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A7 Lactoferrin measurements in maternal milk after preterm and term delivery
S104
Selected abstracts / Early Human Development 88S2 (2012) S101–S115
shed new light on this pathogenetic dispute and may be helpful in determining the direction of research in the future. A7 Lactoferrin measurements in maternal milk after preterm and term delivery M. Rinaldi2 , P. Manzoni3 , M. Albenzio1 , A. Santillo1 , R. Magaldi2 . 1 Dep. PrIME, University of Foggia, Italy; 2 SC Neonatology and IT, AOU, Foggia, Italy; 3 Neonatology and NICU, S. Anna Hospital, Torino, Italy Lactoferrin (LF) is a milk glycoprotein involved in innate immune host defences and exhibits a wide range of biological activities. Human milk from mothers of infants born prematurely undergoes to variations in protein composition with respect to full term delivery [1]. The present study aimed to determine concentrations of LF in human milk from mothers of preterm and term infants, and their variations in colostrums and mature milk. A number of 50 milk samples were collected at 0–72 h, 120–168 h and at >270 h from mothers who delivered preterm and term infants. Milk samples were grouped according to the infants’ gestational age: 24–25 wk (I), 28–31.9 wk (II), 32–34.9 wk (III), 35–37.9 wk (IV), and 38– 41.9 wk (V). Milk was analysed by SDS-PAGE in duplicate. LF amounts (mg/ml) were calculated from a calibration curve obtained loading serial dilutions of a pre-defined standard (LF100, Dicofarm SpA – Rome, Italy). The LF concentrations were also studied in relation to the weight at birth of the infant. Milk from group I exhibited twice as much higher concentrations of LF (mean±SE, 785±141 mg/ml) compared to the other groups in which LF values ranged between 357±55 and 416±72 mg/ml in II and IV, respectively (p < 0.001 in both cases). Inversely, the effect of birth weight on LF level showed significant differences (P < 0.01) between milk fed babies <1,400 g and milk fed babies >3,200 g. Intermediate levels of LF were detected in milk fed babies displaying in-between weights. This study provides further evidence of the occurrence of a gross modulation of LF content inmaternal milk depending on gestational age and birth weight of the infant. Preterm infants should be exposed to higher levels of LF compared to term neonates. Reference(s) [1] Armaforte et al. International Dairy Journal 20 (2010) 715–723. A8 Long term effect of cord blood and gastric aspirate cytokines on lung function I. Sˇ tucin Gantar1 , M. Praprotnik2 , J. Babnik1 , B. Wraber3 , U. Krivec2 , L. Kornhauser Cerar1 . 1 Division of Perinatology, Department of Obstetrics and Gynecology, University Medical Centre Ljubljana, Slovenia; 2 Department of Pulmonology, University Children‘s Hospital, University Medical Centre Ljubljana, Slovenia; 3 Institute of Microbiology and Immunology, Medical Faculty Ljubljana, Slovenia Background: Exposure to prenatal inflammation increases the risk for development of bronchopulmonary dysplasia. Aim: To evaluate the correlation of cord blood and gastric aspirate levels of interleukin-6 and interleukin-8 measured at birth in preterm infants with the lung function at the age of 8 years. Methods: In the period 2000–2002 we recruited 129 infants with gestational age <30 wks, whose concentrations of IL-6 and IL-8 were measured in gastric aspirate and cord blood at birth. In the years 2008 to 2010, all of them were recalled with the aim to perform systematic lung function evaluations at the age of 8 years. Results: A number of 30 formely preterm infants (mean gestational age 27 wks, mean birth weight 955 g) responded for pulmonary function measurement. To exclude major bias, a comparison between study group infants and the non-responders group of infants was done and showed no statistical significant difference with respect to perinatal characteristics, ventilation days, bronchopulmonary dysplasia and the cytokine concentrations. The values of pulmonary function test measurements in these formerly preterm children were lower than the normal standard performances described in term pairs. However, only the difference in FEF 25–75% values was statisticaly significant. The concentrations of IL-6 and IL-8 in cord blood and in gastric aspirate tended to inversely correlate with to all parameters of lung function at the age of 8 years, however only the correlations between the
