Safety and Efficacy of 2.5 mg and 1.25 mg Nebulized Salbutamol Compared with Placebo on Transient Tachypnea of the Newborns: A Triple-Blind Phase II/III Parallel Randomized Controlled Trial.

Background: To evaluate the safety and efficacy of 2.5 and 1.25 mg nebulized salbutamol on Transient Tachypnea of the Newborn (TTN) compared with placebo. Methods: We conducted a triple-blind, phase II/III parallel randomized controlled trial in two university-affiliated hospitals with neonatal intensive care units. Newborns with a confirmed diagnosis of TTN, with gestational age >35 weeks and gestational weight >2 kg were included. Cases of asphyxia, meconium aspiration syndrome, and persistent pulmonary hypertension were excluded. Ninety eligible patients were randomly allocated in three intervention groups (2.5 mg salbutamol, 1.25 mg salbutamol, and placebo), and a single-dose nebulized product was prescribed 6 hours after the birth. Safety outcomes included postintervention tachycardia, hyperglycemia, hypokalemia, and changes in blood pressure. To evaluate the efficacy, the duration of postintervention tachypnea, TTN clinical score, and clinical and paraclinical respiratory indices were assessed. Parents, Outcome assessors, and data analyzer were blind to the intervention. Results: There was no adverse reaction, including tachycardia, hypokalemia, and jitteriness. Both groups of salbutamol recipients showed significant improvement regarding respiratory rate, TTN clinical score, and oxygenation indices compared with the placebo (p-values <0.001). Nonstatistically significant higher hospital stay was observed in the placebo group. Single 2.5 mg salbutamol nebulization showed a little better outcome than the dose of 1.25 mg, although we could not find statistical superiority. Conclusion: The newly applied single high dose of 2.5 mg nebulized salbutamol is safe in treating TTN and leads to notable faster improvement of respiratory status without any considerable adverse reaction. Registry code: IRCT20190328043133N1.

In silico Analysis of Two Novel Variants in the Pyruvate Carboxylase (PC) Gene Associated with the Severe Form of PC Deficiency.

Background: Inborne errors of metabolism are a common cause of neonatal death. This study evaluated the acute early-onset metabolic derangement and death in two unrelated neonates. Methods: Whole-exome sequencing (WES), Sanger sequencing, homology modeling, and in silico bioinformatics analysis were employed to assess the effects of variants on protein structure and function. Results: WES revealed a novel homozygous variant, p.G303Afs*40 and p.R156P, in the pyruvate carboxylase (PC) gene of each neonate, which both were confirmed by Sanger sequencing. Based on the American College of Medical Genetics and Genomics guidelines, the p.G303Afs*40 was likely pathogenic, and the p.R156P was a variant of uncertain significance (VUS). Nevertheless, a known variant at position 156, the p.R156Q, was also a VUS. Protein secondary structure prediction showed changes in p.R156P and p.R156Q variants compared to the wild-type protein. However, p.G303Afs*40 depicted significant changes at C-terminal. Furthermore, comparing the interaction of wild-type and variant proteins with the ATP ligand during simulations, revealed a decreased affinity to the ATP in all the variants. Moreover, analysis of Single nucleotide polymorphism impacts on PC protein using Polyphen-2, SNAP2, FATHMM, and SNPs&GO servers predicted both R156P and R156Q as damaging variants. Likewise, free energy calculations demonstrated the destabilizing effect of both variants on PC. Conclusion: This study confirmed the pathogenicity of both variants and suggested them as a cause of type B Pyruvate carboxylase deficiency. The results of this study would provide the family with prenatal diagnosis and expand the variant spectrum in the PC gene,which is beneficial for geneticists and endocrinologists.

Comparison of the efficacy of inhaled versus infused milrinone in the management of persistent pulmonary hypertension of the newborn in resource-limited settings: A randomized clinical trial.

