Elective bone marrow transplantation in a child with X-linked hyper-IgM syndrome presenting with acute respiratory distress syndrome.

We describe a 10-month-old boy diagnosed with X-linked hyper-IgM syndrome (XHIM) after suffering from life-threatening acute respiratory distress syndrome (ARDS) caused by Pneumocystis carinii pneumonia (PCP), although his previous clinical history and first level laboratory tests investigating immunological function did not indicate immunodeficiency. When the patient's overall condition was good, elective bone marrow transplantation from an HLA-matched older brother was performed successfully. We describe how correct diagnosis and successful treatment were made possible thanks to the involvement of a network of specialists.

Crying of a newborn child: alarm signal or protocommunication?

The purpose of the study was to explore whether the new-born cry is a simple alarm signal or differentiated cries with different meanings. 12 digital audio taped recordings of 6 full-term healthy babies were analysed. Cries of 6 newborns in this preliminary study were recorded in a pain condition after a prick for the hematic check-up the third day after delivery and then while crying spontaneously in the cradle. The sounds were sampled at 44100 Hz with a 16-bit resolution and converted to the .wav format. All the analyses were performed with a software written in the MAT-LAB environment. The most important result was that these new-born children modulated the supralaryngeal tract considerably more in cries following the painful stimulus than in "spontaneous" ones, as would be expected by the hypothesis of crying as "protolanguage."

A rapid and quantitative mass spectrometry method for determining the concentration of acylcarnitines and aminoacids in amniotic fluid.

We describe a quantitative, rapid, sensitive and reproducible tandem mass spectrometry (MSMS) method for the one-step detection of aminoacid (AAs) and acylcarnitine (ACs) concentrations in amniotic fluid. This technology is quicker and more sensitive than other methods used to date since it is possible to determine very low AA and AC concentrations in samples simultaneously in a single run. The high degree of automation allows a large number of pregnancies to be screened for metabolic defects in a very short time.

Neonatal end-of-life decision making: Physicians' attitudes and relationship with self-reported practices in 10 European countries.

CONTEXT: The ethical issues surrounding end-of-life decision making for infants with adverse prognoses are controversial. Little empirical evidence is available on the attitudes and values that underlie such decisions in different countries and cultures. OBJECTIVE: To explore the variability of neonatal physicians' attitudes among 10 European countries and the relationship between such attitudes and self-reported practice of end-of-life decisions. DESIGN AND SETTING: Survey conducted during 1996-1997 in 10 European countries (France, Germany, Italy, the Netherlands, Spain, Sweden, the United Kingdom, Estonia, Hungary, and Lithuania). PARTICIPANTS: A total of 1391 physicians (response rate, 89%) regularly employed in 142 neonatal intensive care units (NICUs). MAIN OUTCOME MEASURES: Scores on an attitude scale, which measured views regarding absolute value of life (score of 0) vs value of quality of life (score of 10); self-report of having ever set limits to intensive neonatal interventions in cases of poor neurological prognosis. RESULTS: Physicians more likely to agree with statements consistent with preserving life at any cost were from Hungary (mean attitude scores, 5.2 [95% confidence interval ¿CI¿, 4.9-5.5]), Estonia (4.9 [95% CI, 4.3-5.5]), Lithuania (5.5 [95% CI, 4.8-6.1]), and Italy (5.7 [95% CI, 5.3-6.0]), while physicians more likely to agree with the idea that quality of life must be taken into account were from the United Kingdom (attitude scores, 7.4 [95% CI, 7.1-7.7]), the Netherlands (7. 3 [95% CI, 7.1-7.5]), and Sweden (6.8 [95% CI, 6.4-7.3]). Other factors associated with having a pro-quality-of-life view were being female, having had no children, being Protestant or having no religious background, considering religion as not important, and working in an NICU with a high number of very low-birth-weight newborns. Physicians with scores reflecting a more quality-of-life view were more likely to report that in their practice, they had set limits to intensive interventions in cases of poor neurological prognosis, with an adjusted odds ratio of 1.5 (95% CI, 1.3-1.7) per unit change in attitude score. CONCLUSIONS: In our study, physicians' likelihood of reporting setting limits to intensive neonatal interventions in cases of poor neurological prognosis is related to their attitudes. After adjusting for potential confounders, country remained the most important predictor of physicians' attitudes and practices. JAMA. 2000;284:2451-2459.

Treatment choices for extremely preterm infants: an international perspective.

