Journal of Pediatric and Neonatal Individualized Medicine (JPNIM) <p>The <strong>Journal of Pediatric and Neonatal Individualized Medicine (JPNIM)</strong> is a peer-reviewed interdisciplinary journal which provides a forum on new perspectives in pediatric and neonatal medicine. The aim is to discuss and to bring readers up to date on the latest in research and clinical pediatrics and neonatology. Special emphasis is on developmental origin of health and disease or perinatal programming and on the so-called ‘-omic’ sciences. Systems medicine blazes a revolutionary trail from reductionist to holistic medicine, from descriptive medicine to predictive medicine, from an epidemiological perspective to a personalized approach. The journal will be relevance to clinicians and researchers concerned with personalized care for the newborn and child. Also medical humanities will be considered in a tailored way.</p> <p>Article submission (original research, review papers, invited editorials and clinical cases) will be considered in the following fields: fetal medicine, perinatology, neonatology, pediatrics, developmental programming, psychology and medical humanities.</p> en-US Journal of Pediatric and Neonatal Individualized Medicine (JPNIM) 2281-0692 <p>© Hygeia Press</p> <p> </p> <h3>Copyright and publishing rights</h3> <p>Regarding copyright, before publication, Authors declare that, in consideration of the action of JPNIM in reviewing and editing their submission, they transfer, assign, or otherwise convey all copyright ownership, including any and all rights incidental thereto, exclusively to the JPNIM Publisher (Hygeia Press di Corridori Marinella).</p> <div> <div> <div> <div> <div> <p>Authors have the opportunity to reuse figures, tables and selected text up to 250 words from their article as finally published, providing that full and accurate credit shall be given to publication in JPNIM and that modifications are noted (otherwise no changes may be made).</p> </div> </div> </div> </div> </div> The importance of screening for critical and severe congenital cardiac diseases by pulse oximetry in the early neonatal age – Position statement of the Hellenic Society of Perinatal Medicine (HSPM) <p class="p1"><strong>Background:</strong> From its first reported use in 2002, the efficiency of pulse oximetry (POX) screening in detecting critical and severe congenital heart disease (c/s-CHD) in term neonates in early days after delivery has been proved by numerous studies. It is low-cost, non-invasive, easy to use, repeatable, time-saving, applicable by even less-skilled nursing staff, proven to have excellent sensitivity and high specificity. When used in addition to the initial physician’s examination before dismissing a newborn home, this postnatal test can increase the clinical accuracy of detecting c/s-CHD. In this sense, it must be used as an early detecting screening test. Its use is more important during the period in which the patent ductus arteriosus (PDA) conceals the signs and symptoms of low cardiac output syndrome (LCOs) or severe cyanosis that will lead to notably hypoxia and acidosis. These free-of-symptoms babies that leave maternity units although critically ill, as well as those that are born at home and assessed by primary care, will benefit the most through a compulsory use of this test. Despite the benefits, it has failed to become a universal screening test for early detection of c/s-CHD, especially in Europe.</p> <p class="p1"><strong>Aim:</strong> To discuss the existing evidence on safe, effective, and efficient screening, using POX in combination with initial pre-discharge physical examination at the end of its stay under maternity services, including births out of medical facilities, for every term baby as a compulsory health screening test in Greece.</p> <p class="p1"><span class="s1"><strong>Methods:</strong> The authors, members of the Hellenic Society of Perinatal Medicine (HSPM), reviewed the existing up-to-date literature and the trend of using this test worldwide and especially in European countries. They also consulted with pioneers and experts in the field.</span></p> <p class="p1"><strong>Results:</strong> Based on published data, the authors clarify existing policies of using POX and initial clinical assessment, aiming to a standardized approach of screening and diagnostic follow-up, when needed. Key issues for future research and evaluation were identified and addressed.</p> <p class="p1"><span class="s1"><strong>Conclusions:</strong> The authors clarify existing policies in the use of POX, aiming to suggest the most appropriate way of using the test for compulsory screening term newborns during the early neonatal period in Greece. Special conditions of screening are being discussed. Public health organizations and private health agencies will have an important role in quality assurance and surveillance of this screening test aiming to significantly reduce morbidity and mortality from c/s-CHD in Greece.