To document excipient exposure in vulnerable preterm babies in a single centre, taking into account chronic lung disease (CLD) as a marker of illness severity.

Excipient exposure after treatment with eight oral liquid medications was determined by retrospectively analysing the drug charts of infants admitted to a neonatal unit.

The Leicester Neonatal Service.

38 infants born between June 2005 and July 2006 who were less than 30 weeks’ gestation and 1500 g in weight at birth and managed in Leicester to discharge.

The 38 infants represented 53% of the eligible target group; 7/38 infants had CLD. During their in-patient stay, infants were exposed to over 20 excipients including ethanol and propylene glycol, chemicals associated with neurotoxicity. Infants with CLD were exposed to higher concentrations of these toxins. Infants were also exposed to high concentrations of sorbitol, with some infants being exposed to concentrations in excess of recommended guidelines for maximum exposure in adults.

Preterm infants are commonly exposed to excipients, some of which are potentially toxic. Strategies aimed at reducing excipient load in preterm infants are urgently required

To assess the effectiveness of utilising a combined approach of clinical signs, metabolic acidosis and absolute blood pressure (BP) values when deciding to treat hypotension in the extremely low birthweight (ELBW) infant.

Retrospective cohort study of all live born ELBW infants admitted to our neonatal intensive care unit over a 4-year period. Patients were grouped as either normotensive (BP never less than GA), hypotensive and not treated (BP<GA but signs of good perfusion; we termed this permissive hypotension) and hypotensive treated (BP<GA with signs of poor perfusion).

118 patients were admitted during this period. Blood pressure data were available on 108 patients. 53% of patients were hypotensive (mean BP in mm Hg less than GA in weeks). Treated patients had lower birth weight and GA, and significantly lower blood pressure at 6, 12, 18 and 24 h. Normotensive patients and patients designated as having permissive hypotension had similar outcomes. Mean blood pressure in the permissive group increased from 26 mm Hg at 6 h to 31 mm Hg at 24 h. In a logistic regression model, treated hypotension is independently associated with mortality, odds ratio 8.0 (95% CI 2.3 to 28, p<0.001).

Blood pressure spontaneously improves in ELBW infants during the first 24 h. Infants hypotensive on GA criteria but with clinical evidence of good perfusion had as good an outcome as normotensive patients. Treated low blood pressure was associated with adverse outcome.

To assess the effect of four NCPAP/NIPPV systems on the rate of bradycardias and desaturation events in very low birthweight infants.

Sixteen infants (mean gestational age at time of study 31 weeks, 10 males) with AOP were enrolled in a randomised controlled trial with a crossover design. The infants were allocated to receive nasal pressure support using four different modes for 6 h each: NIPPV via a conventional ventilator, NIPPV and NCPAP via a variable flow device, and NCPAP delivered via a constant flow underwater bubble system. The primary outcome was the cumulative event rate of bradycardias (<=80 beats per minute) and desaturation events (<=80% arterial oxygen saturation), which was obtained from cardio-respiratory recordings.

The median event rate was 6.7 per hour with the conventional ventilator in NIPPV mode, and 2.8 and 4.4 per hour with the variable flow device in NCPAP and NIPPV mode, respectively (p value<0.03 for both compared to NIPPV/conventional ventilator). There was no significant difference between the NIPPV/conventional ventilator and the underwater bubble system.

A variable flow NCPAP device may be more effective in treating AOP in preterm infants than a conventional ventilator in NIPPV mode. It remains unclear whether synchronised NIPPV would be even more effective.

Postal questionnaire to 235 neonatal units, with telephone follow-up of non-respondents.

The response rate was 90%, and 96% of respondents had a formal NAS guideline. The median number of infants treated annually for NAS was 6 (range 1–100). The method of Finnegan was the most widely used scoring system (52%). Morphine sulphate was the most commonly used first line agent for both opiate (92%) and polysubstance (69%) withdrawal. Dosing regimens varied widely. Units using a maximum daily morphine dose of <400 µg/kg/day were more likely to require the addition of a second agent (76% vs 58%, p = 0.027). Phenobarbitone was the drug of choice to treat seizures secondary to both opiate and polydrug withdrawal in 73% and 81% of units, respectively. 29% of units allowed infants to be discharged home on medication. 58% of these allowed administration of opiates in the community and in almost half of cases this was managed by a parent. Mothers on methadone whose serology was positive for hepatitis B and/or C were four times more likely to be discouraged from breastfeeding.

