The analysis of the complement activation product SC5 b-9 is applicable in neonates in spite of their profound C9 deficiency.

Native complement factors and complement activation products were measured in healthy neonates (n = 72) and in a group of infants with premature prolonged rupture of the membranes (PPROM) without sepsis (n = 10). Vitronectin concentration in normal cord blood was not correlated with gestational age, and the median value was 86.0% of adult values. This was markedly higher than other native complement factors studied (factor B: 35.9%, C4: 45.1%, C3: 56.2%). The concentration of C9 showed a positive correlation with gestational age and was very low, 10.8% of normal adult values in cord blood and 8.3% in the patients. Fifteen percent of the neonates had C9 levels lower than 2% of adult values. The complement activation products Bb and SC5 b-9 were significantly elevated in the patients (159% and 130% of control values, respectively), indicating alternative and terminal pathway activation. In contrast, C4 bc and C3 bc levels were not increased. The maximum amount of SC5 b-9 which could be generated in the neonatal sera by cobra venom factor was highly correlated with C9 concentration (rs = 0.86, p = 0.0001) The profound C9 deficiency found in neonates is correlated with gestational age, limits the capacity to form bacteriolytic C5 b-9 (m) and may predispose for severe invasive bacterial infection. The plasma level of SC5 b-9 under normal conditions was very low, only 0.3% (0.1%-3.0%) of the values obtained after CVF activation of the same samples. Therefore, we suggest that the analysis of SC5 b-9 is applicable also in neonates, in spite of their extremely low C9 levels.

C-reactive protein (CRP) response patterns in neonatal septicaemia.

C-reactive protein (CRP) is an unreliable diagnostic tool in the early diagnosis of neonatal septicaemia. However, serial measurements have been shown to be useful in monitoring the effectiveness of treatment. The aim of the present study was to investigate whether a specific CRP response pattern to different groups of pathogens could be identified during treatment of neonatal septicaemia. Serial CRP measurements from day 1 to 4 in monomicrobial blood culture-proven episodes of septicaemia were reviewed. In 4416 admissions, 180 out of 206 positive blood cultures were monomicrobial; 121 monomicrobial septic episodes were eligible for final analysis of the CRP response during treatment. A low median (M) value (day 1 to 4) was identified in coagulase-negative staphylococci (CONS) (M=23 mg/l), contrasting with high median values in Staphylococcus aureus (M=58 mg/l), group B streptococci (M=51 mg/l), Escherichia coli (M=51 mg/l) and Candida species (M=76 mg/l) (p<0.001). Median CRP values in the two groups were different for each of the treatment days 1 to 4 (p<0.001). An increase (p<0.001) in CRP during the 24 h before initiation of treatment was a sign of late-onset CONS septicaemia. In episodes where antimicrobial treatment failed, CRP levels were moderately elevated the day prior to treatment start and increased continuously thereafter, whereas successful treatment was generally accompanied by a decline in CRP in less than 4 days. The CRP response to CONS is significantly less pronounced than to other commonly encountered pathogens in neonatal septicaemia. A rise in CRP beyond the third day of empirical treatment should give rise to a suspicion of fungal infection or ineffective antibacterial treatment.

Antibiotic susceptibility of blood culture isolates after nearly two decades with netilmicin and ampicillin in neonatal septicaemia.

The aim of the study was to investigate the in vitro antibiotic susceptibility of blood culture isolates after almost 20 years with ampicillin and methicillin as empirical treatment for neonatal septicaemia. All blood culture isolates and their antibiograms obtained in a single tertiary neonatal intensive care unit from 1 January 1989 to 31 December 1994 were reviewed. Two hundred and six blood cultures from 181 infants containing 223 bacterial and 11 fungal isolates were identified during 4416 admissions. Fifteen (6.7%) of the bacterial isolates were resistant to ampicillin and netilmicin. Fourteen per cent of the staphylococcal spp. were susceptible to penicillin while more than 90% were susceptible to netilmicin. The coagulase-negative staphylococci (CONS) were resistant to netilmicin, methicillin and gentamicin in 12%, 49% and 65%, respectively. Eighty-nine per cent of the methicillin-resistant CONS were susceptible to netilmicin as opposed to 17% to gentamicin (p<0.001). Except for one strain of Acinetobacter sp., all Gram-negative bacteria were susceptible to netilmicin. Our data show that the ampicillin-netilmicin combination still provides a high in vitro coverage (93%) against bacteria identified in blood cultures from newborns in our unit. Netilmicin has a significantly better in vitro effectiveness against CONS than gentamicin.

