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Reflections on PDA treatment strategies among neonates with gestational age less than 26 weeks

The objective of this study was to measure lutein and zeaxanthin plasma levels after oral lutein administration in preterm infants. Lutein was given orally in a single dose of 0.5 mg/kg to 10 preterm infants at a mean age of 52 h of life. Plasma lutein and zeaxanthin were measured before and 6, 24, 48, and 120 h after lutein administration. All infants had detectable plasma levels of lutein and zeaxanthin before treatment. Lutein concentration increased by 13.5% at 6 h and by 16.7% at 24 h, and returned to the basal level at 120 h after treatment. Zeaxanthin remained unchanged during the study period. Lutein is well absorbed in preterm infants when given orally. The clinical impact of increasing plasma lutein concentrations on macular development and visual function needs further investigation.

OBJECTIVE: The goal was to assess the feasibility of earlier weaning from the incubator for preterm infants. METHODS: This was a prospective, randomized study with preterm infants with birth weights of <1600 g who were admitted to a neonatal subintensive ward. Findings for 47 infants who were transferred from an incubator to an open crib at >1600 g (early transition group) were compared with those for 47 infants who were transferred from an incubator to an open crib at >1800 g (standard transition [ST] group). The primary outcome of the study was length of stay. Secondary outcomes were the number of infants returned to an incubator, the growth velocity in an open crib and during the first week at home, the proportions of breastfeeding at discharge and during the first week at home, and the hospital readmission rate. RESULTS: The length of stay was significantly shorter in the early transition group than in the standard transition group (23.5 vs 33 days; P=.0002). No infants required transfer back to the incubator. Only 1 infant in the standard transition group was readmitted to the hospital during the first week after discharge. Growth velocities and individual amounts of breastfeeding were similar between the 2 groups. CONCLUSION: In this study, weaning of moderately preterm infants from incubators to open cribs at 1600 g was safe and resulted in earlier discharge.

OBJECTIVE: The goal was to assess the feasibility of earlier weaning from the incubator for preterm infants. METHODS: This was a prospective, randomized study with preterm infants with birth weights of <1600 g who were admitted to a neonatal subintensive ward. Findings for 47 infants who were transferred from an incubator to an open crib at >1600 g (early transition group) were compared with those for 47 infants who were transferred from an incubator to an open crib at >1800 g (standard transition [ST] group). The primary outcome of the study was length of stay. Secondary outcomes were the number of infants returned to an incubator, the growth velocity in an open crib and during the first week at home, the proportions of breastfeeding at discharge and during the first week at home, and the hospital readmission rate. RESULTS: The length of stay was significantly shorter in the early transition group than in the standard transition group (23.5 vs 33 days; P=.0002). No infants required transfer back to the incubator. Only 1 infant in the standard transition group was readmitted to the hospital during the first week after discharge. Growth velocities and individual amounts of breastfeeding were similar between the 2 groups. CONCLUSION: In this study, weaning of moderately preterm infants from incubators to open cribs at 1600 g was safe and resulted in earlier discharge.

BACKGROUND: Candida colonization is an important predictor for development of invasive fungal infection (IFI). We investigated whether early detection of Candida mannan (Mn) in bronchoalveolar lavage fluid (BALF) reduces IFI among preterm infants. METHODS: We conducted an observational study of infants with gestational age of < or =28 weeks, where a group undergoing Candida surveillance cultures (pre-Mn detection group) was compared with a group defined after the initiation of routine use of Candida Mn detection in BALF (Mn detection group). Antifungal treatment was started based on positive microbiologic (surveillance culture or Mn-antigen assay) results. RESULTS: No significant differences were detected when the groups were compared for several predictors of IFI. IFI was observed for 12 (23%) of 51 infants in the pre-Mn detection group, and for 0 (0%) of 29 infants in the Mn detection group (P = 0.003). Surveillance cultures in the pre-Mn detection group became positive at 15.0 +/- 7.2 days after birth, whereas the mean age at time of positive Mn antigen results in the Mn detection group was 4.3 +/- 3.1 days (P < 0.0001). Among 16 infants positive for surveillance cultures, 12 (75%) developed IFI (P < 0.0001). CONCLUSIONS: This study suggests that Candida Mn detection in BALF may be useful for earlier identification and preemptive therapy targeting preterm infants at high risk of IFI.

BACKGROUND: Few neurological assessments are easily performed during the first 6h after birth. AIMS: To assess a cohort of low risk term born newborns within the first 6h and at 48h after birth using the Hammersmith Neonatal Neurological Examination. STUDY DESIGN AND SUBJECTS: A population of low risk term born newborns was examined within 3h from birth or between 3 and 6h. Each infant was re-assessed at 48h, establishing the range and frequency distribution of neonatal neurological scores at each time point. RESULTS: Of the 124 full-term born newborns, 62 were assessed at 0-3h and 62 at 3-6h. All infants were re-assessed at 48h. For 23/34 of the neurological items, the range and median scores were similar across the 3 time points. In the remaining 11 items the three groups had a similar range of scores but the median scores were different with different rates of changes. In 6 of the 11 the median scores at 3-6h were similar to those observed at 48h but they appeared to be 'less mature' at 0-3h. Only in one item the median scores were consistently different at the 3 time points. CONCLUSIONS: Our results suggest that a neurological examination can already be reliably performed soon after birth. These findings will help in the interpretation of the few items that show changes with increasing postnatal age.

