To Örebro University

Purpose: The primary aim was to analyse regional incidences of retinopathy of prematurity (ROP) and frequencies of treatment and their relation to perinatal risk factors during a 3-year period. A secondary aim was to study adherence to the study screening protocol in the different regions.

Methods: A population-based study of neonatal morbidity in extremely preterm infants in Sweden (EXPRESS) was performed during 2004-2007. Screening for ROP was to start at postnatal age 5weeks and to continue weekly until the retina was completely vascularized or until regression of ROP. Logistic regression analyses were used for evaluation of differences in incidence of Any ROP, ROP 3 or more and ROP Type 1 between the seven regions of the country.

Results: The regional incidence of ROP varied between 54% and 92% for Any ROP, between 25% and 43% for ROP stage 3 or more and between 8% and 23% of infants with ROP Type 1, all of whom were treated. There was no significant difference between the regions regarding ROP Type 1, even when adjusting for known risk factors for ROP.

Conclusion: The heterogeneity between the regions regarding the incidence of ROP was reduced with increasing severity of ROP, and there was no heterogeneity regarding frequency of treatment for ROP, which is the most important issue for the children. We cannot exclude observer bias regarding mild ROP and ROP stage 3 in this study.

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 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.

Introduction: Retinopathy of prematurity (ROP) is the most common disease leading to blindness in extreme preterm infants. Current screening guidelines recommend frequent eye examinations. There is a dearth of trained ophthalmologists for these frequent screening procedures. The ANZNN neonatal network report (2013) found that only 6.4% of all screened infants had severe ROP and less than half received treatment. WINROP (online prediction model, Sweden) uses the postnatal weight gain (surrogate marker for low insulin-like growth factor IGF-1 and poor retinal vascular growth) to identify ROP requiring treatment and aims to reduce the number of examinations. Our objective was to validate the WINROP model in an Australian cohort of preterm infants.

Methods: Birth weight, gestational age, and weekly weight measurements were retrieved retrospectively along with the final ROP outcomes and plotted on the online WINROP software.

Results: The sensitivity, specificity, positive predictive value, and negative predictive value of WINROP were 85.7%, 59.0%, 6.98%, and 99.1% respectively for a cohort of 221 preterm infants (Median birth weight, 1040 g; Gestational age, 27.9 weeks). WINROP alarm was signaled in 42.6% of all infants. WINROP did not signal an alarm in one infant who needed treatment. This infant had intra ventricular hemorrhage grade 3-4 and temporary ventricular dilatation.

Conclusions: This is the first Australian study validating WINROP model. Our findings suggest that it lacked sensitivity to be used alone. However, adjusting the algorithm for the Australian population may improve the efficacy and reduce the number of examinations when used along with the current screening guidelines.

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 concentrations of all 3 factors at PMA 32 weeks were significantly associated with severe ROP. Serum concentrations of all 3 factors also strongly correlated with platelet count (p < 0.001).

CONCLUSION: In this article, we show that ROP, platelet counts, and specific pro-angiogenic factors correlate. These data suggest that platelet-released factors might be involved in the regulation of retinal and systemic angiogenesis after extremely preterm birth. Further investigations are needed.

IMPORTANCE: This follow-up study of extremely preterm (EPT) children (<27 weeks' gestational age [GA] at birth) revealed major eye and visual problems in 37.9%(147 of 388) of all EPT infants and in 55.4%(67 of 121) of the most immature subgroups at 6.5 years of age. These major eye and visual problems were strongly associated with treatment-requiring retinopathy of prematurity (ROP). OBJECTIVES To investigate the ophthalmologic outcome of a national cohort of EPT children at 6.5 years of age and to evaluate the impact of prematurity and ROP.

DESIGN, SETTING, AND PARTICIPANTS  All surviving EPT children born in Sweden between April 1, 2004, and March 31, 2007, were included and compared with a matched term control group, as part of a prospective national follow-up study.

