Luca A. Ramenghi

“Sucrose analgesia”: absorptive mechanism or taste perception?

It remains unclear whether “sucrose analgesia” is related to a pre- or postabsorptive mechanism. In a double blind cross over study sucrose reduced the pain response of preterm infants exposed to heel prick blood samples only when it was administered into the mouth. It was ineffective when administered intragastrically.

Magnetic resonance imaging of the infant brain: anatomical characteristics and clinical significance of punctate lesions

Objective: To describe the magnetic resonance imaging (MRI) characteristics of punctate brain lesions in neonates (number, appearance, distribution, and association with other brain abnormalities) and to relate them to neurodevelopmental outcome. Methods: A retrospective analysis was performed of 110 MRI brain scans from 92 infants admitted in 1998 to the neonatal intensive care unit. Results of routine neurodevelopmental follow up (1998–2001) in those infants with punctate brain lesions were analysed. Results: Punctate lesions were observed in 15/50 preterm and 2/42 term infants. In the preterm group, the number of lesions was < 3 in 20%, 3–10 in 27%, and > 10 in 53%. In 14/15 the lesions were linearly organised and located in the centrum semiovale. Other brain abnormalities were absent or minor—that is, “isolated” punctate lesions—in 8/15 and major in 7/15. In the term group, punctate lesions were organised in clusters and no other brain abnormalities were observed. Isolated punctate lesions were observed in 10/17 infants, and a normal neurodevelopmental outcome was seen in 9/10 (mean follow up 29.5 months). One infant showed a slight delay in language development. In the infants with associated brain lesions (7/17, mean follow up 27.5 months), outcome was normal in only two subjects. Conclusions: Punctate lesions are predominantly seen in preterm infants, are usually linearly organised, and border the lateral ventricles. Isolated punctate lesions may imply a good prognosis, because most of these subjects have a normal neurodevelopmental outcome so far.

Intra-oral administration of sweet-tasting substances and infants' crying response to immunization: a randomized, placebo-controlled trial.

The analgesic effects of four solutions administered intra-orally (25 and 50% sucrose solutions, hydrogenated glucose, and a sterile water placebo) were tested in groups of babies receiving routine DTP (diphtheria, tetanus, and pertussis) and HIB (Haemophilus influenzae type B) injections at the first, second, or third immunization. The duration of the baby’s cry during 3 min following DTP and HIB injections was measured as main outcome. For all three immunization groups, the babies receiving the placebo generally spent most time crying. For both the DTP and HIB injections, the difference between 50% sucrose and placebo was most evident in the group receiving the 3rd immunization. Intra-oral administration of the 50% sucrose solution, compared to placebo, appeared to reduce the cry response to painful experiences in babies beyond the neonatal period.

Prenatal pseudocysts of the germinal matrix in preterm infants.

Sonographic characteristics of germinal‐matrix (PGM) pseudocysts of prenatal origin detected on cranial ultrasound in preterm newborns were correlated with their outcomes. PGM cysts were classified as typical or atypical, according to their location. Typical PGM cysts were present at the head of the caudate nucleus or slightly medially, adjacent to the foramen of Monro. Cysts were defined as atypical when they were located subependymally elsewhere.

Cerebral perfusion in infants and neonates: preliminary results obtained using dynamic susceptibility contrast enhanced magnetic resonance imaging

Background: Previous studies have used the dynamic susceptibility contrast enhanced (DSCE) magnetic resonance (MR) imaging technique to measure cerebral perfusion in adults. Objective: To assess the feasibility of the technique in a heterogeneous cohort of sick human infants and identify cerebral perfusion abnormalities. Methods: Perfusion measurements were made by characterising the changing concentration of an injected bolus of contrast agent using a series of MR images acquired during the first pass of the contrast bolus. Qualitative values of relative cerebral blood flow (rCBF) were then calculated from these data on a pixel by pixel basis to generate parametric maps of perfusion. Results: Images of perfusion were successfully calculated from 12 out of 27 neonates and infants, all with established cerebral pathology. Normal vascular anatomical structures such as the circle of Willis were identified within all calculated images. Values of rCBF were generally larger in grey matter than in white matter. In several patients, perfusion abnormalities resulted in structural abnormalities which were detected in conventional MR imaging at follow up. The acquisition of perfusion data was most difficult when the least mature brains were examined because of motion artefacts and a smaller head size with a lower level of rCBF than adults. Conclusions: This preliminary study shows that: (a) maps of rCBF can be acquired from neonates and infants; (b) characterisation of the bolus passage becomes progressively easier as the brain matures; (c) early abnormalities in cerebral perfusion may have negative prognostic implications; (d) the main difficulty when using the DSCE technique to study neonates relates to image artefacts resulting from bulk head motion.

Brain susceptibility to oxidative stress in the perinatal period

Abstract Oxidative stress (OS) occurs at birth in all newborns as a consequence of the hyperoxic challenge due to the transition from the hypoxic intrauterine environment to extrauterine life. Free radical (FRs) sources such as inflammation, hyperoxia, hypoxia, ischaemia-reperfusion, neutrophil and macrophage activation, glutamate and free iron release, all increases the OS during the perinatal period. Newborns, and particularly preterm infants, have reduced antioxidant defences and are not able to counteract the harmful effects of FRs. Energy metabolism is central to life because cells cannot exist without an adequate supply of ATP. Due to its growth, the mammalian brain can be considered as a steady-state system in which ATP production matches ATP utilisation. The developing brain is particularly sensitive to any disturbances in energy generation, and even a short-term interruption can lead to long-lasting and irreversible damage. Whenever energy failure develops, brain damage can occur. Accumulating evidence indicates that OS is implicated in the pathogenesis of many neurological diseases, such as intraventricular haemorrhage, hypoxic-ischaemic encephalopathy and epilepsy.

