Iranian Journal of Neonatology
Volume:12 Issue: 4, Autumn 2021

Perinatal asphyxia is the main cause of neurodevelopmental sequelae and perinatal death. Caspase-3 is a major enzyme associated with apoptosis and increases in hypoxic-ischemic events. There is still no reliable biomarker to predict the severity and outcome of an asphyxial event. In this regard, this study aimed to determine the caspase-3 level and its role as an outcome predictor in perinatal asphyxia.
This paired-group observational analytical cross-sectional study lasted from September 2016 to February 2017. In total, 50 neonates were included in the research and Caspase-3 levels were examined at two different times. Student’s t-test and logistic regression analysis were used for statistical analysis. There were 23 neonates (46%) with hypoxic-ischemic encephalopathy (HIE) and an increase in Caspase-3 level by 0.3135 points from the first to the second examination (t=6.555; P<0.0001). Results of this study showed a significant correlation between the caspase-3 level and mortality in neonates with HIE during both the initial (RR=2.33; P=0.014) and subsequent examinations (RR=2.25; P=0.015).
There is a significant increase in Caspase-3 levels in infants who suffer from perinatal asphyxia which can predict mortality in neonates with HIE.

Urine calprotectin significantly elevates in acute kidney injury (AKI) in adult and pediatric patients. The present study aimed to assess the accuracy of urine calprotectin as a diagnostic marker for (AKI) in neonates. This cross-sectional study assessed urine calprotectin in 100 neonates (80 newborns with confirmed AKI and 20 healthy ones). Random urine calprotectin was measured by Enzyme-linked Immunosorbent Assay (ELISA) and then compared between the two groups. We included the neonates who had received at least 48 h of intravenous fluid and met the inclusion and exclusion criteria. Receiver-operating characteristic (ROC) curve was used to set a cut-off point for urine calprotectin for the prediction of AKI. The overall accuracy and Kappa coefficient were used to assess the agreement between the two methods. A p-value less than 0.05 was considered statistically significant.
Urine calprotectin levels were not significantly higher in neonates with AKI, as compared to those in the healthy ones (146.2 versus 142.4; P=0.1). The results pointed to an optimal cut-off value of 123.5 mg/dl for urine calprotectin with the area under the curve of 0.515 (the sensitivity, specificity, positive predictive value, and negative predictive value were obtained at 77.5%, 40%, 83.7%, and 30.7%, respectively). The overall accuracy and Kappa agreement coefficient were reported as 70% and 0.15, r (P=0.11).
As evidenced by the results of the resent study, although urine calprotectin level elevates in AKI in neonates, it is not more sensitive than gold standards to predict AKI.

Neurosonography has been widely used for screening and early detection of Central Nervous System (CNS) defects, such as intraventricular hemorrhage, hydrocephalus, cerebral edema, or any structural anomalies in the neonatal brain in the neonatal intensive care unit (NICU) of a tertiary level hospital. The present study aimed to assess the detection of CNS abnormalities by neurosonography in critically ill neonates. This prospective cross-sectional study at the Neonatology Unit of the Paediatric Department of Acharya Vinoba Bhave Rural Hospital (AVBRH). A neonate was described as “critically ill” based on detailed maternal history and clinical examination. These neonates were subjected to neurosonography according to the inclusion and exclusion criteria in accordance with the noted protocols and various anomalies. Gestational age, birth weight, clinical examination, investigation, neurosonography finding, and outcomes were evaluated. Neurosonography was performed in 105 critically ill neonates, out of whom 21 cases had abnormal neurosonography findings. Abnormal neurosonography was not significantly correlated with birth weight and gestational age of high-risk neonates (P=0.538 &P=0.130). The most frequent clinical manifestation was respiratory distress syndrome, followed by a neonatal seizure. The mean scores of heart rate, respiratory rate, systolic blood pressure, diastolic blood pressure, and oxygen saturation were obtained at 140±19.81, 54.08±13.07, 90.96±8.66, 54.13±8.39, and 94.39±6.93, respectively. Neurosonography is a useful tool in NICU. It is an acceptable and reliable modality to screen critically ill neonates, assisting the early detection and management of these ill neonates.

