Iranian Journal of Neonatology
Volume:13 Issue: 1, Winter 2022

Neonatal hyperbilirubinemia is a common clinical condition among newborns that requires early detection and medical management to avoid bilirubin toxicity. This study aimed to investigate the role of cord blood alkaline phosphatase (ALP) levels as a predictor of hyperbilirubinemia in full-term neonates.
This cross-sectional study was conducted on full-term newborns within April-August 2019 in several hospitals in Medan, Indonesia. Cord blood ALP levels upon delivery and serum bilirubin levels on 72 h of life were measured.
Out of 147 full-term neonates, the mean cord blood ALP levels and serum bilirubin levels were obtained at 166.3±45.1 IU/l and 9.6±2.3 mg/dl, respectively. There was a significant difference in mean cord blood ALP levels at serum bilirubin levels of >10 mg/dl and ≤10 mg/dl on 72 h of life (196.8±40.7 IU/l and 146.4±37.5 IU/l, respectively; P=0.001). A positive, moderate, and significant correlation was observed between cord blood ALP levels and serum bilirubin levels on 72 h of life (r=0.429; P=0.001). The cut-off value of 163.5 IU/l was associated with 84.7% sensitivity and 77.3% specificity for predicting hyperbilirubinemia in full-term neonates.
There was a positive correlation between cord blood ALP levels and serum bilirubin levels on 72 h of life. Therefore, cord blood ALP may be utilized as a predictor for hyperbilirubinemia in full-term neonates.

Asphyxia may lead to serious complications, among which acute kidney injury (AKI) is the most common. Early diagnosis of AKI can help prevent impaired acid-base, fluid, and electrolyte balance that may lead to life-threatening complications. This study aimed to evaluate the effect of kidney injury molecule-1 (KIM-1) and cystatin-C in the early diagnosis of AKI among asphyxiated neonates.

This case-control study was conducted on 45 asphyxiated neonates, 24 of whom were in the control group and 23 cases were in the case group. Creatinine (Cr), KIM-1, and cystatin-C were measured for participants within 8 h and 4 days after birth and compared between case and control groups.

The mean level of Cr-Standardized KIM-1 measured within 8 h and 4 days after birth was significantly higher in the case group, compared to the control group (P-value<0.05). The mean level of Cr-Standardized cysteine, only 4 days after birth, was significantly higher in the case group, compared to the control group (P-value<0.05). A receiver operating characteristic (ROC) curve analysis demonstrated that between the two biomarkers with two measurements, the KIM-1 Cr-Standardized within 4 days had the highest area under the curve (AUC) (0.751, 95% CI: 0.597-0.905). Moreover, the results of ROC curve analysis showed that Cr-Standardized KIM-1 within 4 days after birth with a critical value of >0.67 ng/ml allowed to predict kidney failure in newborns with 57.1 % sensitivity and 86.4 % specificity.

The findings of the present study show that high-specificity KIM-1 is a good biomarker for the early detection of acute renal failure in asphyxiated infants; however, similar expectations cannot exist with regards to cystatin-C for at least the first 8 h after birth.

Invasive mechanical ventilation in infants suffering from respiratory distress syndrome (RDS) is associated with some complications, such as chronic lung disease, and therefore, the tendency to use non-invasive methods is increasing. The present study aimed to compare the effect of non-invasive continuous positive airway pressure (CPAP) and a combination of high-frequency oscillation ventilation (HFOV) and CPAP in the treatment of RDS in infants. In this clinical trial, 37 infants suffering from RDS admitted to the Neonatal Intensive Care Unit of Hajar Hospital in Shahrekord were randomly assigned to two groups treated with CPAP alone and CPAP plus HFOV. The baseline information, including gestational age, time of birth, weight, gender, duration of hospitalization, duration of oxygenation and CPAP, the time of transition to oral feeding, and hemodynamic parameters, were recorded. The obtained data were analyzed in Stata software. The mean scores of the length of hospitalization, the time to start and complete oral feeding, as well as the duration of CPAP and oxygenation, were higher in the CPAP group, as compared to those in the HPA+CPAP group; nonetheless, the differences were significant only for the duration of oxygenation (P<0.05). As evidenced by the obtained results, the use of HFOV+CPAP led to a more significant reduction in the duration of oxygen therapy, as compared to CPAP, in preterm neonates suffering from RDS.