The majority of units currently use an opiate as the drug of first choice as recommended. Doses utilised and second agents added vary significantly between units. Many of our findings reflect the lack of high-quality randomised studies regarding management of NAS.

Comparison of 10 separate geographically defined European populations, from nine European countries, over a 1-year period (7 months in one region).

All births that occurred between 22⁺⁰ and 31⁺⁶ weeks of gestation in 2003.

Neonatal death rate adjusted for rate of delivery at this gestation.

Rate of delivery of all births at 22⁺⁰–31⁺⁶ weeks of gestation and live births only were calculated for each region. Two regions had significantly higher rates of very preterm delivery per 1000 births: Trent UK (16.8, 95% CI 15.7 to 17.9) and Northern UK (17.1, 95% CI 15.6 to 18.6); group mean 13.2 (95% CI 12.9 to 13.5). Four regions had rates significantly below the group average: Portugal North (10.7, 95% CI 9.6 to 11.8), Eastern and Central Netherlands (10.6, 95% CI 9.7 to 11.6), Eastern Denmark (11.2, 95% CI 10.1 to 12.4) and Lazio in Italy (11.0, 95% CI 10.1 to 11.9). Similar trends were seen in live birth data. Published rates of neonatal death for each region were then adjusted by applying (a) a standardised rate of very preterm delivery and (b) the existing death rate for babies born at this gestation in the individual region. This produced much greater homogeneity in terms of neonatal mortality.

Variation in the rate of very preterm delivery has a major influence on reported neonatal death rates.

To systematically review evidence for the association of TNF (–308A) with BPD.

Systematic review and meta-analysis of genetic association studies.

Six cohort studies in which a total of 804 preterm infants participated were identified. The studies were generally of fair methodological quality. None of the individual studies or a fixed-effects meta-analysis of the six studies found a significant association of TNF (–308A) genotype with the development of BPD: pooled relative risk 1.03 (95% CI 0.85 to 1.25).

These data suggest that the TNF (–308A) polymorphism is not strongly associated with the risk of developing BPD in very preterm infants. The 95% confidence interval is consistent with an association no stronger than a relative increase in risk of 25%. Future research efforts to define genetic predisposition to BPD should focus on alternative candidate genes.

We collected information about patient characteristics, condition at birth, resuscitation details, severity of encephalopathy, hourly temperature record, clinical complications and outcomes before hospital discharge.

120 infants born at a median of 40 (IQR 38–41) weeks’ gestation and weighing a median of 3287 (IQR 2895–3710) g at birth were studied. Cooling was started at a median of 3 h 54 min (IQR 2 h–5 h 32 min) after birth. All but three infants underwent whole body cooling. The mean (SD) rectal temperature from 6 to 72 h of the cooling period was 33.57°C (0.51°C). The daily encephalopathy score fell: median (IQR) 11 (6–15), 9.7 (5–14), 8 (5–13) and 7 (2–12) on days 1–4 after birth, respectively. 51% of the infants established full oral feeding at a median (range) of 9 (4–24) days. 26% of the study infants died. MRI was consistent with hypoxia-ischaemia in most cases. Clinical complications were not considered to be due to hypothermia.

In the UK, therapeutic hypothermia following perinatal asphyxia is increasingly being provided. The target body temperature is successfully achieved and the clinical complications observed were not attributed to hypothermia. Treatment with hypothermia may have prevented the worsening of the encephalopathy that is commonly observed following asphyxia.

To determine the prevalence of significant renal anomalies and the need for routine postnatal renal imaging in infants with isolated SUA.

Consecutive infants born over 6 years with isolated SUA were offered renal sonography at 4–8 weeks of age. The prevalence of clinically significant renal anomalies in these infants was compared with that detected through routine antenatal fetal scanning and postnatal case findings in a geographically defined control cohort.

During the study period, SUA was found in 137 of 33 067 (4.1/1000) live born infants. Infants with isolated SUA (n = 129) were significantly more likely to be preterm and small for gestational age. 122 infants with isolated SUA (95%) underwent renal ultrasonography; only two infants (1.6%, 95% CI 0.20 to 5.5) had clinically significant renal anomalies, a prevalence similar to that in the control cohort (0.4%, 95% CI 0.29 to 0.45; p = 0.74). Four of eight infants with coexistent systemic malformations had abnormal postnatal renal imaging.

The presence of isolated SUA is associated with increased risk of prematurity and fetal growth restriction. In this largest series of isolated SUA, there was no excess of significant renal malformations among infants with isolated SUA. Postnatal renal ultrasonography is not routinely warranted in such infants.