BACKGROUND: The analysis of early patterns of lung disease among preterm infants may help to identify predictors of pulmonary deterioration. OBJECTIVES: To analyze FIO2 requirement in the first 14 days of life among preterm infants and to find predictors of bronchopulmonary dysplasia (BPD). METHODS: Retrospective cohort study. SETTING: 3 Italian level III NICUs. POPULATION: infants born between 240/7 and 276/7 weeks' gestational age (GA) who survived to 14 days. A consecutive sample of 588 infants was analyzed. Daily mode FIO2 in the first 2 weeks of life were analyzed according to the criteria defined by Laughon et al. [Pediatrics 2009;123:1124-1131], who found 3 early respiratory patterns: consistently low FIO2 (LowFIO2), pulmonary deterioration (PD), and early persistent pulmonary deterioration (EPPD). Factors associated with pulmonary deterioration were studied by univariate and multivariate analysis. RESULTS: Forty percent of infants had low FIO2, 18% had pulmonary deterioation, 21% had early persistent pulmonary deterioration, and 21% had a previously unreported pattern (pulmonary improvement, PI). The prevalence of BPD was 7% in the LowFIO2 group, 28% in the PI group, 44% in the PD group, and 62% in the EPPD group (p = 0.000). Infants with lung deterioration were more frequently males (OR = 2.019, CI: 1.319-3.090, p = 0.001), had lower GA (OR = 0.945, CI: 0.915-0.975, p = 0.000), higher incidence of severe respiratory distress syndrome (OR = 2.956, CI: 1.430-6.112, p = 0.003), and lack of postnatal caffeine (OR = 0.167, CI: 0.052-0.541, p = 0.003). CONCLUSIONS: We report 4 distinct patterns of early respiratory disease associated with significantly different prevalence of BPD and discuss risk factors for lung deterioration.

BACKGROUND: Increased activity of the renin-angiotensin-aldosterone system (RAAS) has been reported in the neonatal period. Until now, it has been demonstrated that the RAAS of healthy neonates responds to acute furosemide challenge while no data concerning the responsiveness of RAAS in extremely low birth weight (ELBW) infants are available. OBJECTIVE: To assess urinary aldosterone excretion (UAE) and renal function in ELBW infants who received diuretics for the purpose of reducing the incidence of chronic lung disease (CLD). METHODS: Infants with birth weights < or =1,000 g, at high risk to develop CLD, were studied in a prospective observational study. UAE and renal function were investigated before and after administration of furosemide given in a single dose of 2 mg/kg. RESULTS: UAE and renal function were evaluated in 20 ELBW infants. Diuretic administration resulted in a significant rise in UAE and urinary sodium, potassium and chloride excretion. No change occurred in creatinine clearance, while urine volume increased significantly. CONCLUSIONS: ELBW infants respond to acute furosemide challenge by increasing urine volume, urinary electrolytes and UAE.

Retinopathy of prematurity (ROP) is a multifactorial disease which incidence is increasing with increasing survival of very preterm infants. Pathogenic pathway is characterised by abnormal retinal vascular development modulated by vascular growth factors: low IGF-1 in the first phase and high VEGF in the second phase. Many causal factors are able to influence retinal vascularization: gestational age, birth weight, oxygen administration, perinatal bacterial or fungal infections, and blood transfusions. All risk factors, both oxygen and not-oxygen-regulated, have been studied considering the whole period from hospital birth to the hospital discharge, but it is possible that postnatal risk factors may be determinant in a time-dependent way. Analysis of factors involved in the pathogenesis of ROP suggests that their action begins long before anatomical clinical features become appreciable and this is strengthened by the essential role of risk factors from the first two to four weeks of life, thus preventive strategies in very preterm infants should be carried out since birth.

BACKGROUND: The few existing studies evaluating the reliability of transcutaneous bilirubin monitoring during phototherapy gave controversial results. AIMS: To evaluate the accuracy of transcutaneous bilirubin measurement in a large population of newborn infants, during phototherapy. STUDY DESIGN AND METHODS: Total serum bilirubin and transcutaneous bilirubin on patched and unpatched skin areas were simultaneously measured in newborn infants undergoing phototherapy. Transcutaneous measurements were performed with a multiwavelength transcutaneous bilirubinometer (Respironics BiliCheck). The Passing-Bablok regression and the Bland-Altman plot were used to estimate the relationship between serum and transcutaneous bilirubin. RESULTS: We studied 364 newborn infants with a mean (SD) gestational age of 34.6 (3) weeks and a mean birth weight of 2371 (805) grams. Total serum bilirubin, patched transcutaneous bilirubin and unpatched transcutaneous bilirubin were similar before phototherapy. After 52 (33) hours of phototherapy, the difference between serum bilirubin and patched transcutaneous bilirubin was 0.2 (3.1) mg/dL (not significant) while the difference between serum bilirubin and unpatched transcutaneous bilirubin was 3.2 (3.0) mg/dL (p<0.001). Statistical analysis showed a good agreement between serum bilirubin and patched transcutaneous bilirubin, while unpatched transcutaneous bilirubin underestimates serum levels. The difference between patched and unpatched values was significantly lower in preterm than in term infants (2.8 mg/dL vs. 3.6 mg/dL; p<0.001). CONCLUSION: BiliCheck can be safely used for the evaluation of bilirubin levels in newborn infants under phototherapy. Its reliability on patched skin of the forehead is high enough to consistently reduce blood draws and to ascertain when to discontinue phototherapy. Because of the individual variance, any clinical decision has to be taken on the basis of the transcutaneous bilirubin trend more than on a single v

