Successful Treatment of Candida parapsilosis Fungemia in Two Preterms with Voriconazole.

Herein, we report two preterms with invasive candidiasis refractory to liposomal amphotericin B (AMB) treatment in spite of low MIC levels (MIC: 0.5 mcg/mL). Both of the patients' blood cultures were persistently positive for C. parapsilosis despite high therapeutic doses (AMB: 7 mg/kg per day). After starting voriconazole blood cultures became negative and both of the patients were treated successfully without any side effects. In conclusion, although it is not a standard treatment in neonatal patients, our limited experience with these patients suggests that voriconazole appears to be a safe antifungal agent to be used in critically ill preterm infants with persistent fungemia despite AMB treatment.

Assessment of the place of tubular reabsorption of phosphorus in the diagnosis of osteopenia of prematurity.

AIM: In this study, we aimed to investigate the utility of tubular reabsorption of phosphorus in the diagnosis of osteopenia of prematurity in addition to biochemical markers. MATERIALS AND METHOD: Premature babies with a gestational age of ≤32 weeks and/or a birth weight of ≤1 500 g who were hospitalized in the neonatal intensive care unit between June 2009 and March 2011 were included in the study. These babies were evaluated at the 40th gestational week and serum calcium, phosphorus, alkaline phosphatase, urea, creatinine, urinary calcium and phosphorus levels were measured and tubular reabsorption of phosphorus was determined. The subjects who had bone graphy findings and/or an alkaline phosphatase level of >400IU/L and a phosphorus value of <3.5 mg/dL were considered osteopenic. The levels of tubular reabsorption of phosphorus of the osteopenic patients were compared with the ones of the non-osteopenic patients. The study was initiated after obtaining ethics committee approval (date: 04.29.2009/213). RESULTS: During the study period, a total of 698 premature babies were hospitalized in our neonatology unit. A diagnosis of osteopenia of prematurity was made in 24 of 190 subjects who met the study criteria. The level of tubular reabsorption of phosphorus was compared with the serum calcium, phosphorus and alkaline phosphatase levels measured at the 40th gestational week and alkaline phosphatase was found to be significantly increased in the group with a high tubular reabsorption of phosphorus (≥%95). When the subjects with a phosphorus level of <3.5 mg/dL and an alkaline phosphatase level of >499 IU were compared with the newborns who were found to have a tubular reabsorption of phosphorus of ≥%95 for the objective of evaluating the specificity and sensitivity of tubular reabsorption of phosphorus, the sensitivity, specificity, positive predictive value and negative predictive value of tubular reabsorption of phosphorus in the diagnosis of osteopenia were found to be 27%, 82%, 17% and 89%, respectively. When the osteopenic and non-osteopenic patients were compared in terms of the levels of tubular reabsorption of phosphorus, no statistically significant difference was found. CONCLUSIONS: It was thought that it was not appropriate to use tubular reabsorption of phosphorus alone in the diagnosis of osteopenia of prematurity.

Mother-Child Interactions of Preterm Toddlers.

INTRODUCTION: We aimed to investigate the mother-toddler relationship in preterm toddlers. METHODS: The sample consisted of 18 mothers and their preterm toddlers (group 1) and 20 mothers and their fullterm toddlers (group 2). Anxiety and depressive symptom levels, attachment pattern, and parental attitudes of mothers and social-emotional problems and developmental level of the toddlers were explored to assess possible confounding factors in the mother-toddler relationship. Two researchers rated the Parent Infant Relationship Global Assessment Scales (PIRGAS). RESULTS: Both the mothers in group 1 and group 2 had similar Beck Depression Inventory (BDI) and State and Trait Anxiety Inventory (STAI) scores. However, the mothers who gave birth before 32 weeks of gestation had higher trait anxiety scores than others (46±2.4 vs. 42.3±5.4, p=0.01). The groups had similar Brief Infant Toddler Social Emotional Assessment Scale (BITSEA) problem and competency scores. The parenting style of group 1 revealed that they had higher scores on the Parenting Attitude Research Instrument (PARI) subscale 5 (excessive discipline) (39.6 vs. 32.1; p=0.02). CONCLUSION: Mother-toddler interaction and attachment security were found to be similar in fullterm and moderately preterm healthy toddlers. Our findings suggest that not the preterm birth itself but the medical, developmental, and/or neurological consequences of prematurity may affect the mother-toddler interaction. To explore the independent effect of prematurity in mother-toddler dyadic relationship, longitudinally designed studies are warranted.