Premature birth is linked to neonatal morbidity and mortality worldwide. Neuregulin (NRG) is a trophic factor from the growth factor (GF) of a transmembrane polypeptide, encoded by four different genes, including NRG-1 which acts as an endogenous protector in fetal development. Decreased levels of NRG-1 affect several organs. The relationship between NRG-1 polymorphism and the outcome of neonatal development has been widely studied. There are no studies that have assessed NRG-1 levels and NRG-1 rs35753505 C/T polymorphism in preterm neonates, as well as its association with short-term morbidities in Indonesia.
This cross-sectional study was conducted on preterm neonates with the gestational age of 32-36 weeks in Medan, North Sumatera, Indonesia, from December 2017 to December 2018. It aimed to evaluate the association of NRG-1 levels and NRG1 polymorphism with short-term morbidities. Samples were obtained from cord blood specimens. Enzyme-linked immunosorbent assay (ELISA) was used to determine NRG-1 levels, and NRG-1 polymorphism was sequenced by polymerase chain reaction (PCR). Observations in preterm neonates were made during the first 72 h to assess short-term morbidities.
During the study period, 48 cord blood specimens from preterm neonates were found eligible for analysis. Preterm neonates with low NRG-1 levels had a 10-times higher risk of developing short-term morbidities. The presence of CC and CT genotypes increased the risk of developing short-term morbidities 13.33 times (P=0.003) and 6.19 times (P=0.019), respectively. The presence of the C allele in subjects' genotype increased the risk of short-term morbidities 4.04 times (P=0.001), compared to those with T allele.
As evidenced by the obtained results, preterm neonates with low NRG-1 levels had a higher risk of developing short-term morbidities. Furthermore, there was a significant association between NRG-1 rs35753505 C/T polymorphism and short-term morbidities.

Early-onset neonatal sepsis is recognized as a common and serious problem for neonates. The clinical manifestations of neonatal sepsis are nonspecific and have varied clinical features. Therefore, their diagnosis is based on a combination of clinical presentation, the use of biological tests, and anamnestic arguments. The present study aimed to describe the infection risk factors, as well as clinical, paraclinical, and evolutionary characteristics of newborns with suspected early-onset neonatal sepsis and highlight the importance of C-reactive protein(CRP) to diagnose neonatal sepsis.
This retrospective analytical study was conducted at the National Reference Center for Neonatology and Nutrition at Children's Hospital, University Hospital Centre IbnSina of Rabat, from January 1 to December 31, 2016.
During the study period, 1,199 newborns met the inclusion criteria. Upon admission, 52% of cases were under the age of one day. Symptomatic newborns represented 67.4% of the cases. The hospitalized cases with one or more infection risk factors were represented 80.3% of cases. The CRP was positive (> 20 mg/L) in 698 (58%) newborns. Univariate analysis pointed out that CRP value was significantly associated with age groups (P<0.001), presence of at least one infectious risk factor (P<0.001), as well as the presence of respiratory (P<0.001), cutaneous (P<0.001), circulatory (P=0.02), and neurological (P=0.008) symptoms. The diagnosis of early-onset neonatal infection with a meningeal, pulmonary, or ocular location was retained in 5%, 2%, and 0.2% of cases, respectively. The mortality rate was reported as 7%.
Screening, management, and reduction of early-onset neonatal infection remain a crucial challenge, requiring coordination between pediatricians and obstetricians to obtain reliable data and identify newborns at risk.

The painful procedure of drawing blood from the heel (heel lance) in the neonatal intensive care unit (NICU) is necessary for some diagnostic tests. However, it can have negative effects on the physiological criteria of preterm neonates. This study aimed to compare the effect of lullaby and kangaroo care on the physiological criteria of preterm neonates admitted to the NICU during heel lance.
This clinical trial study was conducted with a crossover design on 60 preterm newborns (30-36 weeks of gestation) admitted to the NICU at Ali ibn Abi Taleb Hospital, Zahedan, Iran, 2019. The neonates were randomly divided into two groups of lullaby and kangaroo care (n=30 each). In the former group, a lullaby was played for the neonates through headphones for 30 min, and in the latter group, the naked neonate was placed in the mother's arms for the same duration. Physiological criteria were recorded before (0 min), during (15 min), and after the procedure (30 min). The collected data were analyzed in SPSS software (version 22) using independent t-tests and Chi-square test.
There was no statistically significant difference between the mean scores of gestation age of neonates in the lullaby (32.63±1.92) and kangaroo care (32.69±1.92) group (P=1.000). The results of the independent sample t-test showed that during the intervention, there was a difference between the mean pulse rate (P=0.015), respiration rate (P=0.003), and arterial oxygen saturation percentage (P<0.01) in preterm neonates. The two groups were significantly different in this regard. However, in the post-intervention stage, no statistically significant difference was observed between the mean pulse rate and respiration rate (P=0.60 and P=0.614, respectively).
Given the positive effect of kangaroo care on the physiological criteria of preterm newborns during heel lance, this non-pharmacological, low-cost, and available method could help nurses working in the NICU improve physiological criteria during heel lance.

