Neonatal Seizures in Low- and Middle-Income Countries: A Review of the Literature and Recommendations for the Management.

Neonatal seizures are a common cause of neonatal intensive care unit (NICU) admission and a significant source of morbidity and mortality worldwide. Over the recent decades, there have been significant improvements in perinatal and neonatal medicine and electroencephalograp hic monitoring that have enhanced the diagnosis and treatment of neonatal seizures in highincome countries. However, the management of neonatal seizures remains a major challenge in low- to middle-income countries, where the availabilityof resources is limited. The purpose of this article is to present a comprehensive review of the current evidence on the etiology, pathophysiology, diagnosis, and treatment of neonatal seizures and to offer practical management recommendations that could be implemented in resource-limited settings. Cite this article as: Spenard S, Ivan Salazar Cerda C, Cizmeci MN. Neonatal seizures in low and middleincome countries: Review of the literature and recommendations for the management. Turk Arch Pediatr. 2024;59(1):13-22.

Turkish Neonatal Society Guideline on the Diagnosis and Management of Germinal Matrix Hemorrhage-Intraventricular Hemorrhage and Related Complications.

Germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) remains an important cause of brain injury in preterm infants, and is associated with high rates of mortality and adverse neurodevelopmental outcomes, despite the recent advances in perinatal care. Close neuroimaging is recommended for both the detection of GMH-IVH and for the follow-up of serious complications, such as post-hemorrhagic ventricular dilatation (PHVD). Although the question when best to treat PHVD remains a matter of debate, recent literature on this topic shows that later timing of interventions predicted higher rates of neurodevelopmental impairment, emphasizing the importance of a well-structured neuroimaging protocol and timely interventions. In this guideline, pathophysiologic mechanisms, preventive measures, and clinical presentations of GMH-IVH and PHVD will be presented, and a neuroimaging protocol as well as an optimal treatment approach will be proposed in light of the recent literature.

Comparison between the use of saline and seawater for nasal obstruction in children under 2 years of age with acute upper respiratory infection.

BACKGROUND/AIM: The effectiveness of isotonic and hypertonic saline solutions used to open the nasal passage and improve clinical symptoms was compared in children under 2 years of age admitted with the common cold. MATERIALS AND METHODS: The study was performed as a randomized, prospective, and double-blind study. The study included 109 children. The children using saline (0.9%) and seawater (2.3%) as nasal drops (the patient group) and the control group (in which nasal drops were not administered) were compared. Seventy-four patients received nasal drops from package A (seawater) in single days and from package B (physiological saline) in double days. RESULTS: The mean age of the patients was 9.0 ± 3.9 months and the numbers of boys and girls were 65 (59.6%) and 44 (40.4%), respectively. There was no significant difference between Groups A and B in terms of nasal congestion (P > 0.05). However, a significant difference was found between the control group and Groups A and B (P < 0.05). CONCLUSION: Relief was seen in nasal congestion, weakness, sleep quality, and nutrition with the use of both saline and seawater in children with the common cold. Seawater or saline drops may be added to standard treatment protocols.

Cord-blood 25-hydroxyvitamin D levels and risk of early-onset neonatal sepsis: a case-control study from a tertiary care center in Turkey.

UNLABELLED: Vitamin D has been linked with immunity, and the immunomodulatory role of this molecule in regulating key elements of the immune system has become an area of intense scientific investigation. We designed a case-control study to investigate whether neonates with early-onset neonatal sepsis (EONS) had lower levels of vitamin D. The primary exposure for the analysis in the study was the cord-blood level of 25-hydroxyvitamin D (25(OH)D). Of the 2571 live births occurring during the 18-month study period, 53 infants were admitted to the neonatal intensive care unit with suspected EONS. After clinical and laboratory confirmation, 40 newborns with EONS and 43 controls were analyzed. Cord-blood 25(OH)D levels of infants in the study group were significantly lower than that of the control group (median 12.6 ng/mL (3.1-78.9) vs. 21 (5-118); p = 0.038, respectively). In multivariate models, a low cord-blood 25(OH)D level (<30 ng/ml) was associated with an increased risk of EONS (OR = 5.6; 95% CI = 1.3-23.5). CONCLUSION: Cord-blood 25(OH)D levels of neonates with EONS were significantly lower than that of the healthy controls, and a low level of cord-blood vitamin D was found to be associated with an increased risk of EONS. Further studies are warranted to confirm this association.

