First Immunisations as per <scp>UK</scp> Schedule in Extreme Preterm Infants—Are They That Scary?

Premature and low birth weight infants are well known to have high mortality and morbidity relating to vaccine-preventable infections in the first year of life [1]. In December 2019, Public Health England published a guidance for parents of premature infants born on or after January 2020 on the updated immunisation schedule, to commence 8 weeks from birth regardless of gestation [2]. The first set of immunisations as per the UK schedule includes Diphtheria, Tetanus, Pertussis, Polio, Haemophilus influenza type B, and Hepatitis B (DTaP/IPV/Hib/HepB) [Infanrix hexa, GSK, Belgium]; Meningococcal group B [Bexsero, GSK, Italy] and Rotavirus [Rotarix, GSK, Belgium], similar to those given to term infants. However, there is still a lack of recent published data on the uptake and tolerability of timely first immunisations in extreme preterm neonates. Preterm infants have an immature immune system and often miss out on the maternally transferred IgG in the third trimester, which offers short-term protection. However, the lack of maternal antibodies in preterm infants may provide an advantage for better immune response without being inhibited by maternal antibodies [2]. Even though available evidence suggests that for several antigens the antibody response to initial doses of immunisations is lower in preterm infants than that of a term infant, protective concentrations are often achieved, and memory is successfully induced [3]. With lack of comparable data on various immunisation schedules, recommendations on the current schedule have been based on limited, but available scientific evidence. In 2014, Sisson highlighted the need for further studies exploring the reasons why immunisations for premature babies are not always given as per the routine schedule. This is despite being known to be a vulnerable population with an increased risk of infection [4]. We present the data from our single-centre retrospective cohort study of all extreme preterm neonates ≤ 27 weeks' gestation who received their first immunisations as per the UK schedule in our neonatal intensive care unit over a 4-year period from January 2020 to December 2023. This review included baseline characteristics and subsequent complications following first immunisations, as shown in Table 1. In total, 29% (52/176) of neonates successfully received their first immunisations as in-patients and were therefore eligible for inclusion in this study, whilst 51% were transferred to their local hospital, and 20% died before day 60. The mean gestational age of our cohort was 25 weeks (IQR: 23 + 5–26 + 5) with a mean birth weight of 688 g (IQR: 546–763). At the time of first immunisations, the mean corrected gestational age was 34 weeks (IQR: 33 + 1–35 + 5) with a mean weight of 1499 g (IQR: 1121–1743). Only just over a third (37%; 19/52) of the eligible neonates were immunised by 60 days, whilst two-thirds (67%; 35/52) received immunisations by 65 days. Nearly a quarter of the cohort (21%; 11/52) had no clear documentation for any medical or parental concerns as a reason for delayed immunisations. Another quarter (25%; 13/52) had symptoms of suspected sepsis at around 60 days of life, leading to a delay. However, post-immunisations, only 13% underwent a septic screen, 4% had documented fever, and 15% had an elevated C-reactive protein. Nearly half of the study population (44%; 23/52) did not experience any adverse effects following immunisations. The commonest adverse effect (40%; 21/52) experienced was fleeting desaturations with or without apnoea. Following this, only a minority (15%; 8/52) required changes to ventilatory settings, such as an increase in oxygen requirement or flow of non-invasive mode of ventilation, and only 2% needed escalation to another modality of non-invasive ventilation. None of the cohort needed escalation from non-invasive to invasive respiratory support. Return to baseline clinical status was achieved in a mean of 2.2 days. While two-thirds of eligible extreme preterm neonates were immunised within a reasonable time frame of 65 days from the recommended 8 weeks (56 days), the rationale for the delay was not clearly documented in almost a quarter of babies. There seems to be some hesitancy among parents and staff regarding timely immunisations, possibly due to anxiety over lower gestation and weight in this cohort compared to borderline preterm or term infants. This could reflect the lack of confidence in the tolerability of immunisations in this population due to limited data available in literature [4]. Interestingly, in a large population-based study in Canada, substantially lower immunisation rates have been observed among extreme preterm infants when they were still hospitalised as opposed to being in the community at the time when immunisations were due [5]. Our study shows that first childhood immunisations as per the recommended UK schedule were relatively well tolerated by extreme preterm infants and the majority only needed a minor increase in non-invasive respiratory support, which could be safely managed in a hospital setting. Our finding on self-limiting cardio-respiratory adverse effects is similar to the summary of findings from the small number of published studies [1, 3, 4]. Our study adds more recent evidence to support the safety of timely first immunisations as per the UK schedule for extreme preterm infants ≤ 27 weeks' gestation in a hospital setting. We appreciate that first immunisations may differ across countries and our conclusions are based only on the UK schedule. Being a retrospective study, our study was limited in being able to study the exact reasons for delay in offering timely immunisations. Difficulty occurred in extracting data from notes due to unclear documentation in several babies. Given the lack of clear documentation of the reason for delay, it is unlikely that this was due to clinical instability as demonstrated by extrapolated data. Therefore, our study also highlights that more reassurance needs to be provided to health care professionals, in addition to parents, to ensure compliance with the national immunisation schedule. Parameters to guide first immunisations should include chronological age and clinical condition [1]. While the immunogenicity of preterm immunisations is unclear and additional booster doses might be needed for effective longer-term protection, it seems prudent to follow the recommended schedule, ensuring earlier protection is provided to high-risk infants. With limited data in this field, it is important to reinforce the need for clear and accurate documentation for not only research purposes but to facilitate high quality care for our patients in a timely manner. Elise Peever: investigation, writing – original draft, writing – review and editing, formal analysis, data curation, methodology, project administration. Rishini Wanigasekara: data curation, investigation, writing – original draft, writing – review and editing, formal analysis, methodology, project administration. Vennila Ponnusamy: supervision, conceptualization, writing – review and editing, visualization, validation, project administration. The authors declare no conflicts of interest.

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