Towards solving the genetic diagnosis odyssey in Iranian patients with congenital anomalies.

Understanding the underlying causes of congenital anomalies (CAs) can be a complex diagnostic journey. We aimed to assess the efficiency of exome sequencing (ES) and chromosomal microarray analysis (CMA) in patients with CAs among a population with a high fraction of consanguineous marriage. Depending on the patient's symptoms and family history, karyotype/Quantitative Fluorescence- Polymerase Chain Reaction (QF-PCR) (n = 84), CMA (n = 81), ES (n = 79) or combined CMA and ES (n = 24) were performed on 168 probands (66 prenatal and 102 postnatal) with CAs. Twelve (14.28%) probands were diagnosed by karyotype/QF-PCR and seven (8.64%) others were diagnosed by CMA. ES findings were conclusive in 39 (49.36%) families, and 61.90% of them were novel variants. Also, 64.28% of these variants were identified in genes that follow recessive inheritance in CAs. The diagnostic rate (DR) of ES was significantly higher than that of CMA in children from consanguineous families (P = 0·0001). The highest DR by CMA was obtained in the non-consanguineous postnatal subgroup and by ES in the consanguineous prenatal subgroup. In a population that is highly consanguineous, our results suggest that ES may have a higher diagnostic yield than CMA and should be considered as the first-tier test in the evaluation of patients with congenital anomalies.

Effect of premature infant oral motor intervention [PIOMI] combined with music therapy on feeding progression of preterm infants: a randomized control trial.

Prematurity may produce long-term complications in the physical and cognitive development of infants. There is a need for interventions that can improve feeding and reduce the length of NICU stay and separation time between the infant and mother. This study aimed to explore the clinical effect of premature infant oral motor intervention [PIOMI] combined with music therapy [MT] on feeding progression in premature infants.Premature infants with gestational ages between 26 and 30 weeks were included in the study. Fifty-two participants were randomly divided into intervention and control groups. All infants received PIOMI, and the intervention group received additional MT. The participants of the two groups were compared based on weight gain, feeding progression, Preterm Oral Feeding Readiness Scale [POFRAS], milk volume, and length of hospitalization. The data were analyzed using independent sample t-tests, covariance tests, and repeated measure ANOVA used to compare three group means.The intervention group reached independent oral feeding 8 days earlier [P = .018] than the control group. Length of hospitalization was 6 days shorter [P = .224] for the intervention group, and the mean volume of milk on the 10th day was 215.38 ± 56.4 in the intervention group and 155.69 ± 68.9 in the control group, respectively [P = .001]. The mean score of the POFRAS scale on the 10th day was 28.65 ± 3.0 in the intervention groups and 20.96 ± 3.3 in the control groups, retrospectively [P = .001]. There was no difference in weight gain between the two groups [P = .522].Conclusion: PIOMI combined with MT was effective for the feeding progression of premature infants, and infants who received both these interventions were discharged sooner than control infants. Thus, MT should be considered part of feeding interventions for preterm infants with gestational ages between 26 and 30 weeks.Trial registration: Clinical trial registration number: IRCT20210502051155N1 on 18/9/2021 What is Known -- What is New: • There is numerous study about the eff ect of music therapy or oral motor interventi on. However, premature Infants havenot been yet studied to determine whether music therapy and oral motor interventi ons may synergize to aid their feedingprogression.

Serum Vitamin D Deficiency in NICU Hospitalized Neonates and Its Association With Neonatal Outcomes.

Objective: Vitamin D deficiency is a major health problem in all age groups. In the present study, we aimed to determine the prevalence of vitamin D deficiency in neonates hospitalized in an intensive care unit (NICU) and its association with clinical neonatal outcomes. Materials and methods: A prospective cross-sectional study was carried out on all neonates hospitalized in the NICU of Children's Medical Center over a period of one year (January-December 2018). Immediately on admission, a serum sample for vitamin D measurement was obtained with another routine blood sampling. Demographic and clinical data including sex, gestational age, the season of birth, serum levels of vitamin D and calcium, the causes of hospitalization, age at admission and neonatal outcomes including length of hospital stay and mortality during hospitalization were assessed. Results: One hundred neonates entered the study. Vitamin D deficiency and insufficiency were present in 95% of neonates. There was a significant association between vitamin D status and birth during winter (p=0.014); hypocalcemia (p=0.025) and older age at NICU admission (p<0.001). The mean value of vitamin D in term neonates was significantly lower than in preterm neonates (p=0.031). There were no correlations between length of hospital stay and neonatal mortality rate with vitamin D status (p=0.876). Conclusion: Vitamin D deficiency and insufficiency were highly prevalent among NICU patients. Maternal vitamin D supplementation during pregnancy may prevent or reduce the risk of low levels of vitamin D in neonates.