Blood culture isolates during 6 years in a tertiary neonatal intensive care unit.

Blood culture results obtained in a single tertiary neonatal intensive care unit are reviewed. In 4416 admissions occurring over 6 y we identified 206 positive cultures (4.7/100 admissions) growing 234 bacterial and fungal isolates in 182 infants. Very early and early onset positive cultures comprised 17% and 22% each. Gram-positive bacteria dominated in very early (61%), early (91%) and late onset (78%) cultures with coagulase-negative staphylococci (CONS) as the most frequent isolate in all groups (22%, 46% and 55%, respectively). The 3 most frequent isolates following CONS were in very early onset cultures Escherichia coli (19%), anaerobic bacteria (17%) and group B streptococci (GBS) (14%), in early onset cultures Staphylococcus aureus (28%), Enterococci (7%), E. coli (6%) and Viridans streptococci (6%) and in late onset cultures S. aureus (15%), Candida species (8%) and E. coli (5%). Infants < or = 999 g birthweight, representing 6% of the admissions, contracted 37% of the positive blood cultures and nearly half (44%) of the CONS isolates. In these patients, a significant increase (p < 0.001) in the number of positive cultures/100 admissions and in the proportion of positive cultures in conjunction with an intravascular catheter were seen (p < 0.001). An intravascular catheter was more often present when CONS were isolated as compared to other organisms (p < 0.05). 23 positive cultures (11.2%), most frequently E. coli, were associated with a fatal outcome. Our microbiological pattern is dominated by a gram-positive flora, which is in agreement with recent European and North American reports, but differs from earlier Scandinavian studies in the proportion of CONS and GBS reported.

Respiratory syncytial virus pneumonia ventilated with high-frequency oscillatory ventilation.

Four infants below 6 months of age with proven respiratory syncytial virus infection in need of assisted mechanical ventilation were successfully treated by high-frequency oscillatory ventilation. One of the four infants fulfilled the criteria for extracorporeal membrane oxygenation before the start of oscillation, and one on the second day on high-frequency oscillatory ventilation. However, extracorporeal membrane oxygenation was not needed in any of the infants. All survived, and three appeared to be without any pulmonary sequelae.

[Collagen analysis in fibroblasts in osteogenesis imperfecta. Clinical benefits]. / Kollagenundersøkelse i fibroblaster ved osteogenesis imperfecta. Klinisk nytte.

We performed collagen analysis in 38 patients with osteogenesis imperfecta. In order to assess the clinical benefit of the analysis, all cases were studied retrospectively. Five patients were children with lethal osteogenesis imperfecta, in whom the diagnosis was confirmed after termination of pregnancy. In the remaining 33 patients, collagen analysis was performed because of clinical suspicion of osteogenesis imperfecta. Child abuse was suspected in seven patients. We found good correlation between the results of collagen analysis and the final diagnoses, which were based on clinical information and observation over time. In this study we also tested a set of diagnostic criteria which seem to be useful in clinical practice. The collagen analysis was of decisive diagnostic value in half (16/33) of the patients, but also in the remaining patients the clinical diagnosis was strengthened. We obtained only one false negative result. Our study indicates that in selected patients where diagnosis is difficult, collagen analysis can be an important tool in establishing the diagnosis osteogenesis imperfecta.

[Survival and morbidity among children with low birth weight]. / Overlevelse og sykelighet blant barn med lav fødselsvekt.