BACKGROUND: Thymosin beta(4), its sulfoxide, and thymosin beta(10) were detected in whole saliva of human pre-term newborns by reversed-phase high performance chromatography coupled to electrospray ion-trap mass spectrometry. METHODOLOGY/PRINCIPAL FINDINGS: Despite high inter-individual variability, concentration of beta-thymosins increases with an inversely proportional trend to postmenstrual age (PMA: gestational age plus chronological age after birth) reaching a value more than twenty times higher than in adult whole saliva at 190 days (27 weeks) of PMA (thymosin beta(4) concentration: more than 2.0 micromol/L versus 0.1 micromol/L). On the other hand, the ratio between thymosin beta(4) and thymosin beta(10) exhibits a constant value of about 4 along all the range of PMA (190-550 days of PMA) examined. In order to investigate thymosin beta(4) origin and to better establish the trend of its production as a function of gestational age (GA), immunohistochemical analysis of major and minor salivary glands of different pre-term fetuses were carried out, starting from 84 days (12 weeks) of gestational age. Reactive granules were seen in all glands with a maximum of expression around 140-150 days of GA, even though with high inter- and intra-individual variability. In infants and adults reactive granules in acinar cells were not observed, but just a diffuse cytoplasmatic staining in ductal cells. SIGNIFICANCE: This study outlines for the first time that salivary glands during foetal life express and secrete peptides such as beta-thymosins probably involved in the development of the oral cavity and its annexes. The secretion increases from about 12 weeks till to about 21 weeks of GA, subsequently it decreases, almost disappearing in the period of expected date of delivery, when the gland switches towards the secretion of adult specific salivary peptides. The switch observed may be an example of further secretion switches involving other exocrine and endocrine glands duri

BACKGROUND: Doppler US to measure abdominal blood flow velocities (ABFV) is increasingly used to investigate intestinal haemodynamics in several clinical conditions in neonates. Studies that provide reference values of ABFV during the entire neonatal period are currently lacking. OBJECTIVE: To make available normal reference values of ABFV and Doppler indices in the coeliac trunk and superior mesenteric artery during the first month of life in term and healthy preterm infants. MATERIALS AND METHODS: ABFV were obtained with colour Doppler US in 69 neonates (12 term, 57 preterm) divided into four gestational age groups (25-28 weeks, 29-32 weeks, 33-36 weeks, and 37-41 weeks). RESULTS: ABFV increased with increasing gestational and postnatal age. We also provide normal reference values of ABFV and Doppler indices to compare with measurements of abdominal blood flow changes during the neonatal period for diagnostic, therapeutic and prognostic purposes. CONCLUSION: These longitudinal reference values provide a useful tool for assessing possible alteration in ABFV secondary to neonatal pathologies.

Background: Thymosin beta(4), its sulfoxide, and thymosin beta(10) were detected in whole saliva of human pre-term newborns by reversed-phase high performance chromatography coupled to electrospray ion-trap mass spectrometry. Methodology/Principal Findings: Despite high inter-individual variability, concentration of beta-thymosins increases with an inversely proportional trend to postmenstrual age (PMA: gestational age plus chronological age after birth) reaching a value more than twenty times higher than in adult whole saliva at 190 days (27 weeks) of PMA (thymosin beta(4) concentration: more than 2.0 mu mol/L versus 0.1 mu mol/L). On the other hand, the ratio between thymosin beta(4) and thymosin beta(10) exhibits a constant value of about 4 along all the range of PMA (190-550 days of PMA) examined. In order to investigate thymosin beta(4) origin and to better establish the trend of its production as a function of gestational age (GA), immunohistochemical analysis of major and minor salivary glands of different pre-term fetuses were carried out, starting from 84 days (12 weeks) of gestational age. Reactive granules were seen in all glands with a maximum of expression around 140-150 days of GA, even though with high inter-and intra-individual variability. In infants and adults reactive granules in acinar cells were not observed, but just a diffuse cytoplasmatic staining in ductal cells. Significance: This study outlines for the first time that salivary glands during foetal life express and secrete peptides such as b-thymosins probably involved in the development of the oral cavity and its annexes. The secretion increases from about 12 weeks till to about 21 weeks of GA, subsequently it decreases, almost disappearing in the period of expected date of delivery, when the gland switches towards the secretion of adult specific salivary peptides. The switch observed may be an example of further secretion switches involving other exocrine and endocrine glands during foeta

We read with great interest the article by Healy et al,1 who evaluated the impact of fluconazole prophylaxis (FP) for extremely low birth weight infants on invasive candidiasis (IC) incidence, IC-related mortality rates, and fluconazole susceptibility of Candida isolated. We wish to make some comments thereon. Healy et al1 demonstrated a decrease of IC in NICU infants, after the introduction of FP, from 0.6% to 0.3%, and a 3.6 fold decrease in ELBW infants. Recent studies have demonstrated that prophylactic use of fluconazole is effective in reducing the incidence of fungal colonization and fungal systemic infections in preterm neonates.2,3 However, because of the lack of larger multicenter randomized trials and data on long term neurodevelopment outcomes as well as concern about unwanted side effects and development of Candida resistance, FP in high risk infants remains controversial. For these reasons, selecting only those infants at highest risk for IC may delay or prevent the emergence of resistance. In recent studies, the criteria chosen to identify “the high-risk neonate” were <1500 g birth weight (BW) and the presence of a central vascular catheter or endotracheal tube.4 These criteria seem to be too wide, because they could regard almost all the population sheltered in a NICU. In our NICU, FP as well as antibiotic prophylaxis did not exist, and Candida-related mortality was nearly 20% in extremely low birth weight infants. To prevent IC, we introduced a protocol of Candida surveillance cultures from stool and bronchoalveolar lavage fluid in intubated infants, and every infant who developed IC was identified and IC-related mortality was eliminated.5 All neonates with IC had a BW of <1000 g, and 15 (94%) of 16 had a gestational age of <27 weeks. Therefore, from our data, neonates with a gestational age of <27 weeks and BW of <1000 g represent the “preterm subpopulation” that would benefit most from FP. A more-precise identification of the higher-risk neonates

