Review Article

Effect of Zinc supplementation on child development: a systematic review and meta-analysis Protocol

Soheila shahshahani, Firoozeh Sajedi, Shiva Fatollahierad

Iranian Journal of Child Neurology, Vol. 15 No. 1 (2021), , Page 9-17


Child development is one of the principal aspects of pediatrics. It is a multidimensional process, on which many factors may have different effects. Zinc is a nutritional trace element that has an essential role
in neuronal activity and, consequently, in brain development. Since Zinc deficiency is prevalent in developing countries, some clinical trials were conducted to evaluate the impact of zinc supplementation on child development. Thus, we decided to run a systematic review in this area to identify the effectiveness of zinc supplements on child development.
This systematic review protocol will include randomized controlled trials studies (RCTs) in which zinc supplementation was used versus placebo or no intervention, zinc supplementation with other micronutrients versus the same micronutrients without zinc. We will evaluate the effect of zinc alone and zinc co-supplementation with iron on child development. We will search the Medline,
Pubmed, EMBASE, ERIC, Psychinfo, the Cochrane Central Register of Controlled Trials (CENTRAL),, WHO International Clinical Trials Registry Platform (ICTRP), ISRCTN
Registry CINAHL, Web of Science and Scopus databases. The and the Cochrane Library website will also be searched for randomized trials which were registered and completed
but not published yet. Two researchers will independently screen titles and abstracts of citations and read the full texts of potentially relevant studies. The data extraction and quality assessment of
the papers will be done independently. Any disagreements that arise between the reviewers in the above-mentioned steps will beresolved through discussion. We will report our findings based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and use the Cochrane Collaboration’s tool for assessing the risk of bias. We will aim to synthesize the results in a meta-analysis if the interventions are similar in methods. Based on the similarities and differences of primary studies, we will use the best statistical methods.
This is a protocol of systematic Review and meta-analysis of the effect of zinc supplementation on child development.
The strengths of this protocol after meta-analysis are as follows:

● We will identify the strengths and weaknesses of each study.
● We will also study if zinc alone and zinc co-supplementation with
iron are useful for improving child development in terms of their age, their nutritional status, dose of the zinc supplementation, type of the zinc supplementation (salt), duration of the intervention and
iron or other nutrient co supplementations.
● We will assume that the measures used for the outcome will be heterogeneous between studies. We know that each study has its own quantity. We will use the random effect models for these heterogeneous data.

Research Article

How Antiepileptics May Change the Serum Level of Vitamin D, Calcium, and Phosphorus in Children with Epilepsy

Sasan Saket, Neda Varasteh, Ali Asghar Halimi Asl, Hedyeh Saneifard

Iranian Journal of Child Neurology, Vol. 15 No. 1 (2021), , Page 19-27

Studies have shown vitamin (Vit) D deficiency and bone disease in long-term use of antiepileptics, especially in young individuals. This study aimed to determine the relationship between antiepileptic drugs
and the level of Vit D, calcium (Ca), and phosphorus (P) in children with epilepsy at the Shohada Hospital from 2016 to 2017.

Methods & Materials
In this case-control study, 60 consecutive children with epilepsy at the Shohada Hospital from 2016 to 2017 under treatment with anticonvulsions for more than six months were enrolled as the case group.
The level of Vit D, Ca, and P was determined in the case group and compared with 60 children without seizure as the control group.
The mean Ca and P were alike across the groups (P > 0.05). The mean Vit D3 level was 31.3 and 40 in the case and control groups, respectively, with significant difference (P=0.0001). The mean Ca and P were alike across the types of drug in the case group (P > 0.05); however, the mean Vit D3 level was lower in the case versus control
group with significant difference (P=0.040).

Totally, according to the obtained results, it may be concluded that treatment with antiepileptic drugs, especially stimulant type, is related to the lower Vit D3 level, but not to the Ca and P levels.


