Search

Cerebellar injury is increasingly recognized through advanced neonatal brain imaging as a complication of premature birth. Survivors of preterm birth demonstrate a constellation of long-term neurodevelopmental deficits, many of which are potentially refera

Aims: The pharmacokinetics (PK) of fluconazole and micafungin differ in neonates compared with children and adults. Dosing instructions in product labels appear to be inconsistent with the emerging scientific evidence. Limited information is available on the safety profile of these agents in neonates. Our objective was to study the population PK and safety of both drugs, randomly administered in neonates with suspected or confirmed systemic candidiasis. Methods: Neonates were randomized 1:1 to fluconazole (loading dose 25 mg kg–1; maintenance dose 12 mg kg–1 day–1 or 20 mg kg–1 day–1, respectively, for infants <30 weeks or ≥30 weeks’ corrected gestational age) or micafungin (loading dose 15 mg kg–1 day–1; maintenance dose 10 mg kg–1 day–1). PK samples were taken on treatment days 1 and 5. Population parameters were determined using NONMEM and Monte Carlo simulations performed to reach predefined targets. Clinical and laboratory data, and adverse events were collected up to 36 weeks’ corrected gestational age or hospital discharge. Results: Thirty‐six neonates were enrolled. The median (range) gestational age was 28.2 (24.1–40.1) and 26.8 (23.5–40.0) weeks for fluconazole and micafungin, respectively. Based on 163 PK samples, the median population clearance (l h–1 kg–1) and volume of distribution (l kg–1) for fluconazole were: 0.015 [95% confidence interval (CI) 0.008, 0.039] and 0.913, and for micafungin were: 0.020 (95% CI 0.010, 0.023) and 0.354 (95% CI 0.225, 0.482), respectively. The loading dose was well tolerated. No adverse events associated with micafungin or fluconazole were reported. Conclusion: Based on Monte Carlo simulations, a loading dose for fluconazole and dosing higher than recommended for both drugs are required to increase the area under the plasma drug concentration–time curve target attainment rate in neonates. [ABSTRACT FROM AUTHOR]

ABSTRACT: Objective: Diffusion‐weighted magnetic resonance imaging (DWI) is a sensitive method for assessing brain maturation and detecting brain lesions, providing apparent diffusion coefficient (ADC) values as a measure of water diffusion. Abnormal ADC values are seen in ischemic brain lesions, such as those associated with acute or chronic hypoxia. The aim of this study was to assess whether ADC values in the fetal brain were different in fetuses with severe intrauterine growth restriction (IUGR) compared with normal controls. Methods: Brain magnetic resonance imaging (MRI) with single‐shot axial DWI (b = 0 and b = 700 s/mm2) was performed in 30 fetuses with severe IUGR (estimated fetal weight < 3rd centile with absent or reversed umbilical artery Doppler flow) and in 24 normal controls of similar gestational age. Brain morphology and biometry were analyzed. ADC values were measured in frontal and occipital white matter, centrum semiovale, thalami, cerebellar hemisphere and pons. Frontal–occipital and frontal–cerebellar ADC ratios were calculated, and values were compared between IUGR fetuses and controls. Results: There was no difference in gestational age at MRI between IUGR and control fetuses (IUGR, 30.2 ± 1.6 weeks vs controls, 30.7 ± 1.4 weeks). Fetal brain morphology and signals were normal in all fetuses. Brain dimensions (supratentorial ± infratentorial) were decreased (Z‐score, < –2) in 20 (66.7%) IUGR fetuses. Compared with controls, IUGR fetuses had significantly lower ADC values in frontal white matter (1.97 ± 0.23 vs 2.17 ± 0.22 × 10–3 mm2/s; P < 0.0001), thalami (1.04 ± 0.15 vs 1.13 ± 0.10 ×10–3 mm2/s; P = 0.0002), centrum semiovale (1.86 ± 0.22 vs 1.97 ± 0.23 ×10–3 mm2/s; P = 0.01) and pons (0.85 ± 0.19 vs 0.94 ± 0.12 ×10–3 mm2/s; P = 0.043). IUGR fetuses had a lower frontal–occipital ADC ratio than did normal fetuses (1.00 ± 0.11 vs 1.08 ± 0.05; P = 0.003). Conclusions: ADC values in IUGR fetuses were significantly lower than in normal controls in the frontal white matter, thalami, centrum semiovale and pons, suggesting abnormal maturation in these regions. However, the prognostic value of these ADC changes is still unknown. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Summary: Traditionally, the cerebellum has been regarded as a central component of the motor system. Recent studies suggest an important role played by the cerebellum in the development of cognitive and social functions. The objective of this study was to evaluate the incidence of cerebellar injury and to define the obstetrical, neonatal, and radiologic characteristics, as well as the functional outcomes in a population of very preterm infants. Methods: This retrospective study included neonates born before 30 weeks of gestational age between March 2004 and July 2007. Infants underwent MRI studies at a term-adjusted age; for each preterm infant with cerebellar injury, we identified two infants for the control group with normal MRI, matched on the basis of gestational age. We collected pertinent demographic, prenatal, and acute postnatal data for all infants. Follow-up assessment was performed at 2 years, using the Brunet-Lezine scale. Results: A total of 148 ex-preterm infants were studied. Cerebellar injury was present in 14 (9 %) cases and associated with supratentorial parenchymal injury in 90 %. Duration of ventilation was longer in children with cerebellar injury, compared to controls (19.5 days vs 16.5 days; P =0.03). The other neonatal criteria analyzed were comparable between the two groups. Global developmental, functional, and social-behavioral deficits were more common and profound in preterm infants with cerebellar injury, with no significant difference. Conclusion: This study confirms the high incidence of cerebellar injury in very preterm infants and the importance of a specific neurobehavioral follow-up. [Copyright &y& Elsevier]