An abrupt increment in the respiratory rate is a sign of neonatal pneumothorax.

OBJECTIVE: The objective of the present study was to investigate the early clinical signs of neonatal pneumothorax. METHODS: A case-control study at a level III referral center from 2006 to 2012 was conducted. For each neonate with pneumothorax (Group I), one control subject (Group II) was identified by selecting an infant born within the same week with a gestational age of ± 7 days and with a birth weight within 10% of the index case. The primary outcome was to investigate the clinical findings preceding the onset of pneumothorax. Secondary outcome was to assess the risk factors. RESULTS: Of the 1375 infants admitted, 39 had a pneumothorax. Patients with pneumothorax showed significantly increased respiratory rates preceding the definitive diagnosis when compared with control patients (median: 16 (0-58) versus 4 (0-10); p < 0.001). An increase in the respiratory rate was found to be a significant clinical parameter preceding the diagnosis of pneumothorax (odds ratio (OR): 1.47, 95% confidence interval (CI): 1.12-2.14, p < 0.001; R(2) = 0.80). Sensitivity and specificity of this sign were found to be 77 and 90%, respectively. CONCLUSION: An abrupt increase in the respiratory rate would be used as a reliable parameter to help determine an impending pneumothorax in neonates.

Neonatal inflammatory submandibular sialadenitis associated with prenatal methyldopa exposure.

Inflammation of a salivary gland is an uncommon condition in the neonatal period, and an isolated form of submandibular acute inflammatory sialadenitis is an exceptionally rare phenomenon. Among various conditions that might lead to submandibular acute inflammatory sialadenitis, maternal use of drugs during pregnancy should be questioned as there may be possible associations. Herein, we describe a late preterm infant who presented with a large submandibular mass. After excluding possible pathogenic causes, maternal use of methyldopa was believed to be the only factor associated with this condition. To the best of our knowledge, no such relationship has been documented in previously published literature.

A descriptive study of transient neonatal feeding intolerance in a tertiary care center in Turkey.

OBJECTIVE: To investigate the characteristic features of transient neonatal feeding intolerance (TNFI) during the hospitalization for birth in the maternity ward. DESIGN: A prospective follow-up study. SETTING: Maternity ward and neonatal intensive care unit (NICU) in an academic medical center. PARTICIPANTS: Term (≥ 37-weeks gestation) infants admitted to the neonatal intensive care unit with recurrent vomiting and refusal to feed between January and December 2011. These infants were prospectively followed-up at 1, 2, 4, 6 months of age in the outpatient clinic. RESULTS: During the study period 1280 infants were evaluated in the maternity ward. Forty-eight (3.75%) neonates with repeated vomiting and refusal to feed were hospitalized from the maternity unit to the NICU Level I on the first postnatal day for further investigation. All infants started vomiting in the first day (median 5.75 hours; interquartile range: 1-24) and recovered by the 48(th) postnatal hour (median 27.5 hours; interquartile range: 14-48 hours). Laboratory and imaging studies showed no abnormalities. After discharge, 6-month follow-up of these infants showed no vomiting or feeding intolerance during well-child visits. CONCLUSIONS: Infants with TNFI can be managed with close observation and supportive measures if they have no other indications of underlying disease. We believe that expectant management and supportive measures under skilled nursing care will prevent unnecessary diagnostic evaluation, mother/infant separation, and prolonged hospital stay.

Detection of cord blood hepcidin levels as a biomarker for early-onset neonatal sepsis.

