Journal club papers
- There are currently over 137 vaccine candidates in preclinical and 23 in early clinical development for COVID-19.
- The Oxford COVID Vaccine Trial Group undertook a Phase 1-2 trial assessing the safety, reactogenicity and immunogenicity of a viral-vectored vaccine expressing spike protein of SARS-CoV2 (n=543), compared to a meningococcal vaccine control (n=534)
- 10 participants also were enrolled in a non-randomised group to receive an additional boost dose of the vaccine
- Additional primary outcomes included efficacy (measured as cases of symptomatic virologically confirmed COVID-19) and safety (measured by the occurrence of adverse events during the 28 days post-vaccine)
- Healthy adults aged 18-55 years with no COVID symptoms or history of laboratory-confirmed infection were randomly assigned 1:1
- Antibody and cellular responses were assessed at baseline and following vaccination
- Local and systemic reactions were more common in the SARS-CoV2 vaccine group (pain, fever, fatigue etc) but were significantly reduced by prophylactic paracetamol
- There were no serious adverse events related to the SARS-CoV2 vaccine
- Immunology:
- The antibody response to the SARS-CoV2 vaccine was similar to levels among patients who had naturally acquired SARS-CoV2
- Spike-specific T-cell responses peaked by day 14, anti-spike antibody (IgG) responses rose by day 28 and were boosted by a second dose of the vaccine
- Neutralising antibody responses against SARS-CoV2 were detected in 91% of participants after a single dose and all participants after a booster dose
In summary the Oxford SARS-CoV2 vaccine shows an acceptable safety profile, with antibody responses increased by a booster dose – these factors and the immune responses support large-scale evaluation in phase 3 trials.
- The ARRIVE trial (Grobman et al NEJM 2018) was a randomised trial of over 6000 participants and found elective induction at 39 weeks lowers the risk of caesarean delivery. However, it is not clear whether these results are applicable to the general population.
- The authors conducted a systematic review of only observational studies (not clinical trials) comparing elective induction of labour at 39 weeks versus expectant management among nulliparous women.
- The primary outcome was caesarean section delivery and several maternal and perinatal morbidities were included as secondary outcomes.
- 6 cohort studies including 66,019 women undergoing induction at 39 weeks and 584,390 women undergoing expectant management were included.
- Elective induction at 39 weeks was associated with a reduced risk of caesarean section (26.4% vs 29.1%, RR 0.83, 95% CI 0.74-0.93) and peripartum infection (2.8% vs 5.2%, RR 0.53, 95% CI 0.39-0.72).
- Induction was also associated with a reduced risk of neonatal respiratory morbidity (0.7% vs 1.5%, RR 0.71, 95% CI 0.59-0.85), meconium aspiration (0.7% vs 3.0%, RR 0.49, 95% CI 0.26-0.92) and NICU admission (3.5% vs 5.5%, RR 0.8, 95% CI 0.72-0.88).
- There was also a significantly lower risk of perinatal mortality of 73% (0.04% vs 0.2%, RR 0.27, 95% CI 0.09-0.76).
These findings confirm those of previous RCTs- but now confirmed in a general population- that elective induction of labour at 39 weeks in nulliparous women is associated with a lower risk of caesarean delivery and improved maternal and perinatal outcomes.
These data provide further evidence to support the premise that an elective induction at 39 weeks’ gestation can reduce the risk of a caesarean section and may have significant perinatal benefits for the baby. Including a reduced risk of perinatal death.
- A retrospective Swedish register-based cohort study investigating the association between maternal aspirin use and bleeding complications.
- Among 313,624 women giving birth from 2013 – 2017, 4,088 (1.3%) reported using aspirin during pregnancy, with 75mg daily aspirin recommended for preeclampsia prophylaxis in Sweden.
- Women using aspirin were more likely to experience bleeding complications, with an increased likelihood of:
- Intrapartum bleeding (2.9% vs 1.5%; adjusted odds ratio 1.63; 95% CI 1.30, 2.05)
- Postpartum haemorrhage (10.2% vs 7.8% aOR 1.23; 95% CI 1.08 – 1.39)
- Postpartum hematoma (0.4% vs 0.1%; aOR 2.21; 95% CI 1.13, 4.34).
- No association was found for antenatal bleeding (aOR 1.22; 95% CI 0.97, 1.54).
- Stratifying by mode of birth, an increased likelihood of bleeding only remained among women who gave birth vaginally and not via caesarean section.
- Neonatal intracranial haemorrhage was also increased among aspirin users (0.07% vs 0.01%; aOR 9.66; 95% CI 1.88, 49.48). However, given the low incidence of this complication (n=20 total), caution is required interpreting this finding.
- While the gestation when aspirin was ceased was not recorded, the Swedish guidelines recommend that aspirin is stopped at 36 weeks gestation.
INTERPRETATION
- These data suggest aspirin may not be completely benign and is associated with a bleeding risk. Of note, low dose aspirin is prescribed at 75 mg in Sweden meaning a higher dose - such as 150 mg – may incur a higher risk of bleeding.
- These findings caution against overly liberal administration of aspirin to prevent pregnancy complications.
- Aspirin should still be offered to women who are at high risk of preeclampsia (defined by international guidelines such as NICE).
- In light of this study and a large RCT which found 81 mg of aspirin is likely to be effective in reducing the risk of preterm preeclampsia by 62% (Hoffman et al Lancet 2020), a dose of 100 mg rather than 150 mg might be considered.