Objective: Neonatal stroke is associated with the N-methyl-D-aspartate receptor (NMDAR)-mediated excitotoxic brain injury. Src family kinases (SFKs) are considered to be the molecular hub for NMDAR regulation. We determined the relationship between SFKs activation and NMDAR tyrosine phosphorylation after neonatal hypoxia-ischemia (HI) and investigated the neuroprotective potential of a selective SFKs inhibitor, PP2 (4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo [3, 4-d] pyramidine), against neonatal brain ischemic injury.Methods: The Rice-Vannucci model was adapted for neonatal HI injury in postnatal day 7 CD1 mice. SFKs activity in the postsynaptic densities was measured by Western blot. NMDAR tyrosine phosphorylation and their association with SFKs were determined by coimmunoprecipitation. Brains from animals treated with PP2 or its inactive analog, PP3, were examined histologically with cresyl violet and iron stain to assess the degree of damage.Results: Neonatal HI resulted in a rapid and transient increase in tyrosine phosphorylation of NMDAR subunits NR2A and NR2B. This upregulation correlated with the enhanced association of Fyn and Src with NR2A and NR2B. SFKs were activated in the postsynaptic densities after HI. Inhibition of SFKs with PP2 attenuated brain injury after neonatal HI, whereas PP3 did not protect the brain from the HI insult.Interpretation: SFKs may play an important role in NMDAR-mediated excitotoxicity and downstream events leading to neuronal death after neonatal HI. Inhibition of SFKs may provide protection against neonatal stroke. Rather than blockade of NMDAR after HI in the developing brain, it may be safer and more beneficial to manipulate components of the NMDAR signaling complex at the postsynaptic density. [ABSTRACT FROM AUTHOR]

Summary: Aims: The objective of this study was to determine the incidence of extended-spectrum beta-lactamase (ESBLS) enterobacteriaceae colonization and infection in hospitalized children. Methods: This prospective study was conducted in a neonatal intensive care unit from 2000 to 2009. We recorded all isolations of ESBLs enterobacteriaceae from clinical samples that were obtained from hospitalized children. Anorectal samples were taken at admission and every 10 days. We systematically recorded cases of confirmed infections that was caused by ESBLs enterobacteriacea. Results: A total of 46 ESBLS pathogens (E coli 58.7 %, Enterobacter cloacae 10.8 %, Klebsiella Pneumonia 19.5%, K. oxytoca 6.5 %, Citrobacter 4.5 %) were isolated during 10 years, the global incidence was 5.1 cases per 1000 admissions. Three infants developed nosocomial infections, E. coli sepsis and pneumonia and Enterobacter cloacae omphalitis. These patients were treated with carbapenem with significant clinical improvement. ESBLs enterobacteriaceae were found first in Klebsiella pneumonia and then predominantly in E. coli. Current efforts have focused on monitoring proper hand hygiene, evaluation of potential reservoirs of bacterial acquisition and transmission, cohorting and isolation of colonized infants, and fostering of effective inter- and intrahospital communication. Carbapenem seems to be safe in newborn and is recommended for the treatment of EBLSEs enterobacteriaceae infections. [Copyright &y& Elsevier]

Résumé La prescription néonatale des antibiotiques pose le problème d’une grande variabilité de pratiques tant au niveau national qu’international. Ceci reflète un manque d’évaluation de cette classe thérapeutique, pourtant largement utilisée. Face à ce constat, un travail d’optimisation de la prescription s’impose pour assurer chez le nouveau-né l’efficacité et la sécurité du traitement et pour diminuer les risques d’acquisition de résistances microbiennes. La prescription doit être sous-tendue par la connaissance des données de pharmacocinétique/pharmacodynamie du développement. Les études rigoureuses, conduites en collaboration entre néonatologues et pharmacologues pédiatres, sont indispensables pour disposer de schémas posologiques validés en néonatologie. Summary There is wide variation in neonatal dosages of antibiotics in clinical practice, both nationally and internationally. This reflects the lack of evaluation of drugs in this therapeutic class, although widely prescribed. Given this situation, optimization of antibiotic prescription is required to ensure efficacy and safety of neonatal treatment and reduce microbial resistance. Rational prescription should be based on the knowledge of developmental pharmacokinetics and pharmacodynamics. Rigorous studies, conducted in collaboration between neonatologists and pharmacologists, are essential to develop and validate evidence-based neonatal dosage regimens. [ABSTRACT FROM AUTHOR]

Résumé L’accident vasculaire cérébral ischémique artériel néonatal (AVCian) est une pathologie rare. Afin d’actualiser les connaissances sur ce sujet, un groupe de travail multidisciplinaire s’est constitué sous l’égide de la Société française de néonatologie et le Centre national de référence de l’AVC de l’enfant afin de proposer des recommandations sur les facteurs de risque, les modalités de transfert et de prise en charge pré-hospitalière, les modalités diagnostiques et thérapeutiques, le traitement, le pronostic et la prise en charge à court et moyen terme. Ces recommandations ont été réalisées selon la méthodologie de la Haute autorité de santé et en fonctions des thématiques proposées par un comité d’experts. Les principales recommandations issues de ce travail sont : (1) l’orientation du patient vers une unité de réanimation ou de soins intensifs néonatals disposant d’une imagerie par résonance magnétique (IRM) facilement accessible et de la possibilité de réaliser une surveillance continue par électro-encéphalogramme ; (2) le phénobarbital est le médicament de première ligne pour le traitement des crises convulsives ; (3) l’IRM réalisée entre j2 et j4 après la survenue de l’AVCian est la meilleure technique pour confirmer le diagnostic et préciser son extension ; (4) un facteur biologique de risque thrombotique ne doit pas être systématiquement recherché après un AVCian, sauf en cas d’antécédent thrombotique veineux familial ; (5) un traitement thrombolytique n’est pas recommandé ; (6) une prise en charge rééducative précoce est recommandée en cas de déficience motrice évidente. Summary Neonatal arterial ischemic stroke (NAIS) is a rare event that occurs in approximately one in 5000 term or close-to-term infants. Most affected infants will present with seizures. Although a well-recognized clinical entity, many questions remain regarding diagnosis, risk factors, treatment, and follow-up modalities. In the absence of a known pathophysiological mechanism and lack of evidence-based guidelines, only supportive care is currently provided. To address these issues, a French national committee set up by the French Neonatal Society (Société française de néonatologie) and the national referral center (Centre national de référence) for arterial ischemic stroke in children drew up guidelines based on an HAS (Haute Autorité de santé [HAS]; French national authority for health) methodology. The main findings and recommendations established by the study group are: (1) among the risk factors, male sex, primiparity, caesarean section, perinatal hypoxia, and fetal/neonatal infection (mainly bacterial meningitis) seem to be the most frequent. As for guidelines, the study group recommends the following: (1) the transfer of neonates with suspected NAIS to a neonatal intensive care unit with available equipment to establish a reliable diagnosis with MRI imaging and neurophysiological monitoring, preferably by continuous video EEG; (2) acute treatment of suspected infection or other life-threatening processes should be addressed immediately by the primary medical team. Persistent seizures should be treated with a loading dose of phenobarbital 20 mg/kg i.v.; (3) MRI of the brain is considered optimal for the diagnosis of NAIS. Diffusion-weighted imaging with apparent diffusion coefficient is considered the most sensitive measure for identifying infarct in the neonatal brain. The location and extent of the lesions are best assessed between 2 and 4 days after the onset of stroke; (4) routine testing for thrombophilia (AT, PC PS deficiency, FV Leiden or FII20210A) or for detecting other biological risk factors such as antiphospholipid antibodies, high FVIII, homocysteinemia, the Lp(a) test, the MTHFR thermolabile variant should not be considered in neonates with NAIS. Testing for FV Leiden can be performed only in case of a documented family history of venous thromboembolic disease. Testing neonates for the presence of antiphospholipid antibodies should be considered only in case of clinical events arguing in favor of antiphospholipid syndrome in the mother; (5) unlike childhood arterial ischemic stroke, NAIS has a low 5-year recurrence rate (approximately 1 %), except in those children with congenital heart disease or multiple genetic thrombophilia. Therefore, initiation of anticoagulation or antithrombotic agents, including heparin products, is not recommended in the newborn without identifiable risk factors; (6) the study group recommends that in case of delayed motor milestones or early handedness, multidisciplinary rehabilitation is recommended as early as possible. Newborns should have physical therapy evaluation and ongoing outpatient follow-up. Given the risk of later-onset cognitive, language, and behavioral disabilities, neuropsychological testing in preschool and at school age is highly recommended. [ABSTRACT FROM AUTHOR]

