The association of microRNAs in the development of retinopathy of prematurity.

INTRODUCTION: Retinopathy of prematurity (ROP) is one of the main reasons of preventable childhood blindness. In the development of ROP, MicroRNAs may be effective in the balance of factors that inhibit and activate angiogenic factors. We aimed to determine the changes in the blood levels of miR-146a, miR-143, miR-210, miR-21, miR-126, miR-211, miR-221, miR-106 and let 7f and to investigate their association with ROP. We hypothesed that the level of these miRNAs changed significantly in ROP cases. MATERIALS AND METHODS: This observational study was conducted prospectively in preterm infants with ROP. Serum levels of 8 miRNAs were measured. The relationship between disease stage and progression with miRNA gene expression was analysed. Preterm infants without ROP were taken as the control group. RESULTS: 47 patients with ROP and 14 controls, were included in the study. In the ROP group, miR-210, miR-146a, miR-21 were statistically significantly lower. In the ROP group the expression level of miR-143 was insignificantly lower, miRNA-221 was insignificantly higher, and miR-106, miR-126 and let 7f were variable. CONCLUSION: It was observed that miR-210, miR-146a, miR-21 and miR-143 were significantly lower in patients with ROP compared to the control group. However, no association could be established between the type of miRNA and stage of ROP. These miRNAs may be used as adjunctive biomarkers for diagnosis of ROP.

Comparison of intermittent versus continuous vancomycin infusion for the treatment of late-onset sepsis in preterm infants.

BACKGROUND: Vancomycin a frequently used antimicrobial for the treatment of late-onset neonatal sepsis. It can be infused either intermittently or continuously, however, there is no consensus on the optimal dosing regimen. AIM: To evaluate microbiological outcomes, clinical response and adverse events of vancomycin when administered via continuos intravenous infusion. METHODS: The files of preterm infants (<34 weeks), who received either intermittent (group I, n = 41) or continuous (group II, n = 36) vancomycin infusion for the treatment of late-onset sepsis, were investigated retrospectively. Clinical and demographic features were recorded. RESULTS: Clinical improvement rates, Töllner scores and microbiological outcomes did not differ significantly between groups. At 48th hour of vancomycin infusion, 52.8% of infants achieved therapeutic concentrations of vancomycin in group II compared with 34.1% of patients in group I (p = 0.002). Thirty-nine percent of infants in group I had supratherapeutic concentrations of vancomycin at 48th hour compared with 5.6% in group II (p = 0.002). Dose adjustment rate in group I did not differ than group II (65.9% vs. 52.8% respectively, p = 0.3). However, when we subdivide group I into two according to dosing intervals, dose adjustment rates were more common in infants with a gestational age <29 weeks for whom intermittent infusion was performed in 18 hours intervals (92.9% vs 51.9% , p = 0.014). CONCLUSION: In preterm infants, continuous and intermittent infusions of vancomycin have similar clinical efficacies. Continuous infusion is well-tolerated and require less blood sampling compared to intermittent infusion especially in infants less than 29 weeks of gestational age.

Association of vitamin D binding protein polymorphisms with bronchopulmonary dysplasia: a case-control study of gc globulin and bronchopulmonary dysplasia.

OBJECTIVE: The pathophysiologies of bronchopulmonary dysplasia (BPD) are inflammation, infection, tissue damage, angiogenesis defects and genetic susceptibility. Because of the role of the vitamin D binding protein (Gc globulin) on these factors, we investigated the relationship between Gc globulin polymorphisms and BPD. STUDY DESIGN: This case-control study was performed with 160 neonates (⩽32 gestational ages, ⩽1500 g). PCR DNA sequence analyses were used for GC gene rs4588 and rs7041 single-nucleotide polymorphisms. RESULT: In the univariate analyses, it was observed that Gc2 was the only variant that was protective against BPD (Odd ratio (OR)=0.47, 95% coinfidence interval (CI)=0.24 to 0.89, P=0.020). In the multivariate analyses, Gc2 decreased the risk of disease (OR=0.15, 95% CI=0.029 to 0.79, P=0.026) independent of gestational age, birth weight, 5-min Appearance, Pulse, Grimace, Activity, and Respiration scores, respiratory distress syndrome and sepsis. CONCLUSION: The Gc2 variant was, after adjusting for confounders, associated with a decrease in the frequency of BPD. Our study adds Gc globulin to the list of candidate genes that potentially contribute to the etiology of the disease.

Nomogram-based evaluation of thyroid function in appropriate-for-gestational-age neonates in intensive care unit.

