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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.Funding: the Thrasher Research Fund and the National Immunisation Schedule Evaluation Consortium through the National Institute for Health and Care Research policy research programme.

ImportanceAvoidant restrictive food intake disorder (ARFID) is a newly recognised eating disorder in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and in the International Classification of Diseases, Eleventh Revision which shows great heterogeneity in its clinical presentation.ObjectivesHere, we examined the clinical characteristics of ARFID and explored the associations between ARFID symptoms and traits of anxiety. We also investigated whether individuals with ARFID show a different clinical presentation based on their biological sex or comorbid autism spectrum disorder (ASD) diagnosis.Design, Setting, and ParticipantsWe recruited 261 consecutive patients from the specialised ARFID outpatient service at the Maudsley Centre for Child and Adolescent Eating Disorders, Michael Rutter Centre, Maudsley Hospital, London, United Kingdom.Main Outcomes and MeasuresThe parents of the patients completed the Pica, ARFID, Rumination Disorder – ARFID – Questionnaire (PARDI-AR-Q), the Revised Children’s Anxiety and Depression Scale (RCADS) and reported biological sex of their offspring. Age, height, and weight were obtained from medical records. Clinicians reported on comorbid ASD diagnosis and anxiety traits using the Current View Tool.ResultsThis cross-sectional study included 261 child and adolescent ARFID patients (133 [51%] female) with a median age of 12.7 years (IQR=9.2 to 15.8). Patients’ BMI-for-age z-scores ranged from −6.75 to 4.07 (median = −1.07, IQR = −2.25 to −0.01).Patients’ comorbid traits of anxiety had the highest correlations with symptoms on the concern about aversive consequences driver of ARFID: panic disorder correlated with physical feelings of panic and anxiety when eating (r=0.53, p=7.74 × 10−31) and being afraid to eat (r=0.42, p=5.13 × 10−21); generalised anxiety correlated with physical feelings of panic and anxiety when eating (r=0.44, p=7.72 × 10−23); and separation anxiety correlated with avoiding eating situations (r=0.36, p=2.01 × 10−15). Sensory sensitivity to the appearance of food positively correlated with separation anxiety (r=0.40, p=1.52 × 10−16) and generalised anxiety (r=0.36, p=7.16 × 10−18).The sensory sensitivities (RR = 0.96; 95% CI, 0.85 to 1.09;P= .53), lack of interest (RR = 1.14; 95% CI, 1.03 to 1.28;P= .02) and concern about aversive consequences (RR = 1.27; 95% CI, 1.03 to 1.56;P= .03) drivers were independent of patient sex. Comorbid ASD was reported in 74 (28%) ARFID patients. Their parents reported higher rates of food-related sensory sensitivities (RR = 1.26; 95% CI, 1.09 to 1.45;P=0.002) and lack of interest (RR = 1.19; 95% CI, 1.05 to 1.34;P=0.006) driving their child’s avoidant and restrictive eating than parents of ARFID patients without ASD (127 [49%]).Conclusions and RelevanceOur study highlights that ARFID patients present with varying combinations and severity of food-related sensory sensitivities, lack of interest and concern about aversive consequences which drive their avoidant and restrictive eating. ARFID does not discriminate between male and female children and adolescents or those with or without ASD. Anxiety and ASD can co-occur with ARFID, and ASD may accentuate food-related sensory sensitivities and lack of interest. Healthcare professionals should be aware of the multi-faceted and heterogenous nature of ARFID; it is important that comprehensive multidisciplinary assessments are administered to sufficiently understand the drivers of the eating behaviour and associated physical health, nutritional, and psycho-social risk and impact.Key PointsQuestionAre the clinical characteristics of avoidant restrictive food intake disorder (ARFID) associated with biological sex, comorbid autism spectrum disorder (ASD) and anxiety traits in patients who present to a specialist ARFID child and adolescent mental health outpatient service?FindingsIn our cross-sectional study, the clinical presentation of ARFID is largely independent of patient sex, comorbid ASD and anxiety.MeaningRegarding these patient characteristics, we detected no marked differences in our patient sample meaning that all patients should be comprehensively assessed by a multidisciplinary team regardless of comorbidity.

Age is the major risk factor for mortality after SARS-CoV-2 infection and older people have received priority consideration for COVID-19 vaccination. However, vaccine responses are often suboptimal in this age group and few people over the age of 80 years were included in vaccine registration trials. We determined the serological and cellular response to spike protein in 100 people aged 80–96 years at 2 weeks after the second vaccination with the Pfizer BNT162b2 mRNA vaccine. Antibody responses were seen in every donor with high titers in 98%. Spike-specific cellular immune responses were detectable in only 63% and correlated with humoral response. Previous SARS-CoV-2 infection substantially increased antibody responses after one vaccine and antibody and cellular responses remained 28-fold and 3-fold higher, respectively, after dual vaccination. Post-vaccine sera mediated strong neutralization of live Victoria infection and although neutralization titers were reduced 14-fold against the P.1 variant first discovered in Brazil they remained largely effective. These data demonstrate that the mRNA vaccine platform delivers strong humoral immunity in people up to 96 years of age and retains broad efficacy against the P.1 variant of concern.