Biological, nutritional and clinical aspects of feeding preterm infants with human milk.

Benefits of breastfeeding are widely recognized, during the last decades human milk has been identified as the normative standard for infant feeding and nutrition. Recent evidence focused on specific bioactive and immunomodulatory factors, such as oligosaccharides, lactose, glycosaminoglycans of human milk and the variability of their concentrations during lactation in both term and preterm milk. Human milk should be fortified with proteins, minerals and vitamins to ensure optimal nutrient intake for preterm VLBWI infants. Best fortification strategies as well as the optimal composition of fortifiers are still object of research. Short and long-term clinical, metabolic, immunologic and neurodevelopmental advantages of breastfeeding ndividualizes fortification - particulary adjustable fortification- has proven to be effective when compared to formula are well documented. Moreover several non-experimental studies observed that clinical feeding tolerance is improved and the attainment of full enteral feeding is quicker by a diet of human milk. In addition, benefits of breastfeeding on psychological and relational aspects have to be considered. Mother’s own milk remains the first choice for all neonates, when it is not available or not sufficient despite significant lactation support, donor milk represents the second best alternative and although some nutritional elements are inactivated by the pasteurization process, it still has documented advantages compared to formula.

Communication in NICUs.

In a Neonatal Intensive Care Unit (NICU) counseling should be a shared culture for all the care givers: it should be developed by all the professionals, to face up to parents' needs of information, explanations, facility of decisions, finding of resources, agreement, help, reassurance, attention. The first essential aspect is the training in counseling skills, by periodic courses for all professionals of the department (physicians, nurses, and physiotherapists). In our department, a professional counselor is present, assisting the medical staff in direct counseling. The counselor's intervention allows a better parent orientation in the situation. A more effective sharing of these rules also facilitates the communication among parents and medical staff. Periodic meetings are established among the medical staff, in which the professional counselor discusses difficult situations to share possible communicative strategies. We wanted to have not only a common communicative style, but also common subjects, independent from the characteristics of each of us. Individuals are often faced with different situations. For every setting that we more frequently face in communication (for example the first interview with a parent of a very preterm infant) we have built an 'algorithm' that follows a pattern: (1) information always given; (2) frequent questions from parents; and (3) frequent difficulties in the communication. Counselling is also a tool to face some critical issue, such as the decision to open the department to parents 24 h on 24, or the promotion of mother's milk use in Very Low Birth Weight Infants (VLBWI).

Critical appraisal of different anthropometric charts to evaluate postnatal growth of preterm infants.

Preterm infants' survival has greatly increased in the last few decades thanks to the improvement in obstetrical and neonatal care. The correct evaluation of postnatal growth of these babies is nowadays of primary concern, although the definition of their optimal postnatal growth pattern is still controversial. Concerns have also been raised about the strategies to monitor their growth, specifically in relation to the charts used. At present, the charts available in clinical practice are fetal growth charts, neonatal anthropometric charts and postnatal growth charts for term infants. None of these, for different reasons, is suitable to correctly evaluate preterm infant growth. Recently, an international project has recently started aiming to create prescriptive standard for the evaluation of postnatal growth of preterm infants (INTERGROWTH-21st). Alternatively, at present, while specific charts for evaluating preterm infant postnatal growth are lacking, the best compromise is likely to be as follows: from birth to term neonatal anthropometric charts; International longitudinal charts WHO 2006 or CDC 2002 from term to childhood.

Cow's milk proteins in human milk.

Cow's milk proteins (CMPs) are among the best characterized food allergens. Cow's milk contains more than twenty five different proteins, but only whey proteins alpha-lactalbumin, beta-lactoglobulin, bovine serum albumin (BSA), and lactoferrin, as well as the four caseins, have been identified as allergens. Aim of this study was to investigate by proteomics techniques cow's milk allergens in human colostrum of term and preterm newborns' mothers, not previously detected, in order to understand if such allergens could be cause of sensitization during lactation. Term colostrum samples from 62 healthy mothers and preterm colostrum samples from 11 healthy mothers were collected for this purpose. The most relevant finding was the detection of the intact bovine alpha-S1-casein in both term and preterm colostrum. Using this method, which allows direct proteins identification, beta-lactoglobulin was not detected in any of colostrum samples. According to our results bovine alpha 1 casein that is considered a major cow's milk allergen is readily secreted in human milk: further investigations are needed in order to clarify if alpha-1-casein has a major role in sensitization or tolerance to cow's milk of exclusively breastfed predisposed infants.

