Lesions In Preterm Infants Research Articles

Cranial ultrasound in preterm infants ≤ 32 weeks gestation—novel insights from the use of very high-frequency (18-5 MHz) transducers: a case series

The quality of cranial ultrasound has improved over time, with advancing technology leading to higher resolution, faster image processing, digital display, and back-up. However, some brain lesions may remain difficult to characterize: since higher frequencies result in greater spatial resolution, the use of additional transducers may overcome some of these limitations. The very high-frequency transducers (18-5 MHz) are currently employed for small parts and lung ultrasound. Here we report the first case series comparing the very high-frequency probes (18-5 MHz) with standard micro-convex probes (8-5 MHz) for cranial ultrasound in preterm infants. In this case series, we compared cranial ultrasound images obtained with a micro-convex transducer (8-5 MHz) and those obtained with a very high-frequency (18-5 MHz) linear array transducer in 13 preterm infants ≤ 32 weeks gestation (9 with cerebral abnormalities and 4 with normal findings). Ultrasound examinations using the very high-frequency linear transducer and the standard medium-frequency micro-convex transducer were performed simultaneously. We also compared ultrasound findings with brain MRI images obtained at term corrected age. Ultrasound images obtained with the very high-frequency (18-5 MHz) transducer showed high quality and accuracy. Notably, despite their higher frequency and expected limited penetration capacity, brain size is small enough in preterm infants, so that brain structures are close to the transducer, allowing for complete evaluation. Conclusion: We propose the routine use of very high-frequency linear probes as a complementary scanning modality for cranial ultrasound in preterm infants ≤ 32 weeks gestation.What is Known:• Brain lesions in preterm infants may remain insufficiently defined through conventional cranial ultrasound scan.• Higher frequency probes offer better spatial resolution but have a narrower filed of exploration and limited penetration capacity.What is New:• Very high-frequency probes were compared with standard medium-frequency probes for cranial ultrasound in infants ≤ 32 weeks' gestation.• Thanks to the smaller skull size of preterm infants, the new very high-frequency transducers allowed a complete and accurate evaluation.

On punctate white matter lesions in preterm infants: Is ultrasound diagnosis feasible?

ObjectivesTo observe hyperechoic nodular or punctate white matter lesions (HNPL) in a population of preterm infants using routine cranial ultrasound (cUS), to describe the characteristics of HNPL, and to compare them with punctate white matter lesions (PWML) detected in magnetic resonance imaging (MRI). DesignRetrospective observational single-center cohort study. SettingLevel 2B neonatal unit in France. Patients307 infants born <33 weeks gestation undergoing routine cUS with a total of 961 cUS performed. Main outcome measuresDescription of lesions (HNPL/PWML): presence or absence, number, size, location, and structural distribution. ResultsAmong the 307 included infants, 63 (20.5%) had at least one cerebral lesion, with 453 HNPL for 63 infants. HNPL were numerous (more than three in 66.6% of cases), primarily grouped in clusters (76.2%), located near the lateral ventricles (96.8%), and measuring more than 2 mm (79%). HNPL were diagnosed on day 29 on average and persisted until term. Overall, 43 MRI were performed in 307 infants, on average 18.9 days after last cUS, in 21 of those the indication was presence of HPNL on cUS. Of these 21 MRI, 14/21 presented 118 PWML compared to 173 HNPL on cUS. In the remaining MRI (7/21), no PWML were detected compared to 47 HNPL on cUS. ConclusionsIn our population of 307 preterm infants, cUS allowed the diagnosis of HNPL, with a large similarity to PWML in MRI and a better sensitivity. But in the absence of data on inter-observer variability, we cannot exclude overdiagnosis of HNPL.

Imaging Deep Haemorrhage and Ischaemia in Preterm Infants' Heads with Time-Domain Near-Infrared Optical Tomography: Phantom Study.