OBJECTIVE: The objective of this study was to help neonatologists to interpret the thyroid hormone results accurately, and also to provide reference ranges and/or nomograms of FT4 (free thyroxine) and thyrotropin against gestational age at postnatal 1 week and 1 month in order to assess thyroid function in AGA (appropriate for gestational age) neonates in intensive care unit. STUDY DESIGN: This is a retrospective study. We included a total number of 515 AGA neonates between 24 and 42 weeks of gestation. Routine results of serum FT4 and TSH that had been analyzed with an immunoassay were collected from existing laboratory data. Least square regression analyses were used to estimate both the mean and the s.d. curves as polynomial functions of gestational age. RESULT: Free T4 levels were correlated with gestational age both at postnatal 1 week (r=0.39, P<0.001) and 1 month (r=0.26, P<0.001). Serum TSH levels at postnatal 1 week and 1 month did not show any correlation with gestational age. Scatterplots of FT4 levels against gestational age at 1 week and 1 month, showing the predicted 2.5th, 50th and 97.5th percentiles and central 95% reference ranges for TSH were provided. CONCLUSION: Gestational age-specific nomograms for FT4 and reference ranges for TSH at postnatal 1 week and 1 month in AGA neonates have been developed. This can help neonatologists to interpret the thyroid hormone results accurately. Further studies providing reference ranges/nomograms for thyroid function in small-for-gestational-age neonates are needed.

Effects of antenatal magnesium sulfate treatment on cerebral blood flow velocities in preterm neonates.

OBJECTIVE: The objective of this study is to investigate the effects of antenatal magnesium sulfate (MgSO4) on cerebral blood flow (CBF) velocities in preterm neonates. STUDY DESIGN: In this prospective case-control study, we included 53 neonates born between 26 and 34 weeks of gestation. Twenty neonates were exposed to MgSO4 antenatally and 33 were not. Serial daily Doppler flow measurements of middle cerebral artery (MCA) were performed. RESULT: Significantly increased MCA mean velocities were found in the MgSO4 group. A progressive increase in serial Doppler measurements of MCA mean velocity from day 1 to day 5 of life was detected in both groups. CONCLUSION: There is significant increase in MCA mean velocities in preterm neonates receiving antenatal MgSO4. This increment in CBF velocities might explain the protective role of MgSO4 in ischemic events and hypoxic brain damage.

Resistin levels in preterms: are they influenced by fetal inflammatory course?

OBJECTIVE: Many different factors are involved in the pathogenesis of preterm deliveries and among them maternal or perinatal infections and inflammatory response have the major role. Researches were carried out about resistin, which is thought to have a role in inflammatory cytokine cycle and it was shown to be associated with growth in neonates. However, no research has been carried out showing its relationship with inflammation in neonates. In this study, we aimed to evaluate the resistin levels in premature neonates and the effect of events such as preterm prelabour rupture of the membranes (PPROMs) and the use of antenatal steroids on these levels. STUDY DESIGN: The study included 118 preterm neonates. Their medical data together with their mothers' were recorded. Serum resistin levels together with interleukin (IL)-6, C-reactive protein (CRP) and procalcitonin were evaluated in the first 2 h of life. RESULT: Mean gestational age and birth weight of babies included in the study were 29.6 ± 2.7 weeks and 1306.4 ± 393.4 g, respectively. Babies with PPROMs had significantly higher levels of resistin ((n=30); 70.7 (7.8 to 568.4) ng ml(-1)) than babies without PPROM ((n=88); 25.9 (5.5 to 528.9) ng ml(-1)) (P=0.005), and the babies of mothers who received antenatal steroids had significantly lower resistin levels ((n=44); 20.8 (5.5 to 159.9) ng ml(-1)) than the babies of mothers who did not ((n=66); 34.6 (7.2 to 568.4) ng ml(-1)) (P=0.015). There were significant correlations between resistin and IL-6 levels and between IL-6 and procalcitonin and CRP levels in babies whose mothers did not receive antenatal steroids. However, no correlation was found between these parameters in babies whose mothers received antenatal steroids. CONCLUSION: Preterm delivery and PPROM involve complex cascade of events including inflammation, and steroids are potent anti-inflammatory agents. Elevated resistin levels in babies with PPROM and suppressed levels in babies whose mothers received antenatal steroids reported in this study might have been observed as a result of the effects of fetal inflammation on resistin levels.

Pleural effusion: a rare complication of hepatitis A.

