Pediatric Ophthalmology

Lundgren P, Klevebro S, Brodin P, Smith LEH, Hallberg B, Hellström A. Leucocytosis is associated with retinopathy of prematurity in extremely preterm infants. Acta Paediatr 2019;108(7):1357-1358.
Lundgren P, Nilsson AK, Hellgren G, Pivodic A, Smith LEH, Hellström A. Association between low fatty acid levels and platelet count in infants with Retinopathy of Prematurity. Acta Paediatr 2020;109(12):2547-2548.
Lundgren P, Hellgren G, Pivodic A, Sävman K, Smith LEH, Hellström A. Erythropoietin serum levels, versus anaemia as risk factors for severe retinopathy of prematurity. Pediatr Res 2019;86(2):276-282.Abstract
BACKGROUND: Preterm infants with anaemia are treated with recombinant human erythropoietin (rhEPO). It is debated whether rhEPO treatment is a risk factor for retinopathy of prematurity (ROP). We evaluated longitudinal EPO and haemoglobin levels, blood transfusions and neonatal morbidities as risk factors for severe ROP. METHOD: This prospective study included 78 Swedish infants, born <28 weeks gestational age (GA), screened for ROP. We tested serum EPO levels on postnatal days 1, 7, 14 and 28 and at postmenstrual ages 32, 36 and 40 weeks. Haemoglobin levels and blood transfusions were recorded during postnatal weeks 1-4. Anaemia was defined as haemoglobin ≤110 g/L. RESULTS: During postnatal week 1, infants with severe ROP requiring treatment (28%) more frequently developed anaemia (42.9% versus 8.0%, P = 0.003) and had higher mean EPO levels (postnatal day 7: 14.2 versus 10.8 mIU/mL, P = 0.003) compared to infants with no or less severe ROP not requiring treatment. In multivariable analyses, GA and anaemia during week 1 remained significant risk factors, but elevated EPO level postnatal day 7 was no longer significant. CONCLUSIONS: Among infants born <28 weeks GA, anaemia during week 1 was a significant risk factor for severe ROP requiring treatment but not elevated EPO levels.
Lundgren P, Hård A-L, Wilde Å, Löfqvist C, Smith LEH, Hellström A. Implementing higher oxygen saturation targets reduced the impact of poor weight gain as a predictor for retinopathy of prematurity. Acta Paediatr 2018;107(5):767-773.Abstract
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 (SpO ) 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 SpO 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 SpO 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.
Lundgren P, Kistner A, Andersson EM, Hansen Pupp I, Holmström G, Ley D, Niklasson A, Smith LEH, Wu C, Hellström A, Löfqvist C. Low birth weight is a risk factor for severe retinopathy of prematurity depending on gestational age. PLoS One 2014;9(10):e109460.Abstract
OBJECTIVE: To evaluate the impact of low birth weight as a risk factor for retinopathy of prematurity (ROP) that will require treatment in correlation with gestational age at birth (GA). STUDY DESIGN: In total, 2941 infants born <32 weeks GA were eligible from five cohorts of preterm infants previously collected for analysis in WINROP (Weight IGF-I Neonatal ROP) from the following locations: Sweden (EXPRESS) (n = 426), North America (n = 1772), Boston (n = 338), Lund (n = 52), and Gothenburg (n = 353). Data regarding GA at birth, birth weight (BW), gender, and need for ROP treatment were retrieved. Birth weight standard deviation scores (BWSDS) were calculated with Swedish as well as Canadian reference models. Small for gestational age (SGA) was defined as BWSDS less than -2.0 SDS using the Swedish reference and as BW below the 10th percentile using the Canadian reference charts. RESULTS: Univariate analysis showed that low GA (p<0.001), low BW (p<0.001), male gender (p<0.05), low BWSDSCanada (p<0.001), and SGACanada (p<0.01) were risk factors for ROP that will require treatment. In multivariable logistic regression analysis, low GA (p<0.0001), male gender (p<0.01 and p<0.05), and an interaction term of BWSDS*GA group (p<0.001), regardless of reference chart, were risk factors. Low BWSDS was less important as a risk factor in infants born at GA <26 weeks compared with infants born at GA ≥26 weeks calculated with both reference charts (BWSDSSweden, OR = 0.80 vs 0.56; and BWSDSCanada, OR = 0.72 vs 0.41). CONCLUSIONS: Low BWSDS as a risk factor for vision-threatening ROP is dependent on the infant's degree of immaturity. In more mature infants (GA ≥26 weeks), low BWSDS becomes a major risk factor for developing ROP that will require treatment. These results persist even when calculating BW deficit with different well-established approaches.
