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2023 | April-June | Volume 2 | Issue 2

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Akhil Maheshwari, Kei Lui, Mario Motta

We Need New Tools to Evaluate Neurological Development in Utero and after Birth

[Year:2023] [Month:April-June] [Volume:2] [Number:2] [Pages:4] [Pages No:iv - vii]

   DOI: 10.5005/newborn-2-2-iv  |  Open Access | 



Pavan Kalamdani, Gayatri Athalye-Jape, Saumil Desai, Nalinikanta Panigrahy, Ju-Li Ang, Amit Upadhyay, Roya Huseynova, Ogtay Huseynov, Anil Rao, Thierry AGM Huisman

Imaging of the Preterm Cerebellum

[Year:2023] [Month:April-June] [Volume:2] [Number:2] [Pages:7] [Pages No:115 - 121]

Keywords: Cerebellar hemorrhage, Cerebellum, Diagnostic imaging, Disruptions, Magnetic resonance imaging, Malformations

   DOI: 10.5005/jp-journals-11002-0061  |  Open Access |  How to cite  | 


Cerebellar injury is being increasingly recognized as a significant complication of preterm birth. A critical phase of cerebellar growth occurs during the third trimester characterized by cellular migration, proliferation, and arborization. This vulnerable developmental phase increases the risk of impaired cerebellar development, especially in preterm infants, given their exposure to adverse extrauterine environments. 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 the breakdown of a body structure that had the 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 magnetic resonance imaging (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 (USG) 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. The role of advanced MRI modalities such as functional MRI, diffusion tensor imaging (DTI), and magnetic resonance (MR) spectroscopy in cerebellar disruptions and malformations are also discussed in some detail.



Glenda McLean, Abdul Razak, Michael Ditchfield, Paul Lombardo, Atul Malhotra

Evaluation of a Cranial Ultrasound Scoring System for Prediction of Abnormal Early Neurodevelopment in Preterm Infants

[Year:2023] [Month:April-June] [Volume:2] [Number:2] [Pages:6] [Pages No:122 - 127]

Keywords: Brain injury, Cerebral palsy, Cranial ultrasound, Early intervention, Neurodevelopmental outcome, Preterm infants, Prognosis

   DOI: 10.5005/jp-journals-11002-0062  |  Open Access |  How to cite  | 


Aim: To evaluate and compare a cranial ultrasound (cUS) scoring system to conventional reporting of cranial ultrasound abnormalities (CUAs) for prediction of early neurodevelopmental outcomes in preterm infants. Materials and methods: This retrospective, single-center study compared cUS scores to results from late ultrasound examination reports for any cUS abnormality (CUA) (any hemorrhage or white matter lesion) or severe CUA [severe intraventricular hemorrhage (IVH)], cystic periventricular leukomalacia (PVL), parenchymal or cerebellar hemorrhage) for predicting early signs of cerebral palsy (CP) or developmental delay in preterm infants. Results: Six-weeks postnatal cUS examinations were analyzed against early neurodevelopmental outcomes at 3–4-months corrected age of 242 preterm infants (median gestational age, 26.5 weeks; interquartile range [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): from −19 to 19]) and specificity (68% vs 64% [95% CI: from −3 to 10]) for predicting CP. Similarly, there was no difference in sensitivity (44% vs 46% [95% CI: from −12 to 7]) and specificity (74% vs 70% [95% CI: from −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: from 12 to 49]) but significantly lower specificity (68% vs 96% [95% CI: from −21 to −34]) for predicting CP. There was higher sensitivity (44% vs 12 % [95% CI: from 23 to 41]) but lower specificity (74% vs 98% [95% CI: from −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. Clinical significance: Objective scoring of cUS examinations on late neonatal scans was found to be similar to conventional reporting of any CUA for the prediction of early neurodevelopmental outcomes in this retrospective study. This indicates that scoring does not value add to the diagnosis of these infants.



Janet L Rothers, Christine M Calton, Jennifer MB Stepp, Melissa D Halpern

Enteral Feeding and Antibiotic Treatment Do Not Influence Increased Coefficient of Variation of Total Fecal Bile Acids in Necrotizing Enterocolitis

[Year:2023] [Month:April-June] [Volume:2] [Number:2] [Pages:5] [Pages No:128 - 132]

Keywords: Antibiotics, Bile acids, Baby, Enteral nutrition, Infant, Necrotizing enterocolitis, Newborn, Neonate

   DOI: 10.5005/jp-journals-11002-0063  |  Open Access |  How to cite  | 


Introduction: Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in preterm infants. In animal models, the 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 the relationships between exposure to enteral feeding types and antibiotic treatments with NEC status and CV-TBA. Materials and methods: Serial fecal samples were collected from 79 infants born with birth weight (BW) ≤1800 gm 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.



