Objective To assess feasibility and safety of providing autologous umbilical cord blood (UCB) cells to neonates with hypoxic-ischemic encephalopathy (HIE). Study design We enrolled infants in the ...intensive care nursery who were cooled for HIE and had available UCB in an open-label study of non-cyropreserved autologous volume- and red blood cell-reduced UCB cells (up to 4 doses adjusted for volume and red blood cell content, 1-5 × 107 cells/dose). We recorded UCB collection and cell infusion characteristics, and pre- and post-infusion vital signs. As exploratory analyses, we compared cell recipients' hospital outcomes (mortality, oral feeds at discharge) and 1-year survival with Bayley Scales of Infant and Toddler Development, 3rd edition scores ≥85 in 3 domains (cognitive, language, and motor development) with cooled infants who did not have available cells. Results Twenty-three infants were cooled and received cells. Median collection and infusion volumes were 36 and 4.3 mL. Vital signs including oxygen saturation were similar before and after infusions in the first 48 postnatal hours. Cell recipients and concurrent cooled infants had similar hospital outcomes. Thirteen of 18 (74%) cell recipients and 19 of 46 (41%) concurrent cooled infants with known 1-year outcomes survived with scores >85. Conclusions Collection, preparation, and infusion of fresh autologous UCB cells for use in infants with HIE is feasible. A randomized double-blind study is needed.
To evaluate the association between cystoid macular edema (CME) observed in very preterm infants and developmental outcomes at 18 to 24 months corrected age.
Cohort study.
Infants born at or less ...than 1500 g or at or less than 30 weeks postmenstrual age who underwent screening for retinopathy of prematurity (ROP) in an intensive care nursery.
Bedside handheld spectral-domain optical coherence tomography (SD OCT; Envisu, Bioptigen, Inc, Research Triangle Park, NC) imaging was obtained from preterm infants who were being screened for ROP and graded for presence of CME, central foveal thickness (CFT), inner nuclear layer thickness, and foveal-to-parafoveal thickness ratio. At 18 to 24 months corrected age, the children were assessed with the Bayley Scales of Infant and Toddler Development, Third Edition.
Scores on the Bayley cognitive, language, and motor subscales.
Among 77 children with SD OCT imaging, 53 were evaluated with the Bayley Scales. Compared with children who did not have CME as infants (n=22), the mean score for children who had CME (n=31) was 7.3 points (95% confidence interval CI, -15.5 to 0.9; P=0.08) lower on the cognitive subscale, 14.1 points (95% CI, -22.7 to -5.5; P=0.002) lower for the language subscale, and 11.5 points (95% CI, -21.6 to -1.3; P=0.03) lower for the motor subscale. Differences were maintained after adjusting for gestational age and birth weight. Severity of CME, as assessed by foveal-to-parafoveal thickness ratio, within the CME group correlated with poorer cognitive (R2=0.16, P=0.03) and motor (R2=0.15, P=0.03) development.
Cystoid macular edema observed on SD OCT in very preterm infants screened for ROP is associated with poorer language and motor skills at 18 to 24 months corrected age. Evaluation of the retina with SD-OCT may serve as an indicator of neurodevelopmental health for very preterm infants in the intensive care nursery.
To evaluate effects of prematurity on early optic nerve (ON) development and the usefulness of ON parameters as indicators of central nervous system (CNS) development and pathology.
Prospective, ...cross-sectional, longitudinal study.
Forty-four preterm infants undergoing retinopathy of prematurity (ROP) screening and 52 term infants.
We analyzed ON from portable handheld spectral-domain optical coherence tomography (SD-OCT) images (Bioptigen, Inc, Research Triangle Park, NC) of 44 preterm and 52 term infants. The highest-quality ON scan from either eye was selected for quantitative analysis. Longitudinal analysis was performed at 31-36 weeks and 37-42 weeks postmenstrual age (PMA). Preterm ON parameters also were assessed for correlation with indicators of cognitive, language, and motor development and CNS pathology.
Vertical cup diameter (vCD), vertical disc diameter (vDD), vertical cup-to-disc ratio (vCDR), cup depth, and indicators of neurocognitive development and CNS pathology.
At 37-42 weeks PMA, preterm infants had larger vCD and vCDR than term infants (908 vs. 700 μm P<0.001 and 0.68 vs. 0.53 μm P<0.001, respectively), whereas cup depth and vDD were not significantly different. Longitudinal changes (n = 26 preterm eyes; mean interval, 4.7 weeks) in vDD and in vCDR were an increase of 74 μm (P = 0.008) and decrease of 0.05 (P = 0.015), respectively. In preterm infants (n = 44), periventricular leukomalacia was associated with larger vCD (1084 vs. 828 μm; P = 0.005) and vCDR (0.85 vs. 0.63; P<0.001), posthemorrhagic hydrocephalus was associated with shallower cup (331 vs. 456 μm; P = 0.030), and clinical magnetic resonance imaging was associated with larger vCDR (0.73 vs. 0.64; P = 0.023). In 23 preterm infants with Bayley Scales of Infant Development scores, larger vCDR was associated with lower cognitive scores (P = 0.049).
This is the first analysis of ON parameters in premature infants using SD-OCT. It demonstrated that by age of term birth, vCD and vCDR are larger in preterm infants who were screened for ROP than in term infants. In this prospective pilot study, ON parameters in these preterm infants associate weakly with CNS pathology and future cognitive development. Future prospective studies with larger numbers are necessary before further conclusions can be made.
