Iranian Journal of Neonatology
Volume:12 Issue: 2, Spring 2021

Although a great improvement has been achieved in the outcome of sick neonates with the effectivewidespread introduction of mechanical ventilation in neonatal intensive care units, a significant proportion of highfatality is still detected among such patients. This study was conducted to identify the complications, outcome, andcauses of death among a sample of critically ill Egyptian neonates subjected to mechanical ventilation using pressurecontrolledmode.  The statistical population of this study were prospectively enrolled in the current study and consisted of 240 eligible patients fulfilling the study inclusion criteria. Those with multiple congenital malformations or post-surgical cases were excluded from the study. The data regarding medical record, clinical examination, indication for mechanicalventilation, complications related to mechanical ventilation, and outcome were collected, recorded, and analyzed. The incidence of complications related to mechanical ventilation was obtained at 104 (43.3%), and VAP observedan increase (20%). Furthermore, the complications related to disease patterns were reported to be 56.7% and 22.5% forsepsis and septic shock. It has been revealed that 124 (51.7%) of the studied neonates had favorable outcomes; however,the remaining 116 (48.3%) of the subjects passed away with a significant increase in the incidence of VAP (P=0.013). Itwas reported that smaller gestational age and lower birth weight were the most significant risk factors. In Egypt; as a developing country, the mortality rate among critically ill neonates undergoing mechanicalventilation with pressure-controlled mode was significantly high, approaching 48.3%, with VAP being the mostcommon cause of death.

Zinc is an important micronutrient that is required for optimal fetal growth and development. Zinc deficiency during pregnancy may interfere with intrauterine fetal ossification. Fetal ossification can be measured with specific bone growth markers, such as procollagen type 1-N terminal propeptide (P1NP). This study aimed to investigate the mean maternal serum zinc levels and assess the correlations of maternal serum zinc levels with cord blood P1NP levels and anthropometric measurements of newborns.
This cross-sectional study was conducted at Universitas Sumatera Utara Hospital and other hospitals in Medan, Indonesia, from April to October 2019. The statistical populations were pregnant mothers and their newborns who met the inclusion criteria. The participants were selected using a consecutive sampling technique. Maternal serum zinc levels and cord blood P1NP levels were measured before delivery; moreover, anthropometric measurements were conducted in this study.
A total of 42 subjects were included in this study with a mean maternal serum zinc level of 52.0±9.0 µg/dL. The proportion of pregnant mothers with low serum zinc levels was high (54.8%). According to the results, there was a significant correlation between maternal serum zinc levels and newborn birth weight (r=0.648) and length (r=0.656), as well as head circumference (r=0.578; P=0.001). There was also a significant and positive linear correlation between maternal serum zinc levels and cord blood P1NP levels (r=0.469; P=0.002).
The mean maternal serum zinc levels during pregnancy were below normal. There were positive significant correlations between maternal serum zinc levels and cord blood P1NP levels with anthropometric measurements of newborns.

It is well known that mother’s milk is the best nutrient for the baby. Some formal studies have investigated its effectiveness and supported it as a safe feasible practice. The effects on other variables are vague since the evidence is not strong to observe significant differences in the outcomes, such as necrotizing enterocolitis (NEC), sepsis, length of hospital stay, and mortality. The present study was carried out to assess the effect of oral therapy with colostrum or breast milk on the clinical outcomes using a questionnaire on clinical outcomes.

A total of 48 babies were randomly assigned to receive 0.2 ml of their own mother’s colostrum, breast milk, or sterile water via oropharyngeal route every 4 h, and it was continued till the baby independently could suck via bottle or breast. The babies were followed since admission until discharge by the unit.

According to the obtained results, there was no statistical difference among the preterm babies who received oral immunotherapy with colostrum, breast milk, and sterile water regarding the clinical outcomes, such as NEC, culture-proven late-onset sepsis, intraventricular hemorrhage, retinopathy of prematurity, chronic lung disease, jaundice, and mortality. The oral therapy with colostrum was observed to have a significant influence on age at discharge (P=0.02).

Oral therapy with colostrum is an alternative method of providing mothers’ milk for babies who are kept nil per oral. Oral therapy with colostrum or breast milk leads to earlier weeks of discharge.