Résumé L’incidence du diabète au cours de la grossesse est en constante augmentation ces dernières années. La détresse respiratoire néonatale est une des complications reconnue du diabète gestationnel, sans que le lien entre les deux n’ait été clairement établi. L’objectif de cette étude était de confirmer l’existence d’une relation entre diabète maternel et détresse respiratoire néonatale sévère et de préciser l’influence des différents types de diabète et de leur traitement sur la survenue de la détresse respiratoire néonatale. Nous avons donc étudié, dans une large cohorte rétrospective, le devenir respiratoire de nouveau-nés singletons de plus de 34 semaines d’aménorrhée (SA), nés à l’hôpital Robert-Debré (Paris, France) entre le 1 er janvier 2007 et le 31 décembre 2013, en fonction du statut maternel : non diabétique (groupe Non-D), diabète gestationnel traité par régime (groupe DTR) et diabète traité par insuline (groupe DTI). Parmi 18 095 nouveau-nés, 412 (2,3 %) ont été admis en unité de soins intensifs néonatals (USI) pour détresse respiratoire dans les premières heures de vie. La prévalence d’admission en fonction du statut maternel avait été de 2,2 % dans le groupe Non-D, 2,1 % dans le groupe DTR, et 5,7 % dans groupe DTI. Un diabète maternel traité par insuline, ainsi que d’autres facteurs périnatals étaient associés à un risque significativement plus important de détresse respiratoire sévère. En analyse multivariée, les nouveau-nés de mère diabétique traitée par insuline avaient un risque de détresse respiratoire sévère accru et indépendant de l’âge gestationnel et de la naissance par césarienne ( incidence rate ratio [IRR] = 1,44 [1,00–2,08]), ce qui n’a pas été observé pour les nouveau-nés de mère diabétique traitée par régime. En conclusion, si les nouveau-nés de mère diabétique traitée par régime ne sont pas plus à risque de détresse respiratoire, ceux dont les mères sont traitées par insuline doivent être particulièrement surveillés, en raison d’un risque accru de détresse respiratoire sévère. Summary While the incidence of diabetes mellitus (DM) during pregnancy has been steadily increasing in recent years, the link between gestational DM and respiratory outcome in neonates has not been firmly established. To address this gap in understanding, we asked whether DM status and its treatment during pregnancy influence risk of neonatal respiratory distress. We conducted retrospective analysis of a large cohort to determine the relationship between maternal DM status (non-DM, insulin-treated DM [DTI], and non-insulin-treated DM [DTR]) and respiratory distress in term and near-term singletons, born at Robert-Debré Hospital over a 7-year period. Of 18,095 singletons delivered at 34 weeks of gestation or later, 412 (2.3%) were admitted to the NICU for respiratory distress within the first hours of life. The incidence of NICU admissions due to respiratory distress was 2.2% in the non-DM group, 2.1% in the DTR group, and 5.7% in the DTI group. Insulin treatment of DM, together with several other perinatal factors, was associated with an increased risk for severe respiratory distress. In a multivariate model, we found that DTI, but not DTR, was a risk factor independent of gestational age and cesarean section, with an IRR of 1.44 (95% CI, 1.00–2.08). The data indicate that newborns of mothers with DM treated with diet are not at risk for severe respiratory distress. Conversely, newborns of mothers with DM treated with insulin are associated with elevated risk for severe respiratory disease and should therefore be closely monitored. [ABSTRACT FROM AUTHOR]