OBJECTIVE: To compare treatment choices of neonatal physicians and nurses in 11 European countries for a hypothetical case of extreme prematurity (24 weeks' gestational age, birth weight of 560 g, Apgar score of 1 at 1 minute). STUDY DESIGN: An anonymous, self-administered questionnaire was completed by 1401 physicians (response rate, 89%) and 3425 nurses (response rate, 86%) from a large, representative sample of 143 European neonatal intensive care units. Italy, Spain, France, Germany, the Netherlands, Luxembourg, Great Britain, Sweden, Hungary, Estonia, and Lithuania participated. RESULTS: Most physicians in every country but the Netherlands would resuscitate this baby and start intensive care. On subsequent deterioration of clinical conditions caused by a severe intraventricular hemorrhage, attitudes diverge: most neonatologists in Germany, Italy, Estonia, and Hungary would favor continuation of intensive care, whereas in the other countries some form of limitation of treatment would be the preferred choice. Parental wishes appear to play a role especially in Great Britain and the Netherlands. Nurses are more prone than doctors to withhold resuscitation in the delivery room and to ask parental opinion regarding subsequent treatment choices. CONCLUSION: An extremely premature infant is regarded as viable by most physicians, whereas after deterioration of the clinical conditions decision-making patterns vary according to country. These findings have implications for the ethical debate surrounding treatment of infants of borderline viability and for the interpretation and comparison of international statistics.

End-of-life decisions in neonatal intensive care: physicians' self-reported practices in seven European countries. EURONIC Study Group.

BACKGROUND: The ethical issue of foregoing life-sustaining treatment for newborn infants at high risk of death or severe disability is extensively debated, but there is little information on how physicians in different countries actually confront this issue to reach end-of-life decisions. The EURONIC project aimed to investigate practices as reported by physicians themselves. METHODS: The study recruited a large, representative sample of 122 neonatal intensive-care units (NICUs) by census (in Luxembourg, the Netherlands, and Sweden) or stratified random sampling (in France, Germany, the UK, Italy, and Spain) with an overall response rate of 86%. Physicians' practices of end-of-life decision-making were investigated through an anonymous, self-administered questionnaire. 1235 completed questionnaires were returned (response rate 89%). FINDINGS: In all countries, most physicians reported having been involved at least once in setting limits to intensive care because of incurable conditions (61-96%); smaller proportions reported such involvement because of a baby's poor neurological prognosis (46-90%). Practices such as continuation of current treatment without intensification and withholding of emergency manoeuvres were widespread, but withdrawal of mechanical ventilation was reported by variable proportions (28-90%). Only in France (73%) and the Netherlands (47%) was the administration of drugs with the aim of ending life reported with substantial frequency. Age, length of professional experience, and the importance of religion in the physician's life affected the likelihood of reporting of non-treatment decisions. INTERPRETATION: A vast majority of neonatologists in European NICUs have been involved in end-of-life limitation of treatments, but type of decision-making varies among countries. Culture-related and other country-specific factors are more relevant than characteristics of individual physicians or units in explaining such variability.

Parental visiting, communication, and participation in ethical decisions: a comparison of neonatal unit policies in Europe.

AIM: To compare neonatal intensive care unit policies towards parents' visiting, information, and participation in ethical decisions across eight European countries. METHODS: One hundred and twenty three units, selected by random or exhaustive sampling, were recruited, with an overall response rate of 87%. RESULTS: Proportions of units allowing unrestricted parental visiting ranged from 11% in Spain to 100% in Great Britain, Luxembourg and Sweden, and those explicitly involving parents in decisions from 19% in Italy to 89% in Great Britain. Policies concerning information also varied. CONCLUSIONS: These variations cannot be explained by differences in unit characteristics, such as level, size, and availability of resources. As the importance of parental participation in the care of their babies is increasingly being recognised, these findings have implications for neonatal intensive care organisation and policy.

The EURONIC Project: a European concerted action on information to parents and ethical decision-making in neonatal intensive care.

The paper presents the background, objectives and methods of a European concerted action project aimed at exploring the transmission of information to parents and the ethical decision-making process in neonatal intensive care from the perspective of health personnel, and in relation to the legal, cultural, social and ethical backgrounds of the various European countries. Eight countries are taking part in the project (France, Germany, Italy, Luxembourg, Spain, Sweden, The Netherlands and the United Kingdom), which is about to be extended also to Central and Eastern Europe (Estonia, Lithuania and Hungary). In each of them, the medical and nursing personnel of a number of randomly selected units will be interviewed through an anonymous, self-administered questionnaire. Information on the organisation and policies of the Units and on the national legislation will also be collected. The key features of the study lie in the multidisciplinary and international approach, the random selection of the sample as a guarantee of representativeness and lack of selection bias, the focus on the staff practices as well as on their attitudes and opinions.