BACKGROUND: The standard treatment for persistent pulmonary hypertension of the newborn (PPHN) is inhaled nitric oxide (iNO), which is not available in Iran. Consequently, other drugs, such as milrinone, are prescribed. So far, no study has investigated the effectiveness of inhaled milrinone in the management of PPHN. The present study aimed to improve the management of PPHN in the absence of iNO. METHODS: In this randomized clinical trial, neonates with PPHN, admitted to the neonatal intensive care unit of Hazrat Ali-Asghar and Akbar-Abadi hospitals, were treated with intravenous dopamine infusion and randomly divided into two groups, receiving milrinone through inhalation or infusion rout. The neonates were evaluated by Doppler echocardiography, clinical examinations, and oxygen demand test. The neonates were also evaluated for the clinical symptoms and mortality in the follow-up. RESULTS: A total of 31 infants, with a median age of 2 days (interquartile range = 4), were included in this study. There was a significant decrease in the peak systolic and mean pulmonary arterial pressure in both inhalation and infusion groups following milrinone administration, with no significant difference between the groups (p = 0.584 and p = 0.147, respectively). There was no significant difference between the two groups regarding the mean systolic blood pressure before and after treatment. Additionally, diastolic blood pressure was significantly lower in the infusion group after treatment (p = 0.020); however, the amount of reduction was not significantly different between the groups (p = 0.928). Overall, 83.9% of the participants achieved full recovery, 75% of whom were in the infusion group and 93.3% in the inhalation group (p = 0.186). CONCLUSION: Milrinone inhalation can have similar effects to milrinone infusion as an adjunct treatment in the management of PPHN. Also, infusion and inhalation of milrinone showed similar safety.

Identification and characterization of the largest deletion in the PCCA gene causing severe acute early-onset form of propionic acidemia.

Whole-exome sequencing (WES) is an excellent method for the diagnosis of diseases of uncertain or heterogeneous genetic origin. However, it has limitations for detecting structural variations such as InDels, which the bioinformatics analyzers must be aware of. This study aimed at using WES to evaluate the genetic cause of the metabolic crisis in a 3-day-old neonate admitted to the neonatal intensive care unit (NICU) and deceased after a few days. Tandem mass spectrometry (MS/MS) showed a significant increase in propionyl carnitine (C3), proposing methylmalonic acidemia (MMA) or propionic acidemia (PA). WES demonstrated a homozygous missense variant in exon 4 of the BTD gene (NM_000060.4(BTD):c.1330G > C), responsible for partial biotinidase deficiency. Segregation analysis of the BTD variant revealed the homozygous status of the asymptomatic mother. Furthermore, observation of the bam file, around genes responsible for PA or MMA, by Integrative Genomics Viewer (IGV) software displayed a homozygous large deletion in the PCCA gene. Comprehensive confirmatory studies identified and segregated a novel outframe deletion of 217,877 bp length, "NG_008768.1:g.185211_403087delinsTA", extended from intron 11 to 21 of the PCCA, inducing a premature termination codon and activation of nonsense-mediated mRNA decay (NMD). Homology modeling of the mutant PCCA demonstrated eliminating the protein's active site and critical functional domains. Thereupon, this novel variant is suggested as the largest deletion in the PCCA gene, causing an acute early-onset PA. These results could expand the PCCA variants spectrum, and improve the existing knowledge on the molecular basis of PA, as well as provide new evidence of pathogenicity of the variant (NM_000060.4(BTD):c.1330G > C.

Identifying and predicting the pathogenic effects of a novel variant inducing severe early onset MMA: a bioinformatics approach.

BACKGROUND: Methylmalonic acidemia (MMA) is a rare metabolic disorder resulting from functional defects in methylmalonyl-CoA mutase. Mutations in the MMAB gene are responsible for the cblB type of vitamin B12-responsive MMA. RESULTS: This study used Whole-exome sequencing (WES), Sanger sequencing, linkage analysis, and in-silico evaluation of the variants' effect on protein structure and function to confirm their pathogenicity in a 2-day-old neonate presenting an early-onset metabolic crisis and death. WES revealed a homozygous missense variant on chromosome 12, the NM_052845.4 (MMAB):c.557G > A, p.Arg186Gln, in exon 7, a highly conserved and hot spot region for pathogenic variants. After being confirmed by Sanger sequencing, the wild-type and mutant proteins' structure and function were modeled and examined using in-silico bioinformatics tools and compared to the variant NM_052845.4 (MMAB):c.556C > T, p.Arg186Trp, a known pathogenic variant at the same position. Comprehensive bioinformatics analysis showed a significant reduction in the stability of variants and changes in protein-protein and ligand-protein interactions. Interestingly, the variant c.557G > A, p.Arg186Gln depicted more variations in the secondary structure and less binding to the ATP and B12 ligands compared to the c.556C > T, p.Arg186Trp, the known pathogenic variant. CONCLUSION: This study succeeded in expanding the variant spectra of the MMAB, forasmuch as the variant c.557G > A, p.Arg186Gln is suggested as a pathogenic variant and the cause of severe MMA and neonatal death. These results benefit the prenatal diagnosis of MMA in the subsequent pregnancies and carrier screening of the family members. Furthermore, as an auxiliary technique, homology modeling and protein structure and function evaluations could provide geneticists with a more accurate interpretation of variants' pathogenicity.