Background: Compromised myocardial function and persistent elevated pulmonary vascular resistance are common among neonates treated with therapeutic hypothermia (TH) for hypoxic-ischemic encephalopathy (HIE). There is a lack of data regarding persistence of cardiac alterations after discharge from the neonatal intensive care unit (NICU)., Methods: We assessed cardiovascular profiles after NICU discharge. Echocardiogram data, including speckle-tracking echocardiography (STE), were extracted from the latest outpatient scan. Data were compared by initial amplitude-integrated encephalography (aEEG) profiles on admission [normal vs. abnormal]., Results: In total, 70 (19%) neonates had a follow-up echocardiogram (22 with initial normal aEEG, 48 with abnormal aEEG). Age at follow-up was similar between the two groups (6.2 vs. 7.7 months, [p = 0.08]). Neonates with an initially abnormal aEEG showed more negative Right Ventricle (RV)-peak global longitudinal strain (-28.2 vs. -26.0%, [p = 0.02]), RV-peak free wall longitudinal strain rate (-1.24 vs. -1.10 [1/second], [p = 0.01]), and RV-peak free wall longitudinal strain rate (-1.50 vs. -1.27 [1/second], [p = 0.001]). These associations remained after multilinear regression analysis, indicating persistent enhanced RV contraction in the abnormal aEEG group., Conclusion: Neonates with initial abnormal aEEG profiles exhibited increased RV contraction after NICU discharge. Future studies should explore long-term cardiovascular follow-up of neonates with HIE, beyond the perinatal period., Impact: What is the key message of your article? Cardiac performance in hypoxic ischemic encephalopathy is linked to adverse outcomes. Survivors with an abnormal aEEG at admission showed increased right ventricular contractility at follow-up, possibly related to an adverse adaptation to the initial insult. What does it add to the existing literature? This study offers insights into long-term cardiovascular outcomes in neonates with HIE, focusing on the link between initial aEEG abnormalities and later RV function. What is the impact? The findings underscore the importance of early cardiovascular assessments and monitoring in neonates undergoing TH for HIE, potentially guiding future follow-up protocols., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Purpose: The primary objective was to evaluate the impact of necrotising enterocolitis (NEC) and spontaneous intestinal perforation (SIP) on mortality and neurodevelopmental outcomes at 2 years' corrected age (CA) in infants born before 32 weeks' gestation (WG)., Methods: We studied neurodevelopment at 2 years' CA of infants with NEC or SIP who were born before 32 WG from the EPIPAGE-2 cohort study. The primary outcome was death or the presence of moderate-to-severe motor or sensory disability defined by moderate-to-severe cerebral palsy or hearing or visual disability. The secondary outcome was developmental delay defined by a score < 2 SDs below the mean for any of the five domains of the Ages and Stages Questionnaire., Results: At 2 years' CA, 46% of infants with SIP, 34% of infants with NEC, and 14% of control infants died or had a moderate-to-severe sensorimotor disability (p < 0.01). This difference was mainly due to an increase in in-hospital mortality in the infants with SIP or NEC. Developmental delay at 2 years' CA was more frequent for infants with SIP than controls (70.8% vs 44.0%, p = 0.02) but was similar for infants with NEC and controls (49.3% vs 44.0%, p = 0.5). On multivariate analysis, the likelihood of developmental delay was associated with SIP (adjusted odds ratio = 3.0, 95% CI 1.0-9.1) but not NEC as compared with controls., Conclusion: NEC and SIP significantly increased the risk of death or sensorimotor disability at 2 years' CA. SIP was also associated with risk of developmental delay at 2 years' CA., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Preterm birth is associated with cerebrovascular development disruption and can induce white matter injuries (WMI). Transfontanellar ultrasound Doppler is the most widely used clinical imaging technique to monitor neonatal cerebral vascularisation and haemodynamics based on vascular indexes such as the resistivity index (RI); however, it has poor predictive value for brain damage. Indeed, these RI measurements are currently limited to large vessels, leading to a very limited probing of the brain's vascularisation, which may hinder prognosis. Here we show that ultrafast Doppler imaging (UfD) enables simultaneous quantification, in the whole field of view, of the local RI and vessel diameter, even in small vessels. Combining both pieces of information, we defined two new comprehensive resistivity parameters of the vascular trees. First, we showed that our technique is more sensitive in the early characterisation of the RI modifications between term and preterm neonates and for the first time we could show that the RI depends both on the vessel diameter and vascular territory. We then showed that our parameters can be used for early prediction of WMI. Our results demonstrate the potential of UfD to provide new biomarkers and pave the way for continuous monitoring of neonatal brain resistivity., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Mickael Tanter is shareholder of SuperSonic Imagine. All other authors declare that they have no conflict of interest.

Background: Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis, resulting in 3 million hospitalizations each year worldwide. Nirsevimab is a monoclonal antibody against RSV that has an extended half-life. Its postlicensure real-world effectiveness against RSV-associated bronchiolitis is unclear., Methods: We conducted a prospective, multicenter, matched case-control study to analyze the effectiveness of nirsevimab therapy against hospitalization for RSV-associated bronchiolitis in infants younger than 12 months of age. Case patients were infants younger than 12 months of age who were hospitalized for RSV-associated bronchiolitis between October 15 and December 10, 2023. Control patients were infants with clinical visits to the same hospitals for conditions unrelated to RSV infection. Case patients were matched to control patients in a 2:1 ratio on the basis of age, date of hospital visit, and study center. We calculated the effectiveness of nirsevimab therapy against hospitalization for RSV-associated bronchiolitis (primary outcome) by means of a multivariate conditional logistic-regression model with adjustment for confounders. Several sensitivity analyses were performed., Results: The study included 1035 infants, of whom 690 were case patients (median age, 3.1 months; interquartile range, 1.8 to 5.3) and 345 were matched control patients (median age, 3.4 months; interquartile range, 1.6 to 5.6). Overall, 60 case patients (8.7%) and 97 control patients (28.1%) had received nirsevimab previously. The estimated adjusted effectiveness of nirsevimab therapy against hospitalization for RSV-associated bronchiolitis was 83.0% (95% confidence interval [CI], 73.4 to 89.2). Sensitivity analyses gave results similar to those of the primary analysis. The effectiveness of nirsevimab therapy against RSV-associated bronchiolitis resulting in critical care was 69.6% (95% CI, 42.9 to 83.8) (27 of 193 case patients [14.0%] vs. 47 of 146 matched control patients [32.2%]) and against RSV-associated bronchiolitis resulting in ventilatory support was 67.2% (95% CI, 38.6 to 82.5) (27 of 189 case patients [14.3%] vs. 46 of 151 matched control patients [30.5%])., Conclusions: In a real-world setting, nirsevimab therapy was effective in reducing the risk of hospitalized RSV-associated bronchiolitis. (Funded by the National Agency for AIDS Research-Emerging Infectious Disease and others; ENVIE ClinicalTrials.gov number, NCT06030505.)., (Copyright © 2024 Massachusetts Medical Society.)

Background: SARS-CoV-2 infection on pregnant women was the subject of many questions since the COVID-19 pandemic., Methods: We aim to assess maternal and neonatal outcomes of SARS-CoV-2 infection contracted during 2nd and 3rd trimesters of pregnancy during the first two COVID-19 waves across a prospective French multicenter cohort study. Patients were included between April 2020 and January 2021 in 10 maternity hospitals in Paris area with two groups (i) pregnant women with a positive SARS-CoV-2 nasopharyngeal RT-PCR between [14WG; 37WG[(symptomatic infection), (ii) pregnant women with a negative serology (or equivocal) at delivery and without a positive SARS-CoV-2 nasopharyngeal RT-PCR at any time during pregnancy (G2 group) MAIN FINDINGS: 2410 pregnant women were included, of whom 310 had a positive SARS-CoV-2 nasopharyngeal RT-PCR and 217 between [14WG; 37WG[. Most infections occurred between 28 and 37 weeks of gestation (56 %). Most patients could be managed as outpatients, while 23 % had to be hospitalized. Among women with a positive RT-PCR, multiparous women were over-represented (OR = 2.45[1.52;3.87]); were more likely to deliver before 37 weeks of gestation (OR = 2.19[1.44;3.24]) and overall cesarean deliveries were significantly increased (OR = 1.53[1.09;2.13])., Conclusions: This study highlights the maternal, obstetrical, and neonatal burden associated with SARS-CoV-2 infections during the first two pandemic waves before availability of vaccines., Trial Registration: NCT04355234 (registration date: 21/04/2020)., Competing Interests: Declaration of competing interests The authors declare no conflict of interest., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Cerebral white matter damage (WMD) is the most frequent brain lesion observed in infants surviving premature birth. Qualitative B-mode cranial ultrasound (cUS) is widely used to assess brain integrity at bedside. Its limitations include lower discriminatory power to predict long-term outcomes compared to magnetic resonance imaging (MRI). Shear wave elastography (SWE), a promising ultrasound imaging modality, might improve this limitation by detecting quantitative differences in tissue stiffness. The study enrolled 90 neonates (52% female, mean gestational age = 30.1  ± 4.5 weeks), including 78 preterm and 12 term controls. Preterm neonates underwent B-mode and SWE assessments in frontal white matter (WM), parietal WM, and thalami on day of life (DOL) 3, DOL8, DOL21, 40 weeks, and MRI at term equivalent age (TEA). Term infants were assessed on DOL3 only. Our data revealed that brain stiffness increased with gestational age in preterm infants but remained lower at TEA compared to the control group. In the frontal WM, elasticity values were lower in preterm infants with WMD detected on B-mode or MRI at TEA and show a good predictive value at DOL3. Thus, brain stiffness measurement using SWE could be a useful screening method for early identification of preterm infants at high WMD risk.Registration numbers: EudraCT number ID-RCB: 2012-A01530-43, ClinicalTrial.gov number NCT02042716., (© 2024. The Author(s).)

