Congenital Cytomegalovirus Infection Screening in Newborns From Saliva Samples by Real-Time Polymerase Chain Reaction Analysis.

OBJECTIVE: Congenital cytomegalovirus infection is the most common congenital infection. Although screening of congenital cytomegalovirus infection with polymerase chain reaction studies in blood, urine, and saliva samples has been developed in recent years, it is not yet in routine use in any country. MATERIALS AND METHODS: In our study, cytomegalovirus deoxyribonucleic acid analysis was per- formed by real-time polymerase chain reaction method in saliva samples taken before the first feeding during the first day following birth in neonates born in a university hospital between January 2021 and January 2022. To support the diagnosis, additionally, cytomegalovirus deoxy- ribonucleic acid positivity in urine and blood samples was investigated in newborns with cyto- megalovirus deoxyribonucleic acid positivity in saliva. RESULTS: Cytomegalovirus deoxyribonucleic acid was investigated in saliva samples of 545 neonates by real-time polymerase chain reaction method in 1-year period and positiv- ity was found in 6 neonates. Since cytomegalovirus deoxyribonucleic acid was found nega- tive by the real-time polymerase chain reaction method in the urine and blood samples of 5 of these neonates, the positivity in the saliva sample was interpreted as false positivity. In 1 case, cytomegalovirus deoxyribonucleic acid positivity was detected in urine and blood samples 5 weeks later. As a result, definite congenital cytomegalovirus infection could not be diagnosed in 545 cases, while possible congenital cytomegalovirus infection was diag- nosed in 1 case. CONCLUSION: It has been concluded that the frequency of congenital cytomegalovirus infection is low in our study group and studying saliva samples showed high false-positive rates. It is seen that saliva is not a suitable sample for detecting cytomegalovirus deoxyribonucleic acid by real-time polymerase chain reaction method.

Effect of different dose regimens of everolimus in a series of neonates with giant cardiac rhabdomyomas.

Everolimus is a mTOR inhibitor that has been increasingly used in high-risk cardiac rhabdomyomas in recent years. There are questions regarding the optimal dose and duration of therapy with everolimus for cardiac rhabdomyomas. The purpose of this study was to examine retrospectively the dosage-efficacy relationship in seven babies diagnosed with rhabdomyoma treated with different everolimus dose regimens retrospectively. Cardiac rhabdomyoma diagnosis was made in six of seven babies during the prenatal period. Indication of everolimus was an obstruction in six patients and supraventricular tachycardia which is resistant to antiarrhythmic drugs in the remaining one patient. The median age was 8 days (range; 2-105 days) at the time of starting everolimus. It was administered at a dose of 0.25 mg twice a day for two days a week in four patients; 0.1 mg/day in two and 0.4 mg/day in one patient. Serum everolimus level was kept between 5 and 15 ng/ml. All seven cases showed significant regression of cardiac rhabdomyoma within four weeks, and supraventricular tachycardia was controlled in two weeks after everolimus administration.This study demonstrates that everolimus was effective in accelerating regression of the cardiac rhabdomyoma. Dose with 2 × 0,25 mg/day, 2 days a week, seems appropriate. However, lower doses such as 0.1 mg/day are also effective. But dose adjustment should be made according to serum level monitoring.

Two cases of MEGDHEL syndrome diagnosed with hyperammonemia.

OBJECTIVES: MEGDHEL [3-methylglutaconic aciduria (MEG), deafness (D), hepatopathy (H), encephalopathy (E), and Leigh-like disease (L)] syndrome is an autosomal recessive disorder caused by mutations in the serine active site-containing protein 1 (SERAC1) gene. MEGDHEL syndrome is clinically characterized by sensorineural hearing loss, encephalopathy, hepatopathy, 3-methylglutaconic aciduria, and Leigh-like lesions on cranial magnetic resonance imaging. During the neonatal period, it has been reported to present with hypoglycemia, hyperammonemia, impaired liver functions, cholestasis, metabolic acidosis, and sepsis-like clinical findings. However, clinical findings in the neonatal period were reported as a result of the retrospective evaluation of patients diagnosed at an older age. Herein we reported two cases diagnosed as MEGDHEL syndrome during neonatal period in two different clinics with sepsis-like findings, impaired liver functions, and ammonia levels high enough to require dialysis. CASE PRESENTATION: One of the cases was born 37 weeks of gestation with a birth weight of 2,060 g and initially presented with respiratory distress and feeding difficulties. The other case admitted to the neonatal intensive care unit had fed problems together with respiratory distress and circulatory failure within the first 24 h after initiation of parenteral nutrition. CONCLUSIONS: MEGDHEL syndrome should be suspected in patients with sepsis-like clinical features and hyperammonemia.