Literature was identified by searching two bibliographical databases between 1980 and 2007. Studies were assessed for quality and stratified according to the definition of bowel dilatation. The data extracted were inspected for clinical and methodological heterogeneity.

The search strategy yielded 1335 potentially relevant citations. Full manuscripts were retrieved for 92 citations. 10 studies (273 patients) were finally included in the systematic review. No difference was found between groups for death within 4 weeks of delivery (OR = 0.62 (95% CI 0.11 to 3.32); heterogeneity p = 0.39) or bowel resection (OR = 3.35 (95% CI 0.82 to 13.74); heterogeneity p = 0.39). There were insufficient data to compare the risk of intrauterine death and length of time to oral feeds. The mean inpatient stay was not significantly different between groups (OR = 16.63 (95% CI 0.98 to 32.28); heterogeneity p = 0.23).

Current available evidence suggests that fetuses with isolated gastroschisis and bowel dilatation are not at increased risk of adverse perinatal outcome compared to those without bowel dilatation. However, there is a paucity of studies, and a randomised controlled trial is urgently needed.

To determine whether this policy had reduced the rates of fungal colonisation and invasive fungal infection.

All neonates of <33 weeks’ gestation born between 1998 and 2003 were studied. Neonates born between January 1998 and October 2000 who did not receive nystatin prophylaxis (group A) were compared with those born between November 2000 and December 2003 who received nystatin prophylaxis (group B). Infant details, blood culture results and the results of weekly surface swabs were recorded.

1459 neonates (group A = 724 , group B = 735) of <33 weeks’ gestation were admitted in the study period. There were no differences in birth weight, gestation, gender or proportion of babies transferred in from other units between the groups. There was a reduction in colonisation from 257 (35.5%) in group A to 132 (18%) in group B. The incidence of invasive fungaemia decreased from 30 (4.1%) to 13 (1.8%) between the two groups. There was also a reduction in mortality between the two groups from 17.8% to 11.8%.

The introduction of a prophylactic nystatin administration policy for babies born before 33 weeks was associated with a significant reduction in fungal colonisation and invasive fungal infection.

The V_T required to maintain adequate partial pressure of carbon dioxide (Pco₂) levels changes as the underlying disease evolves in infants ventilated for prolonged periods.

To obtain normative data for V_T associated with normocapnia in ELBW infants ventilated with Volume Guarantee over the first 3 weeks of life.

Set and measured V_T, peak pressure, respiratory rate and blood gas values were extracted from the records of babies <800 g born January 2003 to August 2005 and ventilated with Volume Guarantee. Data were collected at the time of each blood gas measurement during days 1–2, 5–7 and 14–21. Only the V_T corresponding to Pco₂ values within a defined normal range were included. Descriptive statistics were used to define the patient cohort. Mean V_T and Pco₂ for each patient during each epoch was calculated, and these values were analysed by repeated-measures analysis of variance.

Twenty-six infants, mean (SD) birth weight 615 (104) g, were included. A total of 828 paired blood gas and V_T sets were analysed: days 1–2 = 251; days 5–7 = 185; days 14–17 = 216; days 18–21 = 176. Pco₂ values (mean (SD)) rose from 44.0 (5.4) mm Hg on days 1–2 to 46.3 (5.2) mm Hg on days 5–7 and remained stable during days 14–17 and 18–21 (53.9 (6.8) and 53.9 (6.2) mm Hg, respectively). Mean exhaled V_T rose from 5.15 (0.62) ml/kg on day 1 to 5.24 (0.71) ml/kg on days 5–7, 5.63 (1.0) ml/kg on days 14–17, and 6.07 (1.4) ml/kg on days 18–21 (p<0.05).

Despite permissive hypercapnia, V_T requirement rises with advancing postnatal age in ELBW infants. The increase is greatest during the third week of life, which is probably due to distension of the upper airways (acquired tracheomegaly) and increasing heterogeneity of lung inflation (increased alveolar dead space).

Of 307 extremely preterm (<=25 weeks) survivors born in the UK and Ireland in 1995, 219 (71%) were re-assessed at 11 years of age and compared to 153 classmates born at term, using standardised tests of cognitive ability and academic attainment and teacher reports of school performance and SEN. Multiple imputation was used to correct for selective dropout.