MAIN OUTCOMES AND MEASURES: Visual acuity, refraction in cycloplegia, and manifest strabismus were evaluated and compared with GA at birth and with treatment-requiring ROP. RESULTS The study cohort comprised 486 participants. The mean (SD) GA of the children who were included was 25 (1) weeks, and 45.7%(222 of 486) were female. At a median age of 6.6 years, 89.3%(434 of 486) of eligible EPT children were assessed and compared with 300 control group children. In the EPT group, 2.1%(9 of 434) were blind, 4.8%(21 of 434) were visually impaired according to the World Health Organization criteria, and 8.8% (38 of 434) were visually impaired according to the study criteria. Strabismus was found in 17.4% (68 of 390) and refractive errors in 29.7%(115 of 387) of the EPT children compared with 0% (0 of 299) and 5.9% (17 of 289), respectively, of the control children (P<.001). Altogether at 6.5 years of age, 37.9%(147 of 388) of the EPT children had some ophthalmologic abnormality compared with 6.2%(18 of 290) of the matched control group (95% CI of the difference, 26.1%-37.2%). When treatment-requiring ROP was adjusted for, no significant association between GA and visual impairment could be detected. For refractive errors, the association with GA remained after adjustment for treatment-requiring ROP (odds ratio, 0.72; 95% CI, 0.58-0.91 for each 1-week increment).

CONCLUSIONS AND RELEVANCE: In a Swedish national cohort of EPT children at 6.5 years of age, major eye and visual problems were frequently found. Treatment-requiring ROP was a stronger impact factor than GA on visual impairment and strabismus, but not on refractive errors, as a whole. In modern neonatal intensive care settings, ophthalmologic problems continue to account for a high proportion of long-term sequelae of prematurity.

Aim: This study evaluated the contributions of various prenatal and postnatal predictive factors to a documented high prevalence of ophthalmological abnormalities in children aged 6.5 years who were born extremely preterm.

Methods: We carried out a prospective population-based study of all children born in Sweden at a gestational age of 22 + 0 to 26 + 6 weeks based on the Extremely Preterm Infants in Sweden Study. The main outcome measures were a combined score of visual impairment, refractive errors and strabismus at 6.5 years of age. Models of univariate and multivariable regression were used to analyse potential prenatal and postnatal predictive factors at different clinically relevant time-points from one minute after birth to 30 months.

Results: We focused on 399 known extremely preterm survivors and compared them to 300 full-term controls. Significant antecedents for ophthalmological abnormalities included prematurity per se, retinopathy of prematurity that required treatment, severe bronchopulmonary dysplasia and cerebral palsy. Severe intraventricular haemorrhage was no longer a significant risk factor when we adjusted it for the 30-month cognitive and neuromotor development outcomes.

Conclusion: This time-course risk analysis model showed a changing panorama of significant risk factors for ophthalmological abnormalities in children aged 6.5 years who were born extremely preterm.

Objectives: To evaluate screening for retinopathy of prematurity (ROP) in Sweden and to investigate possible modifications of the present screening guidelines.

Methods: Infants in Sweden with a gestational age (GA) of 31 weeks + 6 days or less are screened for ROP. Data from the Swedish national register for ROP (SWEDROP) during 2008 and 2009 were extracted and compared with a national perinatal quality register.

Results: In SWEDROP, there were 1791 infants born before a GA of 32weeks from January 1, 2008, through December 31, 2009. Another 70 infants were registered in the perinatal quality register but not in SWEDROP (drop-out rate, 3.8% [70 of 1861 infants]). Seven infants died before termination of screening. In the final study cohort (1784 infants), 15.6% had mild ROP and 8.5% had severe ROP. Treatment was performed in 4.4% of the infants, none of whom had a GA at birth of more than 28 weeks. Nine infants with a GA of more than 28 weeks at birth developed stage 3 ROP, which regressed spontaneously. The total number of examinations was 9286 (964 in infants with a GA of 31 weeks), and the mean (range) number of examinations of each infant was 5.2 (1-30).

Conclusions: The SWEDROP, a quality register for ROP, has a national coverage (ie, participation) of 96%. Data from 2008 to 2009 show that it seems possible to reduce the upper limit for screening in Sweden by 1 week, including only infants with a GA of 30 weeks + 6 days or less. However, such a change should be combined with a strong recommendation to neonatologists to refer also severely ill and more "mature" infants.

