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Purpose: To determine the prevalence and causes of blindness and visual impairment among adults in Kogi, Nigeria. Methods: A Rapid assessment of avoidable blindness (RAAB) protocol was used with additional tools measuring disability and household wealth to measure the prevalence of blindness and visual impairment (VI) and associations with sex, disability, wealth, cataract surgical coverage and its effectiveness. Results: Age- and sex-adjusted all-cause prevalence of bilateral blindness was 3.6% (95%CI 3.0–4.2%), prevalence of blindness among people living with additional, non-visual disabilities was 38.3% (95% CI 29.0–48.6%) compared to 1.6% (95%CI 1.2–2.1%; χ2 = 771.9, p<0.001) among people without additional disabilities. Cataract was the principal cause of bilateral blindness (55.3%). Cataract surgical coverage (CSC) at visual acuity (VA) 3/60 was 48.0%, higher among men than women (53.7% vs 40.3%); 12.0% among people with non-visual disabilities; 66.9% among people without non-visual disabilities, being higher among people in the wealthiest two quintiles (41.1%) compared to the lowest three (24.3%). Effective Cataract Surgical Coverage at Visual Acuity 6/60 was 31.0%, higher among males (34.9%) than females (25.5%), low among people with additional, non-visual disabilities (1.9%) compared to people with no additional disabilities (46.2%). Effective CDC was higher among people in the wealthiest two quintiles (411%) compared to the poorest three (24.3%). Good surgical outcome (VA>6/18) was seen in 61 eyes (52.6%) increasing to 71 (61.2%) eyes with best correction. Cost was identified as the main barrier to surgery. Conclusion: Findings suggest there exists inequalities in eye care with women, poorer people and people with disabilities having a lower Cataract Surgical Coverage, thereby, underscoring the importance of eye care programs to address these inequalities. [ABSTRACT FROM AUTHOR]

Retinopathy of Prematurity (ROP) significantly contributes to childhood blindness globally, with a disproportionately high burden in low- and middle-income countries (LMICs) due to improved neonatal care alongside inadequate ROP screening and treatment facilities. This study aims to validate the performance of Postnatal Growth and Retinopathy of Prematurity (G-ROP) screening criteria in a cohort of premature infants presenting at a tertiary care setting in Pakistan. This cross-sectional study utilized retrospective chart review of neonates admitted to the neonatal intensive care unit (NICU) at The Aga Khan University Hospital, Pakistan from January 2018 to February 2022. The complete G-ROP criteria were applied as prediction tool for infants with type 1 ROP, type 2 ROP, and no ROP outcomes. Out of the 166 cases, 125 cases were included in the final analysis, and remaining cases were excluded due to incomplete data. ROP of any stage developed in 83 infants (66.4%), of whom 55 (44%) developed type 1 ROP, 28 (22.4%) developed type 2 ROP, and 19 (15.2%) were treated for ROP. The median BW was 1060 gm (IQR = 910 to 1240 gm) and the median gestational age was 29 wk (IQR = 27 to 30 wk). The G-ROP criteria demonstrated a sensitivity of 98.18% (95% CI: 90.28–99.95%) for triggering an alarm for type 1 ROP. The G-ROP criteria achieved 100% sensitivity (95% CI: 87.66 to 100%) for type 2 ROP. The overall sensitivity of G-ROP criteria to trigger an alarm for any type of ROP was 98.8% (95% CI: 93.47 to 99.97%). Thus, the G-ROP screening model is highly sensitive in detecting at-risk infants for ROP in a Pakistani tertiary care setting, supporting its use in LMICs where standard screening criteria may not suffice. [ABSTRACT FROM AUTHOR]

Photoreceptor cell death can cause progressive and irreversible visual impairments. Still, effective therapies on retinal neuroprotection are not available. Hypoxia-inducible factors (HIFs) are transcriptional factors which strongly regulate angiogenesis, erythropoiesis, intracellular metabolism, and programed cell death under a hypoxic or an abnormal metabolic oxidative stress condition. Therefore, we aimed to unravel that inhibition of HIFs could prevent disease progression in photoreceptor cell death, as recent studies showed that HIFs might be pathologic factors in retinal diseases. Adult male balb/cAJcl (8 weeks old; BALB/c) were used to investigate preventive effects of a novel HIF inhibitor halofuginone (HF) on a murine model of light-induced retinopathy. After intraperitoneal injections of phosphate-buffered saline (PBS) or HF (0.4 mg/kg in PBS) for 5 days, male BALB/c mice were subjected to a dark-adaption to being exposed to a white LED light source at an intensity of 3,000 lux for 1 hour in order to induce light-induced retinal damage. After extensive light exposure, retinal damage was evaluated using electroretinography (ERG), optical coherence tomography (OCT), and TUNEL assay. Light-induced retinal dysfunction was suppressed by HF administration. The amplitudes of scotopic a-wave and b-wave as well as that of photopic b-wave were preserved in the HF-administered retina. Outer retinal thinning after extensive light exposure was suppressed by HF administration. Based on the TUNEL assay, cell death in the outer retina was seen after light exposure. However, its cell death was not detected in the HF-administered retina. Halofuginone was found to exert preventive effects on light-induced outer retinal cell death. [ABSTRACT FROM AUTHOR]

Aim: To investigate reasons for delayed presentation in patients with proliferative diabetic retinopathy (PDR). Methods: A questionnaire was designed to investigate consecutive PDR patients with delayed presentation who visited our center between January 2021 and December 2021. The questionnaire was divided into four sections: knowledge regarding diabetic retinopathy (DR), attitude toward DR treatment, difficulties adhering to follow-up plans, and medical care. The systemic disease status and severity of DR were recorded. Logistic analysis was undertaken to investigate DR treatment refusal and delay factors. Results: A total of 157 patients were included in this study, with an average age of 50.0 ± 11.6 years. The median glycated hemoglobin level (HbA1c) was 7.8% (IQR 2.5%). Among the 157 eyes, most required vitrectomy intervention (144, 91.7%); 17 developed neovascular glaucoma (NVG), while only 13 required additional photocoagulation. Among the 36 patients with undiagnosed DM, the reason for delayed DR presentation was a lack of awareness of DM status among these patients (36 cases, 100.0%). Most of the patients with a known history of DM exhibited inadequate DR knowledge (29, 24.0%), believed their good visual acuity did not require DR screening (98, 81.0%), and had poorly controlled diabetes (113, 93.3%). Factors related to refusing DR treatment were patients with an inability to receive regular diabetes treatment in internal medicine clinics (OR 6.78, 95% CI 1.73–26.59, p = 0.006), patients who could not tolerate discomfort during ophthalmic examination and treatment (OR 15.15, 95% CI 2.70–83.33, p<0.001), and patients who did not have any retinal abnormalities detected and were not informed about the need for regular screening (OR 2.05, 95% CI 1.36–3.09, p<0.001). Conclusions: This study investigated the factors contributing to delayed presentation among patients with PDR. Many individuals in the delayed population were found to have undiagnosed DM. Among patients already aware of their DM status, reasons for delay included insufficient knowledge about DR, negative attitudes toward screening and treatment, and difficulties seeking medical care in real-life situations. Furthermore, there needed to be more improvements in the detection, treatment, and follow-up of DR by internal medicine practitioners and ophthalmologists. [ABSTRACT FROM AUTHOR]

Studies suggest perinatal infection with SARS-CoV-2 can induce adverse birth outcomes, but studies published to date have substantial limitations. We therefore conducted an observational study of 211 births occurring between January 2020-September 2021 in three urban cohorts participating in the Environmental Influences on Child Health Outcomes Program. Serology was assessed for IgG, IgM and IgA antibodies to nucleocapsid, S1 spike, S2 spike, and receptor-binding domain. There were no differences in gestational age (GA), birth weight, preterm birth (PTB) or low birth weight (LBW) among seropositive mothers. However, the few (n = 9) IgM seropositive mothers had children with lower BW (434g, 95% CI: 116–752), BW Z score-for-GA (0.73 SD, 95% CI 0.10–1.36) and were more likely to deliver preterm (OR 8.75, 95% CI 1.22–62.4). Though there are limits to interpretation, the data support efforts to prevent SARS-CoV-2 infections in pregnancy. [ABSTRACT FROM AUTHOR]

Hypothyroidism is the commonest endocrine disorder of pregnancy, with known adverse feto-maternal outcomes. There is limited data on population-based prevalence, risk factors and outcomes associated with treatment of hypothyroidism in early pregnancy. We conducted analysis on data from an urban and peri-urban low to mid socioeconomic population-based cohort of pregnant women in North Delhi, India to ascertain the burden, risk factors and impact of treatment, on adverse pregnancy outcomes- low birth weight, prematurity, small for gestational age and stillbirth. This is an observational study embedded within the intervention group of the Women and Infants Integrated Interventions for Growth Study, an individually randomized factorial design trial. Thyroid stimulating hormone was tested in 2317 women in early (9–13 weeks) pregnancy, and thyroxin replacement started hypothyroid (TSH ≥2.5mIU/mL). Univariable and multivariable generalized linear model with binomial family and log link were performed to ascertain risk factors associated with hypothyroidism and association between hypothyroidism and adverse pregnancy outcomes. Of 2317 women, 29.2% (95% CI: 27.4 to 31.1) had hypothyroidism and were started on thyroxin replacement with close monitoring. Overweight or obesity was associated with increased risk (adjusted RR 1.29, 95% CI 1.10 to 1.51), while higher hemoglobin concentration was associated with decreased risk (adjusted RR 0.93, 95% CI 0.88 to 0.98 for each g/dL) for hypothyroidism. Hypothyroid women received appropriate treatment with no increase in adverse pregnancy outcomes. Almost a third of women from low to mid socio-economic population had hypothyroidism in early pregnancy, more so if anemic and overweight or obese. With early screening and adequate replacement, adverse pregnancy outcomes may be avoided. These findings highlight the need in early pregnancy for universal TSH screening and adequate treatment of hypothyroidism; as well as for attempts to reduce pre and peri-conception overweight, obesity and anemia. Clinical trial registration: Clinical trial registration of Women and Infants Integrated Interventions for Growth Study Clinical Trial Registry–India, #CTRI/2017/06/008908; Registered on: 23/06/2017, (http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=19339&EncHid=&userName=society%20for%20applied%20studies). [ABSTRACT FROM AUTHOR]

Background and objectives: Early detection is critical to achieving optimal outcomes in children with congenital cataract. We hypothesized that detection of congenital cataract in preterm infants would be delayed compared with term/post-term peers due to delayed delivery of whole population child health interventions. Methods: Secondary analysis of data using a nested case-control study approach in a prospective population-based cohort study. Inclusion criteria comprised children diagnosed with congenital cataract requiring surgical intervention during the first two years of life in UK and Ireland in 2009 and 2010. Association between late detection (after eight weeks post-natal age, ie outside the neonatal and infant eye national screening programme) of cataract and preterm birth (gestational age less than 37 weeks) was assessed using multivariable logistic regression. Results: Of 186 children with congenital cataract, 17 children were born preterm (9%, gestational age range 24–37weeks). Neonatal detection occurred in 64/186 (34%), and late detection in 64 children (34%). Late detection was independently associated with premature birth, specifically moderate/late preterm birth (adjusted odds ratio 3.0, 95%CI 1.1 to 8.5). Conclusions: Our findings suggest that, despite enhanced eye surveillance being recommended for those born moderate/late preterm (32+ weeks gestational age, ie not eligible for retinopathy of prematurity screening), congenital cataract is not being effectively detected through the routine screening programme for this vulnerable group. It is necessary to improve the effectiveness of the screening programme, and care must be taken to ensure that competing health care needs of preterm children do not prevent universal child health interventions. [ABSTRACT FROM AUTHOR]