Lundgren P, Athikarisamy SE, Patole S, Lam GC, Smith LE, Simmer K. Duration of anaemia during the first week of life is an independent risk factor for retinopathy of prematurity. Acta Paediatr 2018;107(5):759-766.Abstract
AIM: This study evaluated the correlation between retinopathy of prematurity (ROP), anaemia and blood transfusions in extremely preterm infants. METHODS: We included 227 infants born below 28 weeks of gestation at King Edward Memorial Hospital, Perth, Australia, from 2014-2016. Birth characteristics and risk factors for ROP were retrieved, and anaemia and severe anaemia were defined as a haemoglobins of <110 g/L and <80 g/L, respectively. Logistic regression was used for the analysis. RESULTS: Retinopathy of prematurity treatment was needed in 11% of cases and the mean number of blood transfusions (p < 0.01), and mean number of weeks of anaemia (p < 0.001) and of severe anaemia (p < 0.05), had positive associations with ROP cases warranting treatment. In the multivariate logistic regression analysis, the best-fit model of risk factors included anaemic days during first week of life, with an odds ratio (OR) of 1.46% and 95% confidence interval (CI) of 1.16-1.83 (p < 0.05), sepsis during the first 4 weeks of life (OR 3.14, 95% CI 1.10-9.00, p < 0.05) and days of ventilation (OR 1.03, 95% CI 1.01-1.06, p < 0.05). CONCLUSION: The duration of anaemia during the first week of life was an independent risk factor for ROP warranting treatment and preventing early anaemia may decrease this risk.
Ma KK, Robson CD, Gaier ED, Gise R. Reversal of Visual Loss From Skull Base Osteomyelitis in a Pediatric Patient. J Neuroophthalmol 2021;Publish Ahead of Print
MacKinnon S, Proctor MR, Rogers GF, Meara JG, Whitecross S, Dagi LR. Improving ophthalmic outcomes in children with unilateral coronal synostosis by treatment with endoscopic strip craniectomy and helmet therapy rather than fronto-orbital advancement. J AAPOS 2013;17(3):259-65.Abstract
PURPOSE: To compare long-term ophthalmic outcomes in infants treated for unilateral coronal synostosis (UCS) by endoscopic strip craniectomy (ESC) and helmet therapy with those treated by fronto-orbital advancement (FOA). METHODS: Consecutive patients with UCS, uncomplicated by other suture synostosis, were identified by a retrospective review of medical records. Assessment of presence of amblyopia, cycloplegic refraction, strabismus, and strabismus surgical intervention at all visits was recorded. RESULTS: Between 2004 and 2010, 22 patients were treated by FOA (mean follow-up, 21.5 months) and 21 patients with ESC and helmet therapy (mean follow-up, 23.5 months). The mean aniso-astigmatism was equal; however, the SD was greater for those treated by FOA (P < 0.05). A more severe pattern of strabismus developed in those treated by FOA (P < 0.0001). Those treated by FOA were more likely to have amblyopia (P = 0.0015) and to undergo surgical correction of their strabismus (odds ratio, 6.3:1). CONCLUSIONS: Children with UCS treated with ESC and helmeting had less severe overelevation in adduction, amblyopia, extremes of astigmatism, and less need for strabismus surgery than those treated by FOA. Although the reason for these more favorable outcomes remains uncertain, we speculate that the earlier timing of ESC or differences in the anatomical changes resulting from the two procedures may play a role.