To characterize changes in subfoveal choroidal thickness in preterm infants from 30 to 60 weeks postmenstrual age (PMA).
The prospective, observational Study of Eye Imaging in Preterm infantS ...(BabySTEPS) enrolled infants eligible for retinopathy of prematurity screening per the American Association of Pediatrics guidelines.
Infants imaged with an investigational, handheld OCT at ≥ 4 distinct imaging sessions between 30 to 60 weeks PMA as part of BabySTEPS.
Average choroidal thickness across the central subfoveal 1 mm in each eye at each time point was measured using custom segmentation software, and errors were manually corrected by a trained grader. We prospectively collected birth history data. A segmented mixed model was used to analyze the change in choroidal thickness as a function of PMA, birth weight, and gestational age (GA).
Characterization of normative subfoveal choroidal thickness values and choroidal growth rate between 30 to 60 weeks PMA.
We included 592 imaging sessions of 79 preterm infants (152 eyes). Mean (± standard deviation) GA was 27.5 ± 2.5 weeks. Mean choroidal thickness was 141.4 ± 34.5 μm at 30 weeks, 272.2 ± 83.9 μm at 38 weeks, and 306.2 ± 77.4 μm between 56 and 60 weeks. Between 30 and 60 weeks PMA, choroidal growth followed a biphasic model, with a linear growth rate of 14.8 μm/week (95% confidence interval, 13.6–16.0) from 30 until 38.4 weeks then cessation of growth, with a growth rate of 0.3 μm/week (95% confidence interval, −1.1 to 1.6) from 38.4 to 60 weeks. Infants with extremely low birth weight (ELBW; < 1000 g) and extremely preterm (GA < 28 weeks) infants had significantly slower initial growth rates compared with very low and low birth weight and very preterm and preterm infants (ELBW 13.0 vs. 21.0 μm/week, P < 0.0001; and extremely preterm 13.2 vs. 18.0 μm/week, P = 0.003).
Preterm infant choroidal thickness experiences rapid linear growth from 30 to 38 weeks PMA, at which time growth nearly stops. These foundational measurements and identification of the impact of extremes of low birth weight and prematurity on choroidal development will be essential as researchers begin to understand the role of choroidal development in ocular and retinal health in human infants.
Proprietary or commercial disclosure may be found after the references.
The response of ICU patients to continuously infused ketamine when it is used for analgesia and/or sedation remains poorly established.
To describe continuous infusion (CI) ketamine use in critically ...ill patients, including indications, dose and duration, adverse effects, patient outcomes, time in goal pain/sedation score range, exposure to analgesics/sedatives, and delirium.
Multicenter, retrospective, observational study from twenty-five diverse institutions in the United States. Patients receiving CI ketamine between January 2014 and December 2017.
Chart review evaluating institutional and patient demographics, ketamine indication, dose, administration, and adverse effects. Pain/sedation scores, cumulative doses of sedatives and analgesics, and delirium screenings in the 24 hours prior to ketamine were compared with those at 0-24 hours and 25-48 hours after.
A total of 390 patients were included (median age, 54.5 yr; interquartile range, 39-65 yr; 61% males). Primary ICU types were medical (35.3%), surgical (23.3%), and trauma (17.7%). Most common indications were analgesia/sedation (
= 357, 91.5%). Starting doses were 0.2 mg/kg/hr (0.1-0.5 mg/kg/hr) and continued for 1.6 days (0.6-2.9 d). Hemodynamics in the first 4 hours after ketamine were variable (hypertension 24.0%, hypotension 23.5%, tachycardia 19.5%, bradycardia 2.3%); other adverse effects were minimal. Compared with 24 hours prior, there was a significant increase in proportion of time spent within goal pain score after ketamine initiation (24 hr prior: 68.9% 66.7-72.6%, 0-24 hr: 78.6% 74.3-82.5%, 25-48 hr: 80.3% 74.6-84.3%;
< 0.001) and time spent within goal sedation score (24 hr prior: 57.1% 52.5-60.0%, 0-24 hr: 64.1% 60.7-67.2%, 25-48 hr: 68.9% 65.5-79.5%;
< 0.001). There was also a significant reduction in IV morphine (mg) equivalents (24 hr prior: 120 25-400, 0-24 hr: 118 10-363, 25-48 hr: 80 5-328;
< 0.005), midazolam (mg) equivalents (24 hr prior: 11 4-67, 0-24 hr: 6 0-68, 25-48 hr: 3 0-57;
< 0.001), propofol (mg) (24 hr prior: 942 223-4,018, 0-24 hr: 160 0-2,776, 25-48 hr: 0 0-1,859;
< 0.001), and dexmedetomidine (µg) (24 hr prior: 1,025 276-1,925, 0-24 hr: 285 0-1,283, 25-48 hr: 0 0-826;
< 0.001). There was no difference in proportion of time spent positive for delirium (24 hr prior: 43.0% 17.0-47.0%, 0-24 hr: 39.5% 27.0-43.8%, 25-48 hr: 0% 0-43.7%;
= 0.233). Limitations to these data include lack of a comparator group, potential for confounders and selection bias, and varying pain and sedation practices that may have changed since completion of the study.
There is variability in the use of CI ketamine. Hemodynamic instability was the most common adverse effect. In the 48 hours after ketamine initiation compared with the 24 hours prior, proportion of time spent in goal pain/sedation score range increased and exposure to other analgesics/sedatives decreased.
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