Correlation between Alkaline Phosphatase and Neonatal Jaundice.

Background: Hyperbilirubinemia is one of the most common neonatal disorders and one of the risk factors of neurological complications. So this study was conducted to evaluate the correlation between alkaline phosphatase (ALP) and pathological jaundice. Methods: A case-control was performed on term neonates with and without pathological jaundice who were referred to the Hazrat-e-Ali Asghar Hospital in 2017. In both groups, cases (neonates with pathological jaundice, n=153) and control (neonates with and without pathological jaundice, n=153) levels of alkaline-phosphatase and serum total bilirubin were evaluated with biochemical tests. Moreover, other data were also recorded from their history and clinical examinations. In addition, the severity of jaundice, duration of hospitalization, type of required treatment, and probable complications after the treatment were considered in follow-up. Data were collected by checklist and entered to SPSS v.20. ALP level and its relationship with serum total bilirubin compared between two groups. Results: Mean level of ALP was 411.3 ± 134.2 U/L in the case group and 338 ± 131.4 U/L in the control group. Serum total bilirubin level was 11.9 mg/dl in the case group and 6.2 mg/dl in the control group. ALP levels in the case group were significantly more than the control group (p=0.001). There was no correlation between ALP and serum total bilirubin level in neonates in the case group (p=0.532). There was no statistically significant relationship between alkaline phosphatase level and gender of neonates, but the relationship of ALP level with types of delivery was statistically significant (p=0.002). There was not a significant relationship between ALP level with hospitalization duration (p=0.371). Conclusion: The result of this study showed that there is no correlation between ALP levels and pathological jaundice in patients, although this issue needs to be approved by the other studies.

Effect of Maternal Diet on Any Necrotizing Enterocolitis in Neonates: A Randomized Double-Blind Study.

Background: The etiology of necrotizing enterocolitis (NEC) is controversially discussed. One of the most recently proposed causes of NEC is an allergy to cow's milk protein. This study was designed to evaluate the effect of a maternal diet without bovine protein on the incidence of any NEC in very low birth weight (VLBW) infants. Materials and Methods: A pilot randomized controlled clinical trial was performed at Akbarabadi Hospital, Tehran, Iran, from December 2019 to July 2020, in women with VLBW infants. One hundred twenty mothers with VLBW neonates were randomly assigned to the intervention or the control group (60 in each). In the intervention group, mothers were given a dairy-free diet during the first 14 days after the newborn's onset of feeding. No special diet was given to the control group. The primary outcome of the study was the rate of any NEC in neonates, which was compared between groups. Any NEC was defined as Bell stage I or greater. Results: The minimum and maximum gestational ages were 26 and 33 weeks, respectively. The minimum birth weight of neonates was 700 g. The two groups did not differ significantly in terms of demographic and preinterventional clinical characteristics. Any NEC was reported in 0% and 10% (5/52) of neonates in the intervention and control groups, respectively; the difference was statistically significant (p = 0.028). The NEC symptoms began ∼34 days after birth. Four cases of NEC were classified as Bell stage I, and one was classified as Bell stage II. No statistical association was registered between sex, gestational age, birth weight, and the onset of feeding with the incidence of any NEC. Conclusion: The use of a cow's milk protein-free diet in mothers and exclusive breastfeeding in preterm VLBW infants may reduce the incidence of NEC. We recommend further studies with larger sample sizes in a multicenter setting. The study was registered at the Iranian Registry of Clinical Trials (IRCT20200415047086N1).

