To identify antecedent clinical and health services events in infants (>/=35 weeks gestational age (GA)) who were discharged as healthy from their place of birth and subsequently sustained kernicterus. We conducted a root-cause analysis of a convenience sample of 125 infants >/=35 weeks GA cared for in US healthcare facilities (including off-shore US military bases). These cases were voluntarily reported to the Pilot USA Kernicterus Registry (1992 to 2004) and met the eligibility criteria of acute bilirubin encephalopathy (ABE) and/or post-icteric sequelae. Multiple providers at multiple sites managed this cohort of infants for their newborn jaundice and progressive hyperbilirubinemia. Clinical signs of ABE, verbalized by parents, were often inadequately elicited or recorded and often not recognized as an emergency. Clinical signs of ABE were reported in 7 of 125 infants with a subsequent diagnosis of kernicterus who were not re-evaluated or treated for hyperbilirubinemia, although jaundice was noted at outpatient visits. The remaining infants (n=118) had total serum bilirubin (TSB) levels >20 mg per 100 ml (342 micromol l(-1); range: 20.7 to 59.9 mg per 100 ml). No specific TSB threshold coincided with onset of ABE. Of infants <37 weeks GA with kernicterus, 34.9% were LGA (large for gestational age) as compared with 24.7% of term infants (>37 weeks GA). Although >90% mothers initiated breast-feeding, assessment of milk transfer and lactation support was suboptimal in most. Mortality was 4% (5 of 125) in infants readmitted at age 0.2 mg per 100 ml per hour), contributing factors, alone or in combination, included undiagnosed hemolytic disease, excessive bilirubin production related to extra-vascular hemolysis and delayed bilirubin elimination (including increased enterohepatic circulation, diagnosed and undiagnosed genetic disorders) in the context of known late prematurity (<37 weeks), glucose 6-phosphate-dehydrogenase deficiency, infection and dehydration. Readmission was at age 35 mg per 100 ml had post-icteric sequela...

In a high-risk cohort, a BW-GA-weight-gain model could have reduced the need for examinations by 30%, while still identifying all infants requiring laser surgery. Additional studies are required to determine whether including larger-BW, lower-risk infants would reduce examinations further and to validate the prediction model and nomograms before clinical use.

Background Platelets may act as vascular endothelial growth factor (VEGF) scavengers, possibly limiting neovascularization in retinopathy of prematurity (ROP). The purpose of this study was to investigate the association between thrombocytopenia (platelets <150,000/μL) and the development of type 1 ROP. Methods This was a retrospective 1:1 matched case-control study. Cases required laser; controls developed no or stage 1 ROP and were matched for birth weight within 100 g and gestational age within 1 week. Most recent platelet count prior to laser (case) and matched postmenstrual age (control) were abstracted. Conditional logistic regression was used. Results A total of 91 cases and 91 controls were reviewed. Of the cases, 25% had thrombocytopenia; of controls, 13% (P = 0.034; OR = 2.38; 95% CI, 1.04-5.43). Birth weight, gestational age, postmenstrual age, and culture-proven sepsis were not confounders in multivariate analysis. The association was significant for zone 1 (n = 16; OR = 9.00; 95% CI, 1.14-71.0) but not for zone 2 (OR = 1.43; 95% CI, 0.54-3.75) cases and controls. Conclusions Thrombocytopenia was associated with type 1 ROP, primarily among infants with zone 1 ROP. This effect may result from disease location or disease timing, as posterior disease occurs at an earlier postmenstrual age. Longitudinal studies are required to further examine the roles of cumulative platelet deficits, thresholds, or critical time windows in the observed association.

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Objectives To describe adverse events (AEs) and noteworthy clinical or ocular findings associated with retinopathy of prematurity (ROP) evaluation procedures. Study design Descriptive analysis of pre-defined AEs and noteworthy findings reported in a prospective observational cohort study of infants <1251 g birth weight (BW) who had ROP study visits consisting of both binocular indirect ophthalmoscopy (BIO) and digital retinal imaging. We compared infant characteristics during ROP visits with and without AEs. We compared respiratory support, nutrition, and number of apnea, bradycardia, or hypoxia events 12 hours before and after ROP visits. Results 1,257 infants, mean BW 802 g, had 4,263 BIO and 4,048 imaging sessions (total 8,311 procedures). No serious AEs were related to ROP visits. Sixty-five AEs were reported among 61 infants for an AE rate of 4.9% infants (61/1257) or 0.8% total procedures (65/8311 BIO + imaging). Most AEs were due to apnea, bradycardia, and/or hypoxia (68%), tachycardia (16%), or emesis (8%). At ROP visit, infants with AEs, compared with those without, were more likely to be on mechanical ventilation (26% versus 12%, p=0.04) even after adjustment for weight and PMA. Noteworthy clinical findings were reported during 8% BIO and 15% imaging exams. Respiratory and nutrition support were not significantly different before and after ROP evaluations. Conclusions Retinal imaging by non-physicians combined with BIO was safe. Noteworthy clinical findings occurred during both procedures. Ventilator support was a risk factor for AEs. Monitoring rates of AEs and noteworthy findings are important to the safe implementation of ROP imaging protocols. Trial registration Clinicaltrials.gov: NCT01264276

Background Platelets may act as vascular endothelial growth factor (VEGF) scavengers, possibly limiting neovascularization in retinopathy of prematurity (ROP). The purpose of this study was to investigate the association between thrombocytopenia (platelets <150,000/μL) and the development of type 1 ROP. Methods This was a retrospective 1:1 matched case-control study. Cases required laser; controls developed no or stage 1 ROP and were matched for birth weight within 100 g and gestational age within 1 week. Most recent platelet count prior to laser (case) and matched postmenstrual age (control) were abstracted. Conditional logistic regression was used. Results A total of 91 cases and 91 controls were reviewed. Of the cases, 25% had thrombocytopenia; of controls, 13% (P = 0.034; OR = 2.38; 95% CI, 1.04-5.43). Birth weight, gestational age, postmenstrual age, and culture-proven sepsis were not confounders in multivariate analysis. The association was significant for zone 1 (n = 16; OR = 9.00; 95% CI, 1.14-71.0) but not for zone 2 (OR = 1.43; 95% CI, 0.54-3.75) cases and controls. Conclusions Thrombocytopenia was associated with type 1 ROP, primarily among infants with zone 1 ROP. This effect may result from disease location or disease timing, as posterior disease occurs at an earlier postmenstrual age. Longitudinal studies are required to further examine the roles of cumulative platelet deficits, thresholds, or critical time windows in the observed association.

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