</span></p> Andreas C. Petropoulos George Daskalakis Fani Anatolitou Makarios Eleftheriadis Panos Antsaklis Athina Moutafi Panagiotis Petropoulos Anastasia Varvarigou Antonia Charitou Copyright (c) 2021 © Hygeia Press 2021-06-28 2021-06-28 10 2 e100211 e100211 10.7363/100211 Laryngomalacia, GER, and sleep apnea are BRUEing – Sometimes! <p>Brief resolved unexplained events (BRUE) constitute the newest nomenclature of near-miss SIDS, later on termed ALTE. These events have been putatively assigned to the sleeping state and suspected to involve airway obstruction. The current study in the Journal (Nosetti et al., 2021, <a href="" target="_blank" rel="noopener"></a>) identifies laryngomalacia and gastroesophageal reflux as being frequently associated with BRUE. The potential implications of such associations are discussed.</p> <p> </p> David Gozal Copyright (c) 2021 © Hygeia Press 2021-06-04 2021-06-04 10 2 e100206 e100206 10.7363/100206 Off-label and unlicensed drug treatments in Neonatal Intensive Care Units: a systematic review <p class="p1"><span class="s1">Newborns are particularly susceptible to off-label and unlicensed (OLUL) drug treatments, especially in the intensive care setting, inferring from dosing regimens and indications supported in older populations and built on non-neonatal pathophysiology. This use leads to unpredictable drug effectiveness and safety and, therefore, an increased probability of medication errors and adverse drug reactions. An extensive literature search was conducted in MEDLINE, Scopus, and Web of Science for papers published from 2011 to 2020 considering OLUL drug use in Neonatal Intensive Care Units (NICUs). Of the 902 studies retrieved, 618 after duplicates were removed, 74 full texts were carefully assessed for eligibility and, in the end, 23 published studies were included, representing a total of 6,762 patients in 80 NICUs worldwide. Considering overall prescriptions, 43.5% were OL and 11.1% were UL. Most studies found that more than 50% of the newborns were exposed to at least 1 OLUL drug and 10 of them reported a rate higher than 90%. Most prescribed drug classes in an OL manner were anti-infectives for systemic use drugs, including ampicillin and gentamicin, followed by nervous system drugs such as fentanyl. The most prescribed drug class in a UL manner was nervous system drugs, being caffeine the most prescribed one. The main reasons for OL prescribing included age and dose, and for UL prescribing, modifications of licensed drugs, extemporaneous preparations, or changes in the pharmaceutical forms. Very preterm, lower birth weight, disease severity, and longer length of stay in the NICU were associated with higher OLUL prescribing. These findings show that despite recent attempts by international regulatory authorities to develop more clinical trials in the pediatric population, OLUL drug use is still widespread, particularly among newborns in NICUs. More efforts must be made by these regulatory entities to ensure the development of safer drugs for the neonatal period.</span></p> Fábio Reis Rita Pissarra Henrique Soares Paulo Soares Hercília Guimarães Copyright (c) 2021 © Hygeia Press 2021-07-27 2021-07-27 10 2 e100213 e100213 10.7363/100213 Potential effects of lactoferrin as antiviral and neoadjuvant therapy in pediatric patients with viral gastroenteritis <p class="p1"><span class="s1">Viral gastroenteritis is a prevalent disease in children. Each year, around 111 million children suffer from viral gastroenteritis. Clinical features such as fever, nausea, vomiting, and diarrhea may result in severe cases requiring hospitalization. Current therapies of this disease are symptomatic therapies, which are focused on patient rehydration. Previous studies found that lactoferrin (LF) is a milk protein known to have antiviral potential, suggesting the possibility of utilizing it as an alternative therapy for viral gastroenteritis. This literature review aims to determine the potential effects of LF in treatment and prevention, thereby reducing the incidence and severity of viral gastroenteritis. A literature search for related articles published in the past 20 years was performed on PubMed, EBSCOhost, ProQuest </span><span class="s2">and another source</span><span class="s1"> using the main keywords “lactoferrin, viral, and gastroenteritis”. There were 6 articles assessed in this review. Several clinical trials have shown that giving LF supplements could significantly reduce the duration and the severity of gastroenteritis, especially with high doses of LF (0.49-1 g). Therefore, the efficacy of LF in pediatric gastroenteritis worked in a dose-dependent manner. However, mixed results were reported in the clinical trials assessing the efficacy of LF against viral gastroenteritis, but this could be due to the low doses of LF used. In conclusion, LF could be used as a complementary treatment against pediatric gastroenteritis, but further studies using high LF doses against pediatric viral gastroenteritis need to be evaluated further.