Clinical heterogeneity of immunodysregulation, polyendocrinopathy, enteropathy, X-linked: pulmonary involvement as a non-classical disease manifestation.

PURPOSE: IPEX (Immunodysregulation, Polyendocrinopathy, Enteropathy, X-linked) is a rare X-linked recessive life-threatening disorder characterized by autoimmunity and early death. Pulmonary complication related with IPEX has not been elucidated exactly. Here, we report 4 IPEX patients, 3 of which died from severe pulmonary disease. METHODS: Clinical data and laboratory findings including autoantibodies, immunoglobulin levels as well as number of T, B and NK cells were evaluated. FOXP3 expression and T reg activity were analyzed. The FOXP3 gene was sequenced and RNA analysis was performed. RESULTS: Patient I (PI) presented with nephrotic syndrome at 3 years of age and then developed autoimmune hepatitis without eczema, enteropathy or high IgE and died at 9 years of age due to acute respiratory distress syndrome (ARDS). Two cousins of PI had the same hypomorphic splice site mutation leading to a deletion of 27 amino acids, but normal FOXP3 protein expression and normal suppressive capacity of T reg in a proliferation inhibition assay. However, they exhibited typical symptoms such as eczema, diabetes and enteropathy with eosinophilia at early age (PII, PIII) and were transplanted in infancy. One of them had severe respiratory distress right after birth (PIII). Patient IV from another family presented with chronic diarrhea without autoimmune manifestations and died due to ARDS. CONCLUSION: Lung disease related to IPEX syndrome has not been reported before and this entity could be a critical factor in disease outcome.

Novel homozygous inactivating mutation of the calcium-sensing receptor gene (CASR) in neonatal severe hyperparathyroidism-lack of effect of cinacalcet.

BACKGROUND: NSHPT is a life-threatening disorder caused by homozygous inactivating calcium-sensing receptor (CASR) mutations. In some cases, the CaSR allosteric activator, cinacalcet, may reduce serum PTH and calcium levels, but surgery is the treatment of choice. OBJECTIVE: To describe a case of NSHPT unresponsive to cinacalcet. PATIENT AND RESULTS: A 23-day-old girl was admitted with hypercalcemia, hypotonia, bell-shaped chest and respiratory distress. The parents were first-degree cousins once removed. Serum Ca was 4.75 mmol/l (N: 2.10-2.62), P: 0.83 mmol/l (1.55-2.64), PTH: 1096 pg/ml (9-52) and urinary Ca/Cr ratio: 0.5mg/mg. First, calcitonin was given (10 IU/kg × 4/day), and then 2 days later, pamidronate (0.5mg/kg) for 2 days. Doses of cinacalcet were given daily from day 28 of life starting at 30 mg/m2 and increasing to 90 mg/m2 on day 43. On day 33, 6 days after pamidronate, serum Ca levels had fallen to 2.5 mmol/l but, thereafter, rose to 5 mmol/l despite the cinacalcet. Total parathyroidectomy was performed at day 45. Hungry bone disease after surgery required daily Ca replacement and calcitriol for 18 days. At 3 months, the girl was mildly hypercalcemic, with no supplementation, and at 6 months, she developed hypocalcemia and has since been maintained on Ca and calcitriol. By CASR mutation analysis, the infant was homozygous and both parents heterozygous for a deletion-frameshift mutation. CONCLUSION: The predicted nonfunctional CaSR is consistent with lack of response to cinacalcet, but total parathyroidectomy was successful. An empiric trial of the drug and/or prompt mutation testing should help minimize the period of unnecessary pharmacotherapy.

[Neonatal Candida infections and the antifungal susceptibilities of the related Candida species]. / Neonatal kandida enfeksiyonlari ve etkenlerinin antifungal duyarliliklari