Glomerular filtration rate (GFR) is the best indicator to assess renal function; however, it is difficult to perform it, especially in neonates. Serum creatinine is the most commonly used marker of GFR; nevertheless, it has some limitations since it can be affected by factors other than renal function. Cystatin C, another endogenous marker used to estimate GFR, is not affected by non-renal factors. The results of some studies suggest that serum cystatin C levels are more accurate tests of kidney function than serum creatinine levels. This study aimed to estimate GFR with cystatin C-based formulas among neonates and determine the correlations between these methods and the Schwartz formula. The population of this research consisted of 99 neonates whose serum creatinine and cystatin C levels were measured concurrently. Moreover, the glomerular filtration rate was estimated using the Schwartz formula and 14 cystatin C-based formulas separately. Based on the findings, all GFR values based on cystatin C formulas correlated significantly with each other (p <0.05); however, with one exception, none of these values correlated with Schwartz GFR (P>0.05). The only cystatin C formula that yielded values correlating with the Schwartz formula was CysCrEq, which used serum cystatin C and creatinine concomitantly. It can be concluded that since all GFR values based on cystatin C correlated significantly and cystatin Cwasindependent of non-renal factors, cystatin C reflected the real GFR more accurately than serum creatinine. Nonetheless, further studies with gold standard techniques are required to verify the usefulness of cystatin C-based formulas.

Congenital Adrenal Hyperplasia (CAH) is one of the main causes of ambiguous genitalia. The unusual appearance of internal genitalia in CAH patients is similar to many other conditions which are classified in Disorders of Sex Development (DSD). This study aimed to accurately describe diagnostic ultrasonic features of the uterus and ovaries in CAH patients in order to distinguish it from other causes of ambiguous genitalia. This cross-sectional study was performed in Akbar Children Hospital, Mashhad University of Medical Sciences, Mashhad, Iran, from 2017 to 2020. Ultrasound findings of the uterus and ovaries of 22 female infants (2-60 days of age) with CAH due to 21-hydroxylase deficiency and 47 healthy infants with a similar age were recorded and eventually analyzed in this study. All the healthy infants in the control group had a normal prominent cervix, except for two neonates (95%). In the case group, only 9 (41%) infants had a normal prominent cervix, and other 13 newborns had nearly equal sizes of fundus and cervix. There was a significant difference between the two groups in the fundus-to-cervix ratio (P=0.009). The 77% patients had no follicles in both ovaries, while 28% healthy infants in the control group had no follicles, and the rest had unilateral or bilateral multi-follicular ovaries. After two months following treatment, bilateral multi-follicular ovaries were observed in all patients. The sign of non-follicular ovaries (pseudo-testicular appearance) was significantly more prevalent in the case group (P=0.004). Furthermore, half of infants showed normal pelvic lymph node that mimic a testicular-like appearance due to its uniform hyper-echoic texture. The testicular-like appearance of normal pelvic lymph nodes and non-follicular ovaries in a female infant with CAH. Attention to these usual findings can prevent misdiagnoses of cryptorchidism and time loss to perform other laboratory tests and karyotyping.

Acute kidney injury (AKI) is a clinical syndrome in which the sudden loss of kidney function leads to kidney failure to maintain fluid hemostasis and electrolytes. Considering the increased hospitalization of patients in the neonatal intensive care unit (NICU), the prevalence of AKI due to common diseases, surgical procedures, various drugs, as well as the importance of long-term complications, this study aimed to determine the prevalence and related risk factors for the development of AKI in neonates admitted to NICU. This descriptive cross-sectional study was conducted on 173 newborns admitted to Boo-Ali-Sina Hospital in Sari, Iran, during 2016-2018. Patients’ demographic characteristics, clinical findings, laboratory results, clinical outcomes, and risk-related disease factors were recorded. Data were analyzed using SPSS software (version 16). The prevalence rate of AKI in infants admitted to Neonatal intensive care unit  was 26.6%, consisting of 87% (n=40) prerenal,  8.7% (n=4) renal, and 2.2% (n=1) postrenal AKI cases. Furthermore, 6.4%, 9.2%, and 11% of the patients had grade 1, grade 2, and grade 3 AKI, based on RIFLE criteria. It should be mentioned that RDS, TTN, and seizure were the most common causes of hospitalization in the NICU. The most common laboratory disorders were acidosis, hyponatremia, anemia, and leukocytosis. Furthermore, anemia (89.1% vs. 19.7 %), hypernatremia (8.7% vs. 2.4%), and hyperkalemia (26% vs. 8% ) were significantly greater in AKI than in the non-AKI group. AKI was common in NICU, and accounted for about one-fourth of the admitted patients. The most common type of AKI was prerenal. The patients were equally distributed in all three stages. Eventually, anemia, hypernatremia, and hyperkalemia can be considered risk factors for AKI.

