Neonatal liver failure and haemophagocytic lymphohistiocytosis caused by a new perforin mutation.

UNLABELLED: Acute liver failure is a rare heterogeneous syndrome in neonates. We report of a newborn with haemophagocytic lymphohistiocytosis presenting as acute liver failure. Pancytopenia and multi-organ failure occurred later in the course. He carried two mutations of the perforin gene (PRF-1), one of which not previously described, causing a complete loss of perforin expression and natural killer cell function. CONCLUSION: Perforin expression and function should be promptly assessed in neonatal/infantile acute liver failure, as haemophagocytic lymphohistiocytosis requires specific treatment and represents a contra-indication to liver transplant.

RFT1-CDG: deafness as a novel feature of congenital disorders of glycosylation.

Congenital disorders of glycosylation (CDG) are genetic diseases due to defects in the synthesis of glycans and in the attachment of glycans to lipids and proteins. Actually, some 42 CDG are known including defects in protein N-glycosylation, in protein O-glycosylation, in lipid glycosylation, and in multiple and other glycosylation pathways. Most CDG are multisystem diseases and a large number of signs and symptoms have already been reported in CDG. An exception to this is deafness. This symptom has not been observed as a consistent feature in CDG. In 2008, a novel defect was identified in protein N-glycosylation, namely in RFT1. This is a defect in the assembly of N-glycans. RFT1 is involved in the transfer of Man(5)GlcNAc(2)-PP-Dol from the cytoplasmic to the luminal side of the endoplasmic reticulum. According to the novel nomenclature (non-italicized gene symbol followed by -CDG) this defect is named RFT1-CDG. Recently, three other patients with RFT1-CDG have been reported and here we report two novel patients. Remarkably, all six patients with RFT1-CDG show sensorineural deafness as part of a severe neurological syndrome. We conclude that RFT1-CDG is the first 'deafness-CDG'. CDG should be included in the work-up of congenital, particularly syndromic, hearing loss.

Cannula tip intravascular migration in an infant.

In infants, the tip of a cannula is sometimes used as introducer during peripherally inserted central catheters placement. We report a rare complication of this procedure, characterized by intravascular migration of the cannula tip during peripheral insertion of a central venous catheter. We review this unlikely complication and treatment options.

Survival of children with Down syndrome in Italy.

A cohort of 917 Down syndrome (DS) children born in Italy between 1978 and 1984 was studied for survival through the age of 8 years. The highest mortality occurred in the first month of life (7.9%); survival was about 80% at 1 year, 78% at 2 years, and 76% at 5 years, with small decreases thereafter. At the univariate analysis, survival was lower for subjects with congenital heart disease (CHD), birth weight less than 2,500 g, parity of 3 or plus, maternal age greater than or equal to 35 years, and for those born in Southern Italy compared with Northern Italy. No differences in survival were observed by sex and by socioeconomic status. The Cox proportional hazard model was used to evaluate the effect of each variable adjusted for all the others present in the model. Presence of CHD (odds ratio = 3.27; 95% confidence interval (C.I.) 2.31-4.63), birth in the South (odds ratio = 2.69; 95% C.I. 1.91-3.79), and low birth weight (odds ratio = 1.87; 95% C.I. 1.29-2.72) were independently associated with survival. None of the other variables emerged as a statistically significant prognostic factor. Various hypotheses were considered to interpret the unexpected effect of place of birth on survival. Quality of medical care provided in the South of Italy is the most likely determinant of the high mortality observed among children with DS born in that area of Italy. Such differences in survival within the same country could occur in other developed nations as well.

Increased bilirubin production, ceruloplasmin concentrations and hyperbilirubinaemia in full-term newborn infants.

