Neurodevelopmental outcomes of premature infants with severe intraventricular hemorrhage.

OBJECTIVE: Our objective was to determine the neurodevelopmental outcome at 18-24 months' of corrected age (CA) in preterm infants with severe intraventricular hemorrhage (IVH). METHODS: This was a retrospective cohort study of all preterm infants who were <37 weeks' gestation, had Grade 3-4 IVH, were admitted between January 2009 and December 2010 and discharged. The cohort was divided into three groups. Group 1 was defined as infants born with a birth weight (BW) less than 1000 g, group 2 was defined as infants born with a BW between 1000 and 1500 g and group 3 was defined as infants born with a BW between 1501 and 2500 g. Severe IVH was defined as the presence of grade 3-4 IVH on cranial ultrasound. Cranial ultrasound was performed in the first week of life and subsequently at weekly intervals by a radiologist. A comprehensive assessment including hearing, vision, neurological and developmental evaluation with Bayley Scales of Infant Development, Second edition was performed by the experienced researchers at 18-24 months' CA. Neurodevelopmental impairment (NDI) was defined as at the presence of one or more of the following: cerebral palsy; Mental Developmental Index score lower than 70; Psychomotor Developmental Index score lower than 70; bilateral hearing impairment; or bilateral blindness. RESULTS: From January 2009 to December 2010, a total of 138 infants were diagnosed as severe IVH (grade 3-4). Of them, 74 (71.1%) infants (group 1 = 31, group 2 = 29 and group 3 = 14 infants) completed the follow-up visit and evaluated at 18-24 months' CA. Median Apgar score (p < 0.01) and resuscitation at birth (p < 0.01) were significantly different for groups 1-3. The use of catheterization, need for mechanical ventilation, need for phototherapy, retinopathy of premature and bronchopulmonary dysplasia were significantly higher in group 1 compared to groups 2 and 3 (p < 0.001, p < 0.001, p < 0.01, p < 0.01 and p = 0.014, respectively). The duration of hospitalization and mortality rates consistent with the degree of prematurity were significantly higher in group 1 compared to groups 2 and 3 (p = 0.03 and p = 0.01). Among the long-term outcomes, the rates of CP and NDI did not differ between the groups (p = 0.68 and p = 0.068). CONCLUSION: Our results demonstrated that long-term outcomes of preterm infants did not differ between the groups classified according to the BW at two years of age. This has leaded to the conclusion that severe IVH is alone represents a significant risk factor for poor neurodevelopmental outcome in this already high-risk population.

Effect of mode of delivery on macronutrient content of breast milk.

OBJECTIVE: To determine the effect of delivery type on macronutrient content of colostral milk. MATERIALS AND METHODS: The study was conducted at Zekai Tahir Burak Maternity Teaching Hospital. Colostral milk samples from term lactating mothers who gave birth by vaginal or cesarean delivery (CD) were obtained on the 2nd postpartum day. Milk protein, fat, carbohydrate (CHO) and energy levels were measured by using a mid-infrared human milk analyzer. RESULTS: A total of 204 term lactating mothers were recruited to the study; 111 mothers gave birth by vaginal route and 93 mothers by CD. Protein levels were statistically lower in colostral milk of mothers after CD compared to mothers who delivered vaginally (median 2.4 (range 0.3-6.4) g/dl versus 3 (0.5-6.3) g/dl, respectively; p = 0.036). Colostral fat, CHO and energy levels were similar between groups. In linear regression analysis, CD and maternal age were independently associated with lower protein content in colostrum. CONCLUSION: Vaginal delivery is associated with higher colostrum protein content. Hormonal activity induced by labor pain and uterine contractions might account for the alterations in the protein composition of human milk to facilitate optimal development of important physiologic functions in newborns.

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.

Necrotizing enterocolitis in a newborn following intravenous immunoglobulin treatment for haemolytic disease.