Effects of Fish Oil (SMOFlipid®) and Olive Oil Lipid (ClinOleic®) on Neonatal Morbidities in Preterm Infants.

Objective: Total parenteral nutrition (TPN) is very important for providing optimal nutrition during the critical developmental period of preterm newborns. Thus, there is a need to optimize TPN solutions to reduce morbidities. This study aimed to examine the effects of olive oil (ClinOleic®) and fish oil (SMOFlipid®) therapies on the frequencies of neonatal morbidities. Methods: Premature newborns hospitalized in the neonatal intensive care unit and receiving TPN for at least 14 days were included in the study. Newborns who were hospitalized and received olive oil-based lipid (ClinOleic®) were included in the olive oil group, and those who received omega-3 containing multi-lipid (SMOFlipid®) were included in the SMOFlipid group. Results: This study enrolled a total of 222 very-low-birth-weight premature newborns. The breastfeeding rate in the olive oil group was significantly lower than that in the SMOFlipid group (p<0.05). The rate of necrotizing entercolitis (NEC) in the olive oil group was significantly higher than that in the SMOFlipid group (p<0.05). The rate of bronchopulmonary dysplasia (BPD) in the SMOFlipid group was lower than that in the olive oil group (p<0.05). Conclusions: The rates of BPD and NEC were lower in the fish oil group. In this situation, fish oil therapy may provide protection against the development of BPD and NEC. Prospective studies are needed to determine whether this is caused by lipid therapy or an effect of breast milk.

Vitamin D Deficiency Prevalence in Late Neonatal Hypocalcemia: A Multicenter Study

Objective: Late neonatal hypocalcemia (LNH) is a common metabolic problem associated with hypoparathyroidism, high phosphate intake and vitamin D deficiency, often presenting with seizures. In this cross-sectional study, we aimed to evaluate the role of vitamin D deficiency in LNH in Turkey and to describe the characteristics of affected newborns. Methods: Conducted with a cross-sectional design and with the participation of 61 neonatal centers from December 2015 to December 2016, the study included term neonates with LNH (n=96) and their mothers (n=93). Data were registered on the FAVOR Web Registry System. Serum samples of newborns and mothers were analyzed for calcium, phosphate, magnesium, albumin, alkaline phosphatase, intact parathyroid hormone (iPTH) and 25 hydroxyvitamin D [25(OH)D] levels. Results: The median (range) onset time of hypocalcemia was 5.0 (4.0-8.0) days of age, with a male preponderance (60.4%). The median (range) serum 25(OH)D levels of the neonates and their mothers were 6.3 (4.1-9.05) and 5.2 (4.7-8.8) ng/mL, respectively. The prevalence of vitamin D deficiency (<12 ng/mL) was high in both the neonates (86.5%) and mothers (93%). Serum 25(OH)D levels of the infants and mothers showed a strong correlation (p<0.001). While the majority (93.7%) of the neonates had normal/high phosphorus levels, iPTH levels were low or inappropriately normal in 54.2% of the patients. Conclusion: Vitamin D deficiency prevalence was found to be high in LNH. Efforts to provide vitamin D supplementation during pregnancy should be encouraged. Evaluation of vitamin D status should be included in the workup of LNH.

Can immature platelet fraction be an early predictor for congenital pneumonia?

