We welcome the comment by Knight et al1 , 2 on our paper. We accept the argument that misclassification may play a role in the association we found between SARS-CoV-2 positivity at the time of admission for birth and some adverse pregnancy outcomes, including stillbirth and preeclampsia. Indeed, we paid significant attention to this point in our comment on the findings in our paper, highlighting throughout that we found an association between infection status at the time of admission and these adverse outcomes. In other words, this was a cross-sectional study that we recognize cannot prove causality.
However, as we discussed in our paper, we believe it unlikely that misclassification entirely explains this association. First, throughout the pandemic, there was a statutory requirement to report cases of SARS-CoV-2 infection in healthcare settings. Second, the laboratory-confirmed SARS-CoV-2 infection rate that we observed in women giving birth is very close to that reported for people aged between 25 and 35 years in a contemporaneous national survey of households. Third, although women infected earlier in pregnancy are not included in our “exposed” cohort, this is the case to the same extent for women who had a “good” as for those who had an adverse outcome. Therefore, the conclusion by Knight et al that misclassification may entirely explain the findings seems improbable. Instead, it is likely that SARS-CoV-2 infection at any time during pregnancy increases the risk of stillbirth, but that the odds ratio for that effect lies somewhere between 1.0 and the 2.21 that we reported.
Our study is just part of a growing body of evidence suggesting that SARS-CoV-2 infection increases the risk of stillbirth and certain other adverse pregnancy outcomes, although it remains uncertain how big this effect is.3 We agree that there is a pressing need for a prospective cohort study, based on time-to-event analyses of testing women regularly during their pregnancy, to determine whether this association is causal and accurately assess its strength.
Although we agree that it is important to avoid causing unnecessary anxiety to pregnant women and their families, we believe that it would be a disservice to women to downplay this growing evidence of a link between COVID-19 and stillbirth and other adverse pregnancy outcomes. While awaiting conclusive evidence from a further study, which may take considerable time, we should encourage pregnant women to take the current evidence into consideration when deciding whether to accept an offer of COVID-19 vaccination that has the potential to protect both them and their babies.
Footnotes
Ipek Gurol-Urganci, PhD (Department of Health Services Research, Faculty of Public Health and Policy, London School of Hygiene and Tropical Medicine, London, United Kingdom); Jennifer E. Jardine, MSc (Department of Health Services Research, Faculty of Public Health and Policy, London School of Hygiene and Tropical Medicine, London, United Kingdom); Fran Carroll, PhD (Royal College of Obstetricians and Gynaecologists, London, United Kingdom); Tim Draycott, FRCOG (Royal College of Obstetricians and Gynaecologists, London, United Kingdom; North Bristol NHS Trust Department of Women’ s Health, Westbury on Trym, Bristol, United Kingdom); George Dunn, BA (Royal College of Obstetricians and Gynaecologists, London, United Kingdom); Alissa Fremeaux, MSc (Royal College of Obstetricians and Gynaecologists, London, United Kingdom); Tina Harris, PhD (Centre for Reproduction Research, Faculty of Health and Life Sciences, De Montfort University, Leicester, United Kingdom); Jane Hawdon, PhD (Royal Free London NHS Foundation Trust, London, United Kingdom); Edward Morris, FRCOG (Royal College of Obstetricians and Gynaecologists, London, United Kingdom); Patrick Muller, MSc (Department of Health Services Research, Faculty of Public Health and Policy, London School of Hygiene and Tropical Medicine, London, United Kingdom); Lara Waite, MSc (Royal College of Obstetricians and Gynaecologists, London, United Kingdom); Kirstin Webster, MSc (Royal College of Obstetricians and Gynaecologists, London, United Kingdom); Jan van der Meulen, PhD (Fetal Medicine Unit, St George’ s Hospital, London, United Kingdom); Asma Khalil, MD (Fetal Medicine Unit, St George’ s Hospital, United Kingdom; Vascular Biology Research Centre Molecular and Clinical Sciences Research Institute, St George’ s University of London, United Kingdom).
All authors except J.v.d.M., T.D., and E.M. receive full or partial salary funding provided through the Healthcare Quality Improvement Partnership to the Royal College of Obstetricians and Gynaecologists (RCOG). E.M., T.D., J.E.J., and L.W. are members of the RCOG COVID-19 guidance cell, which produces clinical guidance and policy documents to support the management of pregnant women during the pandemic in the United Kingdom.
References
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