Prediction of the outcome of perinatal asphyxia (PA) is important but formidable. Apgar score has a limited role in predicting the outcome. Urinary uric acid and creatinine ratio (UA/Cr) is an early, noninvasive, and cheap biomarker of PA which may predict its morbidity. This study aimed to determine the urinary UA/Cr in neonates with PA, compare it with UA/Cr in non-asphyxiated neonates, and derive the optimum cut-off value of this ratio to label PA.
This observational cross-sectional study was carried out on 100 term neonates appropriate for gestational age (AGA) with PA (cases) and 100 non-asphyxiated term AGA babies (controls). Urine samples were collected within 24 h of life; moreover, uric acid and creatinine levels were determined by an auto-analyzer.
The mean urinary UA/Cr ratio was significantly higher in the cases, compared to the controls (3.41±0.68 vs. 1.99±0.23) (P<0.0001). The cut-off value of this ratio to label PA was>2.5 with sensitivity, specificity, positive predictive value, and negative predictive value of 98%. Urinary UA/Cr ratio and cord blood pH were significantly correlated with each other (correlation coefficient r=-0.8951, P<0.001). Moreover, the urinary UA/Cr ratio and 5-min Apgar score were also significantly correlated with each other (r=-0.8806, P<0.001).
Urinary UA/Cr ratio is a non-invasive, cheap, and reliable marker for PA with good predictive value in this study.

Hirschsprung's disease (HD) is the most common cause of colon obstruction in neonates. Lack of calretinin immunohistochemistry (IHC) in colon lamina propria could be associated with aganglionosis.
This cross-sectional retrospective study examined 64 patients suspicious of HD and conducted on collected-demographic data and Hematoxylin/Eosin (H & E) results of the surgical rectal biopsy from the archive of Imam Hossein Hospital, Isfahan, Iran. Calretinin IHC was achieved for all the specimens, and the results of the two methods were compared. The receiver operating characteristic (ROC) chart shows sensitivity changes according to (1-specificity). Moreover, sensitivity, specificity, as well as the positive and negative predictive values (PPV and NPV) of calretinin staining in lamina propria and muscularis mucosa, compared to H & E staining, was calculated in this study.
The number of males and females was the same in this study (n=32; 50%). The age of the patients ranged from 1 month to 156 months (13 years). Out of 64 patients, 8 cases were diagnosed with HD, and calretinin staining was negative in 7 patients; moreover, only one case showed weak positive staining. In 56 patients, who were not HD, two patients with negative calretinin staining had a positive H&E staining report. The current study aimed to check the diagnostic value of calretinin IHC in lamina propria of patients suspicious of HD. Compared to H&E staining, which is the routine method in thick wall biopsies, the statistics show that calretinin IHC has a high diagnostic value (P<0.001), sensitivity of 87%, specificity of 96%, PPV of 77%, and NPV of 98%.
In conclusion, calretinin IHC utilized in specimens seems superficial and inadequate; moreover, the association with the high specificity percentage (96%) could help physicians with less invasive biopsy methods, such as endoscopic rectal biopsy.

Neonatal hyperbilirubinemia is a life-threatening and multifactorial disorder affecting about 60%-80% of newborns during their first week of life. Various environmental and genetic factors can contribute to the occurrence of this problem. The present study aimed to investigate the relationship between the two organic anion transporter 2 (OATP2) gene polymorphisms (388A>G and 521T>C) and the risk of neonatal hyperbilirubinemia.