Metabolism and biological functions of human milk oligosaccharides.

It is well known that breastfeeding is beneficial both for its nutritional properties and for the presence of biologically active compounds. Among these, human milk oligosaccharides (HMOs), representing the third largest fraction of human milk, have been assigned important biological functions, such as prebiotic and immunomodulatory and antimicrobial effects. HMOs are synthesized in the mammary gland by glycosyltransferase enzymes and can be divided in core-oligosaccharides, sialo-oligosaccharides, fucosyl-oligosaccharides and sialo-fucosyl-oligosaccharides on the basis of their chemical structure. Glycosyltransferases enzymes are partially regulated by genetic mechanisms; according to the expression of secretory and Lewis' genes, it is possible to classify human milk in 4 different secretory groups. We hereby present a review of the current knowledge concerning HMOs, their metabolism and main biological functions.

Relationship between sleep/wakefulness and gastroesophageal reflux in symptomatic newborns.

The state of sleep/wakefulness is well known to influence esophageal acid exposure and the number of acid refluxes whereas it is uncertain whether the same is true of the non-acid refluxes that predominate in the newborns. To investigate the relationship between sleep/wakefulness and refluxes 45 newborns with gastroesophageal reflux symptoms were studied with combined multichannel intraluminal impedance and pH monitoring. We found that sleep/wakefulness influenced acid and weakly acidic reflux frequency (awake 2.6+/-0.8; asleep 2.1+/-1.1; p=0.006). A negative correlation was found between sleepness periods and the mean reflux duration for both acid (R=0.55;p < 0.001) and weackly acidic (R=0.51;p < 0.001) refluxes. This finding may raise some concerns about the over-prescription of antacid drugs in newborns.

Development and validation of a new HPLC-MS method for meglumine impurity profiling.

We report a new High Performance Liquid Chromatography-Mass Spectrometry (HPLC-MS) method to rapidly detect and quantify meglumine by-products (specifically reducing sugar(s) and nitrogen impurities) that could be present in the meglumine samples. Meglumine is a secondary amine obtained from glucose and it is an excipient used as counter-ion in several pharmaceutical formulations, especially when the concentration of the active pharmaceutical ingredient (API) is so high that the sodium is not a suitable option. Moreover, the increased use of meglumine is related to its ability to improve solubility in aqueous solutions due to the presence of a large number of hydroxyl groups. Thus, even if meglumine is widely used as excipient in pharmaceutical formulations, its impurity profile has never been fully evaluated. Here, we propose the use of a commercial agent that specifically reacts with carbonyl compounds, 1-(4-aminobenzyl)-1,2,4-triazole, with the aim of improving the detection of reducing sugars, such as glucose, after an easy derivatization procedure. Finally, we describe the method validation and the analysis of the impurity profile of meglumine samples from different manufacturers.

Insulin resistance in pre-school very-low-birth weight pre-term children.

AIMS: To evaluate the metabolic pattern of a group of pre-school small- (SGA) and appropriate-for-gestational age (AGA) pre-term very-low-birthweight (VLBW) (<1500 gr) Italian children and retrospectively verify if the growth rate in the first years of life is associated to the laboratory and anthropometric characteristics of these children. METHODS: 58 (16 SGA, 42 AGA) VLBW children, without major congenital malformations/conditions were enrolled; their anthropometric, clinical and (in 34 of them) laboratory characteristics were evaluated at pre-school age (> 2<6 years of corrected age). RESULTS: Clinical, anthropometric and laboratory characteristics at pre-school age were similar in SGA and AGA. Sixty-nine percent of SGA and 51% of AGA children showed a significant weight centile crossing (CC) at 24 months. Fasting serum glucose, insulin and insulin resistance (evaluated by the Homeostasis Model Assessment -HOMA-IR-) were higher in AGA and SGA with CC. The increment in weight standard deviation scores from birth-to-24 months was significantly associated with pre-school BMI SDS, waist, fasting insulin, and HOMA-IR values, both in unadjusted and adjusted models. In a multiple regression model, after multiple adjustments, this increment is the only significant predictor of pre-school insulin (B = 0.19; 95%CI 0.07-0.31; P = 0.006) and HOMA-IR levels (B = 0.20; 95%CI 0.08-0.32; P = 0.004) both in SGA and AGA children. CONCLUSIONS: The adverse metabolic pattern of pre-school VLBW children seems related to post-natal events (rapid weight growth) independently by their being small- or appropriate-for gestational age.

