Sodium bicarbonate infusion during resuscitation of infants at birth.

BACKGROUND: For many years, intravenous sodium bicarbonate has been used to reverse acidosis during newborn resuscitation. However, controversy surrounds its use. Most of the evidence has been derived from studies in animals, adult humans, or in uncontrolled, descriptive experiments. Despite the lack of evidence from the human neonatal population and concerns about its safety, some international resuscitation guidelines still recommend the use of sodium bicarbonate in resuscitation of the newborn. OBJECTIVES: To determine whether an intravenous infusion of sodium bicarbonate, compared to placebo or no treatment, reduces mortality and morbidity (in particular regarding neurodevelopmental outcome) in infants receiving resuscitation in the delivery room at birth. SEARCH STRATEGY: We used the standard search strategy of the Cochrane Neonatal Review Group. Searches were conducted of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2005), MEDLINE (1966 - September 2005), EMBASE (1980 - September 2005) and CINAHL (1982 - September 2005) and Pediatric Research (1987 - September 2005). Unpublished trials were sought by handsearching the conference proceedings of American Pediatric Society/Society for Pediatric Research (1990 - 2005) and European Society for Paediatric Research (1993 - 2005). SELECTION CRITERIA: Randomised or quasi-randomised controlled trials of newborn infants receiving sodium bicarbonate infusion during any resuscitation in the delivery room at birth. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. Study authors were contacted for additional information. MAIN RESULTS: We found one randomised controlled trial that fulfilled the eligibility criteria (Lokesh 2004) that compared treating asphyxiated newborn infants (infants continuing to need positive pressure ventilation at 5 minutes after birth) with sodium bicarbonate infusion (N = 27) versus 5% dextrose (N = 28). They found no evidence of an effect on mortality prior to discharge [Relative risk 1.04 (95% confidence interval 0.49 to 2.21)], abnormal neurological examination at discharge [Relative risk 0.86 (95% confidence interval 0.30 to 2.50)] or a composite outcome of death or abnormal neurological examination at discharge [Relative risk 0.97 (95% confidence interval 0.59 to 1.60)]. There was no statistically significant difference in the incidence of encephalopathy [Relative risk 1.30 (95% confidence interval 0.88 to 1.92)], intraventricular haemorrhage [Relative risk 1.04 (95% confidence interval 0.23 to 4.70)] and neonatal seizures [Relative risk 1.19 (95% confidence interval 0.50 to 2.82)]. No long term neurodevelopmental outcomes were assessed. AUTHORS' CONCLUSIONS: There is insufficient evidence from randomised controlled trials to determine whether the infusion of sodium bicarbonate reduces mortality and morbidity in infants receiving resuscitation in the delivery room at birth.

Quality of care by neonatal nurse practitioners: a review of the Ashington experiment.

The Ashington experiment, an innovative neonatal service run entirely by advanced neonatal nurse practitioners (ANNPs), has been evaluated. This is a report of that evaluation and a review of the benefits, hazards, and implications of nurse practitioner led services.

UK population based study of severe retinopathy of prematurity: screening, treatment, and outcome.

BACKGROUND: Retinopathy of prematurity (ROP) is one of the few causes of childhood blindness in which severe vision impairment is largely preventable. Ophthalmic screening for ROP is required to identify disease that requires treatment whereby the development of potentially blinding disease can be minimised. OBJECTIVES: To make the first UK population based estimate of the incidence of babies with severe ROP (stage 3 or more); to document their clinical characteristics and management and to evaluate the appropriateness of current ROP screening guidelines in the UK. PATIENTS: Cases were recruited through a national surveillance programme with 1 year ophthalmic follow up and data from clinician completed questionnaires. RESULTS: Between 1 December 1997 and 31 March 1999, 233 preterm babies with stage 3 ROP were identified. Severity (location, extent, and presence of plus disease) was associated with degree of prematurity, most severe in the most premature babies. Fifty nine percent were treated. The UK screening protocol was followed in two thirds of cases, but in the remainder it was begun too late or was too infrequent. Three quarters of the cases were followed up at 1 year, and 13% had a severe vision deficit as a result of ROP. CONCLUSIONS: Visual deficit as a result of ROP in premature babies continues to be a severe disability in some of the survivors of neonatal intensive care. Further efforts are needed to organise treatment regionally to improve outcome and standards of practice.

