Does ibuprofen treatment in patent ductus arteriosus alter oxygen free radicals in premature infants?

Introduction Ibuprofen is used widely to close patent ductus arteriosus in preterm infants. The anti-inflammatory activity of ibuprofen may also be partly due to its ability to scavenge reactive oxygen species and reactive nitrogen species. We evaluated the interaction between oxidative status and the medical treatment of patent ductus arteriosus with two forms of ibuprofen. Materials and methods This study enrolled newborns of gestational age ⩽32 weeks, birth weight ⩽1500 g, and postnatal age 48-96 hours, who received either intravenous or oral ibuprofen to treat patent ductus arteriosus. Venous blood was sampled before ibuprofen treatment from each patient to determine antioxidant and oxidant concentrations. Secondary samples were collected 24 hours after the end of the treatment. Total oxidant status and total antioxidant capacity were measured using Erel's method. RESULTS: This prospective randomised study enrolled 102 preterm infants with patent ductus arteriosus. The patent ductus arteriosus closure rate was significantly higher in the oral ibuprofen group (84.6 versus 62%) after the first course of treatment (p=0.011). No significant difference was found between the pre- and post-treatment total oxidant status and total antioxidant capacity in the groups. Discussion Ibuprofen treatment does not change the total oxidant status or total antioxidant capacity. We believe that the effect of ibuprofen treatment in inducing ischaemia overcomes the scavenging effect of ibuprofen.

Dopamine treatment does not need speed recovery of newborns from transient tachypnea.

OBJECTIVE: Transient tachypnea of the newborn (TTN) results from inadequate neonatal lung fluid clearance. Low-dose dopamine induces natriuresis in the kidneys and it has been assumed that, at this low dosage, dopamine increases renal perfusion in critically ill patients. Medium doses have positive inotropic and chronotropic effects via increased ß-receptor activation. Recent studies have demonstrated that dopamine stimulates the clearance of pulmonary edema. Furthermore, ß-adrenergic agonists regulate Na+ channels and Na-K-ATPase activity in the pulmonary epithelium. This study investigated the effect of dopamine at different dosages on TTN treatment. METHODS: A prospective controlled study examined 60 infants with TTN older than 34 weeks of gestation who required at least 24 h of O2 and nasal continuous positive airway pressure (nCPAP) treatment. The infants were randomized into three groups of 20: controls, infants treated with low-dose dopamine (3 µg/kg/min), and infants treated with a medium dose (5 µg/kg/min). The control and study groups were compared in terms of the requirement for mechanical ventilation, and the durations of nCPAP, oxygen requirement, and hospitalization. RESULTS: The requirement for mechanical ventilation, and durations of nCPAP, oxygen requirement, and hospitalization did not differ significantly among the three groups (P=0.54, 0.16 and 0.11, respectively). CONCLUSION: Dopamine treatment in low-moderate doses does not improve the outcome in TTN. Thus, further studies in this area are needed.

THE PREVALENCE OF CONSANGUINEOUS MARRIAGES AND AFFECTING FACTORS IN TURKEY: A NATIONAL SURVEY.

This study was carried out by the Turkish Republic Ministry of Health to determine the prevalence of consanguineous marriage and its correlates with socio-demographic and obstetric risk factors in women in Turkey. The cross-sectional, national-level study was carried out from October to December 2013. The study population was composed of women between the ages of 15 and 65 years living in Turkey. The sample size was calculated as 9290 houses within Turkey's 81 provinces so as to improve the Turkish rural-urban expectations by means of systematic stack sampling according to the Turkish Statistical Institute's address-based vital statistics system. The target sample size was 6364, but only eligible 4913 women, who had been married, were included in the study. The consanguineous marriage frequency in the sample was found to be 18.5%, and of these 57.8% were first cousin marriages. Women living in an extended family and whose education level and first marriage ages were low, and whose perceived economic status was poor, had higher frequencies of consanguineous marriage (p<0.001). Consanguineous marriage frequencies were higher (p<0.001) for women who had spontaneous abortions and stillbirths or who had given birth to infants with a congenital abnormality. In this context, it is important to develop national policies and strategies to prevent consanguineous marriages in Turkey.

Comparison of two natural surfactants for pulmonary hemorrhage in very low-birth-weight infants: a randomized controlled trial.