Myopic Choroidal neovascularization (mCNV) is one of the most common vision-threatening com- plications of pathological myopia among many retinal diseases. Optical Coherence Tomography Angiography (OCTA) is an emerging newer non-invasive imaging technique and is recently being included in the investigation and treatment of mCNV. However, there exists no standard tool for time-efficient and dependable analysis of OCTA images of mCNV. In this study, we propose a customizable ImageJ macro that automates the OCTA image processing and lets users measure nine mCNV biomarkers. We developed a three-stage image processing pipeline to process the OCTA images using the macro. The images were first manually delineated, and then denoised using a Gaussian Filter. This was followed by the application of the Frangi filter and Local Adaptive thresholding. Finally, skeletonized images were obtained using the Mexican Hat filter. Nine vascular biomarkers including Junction Density, Vessel Diameter, and Fractal Dimension were then computed from the skeletonized images. The macro was tested on a 26 OCTA image dataset for all biomarkers. Two trends emerged in the computed biomarker values. First, the lesion-size dependent parameters (mCNV Area (mm2) Mean = 0.65, SD = 0.46) showed high variation, whereas normalized parameters (Junction Density(n/mm): Mean = 10.24, SD = 0.63) were uniform throughout the dataset. The computed values were consistent with manual measurements within existing literature. The results illustrate our ImageJ macro to be a convenient alternative for manual OCTA image processing, including provisions for batch processing and parameter customization, providing a systematic, reliable analysis of mCNV. [ABSTRACT FROM AUTHOR]

Background: Extrauterine growth restriction (EUGR) is common among very low birth weight (VLBW) infants and associated with poor neurodevelopmental outcomes. There are two types of EUGR definitions (cross-sectional and longitudinal) and many growth charts for monitoring postnatal growth. Aims of our study were 1) to compare the rate of small for gestational rate (SGA) and EUGR in a population of VLBW infants, both according to different growth charts (Fenton, INeS charts and Intergrowth-21) and different definitions; 2) to identify risk factors for EUGR. Methods: This is a single centre retrospective observational study, including all VLBW infants born between January 2009 and December 2018. Anthropometric measures were obtained at birth and at discharge and presented as z-scores according to three growth charts (Fenton, INeS charts, Intergrowth-21). Maternal, clinical and nutritional data were retrieved from clinical records. Results: 228 VLBW were included. Percentage of SGA did not change significantly according to the three different growth charts (Fenton 22.4%, INeS charts 22.8%, Intergrowth 28.2%, p 0.27). Prevalence of EUGR was significantly higher when INeS and Fenton charts were used, compared to Intergrowth charts regardless of EUGR-definition (cross sectional-EUGR: Fenton 33.5%, INeS charts 40.9%, Intergrowth-21 23.8%, p 0.001; longitudinal-EUGR (loss of 1SDS): Fenton 15%, INeS charts 20.4%, Intergrowth 4%, p <0.001). In our population a longer time to reach 100 ml/kg/day of enteral feeding increased of 18% the risk of longitudinal EUGR. Late onset sepsis and retinopathy of prematurity were associated with an increased risk of longitudinal EUGR, although not significantly, while having a preeclamptic mother was associated with a reduced risk. Conclusions: We confirmed a wide variability of EUGR rates when using different charts and definitions, highlighting that Intergrowth-21 charts identify less EUGR when compared to INeS and Fenton charts. Standardized criteria for defining EUGR are warranted in order to facilitate comparisons between studies and to improve the nutritional management of VLBW infants. [ABSTRACT FROM AUTHOR]

Introduction: Retinopathy of prematurity (ROP) is a serious eye disease in preterm infants. Generally, the progression of this disease can be detected by screening infants regularly. In case of progression, treatment can be instituted to stop the progression. In Indonesia, however, not all infants are screened because the number of pediatric ophthalmologists trained to screen for ROP and provide treatment is limited. Therefore, other methods are required to identify infants at risk of developing severe ROP. Objective: To assess a scoring model's internal and external validity to predict ROP progression in Indonesia. Method: To develop a scoring model and determine its internal validity, we used data on 98 preterm infants with ROP who had undergone one or more serial eye examinations between 2009 and 2014. For external validation, we analyzed data on 62 infants diagnosed with ROP irrespective of the stage between 2017 and 2020. Patients stemmed from one neonatal unit and three eye clinics in Jakarta, Indonesia. Results: We identified the duration of oxygen supplementation, gestational age, socio-economic status, place of birth, and oxygen saturation monitor setting as risk factors for developing ROP. We developed two models—one based on the duration of supplemental oxygen and one on the setting of the oxygen saturation monitor. The ROP risk and probabilistic models obtained the same sensitivity and specificity for progression to Type 1 ROP. The agreement, determined with the Kappa statistic, between the ROP risk model's suitability and the probabilistic model was excellent. The external validity of the ROP risk model showed 100% sensitivity, 73% specificity, 76% positive predictive value, 100% negative predictive value, positive LR +3.7, negative LR 0, 47% pre-test probability, and 77% post-test probability. Conclusion: The ROP risk scoring model can help to predict which infants with first-stage ROP might show progression to severe ROP and may identify infants who require referral to a pediatric ophthalmologist for treatment. [ABSTRACT FROM AUTHOR]

Background: The study was conducted to determine reference interval (RI) and evaluate the effect of preanalytical variables on Dried blood spot (DBS)-amino acids, acylcarnitines and succinylacetone of neonates. Methodology: DBS samples were collected within 48–72 hours of life. Samples were analyzed for biochemical markers on tandem mass spectrometer at the University of Iowa. Comparison of RI across various categorical variables were performed. Results: A total of 610 reference samples were selected based on exclusion criteria; 53.2% being females. Mean gestational age (GA) of mothers at the time of delivery was 38.7±1.6 weeks; 24.5% neonates were of low birth weight and 14.3% were preterm. Out of the total 610 neonates, 23.1% were small for GA. Reference intervals were generated for eleven amino acids, thirty-two acylcarnitines and succinylacetone concentrations. Markers were evaluated with respect to the influence of gender, GA, weight and time of sampling and statistically significant minimal differences were observed for some biomarkers. Conclusion: RI for amino acids, succinylacetone and acylcarnitine on DBS has been established for healthy neonates, which could be of use in the clinical practice. Clinically significant effect of GA, weight, gender and time of sampling on these markers were not identified. [ABSTRACT FROM AUTHOR]

Background: Previous studies found that infants with retinopathy of prematurity (ROP) who were treated for more posterior disease with a greater number of laser spots developed higher myopia. These studies included multiple physicians with variations in laser density. In treatments by a single physician, laser spot count is a better surrogate for area of avascular retina and anterior-posterior location of disease, so that the relationship with myopia can be better assessed. Methods: Our retrospective study included infants treated with laser for ROP by a single surgeon at a single center. Exclusion criteria were irregularities during laser and additional treatment for ROP. We assessed correlation between laser spot count and change in refractive error over time using a linear mixed effects model. Results: We studied 153 eyes from 78 subjects treated with laser for ROP. The average gestational age at birth was 25.3±1.8 weeks, birth weight 737±248 grams, laser spot count 1793±728, and post-treatment follow up 37±29 months. Between corrected ages 0–1 years, the mean spherical equivalent was +0.4±2.3 diopters; between ages 1–2, it was -1.3±3.2D; and ages 2–3 was -0.8±3.1D. Eyes that received more laser spots had significantly greater change in refractive error over time (0.30D more myopia per year per 1000 spots). None of the eyes with hyperopia before 18 months developed myopia during the follow-up period. Conclusions: Greater myopia developed over time in infants with ROP treated by laser to a larger area of avascular retina. [ABSTRACT FROM AUTHOR]

Objective: We compared birth injuries for spontaneous vaginal (VD) and caesarean section (CS) deliveries in preterm and term pregnancies. Methods: A retrospective cohort study was conducted in a single tertiary center, between January 1st, 2007, and December 31st, 2017. The study included 62330 singleton pregnancies delivered after 24 0/7 weeks gestation. Multivariable analyses compared trauma at birth, birth hypoxia and birth asphyxia in term and preterm deliveries, stratified by mode of birth, VD versus CS. Main outcome measure was trauma at birth including intracranial laceration and haemorrhage, injuries to scalp, injuries to central and peripheral nervous system, fractures to skeleton, facial and eye injury. Results: The incidence of preterm deliveries was 10.9%. Delivery of preterm babies by CS increased from 37.0% in 2007 to 60.0% in 2017. The overall incidence of all birth trauma was 16.2%. When stratified by mode of delivery, birth trauma was recorded in 23.4% of spontaneous vaginal deliveries and 7.5% of CS deliveries (aOR 3.3, 95%CI 3.1–3.5). When considered all types of birth trauma, incidence of trauma at birth was higher after 28 weeks gestation in VD compared to CS (28–31 weeks, aOR 1.7, 95% CI 1.3–2.3; 32–36 weeks, aOR 4.2, 95% CI 3.6–4.9; >37 weeks, aOR 3.3, 95% CI 3.1–3.5). There was no difference in the incidence of birth trauma before 28 weeks gestation between VD and CS (aOR 0.8, 95% CI 0.5–1.2). Regarding overall life-threatening birth trauma or injuries at birth with severe consequences such as cerebral and intraventricular haemorrhage, cranial and brachial nerve injury, fractures of long bones and clavicle, eye and facial injury, there was no difference in vaginal preterm deliveries compared to CS deliveries (p > 0.05 for all). Conclusion: CS is not protective of injury at birth. When all types of birth trauma are considered, these are more common in spontaneous VD, thus favoring CS as preferred method of delivery to avoid trauma at birth. However, when stratified by severity of birth trauma, preterm babies delivered vaginally are not at higher risk of major birth trauma than those delivered by CS. [ABSTRACT FROM AUTHOR]

Glaucoma is the second leading cause of blindness worldwide, and peripapillary atrophy (PPA) is a morphological symptom associated with it. Therefore, it is necessary to clinically detect PPA for glaucoma diagnosis. This study was aimed at developing a detection method for PPA using fundus images with deep learning algorithms to be used by ophthalmologists or optometrists for screening purposes. The model was developed based on localization for the region of interest (ROI) using a mask region-based convolutional neural networks R-CNN and a classification network for the presence of PPA using CNN deep learning algorithms. A total of 2,472 images, obtained from five public sources and one Saudi-based resource (King Abdullah International Medical Research Center in Riyadh, Saudi Arabia), were used to train and test the model. First the images from public sources were analyzed, followed by those from local sources, and finally, images from both sources were analyzed together. In testing the classification model, the area under the curve's (AUC) scores of 0.83, 0.89, and 0.87 were obtained for the local, public, and combined sets, respectively. The developed model will assist in diagnosing glaucoma in screening programs; however, more research is needed on segmenting the PPA boundaries for more detailed PPA detection, which can be combined with optic disc and cup boundaries to calculate the cup-to-disc ratio. [ABSTRACT FROM AUTHOR]