Background: The life course of individuals born very premature is a topic of increasing concern. The association between high early amino acid intake and later high blood pressure (HBP) in preterm neonates is debated., Methods and Results: In a national, prospective, population-based birth cohort, EPIPAGE-2 (Etude Epidémiologique sur Petits Ages Gestationnels), we assessed blood pressure at 5 years. Eligible infants were those born between 24 and 29 weeks of gestation. Infants were distributed in 2 groups of 717 infants matched on propensity score on whether or not they were exposed to high amino acid intake (>3.5 g/kg per day at day 7); 455 control term infants were also enrolled. A value ≥95th percentile of reference values for age and height defined systolic or diastolic HBP. Blood pressure at 5 years of age was assessed for 389 and 385 children in the exposed and nonexposed groups, respectively. Rates (in percent) of systolic and diastolic HBP were 18.0% (95% CI, 14.5%-22.2% ) , 13.3% (95% CI, 10.3%-17.0%), 8.5% (95% CI, 6.5%-11.1%), and 9.0% (95% CI, 6.6%-12.3%), 10.2% (95% CI, 7.5%-13.6%), and 5.4% (95% CI, 3.8%-7.6%) in exposed, nonexposed, and term-born groups, respectively. Exposure to high early amino acid intake and maximal serum creatinine (by 50 μmol/L) between day 3 and day 7 were 2 independent risk factors for systolic HBP (adjusted odds ratio [aOR], 1.60 [95% CI, 1.05-2.43] and aOR, 1.59 [95% CI, 1.12-2.26], respectively) but not for diastolic HBP (aOR, 0.84 [95% CI, 0.50-1.39] and aOR, 1.09 [95% CI, 0.71-1.67], respectively). After adjustment for 5-year weight Z score, the aOR between high early amino acid intake and systolic HBP was 1.50 [95% CI, 0.98-2.30]., Conclusions: These results suggest that mechanisms of childhood systolic HBP involve neonatal renal challenge by high amino acid intake or dysfunction.

Introduction: Neonatal portal vein thrombosis (PVT) is frequently related to umbilical venous catheterization (UVC), but risk factors remain unclear. This study aims to analyze the variables associated to PVT in near- to full-term newborns with UVC, with a focus on newborns exposed to controlled therapeutic hypothermia (CTH) for hypoxic ischemic encephalopathy (HIE)., Methods: This is retrospective cohort study of infants delivered at or after 36 weeks and with a birthweight over 1,500 g. All infants were assessed for UVC location and PVT using ultrasonography performed between day 5 and day 10 after catheterization., Results: Among 213 eligible patients, PVT was diagnosed in 57 (27%); among them, 54 (95%) were localized in the left portal vein branch. With all significant factors in univariate analysis considered, higher gestational age at birth (adjusted OR 1.35; 95% CI: 1.12-1.64, p = 0.002) and duration of UVC placement (adjusted OR 1.36; 95% CI: 1.11-1.67, p = 0.004) were the main risk factors of PVT. Among 87 infants who were cooled for HIE, 31 (36%) had PVT compared to 26 (21%) in infants without CTH. Using a multivariate model including variables linked to treatment procedures only, an increased PVT incidence was statistically associated with UVC duration (adjusted OR 1.33; 95% CI: 1.08; 1.63, p = 0.01) and CTH (adjusted OR 1.94; 95% CI: 1.04-3.65, p = 0.04)., Conclusion: Left PVT was frequently observed in near- to full-term neonates with UVC. Among factors linked to treatment procedures, both duration of UVC and CTH exposure for HIE were found to be independent risk factors of PVT., (© 2024 S. Karger AG, Basel.)