OBJECTIVE: To compare the efficacy of two natural surfactants for pulmonary hemorrhage in very low-birth-weight (VLBW) infants. STUDY DESIGN: A prospective randomized controlled trial was conducted on 42 infants who were divided into two groups, poractant alfa (n = 21) and beractant (n = 21). RESULTS: In both the groups, the mean standard deviation (SD) birth-weight and gestational age were similar (p = 0.33 and 0.89, respectively). Although, the mean oxygenation index (OI) increased after pulmonary hemorrhage compared with baseline value and decreased after surfactant in both groups, variations in OI were more prominent in poractant alfa group (before hemorrhage: 11.9, after hemorrhage: 22.7, 1 hour of surfactant: 14.6, 8th hour of surfactant: 7.8, 24th hour of surfactant: 8.5, p = 0.007 vs. before pulmonary hemorrhage:11.1, after pulmonary hemorrhage: 17.9, 1 hour of surfactant: 12.8, 8th hour of surfactant: 12.8, 24th hour of surfactant: 9.7, p = 0.02). There was no significant difference between the groups for OI values at all time points (p > 0.05). The rates of bronchopulmonary dysplasia (BPD) and mortality related to pulmonary hemorrhage were similar in both the groups. CONCLUSION: Both natural surfactants improved oxygenation when administered for pulmonary hemorrhage in VLBW infants. The type of surfactant seems to have no effect on BPD and mortality rates in these patients.

Universal health coverage in Turkey: enhancement of equity.

Turkey has successfully introduced health system changes and provided its citizens with the right to health to achieve universal health coverage, which helped to address inequities in financing, health service access, and health outcomes. We trace the trajectory of health system reforms in Turkey, with a particular emphasis on 2003-13, which coincides with the Health Transformation Program (HTP). The HTP rapidly expanded health insurance coverage and access to health-care services for all citizens, especially the poorest population groups, to achieve universal health coverage. We analyse the contextual drivers that shaped the transformations in the health system, explore the design and implementation of the HTP, identify the factors that enabled its success, and investigate its effects. Our findings suggest that the HTP was instrumental in achieving universal health coverage to enhance equity substantially, and led to quantifiable and beneficial effects on all health system goals, with an improved level and distribution of health, greater fairness in financing with better financial protection, and notably increased user satisfaction. After the HTP, five health insurance schemes were consolidated to create a unified General Health Insurance scheme with harmonised and expanded benefits. Insurance coverage for the poorest population groups in Turkey increased from 2·4 million people in 2003, to 10·2 million in 2011. Health service access increased across the country-in particular, access and use of key maternal and child health services improved to help to greatly reduce the maternal mortality ratio, and under-5, infant, and neonatal mortality, especially in socioeconomically disadvantaged groups. Several factors helped to achieve universal health coverage and improve outcomes. These factors include economic growth, political stability, a comprehensive transformation strategy led by a transformation team, rapid policy translation, flexible implementation with continuous learning, and simultaneous improvements in the health system, on both the demand side (increased health insurance coverage, expanded benefits, and reduced cost-sharing) and the supply side (expansion of infrastructure, health human resources, and health services).

Oral paracetamol versus oral ibuprofen in the management of patent ductus arteriosus in preterm infants: a randomized controlled trial.

OBJECTIVE: To compare the efficacy and safety of oral paracetamol and oral ibuprofen for the pharmacological closure of patent ductus arteriosus (PDA) in preterm infants. STUDY DESIGN: This prospective, randomized, controlled study enrolled 90 preterm infants with gestational age ≤ 30 weeks, birthweight ≤ 1250 g, and postnatal age 48 to 96 hours who had echocardiographically confirmed significant PDA. Each enrolled patient received either oral paracetamol (15 mg/kg every 6 hours for 3 days) or oral ibuprofen (initial dose of 10 mg/kg, followed by 5 mg/kg at 24 and 48 hours). RESULTS: Spontaneous closure rate for the entire study group was 54%. After the first course of treatment, the PDA closed in 31 (77.5%) of the patients assigned to the oral ibuprofen group vs 29 (72.5%) of those enrolled in the oral paracetamol group (P = .6). The reopening rate was higher in the paracetamol group than in the ibuprofen group, but the reopening rates were not statistically different (24.1% [7 of 29] vs 16.1% [5 of 31]; P = .43). The cumulative closure rates after the second course of drugs were high in both groups. Only 2 patient (2.5%) in the paracetamol group and 3 patients (5%) in the ibuprofen group required surgical ligation. CONCLUSION: This randomized, controlled clinical study compared oral paracetamol with ibuprofen in preterm infants and demonstrated that paracetamol may be a medical alternative in the management of PDA.

