Living systematic reviews are needed to minimise research waste and maximise benefit, argues Shakila Thangaratinam 

When SARS-Cov-2 infection first hit the headlines, the obstetric community started its close watch on developments. From previous experience, we knew the disproportionate risks faced by pregnant women exposed to similar viruses—both severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS) were associated with high maternal mortality rates. [1] Viruses were also known to affect unborn fetuses, such as the congenital abnormalities associated with Zika virus. [2] 

We were in uncharted territory with SARS-Cov-2. Initial case reports and case series provided valuable information on the presentation and outcomes of covid-19 in pregnant women and their babies. [3] Shortly afterwards, an urgent need for new knowledge augmented by the “publish or perish” culture started the massive rise in publications. It was difficult to keep abreast of the individual studies and we needed evidence synthesis to collate the findings.

But not all studies followed the reporting guidelines. Several primary studies and case series reported on a subset of data without acknowledging that they were published elsewhere. Systematic reviews included duplicate data, which in turn affected the validity of the findings. Meta-analyses were performed inappropriately by pooling the data from case reports and case series, thereby biasing the estimates on prevalence, and rates of complications. Reviews overlapped in their search intervals and differed by only a few included studies. The flood of publications, both print and pre-print, meant that the results became outdated within a short time.

A high quality systematic review that addresses all the relevant issues from prevalence and risk factors for covid-19 in pregnancy and its complications, to the effects of treatment is critical to inform clinical practice. 

Our team at the WHO Collaborating Centre for Global Women’s Health in Birmingham is experienced in undertaking evidence syntheses (aggregate, network, individual participant data) addressing the various questions relevant to women and their babies. These reviews usually take between one to two years or longer from conception to publication. But a pandemic requires rapid evidence synthesis, one that is kept up to date. Answering these questions requires a radical rethink in how systematic reviews are conducted and reported, without compromising the fundamental principles.

We realised the need for a living systematic review to assess the impact of covid-19 in pregnancy, one that is continuously updated at pre-specified time points. A few living systematic reviews have been published before, but they are usually updated in yearly intervals or more. [4] However, the continuously emerging new data during the pandemic requires the updates to be done in weeks or months, and not years.  

Undertaking a living systematic review poses unique challenges—both internal and external. 

A continuous and comprehensive review requires a large dedicated team. But with a nationwide lockdown, university research landscapes were in flux. Many clinical academics were redeployed full time to work in hospitals. Remote working meant that new teams often had never met each other in person. Medical students left the campus. 

We found collaboration to be the key to maximising our available resources in challenging circumstances. We established the PregCov-19 living systematic review network with similar research interest groups. This increased the human resource available to deliver the living systematic review. We linked with organisations such as the WHO, Cochrane group in the Netherlands, and EPPI Centre who were conducting regular searches for maternal and neonatal outcomes in covid-19. Medical students also emerged as a valuable force to assist with the research. 

A living systematic review requires a robust platform to communicate the findings after peer review. Currently, very few journals have policy or guidelines to publish living evidence syntheses. The BMJ recently published an Editorial informing readers of their policy in publishing living  reviews, acknowledging that it is new territory. [5] 

We published our living systematic review on covid-19 in pregnant and recently pregnant women in The BMJ, which now offers a strong platform for future updates. [6] Our review findings indicate that pregnant women are less likely to manifest symptoms and more likely to be admitted in intensive care units than non-pregnant similar aged women, and that they may more likely deliver preterm. Further updates with additional studies will allow us to confirm these findings with a higher level of certainty.

The final and the biggest challenge facing authors of living systematic reviews is their sustainability.  In our case, as universities reopen, the capacity of our team will be diminished as researchers refocus on other funded non-covid projects, and the medical students resume their studies. Most often, such projects are fuelled by the goodwill and motivation of researchers. Sustaining such initiatives requires support from funders. A modest investment will go a long way towards sustaining an initiative that minimises research waste and maximises research output.

We continue to expand our collaborative group’s membership with researchers across the world. And with the ever-increasing likelihood of a second wave of covid-19, we need this continuous updating of the evidence base more than ever. 

Shakila Thangaratinam is a professor of maternal and perinatal health and a Consultant Obstetrician. She co-leads the WHO Collaborating Centre for Global Women’s Health at the University of Birmingham. 

Competing interests: see research paper

References

1. Favre G, Pomar L, Musso D, Baud D. 2019-nCoV epidemic: what about pregnancies? The Lancet 2020; 395(10224).
2. Krauer F, Riesen M, Reveiz L, et al. Zika Virus Infection as a Cause of Congenital Brain Abnormalities and Guillain-Barre Syndrome: Systematic Review. PLoS med 2017; 14(1): e1002203.
3. Chen L, Li Q, Zheng D, et al. Clinical Characteristics of Pregnant Women with Covid-19 in Wuhan, China. New Eng J Med 2020.
4. Elliott JH, Synnot A, Turner T, et al. Living systematic review: 1. Introduction-the why, what, when, and how. J Clin Epidemiol 2017; 91: 23-30.
5. Macdonald H, Loder E, Abbasi K. Living systematic reviews at The BMJ. BMJ 2020; 370: m2925.
6. Allotey J, Stallings E, Bonet M, et al. Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis. BMJ 2020;370:m3320