Purpose: To investigate whether recent Swedish guidelines for Retinopathy of Prematurity (ROP) screening, that is, a gestational age (GA) at birth of less than31weeks (w), are applicable in a new national cohort of prematurely born infants.

Methods: SWEDROP is a national register for ROP, initiated in 2006. The present paper reports on data from the register on various aspects of screening for ROP in infants born between 2010 and 2011 and compares the results with those for a previously published cohort born between 2008 and 2009. ResultsDuring the study period, 1744 infants were screened for ROP. Mean GA was 28.4w (22-31), and mean birth weight was 1239g (382-2615). Screening started at postnatal age (PNA) 5.4w (0.4-13.3) and postmenstrual age (PMA) 33.8 w (24.9-50.1) Mean number of examinations was 5.4 per infant (1-38). Mild (stages 1-2) and severe ( stage 3) ROP was found in 15.4% and 8.7%, respectively. Treatment was performed in 4.2% (73/1744) of the infants, but in none with a GA of 30weeks or more. The first treatment was performed at a mean PNA and PMA of 12.7 w (7.7-25.4) and 37.4 w (32.1-51.4), respectively.

Conclusions: Recently introduced new guidelines for ROP screening in Sweden remain applicable. Reassuringly, in infants born between 2010 and 2011, incidence of ROP, frequency and timing of treatment, frequency and timing of examinations and national coverage of ROP screening remained almost identical to those for a previous cohort from 2008 to 2009. The two SWEDROP cohorts provide a basis for discussion among Swedish ophthalmologists and neonatologists on the question of further lowering the upper screening limit with 1week.

Background/aims: Retinopathy of prematurity (ROP) is a sight-threatening disease, requiring efficient screening and treatment. The present study aims to describe various aspects on treatment for ROP in Sweden.

Methods: Data on treatment for ROP in infants born in 2008-2012 were extracted from Swedish national register for retinopathy of prematurity, a web-based national register.

Results: During 2008-2012, 3488 infants with a gestational age (GA) at birth of <31 weeks had been screened for ROP in Sweden. Altogether, 30.3% (1057/3488) of the infants developed ROP and 5.2% (181/3488) were treated. Type 1 ROP was found in at least one eye in 83.2% (149/179) of the treated infants. One third of the eyes (32.2% right, 29.9% left eyes) were treated more than once. Laser was the only treatment in 90% of the eyes. Mean number of laser spots at first laser session was 1177 and 1386 in right and left eyes, respectively. Number of laser spots correlated negatively with GA at birth (p=0.01). There was no change in frequency of treatment or number of laser spots during the 5-year period. Anti-vascular endothelial growth factor injections were performed in 28 eyes, encircling band was used in five eyes and vitrectomies were performed in seven eyes. Twenty-six retinal surgeons performed 9.4 (range 1-37) treatment sessions in the 181 infants.

Conclusions: The present study reveals similar incidences of ROP and frequencies of treatment during the 5-year study period. Many surgeons were involved in treatment of a rather limited number of infants. The results call for national discussions on organisation of ROP treatment.

Objectives To examine differences in growth patterns in preterm infants developing major morbidities including retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), necrotising enterocolitis (NEC) and intraventricular haemorrhage (IVH).

Study design Cohort study of 2521 infants born at a gestational age (GA) of 23–30 weeks from 11 level III neonatal intensive care units in USA and Canada, and 3 Swedish population-based cohorts.

Outcomes Birth weight and postnatal weight gain were examined relative to birth GA and ROP, BPD, NEC and IVH development.

Results Among infants with a birth GA of 25–30 weeks, birth weight SD score and postnatal weight were lower in those developing ROP and BPD. Infants developing ROP showed lower growth rates during postnatal weeks 7–9 in the 23–24 weeks GA group, during weeks 4–6 in the 25–26 weeks GA group and during weeks 1–5 in the 27–30 weeks GA group. Infants with BPD born at 27–30 weeks GA showed lower growth rates during postnatal weeks 3–5. Infants with NEC had lower growth rates after postnatal week 6 in all GA groups, with no significant differences in birth weight SD score. IVH was not associated with prenatal or postnatal growth.