Hemodynamic effects of intravenous morphine infusion in ventilated preterm babies

BACKGROUNDnthe importance of sedation and analgesia of newborn babies in intensive care is only now receiving recognition in many neonatal units.nnnOBJECTIVEnto evaluate the hemodynamic effects of morphine on Cerebral Blood Flow velocities (CBFv), Cardiac Output (CO), Stroke Volume (SV), Mean Arterial Blood Pressure (MABP) and Heart Rate (HR) in ventilated preterm infants, before and during the infusion of a loading dose.nnnDESIGNnprospective, open, non-randomized, before-after intervention study with hemodynamic measurements made by Doppler ultrasound.nnnSETTINGnneonatal Intensive Care Unit, Tertiary Care Center.nnnPATIENTSnsequential sample of 30 ventilated preterm newborns (gestational age (GA) 29 +/- 2 wks, range 27-31, birth weight (BW) 1240 +/- 440 g, range 800-1680).nnnINTERVENTIONneach subject received an intravenous loading dose of morphine (100 mcg/Kg/h) for 2 h, followed by a continuous infusion of 25 mcg/kg/h.nnnMEASUREMENTSnthe following Doppler parameters of the anterior cerebral artery were estimated: Peak systolic flow velocity (Vs), end-diastolic flow velocity (Vd), mean flow velocity (Vm) and Pourcelot Resistance Index (RI). Measurements of CBFv, CO and SV (by Doppler ultrasound), MABP and HR were made 30 min before (baseline values) and at 15 (M15), 30 (M30), 60 (M60) and 120 min (M120), during the morphine loading infusion. Statistical evaluation analysis of variance, significance was calculated by Student-Newman-Kenfeld test.nnnRESULTSnthere were no statistically significant changes in the cerebral and cardiac Doppler parameters before or during the 120 min of morphine loading infusion. There was a non-significant fall in MABP (MABP: Baseline value = 44 +/- 6 mmHg, M120 = 42 +/- 4 mmHg; reduction = 4%) and HR (HR = Baseline value = 148 +/- 12 beats/min., M120 = 140 +/- 16 beats/min.; reduction = 5%).nnnCONCLUSIONSna loading dose of morphine over 2 h did not have any significant effect on MABP or cerebral and cardiac hemodynamics. No adverse effects were noted that could be attributed to morphine therapy.

Impaired brain growth and neurodevelopment in preterm infants with posthaemorrhagic ventricular dilatation.

Aim:u2002 To correlate volumetric magnetic resonance imaging at term with neurodevelopmental outcome at 2u2003years in infants with posthaemorrhagic ventricular dilatation. Preterm infants with posthaemorrhagic ventricular dilatation have high risk of disabilities, but the range is wide and predicting severity of motor and mental disability is difficult.

Neonatal neuroimaging: Going beyond the pictures

The cerebral ultrasound has been used many years for the diagnosis of brain lesions in term and preterm newborns. Major improvements were obtained by the combination of different imaging modalities such as Magnetic Resonance Imaging with the Diffusion Weighted Imaging (DWI) and the new quantitative Diffusion Tensor Imaging (DTI). The clinical use of MRI has been validated over some years especially to depict the perinatal asphyxia lesions in term newborns, but its use in order to diagnose the typical diseases of preterm babies is very recent and useful in identifying a marker able to predict neurological outcome. The imaging correlates for motor impairment are well recognized (periventricular white matter cavitations), but no any imaging correlate for cognitive impairment and neurobehavioral disorders. While DWI has been used in term newborns to identify the ischemic areas with restricted diffusion, it may be also used to characterize brain development in preterm infants with the Apparent Diffusion Coefficient (ADC) and may allow us to detect abnormalities responsible for the non-motor impairments. Recent datas showed that in infants without focal lesions higher ADC values in WM were associated with poorer neurodevelopmental assessment at 2 years. The DTI also allows to detect the Fractional Anisotropy (FA) that measures the microstructure. DTI can also be used to map the WM tracts in the immature brain and may be applied to understand the normal development or the response of the brain to injury. Some WM regions in the preterm brain have a lower FA suggesting that widespread WM abnormalities are present in preterms even in the absence of focal lesions. The complexity of the developing brain can be explained by the new tractography that can assess the connectivity of different WM regions and the association between structure and function, such as optic radiations microstructure and visual assessment score. Technological advances in neonatal brain imaging have made a major contribution to understand the neurobehavioral disorders of the developing brain that have the origin in the early structural cerebral organization and maturation.

Low-grade intraventricular hemorrhage: is ultrasound good enough?

Abstract Objective: To assess diagnostic accuracy of cranial ultrasonography (CUS) in detecting low-grade (i.e. grade I and grade II) germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) in very low birth weight (VLBW) infants. Methods: Among VLBW infants who were admitted to Gaslini Children’s Hospital neonatal intensive care unit between January and November 2012, patients who underwent both serial CUS since birth and magnetic resonance susceptibility-weighted imaging (SWI) at term-equivalent age were included in this retrospective study. Diagnostic accuracy of CUS in detecting low-grade GMH-IVH was assessed in terms of sensitivity and specificity by comparing it to SWI, which was used as the gold-standard technique. Results: Sixty VLBW infants were included in the study. Sensitivity of CUS in detecting low-grade GMH-IVH was low (60%), whilst specificity was 100%. Conclusions: In the present study, CUS sensitivity in detecting grade I–II GMH-IVH proved to be surprisingly low, in contrast with specificity. In other words, we suggest that low-grade GMH-IVH may be underdiagnosed in VLBW infants when assessed exclusively with CUS.