Current Pediatric Reviews - Volume 18, Issue 1, 2022

The present review was carried out to describe publications on the use of methylene blue (MB) in pediatrics and neonatology, discussing dose, infusion rate, action characteristics, and possible benefits for a pediatric patient group. The research was performed on the data sources PubMed, BioMed Central, and Embase (updated on Aug 31, 2020) by two independent investigators. The selected articles included human studies that evaluated MB use in pediatric or neonatal patients with vasoplegia due to any cause, regardless of the applied methodology. The MB use and 0 to 18-years-old patients with vasodilatory shock were the adopted criteria. Exclusion criteria were the use of MB in patients without vasoplegia and patients ≥ 18-years-old. The primary endpoint was the increase in mean arterial pressure (MAP). Side effects and dose were also evaluated. Eleven studies were found, of which 10 were case reports, and 1 was a randomized clinical study. Only two of these studies were with neonatal patients (less than 28 days-old), reporting a small number of cases (1 and 6). All studies described the positive action of MB on MAP, allowing the decrease of vasoactive amines in several of them. No severe side effects or death related to the use of the medication were reported. The maximum dose used was 2 mg/kg, but there was no consensus on the infusion rate and drug administration timing. Finally, no theoretical or experimental basis sustains the decision to avoid MB in children claiming it can cause pulmonary hypertension. The same goes for the concern of a possible deleterious effect on inflammatory distress syndrome.

Background: The pathophysiology of necrotizing enterocolitis (NEC) is not clear, but increasing information suggests that the risk and severity of NEC may be influenced by abnormalities in the enteric nervous system (ENS). Objective: The purpose of this review was to scope and examine the research related to ENS-associated abnormalities that have either been identified in NEC or have been noted in other inflammatory bowel disorders (IBDs) with histopathological abnormalities similar to NEC. The aim was to summarize the research findings, identify research gaps in existing literature, and disseminate them to key knowledge end-users to collaborate and address the same in future studies. Methods: Articles that met the objectives of the study were identified through an extensive literature search in the databases PubMed, EMBASE, and Scopus. Results: The sources identified through the literature search revealed that: (1) ENS may be involved in NEC development and post-NEC complications, (2) NEC development is associated with changes in the ENS, and (3) NEC-associated changes could be modulated by the ENS. Conclusion: The findings from this review identify the enteric nervous as a target in the development and progression of NEC. Thus, factors that can protect the ENS can potentially prevent and treat NEC and post-NEC complications. This review serves to summarize the existing literature and highlights a need for further research on the involvement of ENS in NEC.

With the recognition that only 2% of the human genome encodes for a protein, a large part of the “non-coding” portion is now being evaluated for a regulatory role in cellular processes. These non-coding RNAs (ncRNAs) are subdivided based on the size of the nucleotide transcript into microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), but most of our attention has been focused on the role of microRNAs (miRNAs) in human health and disease. Necrotizing enterocolitis (NEC), an inflammatory bowel necrosis affecting preterm infants, has a multifactorial, unclear etiopathogenesis, and we have no specific biomarkers for diagnosis or the impact of directed therapies. The information on ncRNAs, in general, and particularly in NEC, is limited. Increasing information from other inflammatory bowel disorders suggests that these transcripts may play an important role in intestinal inflammation. Here, we review ncRNAs for definitions, classifications, and possible roles in prematurity and NEC using some preliminary information from our studies and from an extensive literature search in multiple databases including PubMed, EMBASE, and Science Direct. miRNAs will be described in another manuscript in this series, hence in this manuscript we mainly focus on lncRNAs.

Background: The first clinically detectable stage of caries lesion is a non-cavitated white spot lesion (WSL). The detection of early stages of caries lesions allows non-invasive management by fluoride usage, oral hygiene and diet control. There is a lack of information in the literature regarding the prevalence of these caries lesions in preschool children, which is important especially for public health strategies. Objective: The aim of this study was to conduct a systematic review with meta-analysis to verify the WSLs prevalence in primary teeth of preschool children. Methods: A literature search with MEDLINE/PubMed, Scopus, Web of Science, and Open Gray databases was conducted. Included studies fulfilled the eligibility criteria. Meta-analyses were performed using random effects model, for prevalence of pooled WSLs and subgroups analyses. Results: The search strategy identified 4922 potentially relevant articles, with final inclusion of 16 studies. The pooled prevalence of WSLs in primary teeth was 14.0% (95% CI: 8.0-24.0), without publication bias (p=0.2668). For subgroup analyses, an increase in WSLs prevalence for children of low-income economy (24.0%; 95% CI: 20.0-28.0), for age >31 months (22.0%; 95% CI: 12.0-37.0), for validated visual criteria assessment (20.0%; 95% CI: 11.0-33.0), and for tactile assessment with ball-ended probe (26.0%; 95% CI: 11-50.0) were detected. Conclusion: It is suggested that the prevalence of WSLs in primary teeth of preschool children increases in countries with low income economy, with age greater than 31 months or texture assessment with visual validated criteria or ball-ended probe. PROSPERO Registration: Protocol number #CDR42017078434.