Purpose: The study aimed to evaluate risk factors for macular atrophy (MA) associated with myopic choroidal neovascularization (mCNV) during long-term follow-up after intravitreal anti-vascular endothelial growth factor (VEGF) treatment in highly myopic eyes. Methods: The medical records of patients who received intravitreal injection of anti-VEGF agents as mCNV treatment and were followed-up for more than 36 months were retrospectively reviewed. The risk factors for the development of mCNV-MA, which is the fovea-involving patchy atrophy lesion adjacent to mCNV, were investigated using the Cox proportional hazard model. Results: A total of 82 eyes (74 patients) were included in the study. The mean age at anti-VEGF treatment was 56.3 ± 12.5 years (range, 26–77), and the mean follow-up period was 76.3 ± 33.5 months (range, 36–154). During follow-up, mCNV-MA developed in 27 eyes (32.9%), and its occurrence was estimated to be 24.5% at 3 years and 37.3% at 5 years after the first anti-VEGF treatment. Old age (hazard ratio [HR] = 1.054, 95% confidence interval [CI]: 1.018–1.091; P = 0.003) and greater CNV size at baseline (HR = 2.396, CI: 1.043–5.504; P = 0.040) were significant factors for mCNV-MA development. Eyes with a thinner subfoveal choroid were more likely to show faster enlargement of the mCNV-MA during follow-up. Conclusions: In mCNV eyes treated with intravitreal anti-VEGF agents, older age and greater mCNV size at baseline were risk factors for the development of MA during long-term follow-up, which was associated with a poor visual prognosis. [ABSTRACT FROM AUTHOR]

Rationale: Studies identify prenatal household air pollution (HAP) exposure and maternal psychological distress (PMPD) as independent factors contributing to gestational ill-health and adverse birth outcomes. Objective: We investigated the impact of PMPD on fetal biometric parameters (FBP) in HAP-exposed pregnant Nigerian women. Methods: The randomized controlled trial (RCT; ClinicalTrials.gov NCT02394574) investigated effects of HAP exposure in pregnant Nigerian women (n = 324), who customarily cooked with polluting fuels (firewood or kerosene). Half of the women (intervention group) were given CleanCook ethanol stoves to use for 156 days during the study. Once a month, all women were administered an abridged version of the SF-12v2TM health-related quality of life questionnaire to assess psychological distress. Using mixed effects linear regression models, adjusted for relevant covariates, we analyzed associations between the women's exposure to PM2·5 (particulate matter with an aerodynamic diameter<2·5 microns) from HAP, their PMPD scores, and FBP (ultrasound estimated fetal weight [UEFW], head circumference [HC], abdominal circumference [AC], femur length [FL], biparietal diameter [BPD], estimated gestational age [GA] and intrauterine growth restriction [IUGR]), and birth anthropometric measures (birth weight [BW] and birth length [BL]). Results: PMPD negatively impacted UEFW, HC, FL, BPD and BL (p<0·05). Controls (kerosene/firewood users) experienced significantly higher PMPD compared with ethanol-stove users (p<0·05). The mediation analysis revealed that the proportion of the outcome (fetal biometrics, birth anthropometrics, IUGR and GA), which can be explained via PMPD by groups (intervention vs. control) after adjusting for confounding variables was 6·2% (0·062). No significant correlation was observed between levels of PM2.5 exposure and PMPD scores. Conclusions: PMPD was an independent mediator of adverse fetal biometric parameters in pregnant women, who were exposed to HAP from burning of firewood/kerosene. Formulating preventative measures to alleviate maternal distress during pregnancy and reducing exposure to HAP is important from public health perspectives. [ABSTRACT FROM AUTHOR]

This study was conducted to examine retinal sensitivity (RS) in eyes with pachychoroid diseases and to analyze its association with the presence or absence of quiescent choroidal neovascularization (CNV), that can be protective against retinal dysfunction or atrophy in other macular diseases such as age-related macular degeneration. A total of 12 eyes of 12 patients aged ≥45 years having the characteristic findings of central serous chorioretinopathy but not presenting any exudative changes were included in this study. Choroidal vascular hyper permeability (CVH) was identified by indocyanine green angiography, and the presence or absence of CNV was evaluated by optical coherence tomography angiography. RS at 68 points was examined by microperimetry. The average RS corresponding to within and outside CVH was compared. The association between the difference in RS and the presence or absence of CNV was also analyzed. CNV was detected in six eyes (50%). In eyes without CNV, the RS within CVH was similar compared with that outside CVH. However, in eyes with CNV, the RS within CVH was significantly decreased compared with that outside CVH. Multiple regression analysis revealed the presence of CNV as an independent factor associated with RS. In eyes with pachychoroid diseases, RS decreased within the CVH area under the coexistence of nonexudative CNV. [ABSTRACT FROM AUTHOR]

Background: Retinopathy of prematurity (ROP) remains the leading cause for blindness in children. Limited hyperoxia induced proliferative retinopathy (L-HIPR) was recently introduced as a potential animal model for ROP and persistent fetal vasculature; however, the detailed pathological changes remain unclear. Methods: To model L-HIPR, we placed C57BL/6J mice in 65% oxygen from birth to post-natal day 7 (P7). We examined eyes at intervals between P12 and P30. Retinal morphometry, thickness, and preretinal fibrosis were quantified at different time points on histological sections stained with hematoxylin and eosin (H&E) and Masson Trichrome, respectively. Vascular development, angiogenesis, inflammation, and pericyte coverage were analyzed using immunohistochemistry staining in retinal flat mounts and cross sections. Results: In L-HIPR, the hyaloidal vessels persisted until the latest time point in this study, P30 and began to invaginate the peripheral then central retina starting at P12. Central retinal distortion was noted beginning at P17, while the peripheral retina demonstrated a trend of thinning from P12 to P30. We found that L-HIPR was associated with delayed and abnormal retinal vascular development with subsequent retinal inflammation, pericyte loss and preretinal fibrosis. Conclusion: Our study presents a detailed analysis of the L-HIPR animal model demonstrating vitreoretinal pathologic changes, preretinal fibrosis and persistent hyaloidal vessels into adulthood. Based on our findings, we suggest that the persistence and peculiar stepwise migration of the hyaloidal vessels into the retina may provide a potential rescue mechanism for inner retinal development that deserves further study. [ABSTRACT FROM AUTHOR]

Introduction: Cerebral Small Vessel Disease (CSVD), a progressive degenerative disorder of small caliber cerebral vessels, represents a major contributor to stroke and vascular dementia incidence worldwide. We sought to conduct a systematic review of the role of retinal biomarkers in diagnosis and characterization of CSVD. Methods: We conducted a systematic review of MEDLINE, PubMed, Scopus, the Cochrane Library Database, and Web of Science. We identified studies of sporadic CSVD (including CSVD not otherwise specified, Cerebral Amyloid Angiopathy, and Hypertensive Arteriopathy) and the most common familial CSVD disorders (including CADASIL, Fabry disease, and MELAS). Included studies used one or more of the following tools: visual fields assessment, fundus photography, Optical Coherence Tomography and OCT Angiography, Fluorescein Angiography, Electroretinography, and Visual Evoked Potentials. Results: We identified 48 studies of retinal biomarkers in CSVD, including 9147 cases and 12276 controls. Abnormalities in retinal vessel diameter (11 reports, n = 11391 participants), increased retinal vessel tortuosity (11 reports, n = 617 participants), decreased vessel fractal dimension (5 reports, n = 1597 participants) and decreased retinal nerve fiber layer thickness (5 reports, n = 4509 participants) were the biomarkers most frequently associated with CSVD. We identified no reports conducting longitudinal retinal evaluations of CSVD, or systematically evaluating diagnostic performance. Conclusion: Multiple retinal biomarkers were associated with CSVD or its validated neuroimaging biomarkers. However, existing evidence is limited by several shortcomings, chiefly small sample size and unstandardized approaches to both biomarkers' capture and CSVD characterization. Additional larger studies will be required to definitively determine whether retinal biomarkers could be successfully incorporated in future research efforts and clinical practice. [ABSTRACT FROM AUTHOR]

Compelling evidence supports the current international recommendation of at least 150 min/week of leisure-time physical activity (LTPA) during pregnancy. However, the potential relationship between LTPA and birth weight (BW) remains unclear in low- and middle-income countries. The purpose of this study was to examine the association between LTPA during pregnancy and offspring BW in an Amazonian population. Prospective cohort study was carried-out with 500 pregnant women and their offspring followed-up in the MINA-Brazil study, which was conducted in Cruzeiro do Sul, Western Brazilian Amazon. LTPA was assessed in the second (mean 19.6, SD 2.4 weeks) and third (mean 27.8, SD 1.6 weeks) gestational trimesters by a standardised interview and categorised according to the recommended cut-off of at least 150 min/week. We calculated offspring BW z-scores by sex and gestational age. We then explored the effect of LTPA during pregnancy on offspring BW, the association between LTPA and small-for-gestational-age (SGA) or large-for-gestational-age (LGA) births, and the mediating role of excessive and insufficient gestational weight gain (GWG). At least 150 min/week of LTPA during the third gestational trimester was associated with an offspring BW decrease of -0.35 z-score (95% CI: -0.65, -0.05) or -147.9 grams (95% CI: -260.9, -14.8), without increasing the frequency of SGA foetuses either in the second or third gestational trimester (p > 0.05). Excessive GWG mediated the effect of LTPA on the offspring BW (indirect effect = -0.05 z-score [95% CI: -0.10, -0.00] or -34.7 grams (95% CI: -66.1, -3.3]). This mediation effect was not observed for insufficient GWG. LTPA in the third, but not in the second, trimester of pregnancy was inversely associated with offspring BW without increasing the frequency of SGA, an effect that was partly mediated by excessive GWG. [ABSTRACT FROM AUTHOR]

