Neonatal Outcomes of Critical Congenital Heart Defects: A Multicenter Epidemiological Study of Turkish Neonatal Society : Neonatal Outcomes of CCHD.

Critical congenital heart disease (CCHD) is one of the leading causes of neonatal and infant mortality. We aimed to elucidate the epidemiology, spectrum, and outcome of neonatal CCHD in Türkiye. This was a multicenter epidemiological study of neonates with CCHD conducted from October 2021 to November 2022 at national tertiary health centers. Data from 488 neonatal CCHD patients from nine centers were entered into the Trials-Network online registry system during the study period. Transposition of great arteria was the most common neonatal CHD, accounting for 19.5% of all cases. Sixty-three (12.9%) patients had extra-cardiac congenital anomalies. A total of 325 patients underwent cardiac surgery. Aortic arch repair (29.5%), arterial switch (25.5%), and modified Blalock-Taussig shunt (13.2%). Overall, in-hospital mortality was 20.1% with postoperative mortality of 19.6%. Multivariate analysis showed that the need of prostaglandin E1 before intervention, higher VIS (> 17.5), the presence of major postoperative complications, and the need for early postoperative extracorporeal membrane oxygenation were the main risk factors for mortality. The mortality rate of CCHD in our country remains high, although it varies by health center. Further research needs to be conducted to determine long-term outcomes for this vulnerable population.

The propre-save study: effects of probiotics and prebiotics alone or combined on necrotizing enterocolitis in very low birth weight infants.

OBJECTIVE: To test the efficacy of probiotic and prebiotic, alone or combined (synbiotic), on the prevention of necrotizing enterocolitis (NEC) in very low birth weight (VLBW) infants. STUDY DESIGN: A prospective, randomized, controlled trial was conducted at 5 neonatal intensive care units in Turkey. VLBW infants (n = 400) were assigned to a control group and 3 study groups that were given probiotic (Bifidobacterium lactis), prebiotic (inulin), or synbiotic (Bifidobacterium lactis plus inulin) added to breastmilk or formula for a maximum of 8 weeks before discharge or death. The primary outcome was NEC (Bell stage ≥2). RESULTS: The rate of NEC was lower in probiotic (2.0%) and synbiotic (4.0%) groups compared with prebiotic (12.0%) and placebo (18.0%) groups (P < .001). The times to reach full enteral feeding were faster (P < .001), the rates of clinical nosocomial sepsis were lower (P = .004), stays in the neonatal intensive care unit were shorter, (P = .002), and mortality rates were lower (P = .003) for infants receiving probiotics, prebiotics, or synbiotic than controls. The use of antenatal steroid (OR 0.5, 95% CI 0.3-0.9) and postnatal probiotic (alone or in synbiotic) (OR 0.5, 95% CI 0.2-0.8) decreased the risk of NEC, and maternal antibiotic exposure increased this risk (OR 1.9, 95% CI 1.1-3.6). CONCLUSIONS: In VLBW infants, probiotic (Bifidobacterium lactis) and synbiotic (Bifidobacterium lactis plus inulin) but not prebiotic (inulin) alone decrease NEC.

Pre- and postoperative levels of serum brain-derived neurotrophic factor in neonates with congenital heart defects.

BACKGROUND: The objectives of this study were to assess the preoperative and postoperative serum brain- derived neurotrophic factor (BDNF) levels in neonates undergoing surgery for congenital heart defects (CHD). Also to explore the relationship between changes in BDNF levels and the impact of perioperative factors including intraoperative body temperature, aortic cross-clamp time, perfusion time, operation time, inotropic score, vasoactive inotropic score and lactate levels. METHODS: Forty-four patients with CHD and 36 healthy neonates were included in the study. Blood samples for serum BDNF levels were collected three times: preoperatively, and at 24 and 72 hours postoperatively from each patient in the operated group. Additionally, samples were collected once from each individual in the non-operated case group and the control group. Serum BDNF levels were analyzed using the Elabscience ELISA (Enzyme-Linked Immunosorbent Assay) commercial kit. Cranial ultrasonography (USG) was performed on all infants with CHD. Following cardiac surgery, patients underwent second and third cranial USG examinations at 24 and 72 hours postoperatively, respectively. RESULTS: Forty-four consecutive patients with CHD were divided into two groups as follows: the operated group (n=30) and the non-operated group (n=14). Although there were no differences in the baseline serum BDNF levels between the case and control groups, the preoperative serum BDNF levels were significantly lower in the patients operated compared to the non-operated patients. The serum BDNF levels at the 24th hour postoperatively were higher than the preoperative levels. However, no significant correlation was found between the serum BDNF levels at 24 and 72 hours postoperatively as well as the cranial USG findings at corresponding times. CONCLUSIONS: Serum BDNF levels were initially lower in neonates with CHD who underwent surgery, but increased during the early postoperative period. These results suggest that serum BDNF levels are influenced by CHD and the postoperative period.

