Free-radical-induced reperfusion injury has been recognised as an important cause of brain tissue damage after birth asphyxia. Allopurinol reduces the formation of free radicals, thereby potentially limiting the amount of hypoxia–reperfusion damage. In this study the long-term outcome of neonatal allopurinol treatment after birth asphyxia was examined.
Follow-up of 4 to 8 years of two earlier performed randomised controlled trials.
Leiden University Medical Center, University Medical Center Groningen and University Medical Center Utrecht, The Netherlands.
Fifty-four term infants were included when suffering from moderate-to-severe birth asphyxia in two previously performed trials.
Infants either received 40 mg/kg allopurinol (with an interval of 12 h) starting within 4 h after birth or served as controls.
Children, who survived, were assessed with the Wechsler Preschool and Primary Scales of Intelligence test or Wechsler Intelligence Scale for Children and underwent a neurological examination. The effect of allopurinol on severe adverse outcome (defined as mortality or severe disability at the age of 4–8 years) was examined in the total group of asphyxiated infants and in a predefined subgroup of moderately asphyxiated infants (based on the amplitude integrated electroencephalogram).
The mean age during follow-up (n=23) was 5 years and 5 months (SD 1 year and 2 months). There were no differences in long-term outcome between the allopurinol-treated infants and controls. However, subgroup analysis of the moderately asphyxiated group showed significantly less severe adverse outcome in the allopurinol-treated infants compared with controls (25% vs 65%; RR 0.40, 95%CI 0.17 to 0.94).
The reported data may suggest a (neuro)protective effect of neonatal allopurinol treatment in moderately asphyxiated infants.
To compare school performance at age 5 years in children born at full term (39–41 weeks gestation) with those born at early term (37–38 weeks gestation), late preterm (34–36 weeks gestation), moderately preterm (32–33 weeks gestation) and very preterm (<32 weeks gestation).
Population-based cohort (UK Millennium Cohort Study).
Seven thousand six hundred and fifty children born in 2000–2001 and attending school in England in 2006.
School performance was measured using the foundation stage profile (FSP), a statutory assessment by teachers at the end of the child's first school year. The FSP comprises 13 assessment scales (scored from 1 to 9). Children who achieve an average of 6 points per scale and at least 6 in certain scales are classified as ‘reaching a good level of overall achievement’.
Fifty-one per cent of full term children had not reached a good level of overall achievement; this proportion increased with prematurity (55% in early term, 59% in late preterm, 63% in moderately preterm and 66% in very preterm children). Compared with full term children, an elevated risk remained after adjustment, even in early term (adjusted RR 1.05, 95% 1.00 to 1.11) and late preterm children (adjusted RR 1.12, 95% CI 1.04 to 1.22). Similar effects were noted for ‘not working securely’ in mathematical development, physical development and creative development. The effects of late preterm and early term birth were small in comparison with other risk factors.
Late preterm and early term birth are associated with an increased risk of poorer educational achievement at age 5 years.
To measure nursing workload and timely completion of essential tasks in relation to the staffing levels recommended by the British Association of Perinatal Medicine (BAPM) in Staffordshire, Shropshire and Black CountryNewborn Network.
A prospective observational study was conducted measuring the time taken by selected nurses to undertake the necessary tasks for babies receiving different levels of care in the Network's six constituent neonatal units. An independent observer was used. The unit and individual's workload was evaluated against BAPM standards. Delays in essential predetermined tasks were recorded. The impact on quantity of care given and on the number of delayed tasks were compared between those with the recommended workload or less and those overstretched.
Between October 2008 and February 2009, 89 nurses were observed caring for 244 neonates over 534 h. 54% of nursing shifts failed to meet BAPM standards. Nurses with workload greater than the BAPM-recommended levels demonstrated a 28% decrease in median time spent on clinical care per baby. 92 (17%) essential tasks were delayed >1 h or not done. Delays/omissions were more likely when BAPM standards were not met (53% vs 40%, p=0.049). In nursing observations without delays/omissions, accommodating for adequate nursing breaks and working in the same area, nurses could cater for no more than 1.2, 1.5 and 2.7 babies in intensive care, high dependency care and special care, respectively.