Ceruloplasmin possesses antioxidant activity in vitro, but such a property has not been substantiated in vivo so far. However, it has been suggested that the lack of factors protective against oxidative haemolysis might have a role in neonatal hyperbilirubinaemia. Ceruloplasmin and alphafetoprotein concentrations were measured in cord blood in 78 unselected full-term singleton newborn infants without G6PD deficiency and haemolytic disease of the newborn; in the same infants, the carboxyhaemoglobin level was assessed on the fourth day of life and taken as an index of bilirubin production. The relationship between these variables and maximum bilirubin level in the first 4 days was studied by multiple regression analysis. High carboxyhaemoglobin levels and low ceruloplasmin concentrations, but not alphafetoprotein resulted, associated with hyperbilirubinaemia (P < 0.001). No relationship was found between carboxyhaemoglobin and ceruloplasmin levels. These results exclude an important role for ceruloplasmin in protecting against possible oxidative haemolysis in full-term newborn infants. Ceruloplasmin levels in cord blood are most probably related to hepatic metabolism and are better predictors of hyperbilirubinaemia than alphafetoprotein concentrations.

Behaviour of preterm newborns reaching term without any serious disorder.

We studied the behaviour of 20 preterm infants (average gestational age 33 weeks) brought to term, without any serious disorder. These infants were compared with a group of 21 healthy term infants. To evaluate behaviour we used the 26 items of the Brazelton Neonatal Behavioural Assessment Scale (BNBAS). Our preterm infants had on the whole better scores than those reported in the literature for preterm infants with various disorders. Apart from lower ability to bring hand to mouth and in getting used to visual stimuli (these differences are statistically significant) they had, in the items of orientation a lower score only in ability to follow a voice and a face (not statistically significant). These results show that preterm infants reaching term without any serious disorder do on the whole as well as full-term infants. This correlates with the observations of Dubowitz on behaviour and particularly on visual function of preterm infants and confirms the preliminary report of Daum regarding the influence of the type of neonatal pathology on the ability of orientation at the moment of term.

Birth weight discordancy in twins: new definition and standard.

OBJECTIVE: The aim of this study was to improve the definition of birth weight discordancy based on its distribution in the population after a correction in the unlike sex pairs. STUDY DESIGN: The analysis was conducted on 849 Italian twin pairs. Male's birth weight in the unlike sex pairs was corrected by the physiological birth weight difference estimated on 21.595 Italian twins data. Birth weight discordancy was computed as a percentage of the larger twin's birth weight and it was compared by sex pairs and by gestational ages (Kruskal-Wallis test). Kolmogorov-Smirnov test was used to fit a normal distribution to the square-root transformed birth weight discordancy. RESULTS: The estimated physiological birth weight difference between males and females was 4.39%, without any difference among gestational ages. The 90th centile of birth weight discordancy was 23.9% and the 95th centile was 29.2%. CONCLUSIONS: Ninetieth and 95th centiles of the fitted distribution are proposed as cut-off values for the definition of mild and severe birth weight discordancy.

Italian Multicenter Study on Very Low Birth Weight Babies.

The Italian Multicenter Study on Very Low Birth Weight babies (IMS-VLBW) is the first collaborative investigation performed in Italy on the health status of newborns weighing less than 1500 g at birth. Eight Neonatal Intensive Care Units (NICUs) participated in the study: Cagliari, Napoli, Padova, Palermo, Roma, Sassari, Trieste, Udine. Data were analyzed in the Laboratorio di Epidemiologia e Biostatistica of the Istituto Superiore di Sanità. The objectives of the study were established in the following: a) to collect accurate descriptive data on neonatal morbidity, mortality and long term outcome of VLBW babies admitted to NICUs; b) to analyze the risk factors of unfavourable outcome (death or handicap) and to analyze, with respect to outcome, the relationships between risk factors, neonatal diseases and therapeutical procedures; c) to test the feasibility of a multicenter follow-up programme based on the use in all participating Centers of the same diagnostic criteria (the results of follow-up will be presented in a forthcoming paper). In the years 1987 and 1988, 634 newborns weighing 500-1499 g at birth were enrolled in the study. In-hospital mortality for the whole group was 33.1% (65.1% in the 500-999 g birth weight class and 19.2% in the 1000-1499 g class). Mortality was not different for inborn vs outborn babies. A high incidence of unfavourable perinatal conditions was observed in these babies, namely birth asphyxia, sub-optimal care during transport, poor clinical conditions on arrival to the NICU. Neonatal diseases, like respiratory distress syndrome and peri-intra ventricular hemorrhage were also frequent and severe. A logistic regression analysis of pre-admission risk factors of in-hospital death identified eight statistically significant variables: birth weight; gestational age; sex; antenatal steroid stimulation of lung maturity; first minute Apgar score; absence of spontaneous respiration, body temperature and pH on arrival to the NICU. Using the equation derived from the logistic regression analysis a theoretical mortality rate, predicted on the basis of the local incidence of pre-admission risk factors, was calculated for each Center. In no case the predicted mortality was statistically different from the observed one, suggesting that in our study differences in observed mortality rates from one Center to another are largely influenced by pre-admission risk factors.

