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ObjectiveExtremely preterm (EP) impairment rates are likely underestimated using the Bayley III norm-based thresholds scores and may be better assessed relative to concurrent healthy term reference (TR) infants born in the same hospital.Study designBlinded, certified examiners in the Neonatal Research Network (NRN) evaluated EP survivors and a sample of healthy TR infants recruited near the 2-year assessment age.ResultsWe assessed 1452 EP infants and 183 TR infants. TR-based thresholds showed higher overall EP impairment than Bayley norm-based thresholds (O.R. = 1.86; [95% CI 1.56–2.23], especially for severe impairment (36% vs. 24%; p ≤ 0.001).Difficulty recruiting TR patients at 2 years extended the study by 14 months and affected their demographics.ConclusionImpairment rates among EP infants appear to be substantially underestimated from Bayley III norms. These rates may be best assessed by comparison with healthy term infants followed with minimal attrition from birth in the same centers.ClinicalTrials.gov IDTerm Reference (under the Generic Database Study): NCT00063063

This proof-of-principle trial showed that imatinib treatment reduced mast-cell activation and improved airway responsiveness in patients with severe refractory asthma. Many patients with severe asthma do not have adequate disease control despite the use of high-dose inhaled or systemic glucocorticoids. 1 Severe asthma is associated with airway hyperresponsiveness — that is, an exaggerated response to a bronchoconstrictor stimulus — and airway inflammation, both of which persist despite high-dose glucocorticoid therapy. 2 , 3 Increased airway hyperresponsiveness is associated with a progressive loss of lung function, 4 and, among patients with moderate-to-severe asthma, those with airway hyperresponsiveness have a poorer quality of life than those without this trait. 5 In addition, studies have shown that treatment targeting airway hyperresponsiveness leads to more effective control of asthma . . .

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.