Alan C Fenton

Investigating the variations in survival rates for very preterm infants in 10 European regions: the MOSAIC birth cohort

Objective: To investigate the variation in the survival rate and the mortality rates for very preterm infants across Europe. Design: A prospective birth cohort of very preterm infants for 10 geographically defined European regions during 2003, followed to discharge home from hospital. Participants: All deliveries from 22 + 0 to 31 + 6 weeks’ gestation. Main outcome measure: All outcomes of pregnancy by gestational age group, including termination of pregnancy for congenital anomalies and other reasons, antepartum stillbirth, intrapartum stillbirth, labour ward death, death after admission to a neonatal intensive care unit (NICU) and survival to discharge. Results: Overall the proportion of this very preterm cohort who survived to discharge from neonatal care was 89.5%, varying from 93.2% to 74.8% across the regions. Less than 2% of infants <24 weeks’ gestation and approximately half of the infants from 24 to 27 weeks’ gestation survived to discharge home from the NICU. However large variations were seen in the timing of the deaths by region. Among all fetuses alive at onset of labour of 24–27 weeks’ gestation, between 84.0% and 98.9% were born alive and between 64.6% and 97.8% were admitted to the NICU. For babies <24 weeks’ gestation, between 0% and 79.6% of babies alive at onset of labour were admitted to neonatal intensive care. Conclusions: There are wide variations in the survival rates to discharge from neonatal intensive care for very preterm deliveries and in the timing of death across the MOSAIC regions. In order to directly compare international statistics for mortality in very preterm infants, data collection needs to be standardised. We believe that the standard point of comparison should be using all those infants alive at the onset of labour as the denominator for comparisons of mortality rates for very preterm infants analysing the cohort by gestational age band.

Lymphocyte subsets in term and significantly preterm UK infants in the first year of life analysed by single platform flow cytometry

This observational study describes the ranges observed for lymphocyte subsets for significantly preterm infants (<32 weeks) in the first year of life, measured by single platform flow cytometry and compared to identically determined subsets in term infants. After ethical approval 39 term and 28 preterm infants had lymphocyte subset analysis before and after their primary immunization series. Median values with 5th and 95th percentiles of absolute counts and percentages are presented for total lymphocytes, T cells, NK cells, B cells, cytotoxic T cells, helper T cells, dual positive T cells, activated T cells, activated T helper cells (including T regulatory cells), pan memory T cells, pan naïve T cells, memory helper T cells, naïve helper T cells and the T helper/suppressor ratio. The lymphocyte profile of the preterm infants differed from that of the term infants.

Optimising neonatal transfer.

Services for neonatal intensive care in the United Kingdom have evolved in a largely unplanned fashion. Units of different sizes provide various amounts of intensive care, and, with a few exceptions, there is little or no formal regional or subregional organisation. Chronic underresourcing and the salvaging of ever more complex infants have resulted in tertiary neonatal intensive care units operating at full capacity most of the time, a situation compounded by a chronic national shortage of nursing staff. These factors have in turn resulted in an increase in requirements for emergency perinatal transfers.

Rates of very preterm birth in Europe and neonatal mortality rates

Objective: To estimate the influence of variation in the rate of very preterm delivery on the reported rate of neonatal death in 10 European regions. Design: Comparison of 10 separate geographically defined European populations, from nine European countries, over a 1-year period (7 months in one region). Participants: All births that occurred between 22+0 and 31+6 weeks of gestation in 2003. Main outcome measure: Neonatal death rate adjusted for rate of delivery at this gestation. Results: 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. Conclusions: Variation in the rate of very preterm delivery has a major influence on reported neonatal death rates.

Towards safer neonatal transfer: the importance of critical incident review

Background: Critical incidents are common during the inter-hospital transfer of sick patients, and infants are an especially vulnerable group. Aims: To examine the effect of critical incident review on the number of adverse events during inter-hospital transfer of sick infants. Methods: Critical incidents over an eight year period are reported from a single neonatal transfer service before and after major service changes were made. The changes were instigated as part of ongoing critical incident reviews. Results: Changes made as a result of critical incident review significantly reduced the number of incidents contributed to by poor preparation, transport equipment or clinical problems, ambulance delays, and ambulance equipment failure. Conclusions: The continuous process of critical incident reporting and review can reduce the number of adverse events during the transfer of critically ill infants.

Haemophilus influenzae type b immunization in infants in the United Kingdom: Effects of diphtheria/tetanus/acellular pertussis/Hib combination vaccine, significant prematurity, and a fourth dose

OBJECTIVE. To measure anti-polyribosylribitolphosphate (PRP) antibody and anti–tetanus toxoid (TT) antibody responses in UK infants to explore the effects of (1) immunization with an acellular diphtheria/tetanus/pertussis/Haemophilus influenzae type b (DTPHib) combination vaccine, (2) significant preterm delivery, and (3) a fourth dose of conjugated Hib vaccine (PRP-T) in those with a low anti-PRP antibody (<1.0 μg/mL) after primary immunization. METHODS. A prospective study was conducted in 4 tertiary neonatal units at a time when 2 types of DTPHib vaccines were used interchangeably in the United Kingdom for primary immunization: acellular (DTPaHib) and whole cell. Timing and type of all vaccine doses were as per standard UK practice. Blood was taken before and after immunization. A total of 166 preterm and 45 term infants completed the study; 97 (15 term) infants who had anti-PRP antibody <1.0 μg/mL were offered a fourth dose of PRP-T; 61 (55 preterm) then had repeat antibody measurements. Anti-PRP and anti-TT antibody after primary immunization relative to gestation and number of whole cell vaccine doses received was measured, as well as anti-PRP antibody after a fourth dose of PRP-T. RESULTS. A total of 49% of preterm and 33% of term infants had anti-PRP antibody <1.0 μg/mL after full primary immunization. Receipt of 1 or more acellular vaccine doses was associated with lower anti-PRP antibody, a dose response effect being observed. Preterm infants were less likely to have anti-PRP antibody >1.0 μg/mL compared with term infants. A total of 93% of infants who were given a fourth dose had anti-PRP antibody >1.0 μg/mL. Anti-TT antibody responses were satisfactory for all infants but also reduced by each DTPaHib dose received. CONCLUSION. Infants who receive DTPaHib, are significantly preterm, or who do not receive a fourth dose of conjugated Hib vaccine may be at increased risk for Hib disease.