Early-onset neonatal sepsis (EONS) continues to be a severe condition associated with a high mortality and morbidity. However, symptoms and laboratory markers of this serious condition are nonspecific and currently there are no available standard tests to provide perfect diagnostic accuracy. An early recognition and initiation of antimicrobial therapy are essential in order to prevent morbidity and mortality. Hepcidin, the key regulator of iron homeostasis, is also an acute-phase reactant, which has a critical role in inflammation and contributes to host defense by interfering with microorganism's access to iron. Since hepcidin expression is induced by interleukin-6 (IL-6), it also plays role in the innate immune system. Recently, endogenous expression of hepcidin by macrophages and neutrophils in response to bacterial pathogens confirmed its role in innate immunity. The clear link between the hepcidin molecule and innate immunity may be used for the detection of EONS. We hypothesized that an increased level of hepcidin in cord blood may be used as a reliable biological marker of EONS and designed a prospective cohort study to test this hypothesis and collected pilot data. Cord blood samples of all infants born between January 2009 and December 2010 at our university hospital were collected after parental consent and a total of 38 infants were enrolled in the study who fulfilled the sepsis criteria. The range of cord blood hepcidin was found to be significantly increased in newborns with EONS (min-max: 118.1-8400 ng/mL). To the best of our knowledge, this is the first study to investigate the pathophysiologic relevance of hepcidin in EONS and demonstrate increased levels of hepcidin in cord blood as an acute-phase reactant in response to sepsis.

Decreased mean platelet volume in children with acute rotavirus gastroenteritis.

BACKGROUND: The contribution of platelets to the inflammatory response via several platelet derived mediators is well recognized. The role of mean platelet volume (MPV) in infectious and inflammatory disorders, however, has not yet been well-established. While some of the previous studies demonstrated that MPV acted as a positive acute phase reactant, several others suggested its role as a negative acute phase reactant. In the current study, we aimed to assess the role of MPV as an acute phase reactant in children with rotavirus gastroenteritis. METHODS: We undertook a prospective, randomized, controlled, cross-sectional study and enrolled children diagnosed with acute rotavirus gastroenteritis and healthy controls (HC), between August and November 2012. Children with acute gastroenteritis were assigned either in the rotavirus-positive acute gastroenteritis (RPAG) or in the rotavirus-negative acute gastroenteritis (RNAG) group depending on their stool antigen results. Patients were also classified into two groups based on their Vesikari score (< 11: non-severe and ≥ 11: severe). Complete blood count and C-reactive protein (CRP) levels were assessed for all patients. We compared MPV between RPAG, RNAG and HC groups and investigated the association, if any, among MPV, platelets, white blood count and CRP. RESULTS: In total 100 RPAG (54 males; mean age: 38.74 ± 41.45 months), 100 RNAG (58 males; mean age: 32.84 ± 29.64 months) children and 100 HC (43 males; mean age: 33.21 ± 32.55 months) were enrolled into the study. Mean platelet counts were well-matched among groups (p > 0.05). We observed a steady decline in MPV (fL) in the HC, RPAG and RNAG groups (median 7.80, 7.35 and 7.30, respectively; p < 0.0001). We did not find an association between MPV and the clinical score of gastroenteritis (p > 0.05). CONCLUSION: We found that MPV could be used as an acute phase reactant in children with rotavirus gastroenteritis. We believe that the current study will contribute to our understanding of MPV as an inflammatory marker.

Bohn's nodules: peculiar neonatal intraoral lesions mistaken for natal teeth.

Inclusion cysts of transient nature during the neonatal period are developmental lesions, which are seen in the oral cavity of the newborn infant. These lesions are classified into three subtypes according to their localizations. When noticed by the anxious parents on the gingival surfaces, they are often mistaken for natal teeth, which lead to seeking medical attention. Herein, we describe a newborn infant with Bohn's nodules to increase the awareness of the physicians to this benign, self-limiting lesion.

A Rare Cause of Chronic Headache that May Be Misdiagnosed as Migraine: Chronic Carbon Monoxide Poisoning.

Differential diagnosis of primary headache disorders can be challenging for physicians. Although the association of headache with acute carbon monoxide intoxication is very well-defined, in refractory nonspecific headaches associated with chronic low dose exposure to carbon monoxide, CO intoxication is usually overlooked, mostly due to vague symptoms. Herein we present a 15-year-old female patient with chronic carbon monoxide poisoning who was undergoing two years of follow-up care for migraines. Chronic carbon monoxide intoxication may mimic the episodic nature and familial predisposition of migraine attacks. Normal carboxyhemoglobin levels do not exclude the diagnosis, and smoking is a confounding factor. In emergency rooms, patients presenting with headaches had higher levels of carboxyhemoglobin, but, as far as we know, there have been no studies investigating carboxyhemoglobin levels in migraine patients. Chronic carbon monoxide poisoning should be suspected in migraine patients, especially if the attacks occur during winter months.

Social prejudice hindering proper use of car safety seats.