Christopher Q Buchanan, Megan L Lawlor, Chukwuebuka Okafor, Shannon R Kurian, Andrea E Philip, Abigael E Finkle, Jay J McQuillan, Seema Haridas, Joyce M Koenig

Linked Th17 and Calgranulin Responses in Maternal-cord Blood Dyads of Preterm Gestations with Histologic Chorioamnionitis

[Year:2023] [Month:April-June] [Volume:2] [Number:2] [Pages:9] [Pages No:133 - 141]

Keywords: Fetal inflammation, Gamma–delta T cells, Maternal inflammation, S100, S100A8, S100A12, Treg cells

   DOI: 10.5005/jp-journals-11002-0064  |  Open Access |  How to cite  | 


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.



Benjamin R Araya, Alisha A Ziegler, Connie C Grobe, Justin L Grobe, Jeffrey L Segar

Sodium and Growth in Preterm Infants: A Review

[Year:2023] [Month:April-June] [Volume:2] [Number:2] [Pages:6] [Pages No:142 - 147]

Keywords: Growth, Human, Postnatal, Premature, Preterm, Review, Sodium

   DOI: 10.5005/jp-journals-11002-0060  |  Open Access |  How to cite  | 


Aim: 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 efforts over the past 20 years to optimize neonatal nutrition, postnatal growth failure in preterm infants remains a significant problem. Compelling associations have been identified between in-hospital growth failure and cardiometabolic and neurodevelopmental disorders, heightening the need to further identify the optimal nutritional needs of preterm infants. 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 in this population. Sodium intake recommendations are provided based on the interpretation of currently available literature.



Sabrina Rangwani, Gunes Orman, Maroun Mhanna, Akhil Maheshwari, Thierry AGM Huisman

Importance of Neuroimaging in Infants with Microcephaly

[Year:2023] [Month:April-June] [Volume:2] [Number:2] [Pages:10] [Pages No:148 - 157]

Keywords: Aminoacylase-2, Apert, Brain volume, Brain volume loss, Canavan's disease, Cavum septum pellucidum, child abuse, Crouzon, cytomegalovirus, Ex vacuo enlargement of ventricles, Head circumference, Meckel-Gruber syndrome, Melting brain, near-drowning, Neuroimaging, Skull deformities, Thalami, TORCH, Toxoplasma gondii, Trisomy 13, Trisomy 18, Trisomy 21, Twin-to-twin transfusion syndrome, Vein of Galen aneurysmal malformation, Zika virus, Zika

   DOI: 10.5005/jp-journals-11002-0065  |  Open Access |  How to cite  | 


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 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.



Srijan Singh, Jubara Alallah, Astha Amrit, Akhil Maheshwari, Suresh Boppana

Neurological Manifestations of Perinatal Dengue

[Year:2023] [Month:April-June] [Volume:2] [Number:2] [Pages:15] [Pages No:158 - 172]

Keywords: Antibody-dependent enhancement, Congenital dengue, Dengue encephalitis, IgM:IgG ratio, Neonate, Neurotropism, NS1Ag, CYD-TDV (Dengvaxia), TAK-003, Vertical transmission

   DOI: 10.5005/jp-journals-11002-0066  |  Open Access |  How to cite  | 


Dengue viruses (DENVs) are single-stranded RNA viruses belonging to the family Flaviviridae. There are four distinct antigenically related serotypes, DENVs types 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 the 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.



Julliet C Ogu, Ebubechi Adindu, Jenifer Ogu, Akhil Maheshwari, Thierry AGM Huisman

Spinal Ultrasound: A Safe and Valuable, but Underutilized Imaging Modality to Evaluate Epidural Hematomas in Infants

[Year:2023] [Month:April-June] [Volume:2] [Number:2] [Pages:6] [Pages No:173 - 178]

Keywords: Accessibility, Accuracy, Anticoagulation, Antiplatelet therapy, Blood dyscrasias, Cauda equina nerve roots, Coagulopathies, Conus medullaris, Cost-effectiveness, Cost-effective, Epidural anesthesia, Evaluation, Hyperechogenic epidural fat, Hypoechogenic filar cyst, Infant, Imaging, Lumbar puncture, Newborn, Neonate, Neoplasms, Pediatrics, Pregnancy, Spinal hematoma, Spinal epidural hematomas, Epidural venous plexus, Spinal surgery, Spinal ultrasound, Thrombocytopenia, Time-efficient, Trauma, Tubular epidural fluid, Vascular malformations

   DOI: 10.5005/jp-journals-11002-0059  |  Open Access |  How to cite  | 


This paper aims to highlight the utility of spinal ultrasound as a valuable and safe diagnostic tool for spinal epidural hematomas in neonates and young infants. 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 case study where spinal ultrasound successfully diagnosed a spinal epidural hematoma in a neonate. 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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