Among nosocomial infections in the newborns, the incidence of fungal infections has been rising over the last decades. Fluconazole has been a new option for treatment however, expanded use of the drug brought up the development of resistance. In this study, species of the Candida isolates from neonates with candida infections, their antifungal susceptibilities and the effectiveness of the therapy were evaluated. All the species of Candida isolates from blood, urine and sterile body fluids of 54 neonates and their antifungal susceptibilities were evaluated retrospectively over the 13-year period. Demographic characteristics, risk factors, infection foci, Candida species causing infection and their in vitro susceptibilities for fluconazole (FCZ) and amphotericin B (AMB) and treatment responses were analyzed. The antifungal susceptibility testing of isolates was performed by microdilution technique. The median birth weight and gestational age of the study groups were 1735 (660-3990) g and 33 (24-40) weeks, respectively. Among the patients, 19 (35%) were term, while 35 (65%) were preterm [< 32 weeks n = 20 (37%), < 28 weeks n = 7 (13%)]. The percentage of low birth weight infants was 65% (42% was < 1500 g, 13% was < 1000 g). Candida spp. were isolated mostly from blood samples (63%), followed by urine (46%), cerebrospinal fluid (CSF; 5%), peritoneal fluid (3%) and endotracheal aspirate (2%). Multifocal growth was determined in 10 (18%) cases. The isolated species were C.albicans (n =36) as being the most common isolate followed by C.parapsilosis (n = 12), C.tropicalis (n = 1), C.kefyr (n = 1), C.lusitaniae (n = 1), C.pelluculosa (n = 1) and Candida spp. (n = 2). Prior antibiotic use, long term hospitalization, total parenteral nutrition and use of lipid solutions, prematurity and catheter use were determined as the most frequently associated factors causing candidal infections. A congenital abnormality, mainly myeloschisis and hydrocephaly, was detected in 18 (33%) of the cases. Overall FCZ resistance rate was 5.5% and the rate of resistance according to the species was 2.8% for C.albicans and 11% for non-albicans isolates. No resistance was observed to AMB. Initial treatment was FCZ for 78% and AMB for 22% of the newborns. The treatment was switched to AMB in 15 (28%) cases because of no clinical or laboratory response to FCZ although only three of these babies showed resistance to FCZ (MIC ≥ 64 mcg/ml). Among the cases with no clinical/microbiological response, C.albicans was the most frequently (66%) isolated species followed by non-albicans species (33%). All of the isolates in the study group were susceptible to AMB and the rate of FCZ resistance was 5.5%. However, it was noted that the clinical treatment failure was higher than the resistance rate when FCZ was considered. Although antifungal susceptibility tests are helpful for guiding the therapy, in vivo and in vitro differences should be taken into account in case of treatment failure encountered with the use of in vitro effective agents.

A rare cause of perinatal asphyxia: maternal carbon monoxide poisoning.

Carbon monoxide (CO) intoxication has serious adverse effects to the mother and fetus and a result of intrauterine hypoxia, it leads to fetal death or severe neurological sequelae. In this article, a preterm infant who was acutely exposed to CO at the 33rd weeks of gestation before delivery was presented. The baby was delivered by emergent cesarean section at the 34th weeks of gestation due to findings of fetal distress and he had severe hypoxic ischemic encephalopathy leading to death. Results and treatment modalities of CO poisoning during pregnancy were reviewed.

End-of-life decisions in the newborn period: attitudes and practices of doctors and nurses.

The aim of our study was to assess the attitudes and practices of doctors and nurses about end-of-life decisions and compare our results with those observed in different European countries. The data was collected from nurses and doctors, using a standardized questionnaire adapted from the EURONIC study. A total of 250 structured questionnaires were delivered, and 135 (77%) of them were accepted for analysis. The end-of-life decision was taken in 39.4% of the hospitals and personal involvement was 40%. Although an ethical committee was present in the hospitals of 61.5% of responders, a written policy was present in only 3.1% of the units. The mean attitude score was 6.5. Seventy-five percent of the contributors agreed that everything possible should be done to ensure a neonate's survival regardless of the prognosis and 65.2% of responders believed that costs of health care should not affect nontreatment decisions. Most of the responders (65.2%) agreed that severe mental disability as an outcome was equal to or worse than death. In patients in whom medical intervention would be futile, or would not offer sufficient benefit to justify the burdens imposed, hospitals should set up a functional ethical committee in order to decide in matters of withholding or withdrawing intervention.

Percentiles of oxygen saturations in healthy term newborns in the first minutes of life.

The aim of this study was to establish the reference values of preductal oxygen saturation (SpO2) in healthy infants immediately after birth. SpO2 recordings of 200 term neonates (vaginal group;n=150 and cesarean group;n=50) with regular respiratory pattern were evaluated. The median SpO2 values in the first, fifth and tenth minutes were 71, 92, and 98% in vaginal deliveries and 70, 79, and 96% in cesarean deliveries, respectively. SpO2 was significantly lower in the cesarean group at any time after the first minute of life (p<0.0001). The time needed to reach a SpO2>90% was three times longer in cesarean deliveries. Healthy neonates are poorly saturated immediately after birth. The duration to reach a SpO2>90% was longer in infants born by cesarean deliveries.

Quantitative ultrasound and biochemical parameters for the assessment of osteopenia in preterm infants.

