Mario G. Romeo

Bovine Lactoferrin Prevents Invasive Fungal Infections in Very Low Birth Weight Infants: A Randomized Controlled Trial

Background: Lactoferrin is a mammalian milk glycoprotein involved in innate immunity. Recent data show that bovine lactoferrin (bLF) prevents late-onset sepsis in preterm very low birth weight (VLBW) neonates. Methods: This is a secondary analysis of data from a multicenter randomized controlled trial where preterm VLBW neonates randomly received bLF (100 mg/day; group A1), bLF + Lactobacillus rhamnosus GG (106 colony-forming units per day; group A2), or placebo (group B) for 6 weeks. Here we analyze the incidence rates of fungal colonization, invasive fungal infection (IFI), and rate of progression from colonization to infection in all groups. Results: This study included 472 neonates whose clinical, nutritional, and demographical characteristics were similar. Overall, the incidence of fungal colonization was comparable (17.6%, 16.6%, and 18.5% in A1, A2, and B, respectively; P = .89 [A1] and .77 [A2]). In contrast, IFIs were significantly decreased in A1 and A2 (0.7% and 2.0%, respectively) compared with B (7.7%; P = .002 [A1] and .02 [A2]), and this was significantly true both in <1000 g (0.9% [A1] and 5.6% [A2], vs 15.0%) and in 1001 to 1500 g infants (0% and 0% vs 3.7%). The progression rate colonization-infection was significantly lower in the bLF groups: 3.7% (A1) and 12% (A2), vs 41.9%; P < .001 (A1) and P = .02 (A2). No IFI-attributable deaths occurred in the treatment groups, versus 2 in placebo. No adverse effects or intolerances occurred. Conclusions: Prophylactic oral administration of bLF reduces the incidence of IFI in preterm VLBW neonates. No effect is seen on colonization. The protective effect on IFI is likely due to limitation of ability of fungal colonies to progress toward invasion and systemic disease in colonized infants.

Neurodevelopmental outcome at 12 and 18 months in late preterm infants

BACKGROUND Late-preterms represent the 70% of the whole preterm population and are reported to be at higher risk for mortality and morbidity than term infants. AIMS To assess neurodevelopmental outcome in low-risk late-preterm infants at 12 and 18 months corrected age, to compare results of corrected and uncorrected age to those of term-born infants, to analyse the possible influence of gender on outcome. METHODS Sixty-one healthy infants born between 33 and 36 weeks gestational age without major brain lesions were assessed at 12 and 18 months corrected age using the Bayley II scale. A control group of 60 low-risk term born infants underwent the same assessment. RESULTS At 12 and 18 months corrected age late preterms showed a mean mental developmental index (MDI) similar to term infants. Comparing the results of the uncorrected age with term infants, the scores were significantly lower at both 12 and 18 months. No gender differences were observed in term-born infants, while male late-preterm infants showed lower MDI than peer females at both ages. CONCLUSIONS When correcting age for prematurity late-preterms have similar MDI scores to those obtained in term-born infants at 12 and 18 months. In contrast, when using chronological age there is a number of infants with low MDI. As cognitive abnormalities are reported at school age in late preterm infants, our findings raise the question on whether the results obtained using scores uncorrected for age may early identify the infants who will show cognitive difficulties at school age.

Human milk feeding prevents retinopathy of prematurity (ROP) in preterm VLBW neonates