The compliance of parents with child passenger safety (CPS) has been mainly explained by their level of knowledge. Social, ethnic and cultural factors have not been investigated in detail. This study investigated the rate of compliance of parents with CPS guidelines, as well as the factors hindering it. Parents of infants aged 2-10 days were enrolled. The proportions of families obtaining a car safety seat (CSS; 57%) and complying with CPS recommendations (2%) were very low. Most of the parents thought CSS were harmful for infants (mother, 57%; father, 63%), despite having already purchased one. Parents believed their children to be too small to use CSS and cannot sit in CSS because they should lie flat on their backs at all times. These prejudices may be due to the social and cultural circumstances specific to Turkey, or corresponding findings may be found in countries with similar socioeconomic status.

The utility of special radiological signs on routinely obtained supine anteroposterior chest radiographs for the early recognition of neonatal pneumothorax.

BACKGROUND: Bedside chest radiographs used for the confirmation of diagnosis of pneumothorax in the neonatal intensive care unit (NICU) are routinely obtained in the supine position. However, pneumothoraces may not appear in the classically described forms on these radiographs, resulting in a delayed diagnosis. OBJECTIVE: To assess the utility of special radiological signs in the neonatal population for the early recognition of pneumothorax. METHODS: A case-control study was conducted at a level III referral center from January 2006 to December 2012. For each neonate with pneumothorax, one infant was selected for the control group. A senior radiologist and neonatologist experienced in reading chest radiographs evaluated each radiograph for the presence of special radiological signs. RESULTS: Of the 1,375 infants admitted to the NICU during the study period, 39 had a pneumothorax. A total of 223 radiographs were scored and 46% of the neonates were found to have occult pneumothoraces before they were clinically diagnosed. Twenty-six percent had a single sign detected on a radiograph, whereas 20% had multiple signs. The time interval between the appearance of these signs and clinical diagnosis ranged between 0.5 and 27 h. CONCLUSIONS: The present study shows that the recognition of these signs would assist the physician in identifying occult pneumothorax earlier in its course. Physicians dealing with critically ill infants should ensure that they can recognize these radiological signs.

[Borderline cerebellar tonsillar ectopia in a child with headache. Case report]. / Ectopia amigdalina cerebelosa borderline en un niño con cefalea. Caso clínico.

Frequent headache is a symptom that leads to significant distress and functional impairment, both in childhood and in adulthood. Some medical conditions are associated with a higher frequency of headaches. Borderline cerebellar tonsillar ectopia which may be defined as the downward extension of cerebellar tonsils of <5 mm below the foramen magnum is among these conditions. Although questions persist about the clinical significance of this rare entity on headache, there are studies reporting severe headache syndrome in 16% of these patients. We report a 9-year old male patient, who presented to our clinic with a frontal headache of 5 years' duration, and was found to have borderline cerebellar tonsillar ectopia on magnetic resonance imaging. To the best of our knowledge, there has not been a reported case of this coexistence at this early stage of life. We would like to contribute to the literature, owing to the very rare and atypical presentation of this entity in the early childhood period.

Ectopia amigdalina cerebelosa borderline en un niño con cefalea. Caso clínico / Borderline cerebellar tonsillar ectopia in a child with headache. Case report

La cefalea es un síntoma que conlleva un malestar signifcativo y deterioro funcional en quienes lo sufren con frecuencia, tanto en la infancia como en la edad adulta. Algunas afecciones se asocian con una mayor frecuencia de cefaleas. La ectopia amigdalina cerebelosa borderline, defnida como la protrusión de las amígdalas cerebelosas por foramen magnum), es una de esas afecciones. Aunque no está claro el signifcado clínico de esta entidad como causa de cefalea, hay estudios que informaron su asociación en el 16% de los pacientes. Se presenta el caso de un paciente de 9 años que acudió a la consulta por padecer una cefalea frontal de 5 años de evolución. Se diagnosticó ectopia amigdalina cerebelosa borderline mediante una resonancia magnética. Se describe este caso dado lo atípico de la presentación de esta entidad en la infancia.