Jaundice is a prevalent problem among neonates. Patients undergoing phototherapy need a close follow-up of their serum bilirubin levels to determine the treatment response. To make a comparison between transcutaneous bilirubin measurements (TcB) from covered skin areas during phototherapy and total serum bilirubin (TSB) levels.
This prospective observational study was conducted on 30 full-term neonates with indirect hyperbilirubinemia requiring phototherapy.  Some parts of the skin (forehead and sternum) were covered in each neonate using the BiliEclipsephoto opaque patch and this covered site was used to measure TcB during phototherapy and compare it with TSB. Both TSB and TcB estimation were performed on icteric newborns before, as well as 24 and 48 h of exposure to phototherapy.
As demonstrated by the obtained results, TSB was not significantly different from TcB measured at forehead and sternum before phototherapy. Moreover, no significant difference was detected between TSB and TcB from the covered forehead and sternum in 24 and 48 h of phototherapy initiation. There was a highly significant positive correlation between TSB and covered forehead/sternum TcB during phototherapy. There was no significant difference in both covered forehead and sternum TcB according to different used TcB devices.
Measurement of TcB from the covered area of the skin during phototherapy using transcutaneous bilirubin meters is a reliable method to assess TSB in full-term neonates and could lead to a reduction in blood sampling and its complications.

Congenital heart defect (CHD) is one of the leading causes of neonatal death. Although the majority of CHDs are isolated, a significant number of them are associated with noncardiac anomalies. Esophageal Atresia (EA)/ Tracheoesophageal Fistula (TEF) is the most common congenital disorder of the upper GI tract. It is estimated that up to 70% of EA/TEF infants have other associated congenital anomalies such as CHD. This study determined the proportion of heart anomalies among the diseases of the upper GI tract in Imam Reza Hospital of Mashhad. The records of 38 infants with upper GI obstruction who were referred to the Pediatric Cardiology Clinic of Imam Reza Hospital in Mashhad between 2001 and 2017 were evaluated in this retrospective study. Data were coded and entered into SPSS software (version 16) and analyzed using Chi-square and T-test. In this study, 38 babies with upper GI obstruction were evaluated (20 patients were female, 52.6%), and the average birth weight was 2.390 +-0.870 gr. Among the parents, 13 patients (34.2%) were relative (third-degree or more) and 25 patients (65.8%) were nonrelative. The initial and final diagnosis was different at 14 pt (36.8%) that was confirmed with echocardiographic findings. CHDs were divided into two groups in this study. Malformations such as PFO (patent foramen ovale) or FMV without MR (floppy mitral valve without mitral regurgitation) considered as non-important congenital heart diseases. Other malformations that require interventional or medical management such as VSD, ASD, TOF, or other CHDs are considered important CHDs.  Nineteen pt (50%) had important CHD and 16 pt (42.1%) had non-important CHD  and 3 pt (7.9%) had normal echocardiographic findings. The heart defect is the most common associated anomaly in children with EA/TEF, which is divided into two subgroups. The first important one is CHD, which is effective in gastric surgery and management, and VSD is the most common type. The other group is non important CHD such as PFO or FMV without MR that are not effective in their management. The patients with EA/TEF are at risk for low birth weight and preterm delivery.