</span></p> Alver Prasetya Robby Soetedjo Gabriel Tandecxi Brigitte Leonie Rosadi Edward Davis Maureen Miracle Stella Ignatius Ivan Linawati Hananta Copyright (c) 2021 © Hygeia Press 2021-06-26 2021-06-26 10 2 e100214 e100214 10.7363/100214 Relationship between laryngomalacia and sleep-related breathing disorders in infants with brief resolved unexplained events <p class="p1"><strong>Introduction:</strong> Brief resolved unexplained events (BRUE) occur during infancy. It is characterized by one or more symptoms, including skin color change, shortness of breath and unresponsiveness. Laryngomalacia is the most frequent cause of stridor in infants and results in the collapse of the supraglottic structures during inspiration and intermittent obstruction of the upper airways. To our knowledge, the relationship between BRUE and laryngomalacia has been little investigated.</p> <p class="p1"><strong>Methods:</strong> The medical records of 448 children (age &lt; 12 months) treated for BRUE between July 2011 and March 2018 and followed up until March 2020 were retrospectively reviewed. Endoscopic evaluation was performed using a flexible fibrolaryngoscope. All patients underwent a brief polysomnography and 24-h cardiorespiratory monitoring. Cardiorespiratory and oxygen saturation monitoring was continued at home; 94% of patients underwent follow-up.</p> <p class="p1"><strong>Results:</strong> Laryngeal fiberoptic endoscopy revealed laryngomalacia in 11% of children with a clinical history of BRUE. Laryngomalacia was associated with obstructive/mixed apnea in 67%. Home cardiorespiratory monitoring showed a gradual reduction in the number of respiratory events during follow-up and complete resolution of laryngomalacia in 88% of patients.</p> <p class="p1"><strong>Conclusions:</strong> This is the first report that showed follow-up data from cases of BRUE with laryngomalacia. The improvement in laryngomalacia alone, although not complete, was sufficient to improve obstructive events.</p> Luana Nosetti Francesca De Bernardi Eleonora Sica Patrizia Latorre Massimo Agosti Paolo Castelnuovo Giulia Cocciolo Marco Zaffanello Copyright (c) 2021 © Hygeia Press 2021-06-04 2021-06-04 10 2 e100207 e100207 10.7363/100207 The effect of table salt as a treatment of umbilical granuloma in neonates <p class="p1"><span class="s1"><strong>Introduction:</strong> Umbilical granuloma is a widespread problem that may cause anguish to the parents. </span></p> <p class="p1"><span class="s1"><strong>Patients and method:</strong> A randomized controlled study was conducted on 85 neonates aged 2-4 weeks (42 males and 43 females) with a diagnosis of umbilical granuloma. They were randomly divided into 2 groups; group A included 42 patients (20 males and 22 females), and group B included 43 patients (21 males and 22 females). Parents of group A patients were instructed to use a small amount of common salt on the granuloma after cleaning it, and to cover the salt by blaster for 30 minutes to keep it in place; after that, the blaster had to be removed, and the umbilicus was cleaned with sterile cotton and water to remove the salt. The procedure was repeated for 3 days straight. Group B was treated once by applying clean dry silver nitrate sticks (concentration of 20%) on the granuloma; contact with normal skin was avoided. The procedure was performed by the researcher himself at his clinic. Statistical analysis was done by using Fisher Exact test. </span></p> <p class="p1"><span class="s1"><strong>Results:</strong> In group A, 39 (92.9%) responded to treatment by salt, while 3 (7.1%) of them did not respond. In group B, 41 (95.3%) responded to treatment by silver nitrate, while 2 (4.7%) did not respond. There was no significant difference between the two groups, with p-value = 0.676. </span></p> <p class="p1"><span class="s1"><strong>Conclusion:</strong> Umbilical granuloma can be treated with topical application of common salt; such a method can be considered a valid alternative for its effectiveness, safety, and simplicity. </span></p> Mazin Mahmoud Fawzi Copyright (c) 2021 © Hygeia Press 2021-06-09 2021-06-09 10 2 e100239 e100239 10.7363/100239 Category II non-reassuring fetal heart rate pattern and risk of admission to Neonatal Intensive Care Unit <p class="p1"><span class="s1"><strong>Background:</strong> The relationship between non-reassuring fetal heart rate (FHR) pattern, acidemia at birth and neonatal morbidity remains unclear. Our aim was to compare low