Conclusions In this cohort study of extremely preterm infants, we found that the postnatal growth pattern was associated with morbidities such as ROP, BPD and NEC as well as with gestational age at birth.

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 favour-able 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 growthoutcomes. Motivating mothers to provide their infants with their own milk after pre-term birth should be emphasised

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.

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.

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.

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 10 th 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.

Leukocytosis, namely a markedly elevated white blood cell (WBC) count, occurs in 1.3–17.0% of infants admitted to neonatal intensive care units and can be induced by infection, inflammation, stress or medication. Postnatal leukocytosis can also reflect immature granulocytopoiesis in the bone marrow or systemic fetal inflammatory response syndrome, which particularly affects preterm infants (1). Chorioamnionitis and neonatal morbidities, such as sepsis, necrotising enterocolitis, intraventricular hemorrhage, prolonged oxygen support and bronchopulmonary dysplasia, have been associated with leukocytosis in preterm infants (2).

Background: The most severe form of rapidly progressing retinopathy of prematurity (ROP) is termed aggressive posterior ROP (APROP). APROP frequently causes severe visual impairment in affected preterm infants despite timely and appropriate laser treatment.

Objectives: We investigated the postnatal characteristics associated with APROP development in a national Swedish cohort.

Methods: This retrospective, 1:1 matched case-control study included all infants that developed APROP in zone 1 (n = 9) between 2008 and 2012. Control infants, matched for gestational age and birth weight, developed ROP no worse than stage 2 (n = 9). We retrieved data from medical records on infant birth characteristics, postnatal morbidities, and blood analyses from birth to the first ROP treatment. Infectious episodes included sepsis, C-reactive protein ≥10 mg/l, and other clinical signs of infection that required antibiotic treatment. A platelet count <100 × 109/l was considered to be thrombocytopenia.

Results: All APROP cases postnatally developed at least two infectious episodes, one in the first month and one around the time of ROP diagnosis. All APROP cases exhibited thrombocytopenia in the first month, and 6/9 exhibited thrombocytopenia around the time of ROP diagnosis. Compared to the controls, APROP cases more frequently developed necrotizing enterocolitis (8/9 vs. 1/9; p < 0.01) and sepsis (9/9 vs. 3/9; p < 0.01), and they had significantly lower median platelet counts (90 × 109/l, range 4-459, vs. 158 × 109/l, range 20-500; p < 0.001).

Conclusion: Multiple infectious episodes and thrombocytopenia, particularly around the time of ROP diagnosis, were associated with APROP development.

Background: Retinopathy of prematurity (ROP) is a sight-threatening disease affecting extremely preterm infants. The introduction of new ROP screening surveillance systems, with higher sensitivity and specificity than established ROP screening guidelines, has the potential to reduce the number of stressful eye examinations in these infants.

Objectives: To improve the specificity of the WINROP (Weight, Insulin-like growth factor-I, Neonatal, ROP) surveillance system, identifying extremely preterm infants requiring treatment for ROP.

Methods: Two cohorts that had previously been subjected to WINROP analyses were included and reevaluated in this study. The weight at WINROP alarm for extremely preterm infants, born at gestational age <27 weeks, was reevaluated and by establishing 'safe' WINROP alarm weight limits, an intersample reassessment of WINROP alarm was performed. The two cohorts were as follows: (1) the Extremely Preterm Infants in Sweden Study (EXPRESS) cohort, infants born in Sweden during 2004-2007 (n = 407), and (2) extremely preterm infants in a North American cohort, born during 2006-2009 (n = 566).

Results: In the EXPRESS cohort, 12.5% (40/319) of the infants who previously received a WINROP alarm were now reassessed as having no alarm; the specificity of WINROP in EXPRESS increased from 23.9% (86/360) to 35.0% (126/360). In the North American cohort, 15.4% (81/526) were reassessed as having no alarm; the specificity increased from 8.5% (38/447) to 26.6% (119/447). The sensitivity persisted as 97.5% in EXPRESS (45/47) and 98.3% (117/119) in the North American cohort.