OBJECTIVES: To know the mother's frequency with TRAb (TSH receptor antibodies) positivity during pregnancy in the population afferent to Agostino Gemelli Hospital in the five years 2002-2007 and the itself antibodies's role determining fetal and neonatal symptoms. MATERIALS AND METHODS: We performed a prospective analysis with maternal and neonatal variables detection in 16 couples mother-newborn with TRAb positivity during the pregnancy. The method to dose neonatal TRAb is ELISA (enzyme linked immunosorbant assay). RESULTS: The prevalence of newborns of mothers with TRAb positivity during pregancy results 0.1 per thousand (16/16783). The prevalence of neonatal hyperthyroidism, clinical and biochemical, in the studied population results especially elevated equal to about 30% (5/16). The 5 newborns are born to mothers with Basedow disease with TRAb serum levels greater than TRAb levels of newborn without hyperthyroidism: 2 are showed the symptoms of clinical hyperthyroidism and 3 a transient biochemical hyperthirodism. 3 newborns with hyperthyroidism among 5 are born to mother undergo thyroidectomy with L-tiroxina teraphy during the pregnancy. Then the newborns of thyroidectomized mothers also many years before the pregnancy must be considered high risk of developing neonatal hyperthyroidism because of long-lasting persistence of mother's TRAb. The neonatal hyperthyroidism, clinical and biochemical, appears later in newborns of mothers using antithyroid drugs. The pharmacological treatment of neonatal hyperthyroidism was difficult to standardize and highly individualized. CONCLUSIONS: Although the neonatal hyperthyroidism is a very rare disease it is essential to apply specific protocol assistance, both during pregnancy and the neonatal period, in the presence of maternal TRAb positive for the risk of serious cardiovascular complications.

Treatment with activated protein C has been shown to reduce mortality in adult patients with severe sepsis but also to increase risk of bleeding. In patients with predisposition to bleeding, as in preterm infants, the inactivated form of protein C could serve as a safe therapeutic option. We report the case of a preterm neonate who developed severe sepsis on the 28th day of life, who was successfully treated with the inactivated form of protein C for a period of 96 hours.

OBJECTIVE: Intrahepatic cholestasis of pregnancy (ICP) has been associated with prematurity and fetal mortality. Recently, ICP has also been recognised as a risk factor for neonatal respiratory distress syndrome (RDS) in term or near-term neonates. Since fetal mortality is more frequent in pregnancies with an early ICP onset, we speculated that the time of exposure (ET) to maternal bile acids at the delivery (BAdeliv) could be involved in neonatal lung damage too. Study aim was to develop a scoring system to predict the RDS occurrence. DESIGN: We conducted a retrospective analysis of 77 pregnancies complicated by ICP (years 2000-2004) looking for factors associated to the neonatal RDS. We developed a risk score as follows: RDS risk score=BAdeliv x ET/gestational age and we prospectively applied it to 30 neonates from ICP pregnancies (years 2005-2006). RESULTS: ROC analysis indicated 9 as the score with the highest sensitivity (83.3%) and specificity (87.5%). Considering a RDS incidence of about 25% in babies coming from ICP pregnancies, the post-test probability showed a risk increased to 66.7% with a score>9 and reduced to 4.8% with a score

BACKGROUND: Recently, a new sensor for combined assessment of pulse oximetry oxygen saturation (Spo(2)) and transcutaneous monitoring of carbon dioxide partial pressure (PtcCO(2)) has been introduced (TOSCA 500, Radiometer basel AG, Switzerland) [corrected] We designed this study to evaluate the usability and reliability of TOSCA in neonates with birth weight

Application of a neonatal assessment of visual function in a population of low risk full-term newborn.

OBJECTIVES: The objectives of this study were to (1) assess visual function in low-risk preterm infants at 35 and 40 weeks' postmenstrual age, (2) compare preterm visual abilities at term-equivalent age with term-born infants, and (3) evaluate effects of preterm extrauterine life on early visual function. METHODS: Visual function was assessed by using a validated test battery at 35 and 40 weeks' postmenstrual age in 109 low-risk preterm infants who were born at <31 weeks' gestation. The preterm findings were compared with data from term-born infants collected by using the same test protocol. RESULTS: All preterm infants completed both assessments. The 35-week responses were generally less mature than those at 40 weeks. Preterm infants at both ages were significantly more mature than term-born infants for ocular movements and vertical and arc tracking and at 40 weeks for stripe discrimination. In contrast, tracking a colored stimulus, attention at distance, and stripe discrimination were more mature at term age (in both term-born and preterm infants) than at 35 weeks. CONCLUSIONS: Our findings provide data for visual function at 35 and 40 weeks' postmenstrual age in low-risk preterm infants. The results suggest that early extrauterine experience may accelerate the maturation of aspects of visual function related to ocular stability and tracking but does not seem to affect other aspects that may be more cortically mediated.

We report on a premature infant with glucose-6-phosphate dehydrogenase deficiency and severe hyperbilirubinemia. In this patient, all known potential hemolytic agents were excluded and no findings of hemolysis were observed. The crucial role of prematurity in the pathogenesis of this type of jaundice is discussed.

BACKGROUND: We previously reported the neurological findings of the Dubowitz neonatal examination in a cohort of 157 low-risk preterms born between 25 and 33 weeks gestational age (GA) and examined at term equivalent age (TEA). Median and range of scores were wider than those found in term-born infants and preterms showed a different neurological behaviour in specific items. However, the cohort number was too small to draw any definitive conclusion about the distribution of findings. AIMS: We provide normative data from a low-risk cohort of 380 preterm infants; we also assess the findings and their relationship to motor outcome in preterms with major cranial ultrasound (US) abnormality. STUDY DESIGN: We assessed, at TEA, 380 low-risk preterms born <35 weeks gestation (range 25-34.9, median 29) with normal 2 year motor outcome and 85 preterm infants with major US abnormality. RESULTS: At TEA low-risk preterms had less flexor limb tone, poorer head control but better visual following than term-born infants. For 28/34 of the neurological items the range and median scores were similar across gestational ages. In infants with major US lesions the range and median scores differed from low-risk preterms in 20/34 items; 40% of infants developing a diplegia and 80% developing a tetraplegia had >7 items outside the 90th centile; all infants with >12 items outside the 90th centile developed a tetraplegia. CONCLUSIONS: We provide reference values for the neurological examination of low-risk preterms at TEA. In infants with major US abnormality the number of items outside the 90th centile was an indicator of outcome severity.