Assessment of red blood cell transfusion and transfusion duration on cerebral and mesenteric oxygenation using near-infrared spectroscopy in preterm infants with symptomatic anemia.

BACKGROUND: The aim of red blood cell (RBC) transfusion is to improve tissue oxygenation and relieve anemia-related symptoms in preterm infants. We sought to assess regional cerebral (rSO2 C) and mesenteric (rSO2 M) tissue oxygenation using a near-infrared spectroscopy (NIRS) method and vital signs (heart rate, arterial oxygen saturation, mean arterial blood pressure) in symptomatic preterm infants with anemia who received RBC transfusions. STUDY DESIGN AND METHODS: Twenty-three symptomatic patients with anemia who were at least 1 month old, whose gestational age was less than 30 weeks, and whose hematocrit level was not more than 27% were involved in the transfusion group. The control group consisted of preterm infants (Hct ≥ 32) matched for gestational age and postnatal days. The transfusion group was divided into two subgroups based on transfusion duration (2 or 4 hr). Both study groups were monitored for vital signs and rSO2 C, rSO2 M, and mesenteric-cerebral oxygenation ratio (MCOR) via NIRS for 24 hours simultaneously and compared with the control group. NIRS variables and vital signs obtained before, during, and after transfusion were compared both within and between 2- and 4-hour groups. RESULTS: rSO2 C, rSO2 S, and MCOR increased during and after transfusions, while cerebral fractional oxygen extraction (FOEC) and mesenteric fractional oxygen extraction (FOEM) decreased. No significant difference was found between subgroups for NIRS measurements and vital signs. A weak correlation between hemoglobin concentration and FOEC and FOEM was found. CONCLUSION: RBC transfusion improved cerebral-mesenteric oxygenation and MCOR in symptomatic infants with anemia, independent of the transfusion duration.

Is folic acid supplementation really necessary in preterm infants ≤ 32 weeks of gestation?

OBJECTIVES: The aim of this study was to define whether there was folate deficiency in hospitalized preterm infants, and, second, to define the effect of feeding modalities on serum folate levels. METHODS: Infants born ≤ 32 weeks of gestation were included in the study. Blood samples for the determination of serum folate levels were obtained on days 14 and 28 postnatally, as well as 36 weeks postconceptionally (or just before discharge if patients are discharged <36 weeks)--samples A, B, and C, respectively. Infants were divided into 3 groups based on mode of feeding; human breast milk (HBM), fortified HBM (fHBM), or preterm formula (PF). RESULTS: A total of 162 preterm infants were enrolled: 17 (10.5%) of whom received HBM alone, 94 (58%) received fHBM, and 51 (31.5%) were fed with PF. None of the preterm infants developed folate deficiency during the study period. Preterm infants in the fHBM and PF groups had significant higher serum folate levels in samples C when compared with those receiving HBM alone (P < 0.001 for both). Multivariate analysis to evaluate the effects of maternal supplementation, smoking habit, gestational age, birth weight, and cumulative folic acid intake in samples A, B, and C suggested that maternal smoking and maternal folic acid supplementation had significant effects on serum folate levels in sample A and B. CONCLUSIONS: Preterm infants receiving parenteral nutrition with high folic acid content have no risk of folate deficiency during the 2 months of age; however, preterm infants fed orally from birth with HBM or PF with a low folic acid content could be at risk for folate deficiency, especially when mothers are smokers and/or do not receive folic acid supplementation during pregnancy.

Storage at -80°C preserves the antioxidant capacity of preterm human milk.

BACKGROUND AND OBJECTIVE: It is essential to establish optimum parameters for maintaining the quality of stored milk until the moment of consumption with minimal deterioration of its properties. The aim of the study was to evaluate total antioxidant capacity (TAC) and total oxidation status (TOS) of fresh and freeze-stored samples (at -80°C) of preterm human milk (HM). METHODS: Samples of colostrum were collected from 98 healthy women within the first 4 days after delivery. The total milk volume collected (6 ml) was divided in two aliquot parts: 3 ml for the fresh analysis which was done immediately after the extraction and 3 ml for storage under freezing conditions at -80°C for three months. The antioxidant status and oxidative stress of the fresh and stored breast milk were assessed via determination of TAC and TOS levels. RESULTS: The mean gestational age and the birth weight of the infants were 31.26 ± 2.93 weeks and 1620 ± 581.91 g; respectively. There were no significant correlations between maternal age, route of delivery and milk oxidative stress. There was no significant difference between the levels of TAC, TOS and the oxidative stress index in fresh and freeze-stored samples of colostrum in preterm HM (p > 0.05). CONCLUSION: Freeze storage of preterm HM at -80°C for three months preserves the antioxidant capacity without changing oxidative status of HM, which could be noteworthy for the preterm infant nutrition.