Mantagos IS, Kleinman ME, Kieran MW, Gordon LB. Ophthalmologic Features of Progeria. Am J Ophthalmol 2017;182:126-132.Abstract
PURPOSE: To establish the natural history of ophthalmic characteristics in Progeria patients and to determine incidence of ocular manifestations. DESIGN: Retrospective case series of patients with Progeria who were seen between 2007 and 2016. METHODS: Setting: Tertiary-care academic center. PATIENT POPULATION: Fourteen patients (28 eyes) with Hutchinson-Gilford Progeria syndrome were included for statistical analysis from a total of 84 patients who have been enrolled in clinical trials for Progeria at Boston Children's Hospital. Clinical treatment trial patients who were not seen at the Department of Ophthalmology at our hospital, but for whom we had detailed clinical ophthalmologic records, were also included. This essentially represents an estimated 20% of the world's known patients with Progeria. Interventions or Observation Procedures: Complete ophthalmic examination. MAIN OUTCOME MEASURES: Visual acuity, stereoacuity, refraction, clinical findings of slit-lamp and dilated fundus examinations. RESULTS: Ophthalmic manifestations noted were hyperopia and signs of ocular surface disease owing to nocturnal lagophthalmos and exposure keratopathy. Additional ophthalmic manifestations included reduced brow hair, madarosis, and reduced accommodation. Most patients had relatively good acuity; however, advanced ophthalmic disease was associated with reduced acuity. CONCLUSIONS: Children with Progeria are at risk for serious ophthalmic complications owing to ocular surface disease. Children with Progeria should have an ophthalmic evaluation at the time of diagnosis and at least yearly after that. Aggressive ocular surface lubrication is recommended, including the use of tape tarsorrhaphy at night.
Mazel EC, Bailin ES, Tietjen MW, Palmer PA. A Questionnaire Assessing What Teachers of the Visually Impaired Know About Cortical/Cerebral Vision Impairment. Semin Pediatr Neurol 2019;31:41-47.Abstract
Cortical/cerebral visual impairment (CVI) is now the main cause of visual impairment in developed countries, yet it remains poorly understood. Four hundred and ninteen teachers of the visually impaired (TVIs) from across the United States responded to a questionnaire targeted at evaluating the preparedness of TVIs to serve their students with CVI. The TVIs were asked about their background knowledge, their abilities to assess a student with CVI, and their abilities to apply what they know to best help their students. The primary finding was that there is a perceived unmet need for TVIs to receive formal training in CVI during their certification. The results of this survey provide a foundation for future research on CVI knowledge and education among TVIs.
Minaeva O, Sarangi S, Ledoux DM, Moncaster JA, Parsons DS, Washicosky KJ, Black CA, Weng FJ, Ericsson M, Moir RD, Tripodis Y, Clark JI, Tanzi RE, Hunter DG, Goldstein LE. In Vivo Quasi-Elastic Light Scattering Eye Scanner Detects Molecular Aging in Humans. J Gerontol A Biol Sci Med Sci 2020;75(9):e53-e62.Abstract
The absence of clinical tools to evaluate individual variation in the pace of aging represents a major impediment to understanding aging and maximizing health throughout life. The human lens is an ideal tissue for quantitative assessment of molecular aging in vivo. Long-lived proteins in lens fiber cells are expressed during fetal life, do not undergo turnover, accumulate molecular alterations throughout life, and are optically accessible in vivo. We used quasi-elastic light scattering (QLS) to measure age-dependent signals in lenses of healthy human subjects. Age-dependent QLS signal changes detected in vivo recapitulated time-dependent changes in hydrodynamic radius, protein polydispersity, and supramolecular order of human lens proteins during long-term incubation (~1 year) and in response to sustained oxidation (~2.5 months) in vitro. Our findings demonstrate that QLS analysis of human lens proteins provides a practical technique for noninvasive assessment of molecular aging in vivo.
Modest JR, Johnston SC, Majzoub KM, Moore B, Trudell EK, Ramsey JE, Vernacchio L. Results of a primary care-based quality improvement project to optimize chart-based vision screening for preschool age children. J AAPOS 2016;Abstract

PURPOSE: To design chart-based vision screening for preschool-aged children. METHODS: Our program consisted of educational sessions for providers as well as hands-on training for practice staff. We evaluated the intervention through pre- and post-intervention review of medical records. RESULTS: Completion of full vision screening (distance visual acuity in each eye plus stereovision beginning at 3 years of age, as recommended at the time of the project) at well-child visits improved for 5-year-olds (45.0% to 58.2%; risk difference +13.2% [95% CI, 1.7-24.7]) and 4-year-olds (39.3% to 51.4%; risk difference +12.0% [95% CI, 0.7-23.4]) but declined somewhat among 3-year-olds (23.1% to 14.3%; risk difference, -8.8% [95% CI, -17.7 to 0.0]). Risk factors for not being fully screened included being 3 years old (risk ratio of 4.1 compared to 5-year-olds) and being a patient of a small practice (risk ratio of 1.9 compared to large practices). CONCLUSIONS: This quality improvement project showed that screening for visual acuity and stereovision among preschool-aged children using chart-based techniques is difficult to accomplish and unlikely to be consistently successful, especially among 3-year-olds.