Understaffing leads to measurable problems including delays to essential treatment and reduced clinical care. BAPM standards are not aspirational and should be regarded as a minimum. Further research on optimising nursing care efficiency with limited nursing resources is necessary.
To identify the workload related to provision of a neonatal surgical service in a UK neonatal network in order to inform local and national service commissioning.
Data relating to neonatal surgical admissions to a level 3 perinatal centre serving a network with 36 000 births per year collected prospectively over a 5-year period were analysed to identify annual activity. Daily dependency was assessed prospectively over a 6-month period and service costs calculated using existing local tariffs. Admissions from outside the network were excluded from analysis, and allowance was made for refused network admissions.
On average 140 admissions required 2137 cot-days per year. At 80% occupancy, the service requires seven neonatal cots suggesting that there is a national requirement for one neonatal surgical cot per 5000 births. Intensive care, high care (HC) and special care accounted for 37%, 46% and 17% of cot-days, respectively. This equates to an annual service cost of £2m, about £250 000 per 5000 births.
This assessment of the facilities and costs required to provide a neonatal surgical service in a level 3 perinatal centre in the UK may be used to inform network and national commissioning.
To study the organisms causing early and late onset neonatal sepsis, with special reference to multi-drug resistant gram negative bacilli, at two neonatal units (one urban, one rural) in India.
Prospective surveillance study.
There were 159 episodes of sepsis (81 urban and 77 rural) affecting 158 babies. Gram negative bacilli caused 117 infections (68%) and predominated at both centres in both early and late sepsis. Klebsiella pneumoniae was the commonest organism, causing 61 infections (38.3%). In early sepsis (0–2 days), non-fermenting gram negative bacilli caused 42.1% of infections at the urban centre; there were no cases of early Group B Streptococcus sepsis. Late onset sepsis was mainly caused by gram negative bacilli at both centres. Multi-drug resistance of over 80% of early-onset gram negative organisms to ampicillin, third generation cephalosporins and gentamicin indicates that these multi-resistant organisms are almost certainly circulating widely in the community. The overall mortality from early sepsis was 27.3% (9 of 33) and from late sepsis was 26.2% (33 of 126). Gram negative bacilli caused all deaths from early sepsis and 87.5% of deaths from late sepsis.
This study shows that multi-drug resistant gram negative bacilli are a major cause of early and late neonatal sepsis in India and are almost certainly widespread in the community.
The authors previously showed that 48% of infants <800 g were ventilated with tidal volume (VT) < dead space (DS) using volume guarantee (VG) ventilation. Here, The authors sought to confirm those findings under the rigorous conditions of a bench study.
The authors measured the time to wash out CO2 from a 45-ml test lung using end-tidal CO2 monitor (ETCO2). The test lung was filled with 100% CO2, then ventilated using VG at VT ranging from DS+2 ml to DS–1.5 ml. With ventilation, ETCO2 declined exponentially as CO2 was washed out, the rate being proportional to VT – effective instrumental DS. The time from initiation of ventilation to threshold of accurate detection was determined in triplicate.
Halving the theoretical ‘alveolar ventilation’ (DS+2 ml to DS+1 ml) only increased the elimination time by 26%, not the 100%, as predicted by conventional physiology. CO2 washout was less efficient, but still occurred even at VT=DS and VT=DS–1.5 ml. Halving the theoretical ‘alveolar ventilation’ by decreasing respiratory rate from 80 to 40 breaths/min only increased elimination time by 35%, not 100%, as predicted by conventional physiology. Twenty minutes of continuous positive airway pressure prior to ventilation did not alter the elimination time, verifying that CO2 did not diffuse or leak out of the test lung. Size of the endotracheal tube (ETT; 2.5, 3.0 and 3.5 mm) flow rate (4, 6 and 10 l/min) and inspiratory time (0.25 vs 0.35 s) did not affect the results.
Contrary to conventional physiology, effective CO2 elimination appears to be possible with VT<DS even at conventional rates. With small ETT a spike of fresh gas likely penetrates through the DS, rather than pushing it ahead.
To determine the characteristics of dopamine D2 receptor gene (DRD2) polymorphisms in drug-exposed and unexposed neonates and the relationship to neonatal abstinence syndrome (NAS).