Coronavirus disease 2019 (COVID-19) directly increases the risk of preterm delivery. Furthermore, the COVID-19 pandemic may indirectly affect the health status of preterm infants. In the present study, several views have been mentioned regarding the negative effects of this viral disease on postnatal health that require much consideration. A related brief study was conducted in 2020. Previously published works have revealed several adverse effects of the COVID-19 pandemic on the health of preterm neonates. Literature review has demonstrated that several policies have been implemented to protect newborns from the risk of infection in the neonatal intensive care units (NICU). Some of these policies are isolation of COVID-19 positive mothers, mother-infant separation, interruption in skin-to-skin contact and breastfeeding, restrictions associated with the presence of parents in the NICUs. Moreover, postponement of follow-up consultations and deficiency in healthcare services are other critical issues. Urgent measures seem to be implemented to protect preterm neonates and their parents from severe consequences. Some beneficial recommendations are providing adequate professional human resources in the NICUs, improving virtual communication for involving parents in NICU admissions and postnatal follow-up appointments, promoting exclusive breastfeeding for subjects without any contraindications, reminding vaccination schedule by calling or texting, reducing the family financial instability by governmental support, and improving mother-infant bonding with hand and respiratory hygienes.

Kangaroo mother care is essential improves outcomes of premature and low birth weight infants. Even though kangaroo mother care is now recognized by global experts as an integral part of essential newborn care, the adoption and implementation of the kangaroo mother care is still challenging. Aim of this study to explore perceived enablers and barriers of kangaroo mother care among mothers and nurses in neonatal intensive care unit. Descriptive Phenomenological study design was conducted in Tikur Anbessa Specialized referral Hospital at Addis Ababa with 13 mothers and 7 nurses from 10th May -15th July, 2020. In-depth interview used with semi-structured questionnaire and data was collected till saturation of information. Thematic analysis was done with ATLAS.Ti software version 7.5.16 . Major enablers and barriers of practicing kangaroo mother care among mothers and nurses reported that lack of understanding of KMC, family responsibility and workload, lack of awareness of KMC by community, social practice and traditional adaptation were the barriers to practice of KMC. Poor supervision and follow-up, limited resource especially sanitation resource are the major barriers related to health staff and setting. Nurses reported that scale- up of kangaroo mother care was influenced by absence of training, poor attention given by managers and administrative, shortage of rooms and facilities, workload and time shortage. A complex array of barriers and enablers determine a mother’s and nurses ability to provide KMC. Improve the mothers' to practice KMC and to promote the health of preterm infants, supports such as family, community and health professional support needed. Nurses needed in-service education, proper administration and less workload to promote KMC practice.

This study aimed to evaluate the effectiveness of therapeutic hypothermia (TH) among asphyxiated newborns for reducing mortality, adverse clinical events, and short-term outcomes in comparison to asphyxiated newborns not receiving TH.

This non-randomized cohort study was conducted at a tertiary care center. The statistical population of the study consisted of asphyxiated newborns admitted in the neonatal intensive care unit within 24 h of life meeting the laboratory and/or clinical criteria of severe birth asphyxia. Eligible newborns, who received TH, were labeled as recipients and those who did not receive TH were labeled as non-recipients.

Out of 176 studied neonates, 89 cases received TH, while 87 of the subjects did not receive TH. The recipients of TH had a 15.3% lower mortality rate, compared to non-recipients (P<0.05). The incidence of adverse clinical events was similar among both groups. At the time of discharge, 73.2% and 56.8%, 92.6% and 70.1%, 30.4% and 46.2% of recipients and non-recipients were neurologically normal (P=0.01), able to breastfeed (P<0.05), and required anti-epileptics (P<0.05), respectively.

It can be concluded that TH was an effective and feasible therapy with decreased death rate, better neurological status at discharge, and lesser need for anti-epileptics without increasing adverse clinical events at limited-resource settings using low-cost devices.

Pre-pregnancy body mass index (BMI) during the gestation period is a major factor that predicts fetal weight and development. It is also positively associated with an increase in fetal head circumference and femur length. To assess the impact of pre-pregnancy BMI on neonatal anthropometry This multicenter observational study was conducted from July 2010-July 2011. A total of 1,000 mothers were enrolled, and their antenatal records were screened for pre-pregnancy weight, height, and other details. They were assigned to four categories as per their BMI: underweight: BMI<18.5kg/m2, normal:18.5-24.99kg/m2, overweight: 25-29.9kg/m2, and obese: ≥30kg/m2 group. The neonatal anthropometric measurements and other information were retrieved from the neonate's files. Neonates who were admitted to the neonatal intensive care unit (NICU) were followed till their discharge from hospital or mortality. Out of 1,000 cases, 170 (17%) belonged to underweight, 224 (22.4%) to overweight, 86 (8.6%) to obese, and 520 (52%) to the normal group. Overweight and obese women were at a higher risk of developing gestational diabetes mellitus, hypertensive complications during pregnancy, and undergoing cesarean sections. They also had a higher risk of delivering large for gestational age and post-term neonates, whereas underweight women had a significantly higher risk of delivering small for gestational, low birth weight, and premature newborns. Furthermore, a positive correlation was observed between maternal BMI and neonatal anthropometric measurements. As evidenced by the obtained results, both low and high pre-pregnancy BMI is associated with adverse maternal and perinatal outcomes.