Purpose: To investigate changes in the number of preterm infants, low birth weight infants, and infants with fetal growth restriction (FGR) or retinopathy of prematurity (ROP) during the coronavirus disease 2019 (COVID-19) pandemic. Methods: In this retrospective cross-sectional study, we reviewed the medical records of infants born and admitted to the neonatal intensive care unit and growth care unit of Shiga University of Medical Science Hospital before the COVID-19 pandemic (April 1, 2019 to September 30, 2019) and during the pandemic (April 1, 2020 to September 30, 2020). Medical records of infants' mothers were also collected. Preterm infants, low birth weight infants, infants with FGR, infant and maternal factors associated with FGR, and infants requiring treatment for ROP were compared between the two periods. Results: There were fewer infants born at < 28 weeks of gestation, infants with birth weight < 1,500 g, and infants with FGR during the pandemic period than the pre-pandemic period (pre-pandemic: n = 4 vs. during pandemic: n = 0, P = 0.048; pre-pandemic: n = 15 vs. during pandemic: n = 6, P = 0.02; and pre-pandemic: n = 31 vs. during pandemic: n = 12, P = 0.0002, respectively). There were no significant differences in any infant or maternal factors associated with FGR. The number of infants requiring treatment for ROP decreased during the pandemic, although this difference was not statistically significant (pre-pandemic: n = 3 vs. during pandemic: n = 0, P = 0.08). Conclusions: Our findings showed a reduction in the number of infants with FGR during the COVID-19 pandemic. The number of infants born at < 28 weeks of gestation and infants with birth weight < 1,500 g also decreased during the pandemic period. There was a trend toward fewer infants requiring treatment for ROP during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Background: Composition of leukocyte populations in the first month of life remains incompletely characterised, particularly in preterm infants who go on to develop late-onset sepsis (LOS). Aim: To characterise and compare leukocyte populations in preterm infants with and without LOS during the first month of life. Study design: Single-centre prospective observational cohort study. Participants: Infants born <30 weeks gestational age (GA). Outcome measures: Peripheral blood samples were collected at 1, 7, 14, 21 and 28 days of life. Leukocyte populations were characterised using 5-fluorophore-6-marker flow cytometry. Absolute leukocyte counts and frequency of total CD45+ leukocytes of each population were adjusted for GA, birth weight z-scores, sex and total leukocyte count. Results: Of 119 preterm infants enrolled, 43 (36%) had confirmed or clinical LOS, with a median onset at 13 days (range 6–26). Compared to infants without LOS, the adjusted counts and frequency of neutrophils, basophils and non-cytotoxic T lymphocytes were generally lower and immature granulocytes were higher over the first month of life in infants who developed LOS. Specific time point comparisons identified lower adjusted neutrophil counts on the first day of life in those infants who developed LOS more than a week later, compared to those without LOS, albeit levels were within the normal age-adjusted range. Non-cytotoxic T lymphocyte counts and/or frequencies were lower in infants following LOS on days 21 and 28 when compared to those who did not develop LOS. Conclusion: Changes in non-cytotoxic T lymphocytes occurred following LOS suggesting sepsis-induced immune suppression. [ABSTRACT FROM AUTHOR]

Background: The SafeBoosC II, randomised clinical trial, showed that the burden of cerebral hypoxia was reduced with the combination of near infrared spectroscopy and a treatment guideline in extremely preterm infants during the first 72 hours after birth. We have previously reported that a high burden of cerebral hypoxia was associated with cerebral haemorrhage and EEG suppression towards the end of the 72-hour intervention period, regardless of allocation. In this study we describe the associations between the burden of cerebral hypoxia and the 2-year outcome. Methods: Cerebral oxygenation was continuously monitored from 3 to 72 hours after birth in 166 extremely preterm infants. At 2 years of age 114 of 133 surviving children participated in the follow-up program: medical examination, Bayley II or III test and the parental Ages and Stages Questionnaire. The infants were classified according to the burden of hypoxia: within the first three quartiles (n = 86, low burden) or within in the 4th quartile (n = 28, high burden). All analyses were conducted post hoc. Results: There were no statistically significant differences between the quantitative assessments of neurodevelopment in the groups of infants with the low burden of cerebral hypoxia versus the group of infants with the high burden of cerebral hypoxia. The infants in the high hypoxia burden group had a higher–though again not statistically significant—rate of cerebral palsy (OR 2.14 (0.33–13.78)) and severe developmental impairment (OR 4.74 (0.74–30.49). Conclusions: The burden of cerebral hypoxia was not significantly associated with impaired 2-year neurodevelopmental outcome in this post-hoc analysis of a feasibility trial. [ABSTRACT FROM AUTHOR]

Purpose: To assess the prevalence and causes of visual impairment and blindness in a Central European country. The findings may have implications for the planning of further research and development of therapies in order to prevent blindness. Setting: Department of Ophthalmology, Medical University of Graz, Austria. Design: Retrospective, epidemiological study. Methods: The database of the Main Confederation of Austrian Social Insurances was searched for patients with visual impairment, legal blindness or deaf-blindness. This database gathers data from patients of all insurance providers in the country who receive care due to visual impairment and blindness. To determine the prevalence of these conditions, the number of all entries recorded in February 2019 was evaluated. Additionally, all new entries between (January 1st,) 2017, and (December 31st,) 2018, were analysed for distinct characteristics, such as sex, the cause of blindness/visual impairment, and age. Since health care allowances can provide a considerable source of income (459.90€-936.90€ per month), good coverage of practically all patients who are blind and visually impaired in the country can be assumed. Results: On February 2nd, 2019, 17,730 patients with visual impairments, blindness or deaf-blindness were registered in Austria, resulting in a prevalence of these diagnoses of 0.2% in the country. During the observational period from 2017 to 2018, 4040 persons met the inclusion criteria. Of these, 2877 were female (65.3%), and 1527 were male (34.7%). The mean age was 75.7 ± 18.0 years (median 82). Most patients (n = 3675, 83.4%) were of retirement age, while 729 (16.6%) were working-age adults or minors. In total, an incidence of 25.0 (95% confidence limit (CL) 24.3–25.8) per 100,000 person-years was observed from 2017 to 2018. A higher incidence was observed for females (32.2, 95% CL 31.0–33.3) than for males (17.7, 95% CL 16.8–18.5). Incidences where higher for males in lower age groups (e.g. 10–14 years: rate ratio RR = 2.7, 95% CL 1.1–6.8), and higher for females in higher age groups (e.g. 70–74 years: RR = 0.6, 95% CL 0.5–0.8). In total, the most frequent diagnoses were macular degeneration (1075 persons, 24.4%), other retinal disorders (493 persons, 11.2%) and inherited retinal and choroidal diseases (IRDs) (186 persons, 4.2%). Persons with IRDs were significantly younger compared to persons with macular degeneration or retinal disorders (IRDs: median 57, range 2–96 vs 83, 5–98 and 82, 1–98 years, p<0.001). For persons of retirement age, macular degeneration, other retinal disorders and glaucoma were the three most frequent diagnoses. In contrast, among working-aged adults and children, IRDs were the leading cause of visual impairment and blindness (103 persons, 14.1%). Conclusion: These data show that IRDs are the leading cause of blindness and visual impairment in working-aged persons and children in Austria. Thus, these findings suggest to draw attention to enhance further research in the fields of emerging therapies for IRDs. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the short-term effect on body weight (BW) gain after intravitreal bevacizumab (IVB) for retinopathy of prematurity (ROP). Methods: This was a retrospective 1:1 matched case-control study. Infants with ROP treated by IVB or photocoagulation (PC) at Shiga University of Medical Science Hospital between April 2010 and December 2019 were included in the study. To match BWs at treatment between the IVB and PC groups, 1:1 matching for BWs at treatment within 100 g was performed. The BW gains for the 7 days before treatment (pre-treatment week), the 7 days after treatment (first post-treatment week), and the period from 7 to 14 days after treatment (second post-treatment week) were compared between the IVB and PC groups. Results: Following 1:1 matching, 13 infants in both groups were enrolled in the analysis. The weekly BW gain for the first post-treatment week was significantly lower in the IVB group compared with the PC group (86 g vs. 145 g; P = 0.046), whereas the weekly BW gains for the pre-treatment week (173 g vs. 159 g; P = 0.71) and the second post-treatment week (154 g vs. 152 g; P = 0.73) were comparable between the two groups. The short-term inhibitive effect of IVB on BW gain was particularly observed in infants weighing less than 1500 g at treatment (<1500 g: 47 g vs. ≥1500 g: 132 g; P = 0.03). Conclusion: IVB could have a short-term inhibitive effect on BW gain in infants with ROP, and this effect is more likely to occur in infants with a lower BW at the time of treatment. [ABSTRACT FROM AUTHOR]

Retinopathy of prematurity (ROP) is one of the main causes of blindness in children worldwide. Brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase B (TrkB), play critical protective roles in the development and function of neurons and vasculature. Lack of BDNF expression results in increased endothelial cell apoptosis and reduced endothelial cell-cell contact. Premature babies who develop ROP tend to have lower serum BDNF levels. BDNF expression is also significantly lower in mouse retinas following exposure to hyperoxia compared to those reared in room air. Specifically, BDNF promotes angiogenic tube formation of endothelial cells (EC), and it is considered an EC survival factor required for stabilization of intramyocardial vessels. We hypothesized that the activation of TrkB receptor protects retinal vasculature in the mice during oxygen-induced ischemic retinopathy (OIR), a model of ROP. To test this hypothesis, we treated neonatal mice with 7,8-dihydroxyflavone (DHF) (5 mg/kg body weight), a TrkB receptor agonist. We examined its potential protective effects on retinal vessel obliteration and neovascularization, two hallmarks of ROP and OIR. We found that retinas from DHF treated postnatal day 8 (P8) and P12 mice have similar levels of vessel obliteration as retinas from age-matched control mice subjected to OIR. Similarly, DHF showed no significant effect on mitigation of retinal neovascularization during OIR in P17 mice. Collectively, our studies demonstrate that the TrkB receptor agonist DHF provides no significant protective effects during OIR. [ABSTRACT FROM AUTHOR]

Objectives: To investigate differences in brain volumes between children born extremely preterm and term born controls at term age and at 10 years of age. Study design: Children born extremely preterm (EPT), up to 26 weeks and 6 days gestational age, in Stockholm between January 1 2004 to March 31 2007 were included in this population-based cohort study. A total of 45 EPT infants were included at term age and 51 EPT children were included at 10 years of age. There were 27 EPT children included at both time points. Two different control groups were recruited; 15 control infants were included at term age and 38 control children at 10 years of age. The primary outcomes were the grey and white matter volumes. Linear regression, adjusted for intracranial volume and sex, was used. Results: At term age, the extremely preterm infants had significantly smaller grey matter volume compared to the control infants with an adjusted mean difference of 5.0 cm3 and a 95% confidence interval of −8.4 to −1.5 (p = 0.004). At 10 years of age the extremely preterm children had significantly smaller white matter volume compared to the control children with an adjusted mean difference of 6.0 cm3 and a 95% confidence interval of −10.9 to −1.0 (p = 0.010). Conclusion: Extremely preterm birth was associated with reduced grey matter volume at term age and reduced white matter volume at 10 years of age compared to term born controls. [ABSTRACT FROM AUTHOR]