The EPICure study: associations and antecedents of neurological and developmental disability at 30 months of age following extremely preterm birth.

AIMS: To describe perinatal factors associated with later morbidity among extremely preterm children at 30 months of age corrected for prematurity. POPULATION: Of 308 surviving children born at

Fibrin subunits in venous and arterial thromboembolism.

The subunit fibrin composition of thrombi of both venous and arterial origin was examined by sodium dodecyl sulphate gel electrophoresis. The thrombi were recovered by surgical intervention and all had the same fibrin subunit composition. The alpha chains were cross-linked as alpha-chain polymers alpha (p), the gamma chains as gamma-chain dimers (gamma-gamma) while the beta chains were not crosslinked; a further subunit of molecular weight 33 000 was shown to be present in all the fibrins examined and was a degradation fragment of the beta or gamma chains. This data suggests that the crosslinked alpha chains are rate limiting to the lysis of thrombi in vivo. The digestion of pulmonary emboli by plasmin yielded soluble degradation products which were identified as D dimer and E, the latter fragments being the major products obtained by the lysis of in-vitro made plasma clots. The similarity of the composition and lysis of thrombus fibrin to that formed in vitro augurs well for the justification of in-vitro research on mechanisms in thrombolysis.

Diagnosis of primary hydatid cyst of thigh by fine needle aspiration cytology.

Hydatidosis is a parasitic infestation caused by larval form of the tapeworm, Echinococcus granulosus. Primary hydatid cyst in the skeletal muscles and subcutaneous tissue of thigh without involving thoracic and abdominal organs is an exceptional entity, even in countries where the Echinococcus infestation is endemic. We report an unusual case of primary hydatid cyst of thigh in proximity to skeletal muscles. This case illustrates that echinococcal disease should be considered in the differential diagnosis of every subcutaneous cystic mass. This case is presented here for its rarity.

Insulin, insulin-like growth factor I (IGF-I), IGF-binding protein-1, growth hormone, and feeding in the newborn.

The relationship between GH, insulin-like growth factor I (IGF-I), IGF-binding protein-1 (IGFBP-1), and insulin may be critical to the understanding of variation in early growth, especially in the small for gestational age (SGA) baby. To investigate these relationships, we have undertaken 12-h hormone profiles in 26 babies (13 SGA) at a median of 4.5 days of age. GH levels were measured every 10 min; insulin and IGFBP-1 were measured every 20 min. Mean levels of these hormones and IGF-I levels (from a single sample) were related to size at birth. The GH data were analyzed by Pulsar and time series analysis to characterize hormone pulsatility and relationship with feeds. IGF-I levels correlated with birth weight and length (r2 = 0.47; P = 0.004, and r2 = 0.5; P = 0.0005, respectively, after allowing for gestation), whereas mean GH levels were negatively related to birth size (r2 = -0.18; P = 0.04 and r2 = -0.2; P = 0.03 for weight and length, respectively). No direct relationship between mean GH levels and IGF-I was identified. IGF-I levels were higher in appropriate for gestational age (AGA; mean +/- SD, 82+/-61 ng/mL) than in SGA (34+/-22 ng/mL; P = 0.03) babies. Baseline (mean +/- SD, 25.9+/-11.9), mean (33.9+/-14.0), and peak (45.0+/-18.1 microg/L) GH levels were higher in SGA than in AGA babies [17.1+/-8.2 (P = 0.04), 22.5+/-10.4 (P = 0.03), and 30.7+/-15.4 microg/L (P = 0.04), respectively]. Mean IGFBP-1 levels were also higher in SGA than AGA babies (157.4+/-90.7 vs. 62.7+/-43.8 ng/mL; P = 0.01). A positive correlation was identified between changes in insulin and coincident pulses of GH (r = 0.147; P < 0.01), whereas there was an inverse relationship between insulin and IGFBP-1, with a lag time 120 min (r = -0.33; P < 0.0001). In conclusion, these studies indicate that the GH-IGF-I axis is closely related to feeding in the newborn. In SGA babies, low IGF-I and elevated IGFBP-1 reflect the slow growth, but elevated GH and rapid GH pulsatility may be a signal for lipolysis.

Geleophysic dysplasia: a report of three affected boys--prenatal ultrasound does not detect recurrence.

