Enteral Iron Supplementation in Infants Born Extremely Preterm and its Positive Correlation with Neurodevelopment; Post Hoc Analysis of the Preterm Erythropoietin Neuroprotection Trial Randomized Controlled Trial.

OBJECTIVES: To test whether an increased iron dose is associated with improved neurodevelopment as assessed by the Bayley Scales of Infant Development, third edition (BSID-III) among infants enrolled in the Preterm Erythropoietin (Epo) Neuroprotection Trial (PENUT). STUDY DESIGN: This is a post hoc analysis of a randomized trial that enrolled infants born at 24-28 completed weeks of gestation. All infants in PENUT who were assessed with BSID-III at 2 years were included in this study. The associations between enteral iron dose at 60 and 90 days and BSID-III component scores were evaluated using generalized estimating equations models adjusted for potential confounders. RESULTS: In total, 692 infants were analyzed (355 placebo, 337 Epo). Enteral iron supplementation ranged from 0 to 14.7 mg/kg/d (IQR 2.1-5.8 mg/kg/d) at day 60, with a mean of 3.6 mg/kg/d in infants treated with placebo and 4.8 mg/kg/d in infants treated with Epo. A significant positive association was seen between BSID-III cognitive scores and iron dose at 60 days, with an effect size of 0.77 BSID points per 50 mg/kg increase in cumulative iron dose (P = .03). Greater iron doses were associated with greater motor and language scores but did not reach statistical significance. Results at 90 days were not significant. The effect size in the infants treated with Epo compared with placebo was consistently greater. CONCLUSIONS: A positive association was seen between iron dose at 60 days and cognitive outcomes. Our results suggest that increased iron supplementation in infants born preterm, at the doses administered in the PENUT Trial, may have positive neurodevelopmental effects, particularly in infants treated with Epo. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01378273.

High-Dose Erythropoietin in Extremely Low Gestational Age Neonates Does Not Alter Risk of Retinopathy of Prematurity.

INTRODUCTION: The Preterm Erythropoietin (Epo) Neuroprotection (PENUT) Trial sought to determine the safety and efficacy of early high-dose Epo as a potential neuroprotective treatment. We hypothesized that Epo would not increase the incidence or severity of retinopathy of prematurity (ROP). METHODS: A total of 941 infants born between 24-0/7 and 27-6/7 weeks' gestation were randomized to 1,000 U/kg Epo or placebo intravenously for 6 doses, followed by subcutaneous or sham injections of 400 U/kg Epo 3 times a week through 32 weeks post-menstrual age. In this secondary analysis of PENUT trial data, survivors were evaluated for ROP. A modified intention-to-treat approach was used to compare treatment groups. In addition, risk factors for ROP were evaluated using regression methods that account for multiples and allow for adjustment for treatment and gestational age at birth. RESULTS: Of 845 subjects who underwent ROP examination, 503 were diagnosed with ROP with similar incidence and severity between treatment groups. Gestational age at birth, birth weight, prenatal magnesium sulfate, maternal antibiotic exposure, and presence of heart murmur at 2 weeks predicted the development of any ROP, while being on high-frequency oscillator or high-frequency jet ventilation (HFOV/HFJV) at 2 weeks predicted severe ROP. CONCLUSION: Early high-dose Epo followed by maintenance dosing through 32 weeks does not increase the risk of any or severe ROP in extremely low gestational age neonates. Gestational age, birth weight, maternal treatment with magnesium sulfate, antibiotic use during pregnancy, and presence of a heart murmur at 2 weeks were associated with increased risk of any ROP. Treatment with HFOV/HFJV was associated with an increased risk of severe ROP.

Severe ABO Hemolytic Disease of the Newborn Requiring Exchange Transfusion.

ABO incompatibility (ABOi), the most common cause of hemolytic disease of the newborn (HDN), is nearly always mild and treatable with phototherapy. Reports of ABOi HDN requiring neonatal exchange transfusion are extremely rare since the inception of modern guidelines. Here, a case of ABOi HDN clearly met criteria for exchange transfusion. An O-positive African American mother delivered a B-positive neonate that quickly developed hyperbilirubinemia. The neonatal DAT was positive from anti-B and anti-A,B, and maternal IgG titer was 1024. Double volume exchange transfusion resulted in a favorable outcome. Given early discharge of newborns, further understanding of factors predicting severe disease is needed.

Vitamin A status after prophylactic intramuscular vitamin A supplementation in extremely low birth weight infants.

BACKGROUND: Vitamin A supplementation (VAS) is recommended to prevent bronchopulmonary dysplasia (BPD). Our objective was to evaluate the effect of VAS on vitamin A (VA) status. We hypothesized that VAS would improve VA status in extremely low birth weight (ELBW) infants. MATERIALS AND METHODS: Retrospective chart review of infants 1 year before and after initiation of VAS (5000 IU 3 times a week intramuscularly [IM]; total 12 doses). Linear regression was used to model impact of VAS on VA status (retinol level and retinol/retinol binding protein [RBP] ratio). Models were adjusted for time and generalized estimating equations were used to account for intraindividual correlation. RESULTS: Sixty-seven infants (mean gestational age 26 ± 2 weeks; mean body weight 803 ± 142 g) were included; 35 received VAS and 32 did not (no-VAS). Both groups had similar baseline characteristics. Infants who received VAS had mean retinol levels that were 9.0 mcg/dL (95% confidence interval [CI], 4.9-13.2; P < .001) higher and mean retinol/RBP ratios that were 0.21 (95% CI, 0.07-0.36; P = .005) higher than the no-VAS group. Retinol and retinol/RBP ratio increased with time (P < .001). Fewer infants in the VAS group had VA deficiency (retinol/RBP ratios <0.7) compared with the no-VAS group. Culture-positive sepsis was more common in the VAS group (48% vs 12%; P = .002). CONCLUSIONS: VA status in ELBW infants was improved and maintained over the first month of life with IM VAS. Because of concerns for potential risks of repeated injections, further studies are indicated to evaluate the optimal mode of VA delivery in preterm infants.