versus high pH cord blood infants of women detected with a Category II FHR pattern for which the impact is unclear. </span></p> <p class="p1"><span class="s1"><strong>Methods: </strong>A prospective study of 185 low-risk pregnant women in labor at &gt; 37<sup>0/7</sup> weeks of gestation with a singleton fetus was conducted at a single center. Category II trace was defined by the presence of tachycardia or bradycardia, variable and late decelerations, marked variability at least 30 minutes in the 120 minutes prior to delivery. The primary outcome included the need for resuscitation and Neonatal Intensive Care Unit (NICU) admission. The cohort was also stratified into three categories according to admission to NICU and pH threshold ([i] umbilical artery blood pH &lt; 7.15 and admitted; [ii] pH &gt; 7.15 and admitted; [iii] not admitted).</span></p> <p class="p1"><span class="s1"><strong>Results:</strong> 23% (43/185) of infants of women detected with Category II FHR pattern needed NICU admission. Category II FHR pattern was associated with low pH at birth, and the need for resuscitation was more frequent among infants in the lower pH group (73% vs. 10%, p &lt; 0.05). Indices of right (tricuspid annular plane systolic excursion [TAPSE]: 7.3 ± 0.9 mm) and left ventricular performance (fractional shortening: 31% ± 8.9%, transmitral E’/A’ 0.9 ± 0.3) were low compared to normative data for healthy infants. CK, CK-MB, and left-to-right/bidirectional shunts at PFO and PDA were higher overall at 72 hours of age.</span></p> <p class="p1"><span class="s1"><strong>Conclusions:</strong> Category II FHR is associated with resuscitation at birth, NICU admission, and length of hospitalization. </span></p> Laura Mihaela Suciu Amalia Fagarasan Claudiu Marginean Adrianne Rahde Bischoff Patrick J. McNamara Copyright (c) 2021 © Hygeia Press 2021-07-26 2021-07-26 10 2 e100210 e100210 10.7363/100210 Ischemia-modified albumin as a novel marker for diagnosis of necrotizing enterocolitis in newborn infants <p class="p1"><strong>Background:</strong> Necrotizing enterocolitis (NEC) is the most common neonatal gastrointestinal emergency. Ischemia-modified albumin (IMA) is a marker of oxidative stress and ischemia. Its role in early diagnosis of NEC has been little investigated so far.</p> <p class="p1"><strong>Aim: </strong>The objective of our research was to study the role of serum IMA in diagnosis of NEC in newborn infants.</p> <p class="p1"><strong>Material and methods: </strong>The study was carried out on 80 neonates; 40 with NEC and 40 controls, subjected to serum IMA dosage with ELISA.</p> <p class="p1"><span class="s1"><strong>Results:</strong> There was a highly statistically significant increase in IMA in both preterm (60.59 ± 34.97 U/ml) and full-term infants with NEC (60.50 ± 29.88 U/ml) compared to their controls (11.28 ± 3.09 U/ml; 5.34 ± 1.88 U/ml). The positive predictive value of IMA in preterm and full-term with NEC was 100% and 94.74%, while the negative predictive value was 80% and 90.48%, respectively. There was a statistically significant increase in serum level of IMA in stage II NEC compared to stage I NEC as well as in non-survivor cases. Significant positive correlation between serum IMA level and duration of recovery from NEC was detected.</span></p> <p class="p1"><strong>Conclusions:</strong> IMA is a sensitive marker for diagnosis of NEC in full-term and preterm infants and can predict severity of NEC and death.</p> Safaa ELMeneza Asmaa Okasha Manal Abd El-Hafez Naeema Hussein Copyright (c) 2021 © Hygeia Press 2021-05-25 2021-05-25 10 2 e100205 e100205 10.7363/100205 The effects of physical activity on some physiological indices of mother and neonate <p class="p1"><span class="s1"><strong>Background:</strong> Physical activity can bring about more favorable health results for both mother and neonate. </span></p> <p class="p1"><span class="s1"><strong>Objectives: </strong>The purpose of this study was to investigate the effect of physical activity on some physiological indices of mother and neonate.</span></p> <p class="p1"><span class="s1"><strong>Design and methods: </strong>In this <em>ex post facto</em> study, 60 pregnant women (age 26.9 ± 4.0 years, height 161.8 ± 5.2 cm and weight 63.0 ± 4.9 kg) were selected from health centers and private clinics in Shiraz, Iran. Based on the score obtained from completion of a physical activity questionnaire during pregnancy, the participants were classified into 4 groups: 1) active, 2) inactive, 3) becoming active, and 4) becoming inactive. The maternal type of delivery, body weight and body fat percentage, as well as the neonatal birth weight and height and Apgar score at 1 and 5 minutes, were measured. To analyze the data, a one-way ANOVA and Tukey’s post hoc test were used at the level of p ≤ 0.05.