Background: Neonatal renal vein thrombosis (NRVT) is a rare condition with little data available., Methods: We retrospectively analyzed newborns diagnosed with NRVT admitted to 3 pediatric nephrology units in Paris from 2005 to 2020., Results: Twenty-seven patients were analyzed (male = 59%). The median age at diagnosis was 2.5 days (1 - 4.5). Diagnosis was suspected based on at least one of the three cardinal signs of renal vein thrombosis in 93%: flank mass (67%), hematuria (67%) and thrombocytopenia (70%). In all patients, diagnosis was confirmed by ultrasound. All patients had at least one known perinatal risk factor. A prothrombotic risk factor was found in 13 patients (48%). NRVT was unilateral in 70%, involving the left renal vein in 58%. Among 25 treated patients, 19 (76%) received low molecular weight heparin (LMWH) as initial therapy, 2 (8%) received unfractionated heparin and 4 (16%) received fibrinolysis. Median duration of treatment was 8 weeks (4 - 12). Bleeding occurred significantly more often with fibrinolysis than with LMWH/supportive therapy (3 of 4: 75% vs 0 of 4: 0%, p = 0.05). Clot resolution in patients treated with fibrinolysis did not differ significantly from those treated with LMWH/supportive therapy. After a median follow-up of 5.7 years (3 years - 9.9 years), pathological kidney features were observed in 73% of the patients (19 of 26), kidney atrophy in 18 (69%), hypertension in 2 (8%), chronic kidney disease (CKD) in 1 (4%) and proteinuria in 2 (8%)., Conclusions: NRVT remains a challenging condition, which still requires further study because of its associated morbidity. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background and Objective: High variability in vancomycin exposure in neonates requires advanced individualized dosing regimens. Achieving steady-state trough concentration (C 0 ) and steady-state area-under-curve (AUC 0-24 ) targets is important to optimize treatment. The objective was to evaluate whether machine learning (ML) can be used to predict these treatment targets to calculate optimal individual dosing regimens under intermittent administration conditions., Methods: C 0 were retrieved from a large neonatal vancomycin dataset. Individual estimates of AUC 0-24 were obtained from Bayesian post hoc estimation. Various ML algorithms were used for model building to C 0 and AUC 0-24 . An external dataset was used for predictive performance evaluation., Results: Before starting treatment, C 0 can be predicted a priori using the Catboost-based C 0 -ML model combined with dosing regimen and nine covariates. External validation results showed a 42.5% improvement in prediction accuracy by using the ML model compared with the population pharmacokinetic model. The virtual trial showed that using the ML optimized dose; 80.3% of the virtual neonates achieved the pharmacodynamic target (C 0 in the range of 10-20 mg/L), much higher than the international standard dose (37.7-61.5%). Once therapeutic drug monitoring (TDM) measurements (C 0 ) in patients have been obtained, AUC 0-24 can be further predicted using the Catboost-based AUC-ML model combined with C 0 and nine covariates. External validation results showed that the AUC-ML model can achieve an prediction accuracy of 80.3%., Conclusion: C 0 -based and AUC 0-24 -based ML models were developed accurately and precisely. These can be used for individual dose recommendations of vancomycin in neonates before treatment and dose revision after the first TDM result is obtained, respectively., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objective: To investigate long-term outcomes of infants who survive despite life-and-death discussions with families and a decision to withdraw or withhold life-sustaining interventions (WWLST) in one neonatal intensive care unit., Study Design: Medical records for neonatal intensive care unit admissions from 2012 to 2017 were reviewed for presence of WWLST discussions or decisions, as well as the 2-year outcome of all children who survived. WWLST discussions were prospectively recorded in a specific book; follow-up to age 2 years was determined by retrospective chart review., Results: WWLST discussions occurred for 266 of 5251 infants (5%): 151 (57%) were born at term and 115 (43%) were born preterm. Among these discussions, 164 led to a WWLST decision (62%) and 130 were followed by the infant's death (79%). Of the 34 children (21%) surviving to discharge after WWLST decisions, 10 (29%) died before 2 years of age and 11 (32%) required frequent medical follow-up. Major functional limitations were common among survivors, but 8 were classified as functionally normal or with mild-to-moderate functional limitations., Conclusions: When a WWLST decision was made in our cohort, 21% of the infants survived to discharge. By 2 years of age, the majority of these infants had died or had major functional limitations. This highlights the uncertainty of WWLST decisions during neonatal intensive care and the importance of ensuring that parents are informed of all possibilities. Additional studies including longer-term follow-up and ascertaining the family's views will be important., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aim: To assess the 5-year neurocognitive outcomes of children born extremely preterm exposed to prophylactic hydrocortisone to improve survival without bronchopulmonary dysplasia., Method: This was a prespecified secondary analysis of the PREMILOC clinical trial (trial registration: EudraCT no. 2007-002041-20, NCT00623740). The primary outcome was full-scale IQ based on the Wechsler Preschool and Primary Scale of Intelligence., Results: Among 109 surviving children recruited at the Robert Debré Children's Hospital, Paris, outcome data were available for 42 out of 56 infants (75%) in the group treated with hydrocortisone and 41 out of 53 (77%) in the placebo group. Mean scores were not significantly different between the two groups on full-scale IQ (hydrocortisone: 91.9 [SD = 13.9], placebo: 86.3 [SD = 15.4]; mean difference = 5.7, 95% confidence interval [CI] = -1.0 to 12.3, p = 0.10); however, working memory and retention ability were significantly better in the group treated with hydrocortisone. In a multivariate logistic regression including potential confounding variables, hydrocortisone treatment was significantly associated with a greater chance to survive at 5 years of age with a full-scale IQ equal to or greater than 90 compared to placebo (adjusted odds ratio = 4.26, 95% CI = 1.47-12.36, p = 0.008)., Interpretation: This exploratory analysis provides reassuring data regarding the long-term neurodevelopmental safety of prophylactic hydrocortisone in infants born extremely preterm., (© 2022 Mac Keith Press.)

Aim: To examine the effects of an early home-based 8-week crawling intervention performed by trained therapists on the motor and general development of very premature infants during the first year of life., Methods: At term-equivalent age, immediately following discharge from the Neonatal Intensive Care Unit (NICU), we randomly allocated 44 premature infants born before 32 weeks' gestation without major brain damage to one of three conditions in our intervention study: crawling on a mini-skateboard, the Crawliskate (Crawli), prone positioning control (Mattress), or standard care (Control). The Crawli and Mattress groups received 5 min daily at-home training administered by trained therapists for 8 consecutive weeks upon discharge from the NICU. The outcomes of greatest interest included gross motor development (Bayley-III) at 2, 6, 9, and 12 months (primary outcome) corrected age (CA), mature crawling at 9 months CA and general development at 9 and 12 months CA [Ages and Stages Questionnaires-3 (ASQ-3)]. The study was registered at www.clinicaltrials.gov; registration number: NCT05278286., Results: A 3 (Condition) × 4 (Age) repeated measures ANOVA revealed that Crawli group infants had significantly higher Bayley-III gross motor development scores than Mattress and Control group infants. Crawli group infants also scored significantly higher on groups of Bayley-III items related to specific motor skills than infants in the other groups, including crawling at 9 months CA. We found significant differences in favor of the Crawli group in separate one-way ANOVAs at each of the ages we examined. A 3 (Condition) × 2 (Age) repeated measures ANOVA revealed that the Crawli group scored significantly higher than the Control group for the ASQ-3 total score and communication score and significantly higher for the fine motor score than the Control and Mattress groups. We found additional significant differences in favor of the Crawli group for other dimensions of the ASQ-3 in separate one-way ANOVAs at 9 and 12 months CA., Interpretation: Early crawling training on a Crawliskate provides an effective way to promote motor and general development in very premature infants. The findings also provide clear evidence for a link between newborn crawling and more mature crawling later in development., Competing Interests: MB-R, DIA and JP are co-authors on the patent for the crawling device used in the intervention. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Dumuids-Vernet, Forma, Provasi, Anderson, Hinnekens, Soyez, Strassel, Guéret, Hym, Huet, Granjon, Calamy, Dassieu, Boujenah, Dollat, Biran and Barbu-Roth.)