ABO iso-immunization is the most frequent haemolytic disease of the newborn. Treatment depends on the total serum bilirubin level, which may increase very rapidly in the first 48 hours of life in cases of haemolytic disease of the newborn. Phototherapy and, in severe cases, exchange transfusion are used to prevent hyperbilirubinaemic encephalopathy. Intravenous immunoglobulins (IVIG) are used to reduce exchange transfusion. Herein, we present a female newborn who was admitted to the NICU because of ABO immune haemolytic disease. After two courses of 1 g/kg of IVIG infusion, she developed necrotizing enterocolitis (NEC). Administration of IVIG to newborns with significant hyperbilirubinaemia due to ABO haemolytic disease should be cautiously administered and followed for complications.

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.

Impact of probiotics on the course of indirect hyperbilirubinemia and phototherapy duration in very low birth weight infants.

OBJECTIVE: To evaluate the efficacy of orally administered Saccharomyces boulardii (S. boulardii) on the course of hyperbilirubinemia and duration of treatment in very low birth weight (VLBW) infants. METHODS: Infants with a gestational age of ≤ 32 weeks and birth weight of ≤ 1500 g were enrolled. The infants in the study group were given S. boulardii with a dose of 250 mg once a day and the infants in the control group were fed without S. boulardii supplementation. The primary outcome measurements were duration of phototherapy and levels of total bilirubin at the end of phototherapy. RESULTS: A total of 179 infants (81 in the study group and 98 in the control group) were enrolled. The duration of phototherapy was shorter in the study group [1.9 ± 0.86 vs. 2.6 ± 0.9 days, p = 0.000)]. Feeding intolerance was significantly lower in the study group than in the control group (20.9% vs. 47.9%; p = 0.00). CONCLUSION: S. boulardii supplementation at a dose of 250 mg/day is safe for VLBW infants in the short term and effective in reducing the duration of phototherapy in VLBW infants. We suggest that it provides this effect by improving the feeding intolerance and suppressing the reabsorption of bilirubin into the enterohepatic circulation.

Human milk fortification with differing amounts of fortifier and its association with growth and metabolic responses in preterm infants.

BACKGROUND: Fortification of human milk (HM) is a common clinical practice to adapt breast milk to the nutritional needs of very low birth weight (VLBW) infants. The optimal method for HM fortification remains to be determined, and a variety of protocols are currently used in neonatal intensive care units. OBJECTIVE: It is believed that standard fortification is insufficient to meet the needs of VLBW infants. Therefore, we designed a randomized prospective study that investigated the effects of varying levels of blind fortification on short-term growth and metabolic responses of preterm infants. METHODS: Eligible infants were randomized into 3 groups: standard fortification (SF), moderate fortification (MF), and aggressive fortification (AF). Short-term growth, feeding intolerance, and urea, calcium, phosphorus, and alkaline phosphatase levels were assessed. RESULTS: There were 26, 29, and 29 infants in the SF, MF, and AF groups, respectively. The baseline characteristics of the groups were similar. Daily weight gain and length at discharge did not differ among the groups; however, head circumference was significantly higher in the MF and AF groups compared with the SF group. Urea, calcium, phosphorus, and alkaline phosphatase levels were similar between the groups. CONCLUSION: We demonstrated that blind fortification of HM, even with higher amounts than recommended by manufacturers, did not cause any measured adverse effects on the metabolic response of preterm infants. Anthropometric measurements (except head circumference) were not different between the different dosages of fortification.

Effects of different pulmonary surfactants in the prevention of postoperative intraabdominal adhesion formation.

BACKGROUND: After abdominal surgery, the formation of postoperative adhesion is a serious problem. The aim of the study is to evaluate the efficacy of 2 different pulmonary surfactants, poractant and beractant, on adhesion prevention in an experimental model. MATERIALS AND METHODS: An experimental intraabdominal adhesion model was created in 18 adult female rats by cecal abrasion. The rats were randomly assigned to 3 groups. Group I received no further treatment, whereas groups II and III received intraperitoneal poractant and beractant, respectively, before closing the incision. On the 15th postoperative day, all rats underwent relaparotomy, intraabdominal adhesions were scored macroscopically according to Canbaz scoring system, and the cecum in each animal was evaluated microscopically. RESULTS: The median adhesion scores of group II and III rats were significantly lower when compared with group I (P = .02). Group III had a lower median adhesion score than did group II, but this did not reach significance (P > .05). CONCLUSION: These observations suggest that intraperitoneal instillation of both pulmonary surfactants is associated with lower adhesion scores, higher adhesion-free cases, and improved histologic findings.

