Neonatal BCG: a time for change

© 2022 The Authors. Published by BMJ. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: http://dx.doi.org/10.1136/archdischild-2021-323239The BCG vaccination programme in the UK is risk based and has usually been given to eligible babies soon after birth. On advice from the Joint Committee on Vaccination and Immunisation, NHS England and Improvement recently revised the timing of this vaccination to 28 days after birth or soon thereafter. In this article, we highlight the change in timing of vaccination, the rationale and barriers to BCG uptake that this change may pose.Published versio

Neonatal BCG : a time for change

The BCG vaccination programme in the UK is risk based and has usually been given to eligible babies soon after birth. On advice from the Joint Committee on Vaccination and Immunisation, NHS England and Improvement recently revised the timing of this vaccination to 28 days after birth or soon thereafter. In this article, we highlight the change in timing of vaccination, the rationale and barriers to BCG uptake that this change may pose

Pregnancy and neonatal outcomes of COVID-19: The PAN-COVID study

Objective To assess perinatal outcomes for pregnancies affected by suspected or confirmed SARS-CoV-2 infection. Methods Prospective, web-based registry. Pregnant women were invited to participate if they had suspected or confirmed SARS-CoV-2 infection between 1st January 2020 and 31st March 2021 to assess the impact of infection on maternal and perinatal outcomes including miscarriage, stillbirth, fetal growth restriction, pre-term birth and transmission to the infant. Results Between April 2020 and March 2021, the study recruited 8239 participants who had suspected or confirmed SARs-CoV-2 infection episodes in pregnancy between January 2020 and March 2021. Maternal death affected 14/8197 (0.2%) participants, 176/8187 (2.2%) of participants required ventilatory support. Pre-eclampsia affected 389/8189 (4.8%) participants, eclampsia was reported in 40/ 8024 (0.5%) of all participants. Stillbirth affected 35/8187 (0.4 %) participants. In participants delivering within 2 weeks of delivery 21/2686 (0.8 %) were affected by stillbirth compared with 8/4596 (0.2 %) delivering ≥ 2 weeks after infection (95 % CI 0.3–1.0). SGA affected 744/7696 (9.3 %) of livebirths, FGR affected 360/8175 (4.4 %) of all pregnancies. Pre-term birth occurred in 922/8066 (11.5%), the majority of these were indicated pre-term births, 220/7987 (2.8%) participants experienced spontaneous pre-term births. Early neonatal deaths affected 11/8050 livebirths. Of all neonates, 80/7993 (1.0%) tested positive for SARS-CoV-2. Conclusions Infection was associated with indicated pre-term birth, most commonly for fetal compromise. The overall proportions of women affected by SGA and FGR were not higher than expected, however there was the proportion affected by stillbirth in participants delivering within 2 weeks of infection was significantly higher than those delivering ≥ 2 weeks after infection. We suggest that clinicians’ threshold for delivery should be low if there are concerns with fetal movements or fetal heart rate monitoring in the time around infection

Rapid exome sequencing: revolutionises the management of acutely unwell neonates.

Diagnosing acutely unwell infants with a potential genetic diagnosis can be challenging for healthcare professionals. Evidence suggests that up to 13% of critically unwell infants on the neonatal intensive care unit (NICU) have an underlying molecular diagnosis and when identified directly affects treatment decisions in 83%. On 1st October 2019, the National Health Service England (NHSE) launched a nationally commissioned service so that rapid whole-exome sequencing can be offered to critically unwell babies and children with a likely monogenic disorder who are admitted to NICU and paediatric intensive care unit (PICU). We present 7 cases from two neonatal units in the West Midlands (UK), where rapid exome sequencing has revealed a genetic diagnosis. Early genetic diagnosis in this cohort has influenced management in all (100%) cases, and in 57% (4 in 7 cases), it has helped in the decision to reorientate care. In some cases, early diagnosis has reduced the need for invasive and unnecessary investigations and avoided the need for post-mortem investigations. The genetic diagnosis has helped in counselling the families regarding the recurrence risk for future pregnancies. In some cases, this has provided parents with the reassurance of a low recurrence. In others, it has resulted in the offer of prenatal diagnosis or assisted conception technologies. What is Known: • Rapid whole-exome sequencing was commissioned in the UK in October 2019. • It is available for critically unwell babies with a likely monogenic aetiology. What is New: • It helps management planning for rare genetic disorders and future pregnancies counselling. • It can reduce the need for invasive investigations and overall intensive care costs.RD&E staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted.Published version, accepted version (12 month embargo