[The success of maternal feeding with very low birth weight premature infants, singletons and twins: a 10-year experience]. / Successo dell'allattamento materno nei pretermine di peso molto basso singoli e gemelli: un'esperienza di 10 anni.

UNLABELLED: There are very few reports about the feasibility of maternal milk feeding in very low birthweight preterm infants (VLBW), especially in twins. Therefore we conducted a cohort retrospective study to evaluate the feeding patterns of the 226 VLBW discharged from our neonatal intensive care unit from 1987 to 1996. Their gestational age was 30 +/- 2.6 weeks, birthweight 1166 +/- 224 g and they were hospitalized for 67 +/- 37 days (means +/- 1 SD). Of the 226 VLBW 49% were males, 39% had birthweight below 10 degrees centile for gestational age and 56% were born to non-residents in our area. There were 181 single births and 45 (20%) multiple births, of which 16 from pregnancies with 3 or more fetuses. Of the total cases 22% were discharged feeding maternal milk (MM) exclusively and 21% on mixed-feeding, maternal + formula milk (FM). Percentages were respectively 23% and 18% for single newborns, 11% and 29% for twins. Singletons and twins were discharged on FM with comparable percentages (59 and 60%). With passing years we have noticed a significant increase (chi square for linear trend < 0.01) for maternal milk feeding. In the last 2 years 49% of singletons and 38% of twins were discharged on MM, 14% and 24% on MM + FM, and only 37% and 38% on FM only. Between singletons and twins there were no statistically significant differences as far as feeding at discharge is concerned. CONCLUSIONS: most mothers, if correctly informed and encouraged, are able to breast-feed, exclusively or partially, their VLBW offspring, including twins, in the first months of life.

Growth hormone does not prevent catabolic side effects of dexamethasone in extremely low birth weight preterm infants with bronchopulmonary dysplasia--a pilot study.

Recombinant human growth hormone (rhGH) may reduce the catabolic side effects of steroid therapies on children and adults, but this has never been studied in preterm infants. We performed a pilot study on 5 extremely low birth weight preterm infants (gestational age 27 +/- 3 wks, birth weight 824 +/- 160 g) still on mechanical ventilation for bronchopulmonary dysplasia at the postnatal age of 35 +/- 9 days. All were treated for 7 days with dexamethasone (0.5 mg/kg/d i.v.) and subcutaneous rhGH at different doses: 0.1 (n = 1), 0.2 (n = 2) or 0.3 (n = 2) IU/kg/day. Nutrition was kept stable. After 7 days all subjects improved their respiratory condition but body weight remained the same and urinary urea nitrogen and C-peptide were significantly higher (p < 0.001). rhGH intake strongly related to urinary excretion of urea nitrogen (r = 0.78) and C-peptide (r = 0.88). Dexamethasone improves the pulmonary function of very preterm infants with bronchopulmonary dysplasia but induces growth arrest and catabolism which are not prevented, and may be worsened, by rhGH.

Clinical approach to the analysis of causes of death in the first two years of life of very-low-birthweight infants in a multicentre setting.

Mortality in the first 2 years of 634 very-low-birthweight infants admitted to eight neonatal intensive care units in Italy, and the factors associated with the net probability of death from each cause, were studied by means of the Cox proportional hazard model. A clinical classification of the causes of death was used. Overall mortality was 33.7% (intercentre range 12.6-52.9%). The highest cause-specific mortality rates were observed for respiratory problems, intra-ventricular haemorrhage (IVH) and infections (14.5%, 6.3% and 5.7% respectively). The leading causes of death were respiratory problems and IVH in the first week of life, infections from the second week up to the end of the first month, and bronchopulmonary dysplasia (BPD) afterwards. Birthweight < 1000 g, gestational age < 30 weeks, absence of spontaneous respiratory activity, unknown body temperature and pH < 7.20 at admission were associated with death from respiratory problems and IVH. Male sex, birthweight < 1000 g and unknown body temperature at admission were associated with death from BPD. Mortality from infections was higher in one centre; no other differences emerged among the eight NICUs. The classification of the causes of death employed and the use of the net probabilities of death appear as practical and useful instruments to study the relationship between specific aspects of medical care and mortality, and to investigate the reasons for differences in performance between neonatal units.

Area variations in birthweight- and cause of death--specific neonatal mortality rates in Italy.