Monocyte Count in Preterm Neonates With and Without Necrotizing Enterocolitis.

BACKGROUND: Recently, blood monocyte concentration has been introduced as an inventive biomarker for necrotizing enterocolitis (NEC) in low birth weight neonate; therefore, we aimed to examine and compare blood monocyte counts in preterm neonates with and without NEC. METHODS: A case-control study was conducted on 160 preterm neonates in Tehran during 2017. In this study, medical records and laboratory findings of 80 neonates with NEC (case) and 80 neonates (control), who were randomly chosen from among neonates who had survived NEC, were reviewed and CBC outcomes were compared between the groups. RESULTS: We compared 80 cases and 80 controls. The mean gestational age in the NEC and control group was 30.78±2.33 and 31.41±2.16 weeks, respectively. The birth weights in the NEC and control group were 1500±488 and 1562±360 g, respectively. The mean age for developing NEC was 14.14±13.9 days. The absolute neutrophil count (ANC) and absolute lymphocyte count (ALC) did not differ statistically significantly between the two groups. The mean absolute white blood cells (WBC) in the NEC and control group were 11368±7957 and 8268±7505, respectively; absolute WBC was significantly different between the two groups (P=0.001). The mean absolute monocyte count (AMC) in the NEC and control group were 262±193 and 518±691, respectively; the difference in absolute WBC was significant between the two groups (P=0.002). Receiver operating characteristic of AMC values showed a diagnostic accuracy of 0.693 (95% CI: 0.612-0.773) for NEC and 0.738 (95% CI: 0.627-0.850) for stage II and III NEC. CONCLUSION: The result of this study suggest that the concentration of blood monocyte could be an indicator for NEC in the preterm neonate. However, this result should be confirmed by other studies.

Gastrointestinal cancers, ACE-2/TMPRSS2 expression and susceptibility to COVID-19.

Recent studies on the pathophysiology of COVID-19 are indicating that the Angiotensin convertase enzyme 2 (ACE-2) and transmembrane serine protease 2 (TMPRSS2) can act as a major component in the fusion of SARS-Cov-2 with target cells. It has also been observed that the expression of ACE-2 and TMPRSS2 can be altered in malignancies. Shedding light on this matter could be crucial since the COVID-19 pandemic interfered with many gastrointestinal cancer screening programs. Herein we discuss the possibility of severe forms of COVID-19 in patients with gastrointestinal cancers due to the gastrointestinal entry route of SARS-CoV-2 into the human body. The disruption of cancer screening programs caused by the current COVID-19 pandemic could therefore have massive negative health impact on patients affected by gastrointestinal malignancies.

Accuracy of oxygen saturation index in determining the severity of respiratory failure among preterm infants with respiratory distress syndrome.

BACKGROUND: To evaluate the severity of respiratory failure among newborns with respiratory distress syndrome (RDS), oxygenation index (OI) has been implemented. In the present study, we assessed the accuracy of oxygen saturation index (OSI) in determining the severity of respiratory failure. METHODS: A cross-sectional study was carried out in the NICUs of two Iranian Hospitals (Tehran, Iran) in 2018. Preterm neonates with RDS entered the study. Immediately after admission, the severity of RDS was determined based on RDS scoring system. Then, 2 CC of arterial blood was withdrawn and sent to laboratory determining blood gases. Simultaneously, the level of peripheral capillary oxygen saturation (SpO2) was read using pulse oximeter and recorded. OI and OSI were measured using the formulae. Receiver Operating Characteristic curve, Kappa agreement coefficient and accuracy, sensitivity and specificity was used to compare the OI and OSI results. RESULTS: In the study, 95 neonates were considered. Based on ROC curves, the appropriate cut off with AUC = 0.99 for severe respiratory failure was OSI >8. The sensitivity, specificity, negative predicted value, and positive predicted value for the OSI Cut off >8 were 100, 98, 0.97 and 100%, respectively. The overall accuracy and Kappa agreement between OSI and OI was 0.96 and 0.98%, respectively. CONCLUSION: Our results showed that OSI with high sensitivity, specificity values could predict the severity of respiratory failure in preterm neonates with RDS.