Evaluation of the efficacy of amplitude-integrated electroencephalography in the screening of newborns with metabolic disorder admitted to the NICU.

BACKGROUND: Neonate patients with metabolic disorder show encephalopathy and seizures that may lead to morbidity and mortality. Thus rapid detection and treatment of these patients is necessary. Although Amplitude-integrated electroencephalography (aEEG) has been used for more than a decade in the evaluation of infants with encephalopathy but has not been used in the assessment of neonates suffering from metabolic disorders. In this study, we tried to determine the efficacy of aEEG as an easily available diagnostic tool in the diagnosis of neonates with metabolic diseases. METHODS: All cases which admitted to the Neonatal Intensive Care Unit (NICU) of the Children's Medical Center during a one-year period were enrolled. aEEG recordings were obtained by installing 4 electrodes on the infant's head by a trained nurse and aEEG was recorded for at least 24 h with a description of the whole tracing. Clinical information, final outcome and questionnaires, including patient information: symptoms of the disease, gender, age, duration of hospitalization and the type of the metabolic disease were recorded in details. The obtained data was analyzed with the Spss24 software. RESULTS: Only 3 (two girl and one boy) out of 29 aEEGs recordings were abnormal; other patients showed normal aEEGs. The most common clinical and neurological manifestations were seizure (34.5%), hypotonia (31%), and mortality rate was 10.3%. There was no significant correlation between aEEG findings and gender, age, type of disease, laboratory tests findings and positive family history. CONCLUSIONS: Although it has been shown that EEG has a diagnostic value in metabolic diseases, there has been no study on the efficacy of aEEG to evaluate neonates with metabolic diseases. But good accessibility and easy of working with aEEG, promote a tendency to use this procedure as screening tool for metabolic diseases. The current study about aEEG monitoring in these patients, while limited, can be used as a pilot study for further research on this topic. Therefore, a correct judgment in this field requires administration of aEEG on a larger population of neonates with metabolic diseases.

Spectrum of pediatric tumors diagnosed by fine-needle aspiration cytology.

Pediatric tumors differ markedly from adult tumors in their nature, distribution, and prognosis. In this 10-year retrospective study, we present our experience with fine-needle aspiration (FNA) in pediatric patients 18 years of age and younger and correlate relationship between gender with organ, diagnosis, malignancy, and age. In our study, FNA material of pediatric tumors or masses with 18 years aged and younger were analyzed retrospectively.All FNAs in pediatric patients during this time period were identified and analyzed for age, gender, cytologic diagnosis, and site of aspiration. A total 1000 FNAs were performed from January 2007 to October 2015 in 499 children. Regardless the gender, the most frequently aspirated organ was lymph node, comprising 129 of the 499 cases followed by thyroid (112), neck cyst (79), and parotid (35) cases. The majority of the cases were diagnosed as benign lesions (436 of 499 cases). Other 63 cases comprising 40 female and 23 male cases had malignant lesions. There was significant age difference between people with or without malignancy. In malignant cases, there was a significant difference between the age on males and females. In regard to gender and diagnosis, cytologic diagnosis was stratified into 9 broad diagnostic categories: lymphadenitis, benign and malignant thyroid, cyst contents, benign breast, benign and malignant salivary, and negative for malignancy.In conclusion, our study supports the use of FNA cytology (FNAC) in lesions of various anatomic sites in the children less than 18 years old. As a simple, minimally invasive, and rapid procedure, cytopathologists can reliably utilize FNAC in children. The mean age of children receiving a malignant diagnosis was significantly higher than that of benign lesions. The mean age of malignancy in boys is significantly lower than that of girls with malignancy.

Hemophagocytic Lymphohistiocytosis in a Neonate: Case Report.

 Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of pathologic immune activation, occurring as either a familial disorder or a sporadic condition, in association with a variety of triggers. This article will introduce a neonate with HLH in Iran. We report a case of HLH presenting with respiratory distress and fever, hepatosplenomegaly, jaundice and pancytopenia on the second day of life. Typical clinical and laboratory findings were detected in the neonate. HLH was diagnosed according to HLH-2004 guidelines. In spite of initiating the treatment, the disease did not cure. Post-mortem, extensive hemophagocytosis was found in multiple organs. No specific genetic defect was identified. Since HLH is a potentially lethal childhood illness, early diagnosis of this disorder and commences the therapy is important for pediatricians.

Evaluation of Pulse Oximetry in the Early Detection of Cyanotic Congenital Heart Disease in Newborns.

Background: Delayed or missed diagnosis of critical and cyanotic congenital heart disease (CHD) in asymptomatic newborns may result in significant morbidity and mortality. The aim of this study was to determine the accuracy of pulse oximetry screening performed on the first day of life for the early detection of critical and cyanotic CHD in apparently normal newborns. Methods: This cross-sectional study used postductal pulse oximetry to evaluate term neonates born between 2008 and 2011 with normal physical examinations. Functional oxygen saturation < 95% was considered abnormal, and second measurement was done 2 hours later. If the second measurement remained < 95%, an echocardiogram was performed. On enrolment in the study, the following data for each neonate were recorded: gestational age, gender, birth weight, mode of delivery, and mother's age. Results: During the study period, totally 3,846 newborns were evaluated. Of the whole study population, 304 (7.9%) babies had a postductal functional saturation < 95%. The second measurement was also < 95% in 104 (2.7%) neonates. The mean age of the neonates at the time of pulse oximetry was 18.91 ± 8.61 (min = 4.5 and max = 49) hours. Forty-nine percent of the subjects were female and 51% were male. Echocardiography was performed on 81 out of 104 newborns, and 14 (0.36%) of them had CHD. The types of CHD in our patients were tetralogy of Fallot (3 cases), transposition of the great vessels (2 cases), double-outlet right ventricle (2 cases), truncus arteriosus, total anomalous pulmonary venous return, atrioventricular septal defect, pulmonary atresia, persistent pulmonary hypertension, ventricular septal defect, and atrial septal defect (1 case for each type). The best time for pulse oximetry was within 8-24 hours of the newborns' life. Conclusion: Pulse oximetry screening along with clinical examination may be able to assist in the early detection of critical and cyanotic CHD in asymptomatic newborns.

High Flow Nasal Cannulae versus Nasal Continuous Positive Airway Pressure in Neonates with Respiratory Distress Syndrome Managed with INSURE Method: A Randomized Clinical Trial.

BACKGROUND: In recent years, various noninvasive respiratory support (NRS) of ventilation has been provided more in neonates. The aim of this study was to compare the effect of HFNC with NCPAP in post-extubation of preterm infants with RDS after INSURE method (intubation, surfactant, extubation). METHODS: A total of 54 preterm infants with RDS (respiratory distress syndrome) were enrolled in this study. Using a randomized sequence, they were assigned into two groups after INSURE method. The first group received HFNC while the second group received NCPAP for respiratory support after extubation. A comparison was made between these two groups by the rate of reintubation, air leak syndrome, duration of oxygen therapy, hospitalization, the rate of bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), retinopathy of prematurity (ROP), and mortality. Data were analyzed by using the SPSS version 18 software. The statistical analyses included Student's t-test for continuous data and compared proportions using Chi-squared test and Fisher's exact test for categorical data. RESULT: The rate of reintubation was higher in the HFNC compared with the NCPAP group. The rate of either IVH or ROP had no significant differences between the two groups. In addition, duration of oxygen requirement and hospitalization were not statistically different. There was no case of BPD or mortality among these patients. CONCLUSION: This study showed that preterm infants with RDS could manage post-extubation after INSURE method with either NCPAP or HFNC. However, in this single-center study, the rate of reintubation was higher in the HFNC group while further multicenter study might be assigned. Trial Registration Number: IRCT201201228800N1.

Urinary Uric Acid/Creatinine Ratio as a Marker of Mortality and Unfavorable Outcome in NICU-Admitted Neonates.

