Maheshwari A, Lui K, Motta M. We need new tools to evaluate neurological development in utero and after birth. Newborn 2023; 2(2):iv-vii. DOI: 10.5005/newborn-2-2-iv.

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McLean G, Razak A, Ditchfield M, Lombardo P, Malhotra A. Evaluation of a cranial ultrasound scoring system for prediction of abnormal early neurodevelopment in preterm infants. Newborn 2023; 2(2):122–127. DOI: 10.5005/jp-journals-11002-0062.

 

Abstract: Aim: To evaluate and compare a cranial ultrasound (cUS) scoring system to conventional reporting of cranial ultrasound abnormalities (CUA) for prediction of early neurodevelopmental outcomes in preterm infants. 

Material and Methods: This retrospective, single-centre study compared cUS scores to results from late ultrasound examination reports for any cUS abnormality (CUA) (any haemorrhage or white matter lesion) or severe CUA (severe intraventricular haemorrhage (IVH), cystic periventricular leukomalacia (PVL), parenchymal or cerebellar haemorrhage) for predicting early signs of cerebral palsy (CP) or developmental delay in preterm infants.

Results: Six-week postnatal cUS examinations were analysed against early neurodevelopmental outcomes at three−four month corrected age of 242 preterm infants (median gestational age 26.5 weeks (IQR, 4 weeks) and median body weight 880 grams (IQR, 356.5 grams). We did not find any statistically significant differences between cUS score and any CUA for sensitivity (57% vs. 57% [95% confidence interval (CI): -19 to 19]) and specificity (68% vs. 64% [95% CI: -3 to 10]) for predicting CP. Similarly, there was no difference in sensitivity (44% vs. 46%, [95% CI: -12 to 7]) and specificity (74% vs. 70% [95% CI: -5 to 13]) for predicting any developmental delay. However, in comparison to severe CUA, cUS score had significantly higher sensitivity (57% vs. 27%, [95% CI: 12 to 49]) but significantly lower specificity (68% vs. 96%, [95% CI: -21 to -34]) for predicting CP. There was higher sensitivity (44% vs. 12 % [95% CI: 23 to 41]) but lower specificity (74% vs. 98%, [95% CI: -15 to -32]) for any delay. 

Conclusions: Cranial ultrasound score was similar to any reported CUA for predicting neurodevelopmental outcomes; however, when compared to severe CUA, it had better sensitivity but poor specificity for predicting early neurodevelopmental outcomes.

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Key scientific associations: Neonate, newborn, infant, Reporting, cranial ultrasound abnormalities, retrospective, single-centre study, intraventricular haemorrhage, cystic periventricular leukomalacia, parenchymal or cerebellar haemorrhage, cerebral palsy, developmental delay, white matter injury, ventriculomegaly, hydrocephalus, brain atrophy, term equivalent age, outpatient neurodevelopmental assessments, early neurodevelopment clinic assessment, cerebellar haemorrhage, general movements assessment, fidgety age, Hammersmith Infant Neurological Examination, prediction, sensitivity, specificity, MRI scoring systems,  corpus callosum thinning, delayed folding of the cortex, periventricular haemorrhagic infarction, receiver-operator characteristic, diagnostic test accuracy.

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Rothers JL, Carlton CM, Stepp JMB, Halpern MD. Enteral feeding and antibiotic treatment influence do not increase coefficient of variation of total fecal bile acids in preterm infants. Newborn 2023; 2(1):128–132. DOI: 10.5005/jp-journals-11002-0061.

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Abstract:

Introduction: Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency of preterm infants. In animal models, accumulation of ileal bile acids (BAs) is a crucial component of NEC pathophysiology. Recently, we showed that the coefficient of variation of total fecal BAs (CV-TBA) was elevated in infants who develop NEC compared to matched controls. However, neither the type of enteral nutrition nor antibiotic treatments—parameters that could potentially influence BA levels—were used to match pairs. Thus, we assessed relationships between exposure to enteral feeding types and antibiotic treatments with NEC status and CV-TBA.