Background: Health care-associated primary bloodstream infections (BSIs), defined as not secondary to an infection at another body site, including central line-associated BSI, are a leading cause of morbidity and mortality in patients in neonatal intensive care units (NICUs). Our objective was to identify factors associated with severe morbidity and mortality after these infections in neonates in NICUs., Methods: This ancillary study of the SEPREVEN trial included neonates hospitalized ≥2 days in one of 12 French NICUs and with ≥ 1 BSI during the 20-month study period. BSIs (all primary and health care-associated) were diagnosed in infants with symptoms suggestive of infection and classified prospectively as possible (one coagulase-negative staphylococci (CoNS)-growing blood culture) or proven (two same CoNS, or ≥1 recognized pathogen-growing blood culture). BSI consequences were collected prospectively as moderate morbidity (antibiotic treatment alone) or severe morbidity/mortality (life-saving procedure, permanent damage, prolonged hospitalization, and/or death)., Results: Of 557 BSIs identified in 494 patients, CoNS accounted for 378/557 (67.8%) and recognized bacterial or fungal pathogens for 179/557 (32.1%). Severe morbidity/mortality was reported in 148/557 (26.6%) BSIs. Independent factors associated with severe morbidity/mortality were corrected gestational age <28 weeks (CGA) at infection ( P  < .01), fetal growth restriction (FGR) ( P  = .04), and proven pathogen-related BSI vs. CoNS-related BSI ( P  < .01). There were no differences in severe morbidity and mortality between proven and possible CoNS BSIs. In possible BSI, S. epidermidis was associated with a lower risk of severe morbidity than other CoNS ( P  < .01), notably S. capitis and S. haemolyticus ., Conclusions: In BSIs in the NICU, severe morbidity/mortality was associated with low CGA at infection, FGR, and proven pathogen-related BSIs. When only one blood culture was positive, severe morbidity/mortality were less frequent if it grew with S. epidermidis compared to other CoNS. Further studies to help distinguish real CoNS BSIs from contaminations are needed., Study Registration: ClinicalTrials.gov (NCT02598609)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Jaloustre, Cohen, Biran, Decobert, Layese, Audureau, Le Saché, Chevallier, Boukhris, Bolot, Caeymaex, Tauzin and with SEPREVEN study Group.)

Introduction: In 2015, a protocol including early laparoscopy-assisted surgery in the treatment of necrotizing enterocolitis (NEC) was implemented at our institution. Carbon dioxide insufflation during laparoscopy may have an anti-inflammatory effect. We aimed to compare post-operative outcome after early laparoscopy-assisted surgery and classical laparotomy for NEC., Material and Methods: Charts of premature infants undergoing surgery for NEC (2012-2021) were reviewed. Cases operated by early laparoscopy-assisted surgery (2015-2021) were compared to infants operated for NEC between 2012 and 2015 (laparotomy-NEC). Outcomes were post-operative CRP, need for reintervention, mortality, and the occurrence of post-NEC intestinal strictures. CRP was measured on the day of surgery (POD-0), 2 days (POD-2), and 7 days after surgery (POD-7). Data were compared using contingency tables for categorical variables and Student t-test or Mann-Whitney test for continuous variables., Results: Infants with NEC operated by early laparoscopy (n = 48) and laparotomy (n = 29) were similar in terms of perforation (60% vs 58%, p = 0.99) and POD-0 CRP (139 vs 124 mg/L, p = 0.94). Delay between first signs of NEC and surgery was shorter in the laparoscopy group (3 vs 6 days, p = 0.004). Early laparoscopy was associated with a lower CRP on POD-2 (108 vs 170, p = 0.005) and POD-7 (37 vs 68, p = 0.002), as well as a lower rate of post-operative intestinal stricture (34% vs 61%, p = 0.04)., Conclusions: In addition to being safe and feasible in premature infants, early laparoscopic-assisted surgery was associated with decreased NEC-related post-operative inflammation and strictures. A prospective, randomized study is needed in order to evaluate short and long-term effects of laparoscopy in infants with NEC., Level of Evidence: Level III., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Infants born prematurely are at a high risk of developing linguistic deficits. In the current study, we compare how full-term and healthy preterm infants without neuro-sensorial impairments segment words from fluent speech, an ability crucial for lexical acquisition. While early word segmentation abilities have been found in monolingual infants, we test here whether it is also the case for French-dominant bilingual infants with varying non-dominant languages. These bilingual infants were tested on their ability to segment monosyllabic French words from French sentences at 6 months of (postnatal) age, an age at which both full-term and preterm monolinguals are able to segment these words. Our results establish the existence of segmentation skills in these infants, with no significant difference in performance between the two maturation groups. Correlation analyses failed to find effects of gestational age in the preterm group, as well as effects of the language dominance within the bilingual groups. These findings indicate that monosyllabic word segmentation, which has been found to emerge by 4 months in monolingual French-learning infants, is a robust ability acquired at an early age even in the context of bilingualism and prematurity. Future studies should further probe segmentation abilities in more extreme conditions, such as in bilinguals tested in their non-dominant language, in preterm infants with medical issues, or testing the segmentation of more complex word structures.