sensory processing disorder (SPD) is a neurodevelopmental disorder that can negatively affect cognitive, emotional, and behavioral functioning. Therefore, assessing sensory processing is critical in children. This study aimed to provide a current comprehensive list of assessment instruments special about sensory processing in children aged between 0 and 14 years.
Materials & Methods
This systematic review focused on pediatric assessment of sensory processing. five electronic databases (Google Scholar, Web of Science, Scopus, PubMed, and ProQuest) were comprehensively searched for eligible studies, and language restriction (English) was applied. The search strategy consisted of keywords and medical subordinate headings for sensory processing and various pediatric assessment tools.
Thirty-four assessment tools were identified, of which nine met the predefined inclusion criteria. The test of ideational praxis, clinical observations of proprioception, and pediatric clinical test of sensory interaction for balance were clinical observational assessment tools. The final tool was a caregiver or teacher reported questionnaire. The obtained studies evaluated the clinical use and psychometric properties of these nine assessment tools.
The result of this study indicated that each of the sensory processing assessment tools considered various aspects of sensory processing. Selecting the most appropriate assessment tools to measure sensory processing function in children depends on specific components of sensory processing that need to be evaluated.

Risk factors and short-term complications of high-grade intraventricular hemorrhages in preterm neonates in training hospitals of Alborz

AliReza Jashni Motlagh, Azamolmolouk Elasagh, Elham Sedighipour, Mostafa Qorbani

Iranian Journal of Child Neurology, Vol. 15 No. 1 (2021), , Page 47-55



The aim of this study is to determine risk factors and short-term complications of high-grade intraventricular hemorrhages (IVHs) in preterm neonates. Other topics of investigation include the increase in complications of IVH with its severity and the effect of IVH risk factors on the severity of IVH.
Materials & Methods

We conducted a retrospective case-control study of 436 consecutive preterm neonates with high-grade (3, 4) IVHs admitted in training hospitals of Alborz University in Karaj, Iran, from 2012 to 2017. The risk factors and short-term complications were assessed and analyzed in the subjects by SPSS 19.


Out of 10 000 eligible neonates, we identified 1203 premature infants with IVH. A total of 436 infants with IVH grades 3 and 4 were allocated to the case group. The control group consisted of 767 infants with IVH grades 1 and 2. This study revealed that the most common risk factors of IVH include lack of corticosteroid use in 67.2%, low Apgar score in 10%, and surfactant use in 5.7% of the patients. Ten percent (31 cases) had short-term complications (18 hydrocephalus and 13 death cases). Male gender (P = .006) and lower gestational age (P = .0001) contributed to higher grades of IVH.


According to the results obtained in this study, it may be concluded that the lack of corticosteroid use is the most common risk factor for IVH, and short-term complications may be seen in one-tenth of the cases.


The auditory experience is important because makes a major contribution to the development of speech, language, cognitive and social skills. Knowledge of the lexicon grows and develops throughout human-being's life. Input factors, Linguistic and metalinguistic knowledge are effective factors in the acquisition of definitional skills. This study aims to investigate definitional skills in cochlear-implanted (CI) children and their typically developing (TD) peers.

Materials & Methods

 A total of 46 children in third-grade primary-school (16 with cochlear implants and 30 their matched typically normal) were recruited. Verbal definitional task included    14 common high-frequency nouns and 11 common high-frequency verbs. All definitions were scored for both content (semantic) and grammatical form. Statistical analysis was conducted to compare definitional skills between two groups.  


 There were significance difference between CI children and their TD peers for word definition skills in both categories of content and form (p<0.001). The results showed the mean scores of content and form related aspect of word definition in the TD group were approximately twice higher than the CI ones (respectively: M±SD=133±28 ; M±SD= 78±23).


 Children with CI may have trouble in definitional skills. It seems potential cause for lower scores of CI children in definitional skills was lack of auditory experience. Implication for assessment of and intervention for definitional skills in CI children is suggested.


Effects of auditory processing training on speech perception and brainstem plastisity in adolescents with autism spectrum disorders

Maryam Ramezani, Yones Lotfi, Abdollah Moossavi, Enayatollah Bakhshi

Iranian Journal of Child Neurology, Vol. 15 No. 1 (2021), , Page 69-77


Autism spectrum disorder (ASD) is a neurodevelopmental disorderA major problem of ASD is speech perception impairment in the presence of background noise. Additionally, researchers have reported temporal auditory processing impairment in these patients. In the present study, we evaluated the effects of a temporal-based rehabilitation program on improvement of speech perception in the presence of noise using the speech auditory brainstem response (sABR).