Hepatitis A (HAV) infection, which is the most common form of hepatitis in the paediatric age group and which sometimes has a fulminant course, is endemic in Turkey, constituting one of the country's important health problems. Pleural effusion also represents a rare benign complication of acute HAV infections. We describe here a case of Hepatitis A who developed pleural effusion.

Effects of human milk fortifier on the antimicrobial properties of human milk.

OBJECTIVE: To evaluate the effects of addition of human milk (HM) fortifier and iron on the anti-infective properties of HM. STUDY DESIGN: HM samples were collected from 28 lactating mothers who delivered prematurely, within the first week of post-natal life. HM fortifier Eoprotin was used. The effects of this fortifier against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans were evaluated using a filter paper method. The measurements were repeated with pure HM, fortified HM and iron-added HM. RESULTS: HM inhibited the growth of S. aureus, E. coli, P. aeruginosa and Candida. Addition of HM fortifier did not result in any significant difference on this effect. The addition of iron to HM reduced antimicrobial effect against all three bacteria and the Candida. CONCLUSION: Premature HM has strong antimicrobial activity and addition of the milk fortifier Eoprotin does not change this effect, but addition of iron reduces this antimicrobial activity.

Isoniazid and hypoglycaemia in a premature infant.

Severe hypoglycaemia requiring more than 20 mg/kg per minute glucose infusion was seen in a premature infant. The infant was born to a woman with active tuberculosis, and she was on prophylactic isoniazid. Discontinuation of isoniazid resulted in prompt recovery of hypoglycaemia. Further pharmacological studies may be needed to establish a cause and effect relationship.

Transient tachypnea of the newborn (TTN): a role for polymorphisms of surfactant protein B (SP-B) encoding gene?

BACKGROUND: Transient tachypnea of the newborn (TTN) is usually a benign self-limiting respiratory disorder in the immediate neonatal period. The lipophilic surfactant-associated protein B (SP-B) was demonstrated to be the most relevant structural component of the surfactant system for immediate postnatal pulmonary adaptation. We hypothesized genetic variations of surfactant protein B (heterozygous 121 ins 2 mutation er intron 4 polymorphisms) to be related to TTN. PATIENTS AND METHOD: We screened genomic DNA of 83 healthy term neonates (gestational age: 39 (37 - 41) completed weeks [median and range]; birth weight: 3325 +/- 541 grams [mean +/- SD]) and 75 infants presenting with TTN (gestational age: 38 (37 - 41) completed wecks [median and range]; birth weight: 3091 +/- 435 grams [mean +/- SD]) by means of PCR-amplification, fragment length and sequence analysis. TTN was diagnosed an the basis of the clinical signs with respiratory rate > 60 breaths/minute, fraction of inspired oxygen > 0.21, and characteristic radiographic findings within less than 24 hours after birth. Newborns with any infection, pulmonary or cardiac congenital malformations, postnatal asphyxia and infants born to diabetic mothers were excluded. RESULTS: In TTN-group the frequency of male infants (68.4 % versus 44.6 %, p < 0.05) and caeserian section were significantly higher (68.4 % versus 30.1 %, p < 0.05). We did not find any statistical difference in frequency of intron 4 variations between controls and TTN-group (8.4 % versus 10.7 %). None of the infants were heterozygous for the 121ins2 SP-B mutation. CONCLUSIONS: WC conclude polymorphisms of intron 4 and heterozygous 121 ins 2 mutation not to associated with TTN.

Congenital sialidosis.

Congenital sialidosis is a rare disease resulting from the absence of neurominidase and presenting with hydrops fetalis, hepatosplenomegaly, dysmorphic features, vacuolated lymphocytes and extensive vacuolation of the connective tissue. Elevated levels of sialooligosaccharides in the urine is characteristic. We describe a newborn baby with congenital sialidosis and discuss the difficulties in reaching the diagnosis.

Alternative therapies for neonatal autoimmune thrombocytopenia.

OBJECTIVE: This study was performed to test whether corticosteroids were superior to intravenous immunoglobulins (IVIG) in the treatment of neonatal autoimmune thrombocytopenia (NAT). METHODS: All cases received IVIG, and unresponsive cases received corticosteroids. RESULTS: Of 7 babies who received IVIG, only 1 responded. The 6 remaining cases received corticosteroids thereafter, and all of them responded well to this therapy. CONCLUSIONS: Corticosteroids may be more effective than IVIG in NAT.

Neonatal septicemia in a neonatal intensive care unit. Results of four years.