Geleophysic dysplasia is characterized by short stature with short limbs and brachydactyly, a "happy" facial appearance, and joint contractures. Infiltration of heart valves and liver with a mucopolysaccharide-like substance has been demonstrated in some patients. A metabolic pathogenesis is suspected, but has not yet been identified. We report on 3 boys with the condition, 2 of whom are brothers. Serial ultrasound scans were performed on 2 of the cases during pregnancy, but short limbs did not become obvious until after 28 weeks of gestation, making it an uninformative procedure for prenatal diagnosis.

A randomized comparison of total extracorporeal CO2 removal with conventional mechanical ventilation in experimental hyaline membrane disease.

Apnoeic oxygenation (AO) combined with extracorporeal CO2 removal (ECCO2R), using venovenous perfusion across a membrane area of 0.1 m2 has been shown to be feasible in six healthy anaesthetized rabbits. In a further twelve rabbits, ECCO2R has been randomly compared with conventional mechanical ventilation (CMV) following saline lavage to induce respiratory failure. Blood gases were maintained for up to 6 h within the same range (PaO2 = 8-20 kPa, PaCO2 = 4-6 kPa) in two groups of six by varying airway pressures and the oxygen fraction delivered either to the membrane lung (ECCO2R group) or to the ventilator (CMV group). The influence of single hourly sustained inflations (SI) on oxygenation was studied. ECCO2R subjects remained stable and survived. CMV subjects deteriorated and had 80% mortality. Hyaline membranes were absent from ECCO2R subjects and present in all CMV subjects. The response to SI suggests that a lung volume recruitment is maintained during AO for up to 1 h but is ineffective during CMV.

Surveillance of colonization and late-onset septicaemia in neonates.

Twenty-seven newborns had an episode of late-onset sepsis (septicaemia or bacterial meningitis after 48 h of age) over an 18 month period. Preceding or simultaneous surface cultures were available from 26 babies. Colonization with the organism causing sepsis could only be documented in 10 cases. Colonization with aminoglycoside-resistant Gram negative organisms was common but there were only two cases of systemic sepsis with a resistant organism. Pseudomonas aeruginosa frequently colonized babies over the first 8 months of the survey, but subsequently virtually ceased to colonize babies, although it continued to be a common cause of late-onset sepsis. These findings do not support the utility of routine surveillance of organisms colonizing neonates in predicting bacteria causing late-onset sepsis. They also cast doubt on the value of eliminating colonizing organisms by expensive infection control measures.

Closure of the ductus arteriosus and development of pulmonary branch stenosis in babies of less than 32 weeks gestation.

AIMS: To define how often transient pulmonary branch stenosis (PBS) develops after closure of a patent ductus arteriosus (PDA) in babies born at less than 32 weeks gestation; to describe the natural history of PBS and the relation between PBS and a cardiac murmur. METHODS: Fifty three preterm infants born at a gestational age less than 32 weeks and who had PDA diagnosed on echocardiography were recruited. An echocardiogram was performed on alternate days until the ductus arteriosus closed. If PBS was diagnosed, the baby was followed up until PBS resolved. RESULTS: In 59%, PBS developed in one or both branches after closure of the PDA. In 21%, both pulmonary branches were affected. In 79%, the left pulmonary artery alone was involved but the right side was never affected alone. PBS had resolved in 74% by the time the infants reached 40 weeks, in 95% at a corrected age of 6 weeks, and in 100% at a corrected age of 3 months. There is a better correlation between a cardiac murmur and PBS than between a murmur and PDA. CONCLUSIONS: PBS in preterm infants is usually not present at birth but develops after closure of a PDA. PBS resolves by a corrected age of 3 months. The presence of a murmur after closure of a PDA is usually related to PBS and not to reopening of the ductus arteriosus.

Natural history of innocent heart murmurs in newborn babies: controlled echocardiographic study.