Introduction: Vitamin D deficiency is highly prevalent during pregnancy and in premature infants. This study was done to investigate the maternal and infantile levels of vitamin D in preterm infants. Methods: Using available sampling during 2018-2020, the maternal and umbilical cord serum levels of vitamin D were measured in 294 premature infants in Ghaem Hospital, Mashhad, Iran. A researcher- made questionnaire consisting of neonatal demographic and clinical characteristics was used as the data collection tool. Both maternal and placental vitamin D levels were categorized into four classes: severe deficiency (vitamin D<10 ng/ml), moderate deficiency (10.1≤vitamin D≤20 ng/ml), mild deficiency (20.1≤vitamin D≤30 ng/ml) and normal (vitamin D >30.1ng ml). Results: Vitamin D deficiency was seen in 89% of premature infants (46.6% severe, 30.6% moderate, and 11.9% mild). Serum levels of vitamin D were 18.28±13.94 ng/ml and 14.10±9.70 ng/ml in mothers and infants, respectively. The infants below and above 32 weeks exhibited vitamin D values of 10.97±6.31 ng/ml and 18.05±11.64 ng/ml, respectively. The difference in vitamin D levels between boys (12.59±8.40 ng/ml) and girls (16.05±11.45 ng/ml) was found to be significant (P=0.009). Moderate and severe vitamin D deficiency was more common at earlier pregnancy ages (P=0.001). Conclusion: Vitamin D deficiency is more common and severe in preterm infants and their mothers. Controlling vitamin D levels during pregnancy, especially in women at risk of preterm labor and preterm infants, may help reduce prematurity problems.

Background: Malaria is endemic in many states of India. Though there are reports of maternal and congenital malaria from endemic areas, however, there remains a paucity of data from hilly terrains. The present study evaluated the prevalence, clinical and microbiological spectrum of maternal and congenital malaria at a tertiary health care facility in Northern India over a period of 18 months. Methods: In this observational study, mothers along with their newborns were evaluated for malaria by maternal, placental, and cord blood smear examination and rapid point-of-care diagnostic serological tests. Positive cases were confirmed by polymerase chain reaction. Mother-newborn duos were followed up till discharge from the hospital. Results: A total of 843 mothers delivered during the study period and were screened along with their newborns and placentae. A total of Ten (1.18%) mothers had evidence of malarial parasitemia (Plasmodium vivax, n=7 and Pl. falciparum, n=3), however, none of the placental and cord blood samples were positive for malaria. Overall, 127 (15.1%) neonates required admission in neonatal intensive care unit for various morbidities. Incidence of small for gestational age (SGA) was high (n=210; 24.9%). Multivariate logistic regression analysis demonstrated maternal malaria to be an independent contributor for SGA [Odds Ratio (95% Confidence Interval), 10.7 (2.06 - 49.72)]. However, only 2% variance of SGA could be explained by maternal malaria alone. Conclusion: We report an encouragingly lower incidence of maternal malaria in mothers attending for delivery and a ‘Zero’ incidence for placental and congenital malaria during the study period as compared to national data (upto 7.4% in non-immune mothers), although maternal malaria could be a causative factor for SGA.