Who should staff neonatal transport teams

Neonatal transport is variously staffed by diverse combinations of nurses, doctors and paramedical staff. There is no evidence that neonatal transport undertaken with staff from any particular professional background results in improved outcomes for infants; instead, it appears that beneficial outcomes result from using staff who are specifically trained in transport practice, regardless of their professional background. Core transport competencies that are transferrable should be a routine part of the training of transport team members.

Immunogenicity of a Heptavalent Conjugate Pneumococcal Vaccine Administered Concurrently with a Combination Diphtheria, Tetanus, Five-Component Acellular Pertussis, Inactivated Polio, and Haemophilus influenzae Type b Vaccine and a Meningococcal Group C Conjugate Vaccine at 2, 3, and 4 Months of Age

ABSTRACT The immunogenicities of conjugate pneumococcal vaccines have been demonstrated when they are administered at 2, 3, and 4 months of age. There is a paucity of data on the immunogenicity of this vaccine when it is administered concurrently with other vaccines in the primary immunization schedule of the United Kingdom. We immunized 55 term infants at 2, 3, and 4 months of age with the seven-valent pneumococcal conjugate vaccine (PCV7), the meningococcal group C conjugate (MCC) vaccine, and the diphtheria, tetanus, five-component acellular pertussis, inactivated polio, and Haemophilus influenzae type b (DTaP5/IPV/Hib-TT) vaccine. The immune responses to the H. influenzae type b (Hib), MCC, and tetanus vaccines were measured at 2, 5, and 12 months of age; and the immune responses to PCV7 were measured at 2 and 5 months and then either at 12 months or following a 4th dose of PCV7. There were increases in the geometric mean concentrations (GMCs) of all antigens postimmunization. Greater than or equal to 90% of the infants achieved putatively protective levels postimmunization for all vaccine antigens except pneumococcal serotype 6B and Hib. The GMCs of the PCV7 serotypes increased following a 4th dose, although one infant had not reached putative levels of protection against serotype 6B. In conclusion, when infants were vaccinated according to the schedule described above, they had lower postprimary immunization responses to Hib, meningococcus group C capsular polysaccharide, and pneumococcal serotype 6B than the responses demonstrated by use of the other schedules. Despite this finding, there was a good response following a 4th dose of PCV7.

The evidence for high flow nasal cannula devices in infants.

High flow nasal cannula (HFNC) devices deliver an adjustable mixture of heated and humidified oxygen and air at a variable flow rate. Over recent years HFNC devices have become a frequently used method of non-invasive respiratory support in infants and preterm neonates that is generally popular amongst clinicians and nursing staff due to ease of use and being well tolerated by patients. Despite this rapid adoption relatively little is known about the exact mechanisms of action of HFNC however and only recently have data from randomised controlled trials started to become available. We describe the features of a modern HFNC device and discuss current knowledge about the mechanisms of action and results of clinical studies in preterm neonates and infants with bronchiolitis. We also highlight future areas of research that are likely to increase our understanding, inform best clinical practice and strengthen the evidence base for the use of HFNC.

Responses to a conjugate pneumococcal vaccine in preterm infants immunized at 2, 3, and 4 months of age.

ABSTRACT Preterm infants are at an increased risk of invasive pneumococcal disease infection and, additionally, have a diminished response to Haemophilus influenzae type b (Hib) conjugate vaccines. There are little data examining the response of preterm infants to a seven-valent pneumococcal conjugate vaccine (PCV7). We examined the responses of preterm infants immunized at 2, 3, and 4 months of age to PCV7. A total of 133 preterm and 54 term infants were immunized with PCV7 and the Neisseria meningitidis group C (MCC), diphtheria, tetanus, pertussis, polio, and Hib vaccines. Pneumococcal serotype-specific IgG was measured by enzyme-linked immunosorbent assay (ELISA) pre- and postimmunization and at 12 months or following a booster of PCV7. Term and preterm responses were compared using linear and logistic regression analyses. Term infants had higher preimmunization geometric mean concentrations (GMCs) for all serotypes. Preterm infants had lower postimmunization GMCs for serotype 23F. Gestational age affected postimmunization GMCs for serotypes 4, 6B, and 23F. Preterm infants were as likely to have levels of ≥0.35 μg/ml as term infants for all serotypes except 23F. The proportions of infants with titers of ≥0.35 μg/ml for all 7 serotypes were comparable between groups. A total of 28 of 29 term infants who received a booster had levels of ≥0.35 μg/ml for all serotypes. One infant had undetectable levels for serotype 6B. Of the 32 preterm infants boosted, 9 had levels of <0.35 μg/ml for 1 serotype, and 1 had levels of <0.35 μg/ml for 2 serotypes. In nonboosted infants, GMCs for all serotypes except 6B had fallen by 12 months of age. These results support the need for a booster dose in the second year of life.