Preterm birth affects around 7-8% of pregnancies in the UK. There are immunological consequences of preterm birth, epidemiological differences in infectious diseases in the preterm population and differences in immunity after vaccination, both following immunisations received in pregnancy and following vaccines administered to infants themselves. There are also often increased concerns about the side effects experienced by preterm infants following vaccination. It is important that health care professionals and parents are fully informed about the specific issues of vaccination in this group.

BACKGROUND:Pertussis-containing vaccines are routinely offered in the UK at 16-32 weeks of gestation and have been shown to be safe and effective, but there remains debate about the best timing for vaccination. Most research into this has focused on serologic immunity, but breastmilk is also important in infant immunity, and the amount of IgA in breastmilk may impact mucosal immunity. It is important to understand if the timing of vaccination in pregnancy affects the concentration of IgA in breastmilk. METHODS:Participants recruited as part of the MAMA (Maternal Antibody in Milk After Vaccination) and OpTIMUM (Optimizing the Timing of Whooping Cough Immunisations in Mums) trials received a pertussis-containing vaccine during pregnancy, either before 24 weeks, between 24 and 27+6 weeks or between 28 and 31+6 weeks. Samples of colostrum within 24 hours of delivery and breastmilk at 14 days were collected. Pertussis toxin, pertactin, tetanus toxoid and diphtheria toxoid specific-IgA levels were measured using a multiplex immunoassay. RESULTS:There was no difference in specific IgA levels against pertussis toxin, pertactin, tetanus toxoid and diphtheria toxoid between the groups vaccinated within different time periods. For all antigens, there was decay in antigen-specific IgA levels between colostrum and breastmilk at 14 days. CONCLUSION:Our results suggest that the timing of administration of a pertussis-containing vaccine in pregnancy does not impact on antigen-specific IgA concentration in colostrum or breastmilk at 14 days.

The optimal timing of pertussis vaccination in pregnancy is debated, especially to maximise antibody concentrations in infants born preterm. This study investigated immunoglobulin G (IgG) in preterm infants at 5 and 12 months, whose mothers had received a pertussis-containing vaccine at different gestations or were unvaccinated. Results show that vaccination in the early-mid second trimester may result in increased FHA specific IgG concentrations in preterm infants at 5 and 12 months. The BEAR PAW study used residual serum samples from the BEAR Men B study (Babies born Early Antibody Response to Men B vaccination (NCT03125616)).

ObjectiveTo 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.DesignAn open-label, phase IV randomised study conducted across six UK sites.SettingNeonatal units, postnatal wards, community recruitment following discharge.Participants129 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).InterventionsInfants randomised to 4CMenB according to a 2+1 or a 3+1 schedule, alongside routine vaccines.Main outcome measuresSerum 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.ResultsThere 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).ConclusionsBoth 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 numberNCT03125616.

Background Vaccination during pregnancy is an important healthcare intervention for safeguarding the health of the mother and their infants. Ethnic disparities in recruitment to vaccine research studies during pregnancy potentially contribute to health inequalities. The aim of the current study was to explore the barriers and enablers influencing the willingness of pregnant women from ethnic minority backgrounds to participate in vaccine research studies. Methods and findings Semi-structured qualitative online interviews were conducted with 23 pregnant women from diverse ethnic backgrounds in the UK. Interviews were transcribed verbatim, and thematically analysed. Our findings suggest that participants perceived vaccines and vaccine research, in principle, to be beneficial to the individual and to society, and understood the value of vaccination in mitigating severity of disease and protecting the health of mothers and their infants. Apprehension over the safety of vaccination in pregnancy was common and reduced willingness to participate. For those that decided to participate in vaccine trials in pregnancy, this was seen as an act of solidarity, a way to contribute to a collective responsibility for the public health of the community. Personal and community connections and representation—seeing people from their own communities represented in in the recruitment process shapped decisions about vaccine trial participating. Trust and mistrust in health systems, shaped by past experiences of interacting with healthcare professionals were likely to inform whether they would consider participating. Practical considerations such as excessive time commitments related to study procedures, travel and organising childcare were barrier to participation. The level of invasiveness of trial procedures were also a concern, although increased monitoring during the trial was seen as a potential benefit, mitigating some safety concerns. Conclusions Our study reinforcing previously identified barriers to vaccine participation among pregnant women from diverse ethnic communities. This study underlines the need to develop tailored interventions that focus on fostering trust with the aid of community engagement to understand cultural contexts, establishing authentic representation, and address practical considerations, to contribute to enhancing vaccine trial participation in pregnancy in those from diverse ethnic communities.