The neonatal mortality rate in Italy is intermediate between the United States and the Northern European countries, but important regional differences exist within the country. On the basis of national data recorded by the Italian National Statistical Institute, birthweight- and cause of death-specific neonatal mortality rates were calculated for the whole country and for Northern, Central, and Southern Italy. The incidence of very low birthweight (500 to 1499 gm) and moderately low birthweight (1500 to 2499 gm) infants is similar in the three areas, whereas the risk of dying in the first month of life is highest in Southern and lowest in Northern Italy. Respiratory distress syndrome/immaturity is the main cause of neonatal death because of very high percent and component rates among very low birthweight infants and (to a lesser extent) among moderately low birthweight infants. Congenital disorders, which mainly affect normal weight newborns, are the second cause of neonatal death. Infants born in Southern Italy run a significantly higher risk of dying in the neonatal period than infants born in Northern Italy in almost all birthweight/cause of death subgroups, with the largest differences for moderately low birthweight infants. A similar but smaller difference is seen when infants born in Central Italy are compared with their Northern counterparts.

Idiopathic arterial calcification of infancy: effectiveness of prostaglandin infusion for treatment of secondary hypertension refractory to conventional therapy: case report.

A premature baby had severe hypertension associated with idiopathic arterial calcification of infancy. Despite the fact that there was laboratory evidence of renin-mediated hypertension, the disease was refractory to specific renin antagonist and failed to respond to conventional medical treatment. Prostaglandin E1 (PGE1) infusion (dosage range 0.017-0.068 microgram/kg/min) promptly controlled hypertension on two occasions. The drug was given for a total of 65 days and then stopped after the appearance of severe thrombocytopenia; other side effects included sporadic hyperthermia and irritability. Blood pressure was then stabilized satisfactory by a multiple-antihypertensive regimen. In the light of these findings, we believe that PGE1 infusion is a possible therapeutic alternative for babies with idiopathic arterial calcification complicated by severe hypertension refractory to conventional treatment.

Peritoneal dialysis in a 6-weeks old preterm infant with severe theophylline intoxication.

A case of severe, acute accidental theophylline intoxication in a 6-week old preterm infant treated with peritoneal dialysis is reported. Theophylline concentrations in plasma, urine and in the peritoneal lavage fluid were measured during all the procedure. With dialysis theophylline half-life was reduced to 14.8 hours, despite a plasmatic peak level of 133 micrograms/ml, and a significative amount of the drug was removed from the body, leading to a rapid and complete recovery of the child. In our experience peritoneal dialysis can be regarded as a first line emergency procedure in very sick infants with severe theophylline intoxication when more sophisticated methods are not available.

Serum Insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) in growing preterm infants on enteral nutrition.

We analyzed the range of serum concentrations of insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) and their inter-relationships with age and some parameters of nutritional and hormonal status in 46 growing preterm infants on enteral nutrition. 72 nutritional balances were performed, with a cross-sectional study design, at a mean age of 35.3 +/- 17.2 days, equivalent to a mean corrected age (gestational + postnatal age) of 36 +/- 2.3 weeks. Serum concentrations of IGF-I (mean 64 +/- 36 ng/ml) and IGFBP-3 (mean 1.15 +/- 0.53 mg/l) correlated significantly with each other (r = 0.46) and both correlated with body weight (r = 0.43 and 0.34), body length (r = 0.44 and 0.36) and serum concentrations of prealbumin, apolipoprotein A and cholesterol. IGF-I also correlated with urinary excretion of C-peptide (r = 0.32). There was a weak correlation between IGFBP-3 and postnatal age (r = 0.36) but no correlation between IGF-I and IGFBP-3 and correlated age or urinary excretion of growth hormone. In growing preterm infants, at least until 40 weeks of corrected age, serum concentrations of IGF-I and IGFBP-3 seem to be related principally to body weight, body length and nutritional factors, but not to growth hormone.

[Therapy of neonatal infection caused by group B beta-hemolytic Streptococcus]. / La terapia dell'infezione neonatale da streptococco beta-emolitico di gruppo B.

Expectant therapy for early Group B Streptococcus onset septicemia must provide coverage against other microorganism, such as L. Monocytogenes, H. Influenzae and S. Pneumoniae. It is possible to administer a combination of antimicrobial agents with activity against all or the most likely pathogens. Thus initial expectant therapy includes a broad spectrum semisynthetic penicillin (e.g. ampicillin) and an aminoglycoside (e.g. netilmicin). Vancomicin, teicoplanin and cefotaxime may also be used. Supportive therapy consists on temperature control, i.v. administration of fluids, acid-base balance and electrolytes monitoring, seizures control and ventilation. IV immunoglobulins, granulocyte and serum transfusion are also used. The G-Colony Stimulating Factor (G-CSF, filgastrim) usage is also reported.