Effect of Aminophylline in Preventing Renal Dysfunction among Neonates with Prenatal Asphyxia: A Clinical Trial.

BACKGROUND: As there are different views on the effects of aminophylline on neonatal renal function, we intended to observe the effects of aminophylline on renal dysfunction in neonates with prenatal asphyxia. METHODS: This randomized trial was conducted in the Obstetrics and Gynecology Hospital, Tehran, Iran, from June 2016 to May 2017, in neonates with moderate to severe asphyxia during birth. Fifty-six neonates were divided randomly into two groups. The intervention group received one dose of 5mg/kg slow intravenous aminophylline injection and the placebo group received 2 mL/kg of intravenous 10% solution of dextrose saline during the first hour of life. They were monitored and compared for renal functional indices, electrolytes, and complications of asphyxia during the three days of life. RESULTS: The mean of Cr (37.9 ± 8.8 vs 38.5 ± 9.4 and 20.8 ± 4.8 vs 30.1 ± 5.2 µmol/L), GFR (21.55 ± 4.7 vs 20.25 ± 4.4 and 30.8 ± 7.1 vs 20.1 ± 6.5 mL/minute/1.73 m2), Na (135.1 ± 12.4 vs134.5 ± 11.2 and 128.9 ± 11.5 vs 134.2 ± 10.9 mEq/L), and urine output (98.2 ± 25 vs 96.8 ± 23 and 148.7 ± 35 vs 108.8 ± 20 cc) were in the aminophylline treated and placebo group on the 1st and 3rd days, respectively. The mean difference of Cr (-9.3 (-8.9; -9.7) µmol/L); (P = 0.02), GFR (10.7 (10.1; 11.3) mL/minute/1.73 m2) (P = 0.009), Na (-5.3 (-5.9; -4.7) mEq/L) (P = 0.002), and urine volume (39.9 (24.9; 54.9) cc) (P = 0.001) presented statistically significant differences on the third day between the intervention and placebo group. CONCLUSION: Aminophylline was effective in preventing renal dysfunction in neonates with asphyxia. Neonates who received aminophylline indicated a significant improvement in GFR and urine output on the first day of life.

Investigation of association between maternal 25-OH vitamin D serum levels and neonatal early onset sepsis in newborns by evaluating key factors.

BACKGROUND: The goal of this study was to evaluate the relationship between maternal 25-OH Vitamin D serum levels and neonatal early-onset sepsis in newborns by the effective factors. METHODS: A case-control study was done and 64 neonates hospitalized in Akbar Abadi Hospital (Tehran- Iran; 2016) and their mothers were enrolled. The case group consisted of 32 NICU term hospitalized neonates due to neonatal early-onset sepsis. Thirty-two term newborns that referred to hospital for rule out hyperbilirubinemia during the first 72 h of life were also considered as the control. RESULTS: Sixty- four mothers with mean age 28.76 ± 6.60 years and mean gestational age 39.64 ± 1.62 weeks entered the study. There was a significant correlation between sepsis and older age of mothers and low Apgar score (P-value = 0.02, 0.01 respectively). The maternal vitamin D serum level was reversely correlated with neonatal sepsis occurrence (P-value = 0.03). There was a significant correlation between maternal vitamin D supplement intake during pregnancy and lower risk for neonatal sepsis (P-value = 0.003). CONCLUSION: The level of maternal serum Vitamin D was inversely correlated with neonatal sepsis occurrence and intake of vitamin D supplement during pregnancy could decrease the risk of early neonatal sepsis.

Investigation of the relationship between umbilical cord pH and intraventricular hemorrhage of infants delivered preterm.

