| 1. |
- Cakir, B., et al.
(författare)
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Thrombocytopenia is associated with severe retinopathy of prematurity
- 2018
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Ingår i: Jci Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 3:19
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Tidskriftsartikel (refereegranskat)abstract
- 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 x 10(9)/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 expression. Resting platelets with intact granules reduced neovascularization, while thrombin-activated degranulated platelets did not. These data suggest that platelet releasate has a local antiangiogenic effect on endothelial cells to exert a downstream suppression of VEGFA in neural retina. Low platelet counts during the neovascularization phase in ROP is significantly associated with the development of severe ROP in preterm infants. In a murine model of retinopathy, platelet transfusion during the period of neovascularization suppressed retinopathy.
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| 2. |
- Hellström, Ann, 1959, et al.
(författare)
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Effect of Enteral Lipid Supplement on Severe Retinopathy of Prematurity A Randomized Clinical Trial
- 2021
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Ingår i: JAMA Pediatrics. - : American Medical Association (AMA). - 2168-6203 .- 2168-6211. ; 175:4, s. 359-367
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Tidskriftsartikel (refereegranskat)abstract
- 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 (100mg/kg/d) and DHA (50mg/kg/d) (AA:DHA group) or no supplementation within 3 days after birth until 40 weeks' postmenstrual age. MAIN OUTCOMES AND MEASURES The primary outcomewas 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.
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| 3. |
- Ley, David, et al.
(författare)
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Longitudinal infusion of insulin-like growth factor-I and IGF-binding protein-3 complex to five preterm infants: pharmacokinetics and short term safety.
- 2013
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Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 63:1, s. 68-74
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Tidskriftsartikel (refereegranskat)abstract
- 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 decrease prevalence of ROP.Methods:In a phase II pharmacokinetic and safety study, five infants (3 girls) with a median (range) gestational age (GA) of 26+6 (26+0 - 27+2) weeks and birth weight (BW) of 990 (900-1212) g received continuous intravenous infusion of rhIGF-I/rhIGFBP-3. Treatment was initiated during the first postnatal day and continued for median (range) 168h (47-168) in doses between 21 - 111 µg/kg/24h.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. Out of 74 IGF-I samples measured during study drug infusion, 37 (50%) were within target range, 4 (5%) above and 33 (45%) were below. Predicted dose of rhIGF-I/rhIGFBP-3 to establish circulating levels of IGF-I within the intrauterine range in a 1000g infant was 75-100 µg/kg/24h. No hypoglycemia or other adverse effects were recorded.Conclusion:Continuous intravenous infusion of rhIGF-I/rhIGFBP-3 was effective in increasing serum concentrations of IGF-I and IGFBP-3. Administration during study was safe.Pediatric Research (2012); doi:10.1038/pr.2012.146.
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| 4. |
- Löfqvist, Chatarina, 1964, et al.
(författare)
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Association of Retinopathy of Prematurity With Low Levels of Arachidonic Acid A Secondary Analysis of a Randomized Clinical Trial
- 2018
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Ingår i: Jama Ophthalmology. - : American Medical Association (AMA). - 2168-6165. ; 136:3, s. 271-277
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Mice with oxygen-induced retinopathy fed matched diets except for omega-3 long-chain polyunsaturated fatty acids (LC-PUFAs) vs omega-6 LC-PUFAs demonstrate relative antiangiogenic and neuroprotective associations of omega-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. OBJECTIVE To examine the associated risk of retinopathy of prematurity (ROP) from the levels of circulating omega-3 and omega-6 LC-PUFAs. DESIGN, SETTING, AND PARTICIPANTS 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 Hospital in Goteborg, Sweden. MAIN OUTCOMES AND MEASURES Serum phospholipid fatty acids were transmethylated and measured by gas chromatography-mass spectrometry. Mann-Whitney test, logistic regression Spearman rank correlation, and receiver operating characteristic curve analysis were used to compare differences between infants with no ROP and infants who developed ROP. RESULTS Serum levels from 78 infants (43 male [55%]; mean [SD] GA, 25.5 [1.4] weeks) with a known ROP outcome were evaluated. Lower area under the curve (AUC) of arachidonic acid (AA) (20: 4 omega-6) was seen in infants with a later diagnosis of ROP compared with infants with no ROP in the first month of life (mean, 34.05 [95% CI, 32.10-36.00] vs 37.15 [95% CI, 34.85-39.46]; P < .05). In addition, lower levels of AA at 32 weeks' PMA were seen in infants with later severe ROP compared with in those without ROP (mean, 7.06 [95% CI, 6.60-7.52] vs 8.74 [95% CI, 7.80-9.67]; P < .001). In logistic modeling, low postnatal serum levels of AA and GA at birth identified with a sensitivity greater than 90% of infants who developed ROP. CONCLUSIONS AND RELEVANCE Low postnatal levels of the omega-6 LC-PUFAs (AA) are strongly associated with ROP development. Evaluating postnatal AA fraction after birth in addition to GA may be useful for ROP prediction.