concentration of IL-8 in cord blood to FEV1/FVC (r = −0.38, p = 0.04) and to FEF 25–75% (r = −0.44, p = 0.02) reached statistical significance. Conclusion: These results show a negative correlation between concentrations of IL-8 in cord blood at birth with FEF 25–75% and FEV1/FVC values at 8 years of age, which suggests the important role of IL-8 in early airway remodeling. To our knowledge this is the first report showing that intrauterine inflammatory responses could have long term consequences on lung function. A9 Maternal–neonatal colonisation by intrinsically fluconazole-resistant Candida species in a preterm SGA neonate: a case report S. Rizzollo1 , P. Manzoni1 , D. Farina1 , C. Priolo1 , U. Sala1 , L. Barberis1 , C. Carbonara1 , E. Mastretta1 , C. Monetti1 , P. Cigna1 , M.L. Leonessa1 , C. Giovannozzi1 , P. Galletto1 , G. Gomirato1 . 1 Neonatology and NICU, A.O. Regina Margherita-S. Anna, S. Anna Hospital, Torino, Italy Background: Fungal sepsis in preterm infants in NICU has a high burden of morbidity and mortality. The use of fluconazole prophylaxis, as well as in other high-risk categories of patients, significantly reduces the risk of colonisation and infection by Candida spp. (mostly C. albicans), and has been adopted by our NICU for the past 10 years with excellent results [1]. Nevertheless, some Candida species are inherently resistant to fluconazole (C. krusei) or partially resistant being only dose-dependently susceptible (C. glabrata) [2]. Here we describe a clinical case of a preterm infant who carried significant management problems related to his status of colonisation by one of these Candida species that are characterised by variable fungal resistance to fluconazole. Case report: G.C., female, born by emergency cesarean section for placental abruption at 33+2 weeks, with birth weight of 1270 g, Apgar 6/7 at 1st and 5th minute. The mother was treated with prednisone throughout the whole pregnancy for ulcerative colitis. The newborn manifested a good and rapid postnatal adaptation, and maintained well and asymptomatic during the first week of admission to NICU. Serum inflammatory indexes (CRP) always remained normal. Buffer Headset performed on day 1 of life was negative. As a routine, at 3rd day of life, the baby started prophylaxis with fluconazole at a dose of 6 mg/kg every other day, and performed weekly culture surveillance tests. These cultures highlighted the presence of C. glabrata on day 2nd (culture from endotracheal tube), and C. glabrata again on day 8th (culture from stool and gastric aspirate). The culture of Umbilical Catheter performed in 5th day was negative. Susceptibility testing performed on the fungal colonies of C. glabrata retrieved at cultures showed MIC90 comprised between 4 and 8. On 8th and 9th day severe neutropenia was detected (neutrophils <1000/mmc), and therefore – in view of increased baseline risk for sepsis – therapy with G-CSF was instituted (1 dose/day for 3 days) with normalisation of WBC count on day 11th. Despite persisting normality of clinical course, a culture from CVC performed on day 16th turned out positive for C. glabrata. At this point, given the risk of systemic dissemination, we decided to discontinue prophylactic fluconazole therapy and to start systemic treatment with liposomal amphotericin B at a dose of 3→5 mg/kg/day for 15 days. The neonate evoved regularly, all cultures performed on 3rd, 4th and 5th weeks of life turned negative, and on day 35th day she could be discharged without any need of treatment, nor any sequelae. Discussion: One of the major risk factors for the development of sepsis is the fungal colonisation by Candida species, however the variables associated with the progression from colonisation to fungal infection in neonates colonised are still poorly known. Fluconazole is reported to have a good preventive and therapeutic effect on colonisation and infection by most strains of Candida species, and is well tolerated without side effects. A limited number of Candida species, mainly including C. glabrata, are reported to have a dose-dependent susceptibility to fluconazole itself. This finding implies that the use of fluconazole in treatment is not indicated, however no data todate exist on its use in prophylaxis in such cases. In our clinical report, the choice to perform prophylaxis with fluconazole in this neonate has been dictated by the opportunity to limit the