We aimed to evaluate risk factors for growth failure in very low birth weight (VLBW) infants at 18–24 months of corrected age (follow-up1, FU1) and at 36 months of age (follow-up2, FU2). In this prospective cohort study, a total of 2,943 VLBW infants from the Korean Neonatal Network between 2013 and 2015 finished follow-up at FU1. Growth failure was defined as a z-score below -1.28. Multiple logistic regression was used to analyze risk factors for growth failure after dividing the infants into small for gestational age (SGA) and appropriate for gestational age (AGA) groups. Overall, 18.7% of infants were SGA at birth. Growth failure was present in 60.0% at discharge, 20.3% at FU1, and 35.2% at FU2. Among AGA infants, male sex, growth failure at discharge, periventricular leukomalacia, treatment of retinopathy of prematurity, ventriculoperitoneal shunt status and treatment of rehabilitation after discharge were independent risk factors for growth failure at FU1. Among SGA infants, lower birth weight, pregnancy-induced hypertension, and treatment of rehabilitation after discharge were independent risk factors for growth failure at FU1. Mean weight z-score graphs from birth to 36 month of age revealed significant differences between SGA and non-SGA and between VLBW infants and extremely low birth weight infants. Growth failure remains an issue, and VLBW infants with risk factors should be closely checked for growth and nutrition. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate systemic adverse events after screening for retinopathy of prematurity (ROP) performed with mydriatic. Methods: This was a retrospective case series study. Medical records of consecutive patients who underwent screening for ROP with 0.5% phenylephrine and 0.5% tropicamide eyedrops were retrospectively reviewed. The score of abdominal distention (0–5), volume of milk sucked and volume of stool, along with systemic details (pulse and respiration rates, blood pressure and number of periods of apnea) were collected at 1 week and 1 day before ROP examination, and at 1 day after examination. Results were compared between the days before and after examination. Correlation between body weight at the time of examination and the score of abdominal distention was examined. The numbers of infants with abdominal and/or systemic adverse events were compared between pre- and post-examination periods. Results: Eighty-six infants met the inclusion criteria. The score of abdominal distention increased from 2.0 at 1 day before examination to 2.3 at 1 day after examination (p = 0.005), and the number of infants who had worsened abdominal distension increased after examination (p = 0.01). Infants with lower body weight had a higher score of abdominal distention (p < 0.0001, r = −0.57). The number of infants with reduced milk consumption increased after examination (p = 0.0001), as did the number of infants with decreased pulse rate (p = 0.0008). Conclusions: Screening for ROP with mydriatic may have adverse effects on systemic conditions. Infants should be carefully monitored after ROP screening with mydriatic. [ABSTRACT FROM AUTHOR]

Background: Early antenatal care (ANC) reduces maternal and neonatal morbidity and mortality through identification of pregnancy-related complications, yet 44% of Rwandan women present to ANC after 16 weeks gestational age (GA). The objective of this study was to identify factors associated with delayed initiation of ANC and describe differences in the obstetric risks identified at the first ANC visit (ANC-1) between women presenting early and late to care. Methods: This secondary data analysis included 10,231 women presenting for ANC-1 across 18 health centers in Rwanda (May 2017-December 2018). Multivariable logistic regression models were constructed using backwards elimination to identify predictors of presentation to ANC at ≥16 and ≥24 weeks GA. Logistic regression was used to examine differences in obstetric risk factors identified at ANC-1 between women presenting before and after 16- and 24-weeks GA. Results: Sixty-one percent of women presented to ANC at ≥16 weeks and 24.7% at ≥24 weeks GA, with a mean (SD) GA at presentation of 18.9 (6.9) weeks. Younger age (16 weeks: OR = 1.36, 95% CI: 1.06, 1.75; 24 weeks: OR = 1.33, 95% CI: 0.95, 1.85), higher parity (16 weeks: 1–4 births, OR = 1.55, 95% CI: 1.39, 1.72; five or more births, OR = 2.57, 95% CI: 2.17, 3.04; 24 weeks: 1–4 births, OR = 1.93, 95% CI: 1.78, 2.09; five or more births, OR = 3.20, 95% CI: 2.66, 3.85), lower educational attainment (16 weeks: primary, OR = 0.75, 95% CI: 0.65, 0.86; secondary, OR = 0.60, 95% CI: 0.47,0.76; university, OR = 0.48, 95% CI: 0.33, 0.70; 24 weeks: primary, OR = 0.64, 95% CI: 0.53, 0.77; secondary, OR = 0.43, 95% CI: 0.29, 0.63; university, OR = 0.12, 95% CI: 0.04, 0.32) and contributing to household income (16 weeks: OR = 1.78, 95% CI: 1.40, 2.25; 24 weeks: OR = 1.91, 95% CI: 1.42, 2.55) were associated with delayed ANC-1 (≥16 and ≥24 weeks GA). History of a spontaneous abortion (16 weeks: OR = 0.74, 95% CI: 0.66, 0.84; 24 weeks: OR = 0.70, 95% CI: 0.58, 0.84), pregnancy testing (16 weeks: OR = 0.48, 95% CI: 0.33, 0.71; 24 weeks: OR = 0.41, 95% CI: 0.27, 0.61; 24 weeks) and residing in the same district (16 weeks: OR = 1.55, 95% CI: 1.08, 2.22; 24 weeks: OR = 1.73, 95% CI: 1.04, 2.87) or catchment area (16 weeks: OR = 1.53, 95% CI: 1.05, 2.23; 24 weeks: OR = 1.84, 95% CI: 1.28, 2.66; 24 weeks) as the health facility were protective against delayed ANC-1. Women with a prior preterm (OR, 0.71, 95% CI, 0.53, 0.95) or low birthweight delivery (OR, 0.72, 95% CI, 0.55, 0.95) were less likely to initiate ANC after 16 weeks. Women with no obstetric history were more likely to present after 16 weeks GA (OR, 1.18, 95% CI, 1.06, 1.32). Conclusion: This study identified multiple predictors of delayed ANC-1. Focusing existing Community Health Worker outreach efforts on the populations at greatest risk of delaying care and expanding access to home pregnancy testing may improve early care attendance. While women presenting late to care were less likely to present without an identified obstetric risk factor, lower than expected rates were identified in the study population overall. Health centers may benefit from provider training and standardized screening protocols to improve identification of obstetric risk factors at ANC-1. [ABSTRACT FROM AUTHOR]

Objective: The present study seeks to assess the impact of gestational hypertensive disorders on premature newborns below 34 weeks and to establish the main morbidities and mortality in the neonatal period and at 18 months. Materials and methods: A retrospective observational study was carried out with 695 premature newborns of gestational age (GA) between 24 and 33 weeks and 6 days, born alive in the Neonatal ICU of Brasília's Mother and Child Hospital (HMIB), in the period from January 1, 2014, to July 31, 2019. In total, 308 infants were born to hypertensive mothers (G1) and 387 to normotensive mothers (G2). Twin pregnancies and diabetic patients with severe malformations were excluded. Outcomes during hospitalization and outcomes of interest were evaluated: respiratory distress syndrome (RDS), brain ultrasonography, diagnosis of bronchopulmonary dysplasia (BPD), diagnosis of necrotizing enterocolitis, retinopathy of prematurity, breastfeeding rate at discharge, survival at discharge and at 18 months of chronological age and relationship between weight and gestational age. Results: Newborns with hypertensive mothers had significantly lower measurements of birth weight and head circumference. The G1 group had a higher risk small for gestational age (OR 2.4; CI 95% 1.6–3.6; p <0.00), as well as a greater risk of being born with a weight less than 850 g (OR 2.4; 95% CI 1.2–3.5; p <0.00). Newborns of mothers with hypertension presented more necrotizing enterocolitis (OR 2.0; CI 95% 1.1–3.7); however, resuscitation in the delivery room and the need to use surfactant did not differ between groups, nor did the length of stay on mechanical ventilation, or dependence on oxygen at 36 weeks of gestational age. Survival was better in newborns of normotensive mothers, and this was a protective factor against death (OR 0.7; 95% CI 0.5–0.9; p <0.01). In the follow-up clinic, survival at 18 months of chronological age was similar between groups, with rates of 95.3% and 92.1% among hypertensive and normotensive mothers, respectively. Exclusive breastfeeding at discharge was 73.4% in the group of hypertensive women and 77.3% in the group of normotensive mothers. There were no significant differences between groups. Conclusion: Among the analyzed outcomes, arterial hypertension during pregnancy can increase the risk of low weight, small babies for gestational age (SGA), deaths in the neonatal period and enterocolitis, with no differences in weight and survival at 18 months of chronological age. Arterial hypertension presents a high risk of prematurity in the neonatal period, with no difference at 18 months of age. [ABSTRACT FROM AUTHOR]

Introduction: Despite the high burden of hearing loss (HL) globaly, most countries in resource limited settings lack infant hearing screening programs(IHS) for early HL detection. We examined the feasibility of establishing an IHS program in this setting, and in this pilot program measured the prevalence of infant hearing loss (IHL) and described the characteristics of the infants with HL. Methods: We assessed feasibility of establishing an IHS program at a regional referral hospital in south-western Uganda. We recruited infants aged 1 day to 3 months and performed a three-staged screening. At stage 1, we used Transient Evoked Oto-acoustic Emissions (TEOAEs), at stage 2 we repeated TEOAEs for infants who failed TEOAEs at stage 1 and at stage 3, we conducted Automated brainstem responses(ABRs) for those who failed stage 2. IHL was present if they failed an ABR at 35dBHL. Results: We screened 401 infants, mean age was 7.2 days (SD = 7.1). 74.6% (299 of 401) passed stage 1, the rest (25.4% or 102 of 401) were referred for stage 2. Of those referred (n = 102), only 34.3% (35 of 102) returned for stage 2 screening. About 14.3% (5/35) failed the repeat TEOAEs in at least one ear. At stage 3, 80% (4 of 5) failed the ABR screening in at least one ear, while 25% (n = 1) failed the test bilaterally. Among the 334 infants that completed the staged screening, the prevalence of IHL was 4/334 or 12 per 1000. Risk factors to IHL were Newborn Special Care Unit (NSCU) admission, gentamycin or oxygen therapy and prematurity. Conclusions: IHS program establishment in a resource limited setting is feasible. Preliminary data indicate a high prevalence of IHL. Targeted screening of infants at high risk may be a more realistic and sustainable initial step towards establishing IHS program s in a developing country like Uganda. [ABSTRACT FROM AUTHOR]

Background: Endogenous erythropoietin (EPO) concentrations vary widely in preterm infants and may be associated with perinatal risk factors and neurological outcomes. Erythropoietin is elevated in fetal hypoxia but is also a potential neuroprotectant. Methods: In a prospective study of 27 infants ≤ 30 weeks gestation, serum erythropoietin concentrations were measured during the first month of life, on day 1 and weeks 1, 2, and 4, and related to perinatal risk factors and outcomes including retinopathy of prematurity and cerebral injury evaluated near term-equivalent post menstrual age using magnetic resonance imaging with quantitative scoring. Results: Lower birth weight was associated with higher EPO concentrations throughout the first 2 weeks of life (r = -0.6, p < 0.01). Higher day 1 and week 1 EPO concentrations were associated with lower Apgar score at 1 minute (r = - 0.5) and 5 minutes (r = -0.7), respectively (p < 0.01). Higher day 1 EPO concentrations and 2-week area under the curve were associated with increased risk (p = 0.01) and severity (r = 0.5, p < 0.02) of retinopathy of prematurity. Higher EPO concentrations at 2 weeks were associated with increased total brain injury score (r = 0.5, p < 0.05). Conclusion: Elevated endogenous erythropoietin concentrations in the first two weeks of life are associated with lower birth weight and increased risk of adverse outcomes. [ABSTRACT FROM AUTHOR]