Methods: Serial fecal samples were collected from 79 infants born with birth weight (BW) ≤ 1800 g, and estimated gestational age (EGA) ≤ 32 weeks; eighteen of these infants developed NEC. Total fecal BA levels (TBA) were determined using a commercially available enzyme cycling kit. Relationships between CV-TBA and dichotomous variables (NEC status, demographics, early exposure variables) were assessed by independent samples t-tests. Fisher’s exact tests were used to assess relationships between NEC status and categorical variables. Results: High values for CV - TBA levels perfectly predicted NEC status among infants in this study. However, feeding type and antibiotic usage did not drive this relationship.

Conclusions: As in previous studies, high values for the CV-TBA levels in the first weeks of life perfectly predicted NEC status among infants. Importantly, feeding type and antibiotic usage—previously identified risk factors for NEC—did not drive this relationship.

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Key scientific associations: Newborn, neonate, infant, gastrointestinal emergency, ileal bile acids, total fecal bile acids, dichotomous variables, independent samples t-tests, logistic regression, Fisher’s exact tests, intes­tinal gangrene, bowel perforation, short bowel syndrome, emulsification, transport of fats, sterols, fat-soluble vitamins, enterohepatic circulation, detergent, breast milk fortifier, C-reactive protein, serum amyloid A, calprotectin, pro-inflammatory cytokines, heart rate variability, fecal microbiota, proteomics, metabolomics, predictive models.

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Buchanan CQ, Lawlor ML, Okafor C, Kurian SR, Philip AE, Finkle AE, McQuillan JJ, Haridas S, Koenig JM. Linked Th17 and calgranulin responses in maternal-cord blood dyads of preterm gestations with histologic chorioamnionitis. Newborn 2023; 2(2):133-141. DOI: 10.5005/jp-journals-11002-0064.

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Abstract:

Introduction: Maternal–fetal immune crosstalk mechanisms are increasingly identified in the pathogenesis of gestational disorders, including histologic chorioamnionitis (HCA). Although an inflammatory Th17 immune phenotype has been described in preterm neonates with HCA, the associated maternal Th17 response is relatively unknown. To refine our understanding of Th17 biology in this context, we examined Th17 responses in maternal-cord blood dyads of preterm gestations.

Materials and methods: Paired maternal and cord blood (CB) samples were prospectively collected from preterm gestations (23–34 weeks) with HCA or controls. Th17-linked cell frequencies and plasma calgranulin (S100A8, S100A12) levels were determined by flow cytometry and enzyme-linked immunoassay, respectively.

Results: Analyses of 47 maternal-cord blood pairs showed striking parallel increases in Th17 cell frequencies as well as plasma calgranulin levels in the presence of fetal inflammation. Cord blood S100A12 levels were directly correlated with Th17 cell frequencies. In CB cultures, rh-S100A12 promoted in vitro propagation of Th17-type CD4+ cells.

Conclusions: Maternal and CB Th17-linked responses are dually amplified in gestations with HCA, supporting a biological role for maternal–fetal interactions in this disorder. In addition to advancing current knowledge of neonatal Th17 mechanisms, these data shed new light on their association with maternal inflammation.

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Key scientific associations: Maternal-fetal immune crosstalk, preterm premature rupture of membranes, necrotizing enterocolitis, chronic lung disease, placental pathology, T-helper 17 cells, S100 proteins, calgranulins (S100A8, S100A9, S100A12), chorionic plate, placenta, chronic villitis, chronic chorioamnionitis, chronic deciduitis, TCRgd+ T cells, Th17:Treg ratios, Wilcoxon rank test, Fisher’s exact test for categorical data, Pearson correlation coefficient, Treg cells, S100 proteins, Tbet.