The development and organization of newborn screening programs in Turkey.

BACKGROUND: Newborn screening tests have been designed to identify infants with severe disorders that are relatively prevalent and treatable or controllable. Comparing to other countries, the incidence of these diseases are very high in Turkey where the rate of consanguineous marriage is high. METHODS: In this article, it is aimed to evaluate the development and organization of newborn screening programs in Turkey which include phenylketonuria, congenital hypothyroidism and biotinidase deficiency screenings. The point reached today, limitations of the program, expectations and projects for the future are discussed. RESULTS: Today, the point reached in screening programs of the country is appreciable. While the screening rate of the live born babies was 4,7% in 1987, this rate reached to 95% by 2008. Predicted target for newborn screening program at the strategic plan of Ministry of Health for 2010-2014 was to enhance this rate above 95% by the end of 2012. It seems that the envisaged goal has been reached. CONCLUSION: National newborn screening program appears to be conducted successfully and extensively as a result of political determination and performance of health care workers who are in charge of this program. Nevertheless, limited numbers of the nutrition and metabolism clinics and specialists on these branches have caused some access difficulties, waste of time, and financial loss. Therefore, special planning to improve quality and the number of the clinics would be useful.

Chlorhexidine-associated transient hyperchloremia in an infant.

An infant was cleansed with 2% clorhexidine gluconate (CHG) because of repeated sepsis episodes from skin colonization. Asymptomatic hyperchloremia ensued, most likely associated with CHG therapy. Fourty-eight hours after CHG therapy withdrawal, serum chloride levels returned to normal. Hyperchloremia may be a reversible adverse effect of extensive use of CHG.

Role of pentoxifylline and/or IgM-enriched intravenous immunoglobulin in the management of neonatal sepsis.

OBJECTIVE: To investigate the effectivity of pentoxifylline (PTX) and immunoglobulin M (IgM)-enriched intravenous immunoglobulin (IVIG) therapy in the treatment of neonatal sepsis (NS), alone or in combination. STUDY DESIGN: This was a prospective, double-blind, controlled study. Newborns with suspicion of sepsis were enrolled in the study. The patients were separated into four groups according to treatment protocol: Group 1 = placebo, Group 2 = pentoxifylline, Group 3 = IgM-enriched IVIG, and Group 4 = pentoxifylline + IgM-enriched IVIG. Blood samples were taken for C-reactive protein, interleukin-6, neutrophil CD64 expression, and tumor necrosis factor-alfa measurements immediately before treatment (1st day), and measurements were repeated on the 2nd and 4th days of the therapy. RESULTS: A total of 204 patients, 51 in each group, were recruited into the study. There were no significant differences for symptoms of sepsis among groups, except lethargy. No significant differences were observed among the groups according to laboratory data. Overall mortality rate was 8.8%. The rates of morbidities and mortality among study groups were similar. CONCLUSION: PTX and IgM-enriched IVIG therapies, either alone or in combination, did not reduce the rates of morbidities and mortality in NS.

Neurodevelopmental outcomes of very low birth weight preterm infants treated with poractant alfa versus beractant for respiratory distress syndrome.

BACKGROUND: Some controlled trials have shown significant differences in short-term clinical outcomes between poractant alfa and beractant in infants with respiratory distress syndrome (RDS). There is, however, no study showing the differences in long-term outcomes with these treatments. AIM: To determine and compare the neurodevelopmental outcomes of preterm infants with RDS treated with poractant alfa or beractant at 2 years of age. METHODS: This was a prospective, longitudinal, single-center cohort study of infants born at ≤ 1,500 g and/or ≤ 32 weeks between 2008 and 2009 who received either poractant alfa (n = 113) or beractant (n = 102) for RDS. Neurological and developmental assessments were performed at a corrected age of 18 to 24 months. RESULTS: About 33 of 113 infants (29.2%) in the poractant alfa group had neurodevelopmental impairment compared with 36 of 102 (35.2%) in the beractant group, and the results did not differ between the groups (p = 0.339). Similarly, no significant difference was found in the percentage of infants with cerebral palsy (11.5 vs. 16.7%, respectively; p = 0.275). CONCLUSION: Our findings suggest that poractant alfa and beractant are similar in terms of neurodevelopmental outcomes when used for the treatment of RDS in preterm infants.