Stillbirth and the mortality rate in low birthweight infants (less than 2,500 g) have been greatly reduced since 1967. 95% of all infants born in 1991-93 whose birthweight was between 500 and 999 g, and who survived to one year of age, would have died under the same circumstances in 1967-69. This improved survival is not, to any appreciable extent, related to an increase in demand at seven years of age for a basic grant or attendance benefit because of cerebral palsy or mental retardation. The number of basic grant and attendance benefits because of eye diseases has been reduced by about half for 7-year olds whose birthweight was low. On the whole, however, the number of basic grant and attendance benefits increased from about 1% in 1974-85 to 2.2% in 1986-94. This increase can be particularly attributed to skin and lung diseases. These results have been obtained by coordinating the record of the Medical Birth Registry of Norway and the records of the Social Security offices for all births (1,566,763) registered during the years 1967-93.

[Ultrasonography and neuropathological findings in premature infants]. / Ultrasonografi og neuropatologiske funn hos premature barn.

At most maternity units all premature infants are investigated by cranial ultrasonography as a routine. We examined the correlation between autopsy findings and ultrasound examination in 30 premature newborn. The ultrasound examination demonstrated bleeding in 17 (65%) of the 26 cases where autopsy had revealed bleeding. In these 17 patients good correlation was found between the degree of bleeding in the two examinations (ultrasonography and autopsy). In ten patients autopsy showed periventricular leucomalacia, but ultrasonography showed this condition in only two of these. In five cases bleeding made the examination and interpretation of the ultrasound findings difficult. In three patients ultrasonography was thought to be normal, while autopsy demonstrated periventricular leucomalacia.

[Retinopathy of prematurity. Experiences with a routine examination]. / Retinopati ved prematuritet. Erfaringer med et undersøkelsesopplegg.

Retinopathy of prematurity continues to be an important cause of serious visual impairment and blindness in children. We have previously suggested a schedule for ophthalmoscopic examinations to identify the serious cases where there may be indication for cryotherapy. We present our experience from this schedule, which covered premature infants with gestational age below 31 weeks and/or birth weight below 1,500 g. 103 infants in two neonatal intensive care units were monitored according to our schedule. Mean gestational age was 27.4 weeks (23 to 33 weeks). Mean birth weight was 995 g (530 to 1,650 g). Retinopathy was found in 27 infants. Six developed stage 3 "plus" disease and five of these had an indication for cryotherapy. No infant with gestational age over 26 weeks or birth weight over 1,000 g had stage 3 "plus" disease. The incidence of retinopathy in our series was low by international standards. We recommend that routine screening for retinopathy should continue in the above gestational age and birth weight groups. Ophthalmological examinations must begin at 5 to 6 weeks postnatal age.

[Ethical considerations in neonatal medicine]. / Etiske overveielser i nyfødtmedisinen.

Ethical dilemmas are a daily occurrence in neonatal intensive care units. Some of these questions relate to life-and-death issues such as whom to treat or not to treat, if and when to discontinue life support, and organ donation. However, other issues are just as important in daily practice. These include the choice of a framework for ethical discussions, the question of who participates in the discussions, the parents' right to participation and information, the process and timing of decision-making, the ethics of clinical research in subjects unable to consent, respect and communication between health professionals, and the limits of confidentiality. In most of these dilemmas there is no quick and easy route to the one and only true answer. Neonatal health care workers are frequently confronted with ethical dilemmas, and are forced to reflect ethically. In this process, it is essential to be able to listen attentively to others, health workers as well as lay persons, and to integrate their opinions into one's own reflections. These two factors together must form the basis for daily clinical work and for ethical decisions.

[Instruction in neonatal resuscitation. A survey among Norwegian pediatricians]. / Opplaering i gjenopplivning av nyfødte. En rundspørring til norske barneleger.