OBJECTIVE: We measured the level of pH gases in premature infants at birth, and examined the relationship between brain ultrasonography on the third and seventh day after birth. A case-control study conducted at the Neonatal Intensive Care Unit (NICU) of Shahid Akbar Abadi Hospital, Iran, during the years 2016-2017. METHODS: All premature infants who were admitted to NICU were enrolled in the current study. At birth, a blood gas sample was taken from the umbilical cord of the infants. On the third and seventh day after birth, an ultrasound of the brain of each neonate was performed by a radiologist. The umbilical cord was evaluated for blood gases in 72 neonates (mostly boys). RESULTS: Sixty-six newborns had normal sonography, and 16.7% (12 cases) had anomalies. A total of 75% of the 8 infants with intravenous bleeding were girls, which were significantly different from those in the non-hemodynamic group (62.5% male) (P 0.049). However, the type of delivery, mean weight, height, head circumference, the circumference of the chest, and Apgar score did not differ between the two groups. Mean pH, HCO3- and PCO2 in umbilical cord blood gas samples were not significantly different between the two groups with or without intraventricular hemorrhage (IVH). Although it was not related to gender and type of delivery in newborns. CONCLUSION: Blood gases do not help in determining the occurrence of IVH in infants. Nevertheless, it is associated with immaturity and fetal age.

Investigation of the relationship between umbilical cord pH and intraventricular hemorrhage of infants delivered preterm

SUMMARY OBJECTIVE: We measured the level of pH gases in premature infants at birth, and examined the relationship between brain ultrasonography on the third and seventh day after birth. A case-control study conducted at the Neonatal Intensive Care Unit (NICU) of Shahid Akbar Abadi Hospital, Iran, during the years 2016-2017. METHODS: All premature infants who were admitted to NICU were enrolled in the current study. At birth, a blood gas sample was taken from the umbilical cord of the infants. On the third and seventh day after birth, an ultrasound of the brain of each neonate was performed by a radiologist. The umbilical cord was evaluated for blood gases in 72 neonates (mostly boys). RESULTS: Sixty-six newborns had normal sonography, and 16.7% (12 cases) had anomalies. A total of 75% of the 8 infants with intravenous bleeding were girls, which were significantly different from those in the non-hemodynamic group (62.5% male) (P 0.049). However, the type of delivery, mean weight, height, head circumference, the circumference of the chest, and Apgar score did not differ between the two groups. Mean pH, HCO3- and PCO2 in umbilical cord blood gas samples were not significantly different between the two groups with or without intraventricular hemorrhage (IVH). Although it was not related to gender and type of delivery in newborns CONCLUSION: Blood gases do not help in determining the occurrence of IVH in infants. Nevertheless, it is associated with immaturity and fetal age.

RESUMO OBJETIVOS: Medimos o nível de gases de pH em bebês prematuros, no nascimento dos neonatos, e examinamos a relação entre a ecografia cerebral no terceiro e no sétimo dia após o nascimento. Um estudo de casos e controles realizados na Unidade de Cuidados Intensivos Neonatais (UCIN) do Hospital Shahid Akbar Abadi durante os anos de 2016-2017, Irã. MÉTODOS: Todos os recém-nascidos prematuros que deram entrada na UCIN foram inscritos no estudo atual. Ao nascer, foi retirada uma amostra de gás em sangue, do sangue do cordão umbilical dos bebês. No terceiro e sétimo dia após o nascimento, um radiologista realizou uma ecografia do cérebro de cada neonato. O cordão umbilical foi avaliado para detectar gases no sangue em 72 neonatos (em sua maioria do sexo masculino). RESULTADOS: Sessenta e seis recém-nascidos tinham ecografia normal e 16.7% (12 casos) tinham anomalias. 75% das 8 crianças com hemorragia intravenosa eram meninas, que foram significativamente diferentes das do grupo não hemodinâmico (62.5% homens) (P.0.049). Contudo, o tipo de parto, o peso médio, a altura, o perímetro cefálico, a circunferência do tórax e a pontuação de Apgar não foram diferentes entre os grupos. O pH médio, HCO3 e PCO2 nas amostras de gás no sangue do cordão umbilical não foram significativamente diferentes entre dois grupos com ou sem hemorragia intraventricular (Hiv). Apesar de não estar relacionado com o gênero e o tipo de parto em recém-nascidos. Conclusão: os gases sanguíneos não ajudam a determinar o aparecimento de Hiv nos bebês. Contudo, está associado com a imaturidade e idade fetal.

Comparison of Risk Factors Related to Intraventricular Hemorrhage between Preterm Infants Born After Normal and in Vitro Fertilization Conceptions.