Potential risk factors for the development of acute renal failure in preterm newborn infants: a case-control study.

AIMS: To determine in a case-control study possible associations between the development of acute renal failure in preterm newborns and therapeutic interventions, particularly drug treatments. METHODS: The study population was 172 preterm infants of <38 weeks gestation; 71 had acute renal failure and 101 were controls closely matched for gestational age and birth weight. Maternal and neonatal information was collected for both groups through questionnaires and interviews. Routine data on renal variables were also collected. Univariate and multivariate logistic regression analyses were performed. RESULTS: Very low birthweight infants were at high risk of acute renal failure (79% of cases were <1500 g). However, the acute renal failure was transient. Mothers of infants with acute renal failure received more drugs during pregnancy and delivery (mainly antibiotics and non-steroidal anti-inflammatory drugs). Of the possible therapeutic interventions, intubation, catheterisation, and phototherapy were mainly applied to case subjects. A low Apgar score and patent ductus arteriosus were diagnosed in a greater percentage of neonates with acute renal failure. Moreover, in the first few days of life and before diagnosis of acute renal failure, case subjects received more drugs (antibiotics, non-steroidal anti-inflammatory drugs, and diuretics) and for a longer time. In the multivariate logistic analysis, medullary hyperechogenicity (odds ratio (OR) 4.491; 95% confidence interval (CI) 1.879 to 10.731) and ceftazidime administration (OR 5.082; 95% CI 1.493 to 17.297) were associated with a greater risk of acute renal failure. CONCLUSIONS: The results suggest the need for careful monitoring of very low birthweight infants and attention to drug treatments, as it is difficult to differentiate between normality and renal failure in the first few days of life.

6-phosphogluconate dehydrogenase, glucose-6-phosphate dehydrogenase, glucose-6-phosphate isomerase, and hexokinase activity ratios in some human tumor cytosols.

The ratios of some key enzymatic activities of carbohydrate metabolism have been measured in human tumor cytosols. The activities of whole hexokinase (low Km, EC 2.7.1.1 and high Km, EC 2.7.1.2), 6-phosphogluconate dehydrogenase (EC 1.1.1.43), glucose-6-phosphate dehydrogenase (EC 1.1.1.49) and glucose-6-phosphate isomerase (EC 5.3.1.9) change according to a biochemical pattern coherent with cell growth requirements. 6-phosphogluconate dehydrogenase activity was in each sample tested higher than glucose-6-phosphate dehydrogenase activity; this indicates that 6-phosphogluconate, a powerful inhibitor of glucose-6-phosphate isomerase, is unlikely to accumulate and inhibit this enzyme and glucose-6-phosphate channelling into glycolysis.

[Norms for serum prealbumin in newborn infants]. / Standard della prealbumina serica alla nascita.

Serum prealbumin (TPBA) was assayed at birth in 32 healthy term newborns using immunoprecipitation evaluated with kinetic nephelometry.

[Epidemiologic investigation of microorganisms and their sensitivity to antibiotics in a neonatal pathology center 1981-1984]. / Indagine epidemiologica sui microrganismi e sulla loro sensibilità agli antibiotici in un centro di patologia neonatale nel triennio 1981-1984.

The cultures performed over a period of three years in a neonatal pathology unit were studied to determine the epidemiological behaviour of the microorganisms present and variations in time of their sensitivity to antibiotics.

[Surveillance of congenital malformations. Monitoring of polydactyly using the Chen method]. / La sorveglianza delle malformazioni congenite. Monitoraggio della polidattilia con il metodo Chen.

The Chen method was adopted to monitor the principal congenital malformations in a large peripheric center. In 1982 two consecutive alarms showed an evident increase in the prevalence at birth of polydactylia. A retrospective analysis of the main risk factors failed to satisfactorily explain this increase.