A total of 200 neonates, including 100 infants with pathological icterus without a specific cause as the case group and 100 healthy neonates as the control group, were included in this cross-sectional study. Using fresh blood DNA, allelic frequency and genotypic distribution of each variant were determined by polymerase chain reaction-restriction fragment length polymorphism method. The biochemical measurements were also performed for both groups.

The two groups were similar in terms of gender, birth weight, gestational age, diet, and type of feeding. Allelic frequency and genotype distribution of the 388A>G and 521T>C polymorphisms did not show any significant association with hyperbilirubinemia both in crude and modified conditions (P>0.05). Moreover, no significant difference was observed between cases and controls in diplotypes and haplotypes analysis (P>0.05).

As evidenced by the obtained results, the neonates with hyperbilirubinemia were not different from healthy newborns in allelic frequency and genotypic distribution of the two variants of the OATP2 gene. It seems that these two polymorphisms are not correlated with the risk of hyperbilirubinemia in an Iranian neonatal population. Further studies with larger sample sizes are needed to confirm the results of this study.

Hirschsprung's disease (HSCR) may be accompanied by other anomalies, including congenital heart disease (CHD), resulting in additional complications. This study was performed to evaluate the prevalence and type of concomitant CHD in hospitalized children with HSCR.

All HSCR patients (n=129) admitted to Mofid Children's Hospital in Tehran, Iran, from April 2016 to August 2019 were investigated in a descriptive cross-sectional study. Two-dimensional, M-mode and pulsed, continuous, and color Doppler provided echocardiography were applied to evaluate cardiac structure and function.

CHD was observed in 48 (37.2%) cases, and the most common anomalies were Atrial Septal Defect (ASD) in 20 (15.5%), Ventricular Septal Defect (VSD) in 1 (0.8%), Patent Ductus Arteriosus (PDA) in 2 (1.6%), Tetralogy of Fallot in 3 (2.3%), ASD and Pulmonary stenosis in 2 (1.6%), ASD and PDA in 7 (5.4%), ASD and VSD in 3 (2.3%), as well as VSD and PDA in 2 (1.6%) patients.

Cardiac anomalies are relatively prevalent in the Iranian HSCR population participating in the present study. In addition, early echocardiographic evaluation in the setting of HSCR is recommended.

Neonates born between 340/7-366/7 gestational weeks are considered late preterms with fewer risks, compared to smaller babies and more risks for morbidity and mortality than their term peers. The present study aimed to analyze maternal problems, as well as morbidity and mortality of late preterms followed in the Neonatal Intensive Care Unit. A total of 230 neonates' files were analyzed, and demographic characteristics, respiratory, as well as metabolic  and maternal problems, were recorded in this study. Out of 230 neonates, 166 (72, 2%) and 129 (56,1%)  newborns were inborn and male, respectively. Moreover, 23 (10%) neonates were born through vaginal delivery. The mean birth weight of the neonates was estimated at 2532.1±540.3 gr. In total, 66, 71, and 93 infants were 34 0/7 and 34 6/7, 35 0/7-356/7, as well as 36 0/7-36 6/7, respectively. The premature rupture of membranes, placenta previa, ablatio placenta were obtained at 9.1% (n=21), 2.2% (n=5), and 3.5% (n=8), respectively.In addition, preeclampsia (n=24; 10.4%), cholestasis of pregnancy (n=7; 3%), oligohydramnios (n=26; 11.3%), and gestational diabetes mellitus (n=27; 11.7%) were observed in this study. The rates of transient tachypnea of the newborn, respiratory distress syndrome, polycythemia, hypoglycemia, indirect hyperbilirubinemia with intensive phototherapy, and feeding intolerance was estimated at 72.2% (n=166), 7.8% (n=18), 5.6% (n=13), 6.1% (n=14), 4.3% (n=10), and 8.7% (n=20), respectively. Any maternal problems and cholestasis of pregnancy were significantly more likely in 340/7 and 346/7 gestational weeks, compared to others (for any maternal problem and cholestasis of pregnancy: P=0.009 and P=0.012, respectively). Evaluation of the late preterms as terms may lead to neglecting some problems. Therefore, late preterms should be closely monitored, especially for respiratory problems in terms of intensive care requirements.