</span></p> <p class="p1"><span class="s1"><strong>Results:</strong> The mean weight gain in pregnant women in the active group was significantly lower than that of the inactive group (p ≤ 0.05), but there was not a significant difference between the becoming active and becoming inactive groups (p &gt; 0.05). Participation in physical activity does not affect the body fat percentage and type of pregnancy in pregnant women (p &gt; 0.05). Additionally, participation in physical activity does not have a significant effect on the neonate’s growth and health (p &gt; 0.05).</span></p> <p class="p1"><span class="s1"><strong>Conclusions:</strong> It seems that although the participation of pregnant mothers in physical activity is associated with a lower weight gain in pregnancy, there is no significant effect on other physiological indices of mother and neonate.</span></p> Seyed Ali Hosseini Niloofar Arabpour Nasibeh Kazemi Saeedeh Shadmehri Iman Fathi Copyright (c) 2021 © Hygeia Press 2021-06-30 2021-06-30 10 2 e100243 e100243 10.7363/100243 Recurrent intraparenchymal brain hemorrhage in an infant with factor XIII deficiency <p class="p1">Factor XIII deficiency is an autosomal recessive disorder with an incidence of 1 in 1-5 million. On activation factor XIII stabilizes clot formation by cross-linking fibrin strands. Deficiency is characterized by severe bleeding due to impairment in clot formation. We describe a case of a child presenting with drowsiness following a trivial fall and trauma to the head. An emergency CT scan of the brain was suggestive of acute on chronic (recurrent) hemorrhage. Intraoperatively he was noted to have an intraparenchymal multiloculated cystic cavity with a thinned out cortex in the right frontal region. The child underwent right frontal craniotomy and decompression of an intracerebral hemorrhage. He was subsequently diagnosed to have factor XIII deficiency. He is presently on monthly cryoprecipitate prophylaxis with which he has not experienced a recurrence of a similar episode.</p> Devdeep Mukherjee Dibyendu De Satyajit Das Gopikrishna Kurasa Copyright (c) 2021 © Hygeia Press 2021-05-25 2021-05-25 10 2 e100201 e100201 10.7363/100201 Presurgical nasoalveolar molding: an advantageous adjunctive neonatal therapy for cleft lip and palate defects in 2 clinical cases <p class="p1"><span class="s1">The most common congenital craniofacial anomalies are labial-alveolo-palatal clefts. Infants with these deformities may have problems and limitations with breathing, feeding, speaking, hearing, as well as psychological problems. </span></p> <p class="p1"><span class="s1">The treatment protocol for these patients is carried out using an interdisciplinary approach. </span></p> <p class="p1"><span class="s1">Thus, in addition to surgical reconstruction, presurgical neonatal orthopedics have shown considerable advantages in the treatment of such malformations. </span></p> <p class="p1"><span class="s1">Recently, presurgical nasoalveolar molding (PNAM) has been introduced to prevent nasal deformities, and to obtain a satisfactory surgical result and good psychological reintegration. </span></p> <p class="p1"><span class="s1">This article describes, through 2 clinical cases, the technique of preparation of PNAMs, their surgical and clinical advantages, as well as the role of a multidisciplinary approach in effectively managing disorders related to labio-alveolo-palatal clefts. </span></p> Sara Sabir Mohamed Azhari Hasnaa Rokhssi Nadia Merzouk Oussama Bentahar Copyright (c) 2021 © Hygeia Press 2021-07-06 2021-07-06 10 2 e100249 e100249 10.7363/100249 Extremely preterm infant weighing 350 g: too small to survive? <p class="p1">Every year around 15 million premature neonates are born in the world, and this number is continuously increasing. The incidence of premature birth varies between 5% and 18% throughout the world. Despite advancements in medicine and technology and increased evidence-based diagnostic and treatment recommendations, prematurity is the most common cause of death among children under 5 years of age. The sequelae in the survivors of extreme prematurity are mental disability, cognitive impairment, cerebral palsy, blindness, deafness and chronic illness. Considering ethical and economic implications, neonatal survival and morbidity prognosis, resuscitation of neonates of borderline gestation differs in various countries and many international organisations do not recommend active resuscitation and treatment of newborns of up to 25 weeks of gestation. We present a case study of one of the smallest newborns in the world and the smallest newborn known to survive in Lithuania.</p> Ieva Šliaužienė Vaida Aleksejūnė Viktorija Ambroževičiūtė Ilona Aldakauskienė Rūta Jolanta Nadišauskienė Rasa Tamelienė Copyright (c) 2021 © Hygeia Press 2021-06-07 2021-06-07 10 2 e100212 e100212 10.7363/100212