Since growing tumors stimulate angiogenesis, via vascular endothelial growth factor (VEGF), angiogenesis inhibitors (AIs, blockers of the VEGF signaling pathway) have been introduced to cancer therapy. However, AIs often yielded only modest and short-lived gains in cancer patients and more invasive tumor phenotypes in animal models. Combining anti-VEGF strategies with lactate uptake blockers may boost both efficacy and safety of AIs. We assessed this hypothesis by using the ex ovo chorioallantoic membrane (CAM) assay. We show that AI-based monotherapy (Avastin®, AVA) increases tumor hypoxia in human CAM cancer cell xenografts and cell spread in human as well as canine CAM cancer cell xenografts. In contrast, combining AVA treatment with lactate importer MCT1 inhibitors (α-cyano-4-hydroxycinnamic acid (CHC) or AZD3965 (AZD)) reduced both tumor growth and cell dissemination of human and canine explants. Moreover, combining AVA+AZD diminished blood perfusion and tumor hypoxia in human explants. Thus, the ex ovo CAM assay as an easy, fast and cheap experimental setup is useful for pre-clinical cancer research. Moreover, as an animal-free experimental setup the CAM assay can reduce the high number of laboratory animals used in pre-clinical cancer research. [ABSTRACT FROM AUTHOR]

Purpose: According to cross-sectional studies, oxygen saturation is elevated in retinal vessels in diabetic patients. We evaluated how retinal oxygenation (metabolic marker), vessel diameters and retinopathy grade (structural markers) change over time in diabetic patients. Design: Prospective cohort study following screening in a hospital setting. Methods: Retinal oximetry images were acquired in 214 patients with the Oxymap T1 oximeter. Imaging was repeated after a median of 3.0 years (range 0.76–6.8 years). Oxygen saturation and vessel diameters were measured in the right eye. Semiquantitative grading of retinopathy according to international guidelines and red lesion count were performed on fundus photographs. Results: Retinopathy grade according to the international semiquantitative grading system was unchanged. Arteriolar saturation increased by 0.75±0.15 percentage points per year of follow-up (p<0.0001). Venular saturation increased by 1.74±0.26 percentage points per year (p<0.0001) and arteriovenous difference decreased by 0.99±0.20 percentage points per year (p<0.0001). Arteriolar diameters decreased by 2.7±8.5μm (p<0.0001) between visits and venular diameters decreased by 2.4±9.1μm (p = 0.0002). Median increase in red lesion count between visits was 2 lesions (range -128 to 212 lesions, p<0.0001). The change in red lesion count and change in diameters did not correlate with the length of follow-up (p>0.44). Conclusions: Oxygen saturation in larger retinal vessels can increase and arteriovenous difference can decrease over time in diabetic patients without any observable changes in retinopathy grade. The results suggest that changes in retinal oxygen saturation may precede progression of diabetic retinopathy or that oxygen saturation is more sensitive to disease progression than retinopathy grade. [ABSTRACT FROM AUTHOR]

Background: Sarcoidosis is a systemic inflammatory granulomatous disease, frequently affecting the lung. If left untreated, it may end in lung fibrosis. Proangiogenic and profibrotic vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β1, fibroblast growth factor (FGF)-2 and platelet-derived growth factor (PDGF)-AB are a known therapeutical target in pulmonary fibrosing diseases, e.g. IPF, but there is no targeted therapy option for pulmonary fibrosis in sarcoidosis. Objectives: The aim of our study was to determine the association of these markers' serum levels on lung function and the patients' quality of life in a long-term follow-up of sarcoidosis patients, to provide further information for finding targeted therapy options for pulmonary sarcoidosis. Methods: 54 patients with sarcoidosis underwent blood sampling, pulmonary function testing and answered the King's Brief Interstitial Lung Disease (K-BILD) questionnaire at baseline and at three-years follow-up. Serum levels of profibrotic and angiogenic markers were assessed at baseline by enzyme-linked immunosorbent assay. Results: Between 2015 and 2018, 54 patients with biopsy proven sarcoidosis were enrolled. Throughout the observation period, there was a significant decrease in the diffusion capacity for carbon monoxide (DLCO) [%] (-6.5504 ± 13,39, p = 0.001) and forced expiratory volume in one second predicted (FEV1) [%] (-6.07 ± 12.09, p = 0.001). Patients with greater impairment of forced vital capacity (FVC) did have significantly higher serum levels of VEGF (p = 0.03) and PDGF-AB (p<0.001). The K-BILD questionnaire did not change significantly during follow-up. However, patients with worsening K-BILD scores did have significantly higher serum-levels of PDGF-AB (2.67 pg/ml ± 0.93 vs. 1.88 pg/ml ± 0.60, p = 0.004) at baseline, compared to those with unchanged or increasing K-BILD scores. Conclusions: Among patients with pulmonary sarcoidosis, baseline serum levels of VEGF and PDGF-AB were associated with pulmonary function impairment. Furthermore, PDGF-AB was associated with worsening K-BILD scores. No such association was observed for FGF-2 and TGF-ß1. VEGF and PDGF-AB may be possible prognostic and therapeutic targets in sarcoidosis as a fibrosing ILD beyond IPF. [ABSTRACT FROM AUTHOR]

Introduction: Women with polycystic ovary syndrome (PCOS) have increased risk of pregnancy complications, including preterm birth before 37 weeks. However, if this increased risk also includes extremely preterm births (<28 weeks) is unknown. Such information is important to identify women at risk and tailor antenatal care, since child morbidity and mortality become more prevalent with increasing prematurity. Aims: To investigate the association between PCOS and extremely preterm birth, and whether onset of PCOS-related preterm birth is predominantly spontaneous or medically indicated. Material and methods: This was a nationwide register-based cohort study in Sweden. The study population was all live singleton births registered in the Swedish Medical Birth Register 2005–2014 (n = 1 046 448). Women with and without PCOS were compared by severity of preterm birth [extremely (22+0 to 27+6 weeks), very (28+0 to 31+6 weeks) and moderately (32+0 to 36+6 weeks)] and delivery onset mode (spontaneous or medically indicated). Multinomial logistic regression was performed to estimate adjusted odds ratios (aOR) with 95% confidence intervals (CI). Adjustments were made for maternal age, parity, body mass index, smoking, country of birth and year of delivery. Results: During the study period, 1.3% of the women giving birth had PCOS diagnosis. They had an overall higher preterm birth rate than women without PCOS (6.7% and 4.8%, respectively). Women with PCOS had increased odds of preterm birth of all severities, with the highest odds for extremely preterm birth (aOR 2.3; 95% CI 1.7–3.0), particularly of spontaneous onset (aOR 2.7; 95% CI 2.0–3.6). Conclusions: Women with PCOS had more than a two-fold increased risk of extremely preterm birth with spontaneous onset than women without such diagnosis. This can be important in antenatal risk assessment of preterm birth in women with PCOS. Future research is warranted to investigate the biological mechanisms behind preterm birth in women with PCOS. [ABSTRACT FROM AUTHOR]

Background: Hyperglycemia in preterm infants may be associated with severe retinopathy of prematurity (ROP) and other morbidities. However, it is uncertain which concentration of blood glucose is associated with increased risk of tissue damage, with little consensus on the cutoff level to treat hyperglycemia. The objective of our study was to examine the association between hyperglycemia and severe ROP in premature infants. Methods and findings: In 2 independent, monocentric cohorts of preterm infants born at <30 weeks' gestation (Nantes University Hospital, 2006–2016, primary, and Lyon-HFME University Hospital, 2009–2017, validation), we first analyzed the association between severe (stage 3 or higher) ROP and 2 markers of glucose exposure between birth and day 21—maximum value of glycemia (MaxGly1–21) and mean of daily maximum values of glycemia (MeanMaxGly1–21)—using logistic regression models. In both the primary (n = 863 infants, mean gestational age 27.5 ± 1.4 weeks, boys 52.5%; 38 with severe ROP; 54,083 glucose measurements) and the validation cohort (n = 316 infants, mean gestational age 27.4 ± 1.4 weeks, boys 51.3%), MaxGly1–21 and MeanMaxGly1–21 were significantly associated with an increased risk of severe ROP: odds ratio (OR) 1.21 (95% CI 1.14–1.27, p < 0.001) and OR 1.70 (95% CI 1.48–1.94, p < 0.001), respectively, in the primary cohort and OR 1.17 (95% CI 1.05–1.32, p = 0.008) and OR 1.53 (95% CI 1.20–1.95, p < 0.001), respectively, in the validation cohort. These associations remained significant after adjustment for confounders in both cohorts. Second, we identified optimal cutoff values of duration of exposure above each concentration of glycemia between 7 and 13 mmol/l using receiver operating characteristic curve analyses in the primary cohort. Optimal cutoff values for predicting stage 3 or higher ROP were 9, 6, 5, 3, 2, 2, and 1 days above a glycemic threshold of 7, 8, 9, 10, 11, 12, and 13 mmol/l, respectively. Severe exposure was defined as at least 1 exposure above 1 of the optimal cutoffs. Severe ROP was significantly more common in infants with severe exposure in both the primary (10.9% versus 0.6%, p < 0.001) and validation (5.2% versus 0.9%, p = 0.030) cohorts. Finally, we analyzed the association between insulin therapy and severe ROP in a national population-based prospectively recruited cohort (EPIPAGE-2, 2011, n = 1,441, mean gestational age 27.3 ± 1.4, boys 52.5%) using propensity score weighting. Insulin use was significantly associated with severe ROP in overall cohort crude analyses (OR 2.51 [95% CI 1.13–5.58], p = 0.024). Adjustment for inverse propensity score (gestational age, sex, birth weight percentile, multiple birth, spontaneous preterm birth, main pregnancy complications, surfactant therapy, duration of oxygen exposure between birth and day 28, digestive state at day 7, caloric intake at day 7, and highest glycemia during the first week) and duration of oxygen therapy had a large but not significant effect on the association between insulin treatment and severe ROP (OR 0.40 [95% CI 0.13–1.24], p = 0.106). Limitations of this study include its observational nature and, despite the large number of patients included compared to earlier similar studies, the lack of power to analyze the association between insulin use and retinopathy. Conclusions: In this study, we observed that exposure to high glucose concentration is an independent risk factor for severe ROP, and we identified cutoff levels that are significantly associated with increased risk. The clinical impact of avoiding exceeding these thresholds to prevent ROP deserves further evaluation. In this cohort study, Elsa Kermorvant-Duchemin and colleagues examine the association between hyperglycemia and severe retinopathy of prematurity in infants. Author summary: Why was this study done?: Hyperglycemia, i.e., elevated blood glucose, is common in preterm babies, due to the immaturity of glucose regulation mechanisms; it is often treated with insulin infusion, based on weak evidence. A number of studies, with heterogeneity in both setting and design, have suggested that hyperglycemia may be associated with increased risk of morbidity in premature infants, especially severe retinopathy of prematurity, a condition characterized by an abnormal development of the retinal vessels that can lead to blindness. However, current published evidence does not rule out that hyperglycemia may only be a marker of severity of illness and not an independent risk factor for retinopathy of prematurity because not all potential confounding factors were taken into account. It is also uncertain which concentration of blood glucose could be associated with tissue damage in preterm infants, with little consensus on the cutoff level to treat hyperglycemia. What did the researchers do and find?: We used 2 independent cohorts of 863 (primary cohort) and 316 (validation cohort) preterm infants born at <30 weeks' gestation to study the association between severe retinopathy of prematurity and 2 markers of glucose exposure between birth and day 21. We used a third cohort—a prospective, nationwide population-based cohort of 1,441 preterm infants born at <30 weeks' gestation, representing a large variation of practices regarding neonatal management—to examine the impact of strategies to avoid or reduce hyperglycemia on the risk of severe retinopathy of prematurity. Strengthened by multiple sensitivity analyses and external validation, our results support the hypothesis that hyperglycemia is an independent risk factor for severe retinopathy of prematurity and not a mere marker of illness. More importantly, we identified thresholds of combined severity and duration of hyperglycemia above which the risk of severe retinopathy increases significantly. In the nationwide population-based cohort, the analysis of insulin as a protective factor against severe retinopathy of prematurity found a large but not significant effect after controlling for confounding factors. What do these findings mean?: The results suggest that overall average exposure and duration of hyperglycemia matter more than a single high glucose value when determining risk of retinopathy. The thresholds of combined severity and duration of exposure that were identified may help physicians to determine treatment strategies in hyperglycemic premature infants. The clinical impact of avoiding exceeding these thresholds to prevent severe retinopathy of prematurity deserves evaluation. [ABSTRACT FROM AUTHOR]

