 and September 2016. Patients and Intervention Serum samples were obtained from nine extremely preterm infants, gestational age between 22 (+3) and 26 (+5) weeks (+ days), with hyperglycemia (plasma-glucose…
JCI insight, Jan 4, 2018
Retinopathy of prematurity (ROP) is characterized by abnormal retinal neovascularization in respo... more Retinopathy of prematurity (ROP) is characterized by abnormal retinal neovascularization in response to vessel loss. Platelets regulate angiogenesis and may influence ROP progression. In preterm infants, we assessed ROP and correlated with longitudinal postnatal platelet counts (n = 202). Any episode of thrombocytopenia (<100 × 109/l) at ≥30 weeks postmenstrual age (at onset of ROP) was independently associated with severe ROP, requiring treatment. Infants with severe ROP also had a lower weekly median platelet count compared with infants with less severe ROP. In a mouse oxygen-induced retinopathy model of ROP, platelet counts were lower at P17 (peak neovascularization) versus controls. Platelet transfusions at P15 and P16 suppressed neovascularization, and platelet depletion increased neovascularization. Platelet transfusion decreased retinal of vascular endothelial growth factor A (VEGFA) mRNA and protein expression; platelet depletion increased retinal VEGFA mRNA and protein e...
JPEN. Journal of parenteral and enteral nutrition, Jan 21, 2018
Infants born prematurely are at risk of a deficiency in ω-6 and ω-3 long-chain polyunsaturated fa... more Infants born prematurely are at risk of a deficiency in ω-6 and ω-3 long-chain polyunsaturated fatty acids (LC-PUFAs) arachidonic acid (AA) and docosahexaenoic acid (DHA). We investigated how fatty acids from breast milk and parenteral lipid emulsions shape serum LC-PUFA profiles in extremely preterm infants during early perinatal life. Ninety infants born < 28 weeks gestational age were randomized to receive parenteral lipids with or without the ω-3 LC-PUFAs eicosapentaenoic acid (EPA) and DHA (SMOFlipid: Fresenius Kabi, Uppsala, Sweden, or Clinoleic: Baxter Medical AB, Kista, Sweden, respectively). The fatty acid composition of infant serum phospholipids was determined from birth to postmenstrual age 40 weeks, and in mother's milk total lipids on postnatal day 7. Enteral and parenteral intake of LC-PUFAs was correlated with levels in infant serum. Infants administered parenteral ω-3 LC-PUFAs received 4.4 and 19.3 times more DHA and EPA, respectively, over the first 2 weeks ...
JAMA ophthalmology, 2018
Mice with oxygen-induced retinopathy fed matched diets except for ω-3 long-chain polyunsaturated ... more Mice with oxygen-induced retinopathy fed matched diets except for ω-3 long-chain polyunsaturated fatty acids (LC-PUFAs) vs ω-6 LC-PUFAs demonstrate relative antiangiogenic and neuroprotective associations of ω-3 LC-PUFAs. However, supplementing preterm infants with LC-PUFAs has been inconsistent in reducing major preterm morbidities. However, few studies measured serum lipid levels after supplementation. To examine the associated risk of retinopathy of prematurity (ROP) from the levels of circulating ω-3 and ω-6 LC-PUFAs. This longitudinal clinical study was a further analysis of serum lipid levels from a randomized controlled trial cohort of 90 infants born at gestational age (GA) less than 28 weeks. From April 4, 2013, to September 22, 2015, cord blood samples, followed by venous blood samples, were obtained at birth and at 1, 7, 14, and 28 days after birth and then at postmenstrual age (PMA) 32, 36, and 40 weeks at the neonatal intensive care unit at Sahlgrenska University Hospit...
Acta paediatrica (Oslo, Norway : 1992), Jan 14, 2018
Our aim was to perform an in-depth analysis of the composition of fatty acids in milk from mother... more 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. 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. 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...
Current pharmaceutical design, Jan 2, 2017
Insulin-like growth factor 1 (IGF-1) is a mitogenic hormone involved in many processes such as gr... more Insulin-like growth factor 1 (IGF-1) is a mitogenic hormone involved in many processes such as growth, metabolism, angiogenesis and differentiation. After very preterm birth, energy demands increase while maternal supplies of nutrients and other factors are lost and the infant may become dependent on parenteral nutrition for weeks. Low postnatal IGF-1 concentrations in preterm infants are associated with poor weight gain, retinopathy of prematurity (ROP) and other morbidities. We will describe the process by which we aim to develop supplementation with recombinant human (rh) IGF-1 and its binding protein rhIGFBP-3 as a possible therapy to promote growth and maturation and reduce morbidities in extremely preterm infants. In order to calculate a dose of IGF-1 tolerated by neonates, a pharmacokinetic study of transfusion with fresh frozen plasma was performed, which provided a relatively low dose of IGF-1, (on average 1.4 μg/kg), that increased serum IGF-1 to levels close to those obse...
Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society, Jan 27, 2017
Retinopathy of prematurity (ROP) is a multifactorial disease linked to low insulin-like growth fa... more Retinopathy of prematurity (ROP) is a multifactorial disease linked to low insulin-like growth factor (IGF)-I levels and perhaps to postnatal inflammation. Here, we investigated the longitudinal postnatal serum concentrations of pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α in relation to IGF-I levels and ROP. The study cohort included 52 infants born before 31 gestational weeks. The infants were screened for ROP and classified as non-ROP (n=33), non-proliferative ROP (stages 1 and 2; n=10), or proliferative ROP (stage 3, all treated for ROP; n=9). Blood samples were collected at birth, 24h after birth, and then weekly until at least 36weeks postmenstrual age (PMA) (i.e., up to 13weeks after birth). Circulating levels of IL-6 and TNF-α were evaluated in relation to circulating IGF-I levels and ROP. IL-6 levels negatively correlated with IGF-I levels between 5 and 8weeks after birth, (p<0.01 to p<0.05). At birth, the IL-6 and TNF-α levels were ...
Investigative Opthalmology & Visual Science
Adiponectin mediates dietary omega-3 long-chain polyunsaturated fatty acid protection against cho... more Adiponectin mediates dietary omega-3 long-chain polyunsaturated fatty acid protection against choroidal neovascularization in mice.
Growth Hormone & IGF Research, 2016
Retinopathy of prematurity is a potentially blinding disease, which is associated with low neonat... more Retinopathy of prematurity is a potentially blinding disease, which is associated with low neonatal IGF-I serum concentrations and poor growth. In severe cases impaired retinal vessel growth is followed by pathologic neovascularization, which may lead to retinal detachment. IGF-I may promote growth even in catabolic states. Treating preterm infants with recombinant human (rh) IGF-I to concentrations normally found during gestation has been suggested to have a preventative effect on ROP. A recent phase 2 study treating infants (gestational age between 23weeks+0days and 27weeks +6days) with rhIGF-I/IGF binding protein-3 until 30 postmenstrual weeks showed no effect on ROP but a 53% reduction in severe bronchopulmonary dysplasia and 44% reduction in severe intraventricular hemorrhage. Oxygen is a major risk factor for ROP and during the phase 2 study oxygen saturation targets were increased to 90-95%, due to national guidelines, which might have affected ROP rate and severity making increased IGF-I a weaker preventative factor for ROP.
Early Human Development, 2016
The retina is part of the central nervous system and both the retina as well as the brain can suf... more The retina is part of the central nervous system and both the retina as well as the brain can suffer from severe damage after very preterm birth. Retinopathy of prematurity is one of the major causes of blindness in these children and brain neuronal impairments including cognitive defects, cerebral palsy and intraventricular hemorrhage (IVH) are also complications of very preterm birth. Insulin-like growth factor 1 (IGF-1) acts to promote proliferation, maturation, growth and survival of neural cells. Low levels of circulating IGF-1 are associated with ROP and defects in the IGF-1 gene are associated with CNS disorders including learning deficits and brain growth restriction. Treatment of preterm infants with recombinant IGF-1 may potentially prevent ROP and CNS disorders. This review compares the role of IGF-1 in ROP and CNS disorders. A recent phase 2 study showed a positive effect of IGF-1 on the severity of IVH but no effect on ROP. A phase 3 trial is planned.
Biochimica et biophysica acta, 2016
Neovascular eye diseases are a major cause of blindness including retinopathy of prematurity, dia... more 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.
Neonatology, 2016
Retinopathy of prematurity (ROP), a potentially blinding disease, affects preterm infants. High l... more Retinopathy of prematurity (ROP), a potentially blinding disease, affects preterm infants. High levels of oxygen saturation are a well-known risk factor for ROP. To assess the frequency of ROP type 1 needing treatment after improved oxygen monitoring (2011) in a Mexican preterm population selected for WINROP analyses and to retrospectively revalidate WINROP, an online surveillance system identifying infants at risk of developing ROP type 1. Preterm infants born with birth weight (BW) &amp;amp;amp;amp;amp;lt;1,750 g and/or at gestational age (GA) ≤34 weeks, screened for ROP in 2012-2014 at the Hospital Civil de Guadalajara, Mexico were included (n = 151). Eighty-five infants with GA &amp;amp;amp;amp;amp;lt;32 weeks qualified for WINROP analyses. GA, BW, maximal ROP stage, ROP treatment and weekly weights were recorded. The results in the present study were compared to those of a previous WINROP study in the same hospital (2005-2010; n = 352). In the present WINROP cohort, 11.8% of the infants born at GA &amp;amp;amp;amp;amp;lt;32 weeks received treatment compared to 51.0% of the infants in the previous WINROP cohort. One infant (3%) born at GA ≥32 weeks received treatment during the present study period compared to 35.6% during the previous period. WINROP displayed 80.0% sensitivity in infants born at GA &amp;amp;amp;amp;amp;lt;32 weeks in the present study compared to 84.7% in the previous study. Uncontrolled oxygen supplementation is the major risk factor for severe ROP in infants born at GA ≥32 weeks. After improved oxygen monitoring, the frequency of ROP treatment was dramatically reduced at the Hospital Civil de Guadalajara, Mexico.