Moskowitz A, Hansen RM, Eklund SE, Fulton AB. Electroretinographic (ERG) responses in pediatric patients using vigabatrin. Doc Ophthalmol 2012;124(3):197-209.Abstract
The antiepileptic drug vigabatrin is known to cause retinal and visual dysfunction, particularly visual field defects, in some patients. Electroretinography (ERG) is used in an attempt to identify adverse effects of vigabatrin (VGB) in patients who are not candidates for conventional perimetry. We report data from 114 pediatric patients taking VGB referred for clinical evaluation; median age at test was 22.9 (2.4 to 266.1) months, and median duration of VGB use was 9.7 (0.3 to 140.7) months. Twenty-seven of them were tested longitudinally (3 to 12 ERG tests). ERG responses to full-field stimuli were recorded in scotopic and photopic conditions, and results were compared to responses from healthy control subjects. We found that abnormalities of photoreceptor and post-receptor ERG responses are frequent in these young patients. The most frequently abnormal scotopic parameter was post-receptor sensitivity, log σ, derived from the b-wave stimulus-response function; the most frequently abnormal photopic parameter was the implicit time of the OFF response (d-wave) to a long (150 ms) flash. Abnormal 30-Hz flicker response amplitude, previously reported to be a predictor of visual field loss, occurred infrequently. For the group as a whole, none of the ERG parameters changed significantly with increasing duration of VGB use. Four of the 27 patients tested longitudinally showed systematic worsening of log σ with duration of VGB use. In a subset of patients who underwent perimetry (N = 39), there was no significant association of any ERG parameter with visual field defects. We cannot determine whether the ERG abnormalities we found were due solely to the effects of VGB. We caution against over-reliance on the ERG to monitor pediatric patients for VGB toxicity and recommend further development of a reliable test of peripheral vision to supplant ERG testing.
Moustafa GA, Topham AK, Aronow ME, Vavvas DG. Paediatric ocular adnexal lymphoma: a population-based analysis. BMJ Open Ophthalmol 2020;5(1):e000483.Abstract
Objective: To investigate the incidence, clinicopathological characteristics and survival of ocular adnexal lymphoma (OAL) in the paediatric population. Methods and analysis: In this retrospective case series, the Surveillance, Epidemiology and End Results database was accessed to identify individuals with OAL ≤18 years of age, diagnosed between 1973 and 2015. OAL located in the eyelid, conjunctiva, lacrimal apparatus and orbit were included. Main outcome measures were the age-adjusted incidence rates (IRs) per 1 000 000 population at risk (calculated for the period 2000-2015) and descriptive statistics of demographic and clinicopathological features. Results: The IR of paediatric OAL was 0.12 (95% CI 0.08 to 0.16) per 1 000 000. Males (0.15; 95% CI 0.10 to 0.22) and blacks (0.24; 95% CI 0.13 to 0.42) had a higher tendency for OAL development. A total of 55 tumours in 54 children were identified. The majority were localised (78.4%), conjunctival (49.1%) lymphomas. Extranodal marginal zone lymphoma (EMZL, 45.5%, n=25) was the most frequent subtype, followed by diffuse large B-cell lymphoma (DLBCL, 9.1%, n=5), B lymphoblastic lymphoma (7.3%, n=4), follicular lymphoma (5.5%, n=3), Burkitt lymphoma (5.5%, n=3), anaplastic large cell lymphoma (ALCL, 3.6%, n=2), small lymphocytic lymphoma (1.8%, n=1), diffuse large B-cell lymphoma, immunoblastic (1.8%, n=1) and panniculitis-like T-cell lymphoma (1.8%, n=1). Localised, low-grade, conjunctival lymphomas were frequently treated with complete excision with or without radiation, while high-grade and distant tumours usually received chemotherapy. Only 29.1% of paediatric OAL cases were treated with radiation. Three out of five (60%) patients with DLBCL died of lymphoma at a median follow-up of 21 (range 10-86) months, and 1 out of 2 (50%) patients with ALCL died of lymphoma at 23 months from diagnosis. Conclusion: OAL in the paediatric population is rare. The majority of OAL are EMZL and are characterised by excellent prognosis. The histological subtype was found to be the main predictor of outcome with cancer-specific deaths observed in patients with DLBCL and ALCL.
