Insulin-Like Growth Factor-1 and Anti-Vascular Endothelial Growth Factor in Retinopathy of Prematurity: Has the Time Come

Treatment of ROP is currently evolving. Novel therapeutic options are emerging that have the potential to complement existing therapies and improve treatment outcomes. However, any new therapeutic options must be thoroughly evaluated before existing (and successful) treatment paradigms can be amended. This is particularly so when switching from locally effective therapies like photablative laser therapy to systemic pharmacologic treatments that may have hitherto unknown widespread side effects. This review compiles the current knowledge of where and when the two most advanced pharmacologic treatment options for ROP, IGF-1 supplementation and anti-VEGF treatment, may have their place in future therapy regimens for ROP. The requirement for clinical studies is emphasized: these are needed to address safety considerations before any of these interventions can achieve the status of standard clinical care in the very vulnerable population of ROP infants

Preterm infant circulating sex steroid levels are not altered by transfusion with adult male plasma: a retrospective multicentre cohort study

Objective To determine if plasma transfusions with male donor plasma to very preterm infants affect circulatory levels of sex steroids. Design and patients Retrospective multicentre cohort study in 19 infants born at gestational age Setting Three neonatal intensive care units in Sweden. Main outcome measures Concentrations of sex steroids and sex hormone-binding globulin (SHBG) in donor plasma and infant plasma measured before and after a plasma transfusion and at 6, 12, 24 and 72 hours. Results The concentrations of progesterone, dehydroepiandrosterone and androstenedione were significantly lower in donor plasma than in infant plasma before the transfusion (median (Q1-Q3) 37.0 (37.0-37.0), 1918 (1325-2408) and 424 (303-534) vs 901 (599-1774), 4119 (2801-14 645) and 842 (443-1684) pg/mL), while oestrone and oestradiol were higher in donor plasma (17.4 (10.4-20.1) and 16.0 (11.7-17.2) vs 3.1 (1.1-10.2) and 0.25 (0.25-0.25) pg/mL). Median testosterone and dihydrotestosterone (DHT) levels were 116-fold and 21-fold higher in donor plasma than pre-transfusion levels in female infants, whereas the corresponding difference was not present in male infants. Plasma sex steroid levels were unchanged after completed transfusion compared with pre-transfusion levels, irrespective of the gender of the receiving infant. The SHBG concentration was significantly higher in donor than in recipient plasma (22.8 (17.1-33.5) vs 10.2 (9.1-12.3) nmol/L) before transfusion but did not change in the infants after the transfusion. Conclusions A single transfusion of adult male plasma to preterm infants had no impact on circulating sex steroid levels.</p

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Current update on retinopathy of prematurity: screening and treatment

PURPOSE OF REVIEW: Despite current treatments, retinopathy of prematurity (ROP) remains a major cause of blindness in premature infants and the incidence is increasing with increased survival of infants born at very early gestational ages. This review summarizes the recent literature on ROP with a special focus on recent advances in treatment options as well as newly developed methods for disease screening. RECENT FINDINGS: Genetic studies find a genetic predisposition to ROP-linking genes in the Wnt pathway with development of severe ROP. With regard to diagnosis, a new screening method has been developed that allows prediction of ROP risk based on postnatal body weight gain alone. Formerly weight gain postnatally in combination with insulin-like growth factor levels was found to predict treatable ROP. New treatment options for severe cases of ROP have been proposed targeting vascular endothelial growth factor (VEGF). Whether anti-VEGF treatment is well tolerated in preterm infants, however, has to be further evaluated in controlled clinical trials. Finally, new reports from the early treatment ROP group suggest that early laser treatment for type 1 but not type 2 high-risk prethreshold ROP improves visual acuity outcomes at 6 years of age. SUMMARY: With the increasing survival of premature infants and increased incidence of ROP, it is important to screen for ROP risk and treat at-risk patients in a timely manner to preserve their visual function and reduce complications