OBJECTIVES: We aimed to compare the level of significance of risk factors related Intraventricular hemorrhage (IVH) between preterm infants born after IVF and non-IVF conceptions. MATERIALS & METHODS: This historical cohort study was done in four Iranian Hospitals in 2013-2014. Overall, 155 preterm newborns were divided into case (IVF) and control (normal conception) groups. Both groups' demographic data were extracted and recorded. The incidence of IVH and its grades were compared between case and control groups. Significant related risk factors were also considered. RESULTS: No differences were observed between 2 groups except for gestational age and mode of delivery. The incidence of IVH especially grades II and III were significantly higher in the case group (P=0.003). Results showed no correlations between Gestational age (GA), birth weight and number of gestations with the incidence of IVH in the case group (0.059, 0.85 and 0.49, respectively). On the other hand, among GA, birth weight and number of gestations; multi gestations (P=0.0001) was an effective risk factor for IVH occurrence in the controls. CONCLUSION: The incidence of IVH in the IVF group was significantly higher than in the non-IVF group. IVF as an independent risk factor may cause high-grade IVH; however, in the controls, multi gestational pregnancy (P=0.0001) was an effective risk factor for IVH occurrence.

The Value of Urinary Cystatin C Level to Predict Neonatal Kidney Injury.

BACKGROUND: The role of urinary cystatin C to early predict acute kidney injury (AKI) in children and neonates remains uncertain. The present study aimed to assess and compare the level of urinary cystatin C in neonates with and those without AKI. METHODS: This cross-sectional study was performed on 55 available neonates who were involved by AKI and admitted to the neonatal department at Ali-Asghar hospital in Tehran in 2016. 97 neonates with jaundice and normal serum creatinine level were randomly selected as the control group. In both groups and on admission, the urine levels of cystatin C and creatinine were measured. RESULTS: The average urinary level of cystatin C was 162.87 ± 56.50 mmol/mole creatinine in the group with AKI and 68.06 ± 57.16 mmol/mole creatinine in the control group that was significantly higher in former group (p < 0.001). The measurement of cystatin C level in urine could predict kidney injury with a sensitivity of 98.2%, a specificity of 39.2%, a positive predictive value of 47.8%, a negative predictive value of 97.4%, and an accuracy of 60.5%. Assessment of the area under the receiver operating characteristic (ROC) analysis showed that measuring urinary cystatin C level could effectively discriminate kidney injury from normal kidney condition in neonates (AUC = 0.868, 95CI: 0.811 - 0.925, P < 0.001). The best cutoff value of urinary cystatin C level to predict kidney injury was shown to be 41.5 mmol/mole creatinine yielding a sensitivity of 98.2% and a specificity of 46.4%. CONCLUSION: Measurement of cystatin C in urine is an early sensitive method to diagnose neonatal kidney injury.

Influence of high-dose oral erythromycin on feeding intolerance in preterm neonates: A randomized controlled trial.

Background: Feeding intolerance is a common complication in preterm neonates and is responsible for prolonged hospitalization. This study aimed at assessing the effects of high-dose oral erythromycin on feeding intolerance in preterm infants. Methods: A randomized, double blinded, placebo-controlled trial was performed during 2014 and 2015 (Tehran-Iran). Preterm neonates aged >14 days, who met the feeding intolerance criteria were selected for the study and their medical records were randomly assigned into 2 groups by simple randomization. Infants in group A received 10 mg/kg oral erythromycin every 6 hours for 2 days, followed by 4 mg/kg oral erythromycin every 6 hours for 5 days; and infants in group B received placebo with the same route. The number of days until reaching complete oral feeding, day of discharge from NICU, and complications related to intervention were recorded and compared between the 2 groups. Independent samples t test, Mann-Whitney, Fischer exact test, and Chi square were used to analyze the relationships between variables. P-value less than 0.05 was considered statistically significant. Results: A total of 20 infants in group A received erythromycin and 20 infants in group B received placebo. Erythromycin could not alter the mean volume of feeding, duration of parental feeding, length of hospitalization, and frequency of feeding discontinuity (p>0.05); however, mean days to reach complete feeding in group A was significantly shorter than in group B (9.80 vs. 16.80 days; p=0.001). Conclusion: High-dose erythromycin as a rescue measure with no potential adverse effect is beneficial in reducing the time taken to achieve full enteral feeding. However, more extensive investigations are needed to determine the best administration dosage.