AIM: Timely diagnosis and treatment of congenital pneumonia are crucial. A new hematologic parameter, immature platelet fraction, has been used to gather clinical information on the prognosis of thrombocytopenia, as well as to measure inflammatory activity in adult patients. This study aimed to compare immature platelet fraction and sepsis biomarkers in late-preterm infants diagnosed as having congenital pneumonia and to evaluate its predictive value for congenital pneumonia. MATERIAL AND METHODS: Late-preterms were categorized based on infectious vs. non-infectious etiology of respiratory distress. Two sets of blood samples for markers were taken at 12-24 (sample-1) and 48-72 hours (sample-2) after birth. Immature platelet fraction was measured using a Sysmex XN-3000 analyzer. RESULTS: From a total of 30 non-thrombocytopenic late-preterms, 16 were included in the congenital pneumonia group and 14 comprised the transient tachypnea group. The groups were comparable in terms of gestational age, birth weight, and cesarean section rate. The proportion of prolonged membrane rupture was significantly higher in the congenital pneumonia group. Values of immature platelet fraction-1, immature platelet fraction-2, and procalcitonin-2 were significantly higher in the congenital pneumonia group than in the transient tachypnea group. No significant differences were found between the groups in other biomarkers. It was determined that an immature platelet fraction-1 cut-off value of 2.9% could predict congenital pneumonia with a sensitivity of 65%, a specificity of 71.4%, a positive predictive value of 70.5%, and negative predictive value of 63.7% (area under the curve=0.724; p=0.028). CONCLUSION: Immature platelet fraction may have an early predictive role in the diagnosis of congenital pneumonia.

Outcome of posterior urethral valve in 64 children: a single center's 22-year experience.

BACKGROUND: Posterior urethral valve (PUV) is the most serious form of congenital anomalies of kidney and urinary tract (CAKUT) in boys with significant risk of progression to chronic kidney disease (CKD). We present our long-term results in children with PUV. METHODS: Retrospective chart review of 113 children with PUV followed within the years of 1996-2018 was performed. Clinical, laboratory and epidemiologic parameters were analyzed for their impact on renal outcome. RESULTS: The median age of diagnosis was 1.00 month (1.00-132.00) and the median follow-up period was 70 months (60.00-216.00). Antenatal diagnosis was present in 33 patients (51.5%) mainly with bilateral hydronephrosis and oligohydramnios. The most common postnatal presentation was recurrent urinary tract infection (UTI) in 14 cases (21.9%) and incontinence in three cases (4.7%). Vesicoureteral-reflux (VUR) was present in 31 cases (48.4%). All patients had surgery and urinary diversion was needed in 18 (28.2%). Varying stages of chronic kidney disease (CKD) developed in 23 cases (35.9%) and rise in serum creatinine was especially prominent after the 4th year of follow-up. Of 23 CKD patients, seven (10.9%) were in ESRD and on dialysis. Mortality occurred in one (1.5%) patient. Hypertension, proteinuria and high initial serum creatinine (>1.28 mg/dL) were statistically significant risk factors for CKD, as expected. Surprisingly VUR and UTI did not show such a significant impact on CKD development. Antenatal detection was with significantly less risk for CKD. CONCLUSIONS: Our results confirm that PUV has a considerable risk for CKD development. Antenatal diagnosis, management of proteinuria and hypertension may modify this progression. But already injured kidneys still have a potential risk. The need for further research to evaluate the impact of any intervention on long term renal outcome is obvious.

Effects of passive smoking on lung function tests in preschool children born late-preterm: a preventable health priority.

OBJECTIVE: Late-preterm delivery is known to be associated with potential adverse effects on lung development. Passive smoking may result in alterations of pulmonary function in infants born late-preterm. Impulse oscillometry (IOS) is a noninvasive, rapid, and practicable technique that can assess lung function. This study aimed to evaluate the effect of passive smoking on lung function tests in preschool children born late-preterm using IOS. METHODS: The study population consisted of a total of 139 children between 3 and 7 years of age born late-preterm who were being followed-up at our outpatient unit at the time of study period. Late-preterms were subcategorized according to presence or absence of exposure to passive smoking (PS). Those with and without exposure to passive smoking were referred to as PS group (56.1%, n = 78) and non-PS group (43.9%, n = 61), respectively. Resistance (R5-R20), reactance (X5-X20), and resonant frequency were measured by impulse oscillometry (IOS) at 5-20 Hz. RESULTS: Median R5-R20 and Z5 were significantly higher and median X10 was significantly lower in PS group compared to non-PS group (p < .05). CONCLUSIONS: This study demonstrated that passive smoking significantly increases peripheral airway resistance and seems to adversely affect lung function in children born late-preterm.

Impulse oscillometry reference values and correlation with predictors in Turkish preschool children.