BACKGROUND: The survival of neonates who have been admitted to the NICU, especially premature infants with few mortality and morbidity, is the most important attitude. OBJECTIVES: We presumed whether urinary uric acid/creatinine (UUA/Cr) ratio can be a marker of mortality and adverse outcome in neonates which were admitted to the NICU. PATIENTS AND METHODS: All preterm infants admitted to our NICU after birth from March 2014 to April 2015 were enrolled in this prospective cohort study. UUA/Cr was measured during the first day of life. The severity of diseases (indicated by the need for high set-up of mechanical ventilation, complications of prematurity, and duration of stay in the NICU) and neonatal death were considered to be the final unfavorable outcomes. The relationship between the Log-transformation (Ln) urinary uric acid/creatinine ratio and the Apgar score at the first and 5th minute after birth and the duration of stay were analyzed by using linear regression. Statistical analysis was done by using STATA version 11 (STATA Corp, TX, USA). A P < 0.05 was considered to be statistically significant. RESULTS: A total of 362 preterm infants with a mean gestational age of 32.7 (± 3.9) weeks were admitted to the NICU, out of whom 64 (17.6%) had severe disease and 43 (11.8%) died. The mean UUA/Cr ratio was significantly higher in the admitted neonates (3.30 ± 1.95 vs. 1.36 ± 0.42. P = 0.0001). There was a negative correlation between the UUA/Cr ratio and the 1-minute Apgar score (r = -0.17, P = 0.006) and the 5-minute Apgar score (r = -0.19, P = 0.003). The 1-minute Apgar scores were negatively correlated with the outcome (OR = 0.68; P < 0.001) and the duration of stay (ß = -.28; P < 0.001). There was no significant correlation between 5-minute Apgar scores and the outcome. There was a significant positive correlation between the UUA/Cr ratio and an unfavorable outcome (OR = 1.24; CI %95: 1.06 to 1.43, P = 0.006) and increasing duration of stay (ß = 0.17; P = 0.009). CONCLUSIONS: The urinary uric acid/creatinine ratio can be used as a simple, noninvasive parameter of the severity of disease and mortality in NICU-admitted neonates.

Evaluation of Serum Zinc Levels in Hyperbilirubinemic Neonates Before and After Phototherapy.

BACKGROUND: The existing therapeutic methods for neonatal jaundice are costly, time-consuming and potentially risky. Zinc salts can reduce phototherapy duration by precipitating unconjugated bilirubin in the intestine (bilirubin and zinc can form a complex in physiologic pH); however, zinc toxicity is an issue that must be considered since theoretically bilirubin reduction by phototherapy may increase serum zinc levels, making additional zinc supplementation the potential cause of zinc toxicity. OBJECTIVES: So, our purpose was evaluating the serum zinc level alterations before and after phototherapy, in hyperbilirubinemic newborns. MATERIALS AND METHODS: A prospective cohort study was performed at the children's medical center of Tehran University of Medical Sciences from 2012 to 2014. Healthy, full-term exclusively breast fed newborns with non-hemolytic jaundice were enrolled in the study. Participants were divided into two groups based on serum bilirubin levels (TSB < 18 mg/dL and TSB ≥ 18 mg/dL) at admission. Pre- and post-phototherapy total serum zinc level was measured before and 12 - 24 hours after termination of phototherapy. RESULTS: Phototherapy was associated with a significant increase in the serum zinc level in neonates with severe hyperbilirubinemia (TSB ≥ 18 mg/dL) but not in those with mild-moderate hyperbilirubinemia (TSB < 18 mg/dL). In addition, phototherapy caused a significant increase in the rate of zinc with potentially toxic levels (zinc > 200) in only neonates with severe hyperbilirubinemia. CONCLUSIONS: Phototherapy increases serum zinc level by reducing bilirubin level so that additional supplementation of this element can lead potentially to zinc toxicity.

Fournier's Gangrene in a Neonate With Acute Myeloid Leukemia: A Case Report.

INTRODUCTION: Fournier's gangrene is an infective necrotizing fasciitis of external genital and perineal region. Hematologic malignancies and immunocompromised status are predisposing factors. Simultaneous occurrence of Fournier's gangrene and congenital leukemia in neonates is extremely rare. CASE PRESENTATION: We present a case of Fournier's gangrene in a 4-day-old female infant with a necrotic lesion in perineum and no history of trauma or other predisposing condition. Focusing on high blast percentage in blood cell count she was affected by acute myeloid leukemia (M4 type). Pseudomonas aeruginosa was isolated from the blood and wound culture. She was treated with broad spectrum antibiotics and supportive care. The parents refused chemotherapy and the patient was discharged from hospital. Bleeding and DIC was the cause of death in a local hospital few days later. CONCLUSIONS: High index of suspicion is essential for diagnosis and appropriate treatment. Congenital leukemia should be considered in the differential diagnosis of a newborn with clinical features of sepsis and necrotizing fasciitis.