Babies born clinically Small- or Large-for-Gestational-Age (SGA or LGA; sex- and gestational age-adjusted birth weight (BW) <10th or >90th percentile, respectively), are at higher risks of complications. SGA and LGA include babies who have experienced environment-related growth-restriction or overgrowth, respectively, and babies who are heritably small or large. However, the relative proportions within each group are unclear. We assessed the extent to which common genetic variants underlying variation in birth weight influence the probability of being SGA or LGA. We calculated independent fetal and maternal genetic scores (GS) for BW in 11,951 babies and 5,182 mothers. These scores capture the direct fetal and indirect maternal (via intrauterine environment) genetic contributions to BW, respectively. We also calculated maternal fasting glucose (FG) and systolic blood pressure (SBP) GS. We tested associations between each GS and probability of SGA or LGA. For the BW GS, we used simulations to assess evidence of deviation from an expected polygenic model. Higher BW GS were strongly associated with lower odds of SGA and higher odds of LGA (ORfetal = 0.75 (0.71,0.80) and 1.32 (1.26,1.39); ORmaternal = 0.81 (0.75,0.88) and 1.17 (1.09,1.25), respectively per 1 decile higher GS). We found evidence that the smallest 3% of babies had a higher BW GS, on average, than expected from their observed birth weight (assuming an additive polygenic model: Pfetal = 0.014, Pmaternal = 0.062). Higher maternal SBP GS was associated with higher odds of SGA P = 0.005. We conclude that common genetic variants contribute to risk of SGA and LGA, but that additional factors become more important for risk of SGA in the smallest 3% of babies. Author summary: Babies in the lowest or highest 10% of the population distribution of birth weight (BW) for a given gestational age are referred to as Small- or Large-for-Gestational-Age (SGA or LGA) respectively. These babies have higher risks of complications compared with babies with BW closer to the average. SGA and LGA babies may have experienced growth restriction or overgrowth, respectively, but may alternatively just be at the tail ends of the normal growth distribution. The relative proportions of normal vs. sub-optimal growth within these groups is unclear. To examine the role of common genetic variation in SGA and LGA, we tested their associations with a fetal genetic score (GS) for BW in 11,951 European-ancestry individuals. We also tested associations with maternal GS (5,182 mothers) for offspring BW, fasting glucose and systolic blood pressure, each of which influences fetal growth via the in utero environment. We found fetal and maternal GS were associated with SGA and LGA, supporting strong maternal and fetal genetic contributions to birth weight in both tails of the distribution. However, within the smallest 3% of babies, the maternal and fetal GS for BW were higher than expected, suggesting factors additional to common genetic variation are more important in determining birth weight in these very small babies. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy is a microvascular complication of hyperglycaemia. Little is known about the association of glucose metabolism and retinopathy signs in the non-diabetic middle-aged population. We studied prevalence of retinopathy in a subsample of Northern Finland Birth Cohort study (NFBC1966) of 1809 subjects, at 47 years of age, without previously diagnosed type 2 diabetes and/or blood pressure-lowering medication. All participants underwent clinical evaluations including an oral glucose tolerance test (glucose and insulin values measured at 0, 30, 60 and 120 min) and HbA1c. The retinopathy signs were diagnosed by fundus photographs and classified according to the Eurodiab classification scheme. The overall prevalence of newly diagnosed retinopathy was 1.4%. The retinopathy signs were significantly associated with increased 30 min, 1-h and 2-h glucose levels and 2-h insulin level in an OGTT. After adjustment with systolic blood pressure, only 30 min glucose, 1-h glucose and 2-h insulin levels were associated with retinopathy signs. Our findings show the potential role of 30 min and 1-h post-load glucose and 2-h insulin levels as risk factors for retinopathy lesions among the participants without previously diagnosed diabetes or hypertensive medication. [ABSTRACT FROM AUTHOR]

Congenital Zika virus (ZIKV) exposure results in a spectrum of disease ranging from severe birth defects to delayed onset neurodevelopmental deficits. ZIKV-related neuropathogenesis, predictors of birth defects, and neurodevelopmental deficits are not well defined in people. Here we assess the methodological and statistical feasibility of a congenital ZIKV exposure macaque model for identifying infant neurobehavior and brain abnormalities that may underlie neurodevelopmental deficits. We inoculated five pregnant macaques with ZIKV and mock-inoculated one macaque in the first trimester. Following birth, growth, ocular structure/function, brain structure, hearing, histopathology, and neurobehavior were quantitatively assessed during the first week of life. We identified the typical pregnancy outcomes of congenital ZIKV infection, with fetal demise and placental abnormalities. We estimated sample sizes needed to define differences between groups and demonstrated that future studies quantifying brain region volumes, retinal structure, hearing, and visual pathway function require a sample size of 14 animals per group (14 ZIKV, 14 control) to detect statistically significant differences in at least half of the infant exam parameters. Establishing the parameters for future studies of neurodevelopmental outcomes following congenital ZIKV exposure in macaques is essential for robust and rigorous experimental design. [ABSTRACT FROM AUTHOR]

Purpose: To report the clinical presentation and management outcomes of glaucoma in the "Indian Twin cities retinopathy of prematurity (ROP) Screening database." Methods: All children with diagnosis of ROP and glaucoma between 1997 and 2016 from a prospective database were included. Glaucoma was classified as open when anterior chamber (AC) was deep, closed when AC was shallow or flat and neovascular when there was extensive iris neovascularization. ROP was classified based on International classification of ROP. Results: The prevalence of secondary glaucoma in our cohort was 1.36% (82 eyes of 6000 children). Eighty-two eyes of 54 children with secondary glaucoma due to ROP where included in this study. The distribution of glaucoma among the ROP stages included, stage V (58.5%), stage 1V (24.3%), stage III (2.4%) and stage II (1.2%) eyes. Median (interquartile range) duration from birth to glaucoma diagnosis was 7.8 (4.2, 24.9) months. Type of glaucoma was angle closure in 39 (47.6%), open angle in 35 (42.7%) and neovascular in 8 (9.8%) eyes. Retinal interventions included vitreoretinal surgery in 59 (72%), retinal laser in 14 (17%) and intravitreal bevacizumab injection in 19 (23.1%) eyes. The mean (±standard deviation) IOP at presentation was 22.6 ±11.8 mm Hg. Glaucoma was managed medically in 66 (76%) and surgically in 16 (19.5%) eyes. The mean follow up for the entire cohort was 1.14±2.24 years. At final visit, 37% eyes with ROP and glaucoma had ambulatory vision with mean IOP of 16.0±8.1 mm Hg and 56 eyes (68.2%) needed glaucoma medications. Conclusion: In this large ROP cohort, 1.36% eyes developed secondary glaucoma. Majority of them had stage V or IV ROP and 1/5 of them needed glaucoma surgery. Around 1/3rd of the ROP eyes with glaucoma had ambulatory vision. [ABSTRACT FROM AUTHOR]

Background: Retinopathy of prematurity (ROP) is a significant morbidity in preterm babies. Multiple risk factors for severe ROP have been extensively studied, however, only a few studies have included maternal diabetes mellitus (MDM) in their assessment. ROP and diabetic retinopathy are both retinal vascular diseases in which there is leakage and/or neovascularization from damaged retinal vessels. Diabetes may affect ROP development; however, there are conflicting results on the association between MDM and ROP. Objective: To determine if MDM is an independent risk factor for clinically significant ROP (ROP > Stage II) in neonates weighing less than 1500g. Design/Method: We conducted a retrospective cohort study of neonates weighing <1500g who were delivered or transferred into our institution from 2007 through 2017. Logistic regression was used to analyze the association between severe ROP and MDM. The risks for the different stages of ROP from MDM were compared using chi-square linear trend test. Results: We extracted 883 paired maternal-neonatal data. The mean (standard deviation) gestational age and birthweight were 28.5 (2.9) weeks and 1052.7 (300.9) grams, respectively. Of the 883 mothers, 72 (8.2%) had DM. The incidence of ROP and severe ROP was 42.4% (374/883) and 6.5% (57/883) respectively. The odds ratio comparing MDM and severe ROP was 3.47 [95% CI: 1.51–7.96]; p<0.01). Compared to Stage I, the risk of MDM in infants with ROP increased from 1.49 in Stage II ROP to 2.59 in Stages III&IV. Severe ROP was associated with infant steroid use (OR: 5.92 [95% CI: 2.83–12.38]; p <0.01), sepsis (OR: 2.13 [95% CI: 1.09–4.14]; p = 0.03) chorioamnionitis (OR: 1.90 [95% CI: 1.03–3.50]; p = 0.04), and maternal steroid use (OR: 0.51 [95% CI: 0.32–0.79]; p<0.01). Conclusion: Maternal diabetes is associated with ROP and the strength of association increased with increasing severity of ROP. [ABSTRACT FROM AUTHOR]

