An open-label, phase IV randomised controlled trial of two schedules of a four-component meningococcal B vaccine in UK preterm infants.

OBJECTIVE: To compare immunological responses of preterm infants to a four-component meningococcal B vaccine (4CMenB; Bexsero) following a 2+1 vs a 3+1 schedule, and to describe reactogenicity of routine vaccines. DESIGN: An open-label, phase IV randomised study conducted across six UK sites. SETTING: Neonatal units, postnatal wards, community recruitment following discharge. PARTICIPANTS: 129 preterm infants born at a gestation of <35 weeks (64 in group 1 (2+1), 65 in group 2 (3+1)) were included in the analysis. Analysis was completed for postprimary samples from 125 participants (59 in group 1, 66 in group 2) and for postbooster samples from 118 participants (59 in both groups). INTERVENTIONS: Infants randomised to 4CMenB according to a 2+1 or a 3+1 schedule, alongside routine vaccines. MAIN OUTCOME MEASURES: Serum bactericidal antibody (SBA) assays performed at 5, 12 and 13 months of age: geometric mean titres (GMTs) and proportions of infants achieving titres ≥4 compared between groups. RESULTS: There were no significant differences in SBA GMTs between infants receiving a 2+1 compared with a 3+1 schedule following primary or booster vaccination, but a significantly higher proportion of infants had an SBA titre ≥4 against strain NZ98/254 (porin A) at 1 month after primary vaccination using a 3+1 compared with a 2+1 schedule (3+1: 87% (95% CI 76 to 94%), 2+1: 70% (95% CI 56 to 81%), p=0.03).At 12 weeks of age those in the 3+1 group, who received a dose of 4CMenB, had significantly more episodes of fever >38.0°C than those in the 2+1 group who did not (group 2+1: 2% (n=1); 3+1: 14% (n=9); p=0.02). CONCLUSIONS: Both schedules were immunogenic in preterm infants, although a lower response against strain NZ98/254 was seen in the 2+1 schedule; ongoing disease surveillance is important in understanding the clinical significance of this difference. TRIAL REGISTRATION NUMBER: NCT03125616.

Establishing breast feeding in infants with Down syndrome: the FADES cohort experience.

OBJECTIVE: To describe breastfeeding prevalence and maternal experience in infants with trisomy 21. DESIGN: Longitudinal cohort study. SETTING: Participants from UK recruited through websites, social media and local collaborators: neonatologists, community paediatricians and research nurses. SUBJECTS: Infants under the age of 8 months with Down syndrome (DS) recruited to the Feeding and Autoimmunity in Down Syndrome Evaluation Study between 1 September 2014 and 31 August 2017. Seventy participants: median age 20 weeks (IQR 13-29 weeks) at initial questionnaire. MAIN OUTCOME MEASURE: Breastfeeding prevalence at 6 weeks and 6 months among infants with DS. RESULTS: The prevalence of exclusive breast feeding among study participants was similar to the general population (13/61, 21% vs 23% at 6 weeks, 2/54, 4% vs 1% at 6 months). However, the prevalence of breast feeding (exclusive or combination feeding) among the study participants was higher than the general population (39/61 64% vs 55% at 6 weeks, 32/59 54% vs 34% at 6 months). CONCLUSION: Although there may be challenges in establishing breast feeding in infants with DS, our data suggest that exclusive breast feeding is possible for some, and the prevalence of breast feeding is comparable to the prevalence in the general population. TRIAL REGISTRATION NUMBER: ISRCTN12415856.

Schedules for Pneumococcal Vaccination of Preterm Infants: An RCT.

BACKGROUND AND OBJECTIVE: Premature infants have a higher risk of invasive pneumococcal disease and are more likely to have lower vaccine responses compared with term infants. Increasingly, immunization schedules are including a reduced, 2-dose, pneumococcal conjugate vaccine priming schedule. Our goal was to assess the immunogenicity of 3 commonly used 13-valent pneumococcal conjugate vaccine (PCV13) priming schedules in premature infants and their response to a 12-month booster dose. METHODS: Premature infants (<35 weeks' gestation) were randomized to receive PCV13 at 2 and 4 months (reduced schedule); 2, 3, and 4 months (accelerated schedule); or 2, 4, and 6 months (extended schedule). All infants received a 12-month PCV13 booster. Serotype-specific pneumococcal immunoglobulin G (IgG) for PCV13 serotypes was measured by using enzyme-linked immunosorbent assay 1 month after the primary and booster vaccinations. RESULTS: A total of 210 infants (median birth gestation, 29(+6) weeks; range, 23(+2)-34(+6) weeks) were included. After the primary vaccination, 75% (95% confidence interval [CI], 62-85), 88% (95% CI, 76-95), and 97% (95% CI, 87-99) of participants had protective antibody concentrations for at least one-half the PCV13 serotypes for the reduced, accelerated, and extended schedules, respectively. After the booster vaccination, participants receiving the extended schedule had significantly lower (P < .05) geometric mean concentrations compared with reduced (for 9 of 13 serotypes) and accelerated (for 4 of 13 serotypes) schedules, but nearly all participations, regardless of schedule or serotype, had seroprotective IgG concentrations. CONCLUSIONS: A reduced priming schedule of PCV13 resulted in higher post-booster IgG concentrations but lower post-primary concentrations. The optimum vaccine schedule for preterm infants will therefore depend on when they are most at risk for invasive pneumococcal disease.

Lymphocyte subpopulations in premature infants: an observational study.

BACKGROUND AND OBJECTIVES: The infant's immune system evolves over the first months and years of life. Strong correlation exists between lymphocyte count, lymphocyte subpopulations and gestational age at birth. Associations with antenatal and postnatal steroid treatment, infection and chronic lung disease have also been described. Few published studies report the effect of increasing postnatal age (PNA) and comorbidities on lymphocyte subpopulations in premature infants beyond the first 4 months of life. This study aimed to describe changes in lymphocyte subpopulations in preterm infants up to 13 months PNA. METHODS: Premature infants (23-34 weeks completed gestation) from five centres had lymphocyte subpopulations measured at 2, 5 or 7, 12 and 13 months PNA alongside their vaccine responses in a vaccination trial. RESULTS: 393 blood samples from 151 babies were analysed. There was an increase in absolute numbers of total lymphocytes (median cell count 6.21×109/L at 13 months compared with 4.9×109/L at 2 months PNA) and CD3+, CD4+, CD8+, natural killer and B cells with increasing age. At 2 months PNA, there was a positive correlation between gestation and CD3+ and CD4+ counts (r=0.32 and 0.46, respectively) and proportions (r=0.22 and 0.41, respectively), and CD4+:CD8+ ratios (r=0.57), but a negative correlation with CD8+ proportions (r=-0.32). CONCLUSIONS: This longitudinal study describes the distribution of lymphocyte subpopulations in premature infants and provides reference ranges for the major lymphocyte subsets to help guide clinicians when assessing premature infants for immunodeficiency in the first year of life. TRIAL REGISTRATION NUMBER: EudraCT 2007-007535-23.