Relationship of early brain growth pattern measured by ultrasound with neurological outcome at two years of age in very low birth weight infants.

The purpose of this study is to define the impact of early brain growth trajectory in very low birth weight infants (VLBWI) on neurological prognosis at 2 years, assessed using sequential ultrasound (US) scans. This is a prospective cohort study with consecutive inclusion of VLBWI ≤ 32 weeks gestational age and ≤ 1500 g at birth. Total brain volume (TBV) was assessed using sequential 3D-US from birth to discharge. Prognosis at 2 years (corrected age) was assessed using the Bayley Scales of Infant and Toddler Development Third Edition. TBV showed slower growth with postmenstrual age (PMA) in those VLBWI who had an adverse cognitive prognosis compared to those with good cognitive prognosis (mean difference in TBV between prognostic groups from 4.56 cm3 at 28 weeks to 42.58 cm3 at 43 weeks) as well as in those with adverse language prognosis (mean difference in TBV from 2.21 cm3 at 28 weeks to 26.98 cm3 at 43 weeks) although other variables showed more impact than TBV on language prognosis (gestational age at birth, brain injury at term, and socioeconomic status). No association was found between TBV and motor prognosis. Brain growth rate was also significantly higher in those VLBWI who presented good cognitive scores (18.78 + (0.33 × (PMA-33)) cm3/week) compared to those with adverse cognitive outcome (13.73 + (0.64 × (PMA-33)) cm3/week).  Conclusion: Early altered brain growth is associated with poor cognitive prognosis at 2 years of age. Using sequential US monitoring, we can detect early brain growth deviation in patients who will have adverse cognitive outcomes. What is known: • The prediction of neurodevelopmental outcome of VLBWI is mostly based on the presence of brain injury in US and structural magnetic resonance imaging (MRI) at term. • Some studies have related brain volume measured on MRI at term with neurodevelopment outcome. What is new: • VLBWI with adverse cognitive prognosis at two years of age present smaller brain volumes detectable by sequential US during NICU admission. • Brain volume can be estimated from 2D and 3D US and has prognostic value in VLBWI.

Ultrasonographic evaluation of the early brain growth pattern in very low birth weight infants.

BACKGROUND: Preterm infants develop smaller brain volumes compared to term newborns. Our aim is to study early brain growth related to perinatal factors in very low birth weight infants (VLBWI). METHODS: Manual segmentation of total brain volume (TBV) was performed in weekly 3D-ultrasonographies in our cohort of VLBWI. We studied the brain growth pattern related to term magnetic resonance image (term-MRI). RESULTS: We found different brain growth trajectories, with smaller brain volumes and a decrease in brain growth rate in those VLBWI who would later have an abnormal term-MRI (mean TBV 190.68 vs. 213.9 cm3; P = 0.0001 and mean TBV growth rate 14.35 (±1.27) vs. 16.94 (±2.29) cm3/week; P = 0.0001). TBV in those with normal term-MRI was related to gestational age (GA), being small for gestational age (SGA), sex, and duration of parenteral nutrition (TPN) while in those with abnormal term-MRI findings it was related to GA, SGA, TPN, and comorbidities. We found a deceleration in brain growth rate in those with ≥3 comorbidities. CONCLUSIONS: An altered brain growth pattern in VLBWI who subsequently present worst scores on term-MRI is related to GA, being SGA and comorbidities. Early ultrasonographic monitoring of TBV could be useful to detect deviated patterns of brain growth. IMPACT STATEMENT: We describe the brain growth pattern in very low birth weight infants during their first postnatal weeks. Brain growth may be affected in the presence of certain perinatal factors and comorbidities, conditioning a deviation of the normal growth pattern. The serial ultrasound follow-up of these at-risk patients allows identifying these brain growth patterns early, which offers a window of opportunity for implementing earlier interventions.

Ultrasonographic Estimation of Total Brain Volume: 3D Reliability and 2D Estimation. Enabling Routine Estimation During NICU Admission in the Preterm Infant.