The outcome of congenital and nosocomial septicemia has been documented in infants who were admitted to a neonatal intensive care unit over a four-year period. The overall incidence of neonatal septicemia in the neonatal intensive care unit was 5.4 percent. Common causes of neonatal septicemia were gram-negative bacilli and staphylococci. Gram-positive microorganisms were the major causative agents for early-onset septicemia. Since the most common pathogen in cases of nosocomial sepsis was gram-negative bacillus, higher mortality rates were observed in nosocomial sepsis. The overall mortality rate in neonatal sepsis was 44.2 percent. The mortality rate in infants in whom nosocomial septicemia developed was significantly higher than in the infants in whom early-onset septicemia developed. However, as gram-negative colonization of the nursery recently changed to gram-positive microorganisms, the mortality rate is hoped to decrease.

Various associations of human parvovirus B19 infection.

A variety of diseases encountered in association with human parvovirus B19 infection seen at Paediatric clinic during 6 months is presented and their relation to parvovirus B19 is discussed. We conclude that investigation of parvovirus B19 in variable diseases by using the newly developed methods of molecular biology will enlighten many etiopathogenetic mechanisms.

Management of late anemia in Rhesus hemolytic disease: use of recombinant human erythropoietin (a pilot study).

The management of (Rhesus) hemolytic disease of the fetus and newborn includes intrauterine transfusions to prevent the development of hydrops, treatment of the possible hyperbilirubinemia in the immediate postnatal period, and treatment of late anemia. Low levels of serum erythropoietin due to suppression of the bone marrow by multiple intrauterine transfusions is a suggested mechanism for this anemia. The aim of our study was to test whether recombinant human erythropoietin reduced the need for erythrocyte transfusions in these infants. Twenty infants with Rhesus isoimmunization were blindly randomized to treatment and control groups at the 2nd wk of life. The number of intrauterine and exchange transfusions and demographic data were similar in both groups. The infants in the treatment group received recombinant human erythropoietin, s.c. 200 U/kg of body weight three times a week for a period of 6 wk, whereas the infants in the control group received a placebo for the same period. In the treatment group, the mean number of erythrocyte transfusions was significantly lower than that of the control group (1.8 versus 4.2). The reticulocyte counts and Hb levels rose earlier in the treatment group. The platelet and neutrophil counts were similar in both groups throughout the study. This study demonstrates that recombinant human erythropoietin treatment decreases the need for erythrocyte transfusions in the late anemia of infants with Rh isoimmunization. Considering the risks of blood transfusions, this decrease in the donor exposure is worthwhile.

Effects of recombinant human erythropoietin in infants with very low birth weights.

Anaemia of prematurity, a postnatal fall in haemoglobin concentration and haematocrit, is particularly common in those born at less than 32 weeks of gestation. Experimental and clinical data implicate inadequate erythropoietin production as an important reason. In this study recombinant human erythropoietin (r-HuEpo) was used in an attempt to treat or prevent this anaemia and thereby provide an alternative to erythrocyte transfusions. Premature infants (birth weight < or = 1250 g and gestational age < or = 32 weeks), who were likely to need transfusions, were randomly assigned to receive 4 weeks of treatment with either subcutaneously administered r-HuEpo (200 U; n = 12) or placebo (n = 12), three times weekly. All patients had oral supplements of elemental iron at a dose of 3 mg/kg/day. Treatment was started in the third week of life. Reticulocyte counts were significantly raised (P < 0.05) in the group treated with r-HuEpo at the end of treatment. The neonates in the group treated with r-HuEpo needed fewer erythrocyte transfusions than those in the placebo group during treatment. There were no toxic effects attributable to r-HuEpo. The results indicate that treatment of infants with very low birth weights with r-HuEpo will reduce their need for erythrocyte transfusions.

High-dose intravenous immunoglobulin therapy for rhesus haemolytic disease.

Rhesus haemolytic disease is a continuing problem in the newborn especially in countries where the use of anti-D immunoglobulin is not prevalent. The fetuses may need intrauterine transfusions to prevent hydrops faetalis and they also may need exchange transfusions to treat the hyperbilirubinaemia that develops after birth. These interventions expose the baby to several blood donors, hence the risk of infection and exchange transfusions. This study was performed to test whether the use of high-dose intravenous immunoglobulin soon after the birth of these infants reduced the need for exchange transfusions. After randomization, intravenous immunoglobulin was given at a dose of 500 mg/kg to 22 infants in the treatment group. Nothing was given to the 19 controls. The number of exchange transfusions needed decreased significantly in the treatment group. No side-effects of intravenous immunoglobulins were seen.