The effect of mothers' empowerment program on premature infants' weight gain and duration of hospitalization.

BACKGROUND: The readiness of mothers to take care for infants at discharge is a critical issue. Poor readiness of mothers in taking care of premature infants at the time of discharge is associated with potential adverse consequences. This study examined the effect of implementing mothers' empowerment program on the weight gain and duration of hospitalization in premature infants. MATERIALS AND METHODS: This study was a quasi-experimental before-after study with a control group, in which 80 mothers with premature infants who were hospitalized in NICU Level II of two hospitals were recruited in the study. Mothers' empowerment program was implemented as a three-stage training program for the intervention group. Mothers' readiness questionnaire was completed by the mothers before the intervention and at the discharge time. The changes in mean of mothers' readiness scores were compared in both the groups. RESULTS: The mean of daily weight gain in infants of the intervention group (3.95 g) was significantly higher than that of the infants in the control group (-0.9 g) (P = 0.003). The average duration of hospitalization for infants in the intervention and control groups was 15.45 days and 20.95 days, respectively, showing a statistically significant difference (P = 0.003). CONCLUSIONS: Providing training to the mothers regarding how to care for premature infants can be a useful and effective method in the process of weight gain of premature and low-birth newborns, and may shorten the duration of infants' hospitalization.

Evaluation of QT Dispersion in Children with Breath Holding Spells.

OBJECTIVE: Breath holding spells (BHS) are common involuntary reflexes in infancy and early childhood. Differential diagnosis should embrace Long QT Syndrome (LQTS) and paroxysmal abnormalities of rhythm. The aim of this study was to compare QT dispersion (QTd) in children with breath holding spells and normal controls. MATERIALS & METHODS: QT dispersion and Corrected QT(QTc) dispersion were measured in 12 lead surface electrocardiograms in 56 patients with BHS and compared with healthy children of the same age referred to the clinic for regular checkup visits. RESULTS: The most common type of BHS was cyanotic (83.9%). Seven patients (12.5%) had pallid and two patients (3.5%) had mixed spells. There was a history of breath holding spells in 33.9% of the children. QT dispersion was 61.6± 22.5 and 47.1±18.8 ms in patient and control groups, respectively. QTc dispersion (QTcd) was 104 ± 29.6 and 71.9 ±18.2 ms, respectively. There was a significant difference between patient and control groups in terms of QTd and QTcd (P<0.001). CONCLUSION: QTd and QTcd were increased in children with BHS. Therefore, the evaluation of EKG for early diagnosis of rhythm abnormalities seems reasonable in these children.

Deletion/duplication mutation screening of TP53 gene in patients with transitional cell carcinoma of urinary bladder using multiplex ligation-dependent probe amplification.

Bladder cancer is a molecular disease driven by the accumulation of genetic, epigenetic, and environmental factors. The aim of this study was to detect the deletions/duplication mutations in TP53 gene exons using multiplex ligation-dependent probe amplification (MLPA) method in the patients with transitional cell carcinoma (TCC). The achieved formalin-fixed paraffin-embedded tissues from 60 patients with TCC of bladder were screened for exonal deletions or duplications of every 12 TP53 gene exons using MLPA. The pathological sections were examined by three pathologists and categorized according to the WHO scoring guideline as 18 (30%) grade I, 22 (37%) grade II, 13 (22%) grade III, and 7 (11%) grade IV cases of TCC. None mutation changes of TP53 gene were detected in 24 (40%) of the patients. Furthermore, mutation changes including, 15 (25%) deletion, 17 (28%) duplication, and 4 (7%) both deletion and duplication cases were observed among 60 samples. From 12 exons of TP53 gene, exon 1 was more subjected to exonal deletion. Deletion of exon 1 of TP53 gene has occurred in 11 (35.4%) patients with TCC. In general, most mutations of TP53, either deletion or duplication, were found in exon 1, which was statistically significant. In addition, no relation between the TCC tumor grade and any type of mutation were observed in this research. MLPA is a simple and efficient method to analyze genomic deletions and duplications of all 12 exons of TP53 gene. The finding of this report that most of the mutations of TP53 occur in exon 1 is in contrast to that of the other reports suggesting that exons 5-8 are the most (frequently) mutated exons of TP53 gene. The mutations of exon 1 of TP53 gene may play an important role in the tumorogenesis of TCC.