Selected abstracts / Early Human Development 88S2 (2012) S101–S115
shed new light on this pathogenetic dispute and may be helpful in determining the direction of research in the future. A7 Lactoferrin measurements in maternal milk after preterm and term delivery M. Rinaldi2 , P. Manzoni3 , M. Albenzio1 , A. Santillo1 , R. Magaldi2 . 1 Dep. PrIME, University of Foggia, Italy; 2 SC Neonatology and IT, AOU, Foggia, Italy; 3 Neonatology and NICU, S. Anna Hospital, Torino, Italy Lactoferrin (LF) is a milk glycoprotein involved in innate immune host defences and exhibits a wide range of biological activities. Human milk from mothers of infants born prematurely undergoes to variations in protein composition with respect to full term delivery [1]. The present study aimed to determine concentrations of LF in human milk from mothers of preterm and term infants, and their variations in colostrums and mature milk. A number of 50 milk samples were collected at 0–72 h, 120–168 h and at >270 h from mothers who delivered preterm and term infants. Milk samples were grouped according to the infants’ gestational age: 24–25 wk (I), 28–31.9 wk (II), 32–34.9 wk (III), 35–37.9 wk (IV), and 38– 41.9 wk (V). Milk was analysed by SDS-PAGE in duplicate. LF amounts (mg/ml) were calculated from a calibration curve obtained loading serial dilutions of a pre-defined standard (LF100, Dicofarm SpA – Rome, Italy). The LF concentrations were also studied in relation to the weight at birth of the infant. Milk from group I exhibited twice as much higher concentrations of LF (mean±SE, 785±141 mg/ml) compared to the other groups in which LF values ranged between 357±55 and 416±72 mg/ml in II and IV, respectively (p < 0.001 in both cases). Inversely, the effect of birth weight on LF level showed significant differences (P < 0.01) between milk fed babies <1,400 g and milk fed babies >3,200 g. Intermediate levels of LF were detected in milk fed babies displaying in-between weights. This study provides further evidence of the occurrence of a gross modulation of LF content inmaternal milk depending on gestational age and birth weight of the infant. Preterm infants should be exposed to higher levels of LF compared to term neonates. Reference(s) [1] Armaforte et al. International Dairy Journal 20 (2010) 715–723. A8 Long term effect of cord blood and gastric aspirate cytokines on lung function I. Sˇ tucin Gantar1 , M. Praprotnik2 , J. Babnik1 , B. Wraber3 , U. Krivec2 , L. Kornhauser Cerar1 . 1 Division of Perinatology, Department of Obstetrics and Gynecology, University Medical Centre Ljubljana, Slovenia; 2 Department of Pulmonology, University Children‘s Hospital, University Medical Centre Ljubljana, Slovenia; 3 Institute of Microbiology and Immunology, Medical Faculty Ljubljana, Slovenia Background: Exposure to prenatal inflammation increases the risk for development of bronchopulmonary dysplasia. Aim: To evaluate the correlation of cord blood and gastric aspirate levels of interleukin-6 and interleukin-8 measured at birth in preterm infants with the lung function at the age of 8 years. Methods: In the period 2000–2002 we recruited 129 infants with gestational age <30 wks, whose concentrations of IL-6 and IL-8 were measured in gastric aspirate and cord blood at birth. In the years 2008 to 2010, all of them were recalled with the aim to perform systematic lung function evaluations at the age of 8 years. Results: A number of 30 formely preterm infants (mean gestational age 27 wks, mean birth weight 955 g) responded for pulmonary function measurement. To exclude major bias, a comparison between study group infants and the non-responders group of infants was done and showed no statistical significant difference with respect to perinatal characteristics, ventilation days, bronchopulmonary dysplasia and the cytokine concentrations. The values of pulmonary function test measurements in these formerly preterm children were lower than the normal standard performances described in term pairs. However, only the difference in FEF 25–75% values was statisticaly significant. The concentrations of IL-6 and IL-8 in cord blood and in gastric aspirate tended to inversely correlate with to all parameters of lung function at the age of 8 years, however only the correlations between the