The birth of a neonate with a congenital anomaly who is admitted to the neonatal intensive care unit (NICU) is a threat to the formation of paternal bonding.  The present study aimed to assess the effect of fathers’ involvement in the care of neonates with congenital anomalies on father-neonate bonding in NICUs.
This quasi-experimental study with a control group was conducted on fathers of neonates with congenital anomalies admitted to the NICU of Mofid Hospital affiliated to Shahid Beheshti University of Medical Sciences in Tehran, Iran, from January 2019-September 2021. A total of 60 participants were selected via the convenience sampling method and randomly assigned to two groups of experimental and control. The Mother-to-Infant Bonding Scale was used to collect the needed data. The intervention lasted for four weeks. In the first week, fathers attended three sessions on how to provide care; thereafter, over the next three weeks, fathers became involved in the care of their newborns. The data were analyzed in SPSS software (version 21), and a p-value less than  0.05 was considered statistically significant.
After the intervention, there was a statistically significant difference between the mean scores of paternal bonding in two groups of control (4.41±2.51) and experimental (2.21±2.37) (P=0.001), with a lower score indicating a stronger paternal bond. The mean paternal bonding scores decreased to 6.59±17.1 and 4.89±0.54 in the two groups of intervention and control, respectively. The obtained results pointed to a significant difference between the two groups in terms of alterations in bonding scores (P<0.001).
As evidenced by the results of the present study, the participation of fathers in the care of their neonates with congenital anomalies was associated with a greater improvement of father-neonate bonding. Therefore, nurses need to devote more assiduous attention to the involvement of fathers in the care of these neonates.

Hemodynamic significant Patent Ductus Arterisous (hsPDA) is one of the main complications of preterm birth; however, its management needs further research and development. Ductal stealing results in pulmonary hyperperfusion which potentially causes oxygenation disorders and leads to target organ disruptions (i.e. cerebral, abdominal, and renal). Therefore, monitoring tissue oxygenation is essential for detecting organ disorders. Previous studies revealed that near-infrared spectroscopy (NIRS), as a non-invasive method, showed promising results in monitoring tissue oxygenation. This study aimed to analyze the difference in regional oxygen saturation (rSO2) between premature babies with and without hsPDA. This cross-sectional study was conducted on preterm infants aged 3-7 days with 24-336/7 weeks of gestation. hsPDA diagnosis was carried out using echocardiography; defined as >1.5 mm diameter of ductus arteriosus and >1.4 left pulmonary artery and aorta (La/Ao) ratio. The cerebral (rcSO2), abdomen (raSO2), and renal oxygen saturation (rrSO2) were measured through NIRS monitoring. The statistical analysis was conducted using SPSS software (Version 21.0). There were 11 out of 52 infants categorized as hsPDA. The mean±SD birth weight, mean±SD gestational age, and mean±SD ductus diameter in hsPDA was determined at 1213±293 gram; 30.72±2.01 weeks, and 2.84±0.93 mm, respectively. There was no significant difference between the hsPDA and non hsPDA groups in terms of rcSO2 (75.27±9.14% and 79.03±9.11%; P=0.238), raSO2 (65.60±11.07% and 67.48±10.17%; P=0.594), and rrSO2 (76.41±14.98% and 82.61±10.41%; P=0.218). Based on the obtained results, the existence of hsPDA doesn’t affect the oxygenation in cerebral, abdominal, and renal tissues in preterm babies. Moreover, the decision should be made regarding the optimal time for ductal closure.