The occurrence of brain lesions in preterm infants is common and can result in lasting disabilities. To prevent these and to safeguard the brain through therapeutic measures or neuroprotective treatments, it is important to identify cerebral ischaemia/hypoxia and haemorrhage at an early stage. For this purpose, we have successfully developed a cutting-edge time-domain near-infrared optical tomography (TD-NIROT) system, which offers diagnostic imaging for neonatal brain oxygenation. Our objective is to validate the effectiveness of the TD-NIROT in detecting deep ischaemia/hypoxia and haemorrhages through phantom experiments. Spherical silicone phantoms were fabricated to replicate the head of preterm infant. To simulate the lesions, we made two head phantoms and embedded small inclusions mimicking ischaemia and haemorrhage at the depth of 30 mm. Additionally, a spherical interface was constructed to connect the spherical phantom to the imaging system, allowing us to collect time-domain data. Following the data acquisition, we proceeded with image reconstruction. Dice similarity was used as an indicator of the accuracy and similarity between the reconstructed images and the ground truth. The resulting images exhibited an accurate location of haemorrhage and detected the ischaemia with a slightly shifted position with Dice similarity of 0.47 and 0.27. Our experiment validates the capability of our TD-NIROT system in successfully detecting deep haemorrhages and ischaemia within the phantom model. The achieved results suggest a promising level of accuracy in the imaging process. These findings are encouraging to continue this work to ultimately achieve clinical application of the TD-NIROT system in diagnosing and monitoring neonatal brain injuries.

Fetal Zone Steroids Show Discrete Effects on Hyperoxia-Induced Attenuation of Migration in Cultured Oligodendrocyte Progenitor Cells.

Cerebral oxygenation disturbances contribute to the pathogenesis of brain lesions in preterm infants with white matter damage. These children are at risk of developing long-term neurodevelopmental disabilities. Preterm birth is associated with sudden hormonal changes along with an untimely increase in oxygen tissue tension. There is a persistent high postnatal production of fetal zone steroids (FZS), which serve in the fetoplacental unit as precursors for placental estrogen synthesis during pregnancy. The role of FZS in events associated with oxygenation differences and their impact on the developing white matter is not well understood. Therefore, we investigated the effect of hyperoxia (80% O2) and subsequent administration of FZS on the protein composition and migration capabilities of immature oligodendrocytes using the OLN93 (rat-derived OPC) cell line as an experimental model. We tested the effect of the FZS, dehydroepiandrosterone (DHEA), 16α-OH-DHEA, and adiol (5-androstene-3β, 17β-diol). After 24-hour exposure to hyperoxia, we monitored the changes in the proteome profile following treatment and observed significant alterations in pathways regulating cytoskeletal remodelling, cell migration, and cell survival. Additionally, hyperoxia leads to impaired migration of the OLN93 cells in culture. Administration of the FZS showed positive effects on the migration process under normoxic conditions in general. However, under hyperoxic conditions, the trend was less prominent. The observed effects could be related to changes in levels of cofilin/LIMK pathway-associated proteins. Adiol had a negative effect when administered together with estradiol, and the proteomic data reveal the activation of ephrin receptor signalling that might be responsible for the attenuation of migration. The results suggest that FZS can differentially regulate pathways involved in the migration of OLN93 cells. A deeper insight into the precise role of endogenous FZS would be an essential prerequisite for developing new treatment strategies including supplementation of estradiol and other steroids in preterm infants.

Nosological Differences in the Nature of Punctate White Matter Lesions in Preterm Infants.

Background: The pathogenesis of punctuate white matter lesions (PWMLs), a mild form of white matter damage observed in preterm infants, is still a matter of debate. Susceptibility-weighted imaging (SWI) allows to differentiate PWMLs based on the presence (SWI+) or absence (SWI–) of hemosiderin, but little is known about the significance of this distinction. This retrospective study aimed to compare neuroradiological and clinical characteristics of SWI+ and SWI– PWMLs.Materials and Methods: MR images of all VLBW infants scanned consecutively at term-equivalent age between April 2012 and May 2018 were retrospectively reviewed, and infants with PWMLs defined as small areas of high T1 and/or low T2 signal in the periventricular white matter were selected and included in the study. Each lesion was analyzed separately and characterized by localization, organization pattern, and distance from the lateral ventricle. Clinical data were retrieved from the department database.Results: A total of 517 PWMLs were registered in 81 patients, with 93 lesions (18%) visible on SWI (SWI+), revealing the presence of hemosiderin deposits. On univariate analysis, compared to SWI- PWML, SWI+ lesions were closer to the ventricle wall, more frequently organized in linear pattern and associated with lower birth weight, lower gestational age, lower admission temperature, need for intubation, bronchopulmonary dysplasia, retinopathy of prematurity, and presence of GMH-IVH. On multivariate analysis, closer distance to the ventricle wall on axial scan and lower birth weight were associated with visibility of PMWLs on SWI (p = 0.003 and p = 0.0001, respectively).Conclusions: Our results suggest a nosological difference between SWI+ and SWI– PWMLs. Other prospective studies are warranted to corroborate these observations.