Background. Invasive meningococcal disease (IMD) is most common in the first year of life. We hypothesized that preterm infants may have a higher risk of IMD and more severe disease than term infants. We compared the incidence, demographics, clinical presentation, and outcomes of IMD in preterm compared with term infants during the first 5 years after implementation of a national meningococcal group B vaccine (4CMenB) for infants in England. Methods. The UK Health Security Agency conducts enhanced national IMD surveillance with detailed follow-up of all confirmed cases in England. Infants aged <1 year (uncorrected for gestational age) with IMD confirmed between 1 September 2015 and 31 August 2020 were included. Results. There were 393 infant IMD cases (incidence, 12.4/100 000 live births). Among 363 (92.4%) of the infants with known gestational age, the IMD incidence was higher in preterm (<37 weeks' gestation) than in term infants (18.3/100 000 vs 10.9/100 000; incidence rate ratio [IRR], 1.68 [95% confidence interval, 1.23-2.29]; P = .001). The IMD incidence was highest in those born at <32 weeks' gestation (32.9/100 000; incidence rate ratio for <32 weeks' gestation vs term, 3.01 [95% confidence interval, 1.73-5.24]; P <= .001). There were no differences in demographics, clinical presentation, rate of intensive care admission, or case-fatality rate, but preterm infants were more likely than term infants to have >= 1 reported sequela (14 of 39 [35.9%] vs 51 of 268 [19.0%]; P = .02). Conclusions. Preterm infants had a higher incidence of IMD than term infants and the IMD incidence was highest in infants born at <32 weeks' gestation. Preterm infants also had a higher risk of IMD sequelae.

Multivalent diphtheria, tetanus, acellular pertussis and inactivated poliovirus vaccine (DTaP/IPV) has been o,rered to pregnant women in the United Kingdom since 2012. To assess the impact of maternal DTaP/IPV immunisation on the infant immune response to IPV, we measured poliovirus-specific neutralising antibodies at 2, 5 and 13 months of age in a randomised, phase 4 study of Repevax or Boostrix/IPV in pregnancy and in a non-randomised group born to women not given DTaP/IPV in pregnancy. Infants whose mothers received DTaP/IPV were less likely to seroconvert after three IPV doses than those whose mothers did not receive DTaP/IPV. At 13 months of age, 63/110 (57.2 %), 46/108 (42.6 %) and 40/108 (37.0 %) were seropositive to types 1 to 3, compared with 20/22 (90.9 %), 20/22 (90.9 %) and 14/20 (70.0 %) (p-values 0.003, <0.001 and 0.012). UK infants whose mothers are given DTaP/IPV in pregnancy may be insufficiently protected against poliomyelitis until their pre-school booster. C 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.orgilicenses/by/4.0/).

Vaccination during pregnancy could protect women and their infants from invasive Group B Streptococcus (GBS) disease. To understand if neonatal dried blood spots (DBS) can be used to determine the amount of maternally derived antibody that protects infants against invasive GBS disease, a retrospective case-control study was conducted in England between 1 April 2014 and 30 April 2015. The DBS of cases with invasive GBS disease (n = 61) were matched with healthy controls (n = 125). The haematocrit, DBS storage temperature, freeze-thaw cycle, and paired serum/DBS studies were set up to optimise the antibody assessment. The samples were analysed using a multiplex immunoassay, and the results were assessed using parametric and nonparametric tests. Antibody concentrations were stable at haematocrits of up to 50% but declined at 75%. DBS storage at room temperature was stable for three months compared with storage from collection at −20 °C and rapidly degraded thereafter. Total IgG levels measured in DBS and paired serum showed a good correlation (r2 = 0.99). However, due to suboptimal storage conditions, no difference was found in the GBS IgG levels between DBS samples from cases and controls. We have demonstrated a proof of concept that assays utilising DBS for assessing GBS serotype-specific antibodies in infants is viable. This method could be used to facilitate future large sero-correlate studies, but DBS samples must be stored at −20 °C for long term preservation of antibody.