Partial exchange transfusion results in increased cerebral oxygenation and faster peripheral microcirculation in newborns with polycythemia.

AIM: The aim of this study was to assess cerebral and peripheral oxygenation, by using near infrared spectroscopy (NIRS) and microcirculation by using side stream dark field (SDF) imaging in newborns with polycythemia before and after partial exchange transfusion (PET) therapy to investigate treatment effect on tissue oxygenation and microcirculation. METHODS: Polycythemic newborns with venous haematocrit (Htc) >70% or ≥65% with symptoms were included. NIRS measurements for cerebral and peripheral oxygenation and SDF recordings for microcirculatory flow assessment were obtained before and after PET. Fractional tissue oxygen extraction (FTOE) was calculated based on tissue oxygenation index and oxygen saturation. Wilcoxon test was used for statistical analysis. RESULTS: Fifteen newborns were included. Cerebral tissue oxygenation index, microvascular flow index and % of vessels with hyperdynamic flow increased after PET; median (range): 61.27 (51.36-61.87) versus 64.54 (54.1-74.38), 2.74 (2.46-3) versus 3.22 (2.64-3.75) and 0 (0-2.8) versus 3 (0-99.3), respectively. Whereas cerebral fractional tissue oxygen extraction (CFTOE), % of vessels with sluggish flow decreased after treatment; 0.36 (0.22-0.44) versus 0.31 (0.17-0.46), 1.4 (0-69) versus 0 (0-0.9), respectively. Peripheral oxygenation was unchanged. CONCLUSION: Partial exchange transfusion improves microcirculation in polycythemic newborns. Cerebral oxygenation increases and cFTOE decreases suggesting increased blood flow. Microvascular flow increases possibly representing reactive hyperperfusion after hemodilution. Whether these effects are beneficial require further research.

A rare case of severe lactic acidosis in a preterm infant: lack of thiamine during total parenteral nutrition.

Total parenteral nutrition (TPN) is a revolution in neonatal intensive care unit (NICU) care, but this therapy is not without problems. A 35-week-old, 1300 g female infant was transferred to our NICU because of bilious vomiting and feeding problems. When enteral feeding was started again, a severe condition similar to the previous one developed. On the 24th day, the patient underwent surgery with a diagnosis of Hirschprung's disease. One week before surgery, the parenteral solutions were composed without vitamins because intravenous vitamin supplements suitable for infants were not available. Thereafter, the patient suffered from severe hypoglycaemia, and sepsis started to develop, accompanied by a large anion gap and metabolic acidosis which is severe lactic acidosis refractory to massive doses of bicarbonate. The acidosis improved significantly when the patient was treated with thiamin. Although TPN is life saving in the NICU, meticulous attention must be paid while treating a patient with TPN, and all possible nutrients should be provided. In this report, a case of a preterm newborn requiring a prolonged period of TPN and complicated by serious lactic acidosis is presented and discussed.

Language assessment of non-handicapped twins at 5 years of age.

BACKGROUND: The aim of the present study was to determine language levels in twins and singletons born after at least 34 weeks gestation and without identifiable neurological abnormality and to evaluate whether in vitro fertilization (IVF) affects language development in twin pregnancies. METHODS: A prospective study of a large cohort of all children born between 1 January 2001 and 31 December 2003 was carried out at Gazi University Hospital. All live-born twin pairs in which both twins survived were identified, and a comparable sample of families with pairs of singletons were chosen. The Stanford-Binet Intelligence Scale Form and the translated Turkish form of the Peabody Picture Vocabulary Test were completed at 60 months. RESULTS: Even after excluding the most premature twins and those with diagnosable neurological damage, twins performed worse than singletons on language development tests. Twin girls had better scores than twin boys. A statistically significant difference was found between the scores of term and preterm twins. No significant difference was noted when compared according to birth order. Appropriate for gestational age (AGA) twins did better than small for gestational age (SGA) twins in the test scores. All twin girls did not differ from singleton girls, but all twin boys performed worse than singleton boys. Term twins had similar results with term singletons, but preterm twins had lower scores than preterm singletons. SGA singletons had better scores than SGA twins, while AGA twins and singletons did not differ. When the children were compared with regard to method of conception, IVF children had significantly lower scores on the tests than those in the spontaneous conception group. CONCLUSION: It is hoped that the present findings could lead to a more precise assessment of children for speech impairment and, above all, to more efficient preventive intervention. Whatever mechanisms are involved, the present results indicate that twins born as a result of IVF, are at a disadvantage in terms of language development in comparison with spontaneously conceived twins.