Retrospective case-control analysis between drug-exposed and unexposed infants between DRD2 polymorphisms, drug exposure and NAS treatment.
Drug-exposed (n=48) and drug-free (n=49) infants born between March 1999 and December 2006.
Analysis of DNA for the Taq1A, -141Ins/Del and Ser311Cys DRD2 polymorphisms. Drug exposure was determined by antenatal maternal drug and alcohol history. Frequency measures of DRD2 polymorphisms were compared between drug-exposed infants, treatment NAS medication and with control infants.
Tertiary maternity hospital, Sydney, Australia.
All infants were born in a good condition (25.7% <37 weeks gestation). Opiates (methadone and heroin) were used by 45 (93.8%) of drug-exposed mothers. The A2A2 allele was more common in drug-exposed infants (37 (77.0%) versus 23 (46.9%), p=0.003) but the A1A2 allele was more common in control infants (23 (46.9%) versus 4 (8.3%), p=0.00002). The-ins allele was more common in control (39 (79.6%) versus 20 (41.7%), p=<0.01) and unmedicated drug-exposed (14/25 (56%) versus 5/23 (21.7%), p=0.02) infants. The majority of infants (41 (83.7%) controls versus 41 (85.4%), p=1.000) expressed the least common, Ser polymorphism.
DRD2 polymorphisms are detectable from DNA obtained from stored blood spots. The –ins allele is more common in control and unmedicated drug-exposed infants. Further study is recommended to explore postneonatal outcomes especially in relation to neuropsychiatric behaviours.
During air flight, cabin pressurisation produces an effective fraction of inspired oxygen (FiO2) of 0.15. This can cause hypoxia in predisposed individuals, including infants with bronchopulmonary dysplasia (BPD), but the effect on ex-preterm babies without BPD was uncertain. The consequences of feeding a baby during the hypoxia challenge were also unknown.
Ex-preterm (without BPD) and term infants had fitness to fly tests (including a period of feeding) at 3 or 6 months corrected gestational age (CGA) in a body plethysmograph with an FiO2 of 0.15 for 20 min. A ‘failed’ test was defined as oxygen saturation (SpO2) <90% for at least 2 min.
41 term and 30 ex-preterm babies (mean gestational age 39.8 and 33.1 weeks, respectively) exhibited a significant median drop in SpO2 (median –6%, p<0.0001); there was no difference between term versus ex-preterm babies, or 3 versus 6 months. Two term (5%) and two ex-preterm (7%) babies failed the challenge. The SpO2 dropped further during feeding (median –4% in term and –2% in ex-preterm, p<0.0001), with transient desaturation (up to 30 s) <90% seen in 8/36 (22%) term and 9/28 (32%) ex-preterm infants; the ex-preterm babies desaturated more quickly (median 1 vs 3 min, p=0.002).
Ex-preterm babies without BPD and who are at least 3 months CGA do not appear to be a particularly at-risk group for air travel, and routine preflight testing is not indicated. Feeding babies in an FiO2 of 0.15 leads to a further fall in SpO2, which is significant but transient.
The authors had previously found flaws in resuscitation after severe neonatal asphyxia in cases selected on the grounds of suspected malpractice and financial compensation claims. The aim of the present study was to evaluate neonatal resuscitation in the general obstetric population in a setting with skilled attendance at birth.
Observational study.
All infants born in the Stockholm County during 2004–2006 with a gestational age of ≥33 weeks, planned as vaginal delivery, with a normal cardiotocographic recording on admission to hospital and with an Apgar score of <7 at 5 min were included.
Adherence to guidelines for neonatal resuscitation.
Documentation was unsatisfactory in 142 (45%) infants. Other important shortcomings identified were delayed initiation of extensive resuscitation due to late paging or late arrival of attending paediatrician/neonatologist (n=48), and unsatisfactory ventilation related to late intubation and late securing of free airway (n=15).
Substandard care in neonatal resuscitation is not limited to cases of severe asphyxia related to claims for medical malpractice. The overall documentation of neonatal resuscitation needs to be much better to enable accurate and reliable evaluation. Obvious actions to improve standards of care include the paging of skilled personnel at an earlier stage in cases of complicated deliveries and team and skills training in neonatal ventilation.