Background: Hearing loss is an important disorder affecting newborns admitted to NICU. A national hearing screening program using otoacoustic emission testing is an essential tool to identify hearing loss early in neonates, enabling early intervention to avoid further challenges of pediatric deafness. On the other hand, a delay of the auditory pathway maturation in preterm babies compared to term newborns has already been suggested in the literature. Taking this information into account, in this paper, we aim to identify the best time to perform NICU infant hearing screening tests. Objectives: We aim to study the clinical factors and neonatal morbidities that may affect neonatal hearing screening results using otoacoustic emission test in order to decrease the false-positive test results that increase parental anxiety and increase the need for subsequent investigations. Methods: This is a prospective cross-sectional study that included 204 infants who were admitted to a tertiary referral hospital NICU unit between September 2017 and May 2018. Both transients evoked otoacoustic emissions (TEOAE), and distortion product otoacoustic emission (DPOAE) screening tests were performed in order to screen hearing loss. Results: Our study included 204 infants, 52.9 % of which were males and 47.1 % females. There were correlations between both hyperbilirubinemia and ventilation ≥ 5 days and the failure rate of the first OAE test results among NICU infants where the P-values were (p=0.0133) and (p=0.0456), respectively. Moreover, 165 babies (80.9 %) passed the first OAE with a mean birth weight of 2759 gram and mean maternal age of 30.6 years, while 39 babies (19.1 %) failed the test with a mean birth weight of 2436 gram and a mean maternal age of 32 years. There was no statistically significant relation between both maternal age and birth weight with failure of the first screening test. Conclusion: Our study suggests a higher failure rate of the first OAE in NICU infants who had hyperbilirubinemia or ventilation ≥ 5 days. Therefore, our recommendation is to postpone the first phase of hearing screening for those infants until the first scheduled vaccine appointment to achieve high compliance to attendance and decrease distress to the family that can be associated with false-negative results of the test.

Background: Acetaminophen and ibuprofen are the only antipyretics drugs approved in children, and are considered safe and well tolerated. However, data regarding the adverse drug reaction (ADR) profile of these drugs in children are scattered. Aim: The aim of our study is to evaluate the ADRs of acetaminophen and ibuprofen through an observational study over a period of 15 years (January 2005-April 2020). Reports of suspected ADRs to the active substances ‘acetaminophen’ and ‘ibuprofen’ are listed and accessible through the Italian spontaneous reporting database (RAM system) by AIFA (Pharmacovigilance of the Italian Drug Agency). Methods: Acetaminophen ADRs in paediatric populations were 15% of cases, with more frequent involvement of skin and soft tissue (54.36%) and gastrointestinal apparatus (44.09%); liver dysfunction accounts for 5.67%. Results: Ibuprofen paediatric ADRs were 26%: skin and soft tissues in 63.16% of cases, gastrointestinal tract in 47.75%, hematemesis and melena in 6.38%; kidney injury in 2.25% of cases. Conclusion: Children aged 2 to 11 are more frequently affected by ADRs than infants and adolescents. The risk of gastrointestinal and renal side effects is significantly higher with ibuprofen. Hepatobiliary side effects are more frequently linked to acetaminophen. Potentially fatal ADRs have been reported sporadically for both drugs.

Aim: This trial aimed to determine if supplementation with omega-3 fatty acids as an adjunct therapy to antibiotic treatment can have protective effects against renal scar formation after acute pyelonephritis (APN) in pediatric patients. Background: Current evidence points out that besides antibiotic treatment, early administration of antioxidant and anti-inflammatory compounds may be effective in reducing the occurrence of renal damage following APN in children. Objective: The main endpoint of the trial was the comparison of the development of renal scarring formation after APN in an omega-3 fatty acids-treated group and in a control-treated group. Methods: This prospective randomized, controlled trial study was conducted from March 2016 to May 2018 on 60 children with a diagnosis APN in a tertiary hospital in Iran. After the diagnosis of APN based on the clinical signs and symptoms, urine analysis, urine culture, and dimercaptosuccinic acid renal scan (DMSA scan), the patients were randomly allocated into either the control group (n=30 patients: received standard antibiotic treatment only) or the intervention group (n=30 patients: received standard antibiotic-treatment in combination with oral omega-3 fatty acids based on the children’s weight for three consecutive days). A second DMSA scan was performed for the patients at a minimum of six months after treatment. The development of renal scars was evaluated by comparing the baseline DMSA scan lesions with the follow-up DMSA scan lesions. Results: Fifty patients, including 26 and 24 individuals in the control and intervention groups, respectively, completed the entire course of the study. Renal parenchymal involvement based on the baseline DMSA scan was similar in the two groups (p-value =0.85, 0.90, and 0.53 regarding the right, left, and both kidney units together, respectively). Although comparison of the follow-up DMSA scan lesions to the baseline DMSA scan lesions considering the right and left kidneys as separate units between two groups did not reach the significant level, when considering both left and right kidney units together, results showed a statistically significant difference between groups in favor of the intervention group (p-value =0.04). Conclusion: Although preliminary, the results of this study showed that administration of omega-3 fatty acids, a natural supplement with well-known anti-inflammatory and antioxidant properties, as an adjunct therapy to standard antibiotic treatment might significantly reduce the incidence of the occurrence renal scarring following APN in children. Confirmation of these results requires further studies.