Neurodevelopmental outcomes following preterm birth and the association with postmenstrual age at discharge

Objective: To 1) define the prevalence of motor, cognitive, and language delays in preterm infants born < 32 weeks estimated gestational age (EGA) and 2) identify the relationship between the timing of discharge from the NICU and neurodevelopmental outcome in early childhood. Study Design: This retrospective study of 176 preterm infants born < 32 weeks EGA and hospitalized in a level IV NICU captured medical factors, including timing of discharge, from the NICU stay. Standardized developmental testing at 1-2 years corrected age was conducted in the newborn follow-up clinic. Results: At 1-2 years corrected age, the sample had an average cognitive composite score of 91.5 ± 17.4, language composite score of 84.5 ± 17.3, and motor composite score of 88.9 ± 18.4. Lower EGA at birth, necrotizing enterocolitis, patent ductus arteriosus, and oxygen requirement for > 28 days were independently associated with higher postmenstrual age (PMA) at NICU discharge. After controlling for known risk factors, higher PMA at discharge was associated with poorer cognitive outcome [p < 0.001, (-0.16, -0.07), β = -0.35], poorer language outcome [p = 0.049 (-0.10, 0.00), β = -0.15] and poorer motor outcome [p < 0.001, (-0.14, -0.05), β = -0.30]. Conclusion: Poorer cognitive, language, and motor outcomes were associated with longer hospitalization, even after controlling for medical risk factors known to be associated with poorer outcome. This provides further evidence for the potential role of the environment that may be impacting the developmental outcomes of infants hospitalized in the NICU.

A Simple Non-Invasive Biomarker Can Reflect Both the Acute and Chronic Pulmonary Impact of Patent Ductus Arteriosus (PDA) Shunting

The SFR (Sp02/Fi02 ratio) offers a continuous, non-invasive reflection of pulmonary function regardless of whether the baby is ventilated or breathing spontaneously. We hypothesized that significant PDA shunting would impair pulmonary oxygen diffusion, in turn, reflected by decreased SFR; and that early PDA related decreases in SFR will predict subsequent chronic lung disease (CLD). Methods: We retrospectively examined records from preterm neonates <30 weeks gestational age. Ductal shunting was graded for severity by first week echocardiogram. SFR was calculated as SpO2/Fi02 and recorded on day 7 of life and at 36 weeks postmenstrual age (PMA). Results: We studied 104 infants: 65 with closed duct; 17 with hemodynamically insignificant PDA and 22 with hemodynamically significant (hsPDAs). CLD developed in 9 (14%) of those with closed ducts; 6 (35%) of those with hisPDA; and in 12 (55%) of those with hsPDA (p=0.005). Babies with hsPDA had significantly lower SFR values at both time points. SFRs in babies with hisPDA were decreased at 1 week postnatally, but were similar to those of babies with closed ducts at 36 weeks. SFR at 36 wks. was decreased only in infants with hsPDA [[467[461,467] vs. 467[413,471] vs. 369[262,436] respectively; p=0.000148]. Using ROC curve analysis, week 1 SFR was strongly associated with hsPDA (AUC=0.770; p<0.0001) and highly predictive (AUC=0.801; p<0.0001) of CLD at 36 weeks PMA. Conclusion: Early decreases in SFR reflect both the acute and chronic pulmonary impact of PDA shunting, possibly providing the missing link supporting an association between hemodynamically significant PDA and subsequent CLD.

Extended Interval Aminoglycoside Treatment for Klebsiella Pneumoniae Endocarditis in an Extremely Low Birth Weight Neonate

Infective endocarditis (IE) in neonates is associated with high mortality and incidence has been increasing over the past two decades. The majority of very low birth weight infants will be treated with at least one nephrotoxic medication during their hospital course. Over one-quarter of very low birth weight neonates exposed to gentamicin may develop acute kidney injury (AKI); this is particularly worrisome as AKI is an independent factor associated with increased neonatal mortality and increased length of stay. AKI during periods of neonatal nephrogenesis, which continues until 34–36 weeks postmenstrual age, may also have serious effects on the long-term nephron development which subsequently puts infants at risk of chronic kidney disease. Extended interval (EI) aminoglycoside (AMG) dosing has been used for decades in adult populations and has proven to reduce AKI while being at least as effective as traditional dosing, although there is limited published research for using an EI AMG in endocarditis in adults or pediatric patients. We describe an extremely low birth weight neonate, born preterm at 24 weeks gestation treated for Klebsiella pneumoniae IE that required AMG therapy who also had concurrent AKI. We utilized EI AMG combination therapy for treatment of Klebsiella pneumoniae endocarditis with good outcome and encourage others to report their experiences to improve our knowledge of EI AMG in this population.