Background Pertussis vaccination in pregnancy is recommended in many countries to provide protection to young infants. The best timing for this vaccination is uncertain. In the UK, vaccination is recommended between 16 weeks and 32 weeks of gestation. In this trial we aimed to investigate the equivalence of three time periods for pertussis vaccination in pregnancy. Methods In this open-label, equivalence, randomised controlled trial to investigate equivalence of different time windows for pertussis vaccination in pregnancy, participants were randomly assigned (1:1:1 ratio) to receive a pertussis-containing vaccine (Boostrix-inactivated poliovirus vaccine) in one of three gestational age groups, comprising group 1 (<= 23 weeks + 6 days), group 2 (24-27 weeks + 6 days), and group 3 (28-31 weeks + 6 days) using a computer-generated randomisation list. The primary outcome was concentration of pertussis-specific antibodies in the infant born at term at birth. Maternal blood sampling was done before and 2 weeks after vaccination and at delivery, together with a cord sample, and an infant sample was collected at least 4 weeks after primary vaccination. Reactogenicity was assessed for 7 days after vaccination. This trial was registered with ClinicalTrials.gov (NCT03908164). Findings Between May 7, 2019, and Feb 13, 2020, of 1010 women assessed for eligibility, 364 women were recruited and 351 received the intervention (120 in group 1, 119 in group 2, and 112 in group 3). Equivalence of time periods was demonstrated for anti-pertussis toxin and anti-pertactin IgG concentrations. The cord blood geometric mean concentrations of anti-filamentous haemagglutinin IgG were higher with increasing gestational age at vaccination, such that for infants in group 1 (<= 23 weeks + 6 days), equivalence to group 3 (28-31 weeks + 6 days) was not shown. Reported rates of fever were similar between study groups. Interpretation Pertussis vaccination at three different time intervals in pregnancy resulted in equivalent concentrations of IgG antibodies in infants against two of the three pertussis antigens assessed. Overall, these findings support recommendations to vaccinate any time between 16 weeks and 32 weeks of gestation.

Congenital human cytomegalovirus (CMV) infection is the most common congenital infection, affecting around 1 in 200 infants in high-income settings. It can have life-long consequences for up to one in four children, including sensorineural hearing loss and neurodisability. Despite the frequency of congenital CMV and the severity for some children, it is a little-known condition by pregnant women, families and healthcare providers. Timely diagnosis of CMV infection in pregnancy is important to facilitate consideration of treatment with valaciclovir, which may reduce the risk of transmission to the fetus or reduce the severity of the outcomes for infected infants. Recognition of features of congenital CMV is important for neonatologists, paediatricians and audiologists to prompt testing for congenital CMV within the first 21 days of life. Early diagnosis gives the opportunity for valganciclovir treatment, where appropriate, to improve outcomes for affected infants. Further research is urgently needed to inform decisions about antenatal and neonatal screening, long-term outcomes for asymptomatic and symptomatic infants, predictors of these outcomes and optimal treatment for women and infants.

Objective: The study aimed to explore the perspectives of participating pregnant women and Health Care Professionals (HCPs) towards receiving and providing cytomegalovirus (CMV) education so that barriers and facilitators towards incorporating CMV in routine antenatal care could be better understood.Design: This process evaluation phase employed a qualitative design using individual, semi-structured, face-to-face interviews.Setting: Recruitment and interviews took place within a large teaching hospital from an ethnically diverse area of South-west LondonParticipants: The study sample included 20 participants: 15 pregnant women, and five HCPs. All partici-pants were involved in a single centre randomized controlled trial of a digital CMV educational interven-tion in pregnancy.Findings: Pregnant participants expressed a strong desire to receive information about CMV as part of routine antenatal care. Although HCPs were accepting of the need for CMV education, it was evident that they felt unequipped to provide this; reasons included lack of time, uncertainty about clinical path-ways and concern about the potential emotive impact of CMV education. Pregnant women suggested that expressing behaviour changes as risk reduction rather than prevention, made the behaviours feel more achievable and realistic. The support of partners was considered a key factor in the successful adoption of behavioural changes by pregnant women.Key conclusions and implications for practice: There is an onus on HCPs to consider how CMV can be included as part of antenatal education, with messaging framed as risk reducing rather than prevention.(c) 2022 The Authors. Published by Elsevier Ltd.This is an open access article under the CC BY-NC-ND license( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

The aim of this study was to develop a conceptual understanding of women’s readiness to engage in behaviours to reduce the risk of acquiring infections during pregnancy, using cytomegalovirus, the most common congenital infection as a case. Thirty-three pregnant women participated in semi-structured interviews. The findings illustrate that for behavioural change to become viable, it is necessary for individuals to consider barriers or facilitators at the individual, inter-personal and system levels. By widening the theoretical lens beyond individual cognitive determinants, the model places sufficient emphasis on factors, such as collective identity, support networks, interaction with the healthcare system and wider community, relevant to pregnant women.