Development and Validation of a Sensor Prototype for Near-Infrared Imaging of the Newborn Brain.

Imaging brain oxygenation is crucial for preventing brain lesions in preterm infants. Our aim is to build and validate a near-infrared optical tomography (NIROT) sensor for the head of neonates. This sensor, combined with an optoacoustic device, will enable quantitative monitoring of the structural and functional information of the brain. Since the head of preterm infants is small and fragile great care must be taken to produce a comfortable and compact device in which a sufficient number of light sources and detectors can be implemented. Here we demonstrate our first prototype. Heterogeneous silicone phantoms were produced to validate the prototype's data acquisition, data processing, and image reconstruction. Reconstructed optical properties agree well with the target values. The mechanical performance of the new NIROT sensor prototype confirms its suitability for the clinical application.

Secondary expansion of the transient subplate zone in the developing cerebrum of human and nonhuman primates

The subplate (SP) was the last cellular compartment added to the Boulder Committee's list of transient embryonic zones [Bystron I, Blakemore C, Rakic P (2008) Nature Rev Neurosci 9(2):110-122]. It is highly developed in human and nonhuman primates, but its origin, mode, and dynamics of development, resolution, and eventual extinction are not well understood because human postmortem tissue offers only static descriptive data, and mice cannot serve as an adequate experimental model for the distinct regional differences in primates. Here, we take advantage of the large and slowly developing SP in macaque monkey to examine the origin, settling pattern, and subsequent dispersion of the SP neurons in primates. Monkey embryos exposed to the radioactive DNA replication marker tritiated thymidine ([(3)H]dT, or TdR) at early embryonic ages were killed at different intervals postinjection to follow postmitotic cells' positional changes. As expected in primates, most SP neurons generated in the ventricular zone initially migrate radially, together with prospective layer 6 neurons. Surprisingly, mostly during midgestation, SP cells become secondarily displaced and widespread into the expanding SP zone, which becomes particularly wide subjacent to the association cortical areas and underneath the summit of its folia. We found that invasion of monoamine, basal forebrain, thalamocortical, and corticocortical axons is mainly responsible for this region-dependent passive dispersion of the SP cells. Histologic and immunohistochemical comparison with the human SP at corresponding fetal ages indicates that the same developmental events occur in both primate species.

Altered Glutamatergic Metabolism Associated with Punctate White Matter Lesions in Preterm Infants

Preterm infants (∼10% of all births) are at high-risk for long-term neurodevelopmental disabilities, most often resulting from white matter injury sustained during the neonatal period. Glutamate excitotoxicity is hypothesized to be a key mechanism in the pathogenesis of white matter injury; however, there has been no in vivo demonstration of glutamate excitotoxicity in preterm infants. Using magnetic resonance spectroscopy (MRS), we tested the hypothesis that glutamate and glutamine, i.e., markers of glutamatergic metabolism, are altered in association with punctate white matter lesions and “diffuse excessive high signal intensity” (DEHSI), the predominant patterns of preterm white matter injury. We reviewed all clinically-indicated MRS studies conducted on preterm infants at a single institution during a six-year period and determined the absolute concentration of glutamate, glutamine, and four other key metabolites in the parietal white matter in 108 of those infants after two investigators independently evaluated the studies for punctate white matter lesions and DEHSI. Punctate white matter lesions were associated with a 29% increase in glutamine concentration (p = 0.002). In contrast, there were no differences in glutamatergic metabolism in association with DEHSI. Severe DEHSI, however, was associated with increased lactate concentration (p = 0.001), a marker of tissue acidosis. Findings from this study support glutamate excitotoxicity in the pathogenesis of punctate white matter lesions, but not necessarily in DEHSI, and suggest that MRS provides a useful biomarker for determining the pathogenesis of white matter injury in preterm infants during a period when neuroprotective agents may be especially effective.