[Metabolic, hormonal and nutritional effects of long-term theophylline therapy in preterm infants: a case-control study]. / Effetti metabolici, ormonali e nutrizionali della terapia prolungata con teofillina nei nati pretermine: uno studio caso-controllo.

Theophylline is widely used in preterm newborns for the prevention of idiopathic apnoeas, but few controlled studies have evaluated its effects on the nutritional and hormonal status of the infant. For this reason we have studied the effect of long term theophylline administration on 16 laboratory parameters concerning the metabolism of proteins, glucose, lipids, hormones and the glomerular function (blood: hemoglobin, glucose, albumin, prealbumin, urea nitrogen, creatinine, cholesterol, triglycerides, apolipoproteins A-I and B-100, IGF-I, IGFBP-3; urine: urea nitrogen, creatinine, C-peptide, GH). A case-control study was performed on 18 healthy preterm infants who were receiving oral theophylline for the prevention of idiopathic apnoeas. The mean duration of therapy at the moment of the balance study was 31 days (SD 12, range 12-51), the mean daily dose was 4.2 mg/kg (SD 1.0), the plasma range of theophylline concentration was 5 to 15 mg/l. As controls, 18 healthy preterm infants of comparable post-conceptional age, body weight and calories/protein intake at the moment of the study, were selected if they had been never treated with theophylline. No statistically significant differences were found between the two groups for the growth velocity or any of the parameters studied. The only notable exception was hemoglobin, which was significantly lower in theophylline treated infants (mean values 10.5 vs 12.7 g/dl, p 0.005 at t test). In synthesis, long term theophylline treatment in preterm infants seems to be safe from the point of view of growth, glucose, protein and lipid metabolism, hormones and glomerular function, but further studies are needed on the effects of theophylline on neonatal erythropoiesis.

[Nutritional and acute phase proteins in preterm newborns: reference standards and interrelations]. / Proteine nutrizionali e della fase acuta nel neonato pretermine: standard di riferimento ed interrelazioni.

The serum concentrations of 5 "nutritional" and 5 "acute phase" proteins were prospectively studied in 3 groups of newborns with nephelometric methods. Group A: 22 healthy breast fed term newborns aged 4 days; group B: 28 healthy enterally fed preterm newborns (mean gestational age 33.3 weeks); group C: 49 preterm newborns (mean gestational age 29.5 weeks) on parenteral nutrition (PN). Infants with surgical procedures, sepsis and liver or renal diseases were excluded. The serum concentrations of almost all proteins were similar or only slightly different among the 3 groups and never related to the weight and chronological or post-conceptional age. Only prealbumin, apolipoprotein A and B and C4 levels were significantly different between term and preterm newborns. Enterally fed preterm infants had lower concentrations of alpha 1 acid glycoprotein and higher albumin, transferrin and apolipoprotein A than PN fed infants. Since the observed differences were usually quite small, we suggest that--at least in clinical practice--common serum reference values of these proteins should be adopted for all healthy growing newborns, whether preterm or at term, enterally or parenterally fed. The inter-relationships between different proteins were studied. Four of the five nutritional proteins were highly correlated one with another and the same was observed for the 5 acute phase proteins. Nutritional proteins as a group did not correlate with acute phase proteins, with the only exception of alpha 1 acid glycoprotein and apolipoprotein A. Thus, the 2 groups of proteins seem to be regulated by different metabolic systems.

Italian multicentre study on very low-birth-weight babies. Neonatal mortality and two-year outcome.

The Italian multicentre study on very low-birth-weight babies is the first collaborative project in Italy on the health status of newborns weighing 500-1499 g at birth: 634 such babies were admitted in 1987-88 to eight Italian NICUs; 424 infants survived and were followed until two years of age, corrected for prematurity. Logistic regression analysis of pre-admission risk factors of in-hospital mortality identified eight statistically significant variables: birth weight, gestational age, sex, antepartum steroids, 1-min Apgar score and, on admission to the NICU, body temperature, pH and absence of spontaneous respiration. Using the equation derived from the logistic model, a theoretical mortality rate was calculated for each centre, predicted on the basis of the local incidence of preadmission risk factors. In no case was the predicted mortality significantly different from the observed one. At two years of age, 8 children were blind and 48 had motor disability. Of these, 46 had cerebral palsy: based on a functional evaluation score 14 had severe (degree 4), 20 intermediate (degree 3) and 12 mild cerebral palsy (degree 2). Among 25 variables entered in a logistic regression as risk factors for cerebral palsy, only periventricular leukomalacia and acidosis were significantly associated with the outcome.