Er I, Günlemez A, Baydemir C, Kiliçbay F, Ersu R, Uyan ZS. Impulse oscillometry reference values and correlation with predictors in Turkish preschool children. Turk J Pediatr 2019; 61: 560-567. Impulse oscillometry (IOS) is a noninvasive, rapid technique requiring passive cooperation that allows for evaluation of lung function through the measurement of airway resistance and reactance. There are no available reference values for Turkish children. This study is aimed to determine the reference values of IOS parameters and to study their correlation with height, weight, body mass index, and age as predictors in healthy Turkish preschool children. Healthy children between 3-7 years of age who were selected according to ERS/ATS criteria and followed at Kocaeli University outpatient clinic performed IOS. The correlation between the anthropometric predictor variables and resistance and reactance at 5-20 hertz (R5-R20 and X5-X20), the respiratory impedance at 5 hertz (Z5), resistance area (AX) and resonance frequency (Fres) were assessed by regression analysis and stepwise method. 151 children (93 female) with the mean age of 67.9±16.2 months participated in the study. Multilinear regression analysis for IOS values of all children revealed that resistance was significantly correlated with height and reactance was significantly correlated with age (p < 0.05). For girls, height had a negative effect on R5-20, Z5, AX values, while age had a positive effect on X5-20 and a negative effect on Fres (p < 0.05). For boys, weight had a negative effect on R5- 20, Z5 values, while age had a positive effect on X15-20 and a negative effect on AX, Fres (p < 0,05). This study provided reference values of IOS in healthy Turkish children that would be a useful guide for diagnosing and following respiratory diseases in preschool children.

Evaluation of pulmonary functions in preschool children born late-preterm.

AIM: The aim of this study was to evaluate the pulmonary functions of preschool children born late-preterm. MATERIAL AND METHODS: Children aged between 3-7 years who were born at 340/7-366/7 weeks' gestation represented the target sample. Patients with a diagnosis of congenital cardiac, pulmonary and/or muscle diseases were excluded. Respiratory symptoms were evaluated using the modified asthma predictive index and International Study of Asthma and Allergies in Childhood criteria for children aged under and over 6 years, respectively. Skin prick tests were performed. Age-matched healthy controls were chosen according to the criteria proposed by the American Thoracic Society. Lung functions were evaluated using impulse oscillometry study in both groups. Data were recorded in the SPSS program. RESULTS: A total of 139 late-preterms and 75 healthy controls participated in the study. The mean gestational week of the late-preterms was 35.3±0.9 weeks. The main admission diagnosis to neonatal intensive care unit was respiratory distress. In the postdischarge period, 54.1% were hospitalized for pulmonary infections at least once, and 57.8% were passive smoking currently. Aeroallergen sensitivity was detected as 25.8% in the late-preterm group; 34.5% and 15.1% were diagnosed as having asthma and non-asthmatic atopy, respectively. Impulse oscillometry study parameters of R5, R10, and Z5 were higher and X10 and X15 were lower in late-preterms than in controls (p<0.05). Late-preterms with and without respiratory distress in the postnatal period revealed no statistical differences for any parameters. CONCLUSIONS: Our findings suggest that presence of increased peripheral airway resistance in late-preterms as compared to term-born controls.

Neonatal sepsis and simple minor neurological dysfunction.

BACKGROUND: This study examined potential risk factors for and consequences of simple minor neurological dysfunction (SMND), in a group of very low-birthweight newborns followed until preschool age. METHODS: This was a prospective longitudinal study. Children with birthweight <1500 g were assessed at 4-6 years of age. Twenty-eight children with normal neurological examination and 35 children with SMND were included in the final analysis. Risk factors for the development of SMND and its association with certain neuropsychiatric conditions were studied. RESULTS: Based on neonatal data, in children with SMND, Apgar score at 1 min (6.13 ± 2.37 vs 7.66 ± 1.04, P = 0.008) and at 5 min (8.63 ± 1.29 vs 9.45 ± 0.65, P = 0.019) was lower, duration of hospital stay was longer (45.8 ± 21.8 vs 35.1 ± 18.2 days, P = 0.037), and the frequency of sepsis was higher (73.5 vs 25%, P < 0.001). Sepsis was found to be an independent risk factor for SMND (OR, 7.6; 95% CI: 2.2-26.0; P = 0.001). The children with SMND had lower intelligence quotient and higher prevalence of hyperactivity and refraction error. CONCLUSION: Postnatal sepsis was the single most important risk factor for the development of SMND, and these children with SMND are at great risk for certain neuropsychiatric conditions. Preventive strategies, particularly for sepsis in the neonatal period, and early diagnosis and rehabilitation of future neuropsychiatric disorders are needed for better management of these cases.

