Current Pediatric Reviews - Volume 19, Issue 2, 2023

Background: Prenatal Learning is a topic still debated for its existence, although the concept is well known since ancient times. Objective: The present review highlights the impact of various stimuli on learning and memory in prenatal and postnatal life. Methods: For review, various articles from preclinical and clinical studies providing early pieces of evidence of prenatal learning to date were included based on the relevancy of the databases, namely, Scopus, Pubmed, and Google Scholar. Results: Learning is the process of acquiring skills/ preferences/ habits from the experiences of the exposures of the past. These exposures are the stimuli, which help in categorizing learning into associated or nonassociated learning. The stimuli of adults related to auditory, gustatory, olfactory, visual, touch, etc. are also accessible to the prenatal life in utero either directly or indirectly through the mother. The effects of these stimuli are remarkable during prenatal life and can be seen clearly in infants. These stimuli play an important role in prenatal learning and contribute to neuronal development. The present review summarizes the pieces of evidence for each of these types of learning & their impact on the ex utero life, a futuristic view & the scope of understanding prenatal learning. The review also elucidates the factors affecting prenatal learning. Conclusion: Studies from clinical and preclinical studies reflected the impacts of several aspects of an infant’s life and the memory created during prenatal life was found to be most likely carried on to postnatal life.

Background: Early childhood caries (ECC) is the most common chronic disease in young children and a public health problem worldwide. It is characterized by the presence of atypical and fast progressive caries lesions. The aggressive form of ECC, severe early childhood caries (S-ECC), can lead to the destruction of the whole crown of most of the deciduous teeth and cause pain and sepsis, affecting the child's quality of life. Although the multifactorial etiology of ECC is known, including social, environmental, behavioral, and genetic determinants, there is a consensus that this disease is driven by an imbalance between the oral microbiome and host, or dysbiosis, mediated by high sugar consumption and poor oral hygiene. Knowledge of the microbiome in healthy and caries status is crucial for risk monitoring, prevention, and development of therapies to revert dysbiosis and restore oral health. Molecular biology tools, including next-generation sequencing methods and proteomic approaches, have led to the discovery of new species and microbial biomarkers that could reveal potential risk profiles for the development of ECC and new targets for anti-caries therapies. This narrative review summarized some general aspects of ECC, such as definition, epidemiology, and etiology, the influence of oral microbiota in the development and progression of ECC based on the current evidence from genomics, transcriptomic, proteomic, and metabolomic studies and the effect of antimicrobial intervention on oral microbiota associated with ECC. Conclusion: The evaluation of genetic and proteomic markers represents a promising approach to predict the risk of ECC before its clinical manifestation and plan efficient therapeutic interventions for ECC in its initial stages, avoiding irreversible dental cavitation.

Background: Viral bronchiolitis is a common condition and a leading cause of hospitalization in young children. Objective: This article provides readers with an update on the evaluation, diagnosis, and treatment of viral bronchiolitis, primarily due to RSV. Methods: A PubMed search was conducted in December 2021 in Clinical Queries using the key terms "acute bronchiolitis" OR “respiratory syncytial virus infection”. The search included clinical trials, randomized controlled trials, case control studies, cohort studies, meta-analyses, observational studies, clinical guidelines, case reports, case series, and reviews. The search was restricted to children and English literature. The information retrieved from the above search was used in the compilation of this article. Results: Respiratory syncytial virus (RSV) is the most common viral bronchiolitis in young children. Other viruses such as human rhinovirus and coronavirus could be etiological agents. Diagnosis is based on clinical manifestation. Viral testing is useful only for cohort and quarantine purposes. Cochrane evidence-based reviews have been performed on most treatment modalities for RSV and viral bronchiolitis. Treatment for viral bronchiolitis is mainly symptomatic support. Beta-agonists are frequently used despite the lack of evidence that they reduce hospital admissions or length of stay. Nebulized racemic epinephrine, hypertonic saline and corticosteroids are generally not effective. Passive immunoprophylaxis with a monoclonal antibody against RSV, when given intramuscularly and monthly during winter, is effective in preventing severe RSV bronchiolitis in high-risk children who are born prematurely and in children under 2 years with chronic lung disease or hemodynamically significant congenital heart disease. Vaccines for RSV bronchiolitis are being developed. Children with viral bronchiolitis in early life are at increased risk of developing asthma later in childhood. Conclusion: Viral bronchiolitis is common. No current pharmacologic treatment or novel therapy has been proven to improve outcomes compared to supportive treatment. Viral bronchiolitis in early life predisposes asthma development later in childhood.