[Perinatal events and handicaps]. / Eventi perinatali ed handicap.

It is difficult to assess how large is the proportion of handicap in the pediatric age related to perinatal events; this is mainly due to the following reasons: lack of uniform criteria and accuracy in defining both "handicap" and the "perinatal period"; variable involvement of perinatal factors in the genesis of the different types of impairment; and multifactorial origin of most sensory, neural and developmental damages. For the same reasons it is no easy to assess if handicaps of perinatal origin are declining or increasing with time. Cerebral palsy (CP), retinopathy of prematurity (ROP), deafness and relational problems are probably the clinical conditions most strictly related to perinatal events, tough recently biological and familial prenatal factors have also been proposed as important antecedents of CP. No important variation in the incidence of CP has been reported for the last 20 years, notwithstanding a supposed better perinatal care as documented by the decreased neonatal mortality; on the contrary a new epidemic of ROP is being described. This is probably the consequence of the increasing survival of babies at highest risk for subsequent handicap, namely those weighing less than 1500 gm and, chiefly, those weighing less than 1000 gm. Available data on the incidence or prevalence of deafness in infancy do not permit a meaningful analysis of their variations with time. Perinatal asphyxia, neonatal convulsions, intraventricular hemorrhage, CNS leukomalacia, mechanical ventilation and mother-infant separation are probably the most important "markers" of risk for subsequent sequelae; they must be distinguished from the "causes", which are unknown in many instances. Owing to this difficulty it is not possible to establish a straight correlation between perinatal care and handicap. The strategy of intervention must be aimed at the prevention of the situations outlined above, and it must rely both on technical and political solutions, which include the prevention of preterm birth, an effective regionalization of care and a constant evaluation of the results.

[Clavicular fractures in the newborn infant]. / La frattura della clavicola nel neonato.

The frequency of the fracture of clavicle in liveborn infants delivered in the Obstetric Department of the School of Medicine of Sassari was retrospectively evaluated for the years 1977, 1978 and 1979. Moreover, all the fractured live infants born in 1980 were prospectively identified and compared to a group of unmatched controls, which included the live infant born immediately before and that born immediately after the index case. The same procedure was adopted when the fracture was identified in two infants born consecutively. The following variables were studied: date and hour of delivery, sex, birthweight, gestational age, type of labour, presentation and mode of delivery, Apgar at one minute, parity of the mother. There were 108 cases and 194 controls. The frequency of the fracture of clavicle showed a linear increase from 2.2/100 live births in 1977 to 4.8/100 live births in 1980; males were slightly more affected than females and the right clavicle was more frequently fractured than the left one (67% for the four years altogether). In the prospective study the only statistically significant differences between cases and controls were found for birthweight (less than 0.001) and mode of delivery (P less than 0.025): cases weighed more and were more frequently born by instrumental delivery (vacuum or forceps) than controls; none of the fractured infants was born by caesarean section. One of the fractured infants was affected by osteogenesis imperfecta and two other presented a transitory paresis of the omolateral brachial plexus; in the remaining cases the prognosis was good.

[Neurologic pathology in the neonatal period: relation to birth weight and gestational age]. / Patologia neurologica in epoca neonatale: relazione con il peso e l'età gestazionale.