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

Pregnancy and neonatal outcomes of COVID -19: coreporting of common outcomes from PAN-COVID and AAP-SONPM registries

Objective Few large cohort studies have reported data on maternal, fetal, perinatal and neonatal outcomes associated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection in pregnancy. We report the outcome of infected pregnancies from a collaboration formed early during the pandemic between the investigators of two registries, the UK and Global Pregnancy and Neonatal outcomes in COVID‐19 (PAN‐COVID) study and the American Academy of Pediatrics (AAP) Section on Neonatal–Perinatal Medicine (SONPM) National Perinatal COVID‐19 Registry. Methods This was an analysis of data from the PAN‐COVID registry (1 January to 25 July 2020), which includes pregnancies with suspected or confirmed maternal SARS‐CoV‐2 infection at any stage in pregnancy, and the AAP‐SONPM National Perinatal COVID‐19 registry (4 April to 8 August 2020), which includes pregnancies with positive maternal testing for SARS‐CoV‐2 from 14 days before delivery to 3 days after delivery. The registries collected data on maternal, fetal, perinatal and neonatal outcomes. The PAN‐COVID results are presented overall for pregnancies with suspected or confirmed SARS‐CoV‐2 infection and separately in those with confirmed infection. Results We report on 4005 pregnant women with suspected or confirmed SARS‐CoV‐2 infection (1606 from PAN‐COVID and 2399 from AAP‐SONPM). For obstetric outcomes, in PAN‐COVID overall and in those with confirmed infection in PAN‐COVID and AAP‐SONPM, respectively, maternal death occurred in 0.5%, 0.5% and 0.2% of cases, early neonatal death in 0.2%, 0.3% and 0.3% of cases and stillbirth in 0.5%, 0.6% and 0.4% of cases. Delivery was preterm (< 37 weeks' gestation) in 12.0% of all women in PAN‐COVID, in 16.1% of those women with confirmed infection in PAN‐COVID and in 15.7% of women in AAP‐SONPM. Extreme preterm delivery (< 27 weeks' gestation) occurred in 0.5% of cases in PAN‐COVID and 0.3% in AAP‐SONPM. Neonatal SARS‐CoV‐2 infection was reported in 0.9% of all deliveries in PAN‐COVID overall, in 2.0% in those with confirmed infection in PAN‐COVID and in 1.8% in AAP‐SONPM; the proportions of neonates tested were 9.5%, 20.7% and 87.2%, respectively. The rates of a small‐for‐gestational‐age (SGA) neonate were 8.2% in PAN‐COVID overall, 9.7% in those with confirmed infection and 9.6% in AAP‐SONPM. Mean gestational‐age‐adjusted birth‐weight Z‐scores were −0.03 in PAN‐COVID and −0.18 in AAP‐SONPM. Conclusions The findings from the UK and USA registries of pregnancies with SARS‐CoV‐2 infection were remarkably concordant. Preterm delivery affected a higher proportion of women than expected based on historical and contemporaneous national data. The proportions of pregnancies affected by stillbirth, a SGA infant or early neonatal death were comparable to those in historical and contemporaneous UK and USA data. Although maternal death was uncommon, the rate was higher than expected based on UK and USA population data, which is likely explained by underascertainment of women affected by milder or asymptomatic infection in pregnancy in the PAN‐COVID study, although not in the AAP‐SONPM study. The data presented support strong guidance for enhanced precautions to prevent SARS‐CoV‐2 infection in pregnancy, particularly in the context of increased risks of preterm delivery and maternal mortality, and for priority vaccination of pregnant women and women planning pregnancy. Copyright © 2021 ISUOG. Published by John Wiley & Sons Ltd