The main objective of this pilot study was to identify circulatory microRNAs in aqueous or plasma that were reflecting changes in vitreous of diabetic retinopathy patients. Aqueous, vitreous and plasma samples were collected from a total of 27 patients undergoing vitreoretinal surgery: 11 controls (macular pucker or macular hole patients) and 16 with diabetes mellitus(DM): DM-Type I with proliferative diabetic retinopathy(PDR) (DMI-PDR), DM Type II with PDR(DMII-PDR) and DM Type II with nonproliferative DR(DMII-NPDR). MicroRNAs were isolated using Qiagen microRNeasy kit, quantified on BioAnalyzer, and profiled on Affymetrix GeneChip miRNA 3.0 microarrays. Data were analyzed using Expression Console, Transcriptome Analysis Console, and Ingenuity Pathway Analysis. The comparison analysis of circulatory microRNAs showed that out of a total of 847 human microRNA probes on the microarrays, common microRNAs present both in aqueous and vitreous were identified, and a large number of unique microRNA, dependent on the DM type and severity of retinopathy. Most of the dysregulated microRNAs in aqueous and vitreous of DM patients were upregulated, while in plasma, they were downregulated. Dysregulation of miRNAs in aqueous did not appear to be a good representative of the miRNA abundance in vitreous, or plasma, although a few potential candidates for common biomarkers stood out: let-7b, miR-320b, miR-762 and miR-4488. Additionally, each of the DR subtypes showed miRNAs that were uniquely dysregulated in each fluid (i.e. aqueous: for DMII-NPDR was miR-455-3p; for DMII-PDR was miR-296, and for DMI-PDR it was miR-3202). Pathway analysis identified TGF-beta and VEGF pathways affected. The comparative profiling of circulatory miRNAs showed that a small number of them displayed differential presence in diabetic retinopathy vs. controls. A pattern is emerging of unique molecular microRNA signatures in bodily fluids of DR subtypes, offering promise for the use of ocular fluids and plasma for diagnostic and therapeutic purposes. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is a serious retinal disease and is considered as a leading cause of blindness in the world. Ophthalmologists use optical coherence tomography (OCT) and fundus photography for the purpose of assessing the retinal thickness, and structure, in addition to detecting edema, hemorrhage, and scars. Deep learning models are mainly used to analyze OCT or fundus images, extract unique features for each stage of DR and therefore classify images and stage the disease. Throughout this paper, a deep Convolutional Neural Network (CNN) with 18 convolutional layers and 3 fully connected layers is proposed to analyze fundus images and automatically distinguish between controls (i.e. no DR), moderate DR (i.e. a combination of mild and moderate Non Proliferative DR (NPDR)) and severe DR (i.e. a group of severe NPDR, and Proliferative DR (PDR)) with a validation accuracy of 88%-89%, a sensitivity of 87%-89%, a specificity of 94%-95%, and a Quadratic Weighted Kappa Score of 0.91–0.92 when both 5-fold, and 10-fold cross validation methods were used respectively. A prior pre-processing stage was deployed where image resizing and a class-specific data augmentation were used. The proposed approach is considerably accurate in objectively diagnosing and grading diabetic retinopathy, which obviates the need for a retina specialist and expands access to retinal care. This technology enables both early diagnosis and objective tracking of disease progression which may help optimize medical therapy to minimize vision loss. [ABSTRACT FROM AUTHOR]

Background: The effect of red blood cell (RBC) transfusion on retinopathy of prematurity (ROP) is difficult to establish, because ROP may also be influenced by other factors. Therefore, we carried out a systematic review and meta-analysis to explore the relationship between RBC transfusion and the development of ROP. Methods: The PubMed, Embase, Cochrane Library and Web of Science databases were searched from their inception to September 1, 2019. Observational studies that reported the relationship between RBC transfusion and ROP after adjusting for other potential risk factors were included. The combined result was analyzed by a random effect model. Heterogeneity and publication bias were tested, and sensitivity analysis was performed. Results: Of the 2628 identified records, 18 studies including 15072 preterm infants and 5620 cases of ROP were included. A random effect model was used and revealed that RBC transfusion was significantly associated with ROP (pooled OR = 1.50, 95% CI: 1.27–1.76), with moderate heterogeneity among the included studies (I2 = 44.2%). Subgroup analysis indicated that RBC transfusion was more closely related to ROP in the group with a gestational age (GA) ≤32 weeks (OR = 1.77, 95% CI: 1.29–2.43) but not in the groups with a GA ≤34 weeks (OR = 1.36, 95% CI: 0.85–2.18) or a GA <37 weeks (OR = 1.25, 95% CI: 0.86–1.82). No obvious publication bias was found based on the funnel plot and Egger's test. Removing any single study did not significantly alter the combined result in the sensitivity analysis. Conclusions: Our study revealed that RBC transfusion is an independent risk factor for the development of ROP, especially in younger preterm infants. However, there seemed to be no evidence to support an effect of RBC transfusion on ROP in older groups. Further studies addressing this issue in older preterm neonates are warranted. [ABSTRACT FROM AUTHOR]

Background: Inappropriate nutritional intake in premature infants may be responsible for postnatal growth restriction (PGR) and adverse long-term outcomes. Objective: We evaluated the impact of an updated nutrition protocol on very premature infants' longitudinal growth and morbidity, and secondly the compliance to this new protocol. Design: All infants born between 26–32 weeks gestation (GA) were studied retrospectively during two 6-month periods before (group 1) and after (group 2) the introduction of an optimized nutrition protocol, in a longitudinal comparative analysis. Results: 158 infants were included; 72 before and 86 after the introduction of the protocol (Group 1: (mean±SD) birthweight (BW) 1154±276 g, GA 29.0±1.4 weeks; Group 2: BW 1215±332 g, GA 28.9±1.7 weeks). We observed growth improvement in Group 2 more pronounced in males (weight z-score) at D42 (−1.688±0.758 vs. −1.370±0.762, p = 0.045), D49 (−1.696±0.776 vs. −1.370±0.718, p = 0.051), D56 (−1.748±0.855 vs. −1.392±0.737, p = 0.072), D63 (−1.885±0.832 vs. −1.336±0.779 p = 0.016), and D70 (−2.001±0.747 vs. −1.228±0.765 p = 0.004). There was no difference in females or in morbidities between the groups. We observed low compliance to the protocol in both groups: similar energy intake but higher lipid intake in Group 1 and higher protein intake in Group 2. Conclusion: The quality of nutritional care with a strictly-defined protocol may significantly improve weight gain for very preterm infants. As compliance remained low, an educational reinforcement is needed to prevent PGR. Clinical trial registration: This retrospective study was registered by ClinicalTrials.gov under number NCT03217045, and by the CNIL (Commission Nationale de l'Informatique et des Libertés) under study number R2015-1 for the Maternity of the CHRU of Nancy. [ABSTRACT FROM AUTHOR]

The end timing of T waves in fetal electrocardiogram (fECG) is important for the evaluation of ST and QT intervals which are vital markers to assess cardiac repolarization patterns. Monitoring malignant fetal arrhythmias in utero is fundamental to care in congenital heart anomalies preventing perinatal death. Currently, reliable detection of end of T waves is possible only by using fetal scalp ECG (fsECG) and fetal magnetocardiography (fMCG). fMCG is expensive and less accessible and fsECG is an invasive technique available only during intrapartum period. Another safer and affordable alternative is the non-invasive fECG (nfECG) which can provide similar assessment provided by fsECG and fMECG but with less accuracy (not beat by beat). Detection of T waves using nfECG is challenging because of their low amplitudes and high noise. In this study, a novel model-based method that estimates the end of T waves in nfECG signals is proposed. The repolarization phase has been modeled as the discharging phase of a capacitor. To test the model, fECG signals were collected from 58 pregnant women (age: (34 ± 6) years old) bearing normal and abnormal fetuses with gestational age (GA) 20-41 weeks. QT and QTc intervals have been calculated to test the level of agreement between the model-based and reference values (fsECG and Doppler Ultrasound (DUS) signals) in normal subjects. The results of the test showed high agreement between model-based and reference values (difference < 5%), which implies that the proposed model could be an alternative method to detect the end of T waves in nfECG signals. [ABSTRACT FROM AUTHOR]

Importance: Neovascular age-related macular degeneration (nAMD) is a leading cause of blindness with several intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents available for its management such as aflibercept, bevacizumab, and ranibizumab. However, direct comparisons between these three agents among the same patient population are limited. Objective: To assess the rate and growth of complete retinal pigment epithelium and outer retinal atrophy (cRORA) in eyes with nAMD treated with aflibercept, bevacizumab, and/or ranibizumab. Method: Retrospective cohort study of patients with treatment-naïve neovascular AMD seen at an academic hospital between October 2006 and February 2019. Study eyes were treated with intravitreal injections of aflibercept, bevacizumab, and/or ranibizumab and followed for two years. Main outcomes and measures: cRORA prevalence, location, size, and growth rate. Eyes were imaged with Cirrus spectral domain optical coherence tomography (SD-OCT). Presence and size of cRORA were calculated using the FDA-approved Advanced RPE Analysis software. Linear regression models were used to correlate cRORA progression with baseline demographic and ocular characteristics, anti-VEGF drug, and number of injections. Unpaired t-tests, ANOVA, and linear regression models were computed with SAS 9.4. Results: 197 eyes from 158 patients (mean age 78.9, 62.9% women) received an average of 13 anti-VEGF injections over 24 months. 22% developed new cRORA. Mean cRORA area increased from 1.71 mm2 to 2.93 mm2. At 24 months, eyes with 11+ injections had significantly less cRORA area (11+ injections, 4.02 mm2; ≤ 10 injections, 2.46 mm2; p = 0.01) and growth rate (11+ injections, 0.41 mm2/year; ≤ 10 injections, 1.05 mm2/year; p = 0.02). Choice of anti-VEGF drug yielded no significant difference in cRORA progression. Conclusions and relevance: Treating nAMD with aflibercept, bevacizumab or ranibizumab demonstrated comparable cRORA development at 24 months. Number of injections inversely correlated with cRORA area and growth. These results warrant further investigation in the pathophysiology of cRORA in anti-VEGF treated eyes. [ABSTRACT FROM AUTHOR]

Elevated intraocular pressure is the only treatable risk factor for glaucoma, an eye disease that is the leading cause of irreversible blindness worldwide. We have identified cromakalim prodrug 1 (CKLP1), a novel water-soluble ATP-sensitive potassium channel opener, as a new ocular hypotensive agent. To evaluate the pharmacokinetic and safety profile of CKLP1 and its parent compound levcromakalim, Dutch-belted pigmented rabbits were treated intravenously (0.25 mg/kg) or topically (10 mM; 4.1 mg/ml) with CKLP1. Body fluids (blood, aqueous and vitreous humor) were collected at multiple time points and evaluated for the presence of CKLP1 and levcromakalim using a liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) based assay. Histology of tissues isolated from Dutch-belted pigmented rabbits treated once daily for 90 days was evaluated in a masked manner by a certified veterinary pathologist. The estimated plasma parameters following intravenous administration of 0.25 mg/kg of CKLP1 showed CKLP1 had a terminal half-life of 61.8 ± 55.2 min, Tmax of 19.8 ± 23.0 min and Cmax of 1968.5 ± 831.0 ng/ml. Levcromakalim had a plasma terminal half-life of 85.0 ± 37.0 min, Tmax of 61.0 ± 32.0 min and Cmax of 10.6 ± 1.2 ng/ml. Topical CKLP1 treatment in the eye showed low levels (<0.3 ng/mL) of levcromakalim in aqueous and vitreous humor, and trace amounts of CKLP1 and levcromakalim in the plasma. No observable histological changes were noted in selected tissues that were examined following topical application of CKLP1 for 90 consecutive days. These results suggest that CKPL1 is converted to levcromakalim in the eye and likely to some extent in the systemic circulation. [ABSTRACT FROM AUTHOR]