The value of antenatal corticosteroid regimen in lessening respiratory distress risk in preterm neonates has been well known, and accordingly, antenatal corticosteroid therapy was recommended for any pregnant woman likely to deliver between 24 and 34 weeks of gestation. Therefore, this study aimed to assess the association between the administration of antenatal corticosteroids within the ideal interval of one week before birth and the outcomes of preterm neonates.
This prospective cohort study included 80 preterm neonates admitted to the neonatal intensive care unit with gestational age from 32 to 37 complete weeks at Suez Canal University Hospitals, Ismailia, Egypt. The newborns were then divided into groups A (did not receive antenatal corticosteroids; n=40) and B (received antenatal corticosteroids; n=40).
Severe respiratory distress syndrome was significantly less frequent in group B  (P<0.05) with lower levels of need for oxygen supplementation (P<0.05).
Neonates who received antenatal corticosteroids developed less severe respiratory distress, compared to neonates who did not receive this medication. The results favored the use of antenatal corticosteroids to prevent respiratory distress when administrated within the ideal interval of one week before birth.

Examination for retinopathy of prematurity (ROP) is one of the procedures that can be stressful for neonates admitted to a neonatal intensive care unit. This study compared breast milk and sucrose in pain relief and coping with the stress of ROP examination using the Astrid Lindgren and Lund Children’s Hospital Pain and Stress Assessment Scale for Preterm and Sick Newborn Infants (ALPS-Neo).
The present study was carried out on a total of 63 preterm infants (including breast milk group [n=21], sucrose group [n=21], and distilled water group [n=21]). The neonates were given 0.5 ml/kg of breast milk, sucrose, or distilled water 2 min before the examination. The ROP eye examinations were video recorded from 5 min before to 15 min after the examination, and infants’ pain and stress levels were assessed using the ALPS-Neo by two blinded evaluators 5 min before, during, and 5, 10, and 15 min after the examination.
No statistically significant differences were observed during the examinations in the mean scores of the ALPS-Neo among the three groups (P>0.05). However, there were statistically significant differences among the three groups after the examinations (P<0.05) and in the mean duration of stress adaptation (P<0.05). The duration of stress adaptation in the breast milk group was 11.4 min on average which was lower than that reported for the other groups.
ConclusiConcluConclusion 
Breast milk was more effective in the reduction of pain and stress after ROP examinations, compared to sucrose or distilled water.

Exclusive breastfeeding is defined as feeding only breast milk without any other liquids or solids, except for medicine. For mothers with positive human immunodeficiency virus (HIV), adherence to exclusive breastfeeding added with antiretroviral therapy extremely reduces the risk of transmitting the virus to their exposed neonates. Therefore, the World Health Organization has recommended exclusive breastfeeding for exposed infants within the first 6 months of life. This study was performed to identify factors associated with adherence to exclusive breastfeeding among HIV-positive mothers. The required data in this facility based cross-sectional study was collected using a structured questionnaire through a face-to-face interview. Descriptive statistics were used to show the frequency distributions of factors associated with the dependent variable. Logistic regression was applied to identify factors associated with the outcome variable. The odds ratio was used for the measure of association, and statistical tests with p-values of less than 0.05 were considered significant. The proportion of adherence to exclusive breastfeeding among HIV-positive mothers was found to be 80.8% (95% CI: 77.2-84.6). It was revealed that having good knowledge (adjusted odds ratio [AOR]=7.363, CI=3.37-12.98), receiving exclusive breastfeeding counseling during the postnatal period (AOR=4.88, CI=2.68-8.916), timely initiation of exclusive breastfeeding (AOR=4.429, CI=2.378-8.25), and making 4 or more antenatal care visits (AOR=2.557, CI=1.413-4.629) were identified to be the significant factors. The proportion of adherence to exclusive breastfeeding among HIV-positive mothers was found to be low. Interventions that seek to increase exclusive breastfeeding should focus on ensuring four antepartum care visits and postpartum counseling.