Acute lymphoblastic leukemia is the most frequent pediatric malignancy in children, comprising 30% of all pediatric malignancies; adult ALL comprises 5% of all ALL cases, which have a 186.6 per 1 million incidence. In pediatric ALL (pALL), on which this review focuses, approximately 1 in 285 children are diagnosed with cancer before the age of 20, and approximately 1 in 530 young adults between the ages of 20 and 39 years old is a childhood cancer survivor. The survival probability in pALL is now very high, approximately 80-90%. Thus, the most important is to improve supportive care and treatment based on relapse risk, optimally being based on the genetic feature of malignant cells. Improvements made by now are mainly the classifying of subgroups based on genetic characteristics such as aneuploidy or translocation and aligning them with treatment response. Relevant genetic changes in ALL pathogenesis are transcription regulators of lymphoid development (PAX5, IKZF1, EBF1, and LEF1) and/or coactivators (TBL1XR1 and ERG), lymphoid signaling (BTLA, and CD200 TOX), and tumor suppressor genes (CDKN2A, CDKN2B, RB1, and TP53). This review aims to summarize treatment strategies inhibiting tyrosine kinases, influencing different signaling pathways, BCL inhibitors, and anti-CD therapy (anti-cluster differentiation therapy) in pALL. CAR T-cell therapy (chimeric antigen receptors T-cell therapy) is under research and requires further development.

Background: Silver-Russell syndrome (SRS) is a developmental disorder involving extreme growth failure, characteristic facial features and underlying genetic heterogeneity. As the clinical heterogeneity of SRS makes diagnosis a challenging task, the worldwide incidence of SRS could vary from 1:30,000 to 1:100,000. Although various chromosomal, genetic, and epigenetic mutations have been linked with SRS, the cause had only been identified in half of the cases. Material and Methods: To have a better understanding of the SRS clinical presentation and mutation/ epimutation responsible for SRS, a systematic review of the literature was carried out using appropriate keywords in various scientific databases (PROSPERO protocol registration CRD42021273211). Clinical features of SRS have been compiled and presented corresponding to the specific genetic subtype. An attempt has been made to understand the recurrence risk and the role of model organisms in understanding the molecular mechanisms of SRS pathology, treatment, and management strategies of the affected patients through the analysis of selected literature. Results: 156 articles were selected to understand the clinical and molecular heterogeneity of SRS. Information about detailed clinical features was available for 228 patients only, and it was observed that body asymmetry and relative macrocephaly were most prevalent in cases with methylation defects of the 11p15 region. In about 38% of cases, methylation defects in ICRs or genomic mutations at the 11p15 region have been implicated. Maternal uniparental disomy of chromosome 7 (mUPD7) accounts for about 7% of SRS cases, and rarely, uniparental disomy of other autosomes (11, 14, 16, and 20 chromosomes) has been documented. Mutation in half of the cases is yet to be identified. Studies involving mice as experimental animals have been helpful in understanding the underlying molecular mechanism. As the clinical presentation of the syndrome varies a lot, treatment needs to be individualized with multidisciplinary effort. Conclusion: SRS is a clinically and genetically heterogeneous disorder, with most of the cases being implicated with a mutation in the 11p15 region and maternal disomy of chromosome 7. Recurrence risk varies according to the molecular subtype. Studies with mice as a model organism have been useful in understanding the underlying molecular mechanism leading to the characteristic clinical presentation of the syndrome. Management strategies often need to be individualized due to varied clinical presentations.