Conclusions: The specificity of the WINROP surveillance system for extremely preterm infants can be significantly improved by reassessment using the weight at WINROP alarm.

Objective: To evaluate the ability of a postnatal weight-gain algorithm (WINROP) to identify sight-threatening retinopathy of prematurity (ROP type 1) in a nation-based extremely preterm infant cohort.

Methods: This study enrolled all 707 live-born extremely preterm (gestational age [GA] <27 weeks) infants, born 2004-2007 in Sweden; the Extremely preterm Infants in Sweden Study (EXPRESS). WINROP analysis was performed retrospectively in 407 of the infants using weekly weight gain to assess the preterm infant's risk of developing ROP type 1 requiring treatment. GA, birthweight (BW), and weekly postnatal weight measurements were entered into WINROP. WINROP signals with an alarm to indicate if the preterm infant is at risk for ROP type 1.

Results: In this extremely preterm population, WINROP correctly identified 96% (45/47) of the infants who required treatment for ROP type 1. The median time from alarm to treatment was 9 weeks (range, 4-20 weeks).

Conclusions: WINROP, an online surveillance system using weekly weight gain, identified extremely preterm infants at risk for ROP type 1 requiring treatment at an early stage and with high sensitivity in a Swedish nation-based cohort.

Objective: To investigate whether postnatal weight at first detection of retinopathy of prematurity (ROP) can predict preterm infants who will develop severe ROP warranting treatment.

Design: This modern, population-based cohort included 147 infants born at gestational age (GA) <32 weeks in the Gothenburg region during 2011–2012 and screened for ROP at Sahlgrenska University hospital. GA, birth weight (BW), and weekly postnatal weight from birth until postmenstrual age (PMA) 40 weeks data were retrospectively retrieved. Birth weight SD scores (BWSDS) were calculated. ROP data, including first detected ROP stage, maximal ROP stage, ROP treatment, and PMA at first detected sign of ROP were also retrieved. Weight SDS (WSDS) at first ROP detection was calculated.

Results: Stepwise multivariate logistic regression analysis revealed that the best fit-model of risk factors for developing severe ROP warranting treatment included; GA (OR=0.28, CI 95% 0.12 to 0.66, p<0.01) and WSDS at first ROP detection (OR=0.22, CI 95% 0.05 to 0.89, p<0.05).

Conclusions: Low weight and low WSDS at first ROP detection can be useful predictors for ROP warranting treatment.

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.

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 severe ROP development.

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.

Objectives: Poor weight gain during the first weeks of life in preterm infants is closely associated with the risk of developing the retinopathy of prematurity (ROP) and insufficient nutrition might be an important contributing factor. This study aimed to evaluate the effect of energy and macronutrient intakes during the first 4 weeks of life on the risk for severe ROP (stages 3-5).

Study design: A population-based study including all Swedish extremely preterm infants born before 27 gestational weeks during a 3-year period. Each infant was classified according to the maximum stage of ROP in either eye as assessed prospectively until full retinal vascularisation. The detailed daily data of actual intakes of enteral and parenteral nutrition and growth data were obtained from hospital records.

Results: Of the included 498 infants, 172 (34.5%) had severe ROP and 96 (19.3%) were treated. Energy and macronutrient intakes were less than recommended and the infants showed severe postnatal growth failure. Higher intakes of energy, fat and carbohydrates, but not protein, were significantly associated with a lower risk of severe ROP. Adjusting for morbidity, an increased energy intake of 10 kcal/kg/day was associated with a 24% decrease in severe ROP.

Conclusions: We showed that low energy intake during the first 4 weeks of life was an independent risk factor for severe ROP. This implies that the provision of adequate energy from parenteral and enteral sources during the first 4 weeks of life may be an effective method for reducing the risk of severe ROP in extremely preterm infants.

Background: Retinopathy of prematurity (ROP), a potentially blinding disease, affects preterm infants. High levels of oxygen saturation are a well-known risk factor for ROP.

Objectives: 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.

Methods: Preterm infants born with birth weight (BW) <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 <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).

Results: In the present WINROP cohort, 11.8% of the infants born at GA <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 <32 weeks in the present study compared to 84.7% in the previous study.

Conclusions: 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.