Our aim was to study the usefulness of jaundice visual assessment combined with skin bilirubin determination in 517 healthy newborns. Yellowness assessment was made and babies were included in three different bilirubin classes. Skin bilirubin and total serum bilirubin were determined within 10 minutes from the visual assessment. This latter led to underestimation of serum bilirubin in 16.7-40.4% and overestimation in 4.9-35.7% of newborns. Skin bilirubin measurement after the visual assessment decreased the risk of underestimation to 0-9.2% and the risk of overestimation to 2.1-11.1%. The majority of visual assessment errors were performed in the more lighted hours of the morning (75%), while the smallest number (39%) occurred during the afternoon. Skin bilirubin measurement significantly corrected these diagnostic errors (p < 0.001, p < 0.02) without differences during the day. Clinical estimate is unreliable for evaluating the need for serum bilirubin assay. Using the addition of skin bilirubin determination is a more advisable approach.

Percutaneous long lines, routinely used in preterm infants, can be associated with several cardiac complications such as pericardial effusion and consequent cardiac tamponade. We report three patients with pericardial effusion highlighting the importance of cardiac ultrasound monitoring to both early diagnosis and treatment.

Patency of the ductus arteriosus (PDA) and bronchopulmonary dysplasia (BPD) development represent severe affections for premature newborns, therefore the research of early markers for these two conditions is really important. The aim of this study is to analyze epithelial lining fluid (ELF) Neutrophil-gelatinase-associated lipocalin (NGAL) levels for prediction of lung injury or possible involvement of this molecule in PDA. Only scarce and contrasting results have previously been published in this field. In contrast, this molecule, included in a large macromolecular complex together with matrix metalloproteinase-9 (MMP-9), is considered an acceptable marker of infectious/inflammatory processes, cancer monitoring and induction of apoptotic pathway. NGAL was detected in 28 pre-term newborns by means of a commercially available kit in bronchoalveolar lavage fluid (BALF). The results have been corrected to ELF levels, by the urea method, to eliminate bias due to BALF collection. ELF NGAL levels were found significantly increased both in infants developing BPD or in those affected by PDA. By means of multivariate logistic regression analysis the significances were confirmed after adjusting for possible interfering variables such as gestational age and concomitant presence of both PDA and BPD. Our results stress the involvement of NGAL in the mechanisms leading to BPD and also suggest a possible association with PDA, which is often linked to prematurity and BPD development, probably due to the involvement of inflammatory and angiogenetic processes in both pathologies.

No abstract available

AIM: Hour-specific nomogram evaluation of serum or skin bilirubin is a suitable approach for managing neonatal hyperbilirubinemia and it is recommended by American Academy of Paediatrics. We aimed to provide data about skin bilirubin levels during the natural course of hyperbilirubinemia in European healthy neonates. METHODS: We enrolled 2198 healthy newborn infants (gestational age [GA]>or= 35 weeks), from 24 to 96 h of life and performed transcutaneous bilirubin (TcB) measurement, in order to draw the nomogram for 10th, 25th, 50th, 75th and 95th percentiles of skin bilirubin, both for term and near term babies. All measurements were performed with a multiwavelength transcutaneous bilirubinometer (Respironics BiliCheck), within 2 h of the designed time and data were analysed with linear and local smoother regression. RESULTS: We described the peculiar pattern of skin bilirubin increasing rate over different time periods. Bilirubin linearly increases rapidly in the first 48 h and less rapidly from 48 to 72 h, while the increment is insignificant from 72 to 96 h. Conclusion: We provide the first data on skin bilirubin trend in a large predominantly breastfed and healthy European newborn population during the natural course of nonpathologic hyperbilirubinemia. Nomogram and increment rate of skin bilirubin are useful to identify neonates requiring closer evaluation and to plan an adequate follow-up.

Massive fetomaternal hemorrhage (FMH) occurs in approximately 1:1,000 deliveries. In most cases, the cause is not identified. The clinical manifestations and the prognosis of a FMH depend on the volume of the hemorrhage and the rapidity with which it has occurred. We describe two cases of chronic massive fetomaternal hemorrhage with favorable outcome. During the follow-up, both infants showed late-onset neutropenia, which was not previously reported in healthy, growing infants with history of massive FMH

Hepatic hematomas in neonates are uncommon lesions. When they are large or subcapsular in location, they can rupture with clinical signs of hemoperitoneum. We report a case of subcapsular hepatic hematoma (SHH) associated with a high level of alpha-fetoprotein (AFP), for which diagnosis was made with conservative management, following up with the reduction in size at ultrasound examination and the reduction of the level of AFP.