Prenatally detected congenital cystic adenomatoid malformation and postnatally diagnosed trisomy 13: case report and review of the literature.

Congenital cystic adenomatoid malformation (CCAM) is a rare bronchopulmonary malformation characterized by loss of the normal pulmonary tissue. CCAM may be frequently associated with cardiac and renal anomalies. Rarely, CCAM may be seen with chromosome abnormalities. This is the first reported neonatal case of prenatally detected CCAM and postnatally diagnosed trisomy 13.

Combination antifungal therapy with voriconazole for persistent candidemia in very low birth weight neonates.

The purpose of this article is to report our experience with intravenous voriconazole therapy in the treatment of persistent Candida septicemia in very low birth weight (VLBW) neonates. Candidiasis was defined if an infant had a positive blood culture. Ten VLBW newborns developed Candida sepsis, and candidemia persisted in 6 of them despite 3 to 21 days of antifungal therapy with amphotericin B, either conventional or liposomal, and fluconazole. After the addition of voriconazole, clearance of Candida was achieved within 3-7 days of treatment. Antifungal therapy combination with liposomal amphotericin B and voriconazole was continued for at least two weeks after two negative cultures 48 hours apart. We conclude that considering the hazardous effects of Candida infections in preterm newborns, voriconazole can be added to the treatment of fungal sepsis in newborns who still have persistent candidemia despite conventional antifungal management. More clinical information is needed before voriconazole can be used as a first-line drug in antifungal therapy in newborns.

Effect of breast milk and sucrose on pain and perfusion index during examination for retinopathy of prematurity.

OBJECTIVE: The objective of this study is to investigate the effect of breast milk and sucrose on pain scores and perfusion index (PI) and to evaluate the alteration in pain and PI during retinopathy of prematurity (ROP) examination. METHODS: This prospective randomized controlled study was conducted with preterm infants who were born in our hospital, hospitalized in the neonatal intensive care unit and whose gestational week was <32 weeks and birth weight was <1500 g. The preterm infants who would undergo ROP examination were allocated to three groups according to simple randomization method as follows: group 1: only local anesthetic eye drops, proparacaine HCl ophthalmic solution 0.5%, group 2: proparacaine HCl ophthalmic solution 0.5% plus breast milk, and group 3: proparacaine HCl ophthalmic solution 0.5% plus sucrose 24%. Postductal PI, transcutaneous oxygen saturation and heart rate (HR) values were measured before the eye examination (0), at the 30th, 60th, and 90th seconds (s) of the eye examination and 30 s after lasting of the examination in all infants. Pain was evaluated using Neonatal Infant Pain Scale (NIPS) during the examination. RESULTS: Fifty-one preterm neonates were prospectively enrolled into the study. The HR was higher during and after the examination in all infants according to before the examination (p < .001). Transcutaneous oxygen saturation values significantly decreased during the examination in breast milk and sucrose groups (p = .001 and <.001, respectively). While PI was found to be lower at the 60th s compared to the 30th s of the examination in the proparacaine HCl group, no difference was found between the values before and after the examination. Perfusion index was found to significantly decrease during and after the examination compared to the values before the examination in the breast milk group. Perfusion index values were determined to significantly decrease at the 30th and 60th s of the examination in the sucrose group. The NIPS scores during the examination were determined to be higher compared to the NIPS scores before the examination in all groups (p< .001). In the intergroup comparisons, the NIPS scores were found to be higher in the sucrose group compared to the proparacaine HCl group at the 60th s of the examination and higher than that in the breast milk group at the 90th s of the examination (p = .02 and p = .01, respectively). CONCLUSIONS: The present study indicates that alterations may be seen in PI during the ROP examination; in other words, peripheral tissue perfusion could be affected. We consider that eye examination is a very painful procedure, and administering breast milk, sucrose or local anesthetic is not sufficient for reducing pain.

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.

Vascular endothelial growth factor, basic fibroblast growth factor, insulin-like growth factor-I and platelet-derived growth factor levels in human milk of mothers with term and preterm neonates.