Background: The prevalence of wheeze and asthma has risen over recent decades for all age groups, especially children. These disorders can lead to decreased quality of life, missed school, urgent care and emergency department visits, hospitalizations, and increased health care costs. Environmental exposures, including pesticide exposure, are likely a contributing factor to this increased prevalence. Objective: To evaluate the association of pesticide exposure with childhood wheeze and asthma. Methods: We conducted a systematic review evaluating studies of pesticide exposure (measured objectively) and child respiratory outcomes. We searched PubMed, Embase (Elsevier), CINAHL (EBSCO), Scopus (Elsevier), Cochrane Database of Systematic Reviews (Wiley), and ClinicalTrials. gov from 1988 - 2021. Main search keywords included “pesticides”, “insecticides”, “herbicides”, “respiratory”, “asthma” and “wheeze”. Results: Out of 5767 studies, 25 met the inclusion criteria; eight evaluated prenatal pesticide exposure (n=8407), twelve evaluated postnatal exposures (n= 50,488), and five evaluated pre-and postnatal exposures (n=20,919). Main pesticides investigated were dichlorodiphenyldichloroethylene (DDE) (14 studies) followed by organophosphates (7 studies). Primary methods of outcome assessment were questionnaire-based (84%), followed by spirometry (16%), registry data, and blood measures. Studies varied in the strength of evidence relating to study design and measures. Most studies (84%) reported a positive association of exposure with adverse child respiratory health. Conclusion: The studies suggest an association of pesticide exposure and childhood wheeze and asthma. The varying results and methods reinforce the need for more research and standardized approaches to these studies to confirm the suggested association of pesticide exposure and childhood wheeze and asthma.

Aims: We correlate ultrasound, MRI, and clinical findings in neonates with suspected hypoxic ischemic injury. Background: Recent advances in neuroimaging have led to improved detection of subtle insults associated with neurodevelopmental outcomes, beyond more historically described lesions such as large hemorrhages and hydrocephalus. Objective: In this study, we compare cranial ultrasound to MRI for the evaluation of suspected HIE in preterm infants. Methods: 147 premature infant patients with paired ultrasound and MRI exams were retrospectively analyzed to compare imaging finding accuracy and clinical value. Result: We confirm that ultrasound is highly sensitive and specific for hydrocephalus, ventricular prominence, and gross structural abnormalities. Ultrasound is not a substitute for MRI in cases of small hemorrhages or white matter injury, however, certain US findings were associated with Apgar score and MRI sequelae of HIE. Conclusion: Choosing between ultrasound and MRI for preterm neonates at risk for intracranial abnormalities based on their strengths can reduce cost and maximize clinical utility. MRI provides a highly sensitive identification of subtle brain injury, yet ultrasound is correlated with the peripartum clinical picture as measured by Apgar score.

Aims: This case-control study was conducted to identify maternal and placental risk factors of small-for-gestational-age (SGA) and fetal malnutrition. Methods: Cases comprised 104 consecutively delivered SGA neonates (determined as per INTERGROWTH- 21st standard). An equal number of next-born gestation and gender-matched appropriatefor- gestational age (AGA) neonates served as controls. Maternal risk factors were enquired, and placentae were evaluated by clinical and histopathological examination. Nutrition of the neonates was assessed by the clinical assessment of nutrition (CAN) score. Univariate and multivariate logistic regression analysis was done to identify the maternal and placental risk factors. Results: The prevalence of SGA in the present study was 23.9%. Maternal fever [adjusted Odds Ratio (aOR), 95% confidence interval (CI), 16.3 (3.5-124.1); p = 0.001], presence of placental syncytial knots [aOR (95% CI), 2.9 (1.1-9.1); p = 0.04] and placental calcifications [aOR (95% CI), 3(1.1- 8.7); p = 0.03], were identified as independent predictors of SGA using multivariate logistic regression analysis. Malnutrition (SCORE <25) affected 64% of SGA and 16.3% of AGA neonates. The only risk factor significantly associated with malnourished SGA was prematurity, whereas malnourished AGA was significantly associated with prematurity and fetal distress. In-hospital morbidities significantly higher in SGA were perinatal asphyxia, respiratory distress, need for respiratory support, polycythemia, hypoglycemia, and feeding intolerance. Mortality before discharge was 4.8% and 3.8% in SGA and AGA population, respectively (p > 0.05). Neonatal outcomes were comparable among well-nourished, malnourished SGA and AGA groups. Conclusion: Maternal fever, placental syncytial knots, and calcifications were independent risk factors of SGA, whereas prematurity and fetal distress were responsible for malnutrition.