PURPOSES: Secretory phospholipase A2 hydrolyzes phosphoglycerides and it has been shown to be involved in alveolar inflammation and surfactant degradation. It plays an important role in acute lung injury but it has never been studied in newborn infants. We were aimed to investigate the phospholipase A2 activity in neonatal lung injury and its relationship with ventilatory findings. SETTING: Third level university hospital NICU. METHODS: We measured phospholipase activity in broncho-alveolar lavage fluid of 21 neonates with hyaline membrane disease, 10 with pneumonia or sepsis and 10 controls, ventilated for extrapulmonary reasons. Fluid was obtained before surfactant administration on the first day of life and phospholipase activity was measured using an ultrasensitive enzymatic method. Before lavage, lung mechanics in pressure controlled synchronized intermittent mandatory ventilation was analyzed. RESULTS: Phospholipase A2 was higher in babies ventilated for sepsis/pneumonia compared to hyaline membrane disease and to control babies. Phospholipase correlated negatively with dynamic compliance, positively with inspired oxygen fraction, mean airway pressure and oxygenation index. These correlations still remained significant after multivariate analysis, adjusting for possible confounding factors. Phospholipase was not correlated with blood and alveolar pH, gestational age, birth weight, blood gases, Apgar score, tidal volume, surfactant need and ventilation time. CONCLUSIONS: These are the first data about phospholipase A2 in neonates. The enzyme plays a role in neonatal lung injury, especially in infection related respiratory failure. It is associated with lung stiffness, higher mean airway pressure and need for oxygen.

OBJECTIVES: Neonatal respiratory distress syndrome is associated with intrahepatic cholestasis of pregnancy, and bile acids may play a major role in neonatal bile acid pneumonia. Our aim was to demonstrate the bile acid presence in the bronchoalveolar lavage fluid of neonates affected by respiratory distress syndrome who were born from intrahepatic cholestasis of pregnancy and to investigate bile acid mechanisms of action in acute lung injury. METHODS: In this prospective study, we enrolled 10 neonates delivered from intrahepatic cholestasis of pregnancy, affected by respiratory distress syndrome requiring mechanical ventilation (intrahepatic cholestasis of pregnancy group) and 2 control groups. The first group consisted of 20 infants with respiratory distress syndrome delivered from pregnancies without any sign of intrahepatic cholestasis of pregnancy (respiratory-distress-syndrome group), and the second group included 20 neonates with no lung disease who were ventilated for extrapulmonary reasons (no-lung-disease group). We measured bile acid and pH in the bronchoalveolar lavage fluid and serum bile acid levels in the first 24 hours of life. RESULTS: Bile acids were measurable in the bronchoalveolar lavage fluid of all of the infants in the intrahepatic cholestasis of pregnancy group but were absent in the 2 control groups. Bronchoalveolar lavage fluid pH was not different among the 3 groups. Infants in the intrahepatic-cholestasis-of-pregnancy group had significantly higher serum bile acid levels compared with those in both of the control groups. CONCLUSIONS: Bile acids are detectable in the bronchoalveolar lavage fluid of newborns from intrahepatic cholestasis of pregnancy affected by respiratory distress syndrome. Elevated serum bile acid levels in these infants allow us to hypothesize that bile acid reaches the lung after an uptake from the circulation. These findings strongly support a role for bile acid in causing bile acid pneumonia.

Alloimmune thrombocytopenia (AIT) is an important cause of intrauterine hemorrhagic lesions that result from platelet-antigen incompatibility between mother and foetus. Foetal platelets are destroyed by cross-reactive maternal antibodies that cross the placenta. The most serious complication of AIT is foetal intracranial bleeding that may eventually result in intrauterine death or severe neurological impairments.

The role of Candida surveillance cultures for identification of a preterm subpopulation at hightest risk for invasive fungal infection

Secrecy and anonymity related to heterologous assisted reproduction may hide basic newborn data to neonatologists. Secrecy and anonymity are discussed in view of their possible consequences on relational dynamics and on developmental psychology. Nevertheless, they can also involve the offspring's genetic status regarding inheritable diseases. International guidelines have been recently published on this topic. Because no guidelines are 'ideal' unfortunate and possibly dramatic consequences can occur. We aimed to embark on a debate about this matter starting with a real clinical experience. In our case a rarely fatal but widespread disease, together with the lack of knowledge about parental status led, in a fast succession of clinical events, to the unavoidable insurgence of kernicterus.

OBJECTIVE: Intrahepatic cholestasis of pregnancy (ICP) has been associated with prematurity and fetal mortality. Recently, ICP has also been recognised as a risk factor for neonatal respiratory distress syndrome (RDS) in term or near-term neonates. Since fetal mortality is more frequent in pregnancies with an early ICP onset, we speculated that the time of exposure (ET) to maternal bile acids at the delivery (BAdeliv) could be involved in neonatal lung damage too. Study aim was to develop a scoring system to predict the RDS occurrence. DESIGN: We conducted a retrospective analysis of 77 pregnancies complicated by ICP (years 2000-2004) looking for factors associated to the neonatal RDS. We developed a risk score as follows: RDS risk score=BAdeliv x ET/gestational age and we prospectively applied it to 30 neonates from ICP pregnancies (years 2005-2006). RESULTS: ROC analysis indicated 9 as the score with the highest sensitivity (83.3%) and specificity (87.5%). Considering a RDS incidence of about 25% in babies coming from ICP pregnancies, the post-test probability showed a risk increased to 66.7% with a score>9 and reduced to 4.8% with a score

AIM: The aim of this paper was to evaluate usefulness and safety of Meropenem in severe infections in neonatal intensive care unit (NICU) patients. New broad spectrum carbapenem class of -lactam antibiotics has been investigated for the treatment of a wide range of infections, including nosocomial infections with cephalosporin-resistant pathogens, an emergent problem in NICU, and meningitis. Meropenem represents the first cabapenem-class that has received Food and Drug Administration (FDA) approval for use in children 3 months of age and older. The pharmacokinetics of Meropenem has been well studied in preterm neonates. METHODS: We report the use of Meropenem in 26 neonates with median gestational age (GA) of 27 weeks (25-32) and median birth weight of 940 g (510-1900), with severe infections due to Gram-negative or Gram-positive organisms, from 2001 to 2004. The median postnatal age was 21 days (4-75). Meropenem was administrated intravenously in 30 min at dosage of 20 mg/kg every 12 h (every 8 h in Pseudomonas Aeruginosa infections). RESULTS: In all cases Meropenem has been used as second choice. No adverse effects (eosinophilia, trombocytosis or thrombocytopenia, increase in liver enzyme, increase in creatinine, diarrhea, vomiting and seizures) were observed. Clinical and bacterial response was ontaine in all cases but one. CONCLUSIONS: This report suggests that Meropenem may be a useful and safe antimicrobial agent in neonatal infections caused by resistant organisms and in meningitis. Further studies are needed to confirm these results