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| 5. |
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| 6. |
- Najm, Svetlana, et al.
(författare)
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Effects of a lipid emulsion containing fish oil on polyunsaturated fatty acid profiles, growth and morbidities in extremely premature infants: A randomized controlled trial
- 2017
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Ingår i: Clinical Nutrition ESPEN. - : Elsevier BV. - 2405-4577. ; 20, s. 17-23
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Tidskriftsartikel (refereegranskat)abstract
- © 2017 The Authors Background & aims The purpose of the study was to compare the effects of the parenteral emulsion SMOFlipid ® , with 15% fish oil, with Clinoleic ® on retinopathy of prematurity (ROP) and other morbidities and growth, and to compare their impact on longitudinal serum levels of fatty acids. Retinopathy of prematurity, other morbidity and growth were correlated with each parenteral lipid supplement. Methods Ninety infants born at gestational age < 28 weeks were randomized to treatment with SMOFlipid ® or Clinoleic ® . Two thirds (66%) of the infants received parenteral nutrition for up to 14 days birth (median 8, range 2–14 days), and additional 25% of the infants received for up to 28 days after birth (median 21, range 15–28 days). Cord blood samples and then venous blood samples were obtained at ages 1, 7, 14, and 28 days and at postmenstrual age (PMA) 32, 36, and 40 weeks. Breastmilk was collected at postnatal day 7, and at PMA 32 and 40 weeks. Serum phospholipid and breastmilk total fatty acids were analyzed by gas chromatography–mass spectrometry. Treatment groups were compared with regard to ROP, bronchopulmonary dysplasia, necrotizing enterocolitis, patent ductus arteriosus sepsis and growth between birth and 36 weeks. Results Infants on SMOFlipid ® had higher fractions of omega-3 LCPUFA eicosapentaenoic acid (EPA) and slightly higher omega-3 LCPUFA docosahexaenoic acid (DHA) fraction and a decreased arachidonic acid (AA) to DHA ratio from one week after birth up to 32 postmenstrual weeks compared to infants on Clinoleic ® . Treatment groups did not differ in morbidities or growth. Conclusion Supplementation with SMOFlipid ® containing 15% fish oil during parenteral nutrition increased EPA substantially, DHA marginally, reduced AA and decreased AA to DHA ratio. It did not reduce morbidity or affect growth. Since extremely preterm infants accumulate a large deficit of DHA and AA, studies on more prolonged or different levels of DHA and AA supplementation are warranted.
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| 7. |
- Nilsson, Anders K., 1982, et al.
(författare)
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Influence of Human Milk and Parenteral Lipid Emulsions on Serum Fatty Acid Profiles in Extremely Preterm Infants.
- 2019
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Ingår i: JPEN - Journal of Parenteral and Enteral Nutrition. - : Wiley. - 0148-6071 .- 1941-2444. ; 43:1, s. 152-161
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Tidskriftsartikel (refereegranskat)abstract
- 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 of life. Parenteral EPA but not DHA correlated with levels in infant serum. We found linear relationships between dietary EPA and DHA and infant serum levels in the Clinoleic (Baxter Medical AB) group. The volume of administered SMOFlipid (Fresenius Kabi) was inversely correlated with serum AA, whereas Clinoleic (Baxter Medical AB) inversely correlated with serum EPA and DHA.There appears to be no or low correlation between the amount of DHA administered parenterally and levels measured in serum. Whether this observation reflects serum phospholipid fraction only or truly represents the amount of accreted DHA needs to be investigated. None of the parenteral lipid emulsions satisfactorily maintained high levels of both ω-6 and ω-3 LC-PUFAs in infant serum.
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| 8. |
- Nilsson, Anders K., 1982, et al.
(författare)
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Long-chain polyunsaturated fatty acids decline rapidly in milk from mothers delivering extremely preterm indicating the need for supplementation.
- 2018
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Ingår i: Acta paediatrica. - : Wiley. - 1651-2227 .- 0803-5253. ; 107:6, s. 1020-1027
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Tidskriftsartikel (refereegranskat)abstract
- Our aim was 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 seven and a post-menstrual 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.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 require high levels of LCPUFAs. This article is protected by copyright. All rights reserved.
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