The metabolic effects of two different lipid emulsions used in parenterally fed premature infants--a randomized comparative study.

OBJECTIVE: To compare the effects of two different lipid emulsions, based on soybean oil and olive oil respectively on plasma lipid concentrations and acylcarnitine profile of very low birth weight infants. DESIGN: Randomized comparative study. PATIENTS AND METHODS: Forty very low birth weight infants, ≤32 weeks of gestational age and receiving at least 40% of the calorie taken by parenteral nutrition from lipid solution at 14th day of life were evaluated. Group I (n=20) received soybean oil based lipid emulsion (Intralipid®) and Group II (n=20) received olive oil based lipid emulsion (Clinoleic®). MAIN OUTCOME MEASURES: Plasma lipid concentrations and acylcarnitine profile were assessed. RESULTS: Triglyceride, cholesterol, high and low density lipoprotein levels, liver function tests were similar between two groups whereas very low density lipoprotein level was statistically lower in Group I (p<0.05). Free carnitine levels were 15.73±10.67 in Group I and 34.25±22.18 µM in Group II (p=0.012) and hexanoyl carnitine levels 2.18±2.10 in Group I and 0.38±0.12 µM in Group II, respectively (p=0.005). Plasma medium chain acylcarnitine levels were significantly higher in Group I. CONCLUSIONS: Low levels of very low density lipoprotein in Group I may be a way of hemostasis to keep the serum triglyceride within normal levels. Lower free carnitine levels in soybean oil-based group is the result of carnitine need during the mitochondrial transport of long chain fatty acids. In Group I, due to the inefficient transport of medium chain fatty acids into the mitochondria, medium chain acylcarnitines accumulate in plasma. This may be the reason of lower carnitine levels in Group I. We suggest that higher levels of hexanoyl carnitine, reflecting defective mitochondrial transport of hexanoyl which leads immunsupression, may be the cause of higher sepsis risk in Group I.

Antioxidant capacity of fresh and stored breast milk: is -80°C optimal temperature for freeze storage?

OBJECTIVE: To determine total antioxidant capacity and total oxidation status in fresh and freeze stored (at -80°C) breast milk during the stages of lactation. METHODS: Samples of colostrum, transitional and mature milk were collected from 44 healthy women at 3, 8 and 30 days after birth. 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 two months. The antioxidant status and oxidative stress of the fresh and stored breast milk were assessed via determination of total antioxidant capacity and total oxidation status. RESULTS: Antioxidant capacity of transitional and mature milk decreased (p = 0.0001, p = 0.028, respectively); however, antioxidant capacity of colostrum did not change by storage at -80°C (p > 0.05). Total antioxidant capacity of fresh and stored breast milk significantly decreased during the stages of lactation (p < 0.0001, p = 0.028, respectively). Total oxidation status showed no significant difference in fresh and stored breast milk during the stages of lactation (p > 0.05). CONCLUSION: Freeze storage of breast milk at -80°C for two months seems not to be the optimal condition to preserve the antioxidant capacity of breast milk.

Influence of maternal cigarette smoking during pregnancy on neonatal serum folate levels.

PURPOSE: Folate is an essential micronutrient for fetal development because of its role in de novo synthesis of DNA. The aim of this study was to compare neonatal serum folate levels of babies born to smoking and non-smoking mothers. METHODS: Infants of consenting pregnant mothers presenting at ≥37 weeks of gestation were enrolled. Subjects were divided into two groups based on their mother's smoking habits. Blood samples were obtained at birth (from the umbilical cord) and 1 month after delivery for the determination of serum folate levels using a chemiluminescence method. RESULTS: Among 140 consenting subjects, 108 (77%) brought their newborns to their scheduled visit 1 month after delivery, 68 of whom were non-smokers and 40 were smokers. Babies born to smoking mothers had significantly lower serum folate levels compared to those born to non-smoking mothers, both at birth (17.2 ± 5 vs. 24.3 ± 4.9; p < 0.01) and 1 month after delivery (11 ± 4.1 vs. 17.5 ± 4.3; p < 0.01). CONCLUSION: Our study is the first of its kind to demonstrate that smoking results in significant reductions in serum folate levels of newborns. These results suggest that folic acid supplementation may be required for expectant smoking mothers throughout pregnancy, not just during the first trimester. Similar supplementation may also be warranted for infants born to such mothers.