Case Report: Glaucoma in an Infant With Retinopathy of Prematurity

Retinopathy of prematurity (ROP) is a leading cause of childhood blindness that occurs due to incomplete development of retinal blood vessels in preterm infants. Glaucoma is an ocular comorbidity in some patients with ROP, and it may be associated with immature anterior chamber development, ROP itself, or the treatment for ROP. There have been a few reports of narrow-angle glaucoma after laser treatment for ROP. In this case report, we describe the course of a female infant born at 24 weeks and 5 days of gestational age with treatment-requiring ROP treated with laser photocoagulation who subsequently developed very elevated intraocular pressure and shallow anterior chambers without pupillary block. The patient required bilateral ab externo trabeculotomy for elevated intraocular pressure, which normalized after the procedure. The patient has remained stable at the last follow-up at 51 weeks postmenstrual age. Differing from previous glaucoma presentations in this setting, we illustrate a case of elevated intraocular pressure and anterior chamber narrowing after laser therapy without pupillary block or synechiae. The possible multifactorial etiology of glaucoma in this patient, including incomplete angle development, ischemia, and laser treatment, highlight the need for glaucoma screening in patients with ROP, both in the short and long term.

Bronchopulmonary Dysplasia and Risk of Developmental Delay: An EPIPAGE-2 Cohort Study

<b><i>Background:</i></b> Overall and respiratory management of preterm children are constantly evolving, which might have changed both the pathophysiology and neurodevelopmental consequences of bronchopulmonary dysplasia (BPD). <b><i>Objectives:</i></b> The objective of this study is to determine whether the previously shown association between BPD and risk of developmental delay persists. <b><i>Methods:</i></b> The study population was children born before 32 weeks’ gestation from the French prospective cohort EPIPAGE-2. The exposure was BPD assessed at 36 weeks’ postmenstrual age. The main outcome was risk of developmental delay defined by an Age &amp; Stages Questionnaires (ASQ) score below threshold at 24 months’ corrected age. <b><i>Results:</i></b> The analyzed population included 2,706 children. Among those with available ASQ score, 196/1,587 had BPD and 671/1,587 had an ASQ score below threshold. BPD was associated with an ASQ score below threshold (odds ratio 1.52, 95% confidence interval 1.11–2.08; <i>p</i> = 0.008). <b><i>Conclusions:</i></b> BPD was strongly associated with risk of developmental delay.

Benchmarking Geometric Deep Learning for Cortical Segmentation and Neurodevelopmental Phenotype Prediction

The emerging field of geometric deep learning extends the application of convolutional neural networks to irregular domains such as graphs, meshes and surfaces. Several recent studies have explored the potential for using these techniques to analyse and segment the cortical surface. However, there has been no comprehensive comparison of these approaches to one another, nor to existing Euclidean methods, to date. This paper benchmarks a collection of geometric and traditional deep learning models on phenotype prediction and segmentation of sphericalised neonatal cortical surface data, from the publicly available Developing Human Connectome Project (dHCP). Tasks include prediction of postmenstrual age at scan, gestational age at birth and segmentation of the cortical surface into anatomical regions defined by the M-CRIB-S atlas. Performance was assessed not only in terms of model precision, but also in terms of network dependence on image registration, and model interpretation via occlusion. Networks were trained both on sphericalised and anatomical cortical meshes. Findings suggest that the utility of geometric deep learning over traditional deep learning is highly task-specific, which has implications for the design of future deep learning models on the cortical surface. The code, and instructions for data access, are available from https://github.com/Abdulah-Fawaz/Benchmarking-Surface-DL.