Several studies have reported that two promoter variants (c.-3279T>G and c.-3156G>A) in UDP-glucuronosyltransferase (UGT1A1) gene may contribute to neonatal hyperbilirubinemia. However, these variants have not been investigated in Iranian neonates. This cross-sectional study aimed to determine if the UGT1A1 promoter variants are significant risk factors associated with neonatal hyperbilirubinemia.

A total of 178 unrelated neonates, including newborns with neonatal jaundice (n=95) and healthy controls (n=83), were included in this study. Each individual was genotyped by the PCR-RFLP and COP-PCR at nucleotides -3279 and -3156, respectively, using fresh blood DNA. Logistic regression analyses were performed to assess the association of UGT1A1 promoter variants with the presence of significant hyperbilirubinemia. Anthropometric indices and clinical variables were also compared between the different genotype groups.

Allele and genotype analysis of the c.-3279T>G and c.-3156G>A variants showed no significant association with the risk of neonatal hyperbilirubinemia neither in the crude nor after adjustment for gestational age, gender, and birth weight in different genetic models (P>0.05). However, in haplotype-association analysis, only one haplotype (A-T) was found to be associated with the risk of neonatal hyperbilirubinemia (OR=0.19, 95% CI; [0.18–0.20], P=0.001).

This study failed to demonstrate that c.-3279T>G and c.-3156G>A variants alone might contribute to the risk of neonatal hyperbilirubinemia in Iranian neonates. However, the A-T haplotype may play a significant role in increasing the risk of hyperbilirubinemia.

Extremely premature infants are at greater risks of cognitive, behavioral, growth, and developmental problems, compared to the term infants. In addition to physical problems, these infants also incur a lot of emotional costs, stress, and financial burden to the family. This study aimed to explore ethical challenges and factors affecting decisions about initiation, sustain, and termination of the life of extremely premature infants that neonatologists face every day in the clinics.
The present qualitative study was conducted based on a grounded theory. The participants were 21 practitioners who were interviewed after giving consent and being briefed about the study. All interviews were recorded, transcribed, and then analyzed in this study. The data were then analyzed using Strauss-Corbin (1998) method in three phases of open, axial, and selective coding.
During analysis, 1420 initial (open) codes, 19 subcategories, and two specific categories were obtained to explain the ethical challenges of decision-making on the sustaining or terminating the life of extremely premature infants. These categories included 1) Independent decision-making of physicians, followed by two subcategories of "professional decision-making based on knowledge and clinical experience" and "uncertainty about the consequences of consulting with parents", and 2) Improper conditions and facilities, followed by three subcategories of "lack of local scientific resources on medical ethics", "inefficient neonatal intensive care units", and "lack of efficient rules and guidelines". According to the obtained results, factors leading to ethical challenges included the lack of ethical and legal guidelines tailored to clinical conditions, lack of local scientific documentation in accordance with clinical conditions and health facilities available in the Neonatal Intensive Care Unit (NICU), conflicts between the current law on life preservation and moral guidelines, and lack of facilities, manpower, and equipment in the NICU.
A physician’s decision is based on personal scientific and clinical experiences according to the conditions of the wards.