Brain lesions in preterm infants: initial diagnosis and follow-up

Children surviving premature birth present with a wide spectrum of motor, sensory and cognitive disabilities, ranging from slight motor deficits, school difficulties and behavioural problems to cerebral palsy and mental retardation. The anatomic and functional substrate of these problems can be investigated using a variety of imaging techniques. Cranial US coupled with colour Doppler is a well-established method for the initial diagnosis of intraventricular haemorrhage, parenchymal haemorrhagic infarct and periventricular leukomalacia. MRI is useful for the follow-up study of brain maturation. Conventional T1- and T2-weighted sequences, magnetization transfer and diffusion tensor imaging coupled with sophisticated tools of tissue segmentation and analysis at a voxel level offer substantial anatomic and functional information on pathological conditions that define the prognosis of preterm infants.

Injury to the Developing Cerebellum

Advances in neuroimaging techniques for the in vivo study of brain development have expanded the understanding of normal and abnormal cerebellar development in the high-risk fetus and newborn. This, in turn, has provided new insights into the spectrum of structural and functional consequences of injury to the developing cerebellum. Specifically, hemorrhagic cerebellar lesions in preterm infants are associated with significant impairment of subsequent cerebellar growth as well as impaired growth of the contralateral cerebral hemisphere. Furthermore, preterm extrauterine life appears to inhibit cerebellar growth, even in the absence of obvious primary injury. Recent long-term outcome studies in preterm infants who had cerebellar injury suggest a distinct profile of pervasive neurodevelopmental deficits, with a high prevalence of cognitive-behavioral dysfunction. The structure-function relationships between early cerebellar injury and long-term outcome are a fertile area for future research.

Cerebral oxygenation and cerebral oxygen extraction in the preterm infant: the impact of respiratory distress syndrome

Haemodynamic factors play an important role in the etiology of cerebral lesions in preterm infants. Respiratory distress syndrome (RDS), a common problem in preterms, is strongly related with low and fluctuating arterial blood pressure. This study investigated the relation between mean arterial blood pressure (MABP), fractional cerebral oxygen saturation (ScO2) and fractional (cerebral) tissue oxygen extraction (FTOE), a measure of oxygen utilisation of the brain, during the first 72 h of life. Thirty-eight infants (gestational age < 32 week) were included, 18 with and 20 without RDS. Arterial oxygen saturation (SaO2), MABP and near infrared spectroscopy-determined ScO2 were continuously measured. FTOE was calculated as a ratio: (SaO2-ScO2)/SaO2. Gestational age and birth weight did not differ between groups, but assisted ventilation and use of inotropic drugs were more common in RDS infants (P<0.01). MABP was lower in RDS patients (P<0.05 from 12 up to 36 h after birth), but increased in both groups over time. ScO2 and FTOE were not different between groups over time, but in RDS infants ScO2 and FTOE had substantial larger variance (P<0.05 at all time points except at 36-48 h for ScO2 and P<0.05 at 12-18, 18-24, 36-48 and 48-60 h for FTOE). During the first 72 h of life, RDS infants showed more periods of positive correlation between MABP and ScO2 (P<0.05 at 18-24, 24-36 36-48 48-60 h) and negative correlation between MABP and FTOE (P<0.05 at 18-24, 36-48 h). Although we found that the patterns of cerebral oxygenation and extraction in RDS infants were not different as compared to infants without RDS, we suggest that the frequent periods with possible lack of cerebral autoregulation in RDS infants may make these infants more vulnerable to cerebral damage.

Localized persistent pulmonary interstitial emphysema in a preterm infant in the absence of mechanical ventilation

Localized persistent pulmonary interstitial emphysema has rarely been reported in preterm infants in the absence of utilization of mechanical ventilation or continuous positive airway pressure. The relative rarity of this condition might preclude rendering of the correct diagnosis, making patients susceptible to unnecessary surgery and increased morbidity and mortality associated with such intervention. We present a preterm infant who developed respiratory distress and radiographic findings of pulmonary interstitial emphysema on the first day after birth, prior to receiving continuous positive airway pressure or mechanical ventilation. It is important for radiologists to consider localized persistent pulmonary interstitial emphysema in the differential diagnosis of cystic lung lesions in preterm infants, even in the absence of mechanical ventilation. In cases where there is uncertainty, CT imaging can be useful in making the correct diagnosis.