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Kalamdani P, Athalye-Jape G, Desai S, Panigrahy N, Ang J-L, Upadhyay A, Huseynova R, Huseynov O, Rao A, Gupta P, Huisman TAGM. Imaging the preterm cerebellum. Newborn 2023; 2(2):148–157. DOI: 10.5005/jp-journals-11002-0054.

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Abstract: Cerebellar injury is being increasingly recognised as a significant complication of preterm birth. A critical phase of cerebellar growth occurs during the third trimester characterised by cellular migration, proliferation and arborization. This vulnerable developmental phase increases the risk to impaired cerebellar development, especially in preterm infants, given their exposure to adverse extrauterine environment. Cerebellar malformations and disruptions are the types of cerebellar insults encountered. A ‘malformation’ is defined as a non-progressive, congenital morphologic anomaly of a single organ or body part following altered primary development. A ‘disruption’ is defined as a non-progressive, congenital morphologic anomaly following breakdown of a body structure that had normal potential for development. Advances in neonatal neuroimaging with increased use of mastoidal and suboccipital views focusing on the posterior fossa by cranial ultrasound (cUS) and high resolution anatomical and functional MRI have improved the sensitive and specific identification of posterior fossa abnormalities, in particular of cerebellar injury in preterm neonates. This article discusses the various modalities of neuroimaging of the cerebellum with advantages and disadvantages. Ultrasonography is the most easily available and feasible bedside modality of imaging, though it has the disadvantage of not detecting subtle abnormalities like punctate hemorrhages. Conventional T1 and T2 weighted MRI can detect most of the cerebellar malformations and disruptions in preterm infants. But the logistics of MRI at most institutions make it less feasible during the first few weeks of life for extremely preterm neonates. Role of advanced MRI modalities like functional MRI, diffusion tensor imaging, MR spectroscopy in cerebellar disruptions and malformations are also discussed in some detail.

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Key scientific associations: newborn, neonate, infant, cerebellar growth, cellular migration, neuronal proliferation, neuronal arborization, extrauterine environment, neonatal neuroimaging, cranial ultrasound, high resolution anatomical MRI, functional MRI, crossed cerebro-cerebellar diaschisis, Dandy-Walker malformation, motor learning and coordination, closed-loop circuits, cerebro-cerebellar circuits, neurodevelopment, autism-spectrum disorders, language impairment, attention deficit and hyperactivity disorder, external granule precursor cells, hindbrain, Purkinje cells, granule cells, cerebellar neurons, malformations, disruptions, acoustic window, mastoidal fontanelle, subarachnoid space, tentorium cerebelli, cerebellar haemorrhage, cerebellar infarction, volumetric analysis, term-equivalent age, susceptibility-weighted imaging, small punctate haemorrhages, volumetric MRI, spherical harmonic description, diffusion-weighted MRI, Brownian motion of water, fractional anisotropy, diffusion-weighted imaging, random motion of water, diffusion tensor imaging, proton MR spectroscopy, N-acetylaspartate, axonal mitochondria, choline, lactate, functional MRI, blood oxygenation level-dependent (BOLD) sequences, cortico-cerebellar correlation, dyadochokinesis, electroencephalopgraphy, brain volumes, white matter integrity, brain activity, ventricular volume, relative A2 power, excitatory neuronal activity.

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Araya BR, Ziegler AA, Grobe CC, Grobe JL, Segar JL. Sodium and Growth in Preterm Infants - a Review. Newborn 2023; 2(2):142–147. DOI: 10.5005/jp-journals-11002-0060.