Fetal haemoglobin and bronchopulmonary dysplasia in neonates : An observational study

Objective: Early decrease in fetal haemoglobin (HbF) is an indicator of loss of endogenous blood components that might have predictive value for development of bronchopulmonary dysplasia (BPD). The link between HbF and BPD has not been evaluated. Design: Retrospective observational study. Setting: Tertiary level neonatal intensive care unit, referral centre for Southern Sweden. Patients: 452 very preterm infants (<30 gestational weeks) born 2009-2015. Interventions: Regular clinical practice. Main outcome measures: Mean HbF, haemoglobin (Hb) and partial oxygen pressure (PaO2) levels calculated from 11 861 arterial blood gas analyses postnatal week 1. Relationship between HbF (%) and BPD (requirement of supplemental oxygen at 36 weeks' postmenstrual age) and the modifying influence of PaO2 (kPa) and total Hb (g/L) was evaluated. Results: The mean gestational age (GA) at birth was 26.4 weeks, and 213 (56%) infants developed BPD. A 10% increase in HbF was associated with a decreased prevalence of BPD, OR 0.64 (95% CI 0.49 to 0.83; p<0.001). This association remained when adjusting for mean PaO2 and Hb. Infants with an HbF in the lowest quartile had an OR of 27.1 (95% CI 11.6 to 63.4; p<0.001) for development of BPD as compared with those in the highest quartile. The area under the curve for HbF levels and development of BPD in the full statistical model was 0.871. Conclusions: Early rapid postnatal decline in HbF levels was associated with development of BPD in very preterm infants. The association between HbF and BPD was not mediated by increased oxygen exposure. The potential benefit of minimising loss of endogenous blood components on BPD outcome will be investigated in a multicentre randomised trial

Natural History of Retinopathy of Prematurity in Infants Born Before 27 Weeks' Gestation in Sweden

Objective: To investigate the natural history of retinopathy of prematurity (ROP) in 506 extremely preterm infants born before 27 weeks' gestation in Sweden during a 3-year period. Methods:A national population-based study was performed in Sweden from April 1, 2004, to March 31, 2007. According to the study protocol, initial eye examinations were to be performed at postnatal week 5, and examinations were repeated until the retina was completely vascularized or until criteria for treatment were met. The examinations were to be performed weekly, enabling study of the course and severity of ROP. In infants without ROP or with mild ROP without progression during the latest examinations, further examinations were performed weekly or every other week from postmenstrual age 35 weeks. Results: During the study, 368 infants (72.7%) developed ROP. Postmenstrual age at onset of ROP was significantly related to severity of ROP, even when controlling for gestational age (ie, the earlier the onset of ROP, the higher the risk of developing severe ROP). Site of onset of ROP was significantly related to gestational age at birth. The risk of nasal onset was almost doubled for every week of decrease in gestational age at birth. Nasal onset was associated with severe ROP, even after adjusting for gestational age at birth. Conclusion: This population-based study confirms results of the Cryotherapy for Retinopathy of Prematurity study and shows new correlations regarding time and site of onset of ROP, both of which are associated with disease severity

Evaluation of new guidelines for ROP screening in Sweden using SWEDROP - a national quality register

PurposeTo investigate whether recent Swedish guidelines for Retinopathy of Prematurity (ROP) screening, that is, a gestational age (GA) at birth of <31weeks (w), are applicable in a new national cohort of prematurely born infants. MethodsSWEDROP 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. ConclusionsRecently 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

Swedish National Register for Retinopathy of Prematurity (SWEDROP) and the Evaluation of Screening in Sweden

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

Maternal and neonatal factors associated with poor early weight gain and later retinopathy of prematurity

Aim: To identify factors associated with poor early weight gain as reflected in an alarm system, WINROP, and risk of later proliferative retinopathy of prematurity (ROP) in infants with gestational age (GA) < 28 weeks