Materials & Methods

Twenty-eight adolescents with high functional ASD with the mean age of 14.35±1.86 were randomly selected and divided into the ASD group (11 males and three females), and the control group (13 males and one female). All subjects had a normal hearing and intelligence threshold and had no history of neurological disorder. The speech perception test was performed in signal-to-noise ratios of zero and +10. The intervention group received a temporal processing-based auditory rehabilitation program and the control group received a conventional rehabilitation program (P<0.05 was considered significant).


speech perception in noise after rehabilitation was significantly higher in intervention group (P <0.001) and the latency of all sABR waves in the rehabilitation group was lower than that of the control group.


Improvement of speech perception in noisy environments and the reduced latency of sABR waves after a temporal processing-based rehabilitation program and one month later, points to the role of auditory temporal processing training program highlight the role of brainstem neural plasticity in speech processing

Non- Pharmacological Approaches on the Improvement of Sleep Disturbances in Patients with Autism Spectrum Disorder (ASD)

faraz tayyar iravanlou, mohammad soltani, fatemeh alsadat rahnemaei, Fatemeh Abdi, mahnaz ilkhani

Iranian Journal of Child Neurology, Vol. 15 No. 1 (2021), , Page 79-91


Autism is a type of neurodegenerative disorder, affected by genetic and environmental factors. Children with autism spectrum disorder (ASD) have symptoms of attention deficit and behavioral problems. The amount of sleep has a significant effect on a child's mood. Sleep problems in a child with autism are more common than a normal child. The aim of this study was to investigate the effect of non- pharmacological approaches on the improvement of sleep disturbances in patients with ASD.

Materials & Methods

PubMed, EMBASE, Web of Science, Scopus, and Science Direct databases were systematically searched for articles published between January 2009 and May 2019. All original articles from observational and interventional studies were reviewed. The CONSORT Statement and Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist were used to assess the quality of the selected papers.


 A review of 18 eligible articles according to the CONSORT checklist (for interventional studies) and STROBE (for descriptive studies) demonstrated that behavioral interventions, such as cognitive-behavioral therapy, bedtime fading with response cost, and functional behavioral assessment, physical activity such as aerobic exercise, swimming, and aquatic exercise and weighted blankets could be effective in the improvement of sleep disturbances.


Restlessness, tantrum, increased stereotypic activities, reduced learning level and speaking power in children with autism was due to poor sleep quality and sleep deficiency, which could affect their life dimensions. Non- pharmacological approaches to the treatment of sleep disturbances could improve both the sleep quality of these individuals and the quality of their lives in addition to having no adverse effect.      

Neurometabolic Disorder Articles

A Novel Mutation in PEX11β Gene: A Case Report

Hamid Malekzadeh, Marjan Shakiba, Mehrdad Yasaei

Iranian Journal of Child Neurology, Vol. 15 No. 1 (2021), , Page 93-100

PEX11β ([OMIM] 614920) mutation causes an extremely rare subgroup of peroxisomal biogenesis disorders, with only six cases reported to date. In this article, we reported a patient with episodic migrainelike
attacks, delirium, mood and behavior change, polyneuropathy, and history of congenital cataract. Whole exome sequencing showednovel c.743_744delTCinsA mutation in the exon 4 of the PEX11β gene. In contrast to previously reported patients, our case presented milder features and extended the spectrum of the clinical phenotype of this mutation. This study helps to extend the phenotype of this syndrome; besides, recognizing novel mutation variants will provide a better genotype-phenotype correlation and improve clinical clues

Case Report

Novel Homozygous Pathogenic Mutations of LAMA 2 Gene in patients with congenital muscular dystrophy

Negar Khodaienia, Zahra Farjami, Amir Hosein Ashnaei, Neshat Ebrahimi, Navid Chelvarforoosh, Andoni Urtizberea, Ehsan Razmara, Massoud Houshmand

Iranian Journal of Child Neurology, Vol. 15 No. 1 (2021), , Page 101-106

The laminin-α2 subunit is a protein that is encoded by the Laminin α 2 gene (LAMA2) which has the role of adhesion (attachment of cells to one another). Genetics consideration showed that mutation in LAMA2 caused a collection of muscle-wasting conditions called Muscular Dystrophy (MD). This disorder causes disconnection of the muscular cells and degeneration of the musculoskeletal system. In this study, we define the molecular consideration of 3 patients with laminin α 2 deficiency by clinical presentations of congenital muscular dystrophy (CMD). In this regard, 65 exons of LAMA2 gene were amplified by Polymerase Chain Reaction (PCR). Also, MLPA and NGS was done for all patients. Because of negativity of NGS, the gene sequence was performed. The results of searching for rearrangements of the LAMA2 gene enabled us to recognize homozygous pathogenic mutations c.2049_c.2050del, c.7156-2A>G and c,1303C>T. These mutations produce an out-of-frame transcript that will be degraded by nonsense-mediated decay. Therefore, we think these changes are pathogenic ones.