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Abstract: This article is intended to review the relationship between sodium homeostasis and growth, outline reasons why preterm infants may become sodium deficient, and share data from our group and others regarding the potential benefits of dietary sodium supplementation. Background: Despite tremendous effort over the past 20 years to optimize neonatal nutrition, postnatal growth failure in preterm infants remains a significant problem. Compelling associations between in-hospital growth failure and cardiometabolic and neurodevelopmental disorders also indicating a need to identify optimal nutritional needs of preterm infants. Review Results: The impact of sodium deficiency may have on somatic growth is poorly studied and reported upon within the human literature. In contrast, animal studies dating back almost 100 years highlight the nutritional importance of dietary sodium. Sodium homeostasis during early postnatal life is understudied and underappreciated by neonatologists. Conclusion: Insufficient sodium intake during early life is likely a critical yet underappreciated contributor to growth failure. Total body sodium depletion may be an important risk factor driving complications of premature birth. Clinical Significance: Increased awareness of sodium homeostasis in preterm infants may improve outcomes of this population. Sodium intake recommendations are provided based upon interpretation of currently available literature.

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Key scientific associations: neonate, newborn, sodium homeostasis, sodium deficient, sodium supplementation, postnatal growth failure, in-hospital growth failure, neonatal cardiometabolic disorders, neonatal neurodevelopmental disorders, somatic growth, sodium balance, breastmilk, sweat production, sodium transport systems, intracellular compartment, extracellular compartment, human milk fortifier, human milk fortifier hydrolyzed protein concentrated liquid, bovine-based fortifier, human-milk-based fortifier, fractional excretion of sodium, urine sodium excretion, urinary Na+/K+ ratio, renal aldosterone sensitivity, renin-angiotensin-system, urine aldosterone excretion, atrial natriuretic peptide, postnatal adaptation, bone growth, nitrogen retention, muscle protein synthesis, nitrogen accretion, fat free dry weight, sodium depletion, intracellular pH, antiporter, mitogens, sodium deficit, ileostomy, cystic fibrosis, renal sodium reabsorption, interleukin-17, T cell activation, neutrophil mobilization.

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Rangwani S, Orman G, Mhanna M, Maheshwari A, Huisman TAGM. Importance of Neuroimaging in Infants with Microcephaly. Newborn 2023; 2(2):148–157. DOI: 10.5005/jp-journals-11002-0065.  

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Abstract: Microcephaly is diagnosed in infants and children with a head circumference (HC) 2 standard deviations less than average, accounting for age and gender. There is not a standard method of diagnosis, as growth charts vary by country and methodology used. The most popular method of diagnosis is the use of a tape measure to measure a child’s head. There are various conundrums that affect diagnoses: volume of the brain, deformities in skull shape that affect size measurements, and the etiology of microcephaly. The size of the skull is not the most important factor in diagnosing microcephaly, but rather the volume of the brain. Finally, a distinction between primary and secondary microcephaly must be made; primary microcephaly develops prenatally, and secondary microcephaly develops postnatally. The effects of primary microcephaly are generally more severe, but through imaging, it can be detected before birth. This article analyzes various conditions in which neuroimaging can add considerable information to current methods of clinical evaluation. There is a clear need for a multifaceted approach.

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Key scientific associations: fetus, neonate, newborn, head circumference, brain volume, skull deformities, neuroimaging, thalami, cavum septum pellucidum, ex vacuo enlargement of ventricles, brain volume loss, Apert, Crouzon, Canavan's disease, aminoacylase-2, Zika virus, trisomy 13, trisomy 18, trisomy 21, cytomegalovirus, Zika, TORCH, Toxoplasma gondii, twin-to-twin transfusion syndrome, Vein of Galen aneurysmal malformation, melting brain, child abuse, near-drowning, Meckel-Gruber syndrome.

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Singh S, Alallah J, Amrit A, Maheshwari A, Boppana S. Neurological manifestations of perinatal dengue. Newborn 2023; 2(2):158–172. DOI: 10.5005/jp-journals-11002-0066.