Six Italian university centers have taken part in the Perinatal Preventive Medicine Project of the National Research Council since 1973. In this report the preliminary data on neonatal neurological disorders of 38775 single not malformed infants are presented. Neurological abnormality has been defined by the presence of at least one of the following symptoms: seizures, hypertonia, hypotonia, apneic spells. The relative frequencies of seizures vary from a minimum of 0.28% to a maximum of 0.75% in the six centers. The frequencies of the other symptoms demonstrate a greater variability among centers. Males are more affected than females. The relative frequency of neurological abnormalities is higher among babies with low birthweight, short gestational age or retarded intrauterine growth. Also, the frequency of seizures is higher among babies with low birthweight or retarded intrauterine growth while the relationship between seizures and gestational age is not clear.

Mortality in the first week of life and mode of delivery.

11 923 singletons with birthweight greater than 775 g born consecutively at the 2nd School of Medicine of Naples during a four-year period (November 1975 to October 1979) were the subjects of the study. Mortality in the first week of life was 10.9, 9.7, 6.7 and 10.7 per 1 000 respectively in the four years. The total variability of the crude death rates was reduced by 21.4% after standardization for birthweight distribution alone and by 28.6% when both birthweight and mode of delivery were taken into account. Therefore only a small fraction of the variations in mortality can be ascribed to changes in the distribution of modes of delivery during the study period. Most of these variations are probably related to the quality of perinatal care, which seems to have improved only for babies under 1 526 g. Birthweight specific mortality in relation to mode of delivery is further discussed.

Favism in a female newborn infant whose mother ingested fava beans before delivery.

We describe a case of favism in a female newborn infant with glucose-6-phosphate dehydrogenase (G6PD) deficiency whose mother had ingested fava beans 5 days before delivery. At birth there were clinical and hematologic signs of hemolytic anemia, hemoglobinuria, and no blood group immunization. Study of the G6PD activity and 2-deoxy-glucose-6-phosphate utilization rate revealed that the infant and the mother were heterozygous for G6PD deficiency.

Frequency of and risk factors for allergy in primary school children: results of a population survey.

During May 1986, a survey to assess the frequency of allergic disorders was conducted among primary school children of Alghero, Sardinia, using a structured self-administered questionnaire. The following problems were investigated: allergic conjunctivitis, asthma, wheezing, allergic rhinitis, urticaria and eczema. Of the original 1823 questionnaires distributed, 1961 (92.8%) were completed by parents and returned. Overall, 238 children (14.1%) were reported to have shown at least one episode of one or more of the above and were regarded as 'allergic'. Among the potential risk factors investigated, statistically significant differences (P less than 0.05) between allergic and non-allergic children were only found for history of allergy in at least one parent (odds ratio, OR = 2.2) and exposure to passive smoking (OR = 1.4).

Epidemiology and genetics of microtia-anotia: a registry based study on over one million births.

The epidemiology and genetics of microtia-anotia (M-A) were studied using data collected from the Italian Multicentre Birth Defects Registry (IPIMC) from 1983 to 1992. Among 1,173, 794 births, we identified 172 with M-A, a rate of 1.46/10,000; 38 infants (22.1%) had anotia. Of the 172 infants, 114 (66.2%) had an isolated defect, 48 (27.9%) were multiformed infants (MMI) with M-A, and 10 (5.8%) had a well defined syndrome. The frequency of bilateral defects among non-syndromic cases was 12% compared to 50% of syndromic cases (p = 0.007). Among the MMI only holoprosencephaly was preferentially associated with M-A (four cases observed upsilon 0.7 expected, p = 0.005). No significant variations were identified in the prevalence of non-syndromic cases by geographical area (range 0.62-2.37/10,000 births) or by five month time periods (range 0.21-2.58/10,000 births), nor was there evidence of time trends. When M-A cases were compared to controls, we found that mothers with parity 1 had a higher risk of giving birth to an MMI with M-A, and that mothers with chronic maternal insulin dependent diabetes were at significantly higher risk for having a child with M-A. MMI with M-A had higher rates of prematurity, low birth weight, reduced intrauterine growth, and neonatal mortality than infants with isolated M-A and controls. Babies with isolated M-A had, on average, a lower birth weight than controls; the difference was higher for females. The analysis of pedigrees and familial cases suggests an autosomal dominant trait with variable expression and incomplete penetrance in a proportion of cases, or a multifactorial aetiology. Three cases had consanguineous parents, but the absence of M-A among previous sibs does not support autosomal recessive inheritance.