BACKGROUND Retinopathy of prematurity (ROP) is a multifactorial disease, but little is known about its relationships with neonatal nutritional policies. Human, maternal milk is the best possible nutritional option for all premature infants, including those at high risk for severe complications of prematurity, such as ROP. OBJECTIVE This is a secondary analysis of data collected during two multicenter RCTs performed consecutively (years 2004 through 2008) by a network of eleven tertiary NICUs in Italy. The two trials aimed at assessing effectiveness of fluconazole prophylaxis (Manzoni et al., N Engl J Med 2007 Jun 14;356(24):2483-95), and of bovine lactoferrin supplementation (Manzoni et al., JAMA 2009 Oct 7;302(13):1421-8), in prevention of invasive fungal infection, and of late-onset sepsis in VLBW infants, respectively. We tested the hypothesis that exclusive feeding with fresh maternal milk may prevent ROP of any stage - as defined by the ETROP study - in VLBW neonates, compared to formula feeding. METHODS We analyzed the database from both trials. Systematic screening for detection of ROP was part of the protocol of both studies. The definition of threshold ROP was as defined by the ETROP study. Univariate analysis was performed to look for significant associations between ROP and several possible associated factors, and among them, the type of milk feeding (maternal milk or formula for preterms). When an association was indicated by p < 0.05, multiple logistic regression was used to determine the factors significantly associated with ROP. RESULTS In both trials combined, 314 infants received exclusively human maternal milk (group A), and 184 a preterm formula because their mothers were not expected to breastfeed. The clinical, demographical and management characteristics of the neonates did not differ between the two groups, particularly related to the presence of the known risk factors for ROP. Overall, ROP incidence (any stage) was significantly lower in infants fed maternal milk (11 of 314; 3.5%) as compared to formula-fed neonates (29 of 184; 15.8%) (RR 0.14; 95% CI 0.12-0.62; p = 0.004). The same occurred for threshold ROP (1.3% vs. 12.3%, respectively; RR 0.19; 95% CI 0.05-0.69; p = 0.009). At multivariate logistic regression controlling for potentially confounding factors that were significantly associated to ROP (any stage) at univariate analysis (birth weight, gestational age, days on supplemental oxygen, systemic fungal infection, outborn, hyperglycaemia), type of milk feeding retained significance, human maternal milk being protective with p = 0.01. CONCLUSIONS Exclusive human, maternal milk feeding since birth may prevent ROP of any stage in VLBW infants in the NICU.

Longitudinal cognitive assessment in healthy late preterm infants.

BACKGROUND Longitudinal cognitive development in late preterm (LP) infants has not been previously evaluated, using structured assessments. AIM To assess longitudinally cognitive development in a population of healthy LP infants from 12 months to preschool age. METHODS Sixty-two low-risk LP infants (33-36 weeks gestation) with normal or only minor findings on their cranial ultrasound scans were included in the study. They were assessed at 12 and 18 months corrected age using the Bayley Scales of Infant Development II to obtain the mental development index (MDI) and then at preschool age (mean age 62 ± 7 months) using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-R). RESULTS The MDI scores obtained at both 12 and 18 months corrected age were within the reported normative range. Using uncorrected ages, their scores were lower at both ages than those obtained using CA (p < 0.01). Full-scale IQ scores within the reported normal range were obtained at 5 years using the WPPSI-R for all but 6 children. Females had significantly higher scores than males (p < 0.001) for the MDI at both 12 and 18 months corrected and uncorrected age. No gender differences were found at preschool age using the WPPSI-R. CONCLUSIONS Our results suggest that over 90% of the low-risk late preterms reach an MDI and IQ at preschool age within normal range.

Early assessment of visual function in preterm infants: how early is early?

BACKGROUND Several studies reported on various aspects of visual function at term age and in the first months after birth but less has been reported in preterm infants before they reach termequivalent age. AIMS To assess the suitability of a battery of tests of visual function for use in infants born at <33weeks gestation (GA) and assessed before 34weeks post-menstrual age (PMA); to evaluate the distribution of the findings according to GA, and to compare the data with those previously published on preterm infants assessed at 35weeks PMA. STUDY DESIGN Cross-sectional study. SUBJECTS Sixty-four preterm infants with a GA <33weeks were studied. OUTCOME MEASURES We used a battery of visual function tests previously validated at 35 and 40weeks PMA in low-risk preterm infants. All the infants in this current study underwent the same assessment before 34weeks PMA. RESULTS Before 31weeks PMA most infants could not be reliably assessed because of clinical instability, whilst after 31weeks PMA most infants could be assessed and they showed progressive maturation in their responses with PMA. Some items (spontaneous ocular motility, horizontal tracking, tracking a coloured stimulus, and ocular fixation) showed similar results at 32-33weeks PMA to those found in low-risk preterm at 35weeks PMA. Ocular movements to a target and arc tracking were the items with the most immature responses. CONCLUSIONS Our results provide further evidence that a structured assessment of visual function can be used in clinical routine and for research purposes in infants as young as 31weeks PMA.