The Comparison of Three Assessment Scales in a Neonatal Unit in Poland

The aim of this study was to analyse the relationship between the following three assessments: the Neonatal Behavioral Assessment Scale (NBAS), the Alberta Infant Motor Scale (AIMS), and the General Movement Assessment (GMA). 29 patients from the neonatal unit of the Gynecology and Obstetrics Clinical Hospital were examined. The study was conducted between feedings by a person properly trained in the use of the NBAS, the AIMS, and the GMA. The average postmenstrual age of the examined newborns was 35.6 weeks. The average week of gestation was the 29th, the average birth weight was 1469 g, and the Median Apgar score in the fifth minute of life was 7. A relationship was found between the AIMS and the NBAS. It was concluded that the Neonatal Behavioral Assessment Scale and the Alberta Infant Motor Scale may be used to determine the motor development of preterm infants. Moreover, it is advisable to use more than one assessment method in order to adjust the intervention.

Administration of zinc to preterm infants with hypozincemia does not reduce serum copper concentrations in most cases: a single-center retrospective observational study

Background Zinc is an essential trace element involved in various physiological functions. In Japan, zinc acetate dihydrate is administered to neonates and infants with hypozincemia. Since serum copper concentrations are reduced by the administration of zinc, we retrospectively investigated changes in serum zinc and copper concentrations in preterm infants with hypozincemia receiving zinc acetate dihydrate. Methods Sixty-three preterm infants were included in the present study. Serum zinc and copper concentrations, doses, and other clinical characteristics were retrieved from electronic medical records. Results The medians and interquartile ranges of the dosage and duration of zinc acetate dihydrate were 2.1 (1.8–2.5) mg/kg/day and 12.0 (10.0–13.0) days, respectively. Its administration increased serum zinc concentrations in 39 patients (61.9%) and to more than 70 μg/dL in 16 patients (25.4%). The group with a serum zinc concentration of 70 μg/dL or higher after administration had a significantly higher zinc dose of 2.5 mg/kg/day than the group with a serum zinc concentration of less than 70 μg/dL. Serum copper concentrations did not decrease in 44 patients (69.8%). In the group with a decreased serum copper concentration, postmenstrual age and body weight were significantly lower, while serum zinc concentrations were significantly higher at the start of administration. Conclusion The present results showed that when zinc acetate dihydrate was administered to preterm infants with hypozincemia, it was possible to increase serum zinc concentrations without decreasing serum copper concentrations in many cases. However, caution may be required when administering zinc to preterm infants with a lower postmenstrual age or milder hypozincemia because serum copper concentrations may decrease.

Inter-eye comparison of retinal vascular growth rate and angiographic findings following unilateral bevacizumab treatment

Purpose To compare retinal vascularization progression rate, final retinal vascularization, and fluorescein angiography (FA) findings in infants who received intravitreal bevacizumab (IVB) treatment in one eye and with spontaneous regression in the other eye. Methods Thirty eyes of 15 infants who underwent IVB in one eye due to asymmetric retinopathy of prematurity, and who had pre-treatment fundus photographs and fluorescein angiography images were included in the study. Horizontal disc diameter (DD), optic disc-to-fovea distance (FD), and the length of temporal retinal vascularization (LTRV) distance were measured by evaluating pre-treatment and FA images. Results The mean ages at the time of treatment and FA were 40.38 ± 3.35 and 68.72 ± 10.52 weeks postmenstrual age, respectively. The pre-treatment LTRV/FD ratio was 3.11 ± 0.41 in the treated eyes and 3.26 ± 0.43 in the non-treated eyes (p = 0.053). The final LTRV/FD ratio was 4.23 ± 0.38 in the treated group and 4.33 ± 0.37 in the non-treated group (p = 0.286). Staining of the vessels, hyperfluorescent focus, and irregular branching of the vessels were similar between the groups, respectively (p = 1.000; p = 0.250; p = 0.625). Conclusion The progression rate of retinal vascularization and angiographic findings were similar between the treated eyes and the non-treated eyes. Our study suggests that incomplete retinal vascularization in eyes treated with anti-vascular endothelial growth factor (VEGF) is due to the nature of the disease, and anti-VEGF treatment was not to cause cessation in vascular progression.