Evaluation of lung function on impulse oscillometry in preschool children born late preterm.

BACKGROUND: There is a paucity of data on lung physiology in late-preterm children, who may be exposed to a risk of decline in lung function during childhood. In this study, we evaluated lung function in preschool children born late preterm using impulse oscillometry (IOS), and compared the results with those obtained in healthy term-born children. METHODS: Children between 3 and 7 years of age who were born late preterm and who were being followed up at the outpatient clinic were included as the late-preterm group. Age-matched healthy term-born children served as controls. A total of 90 late-preterm and 75 healthy children were included in the study. At 5-20 Hz, resistance (R5-R20), reactance (X5-X20), impedans (Z5) and resonant frequency were measured on IOS. RESULTS: Mean IOS R5 and R10 were significantly higher in the late-preterm group than in the control group (P < 0.05). Mean R5, R10 and Z5 were statistically higher in late-preterm children who had been hospitalized for pulmonary infection compared with the control group (P < 0.05). Mean R5, R10, R15, R20 and Z5 were significantly higher, and mean X10 and X15 significantly lower in late-preterm children with passive smoking compared with late-preterm children without passive smoking and controls (P < 0.05). CONCLUSION: Children born late preterm had signs of peripheral airway obstruction on IOS-based comparison with healthy term-born controls. Besides the inherent disadvantages of premature birth, hospitalization for pulmonary infection and passive smoking also seemed to adversely affect lung function in children born late preterm.

The effect of IVF pregnancies on mortality and morbidity in tertiary unit.

BACKGROUND: There are several studies that have shown an increased risk of premature birth and developmental abnormalities with in vitro fertilization (IVF); however, the data on preterm mortality and morbidity are limited. AIM: Our aim is to investigate whether IVF had an effect on the mortality and morbidity in neonates admitted to the neonatal intensive care unit. METHODS: A total of 940 term and preterm babies who were admitted to the intensive care unit over a period of 2 years were enrolled. Of these, 121 babies were born after IVF and 810 were born after a natural conception and 9 were born after ovulation induction. Of these, 112 preterm babies were born after IVF and 405 preterm babies were born after a natural conception. RESULTS: In the IVF group, the gestational age and birth weight were significantly lower than in the non-IVF group. Additionally, in the IVF group, multiple births were significantly higher than in the non-IVF group. IVF pregnancies increase preterm delivery but did not increase preterm mortality, and preterm morbidity did not differ among groups, except for intraventricular hemorrhage (IVH). Gestational age was shown to be the primary risk factor for IVH using a logistic regression analysis. Also when newborns at gestational age <32 weeks were compared using regression analysis, gestational age was the major risk factor for IVH. CONCLUSION: IVF appears to be associated with premature delivery and the known risks associated with prematurity.

Positioning of infants in the neonatal intensive care unit for lumbar puncture as determined by bedside ultrasonography.

Realising the paucity of data in the standardisation of the optimal position for lumbar puncture (LP) in hospitalised neonates, we have designed an observational study to measure the interspinous distance in infants in a university hospital setting. The infants were placed in two lateral recumbent and two upright positions (lateral recumbent without flexing the hips, lateral recumbent with maximal hip flexion, sitting without flexing the hips and sitting with maximal hip flexion) with concomitant heart rate (HR), transcutaneous oxygen saturation (OS) and interspinous distance (with ultrasonography) measurements. Having the patient sit with maximal hip flexion provided the largest interspinous space for the grand majority of the infants. Sitting positions with/without flexion have resulted in significant increases in HR with respect to lateral recumbent position without flexion. Although statistically significant drops in OSs have been observed between lateral recumbent and sittting with flexion, lateral recumbent with flexion and sitting without flexion, and lateral recumbent with flexion and sitting with flexion positions; no adverse hypoxic events occurred during positioning. Sitting flexed position, which seems to be sufficiently safe and serve to enhance the success rate of a LP, should be favoured for sick neonates whenever the infant's condition permit a spinal tap.