Many studies have recently analyzed the modulation of the intestinal microflora showing a benefic effects reducing the number of enteritis, improving the oligoelements absorption and stimulating the immunitary system. To do so three way are available: the use of prebiotics, the use of probiotics and the symbiotic way. Prebiotics are non-digestible oligosaccharides that can stimulate selectively the growth bifidogenus bacteria. Probiotics are dietary supplements made of live micro-organisms which improve the microbial environment of the gut. In this review literature is examined the possible efficacy of prebiotics and probiotics in the pediatric age; however, the studies available do not permit to obtain definitive conclusions

OBJECTIVE: Mannose-binding lectin (MBL2) is a collectin molecule able to activate the complement system and the subsequent inflammatory mechanisms. Several MBL2 genetic variants have been described, including the six variants studied in this report, which are those analyzed in most detail in the medical literature. DESIGN: The present study analyzes the prevalence of MBL2 gene variants in preterm newborns and associates individual genotypes with pulmonary outcome variables. All polymorphisms were analyzed by means of a commercially available reverse dot-blot kit. SETTING: Tertiary neonatal intensive care unit. PATIENTS AND PARTICIPANTS: Seventy-five consecutive preterm newborns. MEASUREMENTS AND RESULTS: Two variants were particularly analyzed: -550G > C and R52C. The first one is known to be associated with lower protein synthesis when included in specific haplotypes. The homozygous and heterozygous -550G > C mutations were significantly associated with protective effects regarding different lung outcome variables, including shorter duration of mechanical ventilation, hours of continuous positive airway pressure and lower number of hemotransfusions. In contrast, the heterozygous R52C mutation was associated with unfavorable outcome, including higher bronchopulmonary dysplasia prevalence. Multivariate logistic regression analysis showed that these associations were independent of gestational age and birth weight. In addition, four groups of patients were defined on the basis of haplotype combinations. Those known to be associated with low serum MBL2 levels were linked to a better outcome in terms of factors such as hours of mechanical ventilation, continuous positive airway pressure, number of hemotransfusions and bronchopulmonary disease development. CONCLUSIONS: The four haplotype combination groups may have a potential diagnostic use as opposite risk factors for lung disease of prematurity

A 1 year follow-up investigation of salivary acidic proline-rich proteins (aPRPs) in preterm and at-term newborns using HPLC-ESI-IT-MS showed that (i) this class of proteins is constitutive rather than inducible, as it is still found in the oral cavity of preterm newborns from 180 days of postconception age (PCA); (ii) the expression of PRH-2 locus anticipates that of PRH-1, since Db isoforms are expressed some months after the PRP-1 and PRP-2 isoforms. The evaluation of the relative abundances of the different aPRPs isoforms and derivatives (differently phosphorylated and cleaved) as a function of PCA showed that (iii) the proteolytic enzymes generating truncated isoforms are also constitutive because they are fully active since 180 days of PCA; (iv) the kinase involved in aPRP phosphorylation is not fully mature in preterm newborns, but its activity increases with PCA, synchronizing with that of at-term newborns and reaching the adult levels at about 500-600 days of PCA, in concomitance with the beginning of deciduous dentition.

Hepatic hematomas in neonates are uncommon lesions. When they are large or subcapsular in location, they can rupture with clinical signs of hemoperitoneum. We report a case of subcapsular hepatic hematoma (SHH) associated with a high level of alpha-fetoprotein (AFP), for which diagnosis was made with conservative management, following up with the reduction in size at ultrasound examination and the reduction of the level of AFP

BACKGROUND: About 1-2% of infants born to mothers with Graves' disease or Hashimoto's thyroiditis develop neonatal hyperthyroidism because of transplacental passage of IgG stimulating TSH receptors (TRAb). OBJECTIVE: To evaluate the effect of maternal total thyroidectomy on neonatal clinical course. METHODS: We describe two brothers born to a mother with Graves' disease, before and after total thyroidectomy. RESULTS: The first child showed persistent tachycardia, the presence of TRAb and a laboratory pattern of hyperthyroidism. Lugol's solution was started and then propylthiouracil was added. Digitalis, furosemide and diazepam were necessary for treatment of heart failure, hypertension and irritability. On the 70th day of life, hormone serum levels normalized and treatment was interrupted. TRAb normalized by the third month of life. The second infant was born 2 years after the mother underwent total thyroidectomy. In spite of a laboratory pattern of hyperthyroidism and positivity to TRAb, he showed only considerable weight loss, and no therapy was required. CONCLUSIONS: TRAb may persist after total thyroidectomy: clinical and instrumental follow-up of the newborn is recommended.