Twin reversed arterial perfusion (TRAP) sequence is a rare disorder of monochorionic twins in which the placental anastomoses results in transitioning the blood from the normal fetus to the acardiac twin by a reversed arterial flow. This study aimed to investigate the radiofrequency ablation (RFA) outcome of the umbilical cord occlusion of acardiac twin to reduce TRAP sequence in monochorionic diamniotic pregnancies.

This prospective study investigated 25 cases of monochorionic diamniotic twin pregnancy with one acardiac fetus and selective reduction by RFA in the second trimester of gestational age in a referral hospital affiliated to Tehran University of Medical Sciences, Tehran, Iran, from 2018 to 2019.

The mean±SD of gestational age in RFA and delivery were 20.0±3.8 and 35w±6.0 days, respectively, with a survival rate of 84%. A total of nine neonates were admitted to the neonatal intensive care unit, and four miscarriages were recorded in less than 24 weeks. The RFA procedure was successful in all pregnancies for selective termination of the acardiac twin.

RFA was a safe and reasonable method in a selective-fetal reduction in acardiac twins for monochorionic pregnancies.

Salivary gland anlage tumor (SGAT) is a rare but benign tumor of the nasopharynx that most commonly presents with symptoms of obstruction, including severe respiratory distress. There are multiple reports of SGAT in the literature proposing it as an important differential diagnosis of nasal obstruction in the early weeks of life. However, primary manifestations other than respiratory distress have not been reported with SGAT.

Case report:

 An18-hour-old neonate presented with feeding intolerance and coffee ground vomiting since the 6thhour of birth and was admitted to the neonatal intensive care unit. An orogastric tube was inserted for irrigation, and secretions were persistently bloody after 24 hours. At the 36th hour of birth, mild subcostal retraction developed with a slight increase in the respiratory rate as well as bloody secretions from the nose.  At the 48th hour, subcostal retraction became severe accompanied by tachypnea. All symptoms resolved completely within 2 hours of spontaneous vomiting containing a polypoid mass.

The SGAT should be considered a differential diagnosis of nasopharyngeal obstruction in the early weeks of life.

Primary craniosynostosis is a form of premature fusion of the cranial sutures, which commonly occurs prenatally. The condition appears in both syndromic and nonsyndromic forms.

Case report:

 The cause of most cases of primary craniosynostosis are unknown, with genetic syndromes explaining 10%–20% of cases. The most prevalent syndromes associated with primary craniosynostosis are Crouzon, Apert, and Pfeiffer. Scaphocephaly is the most typical form of craniosynostosis that occurs due to premature closure of the sagittal suture. Frontal plagiocephaly is another form of this condition that is caused by the premature fusion of a sphenofrontal or coronal suture. The suture line palpation at birth usually exhibits a bony ridge. In these case, head CT or skull radiograph may be prescribed. Some genetic types of craniosynostosis are triggered by FGFR1, TWIST, FGFR2, or FGFR3 mutations.

A rare congenital condition, Apert syndrome is associated with craniosynostosis and severe symmetrical syndactyly of the feet and hands. In this case study, the goal has been to present a newborn with all characteristics of a classical Apert syndrome.

Fetal echocardiography is a useful tool for diagnosing fetuses with congenital heart diseases, and it is best to be conducted between 17 and 19 weeks of gestational age. However, fetal echocardiography can be performed at other ages of pregnancy for a variety of reasons. This study describes one fetus with pulmonary valvar stenosis based on the fetal echocardiogram in the uterus.

Case report:

 This study describes one fetus with pulmonary valve stenosis based on the fetal echocardiogram in the uterus. We referred the family to a hospital with neonatal intensive care unit admission. After birth, we followed her serially and confirmed pulmonary valve stenosis, which increased in severity after two months. Subsequently, we performed a percutaneous balloon valvuloplasty.

Our findings showed that some cardiac defects could vary in severity during pregnancy and post-birth. There was clear evidence that pulmonary valvar stenosis was a lesion developed during the fetus's lifetime to tolerate the lesion. Although pulmonary stenosis progressed in the early months after birth, it was easily treated through balloon angioplasty.