AIM: To define the origin and the natural history of innocent heart murmurs in newborn infants. METHODS: Fifty healthy babies born at term with the clinical diagnosis of an innocent heart murmur and 50 controls without a murmur were studied. Each baby had a complete two dimensional and pulsed Doppler echocardiogram and those with any abnormality were followed up at 6 weeks, 3 months, and 6 months until the murmur had disappeared or the heart was totally normal. Babies with congenital heart disease were excluded from the study. RESULTS: Pulmonary branch stenosis (PBS) was found in 25 (50%) of the study group and in six (12%) controls; patent ductus arteriosus (PDA) in 30 (60%) subjects and in six (12%) controls; and a patent foramen ovale (PFO) in 50 (100%) subjects and in 41 (82%) controls. At 6 weeks the murmur had disappeared in 64% of babies. PBS was still present in eight of 22 (36%) babies at 6 weeks, in 12% at 3 months, but in none at 6 months. At 6 weeks, seven of the eight with PBS still had a murmur compared with two of 14 (14%) babies in which the PBS had resolved (P < 0.005). At 6 weeks the PDA had closed in all patients but the foramen ovale was still patent in 29 of 44 (66%) subjects and nine of 33 (27%) controls. The closure of the PFO was not influenced by its size at birth. CONCLUSIONS: An innocent heart murmur in a baby born at term is often related to PBS, particularly if the murmur is still present after 24 hours of age, when most PDA have closed. At 6 weeks the murmur had disappeared and the PBS had resolved in 64% of the babies. PBS had resolved in all babies at 6 months.

The EPICure study: growth and associated problems in children born at 25 weeks of gestational age or less.

AIM: To define growth outcomes of a geographically defined population of extremely preterm babies. POPULATION: The EPICure study identified all surviving children in the United Kingdom and Ireland born at < or = 25 weeks 6 days gestation between March and December 1995. Of 308 survivors, 283 (92%) were evaluated at 30 months of age corrected for prematurity. METHODS: Growth was measured as part of a medical and full neurodevelopmental assessment. Growth parameters were evaluated in relation to other 30 month outcomes and perinatal variables. RESULTS: The children were smaller in each of the five growth measures compared with published population norms: mean (SD) standard deviation scores were -1.19 (1.32) for weight, -1.40 (1.37) for head circumference, -0.70 (1.19) for height, -1.00 (1.38) for body mass index, and -0.75 (0.95) for mid-upper arm circumference. Despite being of average size at birth, children were significantly lighter with smaller head circumferences at the expected date of delivery, compared with population norms, and only weight showed later catch up, by 0.5 SD. Poorer growth was found in children whose parents reported feeding problems and with longer duration of oxygen dependency, as a marker for neonatal respiratory illness. Although severe motor disability was associated with smaller head circumference, overall there was no relation between Bayley scores and head growth. CONCLUSIONS: Poor growth in early childhood is common in extremely preterm children, particularly when prolonged courses of systemic steroids have been given for chronic lung disease. Improving early growth must be a priority for clinical care.

Early onset group B streptococcal neonatal infection in Oxford 1985-96.

Of 74,920 babies live born in Oxford between 1985 and 1996, 41 (0.5 per 1000 95% CI 0.4-0.7) developed definite, culture confirmed, early onset (< 48 hours) group B streptococcal infection and 32 (0.4 per 1000 95% CI 0.3-0.6) developed probable infection (sepsis plus colonisation). There was no significant variation in incidence with time. The mortality from definite infection was 19.5%, and from probable infection 6%. These data suggest that the incidence of group B streptococcal infection in Oxford is considerably lower than that reported in the USA.

Comparison of mortality and rates of cerebral palsy in two populations of very low birthweight infants.

Comparisons of mortality and rates of cerebral palsy in different populations can be confusing. This is illustrated by comparing two populations of very low birthweight infants born in the 1980s, one from the Netherlands, the other from the UK (Oxford region). Although a number of biases were controlled for while comparing two large geographically defined populations, by assessing the survivors at similar ages and describing their health status in a standard way, some problems in interpretation of outcome remained. Differences in registration practice of live births at early gestational ages, as well as differences in withholding or withdrawing treatment, which occurred in about half of the cases of neonatal death in the Netherlands and in about one third of those in the Oxford region, may have influenced the incidence of registered live births, neonatal mortality, and the rate of cerebral palsy.

Immaturity of electrophysiological response of the neonatal auditory brainstem to high repetition rates of click stimulation.