Frequent headache is a symptom that leads to signifcant distress and functional impairment, both in childhood and in adulthood. Some medical conditions are associated with a higher frequency of headaches. Borderline cerebellar tonsillar ectopia which may be defned as the downward extension of cerebellar tonsils of < 5 mm below the foramen magnum is among these conditions. Although questions persist about the clinical signifcance of this rare entity on headache, there are studies reporting severe headache syndrome in 16% of these patients. We report a 9-year old male patient, who presented to our clinic with a frontal headache of 5 years' duration, and was found to have borderline cerebellar tonsillar ectopia on magnetic resonance imaging. To the best of our knowledge, there has not been a reported case of this coexistence at this early stage of life. We would like to contribute to the literature, owing to the very rare and atypical presentation of this entity in the early childhood period.

Ectopia amigdalina cerebelosa borderline en un niño con cefalea. Caso clínico / Borderline cerebellar tonsillar ectopia in a child with headache. Case report

La cefalea es un síntoma que conlleva un malestar signifcativo y deterioro funcional en quienes lo sufren con frecuencia, tanto en la infancia como en la edad adulta. Algunas afecciones se asocian con una mayor frecuencia de cefaleas. La ectopia amigdalina cerebelosa borderline, defnida como la protrusión de las amígdalas cerebelosas por foramen magnum), es una de esas afecciones. Aunque no está claro el signifcado clínico de esta entidad como causa de cefalea, hay estudios que informaron su asociación en el 16% de los pacientes. Se presenta el caso de un paciente de 9 años que acudió a la consulta por padecer una cefalea frontal de 5 años de evolución. Se diagnosticó ectopia amigdalina cerebelosa borderline mediante una resonancia magnética. Se describe este caso dado lo atípico de la presentación de esta entidad en la infancia.(AU)

Frequent headache is a symptom that leads to signifcant distress and functional impairment, both in childhood and in adulthood. Some medical conditions are associated with a higher frequency of headaches. Borderline cerebellar tonsillar ectopia which may be defned as the downward extension of cerebellar tonsils of < 5 mm below the foramen magnum is among these conditions. Although questions persist about the clinical signifcance of this rare entity on headache, there are studies reporting severe headache syndrome in 16% of these patients. We report a 9-year old male patient, who presented to our clinic with a frontal headache of 5 years duration, and was found to have borderline cerebellar tonsillar ectopia on magnetic resonance imaging. To the best of our knowledge, there has not been a reported case of this coexistence at this early stage of life. We would like to contribute to the literature, owing to the very rare and atypical presentation of this entity in the early childhood period.(AU)

Is PFAPA syndrome really a sporadic disorder or is it genetic?

Periodic fever syndromes are a group of disorders sharing similar symptoms, characterized primarily by regularly recurring fevers. PFAPA syndrome, one of the members of this group of disorders, is a clinical entity of unknown etiology which is frequently seen in the early childhood. Currently, the pathogenesis and the genetic basis of most of the disorders in the periodic fever spectrum are known, other than that of PFAPA syndrome. Although, classically PFAPA syndrome is known as a sporadic disease, we propose that it is not sporadic. We think that PFAPA syndrome may be an inherited disease and this hypothesis is supported by the clinical mimicry of PFAPA syndrome with other periodic fever syndromes with well-known genetic transmissions, frequent occurrence of the condition in members of the same family and emergence of common genetic mutations in the periodic fever syndrome spectrum. Moreover, our clinical observation that most of the patients diagnosed with PFAPA syndrome were of the same families strongly suggest a probable genetic transmission of this disorder. We have decided to discuss this hypothesis to contribute to the literature and assist our colleagues who are dealing with this commonly overlooked and often misdiagnosed disorder.

Do not overlook an umbilical cord hernia before clamping.

An umbilical cord hernia is a rare midline abdominal defect. These masses may be easily overlooked at birth, which may result in an intestinal injury due to careless proximal application of the cord clamp. Herein, we present a newborn infant with an umbilical cord hernia who was managed by primary closure of the lesion.

Is acute dystonia an emergency? Sometimes, it really is!

Most cases of acute dystonia are mild and easy to manage; nevertheless, some of them can be fatal because of the involvement of certain muscle groups such as the laryngeal muscles, thus requiring urgent intervention. In the literature, approach to life-threatening acute dystonia has not been investigated thoroughly, although the diagnosis is a challenge, and treatment should be offered immediately. Herein the management of life-threatening acute dystonia is discussed via 2 case reports.