The role of spontaneous general movement assessment in the neurological outcome of cerebral lesions in preterm infants

The role of spontaneous general movement assessment in the neurological outcome of cerebral lesions in preterm infants

The role of spontaneous general movement assessment in the neurological outcome of cerebral lesions in preterm infants

To study the relationship among the quality, type, and trajectory of general movements in preterm infants and neonatal cranial ultrasonography findings and neurological outcome. Forty preterm newborn infants, with gestational ages under 35 weeks, had their general movements recorded through video-tape during the preterm, term (37th - 42nd postconceptional weeks of age) and post-term (49th - 56th postconceptional weeks of age) periods, and were prospectively followed up to one-year conceptional age. Our results showed that the quality of general movements, particularly in the post-term period (p = 0.009), were related with the presence of severe cerebral lesions in the neonatal cranial ultrasonography and the neurological outcome. While the presence of severe ultrasonography lesions was associated with an adverse neurological outcome (p = 0.01), the finding of normal general movements patterns was associated with a normal neurological outcome, with negative predictive values of 100%, for the preterm, and 80%, for both term and post-term periods. When concurrently used, these evaluation methods may increase the specificity and sensitivity in detecting the group of preterm infants at high risk for neurological disturbances in long-term follow-up.

Management of the Umbilical Cord

After completing this article, readers should be able to: 1. Describe the most serious infection that may result from inappropriate management of the umbilical cord and potential sources. 2. Describe the relationship between infant bacterial colonization and postpartum infection. 3. List the most common neonatal staphylococcal infections. 4. List the factors that affect the timing of cord separation. 5. Delineate the probable causes of drainage from the umbilical stump. This review addresses several aspects of the care of the umbilical cord: how to ligate and cut it, what (if anything) to apply to it, the problems that may be associated with ligation and cutting, and the natural history of cord separation. The traditional method of ligating the umbilical cord was to use string or twine to tie the cord before cutting it. In Southern Sudan, fine stringlike roots are used to tie the cord. More recently in the United States, special cotton tape (umbilical tape) was used and still is found on most trays used for insertion of catheters into umbilical blood vessels. Because the umbilical cord tends to shrink after birth, these types of ligature proved somewhat unreliable in preventing hemorrhage. Although the umbilical arteries tend to constrict rapidly after birth because of the muscular walls, this does not occur with the umbilical vein. Consequently, more efficient and effective methods of ligation were sought in the middle of the 20th century. The first method was to use constricting rubber bands, which were effective, but somewhat difficult to apply. This method recently found favor in a developing country (Ethiopia). However, the more usual method in developed countries currently is plastic or metal clamps, which produce safe, reliable constriction. In particular, the plastic Hollister® clamp (Double-Grip Umbilical Cord Clamp, Hollister, Libertyville, IL) has been very successful in preventing bleeding from the cord. These devices are removed …

Caffeine does not affect excitotoxic brain lesions in newborn mice

Caffeine is frequently administered to human pre-term newborns although its neurological impact has not been fully evaluated. In the present study performed in mice, we examined the effects of caffeine administration on neonatal excitotoxic lesions of the periventricular white matter, which mimics several aspects of human periventricular leukomalacia. In this model, caffeine exposure did not worsen white matter lesions. These data suggest that neonatal caffeine administration might not affect clastic lesions in pre-term infants.

Gastroesophageal Endoscopic Findings and Gastrointestinal Symptoms in Preterm Neonates With and Without Perinatal Indomethacin Exposure