Some of the neonatal intensive care units (NICUs) partially lack the standard protocols for controlling noise and light. The healthy physical environment of NICUs is crucial for the continued normal development of preterm neonates. The present study aimed to assess the physiological changes (including heart rate, respiratory rate, blood pressure, temperature, and oxygen saturation) induced by noise and ordinary light often existing in NICUs in a sample of preterm neonates admitted to the private ward of NIUCU due to their low-birth weights.
The present study included 100 preterm neonates, 50 neonates were exposed to noise which is often induced in the open ward of NICU, and the other 50 newborns were exposed to cyclical light.
During noise exposure, neonates in the private ward displayed a significant increase in heart rate, respiratory rate, as well as systolic and diastolic blood pressure. Moreover, they showed a marked decrease in oxygen saturation in the first and second days in the NICU. Furthermore, the neonates exposed to dim light demonstrated a significant decrease in heart rate, respiratory rate, systolic and diastolic blood pressure, as well as a significant increase in oxygen saturation, compared to those exposed to ordinary light on the first and second days. Nonetheless, body temperature did not show any significant change with noise or light exposure either on the first day or the second one.
As evidenced by the obtained results, exposure to excessive light and noise was associated with significant changes in preterm neonates' vital signs. Moreover, the findings highlighted the inadequacy of the current conditions in a sample of Egyptian NICUs for ideal neonatal care. In order to create a favorable environment to help better growth and prevent prematurity complications, it is recommended to devote more assiduous attention to the care conditions of neonates in NICUs in Egypt.

There is a dearth of studies in Iran on the efficacy of probiotics in reducing necrotizing enterocolitis (NEC), yielding contradictory results. Therefore, the present study aimed to assess the effect of probiotics on milk tolerance and the prevention of NEC in preterm neonates.
This randomized triple-blind clinical trial study was conducted on all preterm neonates between 30 and 36 weeks gestation and birth weight >1250 g hospitalized in the neonatal intensive care unit (NICU) at Bentolhoda Hospital in Bojnurd, Iran. Thereafter, 76 eligible neonates were randomly assigned to two groups of oral placebo (n=38) and BB care probiotic (n=38). Subsequently, the following information was extracted based on the hospital checklist: early or late NEC (after 7 days of birth), types of NEC (grade I, II, and III), length of hospitalization, time to reach complete oral nutrition, weight at discharge, and milk tolerance.
In the current study, 52.6% and 47.4% of newborns in control and intervention groups were male, and no significant difference was observed between the two groups (P= 0.646). The incidence of NEC was significantly reduced among the intervention group. The feeding onset in the placebo group was significantly later, as compared to that in the intervention group. A significant difference was detected between the two groups in the length of hospital stay and weight gain during hospitalization.
As evidenced by the obtained results, the administration of probiotics in preterm neonates might prevent NEC. Moreover, it can shorten the onset time of feeding and hospitalization duration.

Complications during pregnancy is one of the variables increasing the maternal death rate.  To reduce or prevent maternal and perinatal morbidity and mortality, antenatal care (ANC) visits were implemented. An antenatal care visit is pregnancy monitoring which is intended to inspect the health of the mother in general, including complications of pregnancy. It also aims to prepare a well-born neonate and a healthy mother; therefore, adherence to ANC is important. This study was conducted to determine the maternal determinant variables related to adherence to ANC.
This cross-sectional study was carried out with an analytical approach. The statistical population of the research consisted of 30 pregnant women who were in the third trimester. The research design indicated the correlation between variables. A univariate data was used for the analysis of variables, namely maternal age, parity, and pregnancy diagnosis. While the bivariate analysis was performed using Fisher’s exact test. The study was conducted in Slawi Primary Health Centre, Indonesia.
The results showed that 86.67% of pregnant women conducted ANC visits regularly. According to maternal determinants, it was revealed that ANC had a correlation with age and parity (P=0.02 and P=0.04, respectively). However, there was no correlation between pregnancy diagnoses and ANC (P=0.08).
There were correlations of age and parity with ANC; nevertheless, no correlation was found between pregnancy diagnosis and ANC.

Personal protective equipment (PPE) is one of the protective equipment that health workers can use to protect themselves against coronavirus disease 2019(COVID-19); however, it is accompanied by some problems for medical staff. Since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not transmitted through healthy skin, the hypothesis was examined as to whether the cotton gown could be used instead of PPE.

The medical staff of the Neonatal Care Unit took care of 51 patients with 1180 shifts. During the first and a half months, the medical personnel used a special PPE package for providing care of  patients, which included an air-impermeable plastic gown with a head-to-toe cover, an N95 mask, gloves, and a face shield. However, from the beginning of the epidemic, doctors used cotton surgical gowns instead of the ones in the package. Following that, the nursing team gradually replaced the air-impermeable plastic gowns with cotton surgical gowns, and finally, all the staff used the cotton gowns. 