Hepatic hematomas in neonates are uncommon lesions. When they are large or subcapsular in location, they can rupture with clinical signs of hemoperitoneum. We report a case of subcapsular hepatic hematoma (SHH) associated with a high level of alpha-fetoprotein (AFP), for which diagnosis was made with conservative management, following up with the reduction in size at ultrasound examination and the reduction of the level of AFP

BACKGROUND: We have previously developed and described a battery of 9 items suitable for assessing different clinical aspects of visual function in newborn infants. AIM OF THE STUDY: Application of the test battery to a cohort of low risk term-born infants at 48 and 72 h after birth 1) to define the normative distribution of results for each item and 2) to document any effect of postnatal age. STUDY DESIGN AND SUBJECTS: 124 term-born low risk infants were assessed at 48 h; fifty of them were re-assessed 24 h later at 72 h. RESULTS: The visual test battery was successfully completed in 110 of the 124 infants assessed at 48 h and in all the 50 infants assessed at 72 h after birth. For 3 of the 9 items (fixation on a black/white target of concentric circles, on a coloured (red/yellow) face and horizontal tracking), the findings were very similar at both ages. For the remaining 6 items the range of findings was wider. There was a statistical difference in the responses obtained at 48 and 72 h for vertical and arc tracking (p<0.05) and the ability to discriminate stripes and attention at distance (p<0.001). CONCLUSION: Our results provide information on the visual abilities in a low risk population of term-born infants and the distribution of frequency of their visual responses to our battery of visual tests. These findings may be used as reference data when using our visual test battery in both clinical and research settings.

Neonatal lupus syndrome is considered a model of passively acquired autoimmune disease. The first 10 newborns born to mothers with connective tissue disease and positive for anti-SSA/Ro antibodies enrolled in a follow-up program to evaluate the incidence of cardiac, hepatobiliary, hematologic, echoencephalographic, and cutaneous manifestations until 9 months of age are described in this study. No congenital heart block was observed, but only transient rhythm alterations were observed. In all, 1 infant showed typical neonatal lupus syndrome skin lesions at 3 months of age. During the neonatal period, echoencephalographic alterations were found more frequently, whereas at follow-up, hepatic and hematologic alterations were more often observed. In all, 1 baby showed persistent neutropenia. A standard program that enrolls all infants born to mothers with anti-SSA/Ro autoantibodies, who are at risk of developing neonatal lupus syndrome, should also include tests performed some time after birth, as a number of clinical manifestations might appear at a late stage.

AIM: To assess the correlation of echocardiographic signs of myocardial damage to serum cardiac troponin T (cTnT) concentrations in newborn infants with perinatal asphyxia. METHODS: Electocardiograms (ECG) and echocardiograms (Echo) were obtained during the first 24 h of life from 29 asphyxiated and 30 control infants and correlated with cTnT concentrations. The echocardiographic parameters included systolic ventricular performance, preload, afterload, diastolic function, stroke volume (SV), left ventricular output (LVO), hyperechogenity of the papillary muscles and insufficiency of the atrioventricular valves. RESULTS: LVO and SV were lower but CTnT were significantly higher in asphyxiated than in control infants: 0.15 (010-0.23) vs. 0.05 (0.02-0.13), p < 0.001). Asphyxiated infants with signs of myocardial damage were associated with significantly higher cTnT than those without, 0.20 (0.11-0.28) and 0.11 (0.05-0.14 ug/L), p = 0.04. CONCLUSION: Cardiac troponin may prove to be valuable in evaluating myocardial damage in birth asphyxia. However, the degree of prematurity may complicate the assessment.

OBJECTIVES: Early provision of protein has been shown to limit catabolism and could improve growth. Our objective was to determine whether early aggressive protein intake improved growth outcomes of extremely low birth weight (ELBW) infants. PATIENTS AND METHODS: ELBW infants were included in the study if they had no major congenital anomalies or renal failure and were still hospitalized at 36 weeks postmenstrual age. In 25 infants (HP) the early protein intake was planned to be 20% greater than in 31 historical controls (SP). RESULTS: The 2 groups were similar in the baseline characteristics. The mean protein intake during the first 14 days of life was significantly greater in the HP group (3.1 +/- 0.2 vs 2.5 +/- 0.2 g/kg/d; P<0.0001). HP group showed lower postnatal weight loss (-3.1%; 95% confidence interval [CI] -5.9, -0.2) and earlier regain of birth weight (-4.1 days; 95% CI -6.6, -1.7). Mean blood urea nitrogen and bicarbonate levels were similar; mean serum glucose level was lower in the HP group (-21,7 mg/dL; 95% CI -41.9,-1.5). HP infants had a reduced fall in weight z score (-0.57; 95% CI -1.01, -0.12) and in length z score (-0.51; 95% CI -0.97, -0.05) from birth to discharge. CONCLUSION: Early high protein intake was associated with improved weight and length growth outcomes at discharge. These findings highlight the benefits of aggressive protein intake immediately after birth.

no abstract available

OBJECTIVES: To compare the accuracy of a new transcutaneous bilirubinometer, BiliMed (Medick SA, Paris, France) with BiliCheck (Respironics, Marietta, GA, USA), a widely available instrument, and with total serum bilirubin measurement. DESIGN: A prospective double-blind study comparing the two devices was carried out. 686 healthy newborns needing measurement of their bilirubin were enrolled over a 4-month period. Serum and transcutaneous bilirubin measurements were taken with both devices within 15 minutes. The order of use of the instruments was randomised. SETTING: Well-baby nursery ward in a university hospital, tertiary referral centre. RESULTS: The linear regression analysis showed a better correlation between BiliCheck and serum bilirubin (r = 0.75) than between BiliMed and serum bilirubin (r = 0.45). BiliCheck variability (+/-2 SD of the mean bias from serum bilirubin) was within -87.2 to 63.3 micromol/l, while BiliMed variability was within -97.5 to 121.4 micromol/l. The receiver operating characteristic analysis (for serum bilirubin levels >205.2 micromol/l or >239.4 micromol/l) showed significantly higher areas under the curve for BiliCheck than those for BiliMed (p<0.001). CONCLUSIONS: Despite the potential practical advantages of BiliMed, its reduced diagnostic accuracy in comparison with BiliCheck does not justify its use in clinical practice.