Cantrell's pentalogy (CP) is a rare congenital disease caused by morphological changes in the mesoderm. Defects of the lower sternum with ectopia cordis, midline supraumbilical abdominal wall, anterior diaphragm, diaphragmatic pericardium, and cardiac alterations are the related symptoms.

The case report is a newborn boy with a prenatal diagnosis of abdominal wall defect caused by pentalogy of Cantrell class 1 and initial measures were taken to prevent adverse outcomes.  Congenital syndromic disease, such as CP, is likely to be treated with early prevention and adequate prenatal controls. Also, early diagnosis facilitates effective clinical and surgical management and thus leads to a positive prognosis.

Finally, it has been established that proper decision-making about therapeutic possibilities during the early years may improve the quality of life and longevity in this population.

Lumbosacral agenesis or caudal regression syndrome (CRS) is a rare congenital malformation represented with symmetrical sacrococcygeal or lumbosacrococcygeal agenesis with a varied incidence between 1 per 25000 live births to 2.5 per 100000 live births. Additionally, manifold abnormalities may be associated with CRS, including  spinal cord malformations, cardiac malformations, lipomyelomeningocele, orthopedic deformities, renal agenesis, neurogenic bladder, tethered-cord, sacral agenesis, and anorectal atresia.

We report a case of a male neonate delivered to a 28-year-old diabetic mother at 38 weeks’ gestation diagnosed with CRS. In this case, lumbosacral agenesis, hip dislocation, and club foot deformities along with cardiac abnormalities, including small patent ductus arteriosus (PDA), atrial septal defect (ASD), hypertrophic cardiomyopathy (HCM) without left ventricular outlet obstruction were seen.

Having the 200-fold increased relative risk of developing CRS in infants of diabetic mothers in mind, this case report provides evidence that uncontrolled maternal diabetes might increase the risk of CRS  in infants.

The oculo-auriculo-vertebral spectrum (OAVS) includes three closely related rare congenital diseases of different severity with an incidence of 1/3500-7000 individuals. The involvement is usually unilateral; however, bilateral involvement may also occur. In addition to craniofacial anomalies, defects in the cardiovascular, genitourinary, vertebral, and central nervous systems can be observed as well. The phenotype of the cases is highly variable. Goldenhar syndrome is the most severe form of this condition.

In total, three instructive cases of Goldenhar syndrome with different features have been reported in the present case study. The most common ear anomalies among these three cases included external auditory canal atresia, helix deformities, preauricular skin tag and/or ear pitting, microtia, and conductive hearing loss. The second case was presented with hemifacial microsomia on the more severely affected right side, and the third case had bilateral Brushfield spots and a dermolipoma ophthalmological findings.

Based on the findings of the present study, OAVS should also be considered in the differential diagnosis of the cases with facial and ear anomalies.

Recto-urethral prostatic fistula (RUPF) is a rare form of anorectal malformation (ARM). Its prenatal diagnosis and management with a minimum consequence are challenging. This study aimed to present diagnostic and therapeutic modalities in a patient with RUPF.

A 32-year-old pregnant woman with no relevant medical or surgical history at 27 weeks of gestation was referred to our department of pediatric surgery. Prenatal ultrasound showed loop dilatations and enterolithiasis. Fetal magnetic resonance imaging (MRI) imaging confirmed the diagnosis of ARM and suggested the presence of a recto-urinary fistula. There was no other associated malformation. Parents decided on the continuation of pregnancy after counseling. A 2300 g male was born at 37 weeks of gestation in February 2019. Colostomy followed by laparoscopic pull-through were performed. Expectations of the physician and parents were met after a one-year follow-up period.

Fetal MRI had the potential to diagnose ARM more accurately than ultrasound. Moreover, laparoscopic pull-through was safe and feasible.