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Abstract: Dengue viruses (DENV) are single-stranded RNA viruses belonging to the family Flaviviridae. There are four distinct antigenically-related serotypes, DENV type 1, 2, 3, and 4. These are all mosquito-borne human pathogens. Congenital dengue disease occurs when there is mother- to-fetus transmission of the virus and should be suspected in endemic regions in neonates presenting with fever, maculopapular rash and thrombocytopenia. Although most of the infected infants remain asymptomatic, some can develop clinical manifestations such as sepsis-like illness, gastric bleeding, circulatory failure, and death. Neurological manifestations include intracerebral hemorrhages, neurological malformations and acute focal/disseminated encephalitis/encephalomyelitis. Dengue NS1Ag, a highly-conserved glycoprotein, can help detection of cases in the viremic stage. We do not have proven specific therapies yet; management is largely supportive and is focused on close monitoring and maintaining adequate intravascular volume.

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Key scientific associations: Congenital dengue, neonate, newborn, NS1Ag, DENV, Aedes aegypti, Aedes albopictus, thrombocytopenia, CYD-TDV (Dengvaxia), TAK-003, vertical transmission, dengue encephalitis (DE), hematocrit, platelets, fever, pregnant women, endemic dengue, hyperendemic dengue, primary and secondary infection, antibody dependent enhancement (ADE), Hemoconcentration, petechiae, hemorrhages, DENV 2, bleeding, anti-dengue IgM, RT-PCR, flavivirus, Dengue NS1Ag, encephalomyelitis, CYD-TDV, E-glycoprotein, DC-SIGN, CLEC5A, NS1, N2A, N2B, N3, N4A, N4B, N5, T-helper cells, tumor necrosis factor, interleukin-10, antibody-dependent enhancement, IgM:IgG ratio, myositis, myelitis, rhabdomyolysis, neurotropism, neuroinvasive, soluble vascular cell adhesion molecule, soluble intercellular adhesion molecules, endothelial hyperpermeability, pericytes, glia, astrogliosis, cellular hypertrophy, glial fibrillary acidic protein, vimentin, nestin, microcephaly, anencephaly, dengue shock syndrome, dengue nonstructural 1, dengue NS1Ag, Toxoshynchites splendors, brain-evoked response auditory, visual-evoked potential, encephalitic, encephalomyelitis, susceptibility-weighted MRI, Reye's syndrome, lovastatin, balapiravir, celgosivir, CYD-TDV, Dengvaxia, TAK-003, DENV-2/-4chimeric strain.

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Ogu JC, Adindu E, Ogu J, Maheshwari A, Huisman TAGM. Spinal ultrasound: a safe and valuable, but underutilized imaging modality to evaluate epidural hematomas in infants. Newborn 2023; 2(2):173-178. DOI: 10.5005/jp-journals-11002-0059.

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Abstract: This paper aims to highlight the utility of spinal ultrasound as a diagnostic tool for spinal epidural hematoma in neonates and young infants. Spinal ultrasound has emerged as a valuable and safe imaging modality for evaluating spinal hematomas in this patient population. The accessibility, cost-effectiveness, and accuracy of spinal ultrasound make it an appealing alternative to magnetic resonance imaging (MRI). However, despite its potential benefits, spinal ultrasound remains underutilized in clinical practice. In this paper, we present a series of cases where spinal ultrasound successfully diagnosed a spinal epidural hematoma in neonates. Additionally, a comprehensive review of current literature demonstrates a consensus on the advantages of spinal ultrasound for assessing spinal lesions in young infants and neonates. The findings of this study emphasize the importance of incorporating spinal ultrasound into clinical practice for more timely and convenient diagnosis of suspected spinal epidural hematoma in neonates and young infants.

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Key scientific associations: newborn, neonate, infant, imaging, pediatrics, spinal hematoma, spinal epidural hematomas, accessibility, cost-effectiveness, accuracy,  spinal surgery, lumbar puncture, epidural anesthesia, trauma, anticoagulation, neoplasms, coagulopathies, vascular malformations, cauda equina nerve roots, conus medullaris, hyperechogenic epidural fat, hypoechogenic filar cyst, tubular epidural fluid, anticoagulation, antiplatelet therapy, trauma, pregnancy, coagulopathies, blood dyscrasias, thrombocytopenia, epidural venous plexus, cost-effective, time-efficient, evaluation.

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