and for the PENUT Consortium BACKGROUND: Outcomes of extremely low gestational age neonates (ELGANs) may be adversely impacted by packed red blood cell (pRBC) transfusions. We investigated the impact of transfusions on neurodevelopmental outcome in the Preterm Erythropoietin (Epo) Neuroprotection (PENUT) Trial population. METHODS: This is a post hoc analysis of 936 infants 24-0/6 to 27-6/7 weeks' gestation enrolled in the PENUT Trial. Epo 1000 U/kg or placebo was given every 48 h × 6 doses, followed by 400 U/kg or sham injections 3 times a week through 32 weeks postmenstrual age. Six hundred and twenty-eight (315 placebo, 313 Epo) survived and were assessed at 2 years of age. We evaluated associations between BSID-III scores and the number and volume of pRBC transfusions. RESULTS: Each transfusion was associated with a decrease in mean cognitive score of 0.96 (95% CI of [−1.34, −0.57]), a decrease in mean motor score of 1.51 (−1.91, −1.12), and a decrease in mean language score of 1.10 (−1.54, −0.66). Significant negative associations between BSID-III score and transfusion volume and donor exposure were observed in the placebo group but not in the Epo group. CONCLUSIONS: Transfusions in ELGANs were associated with worse outcomes. We speculate that strategies to minimize the need for transfusions may improve outcomes.
on behalf of the PENUT Trial Consortium* Objective To evaluate whether extremely low gestational age neonates (ELGANs) randomized to erythropoietin have better or worse kidney-related outcomes during hospitalization and at 22-26 months of corrected gestational age (cGA) compared with those randomized to placebo. Study designWe performed an ancillary study to a multicenter double-blind, placebo-controlled randomized clinical trial of erythropoietin in ELGANs. ResultsThe prevalence of severe (stage 2 or 3) acute kidney injury (AKI) was 18.2%. We did not find a statistically significant difference between those randomized to erythropoietin vs placebo for in-hospital primary (severe AKI) or secondary outcomes (any AKI and serum creatinine/cystatin C values at days 0, 7, 9, and 14). At 22-26 months of cGA, 16% of the cohort had an estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m 2 , 35.8% had urine albumin/creatinine ratio >30 mg/g, 23% had a systolic blood pressure (SBP) >95th percentile for age, and 40% had a diastolic blood pressure (DBP) >95th percentile for age. SBP >90th percentile occurred less often among recipients of erythropoietin (P < .04). This association remained even after controlling for gestational age, site, and sibship (aOR 0.6; 95% CI 0.39-0.92). We did not find statistically significant differences between treatment groups in eGFR, albumin/creatinine ratio, rates of SBP >95th percentile, or DBP >90th or >95th percentiles at the 2 year follow-up visit.Conclusions ELGANs have high rates of in-hospital AKI and kidney-related problems at 22-26 months of cGA.Recombinant erythropoietin may protect ELGANs against long-term elevated SBP but does not appear to protect from AKI, low eGFR, albuminuria, or elevated DBP at 22-26 months of cGA.
Diagnosis of cerebral palsy (CP) after perinatal stroke is often delayed beyond infancy, a period of rapid neuromotor development with heightened potential for rehabilitation. This study sought to assess whether the presence or absence of motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) could be an early biomarker of atypical development within the first year of life. In 10 infants with perinatal stroke, motor outcome was assessed with a standardized movement assessment. Single-pulse TMS was utilized to assess presence of MEPs. Younger infants (3–6 months CA, n = 5, 4/5 (80%)) were more likely to present with an MEP from the more-affected hemisphere (MAH) compared to older infants (7–12 months CA, n = 5, 0/5, (0%)) (p = 0.048). Atypical movement was demonstrated in the majority of infants with an absent MEP from the MAH (5/6, 83%) compared to those with a present MEP (1/4, 25%) (p = 0.191). We found that age influences the ability to elicit an MEP from the MAH, and motor outcome may be related to MAH MEP absence. Assessment of MEPs in conjunction with current practice of neuroimaging and motor assessments could promote early detection and intervention in infants at risk of CP.
Background Perinatal brain injuries often impact the corticospinal system, leading to motor impairment and cerebral palsy. Although transcranial magnetic stimulation (TMS) has been widely used to study corticospinal connectivity in adults and older children, similar studies of young infants are limited. Objectives The objective was to establish the safety and feasibility of advanced TMS assessments of the corticospinal connectivity of young infants with perinatal brain injury. Design This was a pilot, cross-sectional study of 3- to 12-month-old (corrected age) infants with perinatal stroke or intracranial hemorrhage. Methods Six participants (2 term, 4 preterm) were assessed with stereotactic neuronavigation-guided TMS. Single-pulse TMS was applied to each hemisphere and responses were recorded simultaneously from both upper limbs. During data collection, vital signs and stress responses were measured to assess safety. Developmental motor outcomes were evaluated using the General Movements Assessment and Bayley Scales of Infant and Toddler Development (3rd edition). A clinical diagnosis of cerebral palsy was recorded, if available. Results No adverse events occurred during TMS testing. All sessions were well tolerated. Contralateral motor evoked responses were detected in 4 of 6 participants. Both contralateral and ipsilateral responses were observed in 2 of 6 participants. Limitations TMS responses were not obtained in all participants. This could be related to the location of brain injury or developmental stage of the corticospinal system controlling the wrist flexor muscle group from which responses were recorded. Conclusions This study provides a summary of the framework for performing novel TMS assessments in infants with perinatal brain injury. Implementing this approach to measure corticospinal connectivity in hypothesis-driven studies in young infants appears to be justified. Such studies could inform the characterization of corticospinal development and the neural mechanisms driving recovery following early interventions.
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