ABSTRACTBackgroundThe aim of this study was to investigate whether perinatal indomethacin treatment has effects on the development of esophageal and gastric lesions in preterm infants and to evaluate other potential etiologic factors behind these lesions.MethodsSixty‐nine infants were born at less than 33 weeks' gestation. Forty‐five of these infants underwent treatment with perinatal indomethacin (study group) and 24 did not (control group). All underwent upper gastrointestinal tract endoscopy and biopsy during the neonatal period. The correlation between gastrointestinal symptoms, abnormal endoscopic findings, and the factors correlating with the development of esophageal and gastric mucosal lesions was evaluated.ResultsAbnormal endoscopic findings were equally common in the study group (77.8%) and in controls (83.3%). There was no dependence between gastrointestinal symptoms and endoscopic findings because only 15 infants (21.7%) were symptomatic before endoscopy. The interval between endoscopy and the last perinatal indomethacin dose correlated significantly with abnormal esophageal findings and gastric mucosal lesions. Shorter duration of enteral feeding before endoscopy correlated with greater risk of abnormal esophageal findings. Older gestational age and need of ventilator treatment at the time of endoscopy remained the risk factors associated with abnormal gastric findings.ConclusionsEsophageal and gastric lesions diagnosed by endoscopy correlate poorly with the gastrointestinal symptoms of patients. Short duration of enteral feeding seems to be correlated with an increased risk of esophageal mucosal lesions, increasing gestational age and ventilator treatment with gastric mucosal lesions, and perinatal indomethacin with esophageal and gastric mucosal lesions in preterm infants. Ventilator‐treated preterm infants not receiving enteral nutrition and patients with indomethacin exposure might benefit from ulcer prophylaxis.

Gastroesophageal endoscopic findings and gastrointestinal symptoms in preterm neonates with and without perinatal indomethacin exposure.

The aim of this study was to investigate whether perinatal indomethacin treatment has effects on the development of esophageal and gastric lesions in preterm infants and to evaluate other potential etiologic factors behind these lesions. Sixty-nine infants were born at less than 33 weeks' gestation. Forty-five of these infants underwent treatment with perinatal indomethacin (study group) and 24 did not (control group). All underwent upper gastrointestinal tract endoscopy and biopsy during the neonatal period. The correlation between gastrointestinal symptoms, abnormal endoscopic findings, and the factors correlating with the development of esophageal and gastric mucosal lesions was evaluated. Abnormal endoscopic findings were equally common in the study group (77.8%) and in controls (83.3%). There was no dependence between gastrointestinal symptoms and endoscopic findings because only 15 infants (21.7%) were symptomatic before endoscopy. The interval between endoscopy and the last perinatal indomethacin dose correlated significantly with abnormal esophageal findings and gastric mucosal lesions. Shorter duration of enteral feeding before endoscopy correlated with greater risk of abnormal esophageal findings. Older gestational age and need of ventilator treatment at the time of endoscopy remained the risk factors associated with abnormal gastric findings. Esophageal and gastric lesions diagnosed by endoscopy correlate poorly with the gastrointestinal symptoms of patients. Short duration of enteral feeding seems to be correlated with an increased risk of esophageal mucosal lesions, increasing gestational age and ventilator treatment with gastric mucosal lesions, and perinatal indomethacin with esophageal and gastric mucosal lesions in preterm infants. Ventilator-treated preterm infants not receiving enteral nutrition and patients with indomethacin exposure might benefit from ulcer prophylaxis.

Unilateral thalamic lesions in premature infants: risk factors and short-term prognosis.

The aim of the study was to assess incidence, risk factors, clinical symptomatology and short-term outcome of unilateral thalamic lesions in preterm infants, as detected by ultrasound. Sixteen preterm infants, born after a gestational age of less than 35 weeks, with a unilateral thalamic lesion, but without additional significant cerebral lesions, were included. Their follow-up data were compared to those of a selected control group consisting of healthy premature infants. In addition, the neonatal clinical data of the patients with a thalamic lesion were compared to data of the healthy control group and of a general control group, consisting of a non-selected year-cohort of preterm infants. During the study period, the incidence of unilateral thalamic lesions was 5.3% among preterm infants. Ultrasound was not able to distinguish between hemorrhagic and ischemic lesions. The infants with a unilateral thalamic lesion had a more complicated respiratory course and were ventilated significantly longer than infants without such a lesion. The infants with a thalamic lesion had disturbances in tone, persisting throughout infancy, while the healthy control group showed only transient disturbances in tone.

Antenatal onset of haemorrhagic and/or ischaemic lesions in preterm infants: prevalence and associated obstetric variables

AIMTo assess the prevalence of an antenatal onset of haemorrhagic and/or ischaemic lesions in preterm infants; to identify possibly related obstetric risk factors.METHODSA prospective cohort study was made of 1332...