Single versus multiple dose intravenous immunoglobulin in combination with LED phototherapy in the treatment of ABO hemolytic disease in neonates.

Intravenous immunoglobulin (IVIG) has been found to decrease hemolysis in neonatal jaundice due to blood group incompatibility, but a consensus on its usage has not been reached. We conducted a study to compare single versus multiple dose of IVIG in combination with light emitting diode (LED) phototherapy in patients with neonatal jaundice secondary to ABO blood incompatibility, and compared the efficacy of these treatments with that in a group of patients who received LED phototherapy solely. Thirty-nine term neonates with ABO blood group incompatibility were enrolled in the study. Group I received one dose of IVIG (1 g/kg) and LED phototherapy, and group II two doses of IVIG (1 g/kg) and LED phototherapy, whereas group III received LED phototherapy only. In group I, exchange transfusion was performed in one patient (6%) and in group II in one patient (10%). In the control group, none of the patients required exchange transfusion. Duration of LED phototherapy was 4.3 ± 0.7 days in group I + II (IVIG group), 3.9 ± 0.6 days in group III (P = 0.06). Lowest hematocrit level in group I + II was 35.0 ± 7.8 and group III was 38.9 ± 4.2, this was statistically significant (P = 0.034). IVIG therapy, single or multiple, did not affect exchange transfusion, need of erythrocyte transfusion and hospitalization time when used in combination with LED phototherapy in the treatment of ABO hemolytic jaundice in neonates.

Randomised controlled trial of prophylactic fluconazole versus nystatin for the prevention of fungal colonisation and invasive fungal infection in very low birth weight infants.

BACKGROUND: Invasive fungal infections are a major cause of morbidity and mortality in preterm infants. The authors conducted the first prospective, randomised controlled trial of nystatin compared with fluconazole for the prevention of fungal colonisation and invasive fungal infection in very low birth weight (VLBW) neonates. METHODS: During a 12-month period, all VLBW neonates were assigned randomly to receive nystatin (1 ml suspension, 100 000 U/ml, every 8 h), fluconazole (3 mg/kg body weight, every third day) or placebo from birth until day 30 of life (day 45 for neonates weighing <1000 g at birth). The authors performed weekly surveillance cultures and systemic fungal susceptibility testing. RESULTS: During the study period, 278 infants (fluconazole group, n=93; nystatin group, n=94; control group, n=91) weighing <1500 g at birth were admitted. There were no differences in birth weight, gestation, gender or risk factors for fungal infection among the groups. Fungal colonisation occurred in 11.7% of the nystatin group and 10.8% of the fluconazole group, as compared with 42.9% of the control group. The incidence of invasive fungal infection was 4.3% in the nystatin group and 3.2% in the fluconazole group, as compared with 16.5% in the control group. There were no differences in fungal colonisation and invasive fungal infection between the nystatin and fluconazole groups. CONCLUSIONS: Prophylactic nystatin and fluconazole reduce the incidence of colonisation and invasive fungal infection in VLBW neonates. The authors believe that nystatin is an alternative to fluconazole, because nystatin is safe, inexpensive, well tolerated and effective.

Comparison of total oxidant/antioxidant status in unconjugated hyperbilirubinemia of newborn before and after conventional and LED phototherapy: A prospective randomized controlled trial.

PURPOSE: We evaluated and compared the oxidant and antioxidant status of hyperbilirubinemic infants before and after the two forms of phototherapy: conventional and LED phototherapy, in order to identify the optimal treatment method. METHOD: Thirty newborns exposed to conventional (Group I) phototherapy and 30 infants exposed to LED phototherapy (Group II) were studied. The serum total antioxidant capacity (TAC) and the total oxidant status (TOS) were assessed by EREL's method. RESULTS: There were no statistically significant differences in TAC or TOS levels between Group I and Group II prior to phototherapy, and no statistically significant difference in TAC levels between the two groups after phototherapy; however, TOS levels were significantly lower in Group II compared to Group I after phototherapy. Oxidative stress index (OSI) increased after conventional phototherapy (p < 0.05) CONCLUSION: The increase in TOS following conventional phototherapy was not not observed following LED phototherapy. This difference should be considered when using phototherapy.