Extremely preterm children had significantly lower scores than classmates for cognitive ability (–20 points; 95% CI –23 to –17), reading (–18 points; –22 to –15) and mathematics (–27 points; –31 to –23). Twenty nine (13%) extremely preterm children attended special school. In mainstream schools, 105 (57%) extremely preterm children had SEN (OR 10; 6 to 18) and 103 (55%) required SEN resource provision (OR 10; 6 to 18). Teachers rated 50% of extremely preterm children as having below average attainment compared with 5% of classmates (OR 18; 8 to 41). Extremely preterm children who entered compulsory education an academic year early due to preterm birth had similar academic attainment but required more SEN support (OR 2; 1.0 to 3.6).

Extremely preterm survivors remain at high risk for learning impairments and poor academic attainment in middle childhood. A significant proportion require full-time specialist education and over half of those attending mainstream schools require additional health or educational resources to access the national curriculum. The prevalence and impact of SEN are likely to increase as these children approach the transition to secondary school.

Data on neonates transferred for surgical care from January to December 2007 were obtained from the National Neonatal Audit Programme database. Information on origin and destination of transfer was used to assess what proportion of infants required transfer to another network or, in the six network centres without a surgical service, to a more distant surgical centre than appropriate.

Information was available from 18 of the 24 neonatal networks and identified 484 infants transferred for surgery for whom complete data were available. Ninety-one infants (18.8%) were transferred out of network or to a more distant centre than appropriate. This compares with 3.6% for all network patients and far exceeds the maximum figure of 5% recommended by the National Audit Office. Only one network was able to use a single surgical centre for transfers, and the median number of surgical units accessed in the year was 3 (range 1–8).

Neonates requiring surgical care in England often need transfer beyond the local network. The reasons for this need further investigation by a prospective audit of access to neonatal surgical care.

Case–control study.

Medium/high-care neonatal unit of a large district general hospital.

Preterm infants (<37 weeks’ gestational age).

Early discharge with tube feeding under close supervision by paediatric nurse specialists or regular follow-up of preterm infants discharged with oral feeding.

Duration of breast feeding assessed by telephone interview 6 months after birth.

There were 50 preterm infants in the early discharge group and 78 in the control group. Mothers in the early discharge group continued to breast feed longer than mothers in the control group (log rank test, p = 0.028). Four months after discharge, 63% of preterm infants in the control group were fed formula compared to 36% in the early discharge group (95% CI for difference 9% to 43%, p = 0.04). The relative risk of breast feeding cessation 6 months after birth in the early discharge group compared to the control group was 0.63 (95% CI 0.41 to 0.96). After adjustment for smoking, gestational age and birth weight, this relative risk was 0.67 (95% CI 0.43 to 1.05).

Close supervision and follow-up by paediatric nurse specialists of preterm infants discharged early with tube feeding appears to increase duration of breast feeding. A randomised controlled trial to confirm these findings is warranted.

We tested 27-gauge polyurethane Premicath and 24-gauge silicone ECC (both Vygon, Norristown, PA) catheters. Burst pressures were determined by applying a slowly ramped pressure to catheters that were occluded at the tip. Flow–pressure relationships were defined by increasing flow rates through patent catheters from 5 to 499 ml/h. Pressure changes during the manual flushing of catheters were determined for patent and occluded catheters and with different syringe sizes.

The mean burst pressure for polyurethane catheters (1730.8 kPa, 95% CI 1634.7 to 1826.8) was higher than for silicone catheters (275.6 kPa, 95% CI 240.4 to 310.8). Polyurethane catheters demonstrated an approximately fivefold greater margin of safety above manufacturer recommended operating pressures before burst compared to silicone catheters. Pressures remained at safe levels in both catheters over the range of flows generally used in neonatal practice. Hand-flushing of obstructed silicone catheters caused rupture in 5/6 silicone catheters tested, in comparison to 0/16 polyurethane catheters.

Polyurethane central venous catheters have a greater pressure tolerance than silicone catheters and are less likely to rupture under experimental conditions. Obstructed silicone catheters rupture easily when flushed. Catheters were not tested in human infants.

52 children with cPVL were compared to 46 preterm and 395 term controls using retrospective cohort analysis. IL-6 genotyping was performed using an allele specific polymerase chain reaction technique.

IL-6 G(–174)C polymorphisms did not differ between groups, but an association between mental retardation and the IL-6 C/C (78%) and G/C (43%) genotypes compared to the G/G (25%) genotype was found (p = 0.003 and 0.043, respectively; RR 3.11 (95% CI 1.54 to 6.29) and 1.79 (95% CI 1.10 to 2.92), respectively).

The IL-6 (–174) C/C and G/C genotypes were associated with mental retardation in cPVL and seem to modify the severity of perinatal brain injury.