Neonatal hyperbilirubinemia and organic anion transporting polypeptide-2 gene mutations.

The aim of this study was to investigate the genotypic distribution of organic anion transporting polypeptide 2 (OATP-2) gene mutations and the relationship with hyperbilirubinemia of unknown etiology. Polymerase chain reaction, restriction fragment length polymorphism, and agarose gel electrophoresis techniques were used for detection of OATP-2 gene mutations in 155 newborn infants: 37 with unexplained hyperbilirubinemia, 65 with explained hyperbilirubinemia, and 53 without hyperbilirubinemia. In the OATP-2 gene, we identified A→G transitions at nucleotide positions 388 and 411 and observed six polymorphic forms. The 388/411-411 mutation was the most common form (43%) in subjects with hyperbilirubinemia of unknown etiology. Male sex [odds ratio (OR): 3.08] and two polymorphic forms of the OATP-2 gene [the 388/411-411 A→G mutation (OR: 3.6) and the 388-411 mutation (OR: 2.4)] increased the risk of neonatal hyperbilirubinemia. In male infants with the 388 A→G mutation of the OATP-2 gene, the levels of unconjugated bilirubin in plasma were significantly increased compared with those observed in females. The polymorphic forms of 388 nucleotide of the OATP-2 gene were identified as risk factors for hyperbilirubinemia of unknown etiology.

Acute renal failure SNAPPE and mortality.

BACKGROUND: The aim of the present study was to determine, using the score for neonatal acute physiology and perinatal extension II (SNAPPE-II), whether there is an association with acute renal failure (ARF) and whether it is possible to identify newborns at risk for ARF prior to a rise in creatinine in newborns. METHODS: Information on postnatal risk factors and SNAPPE-II on the first day of life (non-ARF group, n= 475; ARF group, n= 78) were collected. Renal failure was defined as serum creatinine level >1 mg/dL and >1.3 mg/dL (for ≥ 33 weeks and < 33 weeks, respectively) after 48 h of life. RESULTS: In newborns with ARF (n= 78), the median (range) of SNAPPE-II and mortality rate were significantly higher than those of the control group. Patent ductus arteriosus (PDA), disseminated intravascular coagulation (DIC), SNAPPE-II, and resuscitation were identified as independent predictors of ARF in infants on forward stepwise logistic regression. Sepsis, respiratory distress syndrome, ARF, DIC, and SNAPPE-II were identified as independent predictors of mortality in infants on the same analysis. CONCLUSIONS: SNAPPE-II on the first day of life was significantly higher among babies with ARF, suggesting a positive association between higher scores and the development of ARF and mortality, but based on receiver operating characteristic curve results, SNAPPE-II at admission did not enhance the assessment of risk for ARF prior to a rise in creatinine.

Effect of silicon gel sheeting in nasal injury associated with nasal CPAP in preterm infants.

We conducted this study to investigate the efficacy of the silicon gel application on the nares in prevention of nasal injury in preterm infants ventilated with nasal continuous positive airway pressure (NCPAP). Patients (n=179) were randomized into two groups: Group 1 (n=87) had no silicon gel applied to nares, and in Group 2 (n=92), the silicon gel sheeting was used on the surface of nares during ventilation with NCPAP. Nasal injury developed in 13 (14.9%) neonates in Group 1 and 4 (4.3%) newborns in Group 2 (OR:3.43; 95% CI: 1.1-10.1; P<0.05). The incidence of columella necrosis was also significantly higher in the Group 1 (OR: 6.34; 95% CI: 0.78-51.6; P<0.05). We conclude that the silicon gel application may reduce the incidence and the severity of nasal injury in preterm infants on nasal CPAP.

Botulinum toxin for the correction of asymmetric crying facies.

The clinical hallmark of asymmetric crying facies (ACF) is a symmetric appearance of the oral aperture and lips at rest, but significant depression of one side of the lower lip with animation (crying or smiling). ACF can resolve spontaneously in the first year of life, but surgical intervention may be required at some point to ensure a good cosmetic outcome. The authors report on the successful use of botulinum toxin type A to achieve temporary facial symmetry in two children with ACF with results lasting up to six months and suggest that such treatments may be helpful in providing more time to consider and/or plan surgical intervention.