Postnatal risk factors associated with hearing loss among high-risk preterm infants: tertiary center results from Turkey.

The aim of this study was to determine the postnatal risk factors associated with hearing loss as well as the prevalence of hearing loss among high-risk preterm infants in newborn hearing screening (NHS). We performed a retrospective study of high-risk preterm infants born with a gestational age ≤32 weeks and/or a birth weight ≤1,500 g. A NHS procedure was performed by automated auditory brainstem response (AABR) and automated evoked otoacoustic emission (TEOAE). Infants who failed TEOAE or AABR or both tests were referred to a tertiary audiology center for diagnosis confirmation and management. Postnatal risk factors associated with hearing loss were evaluated and compared for preterm infants with and without hearing loss. 1,360 high-risk preterm infants were assessed. Permanent hearing loss was found in 19 (1.4%) infants. Multivariate analysis revealed that proven sepsis (p = 0.019), mechanical ventilation ≥5 days (p = 0.024), loop diuretics (p = 0.001), patent ductus arteriosus ligation (p = 0.018) and operation for retinopathy of prematurity (ROP) (p = 0.034) were significant related factors for the hearing loss. This study showed a low prevalence of hearing loss and an association between operation for ROP and hearing loss in preterm infants, which has not been defined previously. Our results suggest that every neonatal intensive care unit should determine their own risk factors and take precautions to prevent hearing loss for these high-risk preterm infants.

Cytomegalovirus infection in preterm triplets transmitted via breast milk.

Cytomegalovirus (CMV) may transmit perinatally or from breast milk. The risk for development of symptomatic CMV disease in very-low-birth-weight premature infants after transmission from maternal breast milk is not clear. There are scarce data in the literature about congenital CMV infection in multiple pregnancies, being mostly with twin gestations. Here we present a unique case of triplets with CMV infection transmitted via breast milk.

Beneficial effects of Etanercept on experimental necrotizing enterocolitis.

PURPOSE: Tissue damage in necrotizing enterocolitis (NEC) of infants occurs as a result of an uncontrolled inflammatory response. The aim of this study was to investigate any potential anti-inflammatory effects that Etanercept may have on the inflammatory response in an experimental NEC model in newborn rats. METHODS: Newborn pups were randomized into three groups immediately after birth (Control, NEC + Placebo and NEC + Etanercept). Pups in the NEC + Placebo and NEC + Etanercept groups were subjected to an NEC-inducing protocol (hypercarbia, hypothermia and hyperoxia) twice a day for 3 days. Pups in the NEC + Etanercept group were given an intraperitoneal injection of Etanercept. Rats were harvested for biochemical and histopathological examinations. RESULTS: The histopathological injury score of rats in the NEC + Placebo group was significantly higher compared to the NEC + Etanercept and Control groups (p < 0.05 for both comparisons). Tissue levels of tumor necrosis factor-α, interleukin-1ß, and malondialdehyde were higher in the placebo group compared to the Etanercept group. CONCLUSION: Our results suggest that Etanercept attenuates intestinal tissue damage in NEC by reducing inflammation and blocking the production of free-oxygen radicals, while also reducing tissue levels of tumor necrosis factor-α and interleukin-1ß.

Successful management of twin anemia/polycythemia sequence by syngeneic partial exchange transfusion.

Twin anemia/polycythemia sequence (TAPS) is characterized by large intertwin hemoglobin (Hb) differences without signs of twin oligopolyhydramnios. The spontaneous form complicates approximately 3-5% of monochorionic twin pregnancies. TAPS placentas are characterized by the presence of only very few and small unidirectional arteriovenous anastomoses, which allow a slow transfusion of blood from the donor to the recipient, gradually leading to highly discordant Hb levels. Neonatal morbidity in TAPS appears to be mainly limited to hematological problems at birth. Donor twins may be severely anemic and require blood transfusions, whereas recipient twins may be severely polycythemic and require partial exchange transfusion (PET). We herein report monochorionic twins with TAPS: the anemic twin was transfused with the blood concomitantly obtained from the polycythemic co-twin during PET. To our knowledge this is the first therapeutic approach using a recipient twin's whole blood as a donor source instead of a foreign blood donor. In this case, we have approached this recently (un)known form of chronic fetofetal transfusion from a different aspect. In our opinion, this will lead to new postnatal therapeutic approaches for optimal TAPS management.

Surgery for rheumatic valve disease in pregnancy: what about the newborn?

