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ObjectivesTo compare serum ferritin and RET-He values among extremely low gestational age neonates ELGANs with other markers of iron-deficient erythropoiesis.Study DesignThis is a secondary analysis of the NICHD Darbepoetin Trial. Study data from placebo recipients who had a serum ferritin, a RET-He, and a mean corpuscular volume (MCV) measurement within a 24-hour period were analyzed for correlation.ResultsMixed linear regression models showed no association between ferritin and RET-He at both early (β = 0.0016, p = 0.40) and late (β = −0.0001, p = 0.96) time points. Positive associations were observed between RET-He and MCV at baseline, early, and late time points (p < 0.01, =0.01, <0.001, respectively), while ferritin was not associated with MCV at any time point.ConclusionsOur study shows that RET-He is better correlated with MCV as a marker of iron-limited erythropoiesis than ferritin. The results suggest that ferritin is limited as a marker of iron sufficiency in premature infants.Study IdentificationFDA IND Number 100138; ClinicalTrials.gov number NCT03169881; NRN ID number NICHD-NRN-0058 (Darbe).

Objective: Aggressive phototherapy (AgPT) is widely used and assumed to be safe and effective for even the most immature infants. We assessed whether the benefits and hazards for the smallest and sickest infants differed from those for other extremely low-birth-weight (ELBW; ⩽1000 g) infants in our Neonatal Research Network trial, the only large trial of AgPT. Study Design: ELBW infants ( n =1974) were randomized to AgPT or conservative phototherapy at age 12 to 36 h. The effect of AgPT on outcomes (death, impairment, profound impairment, death or impairment (primary outcome), and death or profound impairment) at 18 to 22 months of corrected age was related to BW stratum (501 to 750 g; 751 to 1000 g) and baseline severity of illness using multilevel regression equations. The probability of benefit and of harm was directly assessed with Bayesian analyses. Result: Baseline illness severity was well characterized using mechanical ventilation and FiO 2 at 24 h age. Among mechanically ventilated infants ⩽750 g BW ( n =684), a reduction in impairment and in profound impairment was offset by higher mortality ( P for interaction <0.05) with no significant effect on composite outcomes. Conservative Bayesian analyses of this subgroup identified a 99% (posterior) probability that AgPT increased mortality, a 97% probability that AgPT reduced impairment, and a 99% probability that AgPT reduced profound impairment. Conclusion: Findings from the only large trial of AgPT suggest that AgPT may increase mortality while reducing impairment and profound impairment among the smallest and sickest infants. New approaches to reduce their serum bilirubin need development and rigorous testing.

In this randomized trial of infants with a birth weight of 1000 g or less, as compared with conservative phototherapy, aggressive phototherapy did not significantly reduce the rate of death or neurodevelopmental impairment at 18 to 22 months of corrected age but did reduce the rate of neurodevelopmental impairment. Preplanned subgroup analyses suggested a possible increased mortality with aggressive phototherapy in infants weighing 501 to 750 g at birth. These results will help guide decisions about the use of aggressive phototherapy in infants of extremely low birth weight. In infants with a birth weight of 1000 g or less, aggressive phototherapy did not significantly reduce the rate of death or neurodevelopmental impairment at 18 to 22 months of corrected age but did reduce the rate of neurodevelopmental impairment. It is controversial whether modest elevations of total serum bilirubin (hereafter referred to simply as “bilirubin”) cause brain damage in preterm infants. 1 – 4 Some observational studies of preterm infants have suggested that bilirubin levels as low as 5 mg per deciliter (86 μmol per liter) or even lower may cause neurodevelopmental deficits. 5 – 8 However, other observational studies have suggested that moderately higher bilirubin levels have no neurotoxic effects 9 – 11 or might even benefit these infants, 12 because bilirubin is an antioxidant. Phototherapy is considered to be effective and safe in reducing bilirubin levels. 13 However, it has been studied in only one . . .

Prenatal tobacco smoke exposure (TSE) and prematurity are independent risk factors for abnormal neurodevelopment. The objectives were to compare differences in Bayley-III cognitive, language, and motor scores at 2 years corrected age (CA) in 395 infants born very preterm (≤ 32 weeks gestation) with and without prenatal TSE. We performed multivariable linear regression analyses to examine associations between prenatal TSE and neurodevelopmental outcomes and a mediation analysis to estimate direct effects of prenatal TSE on outcomes and indirect effects through preterm birth. In total, 50 (12.6%) infants had prenatal TSE. Infants with prenatal TSE had lower mean [95% CI] Cognitive score (82.8 [78.6, 87.1]) vs. nonexposed infants (91.7 [90.1, 93.4]). In children with and without prenatal TSE, there were significant differences in mean [95% CI] Language scores (81.7 [76.0, 87.4] vs. 92.4 [90.2, 94.6], respectively) and mean [95% CI] Motor scores (86.5 [82.2, 90.7] vs. 93.4 [91.8, 95.0], respectively); scores remained significant after controlling for confounders. Preterm birth indirectly mediated 9.0% of the total effect of prenatal TSE on Cognitive score (P = NS). However, 91% of the remaining total effect was significant and attributable to TSE’s direct harmful effects on cognitive development (β = − 5.17 [95% CI − 9.97, − 0.38]). The significant association is largely due to TSE’s direct effect on cognitive development and not primarily due to TSE’s indirect effect on preterm birth.

Infants born very preterm (VPT) are at high risk of motor impairments such as cerebral palsy (CP), and diagnosis can take 2 years. Identifying in vivo determinants of CP could facilitate presymptomatic detection and targeted intervention. Our objectives were to derive micro‐ and macrostructural measures of sensorimotor white matter tract integrity from diffusion MRI at term‐equivalent age, and determine their association with early diagnosis of CP. We enrolled 263 VPT infants (≤32 weeks gestational age) as part of a large prospective cohort study. Diffusion and structural MRI were acquired at term. Following consensus guidelines, we defined early diagnosis of CP based on abnormal structural MRI at term and abnormal neuromotor exam at 3–4 months corrected age. Using Constrained Spherical Deconvolution, we derived a white matter fiber orientation distribution (fOD) for subjects, performed probabilistic whole‐brain tractography, and segmented nine sensorimotor tracts of interest. We used the recently developed fixel‐based (FB) analysis to compute fiber density (FD), fiber‐bundle cross‐section (FC), and combined fiber density and cross‐section (FDC) for each tract. Of 223 VPT infants with high‐quality diffusion MRI data, 14 (6.3%) received an early diagnosis of CP. The cohort's mean (SD) gestational age was 29.4 (2.4) weeks and postmenstrual age at MRI scan was 42.8 (1.3) weeks. FD, FC, and FDC for each sensorimotor tract were significantly associated with early CP diagnosis, with and without adjustment for confounders. Measures of sensorimotor tract integrity enhance our understanding of white matter changes that antecede and potentially contribute to the development of CP in VPT infants. Infants born very preterm are at high risk of motor impairments such as cerebral palsy. We report biomarkers of sensorimotor white matter tract integrity, derived from diffusion MRI at term‐equivalent age, that are associated with early diagnosis of cerebral palsy.