Objectives: The aim of this study is to explore if manually segmented total brain volume (TBV) from 3D ultrasonography (US) is comparable to TBV estimated by magnetic resonance imaging (MRI). We then wanted to test 2D based TBV estimation obtained through three linear axes which would enable monitoring brain growth in the preterm infant during admission. Methods: We included very low birth weight preterm infants admitted to our neonatal intensive care unit (NICU) with normal neuroimaging findings. We measured biparietal diameter, anteroposterior axis, vertical axis from US and MRI and TBV from both MRI and 3D US. We calculated intra- and interobserver agreement within and between techniques using the intraclass correlation coefficient and Bland-Altman methodology. We then developed a multilevel prediction model of TBV based on linear measurements from both US and MRI, compared them and explored how they changed with increasing age. The multilevel prediction model for TBV from linear measures was tested for internal and external validity and we developed a reference table for ease of prediction of TBV. Results: We used measurements obtained from 426 US and 93 MRI scans from 118 patients. We found good intra- and interobserver agreement for all the measurements. US measurements were reliable when compared to MRI, including TBV which achieved excellent agreement with that of MRI [ICC of 0.98 (95% CI 0.96-0.99)]. TBV estimated through 2D measurements of biparietal diameter, anteroposterior axis, and vertical axis was comparable among both techniques. We estimated the population 95% confidence interval for the mean values of biparietal diameter, anteroposterior axis, vertical axis, and total brain volume by post-menstrual age. A TBV prediction table based on the three axes is proposed to enable easy implementation of TBV estimation in routine 2D US during admission in the NICU. Conclusions: US measurements of biparietal diameter, vertical axis, and anteroposterior axis are reliable. TBV segmented through 3D US is comparable to MRI estimated TBV. 2D US accurate estimation of TBV is possible through biparietal diameter, vertical, and anteroposterior axes.

Pleural line thickness reference values for preterm and term newborns.

BACKGROUND: In lung ultrasound (LUS), the pleural line is an artifact whose thickness depends on the underlying lung pathology. To date there are no published studies on normal values of pleural line thickness (PLT) in newborns. OBJECTIVE: The aim of our study is to describe normal PLT values in term newborn (TN) and preterm newborn (PTN). METHODS: We recruited eupneic TN and PTN, under 34 weeks of gestation, on their first 24 hours of life. Newborns presenting any respiratory distress since birth were excluded. LUS was performed in four areas: upper anterior, lower anterior, lateral and posterior. At each location, we measured PLT and values where compared. Intraobserver and interobserver agreement were assessed using the intraclass correlation coefficient (ICC), and the kappa coefficient. RESULTS: We included 23 TN with a median birth weight of 3365 g (interquartile range [IQR] 3100-3575 g) and a median gestational age of 39 weeks (IQR, 38-40 weeks). In the PTN group, 23 patients were included with a median birth weight of 1350 g (IQR, 1150-1590 g) and a median gestational age of 31 weeks (IQR, 30-32 weeks). Median PLT values were less than 1 mm, and there were no significant differences between groups at any locations, with the exception of the left lower anterior field (0.79 mm [IQR, 0.72-0.89 mm] vs 0.68 mm [IQR, 0.62-0.72 mm]). Intraobserver agreement was high: consistency ICC 0.77 (95% confidence interval [CI], 0.32-0.92) and absolute ICC 0.78 (95% CI, 0.34-0.93). Interobserver agreement was high for the definition of thin pleural line as less than 1 mm. CONCLUSIONS: TN and asymptomatic PTN have similar PLT values. Overall, PLT in healthy newborns should be less than 1 mm.

Reproducibility and reference values of diaphragmatic shortening fraction for term and premature infants.