Human milk is a complex biological fluid. It contains many nutrients, anti-infectious and biologically active substance. Human milk also contains many angiogenic polypeptides. We have determined four of these: Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (b-FGF), insulin-like growth factor- I (IGF-I) and platelet-derived growth factor (PDGF). The aim of this study was to compare the concentrations of VEGF, b-FGF, IGF-I and PDGF in human milk collected from mothers with preterm and term neonates. Human milk samples were collected from 29 mothers of preterm (<37 weeks) and from 29 mothers of term (38>weeks) infants at days 3, 7 and 28 postpartum. Milk samples were analyzed for VEGF, b-FGF and PDGF by enzyme-linked immunosorbent assay and IGF-I was measured by radioimmunoassay method. Human milk levels of VEGF, IGF-I and b-FGF were significantly higher (p<0.001). Furthermore, within-preterm group concentrations of VEGF, IGF-I and PDGF significantly differed during postpartum days 3-7-28 (p<0.001, p<0.05, p<0.001, respectively), but did not do so for b-FGF concentrations. In term groups, concentrations of IGF-I and VEGF significantly differed (p<0.05, p<0.001, respectively), but did not do so for concentrations of b-FGF and PDGF. This is the first report of simultaneous measurements of four major angiogenic factors in human milk collected from mothers with preterm and term. Our results suggest that three of four angiogenic factors, VEGF, b-FGF and IGF-I, are higher concentration in human milk which collected from preterm mothers than those of terms.

Nosocomial transmission of Candida pelliculosa fungemia in a pediatric intensive care unit and review of the literature.

Horizontal transmission of Candida species in the hospital environment and the fungemia rates have increased in the past decade. We describe a nosocomial cluster of fungemia caused by Candida pelliculosa (teleomorph Pichia anomala) in four infants hospitalized in the pediatric intensive care unit. Candida isolates had strictly related fingerprints, as generated by randomly amplified polymorphic DNA analysis using five different primer sets. The four babies were all treated successfully and recovered. All of the isolates were susceptible to the antifungals tested including amphotericin B, flucytosine, fluconazole, miconazole, micafungin, itraconazole, and voriconazole. Infection control procedures were adapted in the unit and no relapse was detected. In addition, 30 publications presenting 450 pediatric and 28 adult cases are reviewed.

Hemolytic anemia caused by non-D minor blood incompatibilities in a newborn.

Hyperbilirubinemia is one of the most widely seen cause of neonatal morbidity. Besides ABO and Rh isoimmunization, minor blood incompatibilities have been also been identified as the other causes of severe newborn jaundice. We report a newborn with indirect hyperbilirubinemia caused by minor blood group incompatibilities (P1, M, N, s and Duffy) whose hemolysis was successfully managed with intravenous immunoglobulin therapy. A thirty-two gestational weeks of preterm male baby became severely icteric on postnatal day 11, with a total bilirubin level of 14.66 mg/dl. Antibody screening tests revealed incompatibility on different minor groups (P1, M, N, s and Duffy (Fya ve Fyb)). On postnatal day thirteen, the level of bilirubin increased to 20.66 mg/dl although baby was under intensive phototherapy. After the administration of intravenous immunoglobulin and red blood cell transfusion, hemoglobin and total bilirubin levels became stabilised. Minor blood incompatibilities should be kept in mind during differential diagnosis of hemolytic anemia of the newborn. They share the same treatment algorithm with the other types hemolytic anemia. New studies revealed that intravenous immunoglobulin treatment in hemolytic anemia have some attractive and glamorous results. It should be seriously taken into consideration for treatment of minor blood incompatibilities.

Neonatal cerebral sinovenous thrombosis: Two cases, two different gene polymorphisms and risk factors.

Turan Ö, Anuk-Ince D, Olcay L, Sezer T, Gülleroglu K, Yilmaz-Çelik Z, Ecevit A. Neonatal cerebral sinovenous thrombosis: Two cases, two different gene polymorphisms and risk factors. Turk J Pediatr 2017; 59: 71-75. Cerebral sinovenous thrombosis (CSVT) is a rare disease in the neonatal period and also the greatest risk of neonatal mortality and morbidity. In this report, we presented two cases with CSVT and different risk factors. One of these cases had methylenetetrahydrofolate reductase (MTHFR) C677T homozygous polymorphism and the other case had both MTHFR A1298C homozygous polymorphism, plasminogen activator inhibitor-1 (PAI-1) 4G/ 5G polymorphism and elevated lipoprotein a. Early diagnosis and prompt initiation of therapy of neonatal CSVT may prevent neonatal mortality and poor long-term neurodevelopmental outcomes.

Congenital hairy polyp and autoamputation in an infant with acute otitis media.

Hairy polyp is a rare, benign tumor that frequently localizes in the nasopharynx and oropharynx. The embryogenesis of hairy polyp is not known precisely. The clinical profile can vary depending on the size and location of the tumor. In this report, we present a case with hairy polyp who was admitted with acute otitis media and completely recovered after spontaneous autoamputation.