Changes in brainstem auditory evoked response (BAER) with varying stimulus repetition primarily represent neural processes concerning the efficacy of synaptic transmission in the brainstem auditory pathway. In this study the BAER to different rates of clicks was recorded from 16 term neonates. The results were compared with those from 16 adults to examine whether the degree of maturation of synaptic transmission of the neonatal brainstem auditory pathway parallels that of general function of the pathway. All BAER wave latencies and interpeak intervals increased linearly and wave amplitudes reduced with increasing click rate. The absolute rate-dependent changes in BAER measures were much greater in the neonates than in the adults, reflecting a significant immaturity in the efficacy of synaptic transmission in the neonatal auditory brainstem and in the ability of the neonatal brainstem to process rapid acoustic stimulation. When the data obtained at higher click rates at various age groups were analyzed as percentages, using the BAER measurements at conventionally used slow rate (21/s) of clicks as the denominators, the changing rates (%), or relative changes, of most BAER measures at higher rates in the neonates were still greater than those in the adults. Therefore, the rate-dependent BAER changes in the neonates are relatively less mature than general aspects of the BAER, reflected by the BAER elicited with conventionally used slow rates of clicks. These findings suggest that synaptic efficacy in the neonatal brainstem auditory pathway is relatively less mature than general function of the pathway and thus may be more susceptible to unfavourable perinatal conditions.

New birthweight and head circumference centiles for gestational ages 24 to 42 weeks.

Based on 20,713 singleton livebirths at the John Radcliffe Hospital, Oxford, in 1978-1984, we calculated new birthweight and head circumference values for males and females between 24 and 42 weeks of gestation. Among the 803 babies born at or before 34 weeks of gestation, 28% were delivered electively for fetal problems; they were considerably lighter and had smaller heads than infants born after spontaneous preterm labour. As we and others have recommended elsewhere, the electively delivered preterm infants were excluded from the calculation of the new birthweight and head circumference centiles. In our series males were heavier and had larger head circumferences than females at most gestational ages. There were consistent and statistically significant differences in birthweight at all gestational ages from 37 weeks and in head circumference at all gestational ages from 35 weeks.

Electrical impedance plethysmography: its use in studying the cerebral circulation of the rabbit.

Electrical impedance plethysmography (EIP) is a noninvasive method that may be useful for both the continuous and serial measurement of changes in pulsatile cerebral blood volume and perhaps cerebral blood flow (CBF). It has not been well validated by comparison with other methods. To attempt to validate the EIP technique, the relationship between the peak amplitude of the transcranial, cardiac-synchronous impedance waveform (dZp) and cerebral blood flow measured by the radiolabelled microsphere technique (CBFrlm) and laser Doppler spectroscopy (CBFlds) was studied in rabbits. CBF was altered by inducing hypertension using metaraminol, hypotension by controlled haemorrhage or hypocarbia by hyperventilation. Twenty-three comparisons between dZp and CBFlds and 19 comparisons with CBFrlm were made in eight rabbits. The percentage change between each measurement using the three techniques in each animal was calculated. Using pooled data from all the animals, the linear regression equations were dZp = 0.5 CBFrlm + 33 (r = 0.38, p = 0.22, SE = 79) and dZp = 0.84 CBFlds + 19.6 (r = 0.46, p = 0.09, SE = 72). It is concluded that, in the anaesthetised rabbit, when large changes in CBF are induced by the manoeuvres described above, changes in dZp correlate very weakly with changes in either cortical or global CBF, and are influenced by other factors such as pulsatile intracranial blood volume.

Functional abilities at age 4 years of children born before 29 weeks of gestation.

OBJECTIVES: To assess the rate of impairment and disability among babies born very preterm and to investigate the association between such impairment and gestational age at birth. DESIGN: Cohort study of a geographically defined population of babies. SETTING: Oxford Regional Health Authority. SUBJECTS: All babies born alive before 29 weeks of gestation to mothers resident in the region during 1984-6. MAIN OUTCOME MEASURES: Survival rates and rates of impairment and disability among survivors at the age of 4 years. RESULTS: Of the 342 babies, half (170) survived to be discharged home. Of the 164 survivors to age 4 years, 153 (93%) were assessed. A total of 35 (23%; 95% confidence interval 16% to 30%) were severely disabled and only 54 (35%; 28% to 43%) were unimpaired. The risk of impairment and disability increased with decreasing gestational age at birth (p < 0.003). CONCLUSIONS: With the increasing survival rate among babies born before 29 weeks of gestation, we need urgently to establish reliable ways of monitoring the proportion of survivors who have a disability.