Background: Pertussis is a highly infectious respiratory illness caused by the bacteria Bordetella pertussis. A resurgence of pertussis, even in countries with good vaccine coverage, has led to an increase in infant deaths. In response to this, many countries have introduced pertussis vaccination in pregnancy. This strategy is effective at preventing infant disease, but there remains uncertainty about what gestational timing is best to ensure maximal protection of the infant. These uncertainties are the rationale for this randomised controlled trial and a sub-study investigating pertussis-specific antibody in breastmilk. Protocol: We will recruit 354 pregnant women and will randomise them to receive their pertussis vaccination in one of three gestational age windows: ≤23+6, 24-27+6 and 28-31+6 weeks of gestation. Vaccination will be with Boostrix-IPV® and participants will be asked to complete a symptom diary for seven days following vaccination. Blood sampling will be performed prior to vaccination, two weeks following vaccination and at the time of delivery. A cord blood sample will be collected at delivery and a blood sample collected from the infant 4-10 weeks after completion of the primary immunisations. Individuals participating in the breastmilk sub-study will provide a sample of colostrum within 48 hours of delivery and samples of breastmilk at two weeks and around five-six months. Blood samples will be analysed using enzyme linked immunosorbent assay (ELISA) techniques for pertussis toxin, filamentous haemagglutinin and pertactin. A subset of serum samples will also be analysed using a functional assay. Colostrum and breastmilk samples will be analysed using functional assays. Discussion: Although pertussis vaccination has been shown to be safe and effective in pregnancy there remains debate about the optimal timing for the administration during pregnancy. This study will investigate antibody responses in serum and breastmilk when vaccination is performed in three different time periods. Clinicaltrials.gov registration: NCT03908164 (09/04/2019)

Pertussis is an infectious disease of the respiratory tract caused by the Gram-negative bacterium Bordetella pertussis. Pertussis vaccines have led to a significant reduction in the incidence and severity of pertussis in infants worldwide. Despite this decrease in incidence, pertussis remains one of the principal causes of vaccine-preventable death; the World Health Organization reported an estimated 24.1 million cases and 160,700 paediatric deaths in 2014. Pertussis infection can occur at any age. In the last 20 years, there has been an increase in the number of adolescent and adult cases reported in high-income countries, including those with high vaccination coverage. These cases represent a potential source of infection for unimmunized infants, who typically have a more severe course with higher mortality. Pertussis infection in previously immunized adults, elderly individuals or young infants frequently presents with atypical symptoms and can easily be overlooked as a diagnosis. This review provides a summary of Bordetella pertussis and discusses diagnostic tests, treatment and prevention.

Maternal vaccination is an effective means of protecting pregnant women, their fetuses, and infants from vaccine-preventable infections. Despite the availability of sufficient safety data to support the use of vaccines during pregnancy, maternal immunization remains an underutilized method of disease prevention, often because of concerns from both healthcare providers and pregnant women about vaccine safety. Such concerns have been reflected in the low uptake of the COVID-19 vaccine among pregnant women seen in many parts of the world. Here, we present an update of the current recommendations for the use of vaccines during pregnancy, including the evidence supporting the use of novel vaccine platforms. We also provide an overview of the data supporting the use of COVID-19 vaccines in pregnancy and an update of the status of vaccines that are currently under development for use in pregnant women.

Vaccination in pregnancy is an effective tool to protect both the mother and infant; vaccines against influenza, pertussis and tetanus are currently recommended. A number of vaccines with a specific indication for use in pregnancy are in development, with the specific aim of providing passive humoral immunity to the newborn child against pathogens responsible for morbidity and mortality in young infants. However, the current understanding about the immune response to vaccination in pregnancy is incomplete. We analysed the effect of pregnancy on early transcriptional responses to vaccination. This type of systems vaccinology approach identifies genes and pathways that are altered in response to vaccination and can be used to understand both the acute inflammation in response to the vaccine and to predict immunogenicity. Pregnant women and mice were immunised with Boostrix-IPV, a multivalent vaccine, which contains three pertussis antigens. Blood was collected from women before and after vaccination and RNA extracted for analysis by microarray. While there were baseline differences between pregnant and non-pregnant women, vaccination induced characteristic patterns of gene expression, with upregulation in interferon response and innate immunity gene modules, independent of pregnancy. We saw similar patterns of responses in both women and mice, supporting the use of mice for preclinical screening of novel maternal vaccines. Using a systems vaccinology approach in pregnancy demonstrated that pregnancy does not affect the initial response to vaccination and that studies in non-pregnant women can provide information about vaccine immunogenicity and potentially safety.