OBJECTIVE: Our study aimed to evaluate the feasibility of quantitative ultrasound (QUS) evaluation in osteopenia of prematurity and to compare the results to biochemical parameters. METHODS: QUS assessment of bone was performed at the end of the first postnatal week and at term-corrected age (CA) in premature infants (N = 30) and within the first week in full-term infants (N = 25). On the same day of measurement of QUS, the serum calcium, phosphorus (inorganic), and alkaline phosphatase (ALP) activity were measured in the preterm infants. RESULTS: The median of tibia z score at term-CA in premature infants was significantly lower compared to that of first postnatal week (-1 and 0.4, respectively; p < 0.0001) and it was also lower than that of term-matched controls (0.0; p = 0.001). Preterm infants at term-CA had lower weights and lengths in comparison to term infants. The median ALP value was 585 IU/L at the first postnatal week and 703 IU/L at term-CA in preterm infants (p = 0.003). The median tibia z score of infants with ALP >or=900 IU/L was significantly lower than that of the infants with ALP <900 IU/L (-1.4 vs. 0.1; p = 0.001). An inverse correlation was found between ALP levels and tibia z score at term-CA in preterm infants (rho = -0.61, p = 0.01). CONCLUSIONS: Bone density of preterm infants at term-CA was lower than that at first postnatal week. Serum ALP levels increased during the first postnatal weeks. The tibia z scores were correlated to serum ALP levels. QUS is a good screening tool for the detection of osteopenia.

Use of recombinant factor VIIa in a preterm infant with coagulopathy and subdural hematoma.

Activated recombinant factor VIIa was administered to a preterm infant with bleeding diasthesis and a huge subdural hematoma that could not be controlled by the blood products. The coagulation tests were normalized the following day. Recombinant factor VIIa can be a choice in selected cases with intractable bleedings unesponsive to conventional replacement therapy.

Report of three cases: congenital chylothorax and treatment modalities.

Chylothorax is the most common cause of pleural effusion in the newborn. We report three patients with congenital chylothorax and discussed the clinical course and treatment options. Cases 1 and 2 with congenital chylothorax were treated by chest tube placement and total parenteral nutrition (TPN), and were fed a formula rich in medium-chain triglyceride. They were discharged home without any sequelae. Our 3rd case with chylothorax did not respond to the conventional therapies. Octreotide infusion was tried without any benefits and necessitated surgical intervention, but the infant developed chronic lung disease requiring nasal oxygen therapy until three months of age. All three patients developed complications of chylothorax treatment like chest tube dysfunction, pneumothorax, nosocomial sepsis, and cholestasis. Management of congenital chylothorax necessitates a multidisciplinary approach. Treatment options include pleural drainage, cessation of enteral feeding and initiation of TPN. Experience with octreotide treatment is limited. Surgery should be reserved for severe and refractory cases.

Is the mycobacteria-derived purified protein response in atopic asthmatic children different?

BACKGROUND: The response to mycobacteria-derived purified protein (PPD) is mediated primarily by T-helper-1 response and is expected to be inhibited in atopic diseases. The aim of this study was to investigate whether the PPD response is different in atopic asthmatic children. METHODS: 40 atopic asthmatic children (mean age 8.3 +/- 4.9 years) and 40 healthy age- and sex-matched children who had received bacillus Calmette-Guerin (BCG) vaccination were included in the study. Five PPD units were administered intradermally to all children and were interpreted after 48 h. RESULTS: There was no correlation between serum total IgE level and PPD induration (p=0.054). The PPD induration was not statistically different between the children who used inhaled corticosteroid and those who did not. Although the PPD positivity (induration > or =5 mm) rate was higher in atopic asthmatic children (50%) than in healthy children (32.5%), the difference was not found to be statistically significant. The PPD induration in atopic asthmatic children (7.41 +/- 5.58 mm) was found to be greater than the one in healthy children (5.21 +/- 3.39) (p < 0.039). The induration in atopic asthmatic children (5.21 +/- 3.77) and healthy children (4.43 +/- 2.32) did not show a difference in children who where vaccinated only once with BCG, but it was found to be statistically significantly greater in atopic asthmatic children (12.50 +/- 5.90) than healthy children (7.08 +/- 4.70) who were vaccinated with BCG twice (p <0.012). The proportion of having a PPD induration of > or =10 mm was found to be higher in atopic asthmatic children than in the healthy ones (32.5 vs. 12.5%) (p <0.032). CONCLUSION: Our data showed that the PPD response was stronger in BCG-vaccinated atopic asthmatic children than in healthy BCG-vaccinated ones.