Journal Club Papers
Preliminary safety data of COVID-19 vaccination during pregnancy was assessed using data obtained from 1) V-safe: a smart phone surveillance system created for the COVID-19 vaccination in the US and 2) the CDC and FDA Vaccine Adverse Events Reporting System (VAERS), to which healthcare workers are required to report any pregnancy related complication requiring hospitalisation or anomalies.
- 35,691 pregnant women self-enrolled in the V-safe surveillance system after receiving either the Pfizer-BioNTech or Moderna vaccines.
- Most reported being pregnant at the time of vaccination (86.5%), with the remainder having a positive pregnancy test after vaccination.
- Injection site pain (88.1%), fatigue (29.6%), headache (18.1) and myalgia (11.6%) were the most commonly reported symptoms of both vaccines and were more frequently reported after the second dose (91.9%, 71.5%, 55.4%, 54.1% respectively). Results were similar to non-pregnant vaccinated women, with the exception of slightly higher likelihood of nausea and vomiting among pregnant women receiving their second dose.
- Of the 35,691 women enrolled in V-safe, a sub-cohort of 3,958 were enrolled in a more detailed review of pregnancy outcomes. Among these women, 92 (2.3%) received their first dose during the periconception period, 1,132 (28.6%) during 1st trimester, 1,714 (43.3%) during 2nd trimester and 1,019 (25.7%) during 3rd trimester.
- At the time of analysis 827 (20.9%) participants had a completed pregnancy; 712 (86.1%) resulted in a live birth, 104 (12.6%) in a spontaneous abortion (96/104 <13 weeks), 10 (1.2%) in induced abortion or ectopic pregnancy and 1 (0.1%) in stillbirth.
- Among liveborn infants, adverse outcomes included: preterm birth (60/636 [9.4%] who received a first dose <37 weeks), SGA (23/724 [2.2%]) and major congenital anomalies (16/724 [2.2%]). Of the 16-reported congenital anomalies, none received vaccinations during periconception or the first trimester. The authors report that the incidences of adverse outcomes are comparable to those published prior to COVID-19 among non-vaccinated women.
- The study was significantly limited by the fact that there were only 827 with a completed pregnancy, data collection relied on self-reported information and a control population was not recruited (thus, more data on pregnancy outcomes would be most welcome).
These limitations again highlight the need to include pregnant women in larger RCTs of COVID-19 vaccination.
- This prospective cohort studies assessed the immunogenicity of the COVID-19 Pfizer and Moderna vaccines among pregnant and lactating women.
- 103 vaccinated women were enrolled including 57 non-pregnant and non-lactating, 30 pregnant and 16 lactating. Additionally, 22 unvaccinated pregnant women with confirmed COVID-19 infection were included.
- Vaccination elicited an antibody response across all groups with median IgG binding antibody titres of 37,839 among non-pregnant, 27,601 pregnant and 23,497 among lactating women.
- 9 paired maternal and infant cord blood samples were used to evaluate the trans-placental transfer of vaccine elicited binding and neutralizing antibodies. Among these, the median maternal serum IgG binding antibodies titres at delivery were 14,953 compared to 19,873 in cord blood.
- Neutralizing antibodies were also present in breastmilk following vaccination but at very low levels, with median breastmilk IgG titres of 97 and IgA of 25 (possibly these levels are too low to offer additional neonatal protection).
Together these preliminary findings provide reassuring evidence that both the Pfizer and Moderna vaccines appear safe for use during pregnancy and elicit comparable immune responses to non-pregnant vaccinated women.
Additionally, vaccine-induced antibodies in cord blood suggest transfer of maternal antibodies, which may confer some newborn protection. Transfer of antibodies into the breastmilk appears low.
A heart-warming intervention trial published in NEJM and funded by the Bill and Melinda Gates Foundation.
- "Kangaroo mother care” is a newborn care that involves skin-to-skin contact between the baby and mother/caregiver and is known to reduce mortality amongst low birthweight infants (<2.0kg) when initiated after stabilisation. However, the majority of infant deaths occur before stabilisation (45% within 24 of hours of birth).
- This RCT was conducted between 2017 - 2020 across five countries – Ghana, India, Malawi, Nigeria and Tanzania.
- Infants with a birthweight between 1.0 and 1.799kg (any gestational age) were randomised to:
- immediate kangaroo mother care (intervention): mothers were asked to identify one or two adult women who could act as additional surrogate providers of kangaroo mother care; or
- conventional care in an incubator/radiant warmer until their condition stabilised followed by kangaroo mother care
- Primary outcomes: death in the neonatal period (first 28 days of life) or within the first 72 hours of life.
- A total of 3,211 infants (and their mothers) were recruited and randomised.
- The mean gestational age was 32+6 weeks and birthweight 1.5kg for both groups.
- The median daily duration of skin-to-skin contact in NICU was 16.9 hours (IQR 13.0-19.7) in the intervention group and 1.5 hours (IQR 0.3-3.3) in the control group.
- Neonatal death occurred within 28 days in 191 (12%) infants in the intervention group and 249 (15.7%) infants in the control group:
- RR 0.75 (95%CI 0.64-0.89 p=0.001)
- NNT to prevent one death 27 (95%CI 17-77)
- The trial was stopped early at the recommendation of the data and safety monitoring board given the clear finding of reduced mortality amongst the intervention group.
- The authors concluded that immediate kangaroo mother care has considerable benefits through lowering mortality among very low birthweight babies.
For a local view on the findings and applicability of this study to our setting, we consulted one of our Neonatologists Julia Charlton.
- The initiative, infrastructure and cooperation required between obstetric and neonatal teams to allow this to happen must be applauded. The length of time mothers could spend with their babies is impressive and even if sporadic, kangaroo care is important in the care of very small babies.
- However, the equivalent sized neonates in Australia have a 28-day survival of around 98%. This study excluded infants who were too sick to participate or who were not spontaneously breathing by 60 minutes – exactly the babies likely to make up the 2% mortality in Australia. With such a low relative mortality rate (likely close to zero) the Number Needed to Treat (NNT) to show benefit in high-resource settings would be exponentially higher.
- Whilst we cannot generalise the findings of this study to our highly developed and resourced intensive care environment, we can extrapolate some humbling knowledge:
- 1) Barriers to kangaroo care can be overcome even in low-resource settings.
- 2) We probably keep our moderately preterm babies in hospital too long rather than at home with their families who all have piped running water.