concentration of IL-8 in cord blood to FEV1/FVC (r = −0.38, p = 0.04) and to FEF 25–75% (r = −0.44, p = 0.02) reached statistical significance. Conclusion: These results show a negative correlation between concentrations of IL-8 in cord blood at birth with FEF 25–75% and FEV1/FVC values at 8 years of age, which suggests the important role of IL-8 in early airway remodeling. To our knowledge this is the first report showing that intrauterine inflammatory responses could have long term consequences on lung function. A9 Maternal–neonatal colonisation by intrinsically fluconazole-resistant Candida species in a preterm SGA neonate: a case report S. Rizzollo1 , P. Manzoni1 , D. Farina1 , C. Priolo1 , U. Sala1 , L. Barberis1 , C. Carbonara1 , E. Mastretta1 , C. Monetti1 , P. Cigna1 , M.L. Leonessa1 , C. Giovannozzi1 , P. Galletto1 , G. Gomirato1 . 1 Neonatology and NICU, A.O. Regina Margherita-S. Anna, S. Anna Hospital, Torino, Italy Background: Fungal sepsis in preterm infants in NICU has a high burden of morbidity and mortality. The use of fluconazole prophylaxis, as well as in other high-risk categories of patients, significantly reduces the risk of colonisation and infection by Candida spp. (mostly C. albicans), and has been adopted by our NICU for the past 10 years with excellent results [1]. Nevertheless, some Candida species are inherently resistant to fluconazole (C. krusei) or partially resistant being only dose-dependently susceptible (C. glabrata) [2]. Here we describe a clinical case of a preterm infant who carried significant management problems related to his status of colonisation by one of these Candida species that are characterised by variable fungal resistance to fluconazole. Case report: G.C., female, born by emergency cesarean section for placental abruption at 33+2 weeks, with birth weight of 1270 g, Apgar 6/7 at 1st and 5th minute. The mother was treated with prednisone throughout the whole pregnancy for ulcerative colitis. The newborn manifested a good and rapid postnatal adaptation, and maintained well and asymptomatic during the first week of admission to NICU. Serum inflammatory indexes (CRP) always remained normal. Buffer Headset performed on day 1 of life was negative. As a routine, at 3rd day of life, the baby started prophylaxis with fluconazole at a dose of 6 mg/kg every other day, and performed weekly culture surveillance tests. These cultures highlighted the presence of C. glabrata on day 2nd (culture from endotracheal tube), and C. glabrata again on day 8th (culture from stool and gastric aspirate). The culture of Umbilical Catheter performed in 5th day was negative. Susceptibility testing performed on the fungal colonies of C. glabrata retrieved at cultures showed MIC90 comprised between 4 and 8. On 8th and 9th day severe neutropenia was detected (neutrophils <1000/mmc), and therefore – in view of increased baseline risk for sepsis – therapy with G-CSF was instituted (1 dose/day for 3 days) with normalisation of WBC count on day 11th. Despite persisting normality of clinical course, a culture from CVC performed on day 16th turned out positive for C. glabrata. At this point, given the risk of systemic dissemination, we decided to discontinue prophylactic fluconazole therapy and to start systemic treatment with liposomal amphotericin B at a dose of 3→5 mg/kg/day for 15 days. The neonate evoved regularly, all cultures performed on 3rd, 4th and 5th weeks of life turned negative, and on day 35th day she could be discharged without any need of treatment, nor any sequelae. Discussion: One of the major risk factors for the development of sepsis is the fungal colonisation by Candida species, however the variables associated with the progression from colonisation to fungal infection in neonates colonised are still poorly known. Fluconazole is reported to have a good preventive and therapeutic effect on colonisation and infection by most strains of Candida species, and is well tolerated without side effects. A limited number of Candida species, mainly including C. glabrata, are reported to have a dose-dependent susceptibility to fluconazole itself. This finding implies that the use of fluconazole in treatment is not indicated, however no data todate exist on its use in prophylaxis in such cases. In our clinical report, the choice to perform prophylaxis with fluconazole in this neonate has been dictated by the opportunity to limit the