High-dose ibuprofen for patent ductus arteriosus in extremely preterm infants: a randomized controlled study.

Our aim was to assess the hypothesis that a high-dose regimen of ibuprofen is more effective than the standard-dose regimen in closing patent ductus arteriosus (PDA) without increasing adverse effects. Infants of gestational age <29 weeks, with respiratory distress syndrome (RDS) and echocardiographic evidence of significant PDA at 12-24 h of life, were randomized to receive a standard (10-5-5 mg/kg/day) or high-dose (20-10-10 mg/kg/day) course of ibuprofen. We studied 70 infants, 35 of whom received the standard dose of ibuprofen and the other 35 the high dose. Of the infants treated with the standard-dose regimen, 37% had persistent PDA as compared with 14% of those treated with the high-dose regimen (P = 0.03). No differences in the occurrence of adverse effects were observed between the two groups. The high-dose ibuprofen regimen is more effective than the standard-dose regimen in closing PDA in preterm infants <29 weeks of gestation without increasing the adverse effect rate.

[Introduction to the principles of neonatal resuscitation]. / Introduzione ai principi della rianimazione neonatale.

WHO has estimated that as many as 10% of all newborn infants need some intervention at birth and approximately 1% more extensive intervention. If this is correct, up to 13-14 million of the world's annual newborn infants need intervention and of these approximately 1.5 million will need intensive therapy. Each year at least 1.16 million newborn babies die in sub-Saharan Africa. This region has the highest risk of newborn deaths and the slowest progress in reducing mortality. The transition from intrauterine to extrauterine life is extremely hazardous, with probably more radical physiologic adjustments required during and immediately following the birth process than at any other point in a human lifetime. Although certain episodes of fetal asphyxia cannot be prevented a prompt and skilled resuscitation may prevent lifelong adverse sequelae. Optimal resuscitation procedures should therefore become high priority. The ILCOR, the AHA and the AAP have established their new guidelines for newborn resuscitation on review of the evidence for each step. There still are a number of unanswered questions regarding newborn resuscitation (the ideal ratio of chest compressions to ventilation, the benefits and risks of supplementary oxygen, the indications for volume therapy, the optimal glucose level in infants that required resuscitation, the better ventilation in a newborn at birth.

Use of netilmicin once or twice daily in preterm newborns: evaluation of nephrotoxicity by urinary alpha1-microglobulin and retinol binding protein.

Since aminoglycoside efficacy is proportional to serum peak/MIC ratio and linked to post antibiotic effect, use of netilmicin once rather than twice a day has been proposed. On the other hand netilmicin might play a role in drug-induced nephrotoxicity, mainly on proximal tubule. Urinary retinol binding protein (RBP) and alpha1 microglobulin (alpha1m) are early and specific indicators of tubular damage and dysfunction. 21 preterm neonates (GA < 37 weeks) were divided in two groups on the basis of netilmicin administration modality (1: once a day, 2: twice a day, both for 7 days, at 5 mg/kg/die) and differences in netilmicin tolerability were assessed by evaluation of alpha1m and RBP levels by immunonephelometric method. No significant differences were found between the two groups either considering levels at time 1 and at time 2, or considering the difference between time 1 and 2 (Delta1/2). In our study once-daily dosing schedule shows similar low rates of nephrotoxicity, compared with multiple daily dosing schedule: this result may support the general adoption of once-daily dosing of netilmicin in clinical practice.

[Cleft palate and cortico-therapy during pregnancy]. / Division palatine et corticotherapie au cours de la grossesse.

A child with cleft palate is described who was born to a mother who received corticosteroid therapy early in pregnancy. The relationship between the cleft palate and the dose and timing of the corticosteroid therapy is discussed.

[The efficacy of aztreonam in a "bolus dose" in the therapy of urinary tract infections in neonates]. / Efficacia dell'aztreonam in "bolus dose" nella terapia delle infezioni delle vie urinarie nel neonato.

A "bolus dose" of aztreonam was used to treat a sample group of 46 neonates suffering from urinary tract infections caused by bacteria thought to be sensitive to aztreonam. This treatment proved efficacious in approximately 80% of cases.