After three months, all medical staff was evaluated for clinical signs of COVID-19, such as fever, cough, nausea, and headache. During these three months, no symptoms or absence due to illness were observed in the staff. It should be mentioned that the antibody titer was not evaluated at the end of the study.

A retrospective review of the staff showed that the cotton surgical gown protected the staff against COVID-19. Accordingly, the cotton surgical gown can be used in medical centers to replace PPE sets containing an air-impermeable plastic gown with a head-to-toe cover. The result of this study can improve some of the problems of the medical staff.

Necrotizing enterocolitis is the leading cause of intestinal perforation and pneumoperitoneum in neonates. In addition, neonatal pneumoperitoneum includes several conditions requiring surgery, such as gastric and duodenal perforation, intestinal atresia, volvulus, meconium ileus, and Hirschsprung’s disease. A type of pneumoperitoneum in which intra-abdominal free air is detected through direct X-ray; however, no cause is found clinically and radiologically during the surgery is named “benign pneumoperitoneum”.

Case report: 

This case report presents a 5-day-old male newborn who is presented with complaints of abdominal color change and vomiting and is diagnosed with Idiopathic Benign Pneumoperitoneum (IBP) during the operation. Neonatal pneumoperitoneum usually occurs as a result of perforation and requires emergency surgery. Rare cases of IBP should also be kept in mind. Unnecessary surgery can be prevented by establishing a differential diagnosis with clinical, laboratory, and imaging methods.  

This case demonstrated that laparotomy is not a true routine in neonates with IBP if a timely diagnosis is established.

Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome is a rare autosomal recessive disorder mostly affecting the liver, kidney, skin, as well as central nervous and musculoskeletal systems. This multisystemic disease results from mutations in the vacuolar protein sorting 33B (VPS33B) or VPS33B- interacting protein, and apical-basolateral polarity regulator (VIPAR) genes. This is a lethal disorder from which few patients can survive at the first year of their life. This syndrome exhibits a wide range of phenotypes, such as ichthyosis, hypothyroidism, agenesis of the corpus callosum, and congenital cardiovascular anomalies.

Case report: 

Here, we present the case of a 32-day-old male neonate with respiratory distress admitted to Children's Medical Center Hospital in Tehran, Iran, in August 2019. He had ichthyosis, cholestasis with arthrogryposis as bilateral clubfeet, developmental dysplasia of the hip, and flexion contractures in upper limbs. During hospitalization, he received Shohl’s solution for metabolic acidosis, intravenous antibiotics, fat-soluble vitamins, and levothyroxine. Other  presentations in our case included  ichthyosis, failure to thrive, congenital heart disease, and hypothyroidism.

Timely diagnosis, supportive care and genetic counseling should be provided for better outcome.   Keywords:

Coronavirus disease 2019 (COVID-19) in neonates is an emerging challenge to pediatricians. The majority of the neonates with COVID-19 reported so far are suspected to be infected due to postnatal transmission. Vertical transmission has already been reported in two case-cohort studies.

Case report: 

A 32-week preemie with a birth weight of 2 kg was admitted to the neonatal intensive care unit due to respiratory distress. The case was born to a primigravida mother with a history of preterm premature rupture of membranes. The neonate developed arterial thrombosis on the first day of life and subsequent gangrene of the right foot and tested positive for serology and reverse transcription polymerase chain reaction (RT-PCR) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with elevated inflammatory markers (C-reactive protein, D-dimer, serum ferritin, lactate dehydrogenase). Since the mother was asymptomatic, she was not tested for SARS-CoV-2 antenatally. After the confirmation in the neonate, the mother was also tested for SARS-CoV-2 and tested positive by RT-PCR as well as serology.

This rare presentation calls for further research in transmission patterns either antenatally or vertical transmission. This report emphasized the possibility of vertical transmission of COVID-19 in neonates from asymptomatic mothers, with significant, early-onset neonatal infection in the form of thrombosis.