Background: Early-onset neonatal sepsis (EOS) is a rare condition but an important cause of severe morbidity and mortality in neonates., Methods: This is a prospective observational study in neonates born at ≥34 weeks of gestation (WG). The primary endpoint was EOS, defined by isolation of pathogenic species from blood culture and/or cerebrospinal fluid culture within 72 hours after birth. Data on EOS were collected exhaustively from all maternity wards in Paris area (April 2019-March 2021)., Results: 108 EOS were recorded (annual incidence, 0.32 per 1000 live births; 95% CI 0.26 to 0.38). In term infants, the most frequent pathogens were group B Streptococcus (GBS) (n=47) and Escherichia coli (n=20); in late preterm infants, the most frequent pathogens were E. coli (n=15) and GBS (n=7). Fifteen meningitis cases were diagnosed. Five E. coli strains (14%) were resistant to both amoxicillin and gentamicin, which is an empiric treatment for EOS. Of the 54 infants with GBS infections, 35 were born from mothers with negative GBS prepartum screening test and 8 from mothers with no screening. Two deaths were reported, both in term infants ( Proteus mirabilis and E. coli )., Conclusion: In neonates ≥34 WG born in the Paris area, GBS was twice as frequent as E. coli in term infants. EOS was six times more frequent in late preterm than in term infants and was due to E. coli in 60% of cases. Prevention of GBS EOS and empiric antibiotic treatment of EOS could be improved., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To evaluate whether urine output (UO), rarely assessed in the literature, is associated with relevant neonatal outcomes in very preterm infants, and which UO threshold may be the most clinically relevant., Design: Retrospective cohort study., Setting: Two Level IV neonatal intensive care units., Patients: Very preterm infants born between 24 0/7 and 29 6/7 weeks of gestation documented with eight UO measurements per day between postnatal day 1 and day 7., Main Outcome Measures: Composite outcome defined as death before discharge, or moderate to severe bronchopulmonary dysplasia, or severe brain lesions. The association between this outcome and UO was studied using several UO thresholds., Results: Among 532 infants studied, UO <1.0 mL/kg/hour for at least 24 consecutive hours was measured in 55/532 (10%) infants and the primary outcome was recorded in 25 patients. The association between a UO threshold <1.0 mL/kg/hour and the primary outcome was found marginally significant (crude OR 1.80, 95% CI 1.02 to 3.16, p=0.04). The primary outcome was recorded in 112/242 (46%) patients with a UO <2.0 mL/kg/hour and only 64/290 (22%) patients with a UO ≥2.0 mL/kg/hour (p<0.001). This UO threshold was found significantly associated with the primary outcome (crude OR 3.1, 95% CI 2.1 to 4.7, p<0.001), an association confirmed using a multivariate logistic regression model including baseline covariates (adjusted OR 3.7, 95% CI 2.2 to 6.4, p<0.001)., Conclusion: A UO <2 mL/kg/hour over 24 hours between postnatal day 1 and day 7 strongly predicts neonatal mortality or severe morbidities in very preterm infants., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: KCNQ2-epileptic encephalopathy (EE) is a neonatal epilepsy syndrome characterized by a typical clinical presentation and EEG recording, but without any brain or cortical abnormal development on MRI. Most of the patients have a severe developmental impairment. The epileptogenic mechanisms are thought to be the result of the changes of the M-current density causing a change of brain excitability. Although recent studies allow us to better understand the physiopathology of KCNQ2-EE, the neuropathology of this ion channel dysfunction has only been previously described in a single case report., Methods: We report the neuropathology study of a case of KCNQ2-EE with a typical electro-phenotype due to a de novo heterozygous single nucleotide pathogenic variant in the exon 5 of the KCNQ2 gene (NM&#95;172107.2:c.802C>T; p.Leu268Phe)., Results: At the macroscopic level, the brain had a normal structure with a normal neocortical gyral pattern. At the histological level, the cortex had a usual six-layer lamination in all lobes but blurred gray-white matter boundaries due to excessive heterotopic neurons in deep white matter were observed. This diffuse mild malformation of cortical development is suggestive of a neuronal migration disorder., Conclusion: In recent years, our understanding of the role of ion channel dysfunctions in early brain development has expanded from the occurrence of EE to brain malformation. Through this rare neuropathological report, we emphasize the role of KCNQ2 channels in the process of cortical development. As for other genetic neonatal onset epilepsies, more reports are needed to further delineate the range of neuropathological abnormalities for KCNQ2-EE., (Copyright © 2022. Published by Elsevier Ltd.)

Background and Objectives: The current threshold used for oliguria in the definition of neonatal AKI has been empirically defined as 1 ml/kg per hour. Urine output criteria are generally poorly documented, resulting in uncertainty in the most accurate threshold to identify AKI in very preterm infants with known tubular immaturity., Design, Setting, Participants, & Measurements: We conducted a bicentric study including 473 very preterm infants (24 0/7 -29 6/7 weeks of gestation) born between January 2014 and December 2018 with urine output measurements every 3 hours during the first 7 days of life and two serum creatinine measurements during the first 10 days of life. AKI was defined using the neonatal Kidney Disease Improving Global Outcomes (KDIGO) definition. We tested whether higher urine output thresholds (1.5 or 2 ml/kg per hour) in modified AKI definitions may better discriminate neonatal mortality compared with the current definition., Results: Early-onset AKI was developed by 101 of 473 (21%) very preterm infants. AKI was diagnosed on the basis of urine output criteria alone (no rise in creatinine) for 27 of 101 (27%) participants. Early-onset AKI was associated with higher risk of death before discharge (adjusted odds ratio, 3.9; 95% confidence interval, 1.9 to 7.8), and the AKI neonatal KDIGO score showed good discriminative performance for neonatal mortality, with an area under the receiver operating characteristic (ROC) curve of 0.68 (95% confidence interval, 0.61 to 0.75). Modified AKI definitions that included higher urine output thresholds showed significantly improved discriminative performance, with areas under the ROC curve of 0.73 (95% confidence interval, 0.66 to 0.80) for the 1.5-ml/kg per hour threshold and 0.75 (95% confidence interval, 0.68 to 0.81) for the 2-ml/kg per hour threshold., Conclusions: Early-onset AKI was diagnosed on the basis of urine output exclusively for a quarter of the cases. Furthermore, modified AKI definitions that included higher urine output improved the discriminative performance for predicting mortality., (Copyright © 2022 by the American Society of Nephrology.)

To our knowledge, there are no studies recording the reading eye movements of children born prematurely. We examined the oculomotor patterns during reading of 23 children born prematurely ( M age = 7.8, SD = 0.2 years) to compare them with those from two groups of children born at full-term who were matched for chronological age or reading age, respectively. We found the oculomotor reading pattern in children who were preterm to be similar to that of children who were full-term and matched for reading age; this shared pattern was characterized by longer duration of fixations, frequent prosaccades of smaller amplitude and several backward saccades. In contrast, when these two groups were compared to full-term children matched for chronological age, the latter group showed significantly shorter duration of fixations, less frequent saccades and larger amplitude prosaccades. Thus, the oculomotor pattern we observed in 7-year-old children who were either preterm or reading-delayed, relative to their age-matched peers, reflected delayed development of brain areas involved in reading-related eye movements.

Aim: Eye movements have rarely been explored in preterm born children. The aim of this study was to compare horizontal eye movements in children born preterm and full term when they reached 8 years of age., Methods: Eye movements were recorded in 24 preterm born children (18 boys) and 26 matched controls (19 boys), recruited by a French hospital, using an eye tracker. This identified different types of visually guided saccades, namely step, gap, overlap and antisaccades and pursuit eye movements. The saccades task measured the latency and the percentage of anticipatory and express saccades and errors. The pursuit task measured the gain and percentage of intrusive saccades., Results: This study confirmed that children born at 24-28 weeks of gestation demonstrated a global deficit in inhibitory processes compared to children born full term. The saccades were less precise in the preterm group, anticipatory and express saccades were elevated and there was a high occurrence of intrusive saccades during pursuit movements., Conclusion: These findings suggest that preterm born children have immature brain structures, particularly the parietal and frontal cortexes that are responsible for both saccade and pursuit performance. These could have been the cause of the abnormal inhibitory control measured in this study., (©2021 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)