Munro RJ, Fulton AB, Chui TYP, Moskowitz A, Ramamirtham R, Hansen RM, Prabhu SP, Akula JD. Eye growth in term- and preterm-born eyes modeled from magnetic resonance images. Invest Ophthalmol Vis Sci 2015;56(5):3121-31.Abstract

PURPOSE: We generated a model of eye growth and tested it against an eye known to develop abnormally, one with a history of retinopathy of prematurity (ROP). METHODS: We reviewed extant magnetic resonance images (MRIs) from term and preterm-born patients for suitable images (n = 129). We binned subjects for analysis based upon postmenstrual age at birth (in weeks) and ROP history ("Term" ≥ 37, "Premature" ≤ 32 with no ROP, "ROP" ≤ 32 with ROP). We measured the axial positions and curvatures of the cornea, anterior and posterior lens, and inner retinal surface. We fit anterior chamber depth (ACD), posterior segment depth (PSD), axial length (AL), and corneal and lenticular curvatures with logistic growth curves that we then evaluated for significant differences. We also measured the length of rays from the centroid to the surface of the eye at 5° intervals, and described the length versus age relationship of each ray, Lray(x), using the same logistic growth curve. We determined the rate of ray elongation, Eray(x), from Lraydy/dx. Then, we estimated the scleral growth that accounted for Eray(x), G(x), at every age and position. RESULTS: Relative to Term, development of ACD, PSD, AL, and corneal and lenticular curvatures was delayed in ROP eyes, but not Premature eyes. In Term infants, G(x) was fast and predominantly equatorial; in age-matched ROP eyes, maximal G(x) was offset by approximately 90°. CONCLUSIONS: We produced a model of normal eye growth in term-born subjects. Relative to normal, the ROP eye is characterized by delayed, abnormal growth.

Nguyen JQN, Resnick CM, Chang Y-H, Hansen RM, Fulton AB, Moskowitz A, Calabrese CE, Dagi LR. Impact of obstructive sleep apnea on optic nerve function in patients with craniosynostosis and recurrent intracranial hypertension. Am J Ophthalmol 2019;Abstract
PURPOSE: Assessment of combined impact of intracranial pressure (ICH) and obstructive sleep apnea (OSA) on optic nerve function in children with craniosynostosis (CS). DESIGN: Retrospective cross-sectional study METHODS: Patients treated at Boston Children's Hospital for CS who had an ophthalmic examination that included pattern reversal (pr)VEP (2013-2014) and history of ICH based on direct measurement, papilledema, or classic features on neuroimaging and during cranial vault expansion were included. History of OSA was determined by polysomnography and associated conditions, including apnea and (adeno)tonsillectomy. Subjects were divided into four groups: (1) resolved ICH absent history of OSA; (2) resolved ICH with history of OSA; (3) recurrent ICH absent history of OSA; and (4) recurrent ICH with history of OSA. Predictor variables included latency of P100 component of prVEP, best-corrected visual acuity, optic nerve appearance, visual fields and global RNFL. Primary outcome was association of prolonged P100 latency with resolved versus recurrent ICH and OSA. RESULTS: Twenty-eight children met inclusion criteria (mean age 11.6 ± 6.9 years): group 1 (N = 3); group 2 (N = 6); group 3 (N = 8); group 4 (N = 11). P100 latencies were not prolonged in groups 1 and 2. Three of 8 in group 3 and 9 of 11 in group 4 had prolonged P100 latency. Group 4 was significantly worse than group 3 (P=0.005). CONCLUSIONS: History of OSA, in addition to recurrent ICH, is associated with greatest risk of optic neuropathy with CS. Ophthalmologists should encourage early management of OSA as well as ICH to optimize ophthalmic outcomes.