BACKGROUND: Valvular heart disease constitutes the majority of all causes of cardiac disease in pregnancy. The significant physiological haemodynamic changes of pregnancy may cause serious cardiac problems leading to severe maternal and foetal morbidity and mortality. In this study, we evaluate the effect of maternal rheumatic valvular disease requiring definitive operation concurrent with caesarian delivery on maternal and foetal outcome. METHODS: Between 2003 and 2010, a total of nine pregnant women and nine live births were examined. Immediately after caesarean section, the newborns were examined by the neonatologist and transferred to the neonatal intensive care unit. All the mothers were followed routinely with clinical and echocardiographic examinations. RESULTS: The age at the time of delivery ranged between 21 and 36 years (median 31 years). Postoperative period of mothers was uneventful and mean hospital stay was 7.56±3.97 days. Birth weight for the newborns was ranged between 1370 and 2900g. Six of the newborns were premature (≤37 weeks). Four newborns were small for gestational age (SGA). There was no mortality in newborns. Hospital stay for the newborns ranged between four and 54 days. CONCLUSIONS: Careful follow-up of pregnancies with valvular heart diseases and determining the optimal time of cardiac intervention are the essential issues. We suggest that careful follow-up of both mother and foetus until at least the 28th gestational week, following which combined caesarian section and cardiac surgery can be performed.

Protective effects of colchicine in an experimental model of necrotizing enterocolitis in neonatal rats.

BACKGROUND: The pathophysiology of necrotizing enterocolitis (NEC) includes the massive production of endogenous cytokines with exaggerated activation of inflammatory pathways. Colchicine has been used as an anti-inflammatory agent. The aim of this study was to investigate the possible beneficial effects of colchicine in a neonatal rat model of NEC. MATERIALS AND METHODS: We randomly divided rat pups into three groups: a control group, a saline-treated NEC group, and a colchicine-treated NEC group. We induced NEC by hyperosmolar enteral formula feeding and exposure to hypoxia/reoxygenation after cold stress. Intestinal samples were harvested for biochemical and histopathologic analyses. RESULTS: The grade of intestinal injury of pups in the saline-treated NEC group was significantly higher than in the control and colchicine-treated groups (P < 0.001 and 0.003, respectively). The median level of intestinal malondialdehyde was significantly higher in the saline-treated NEC group compared with the control group (P = 0.006) or the colchicine-treated NEC group (P = 0.015). We observed significantly higher activity levels of intestinal superoxide dismutase and glutathione peroxidase in the colchicine-treated NEC group compared with the saline-treated NEC group (P = 0.033 and 0.030, respectively). The tissue levels of tumor necrosis factor-α and interleukin-1ß were significantly higher in the saline-treated NEC group compared with the colchicine-treated NEC group (P < 0.001 and 0.003, respectively). CONCLUSIONS: We observed that in this model of NEC, colchicine had favorable effects on intestinal histologic and biochemical changes.

Serum ibuprofen levels of extremely preterm infants treated prophylactically with oral ibuprofen to prevent patent ductus arteriosus.

AIM: The aim of this study was to explore the effects of early oral ibuprofen administration on the incidence of hemodynamically significant patent ductus arteriosus (hsPDA) and define the association between serum ibuprofen levels and ductal closure. METHOD: Preterm infants with a gestational age of <28 weeks and/or birth weight of <1,000 g were randomized either to the intervention (ibuprofen prophylaxis) or control group. The intervention group received oral ibuprofen 10 mg/kg within 12-24 h after birth followed by 5 mg/kg at 24 and 48 h. Serum ibuprofen levels after the treatment were analyzed in the intervention group, and the incidence of hsPDA and complication rates were compared between two groups. RESULTS: Nineteen infants who received one course (three doses) of prophylactic ibuprofen in the intervention group and 17 infants in the control group who underwent an echocardiographic examination on the fourth day of life were analyzed. hsPDA was observed in five (26 %) infants in the intervention group and ten (58 %) infants in the control group (p = 0.09). In the intervention group two infants experienced gastrointestinal bleeding two infants had spontaneous intestinal perforation, and two infants developed acute kidney failure. Mean serum ibuprofen level was 28.7 ± 16.9 mg/L in the intervention group, and there was no correlation between ibuprofen level obtained on the fourth day and ductal closure. CONCLUSION: Oral ibuprofen prophylaxis reduces the rates of hsPDA even it is not statistically significant. The ductal closure rate did not correlate with serum ibuprofen levels. Due to high prevalence of adverse events observed, our data do not support the use of oral ibuprofen for prophylaxis of hsPDA.