BACKGROUND: New ultrasound measurements to diagnose diaphragmatic dysfunction, including diaphragmatic shortening fraction (DSF), have been studied in adults and children, but there are no data on reference values for neonates. OBJECTIVE: To describe DSF reference values for term neonate (TN) and preterm neonate (PTN), and to calculate its reproducibility. METHODS: We included asymptomatic TN and PTN during their first 24 hours of life. We measured DSF at the zone of apposition in both hemithoraces. Reproducibility of image acquisition, including inter- and intra-rater agreement of the measurements were calculated among an experienced and a novel operator (after completion of a 1-day course on lung ultrasound [LU] and performance of 10 diaphragm ultrasounds [DUs] under supervision), and a more-trained examiner (completion of a 1-day course on LU and performance of 60 DUs under supervision). RESULTS: Two groups of 33 TN and 33 PTN were studied. Median DSF values did not differ between the groups, although diaphragm thickness was higher in the TN group. Intra-observer reproducibility: the intraclass correlation coefficient (ICC) was 0.95 (95% confidence interval [95% CI] 0.86-0.98). Interobserver reproducibility with novel operator had an ICC of 0.42 (95% CI -0.74 to 0.81), and with a more experienced operator improved to 0.76 (95% CI 0.27-0.92). Both intra- and interobserver agreement were high. CONCLUSIONS: Asymptomatic TN and PTN have similar DSF values in the first 24 hours of life. The intra- and interobserver agreement is high. Reproducibility is acceptable, but intensive training is necessary to perform adequate DU.

Anakinra as rescue therapy for steroid-dependent idiopathic recurrent pericarditis in children: case report and literature review.

In approximately 5% of patients with idiopathic recurrent pericarditis, the disease usually follows a chronic relapsing course, and children can develop dependence and side effects of prolonged high-dose corticosteroid regimens. In this setting anakinra, a recombinant human interleukin-1 competitive receptor antagonist that blocks the biologic effects of interleukin-1, thereby reducing systemic inflammatory responses, appears to be one of the most promising strategies. We report an adolescent with steroid-dependent idiopathic recurrent pericarditis that was successfully treated with anakinra, highlighting that this therapeutic option seems to be an effective, rapidly acting, steroid-sparing, and relatively safe agent for the treatment of this entity in children.

Normal Cerebellar Growth by Using Three-dimensional US in the Preterm Infant from Birth to Term-corrected Age.

Purpose To establish cross-sectional and longitudinal reference values for cerebellar size in preterm infants with normal neuroimaging findings and normal 2-year neurodevelopmental outcome by using cranial ultrasonography (US). Materials and Methods This prospective study consecutively enrolled preterm infants admitted to a neonatal intensive care unit from June 2011 to June 2014 with a birth weight of less than or equal to 1500 g and/or gestational age (GA) of less than or equal to 32 weeks. They underwent weekly cranial US from birth to term-equivalent age and magnetic resonance (MR) imaging at term-equivalent age. The infants underwent neurodevelopmental assessments at age 2 years with Bayley Scales of Infant and Toddler Development, 3rd edition (BSID-III). Patients with adverse outcomes (death or abnormal neuroimaging findings and/or BSID-III score of <85) were excluded. The following measurements were performed: vermis height, craniocaudal diameter, superior width, inferior width, vermis area, and transcerebellar diameter. Statistical analyses were conducted by using multilevel analyses. Results A total of 137 infants with a mean GA at birth of 29.4 weeks (range, 25-32 weeks) were included. Transcerebellar diameter increased by 1.04 mm per week on average; vermis height and craniocaudal diameter increased by 0.55 mm and 0.59 mm, respectively. Superior vermian width increased by an average of 0.45 mm, whereas inferior vermian width increased by an average of 0.51 mm per week. Vermis area was found to increase by 0.22 cm2 per week on average. The sex effect was significant (female lower than male) for vermis height (P < .05), craniocaudal diameter (P < .05), inferior vermian width (P <. 05), and vermis area (P <. 05). Conclusion Cross-sectional and longitudinal reference values were established for cerebellar growth in preterm infants, which may be included in routine cranial US.