Neonatal resuscitation requires a combination of theoretical knowledge and practical, hands-on skill. By means of a mailed questionnaire we surveyed the training programmes in paediatric departments in Norway. Most departments provide some kind of instruction for new staff members, but several had no structured programmes for maintaining the skills of existing staff. Many departments are too small to provide adequate clinical material for necessary instruction and maintenance of skills. Thus, other kinds of teaching materials should be used. Several departments continue to use recently expired patients for such training, although the Council for Medical Ethics, under the Norwegian Medical Association, has pronounced this practice unethical. We join others who suggest that the Council's position should be reevaluated.

[Resuscitation of newborn infants]. / Resuscitering av nyfødte.

We review techniques and approaches used in the resuscitation of newborns. Charts and tables are provided with respect to what equipment is needed, length of catheter and tube, and drug doses. All maternity centres and neonatal units need to train their staff in the proper procedures and techniques for the resuscitation of newborn infants. This training is an integral part of quality control measures. The present article is intended as an aid in the training of medical personnel, and may be used to support other means of instruction such as audiotapes, videotapes, lectures, and hands-on exercises.

[Transport from a subregional neonatal unit. Experiences from Vestfold Central Hospital during an 11-year period 1982-92]. / Transporter fra en subregional neonatalenhet. Erfaringer fra Vestfold sentralsykehus i 11-årsperioden 1982-92.

A key element of neonatal regionalization is the establishment of transport links between centres of tertiary care and subregional centres. During the 11-year period 1982-92, 186 transports were undertaken from the neonatal unit, Vestfold Central Hospital, for a total of 180 patients, or 0.8% of all live born infants (n = 23,652). 64 patients (36%) were referred for prematurity/respiratory distress syndrome (IRDS), 81 (45%) for congenital malformations, and 35 (19%) for other conditions. Transports for prematurity/IRDS declined significantly from the the first 6-year period 1982-87 to the last 5-year period 1988-92 (3.6 vs. 1.8 per 1,000 live born infants; p < 0.01), owing to the establishment of a local respirator treatment programme for severe IRDS. In 71 (38%) transports the infants were mechanically ventilated. Seven (10%) suffered in-transport complications related to the endotracheal tube. At arrival, significantly more patients were anaemic (Hb < 14 g%; transports before 48 hours after birth), alcalotic (pH > 7.50), hypocapnic (PCO2 < 4 kPa) or had a base excess < -10 mmol/l than before transportation (p < 0.05). There was a tendency towards more patients with hypothermia (tp < 36 degrees C), acidosis (pH (< 7.20) and hypercapnia (PCO2 > 10 kPa) at arrival than before transportation (p > 0.05). No deaths occurred during transport. However, two infants died within two hours after arrival, giving a transport-related mortality rate of 1%. Transporting critically ill neonates implies discontinuity of treatment and monitoring of these infants. Optimal stabilization before transportation, and scrupulous work on technical details are of utmost importance.

[Diagnosis and treatment of infections in a neonatal unit--viral infections, spirochete infections and toxoplasma infections]. / Diagnostikk og behandling av infeksjoner i en neonatalavdeling--virus-, spiroket- og toxoplasmainfeksjoner.

Viral and protozoal infections are often suspected as causes of neonatal illness or congenital anomalies. The TORCH titer has traditionally been the foremost diagnostic tool in this context, but it is now becoming increasingly clear that this tool is inadequate, partly for conceptual reasons, but also because of the often uncritical way in which it is used. During a recent critical review of our routines and practices for diagnosis and treatment of neonatal infections we also revised our approach to the diagnosis and treatment of suspected pre- or perinatally acquired viral, spirochetal, and protozoal illnesses. The resulting guidelines, originally intended for our house staff, are presented here.

[Diagnosis and treatment of infections in a neonatal unit--bacterial and fungal infections]. / Diagnostikk og behandling av infeksjoner i en neonatalavdeling--bakterie- og soppinfeksjoner.

Following an outbreak of Candida septicemia in our intensive care nursery we reviewed our routines for diagnosis and treatment of neonatal infections. The revision resulted in a set of written guidelines for septic work-ups, initiation and discontinuation of antibiotic therapy, and choice of antibiotics. In this article we present the guidelines for dealing with bacterial and fungal infections, along with relevant comments.