Infant Neurological Examination from 3 to 12 Months : Predictive Value of the Single Items

The prognostic value of the single items of a standardised neurological examination, the Hammersmith Infant Neurologic Examination (HINE), was explored longitudinally in 658 infants at 3, 6, 9 and 12 months post-term age. ROC curves were built based on the presence/absence of cerebral palsy at 2 years of age. Global HINE scores showed very high prediction (ROC curve areas above 0.9) at all ages. The items with the highest predictive value were always movement quality and quantity. In the first semester, among the most predictive items were those assessing tone, while beyond that time they were reflexes and reactions. Our results show that the high predictive value of the HINE across the first year of life is granted by the successful combination of different groups of items for each age-period. This should be recognised in clinical practice when assessing the significance of individual neurological profiles.

Neurological examination of late-preterm infants at term age

BACKGROUND Late-preterm infants represent 70% of the whole preterm population. AIMS To establish the range and frequency distribution of neonatal neurological scores in a large cohort of low risk late-preterm infants and the possible differences with full-term infants. METHODS Three hundred-seventy-five healthy infants born between 34 and 36 weeks gestational age (GA) without major brain lesions were assessed between 39 and 41 weeks post-menstrual age using the Hammersmith Neonatal Neurologic Assessment and compared to the scores obtained using the same examination in full-term infants. RESULTS Infants born at 35 and 36 weeks GA had similar median scores in 32 of the 34 items. Infants born at 34 weeks GA had a different profile of scores compared to those born at 35 and 36 weeks, mainly in the tone items. While in infants born at 34 weeks the assessment at term age showed similar median scores to those obtained in full-term infants in 25/34 items, in those born at 35 and 36 GA the number of scores similar to full-term infants increased to 29/34. The main differences involved the tone items, with more marked flexor tone in the limbs and better head control for those born at 35 and 36 weeks. CONCLUSIONS This data can help as reference data when examining late-preterm infants at term age to see where the individual child stands compared to age matched low risk infants and to identify signs that are outside the reported range in infants with lesions or other risk factors.

Thrombomodulin serum levels in ventilated preterm babies with respiratory distress syndrome

Abstract A soluble form of thrombomodulin (TM), an anticoagulant proteoglycan of the endothelial cell membrane, considered a marker of vascular endothelial damage, was measured in plasma of preterm infants with respiratory distress syndrome (RDS). In these patients, lung immaturity leads to endothelial leak of plasma proteins and to surfactant inhibition. In 18 babies with RDS, plasma TM concentration was significantly elevated compared with values of a matched group of babies without pulmonary disease (276.1 ng/ml vs 141.3 ng/ml) (P<0.05). Furthermore, TM levels of mechanical ventilated babies (IPPV) with severe RDS were higher than those of babies with moderate RDS and treated with nasal CPAP (340.9 ng/ml vs 174.2 ng/ml) (P<0.05). Conclusion These data show that TM can be used as marker of pulmonary endothelial damage in preterm babies treated with mechanical ventilation for RDS and suggest early intervention with exogenous surfactant to limit alveolar protein leakage and surfactant inactivation.

The forward parachute reaction and independent walking in infants with brain lesions

Aim  The aim of this study was to assess the onset of forward parachute reaction (FPR) in infants with brain lesions and its correlation with age of walking.

Surgical treatment of congenital rhabdoid tumor in a 10-day-old newborn.

BackgroundMalignant rhabdoid tumors are rare and aggressive tumors of pediatric age. The primary tumor can occur in different localizations, but it mainly involves kidney, soft tissue, or central nervous system. It has been associated to a poor diagnosis. MethodsThe authors present the case of a 10-day-old newborn affected by a bulky nasofronto-orbitary neoplasm. The patient underwent radical surgical treatment and further excision of a preauricular metastasis combined with postoperative chemotherapy treatment. ResultsThe authors adopted a diagnostic and therapeutic protocol according to international guidelines, not without difficulty because the first histological report showed esthesioneuroblastoma. The rarity and aggresivity of rhabdoid tumor and the precocity of onset in our patient presented a difficulty to define prognostic factors and survival rates, as well as therapeutic plan of treatment. ConclusionsThe authors underline the importance of a correct prenatal diagnosis and an early surgical treatment to reach the complete healing of the patient.