The prediction of later neurodevelopmental status of preterm infants at ages 7 to 10 years using the Bayley Infant Neurodevelopmental Screener.

The aim of this study was to see whether the scores of the Bayley Infant Neurodevelopmental Screener of 45 high-risk preterm infants (gestational age 26-37 wk) between the ages of 3 and 24 months predicted neurodevelopmental status at 7 to 10 years of age. Neurodevelopmental status of 45/122 preterm infants, grouped according to their gestational ages of 26 to 29, 30 to 32, and 33 to 37 weeks, were previously evaluated by Bayley Infant Neurodevelopmental Screener. The scores were categorized as low or high-moderate. Verbal and performance scores of Wechsler Intelligence Scale for Children-Revised (WISC-R) of those patients were assessed between 7 and 10 years. The patients with high-moderate-risk scores of Bayley Infant Neurodevelopmental Screener at all times, regardless of their gestational age, had lower performance, verbal, and total scores of WISC-R than those of who had low Bayley Infant Neurodevelopmental Screener risk scores. High-moderate risk score of Bayley Infant Neurodevelopmental Screener at 7 to 10, and 16 to 20 months, of all patients especially showed good prediction for identifying lower verbal and performance scales. For 7 to 10 months, verbal scale: positive predictive value = 92.3%, negative predictive value = 44.4%, sensitivity = 70.58%, and specificity = 80%; performance scale: positive predictive value = 100%, negative predictive value = 30%, sensitivity = 68.18%, and specificity = 100%. For 16 to 20 months, verbal scale: positive predictive value = 90%, negative predictive value = 37.5%, sensitivity = 64.3%, and specificity = 80%; performance scale: positive predictive value = 90%, negative predictive value = 12.5%, sensitivity = 56.3%, and specificity = 50%. Bayley Infant Neurodevelopmental Screener shows good prediction of later verbal and performance scores of Wechsler Intelligence Scale-Revised for Children as early as 7 to 10 months, which gives us the opportunity to start early intervention.

Cerebral hemodynamic changes and pain perception during venipuncture: is glucose really effective?

Newborns are exposed to a considerable number of painful stimuli. This study is aimed to investigate the effects of 30% glucose solution and nonnutritive sucking on pain perception during venipuncture. Twenty-five term infants were randomized as receiving 30% dextrose (group 1) or sterile water (group 2). Neonatal Infant Pain Scale scores, skin conductance algesimeter recordings, and near-infrared spectroscopy measurements were recorded during the procedure. Neonatal Infant Pain Scale and skin conductance algesimeter results were decreased in both groups from that during venipuncture to after the procedure. Group 1 had lower Neonatal Infant Pain Scale scores compared with group 2 after venipuncture, different from the skin conductance algesimeter, where no difference was observed between groups. In group 1, cerebral blood volume increased after venipuncture. Glucose does not attenuate the Neonatal Infant Pain Scale score and skin conductance algesimeter index during venipuncture, but it leads to a lower Neonatal Infant Pain Scale score after venipuncture unlike the skin conductance algesimeter index, which was not lowered.

Intravenous Immunoglobulin G Treatment in ABO Hemolytic Disease of the Newborn, is it Myth or Real?

Intravenous Immunoglobulin G (IVIG) therapy has been used as a component of the treatment of hemolytic disease of the newborn. There is still no consensus on its use in ABO hemolytic disease of the newborn routinely. The aim of this study is to determine whether administration of IVIG to newborns with ABO incompatibility is necessary. One hundred and seventeen patients with ABO hemolytic disease and positive Coombs test were enrolled into the study. The subjects were healthy except jaundice. Infants were divided into two groups: Group I (n = 71) received one dose of IVIG (1 g/kg) and LED phototherapy whereas Group II (n = 46) received only LED phototherapy. One patient received erythrocyte transfusion in Group I, no exchange transfusion was performed in both groups. Mean duration of phototherapy was 3.1 ± 1.3 days in Group I and 2.27 ± 0.7 days in Group II (p < 0.05). Mean duration of hospital stay was 5.34 ± 2.2 days in Group I and 3.53 ± 1.3 days in Group II (p < 0.05). Mean duration of phototherapy was 4.0 ± 1.5 days and 2.73 ± 1.1 days in double and single doses of IVIG respectively, and this was statistically significant (p < 0.05). IVIG therapy didn't decrease neither phototherapy nor hospitalization duration in infants with ABO hemolytic disease. Meticulus follow-up of infants with ABO hemolytic disease and LED phototherapy decreases morbidity. IVIG failed to show preventing hemolysis in ABO hemolytic disease.