Nihalani BR, VanderVeen DK. Benchmarks for outcome indicators in pediatric cataract surgery. Eye (Lond) 2017;31(3):417-421.Abstract

PurposeThe purpose of this study was to establish benchmarks for outcome indicators that may help ascertain the quality of pediatric cataract surgery with primary intraocular lens (IOL) implantation.Patients and methodsA retrospective chart review of patients older than 2 years undergoing cataract surgery with primary IOL implantation, by multiple surgeons in a tertiary-care center, from November 2005 to February 2016 was conducted. Patients with ocular comorbidities that would affect the outcomes were excluded. The outcome measures chosen were as follows: (1) final best corrected Snellen visual acuity (BCVA) in patients who had bilateral cataract surgery analyzed at the last clinic visit; (2) prediction error (PE)=expected refraction-actual refraction. Mean PE and mean absolute PE were assessed 1 month postoperatively, irrespective of age or laterality.ResultsMean age at surgery was 8.3±4.6 years and mean follow-up duration was 3.7±2.7 years. The results of outcome measures were as follows: (1) BCVA was 20/40 or better in 96% (n=124 eyes, mean patient age: 8.3±4.6 years). Remaining five eyes had amblyopia with two eyes having BCVA worse than 20/100 that did not respond to amblyopia treatment. (2) Mean PE was 0.3±1.1 D and mean absolute PE was 0.9±0.7 D. PE was within ±0.5 D in 43.0%, ±1.0 D in 66%, and ±2.0 D in 95% (n=235 eyes).ConclusionGood visual acuity after cataract surgery should be expected for children with bilateral cataracts, setting a high benchmark similar to that recommended in adult cataract surgery. Prediction error is greater in pediatric eyes than in adult eyes, setting a lower benchmark. This study establishes benchmark for outcome indicators in pediatric patients older than 2 years undergoing cataract surgery with primary IOL implantation.

Nilsson AK, Löfqvist C, Najm S, Hellgren G, Sävman K, Andersson MX, Smith LEH, Hellström A. Influence of Human Milk and Parenteral Lipid Emulsions on Serum Fatty Acid Profiles in Extremely Preterm Infants. JPEN J Parenter Enteral Nutr 2019;43(1):152-161.Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Nilsson AK, Löfqvist C, Najm S, Hellgren G, Sävman K, Andersson MX, Smith LEH, Hellström A. Long-chain polyunsaturated fatty acids decline rapidly in milk from mothers delivering extremely preterm indicating the need for supplementation. Acta Paediatr 2018;107(6):1020-1027.Abstract
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.
Nilsson AK, Andersson MX, Sjöbom U, Hellgren G, Lundgren P, Pivodic A, Smith LEH, Hellström A. Sphingolipidomics of serum in extremely preterm infants: Association between low sphingosine-1-phosphate levels and severe retinopathy of prematurity. Biochim Biophys Acta Mol Cell Biol Lipids 2021;1866(7):158939.Abstract
BACKGROUND: Extremely preterm infants are at risk of developing retinopathy of prematurity (ROP) that can cause impaired vision or blindness. Changes in blood lipids have been associated with ROP. This study aimed to monitor longitudinal changes in the serum sphingolipidome of extremely preterm infants and investigate the relationship to development of severe ROP. METHODS: This is a prospective study that included 47 infants born <28 gestational weeks. Serum samples were collected from cord blood and at postnatal days 1, 7, 14, and 28, and at postmenstrual weeks (PMW) 32, 36, and 40. Serum sphingolipids and phosphatidylcholines were extracted and analyzed by LC-MS/MS. Associations between sphingolipid species and ROP were assessed using mixed models for repeated measures. RESULTS: The serum concentration of all investigated lipid classes, including ceramide, mono- di- and trihexosylceramide, sphingomyelin, and phosphatidylcholine displayed distinct temporal patterns between birth and PMW40. There were also substantial changes in the lipid species composition within each class. Among the analyzed sphingolipid species, sphingosine-1-phosphate showed the strongest association with severe ROP, and this association was independent of gestational age at birth and weight standard deviation score change. CONCLUSIONS: The serum phospho- and sphingolipidome undergoes significant remodeling during the first weeks of the preterm infant's life. Low postnatal levels of the signaling lipid sphingosine-1-phosphate are associated with the development of severe ROP.