The effect of empowerment program on "perceived readiness for discharge" of mothers of premature infants.

OBJECTIVES: Poor readiness of mothers to take care of their premature infant at the time of hospital discharge is associated with potential adverse consequences. The aim of this study was to examine the effect of empowerment program on "perceived readiness for discharge" of mothers of premature infants at the time of discharge. METHODS: A quasi-experimental before-after study design with consecutive inclusion of all mother-child pairs was used to conduct the study. Eighty mothers and their premature infants (40 pairs of mother-infant in the experimental group and 40 pairs of mother-infant in the control group) were recruited in the study. The program to empower the parents was implemented as a 3-stage training plan for the experimental group. "Parent discharge readiness" questionnaire was completed by mothers before intervention and at discharge time, and was evaluated by nurses at discharge time. The groups were compared in terms of readiness for discharge according to the scores given by mothers and nurses. RESULTS: At discharge time, there was a statistically significant difference between technical readiness of control and experimental groups according to mothers' self-report (p < 0.001) and nurse evaluation (p < 0.0001). Also, there was a statistically significant difference between emotional readiness of mothers in control and experimental groups according to mothers' self-report (p < 0.0001) and nurse evaluation (p = 0.003). CONCLUSION: The implementation of empowerment program is an effective strategy to promote the readiness of mothers of premature infants at discharge time.

Evaluation of specificity and sensitivity of gastric aspirate shake test to predict surfactant deficiency in Iranian premature infants.

INTRODUCTION: Respiratory failure secondary to pulmonary surfactant deficiency is an important cause of severe respiratory distress in term and preterm infants. The aim of this study was to evaluate the specificity and sensitivity of gastric aspirate shake test (GAST) to predict surfactant deficiency in newly born premature infants in Arash Hospital (Iran) during 2012-13. METHODS: In this case-control study, the case group comprised 69 premature infants (gestational age<37 weeks) who were admitted to the neonatal intensive care unit due to respiratory distress. The control group included 50 healthy infants .GAST test was done. The subjects were finally categorized as healthy or surfactant-deficient based on clinical and radiological assessments. RESULTS: Using statistical methods the sensitivity, specificity, and positive and negative predictive values of GAST were 60%, 75%, 15%, and 52%, respectively. There was a significant difference between respiratory distress syndrome (RDS) scores and receiving surfactant in neonates with gestational age below 34 weeks. Moreover, there were significant differences between GAST results and both radiological findings of RDS and receiving oxygen in premature infants (gestational age<34 weeks). Negative GAST results were more prevalent in neonates who were born to mothers with hypothyroidism, preeclampsia, diabetes mellitus, and premature rupture of membranes. However, this difference was not significant. CONCLUSION: According to our findings, the application of GAST on gastric aspirate secretions is not a useful method to predict surfactant deficiency. Therefore, decisions for RDS management must be made based on clinical and radiological findings.

Ethical challenges in the neonatal intensive care units: perceptions of physicians and nurses; an Iranian experience.

The challenging nature of neonatal medicine today is intensified by modern advances in intensive care and treatment of sicker neonates. These developments have caused numerous ethical issues and conflicts in ethical decision-making. The present study surveyed the challenges and dilemmas from the viewpoint of the neonatal intensive care personnel in the teaching hospitals of Tehran University of Medical Sciences (TUMS) in the capital of Iran. In this comparative cross-sectional study conducted between March 2013 and February 2014, the physicians' and nurses' perceptions of the ethical issues in neonatal intensive care units were compared. The physicians and nurses of the study hospitals were requested to complete a 36-item questionnaire after initial accommodations. The study samples consisted of 284 physicians (36%) and nurses (64%). Content validity and internal consistency calculations were used to examine the psychometric properties of the questionnaire. Data were analyzed by Pearson's correlation, t-test, ANOVA, and linear regression using SPSS v. 22. Respecting patients' rights and interactions with parents were perceived as the most challenging aspects of neonatal care. There were significant differences between sexes in the domains of the perceived challenges. According to the linear regression model, the perceived score would be reduced 0.33 per each year on the job. The results of our study showed that the most challenging issues were related to patients' rights, interactions with parents, communication and cooperation, and end of life considerations respectively. It can be concluded, therefore, that more attention should be paid to these issues in educational programs and ethics committees of hospitals.