Acute transverse myelitis of childhood due to novel coronavirus disease 2019: The first pediatric case report and review of literature

Habibeh Nejad Biglari, Reza Sinaei, Sara Pezeshki, Fatemeh Khajeh Hasani

Iranian Journal of Child Neurology, Vol. 15 No. 1 (2021), , Page 107-112

The global coronavirus disease 2019 (COVID-19) pandemic appears to have some streaks of severity in pediatrics. These streaks include variable signs of respiratory distress, a new entity called multisystem
inflammatory syndrome, and some evidences of neurological symptoms involving both central and peripheral nervous systems.
Here, we described the first pediatric patient with COVID-19 who presented with acute transverse myelitis. An 11-year-old otherwise healthy girl presented to our clinic with acute onset of lower limbs paresis, urinary and fecal retention, alongside epigastric pain, and fever for 3 days. A neurological examination revealed a severe flaccid paraplegia in her lower limbs associated with a sensory level at T5. She was evaluated systematically for all probable causes of her symptoms, and finally, due to having a positive nasopharyngeal PCR test, she was considered to suffer from post-COVID-19 transverse myelitis. She underwent intravenous-immunoglobulin, methylprednisolone pulse, and other supportive cares without obvious results. Therefore, she underwent seven sessions of plasma exchange with little effects on muscle strength. The focal inflammation and injury of the spinal cord, otherwise known as transverse myelitis, have a wide array of potential etiologies. Transverse myelitis has been well documented to be the result of viral and bacterial infections. We believe our patient was not involved in a cytokine storm status due to good CRP, IL-6 and Ferritin levels. Albeit, we cannot certainly consider the patient to have a direct viral impact or involved in a late immunity process. To our knowledge, this is the first report of TM in the field of pediatrics occurred after COVID-19. Thus, this is critical to note that children can present with some severe types of COVID-19.

COVID-19 pneumonia in a child with hepatic encephalopathy: A case study

Naghi Dara, Naghmeh Sharifi, Masoud Ghanbari Boroujeni, Amirhossein Hosseini, Aliakbar Sayyari

Iranian Journal of Child Neurology, Vol. 15 No. 1 (2021), , Page 113-118

Coronavirus disease 2019 (COVID-19) is caused by the seventh coronavirus, known as the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2). Children often have milder diseases than adults with very rare mortality. Gastrointestinal manifestations and a mild increase in liver enzymes have been reported in 8.8% to 53% of COVID-19 cases. However, liver failure is extremely rare and has not been reported so far in the literature. The prevalence of comorbidities is not clear in children with COVID-19. Here, we reported a fatal case of simultaneous pneumonia secondary to SARS-CoV-2and acute liver failure in a 14-year-old boy with liver cirrhosis.


A case of recurrent urinary tract infections with neurogenic bladder due to spinal tumors

Mitra Naseri, Farah Ashrafzadeh, Mohammad Faraji Rad, Nourieh Sharifi

Iranian Journal of Child Neurology, Vol. 15 No. 1 (2021), , Page 119-124

Neuroblastic tumors are the most common extracranial solid tumors in children. They are manifested by different clinical presentations ranging from cord compression symptoms to asymptomatic cases. A 2.5-year girl with a history of vaginal delivery at 39 gestational weeks and low Apgar score presented by repeated episodes of urinary tract infections and progressive paraplegia started at the age of 8 months.
Brain MRI and EEG were normal. Voiding cystourethrography revealed grade II vesicoureteral reflux in the left kidney. Lumbar MRI with and without contrast showed a dumbbell shape mass, the hyper signal in T2 -weighted image and low signal in T1 -weighted image, extramedullary, and intramural with mass effect on the cord.
Microscopic examination of tissue obtained by surgery reported ganglioneuroma.
Our case was interesting because of her presentation, neurogenic bladder associated with repeated episodes of urinary tract infections, and secondary paraplegia. Neurogenic bladder dysfunction is rarely reported in cases with ganglioneuroma.