A chromosomal-effect study of intensive phototherapy versus conventional phototherapy in newborns with jaundice.

In this study, we aimed to make a comparison between chromosomal effects caused by conventional phototherapy and intensive phototherapy in jaundiced newborns. The study group included 83 newborns with gestation age of > or =35 weeks, and on days 3-10 after birth. Newborns were divided into four groups on the basis of total serum bilirubin (TSB) levels upon admission and need for phototherapy. The intensive group (n=19) consisted of newborns who received light-emitting diode (LED) phototherapy, the conventional group (n=23) consisted of newborns who received conventional phototherapy, the jaundiced control group (n=21) consisted of newborns whose TSB levels were higher than 10mg/dL (average = 13.7 + /-1.5 mg/dL) on admission and who did not receive phototherapy, and the non-jaundiced control group (n=20) consisted of newborns whose TSB levels were less than 5 mg/dl (average = 3.6 +/- 0.8 mg/dL). TSB level of the intensive group at admission was 20.2 +/- 1.3 mg/dL, whereas the level of conventional group was 19.6 +/- 1.5 mg/dL. Blood samples were taken from all infants on admission to determine sister chromatid exchange (SCE1) frequency. Blood sampling was repeated on discharge (SCE2) of infants who had received phototherapy. Demographic information, hospitalization details and the rate of decline in TSB were recorded, and frequencies of SCE1 and SCE2 were compared. There was no difference in demographic information among the four groups. SCE1 frequencies in 50 metaphases were evaluated in the intensive, conventional, jaundiced control and non-jaundiced control groups, and the SCE1 frequency was determined as 9.37/cell, 9.54/cell, 9.23/cell and 6.17/cell, respectively. The SCE1 frequency of the jaundiced groups (intensive, conventional and newborns-with-jaundice control group) was significantly higher than that in the non-jaundiced control group (p = 0.001). There was no significant difference between the intensive group and the conventional group in SCE2 frequency (13.5/cell vs. 13.55/cell, p = 0.39). SCE2 frequency was higher than SCE1 frequency in both the intensive and conventional groups (p = 0.001). A strong correlation was found between admission TSB and SCE1 frequency (p = 0.001; r = 0.79). The rate of decline in TSB was higher in the intensive group compared with the conventional group (0.26mg/(dLh) vs. 0.14 mg/(dLh); p = 0.001). We found that intensive and conventional phototherapies similarly increase SCE frequency in newborns. There was a strong, positive correlation between the TSB-on-admission level and SCE1 frequency. In the light of this study, we may conclude that intensive and conventional phototherapies may have an effect on chromosomes in jaundiced newborns. TSB levels higher than 10mg/dL are, too, reported hazardous on chromosomes. Further studies are warranted to elucidate this relationship.

Effect of different doses of vitamin D on osteocalcin and deoxypyridinoline in preterm infants.

BACKGROUND: Metabolic bone disease of prematurity is a common problem in preterm infants. The aim of the present paper was to measure the effect of vitamin D, in order to see the relation between vitamin D and urinary excretion of deoxypyridinoline (DPD), serum osteocalcin (OC), calcium (Ca), inorganic phosphorus (P), and alkaline phosphatase (ALP). METHODS: Three different doses of vitamin D, 200 IU/kg (group 1, 11 infants), 400 IU/kg (group 2, 15 infants) and 800 IU/kg bodyweight/day (group 3, 11 infants), were administered to a total of 37 preterm infants between 15th day of birth until the 30th day of birth. RESULTS: There were no significant differences in levels of serum Ca and P before and after vitamin D supplementation in all groups. Serum ALP levels were increased in all but significantly only in groups 1 and 3. Serum OC levels were also increased in each group by the treatment. Urinary DPD excretion was increased gradually by the increase in vitamin D intake, but it was significant only in group 3. CONCLUSION: High dose of vitamin D supplementation might accelerate bone turnover and increased urinary DPD levels might reflect increased bone resorption. To the best of the authors' knowledge this is the first study comparing the effects of different vitamin D dose, by the means of urinary collagen cross-links, on bone turnover in preterm infants.