Background Congenital cytomegalovirus (CMV) is the most common infectious cause of congenital disability, which can cause lifelong impairments including sensorineural hearing loss and developmental delay. This study aimed to explore the experiences of parenting a child with congenital CMV and the impact this has on families.Methods Ten parents living with a child with congenital CMV in the UK participated in semistructured interviews and data were analysed using thematic analysis.Results The findings illustrate that delays in making the diagnosis of congenital CMV are associated with parental distress and lack of knowledge about CMV among medical professionals can exacerbate this distress. Parents expressed frustration about not knowing about CMV infection during their pregnancies and therefore not having the opportunity to take measures to reduce their risk of acquiring CMV while pregnant. The uncertainty about the long-term outcomes of children with congenital CMV adds additional emotional burden for parents. Family and wider societal networks have the potential to facilitate coping and alleviate stress, but the lack of awareness of CMV acts as a barrier to receiving support from family and friends.Conclusions There is a need to increase awareness of CMV among medical professionals, pregnant women and wider society to improve the diagnostic process and to provide better support for families caring for children with congenital CMV infection.

Background: Congenital cytomegalovirus infection is the most common nongenetic cause of sensorineural hearing loss in childhood and an important cause of neurodisability. There is no licensed cytomegalovirus (CMV) vaccine and no antenatal treatment for congenital CMV that is routinely recommended in clinical practice in the United Kingdom. Objectives: To review the published literature for studies that evaluated preventative hygiene-based interventions in pregnancy for their impact on knowledge about CMV prevention, the uptake of preventative behaviors or the acquisition of CMV in pregnancy. Search Strategy: Searches were carried out in Medical Literature Analysis and Retrieval System Online and Cumulative Index of Nursing and Allied Health Literature databases. Selection Criteria: All human studies, limited to women of childbearing age were included. Data Collection and Analysis: Two reviewers independently assessed the quality of the methods and results of included articles. Extracted data were classified using Cochrane guidelines. Main Results: Seven studies met the inclusion criteria. These show that preventative measures are acceptable to pregnant women, can impact their behavior and have the potential to reduce CMV in pregnancy. They are limited by several factors; sample size, nonrandomized trial design and interventions that are beyond routine clinical practice. Conclusions: An effective intervention that changes behavior in pregnancy and reduces the risk of CMV acquisition is needed as part of routine care. There is currently insufficient evidence about the form that this intervention should take. Registration: PROSPERO registration number: CRD42017069666.

Vaccination in pregnancy can provide protection for pregnant women and their infants against a number of pathogens and there are national and international recommendations for influenza, pertussis and tetanus. There are some circumstances in which other vaccinations may be considered in pregnancy, for example in a particular location where there is a high incidence of a disease, in an outbreak, before foreign travel or if exposure is likely. Here we provide an overview of some vaccines in pregnancy which are offered in specific circumstances outside of national programs with a review of the available evidence for their use.

Background: Congenital cytomegalovirus infection is the most common nongenetic cause of sensorineural hearing loss in childhood and an important cause of neurodisability. There is no licensed cytomegalovirus (CMV) vaccine and no antenatal treatment for congenital CMV that is routinely recommended in clinical practice in the United Kingdom. Objectives: To review the published literature for studies that evaluated preventative hygiene-based interventions in pregnancy for their impact on knowledge about CMV prevention, the uptake of preventative behaviors or the acquisition of CMV in pregnancy. Search Strategy: Searches were carried out in Medical Literature Analysis and Retrieval System Online and Cumulative Index of Nursing and Allied Health Literature databases. Selection Criteria: All human studies, limited to women of childbearing age were included. Data Collection and Analysis: Two reviewers independently assessed the quality of the methods and results of included articles. Extracted data were classified using Cochrane guidelines. Main Results: Seven studies met the inclusion criteria. These show that preventative measures are acceptable to pregnant women, can impact their behavior and have the potential to reduce CMV in pregnancy. They are limited by several factors; sample size, nonrandomized trial design and interventions that are beyond routine clinical practice. Conclusions: An effective intervention that changes behavior in pregnancy and reduces the risk of CMV acquisition is needed as part of routine care. There is currently insufficient evidence about the form that this intervention should take. Registration: PROSPERO registration number: CRD42017069666.