The Efficacy of Omega-3 Supplement on Prevention of Retinopathy of Prematurity in Premature Infants: A Randomized Double-blinded Controlled trial.

BACKGROUND: The present study aimed to assess the efficacy of omega-3 in treating ROP in premature infants. METHODS: This randomized double-blinded controlled trial was performed on 160 premature infants with gestational age lower than 32 weeks and birth weight < 1500 grams who were at risk of ROP development (Tehran, Iran-2013). Children were randomly assigned to two groups. The intervention group received 300 mg omega-3 daily and the control group received sterile water as the placebo. The severity of ROP was defined according to the International Classification of ROP. RESULTS: The frequency of ROP was 7.5% in the group received omega-3 and 20.0% in the placebo group with a significant difference (p = 0.021). Regarding the severity of ROP in the intervention group, ROP grade I was found in two patients and ROP grade II in four patients; while ROP grade I, II, and III were revealed in 6, 6, and 4 patients in placebo group indicating a significant difference between the two groups (p = 0.001). Using the multivariate logistic regression modeling with the presence of gender, gestational age, and birth weight, the use of omega-3 was associated with reduced risk for ROP (p = 0.045). CONCLUSION: The use of omega-3 supplement can be an appropriate treatment option for the treatment of ROP in premature infants.

Does Adding Intravenous Phosphorus to Parenteral Nutrition Has Any Effects on Calcium and Phosphorus Metabolism and Bone Mineral Content in Preterm Neonates?

The use of parenteral nutritional supplementation of phosphorus may lead to exhibit higher plasma phosphate concentrations and less radiological features in premature neonates susceptible to osteopenia. The present study aimed to assess the beneficial effects of adding intravenous phosphorus to total parenteral nutrition (TPN) on calcium and phosphorus metabolism in preterm neonates by measuring bone mineral content. This open-labeled randomized clinical trial was conducted on premature neonates who were hospitalized at NICU. The neonates were randomly assigned to two groups received TPN with intravenous sodium glycerophosphate or Glycophos (1.5 mmol/kg/day) or TPN without sodium glycerophosphate. At the end of the four weeks of treatment, the presence of osteopenia was examined using DEXA Scan. After completing treatment protocols, the group received TPN with intravenous Glycophos had significantly lower serum alkaline phosphatase (360±60 versus 762±71, P<0.001), as well as higher serum calcium to creatinine ratio (1.6±0.3 versus 0.44±0.13, P<0.001) compared to the control group received TPN without Glycophos. Those who received TPN with intravenous Glycophos experienced more increase in bone mineral density than those in control group (0.13±0.01 versus 0.10±0.02, P<0.001). There was no significant difference in serum calcium and serum vitamin D between the case and control groups. Adding intravenous sodium glycerophosphate to TPN in premature neonates can compensate the lack of bone mineral content and help to prevent osteopenia.

The effectiveness of earmuffs on the physiologic and behavioral stability in preterm infants.

BACKGROUND: The use of earmuffs can protect preterm infants against negative effects of high noise levels in the neonatal intensive care unit. This study was aimed at assessing the effectiveness of the earmuffs on the physiologic and behavioral responses in preterm infants. METHODS: A crossed over controlled trial was conducted at Aliasghar Hospital (Tehran, Iran) in 2014. Thirty-six preterm infants cared in closed incubators, 18 cases wore a pair of silicon earmuffs in the first day and the others were worn it at the second day. During 2 consecutive days, all subjects were observed as their own controls (without earmuffs). Physiologic (body temperature, heart rate, respiratory rate, systolic, diastolic pressures, arterial Oxygen Saturation) and behavioral responses (according to the Anderson behavioral state scoring system) were assessed every 2 h for 8 h long during daytime for two consecutive days. RESULTS: The application of earmuffs could decrease the rate of the heart and respiratory while could increase the amount of oxygen saturation (p < 0.05). The results also showed that the preterm infants with earmuffs had lower ABSS score and a better light sleep compared to those without earmuffs (2.38 ± 0.47 versus 4.8 ± 0.97, p < 0.05). CONCLUSION: The results indicated that using the earmuffs reduces the level of noise in NICUs following by improving the preterm neonates' physiological stability and behavioral states of ABSS.