Background: One of the most common problems in preterm neonates is retinopathy of prematurity (ROP). It has been shown antioxidants may be effective in preventing the development and progression of ROP. Considering the antioxidant properties of bilirubin, we decided to investigate the bilirubin level in neonates with ROP and compare it with healthy neonates. Methods: This case-control study was performed on VLBW neonates admitted to the NICU of Ghaem Hospital in Mashhad between 2014 and 2020 for a Jaundice evaluation. Complete neonate’s characteristics, maternal history and laboratory results were collected in a questionnaire. Then the neonates were examined for ROP by a fellowship of the retina of an ophthalmologist at 32 weeks or four weeks after birth. The highest bilirubin levels during their hospitalization were also recorded. Results: Of 427 neonates examined, 121 (37.7%) had a normal eye examination, and 266 (62.3%) had ROP. The mean weight, gestational age and bilirubin were 1455.8 ± 431.4 grams, 31.6 ± 2.3 weeks and 8.8 ± 2.4 mg/dl, respectively. There was a significant difference between controls and neonates with ROP with regard to birth weight, duration of intermittent positive pressure ventilation (IPPV), duration of oxygen therapy, first and fifth minute Apgar scores, the maximum level of bilirubin and gestational age (P < 0.05). It was observed that the maximum level of bilirubin was lower in neonates with higher stages of ROP. Conclusion: According to the results of this study, higher levels of bilirubin in neonates may be a protective factor against ROP. Moreover, increased levels of bilirubin are associated with reduced severity of ROP. Therefore, prophylaxis phototherapy in premature infants may need to be reconsidered.

Background & Aim of the Work: β-Thalassemia (βT) is highly prevalent in some countries like Egypt. Accurate data about actual disease prevalence and heavily prevalent geographic locations are essential to help in early detection and in setting up effective preventive programs. We aim for screening βT carriers among Egyptian high school students in the Delta region. Subjects and Methods: A cross-sectional multicenter study was carried out on 4320 randomly selected students from four governorates of the Nile Delta region, Egypt. All patients were to be tested for their complete blood count. Those with microcytic hypochromic anemia not caused by iron deficiency were tested for βT carrier status using high-performance liquid chromatography. Results: The total prevalence of βT carrier rate was 6.13%. The highest prevalence was detected in Al-Sharkia Governorate, reaching 7.89%, followed by 6.90% in Al-Gharbia Governorate. Al- Dakahilia and Al-Menoufia showed lower rates of 4.86% and 3.73%, respectively. Conclusion: Despite the premarital national screening program for βT in Egypt, the carrier rate is still high. More effort should be done into the proper implementation of national prevention programs.

Background: Although coronavirus disease-2019 (COVID-19) seems to be milder in children than in adults, children may exhibit severe multisystemic involvement, supported by growing evidence of this incidence in neonates. This case report aimed to demonstrate an inflammatory response syndrome in a full-term neonate born from a 35-old-year woman infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Case Presentation: A full-term neonate girl with uneventful perinatal history was admitted with mild tachypnea at the first hour of birth and gradually worsened, resulting in subsequent ventilator support on the second day. The nasal SARS-CoV-2 real-time polymerase chain reaction (RT-PCR) test was positive in several cessations from the time of admission until the tenth day. She revealed cardiomegaly, a diffuse opacification of lungs in the chest radiograph, both side ventricular hypertrophy, valvular regurgitation, and severe pulmonary hypertension on echocardiography. She underwent treatment with surfactant, antibiotics, paracetamol, inotropes, and sildenafil, with beneficial effects. In the lack of a positive fluid culture, she developed necrotizing enterocolitis, transaminitis, and a generalized rash on day six. Furthermore, her mild brain edema that occurred on the second day developed into hydrocephaly. The patient was considered MIS-N and successfully treated with methylprednisolone pulse and intravenous immunoglobulin. She was discharged after 29 days and followed for eight months with persistent mild hydrocephalous and possible evidence of cerebral palsy. Conclusion: We conclude that maternal exposure to COVID-19 may potentially be associated with multisystem inflammation in the early neonatal period. However, this condition is relatively rare. Immunomodulatory agents may be beneficial in this condition.