METHOD
During the second wave of the COVID-19 pandemic in Denmark, we conducted
a prospective cohort study entitled the “CareMum COVID-19 study” from
August 20th, 2020 to March 1st,
2021, at the Department of Obstetrics and Gynaecology, Copenhagen
University Hospital – North Zealand with approximately 4000 annual
deliveries.
We included pregnant women who tested positive for SARS-CoV-2 in a
pharyngeal swab at a test centre or during a routine test when entering
the antenatal clinic or labour ward. Women were eligible if they were to
deliver within the study period and were able to give written and oral
informed consent in English or Danish. Inclusion took place either
during pregnancy at the antenatal clinic or when women were admitted for
delivery. All participants had vaginal swabs and maternal blood samples
done at the time of inclusion. If included during pregnancy, the samples
were repeated at delivery where an umbilical cord blood sample was also
taken. At the time of delivery, two vaginal swabs were done – the
first, during the initial vaginal examination, and the second, during
the active phase of delivery or immediately after. Vaginal swabs were
frozen at -20°C until analysis (0-30 days, median 5 days). A maternal
blood sample was taken just before or immediately after delivery, and an
umbilical cord blood sample was performed immediately after birth. Blood
samples were frozen at -80°C until analysis.
In some cases, swabs from the neonate and the placenta, as well as a
placental histopathological examination and one fetal autopsy, was
performed on clinical indications. Placental swabs were done from both
the maternal and the fetal side, and neonatal swabs from the axillary
fold, naso-, and oropharynx. These samples were not part of the study
protocol, but results are described when present.
Pharyngeal swabs as well as vaginal and placental swabs were analysed by
RT-PCR as part of the routine diagnostics (see supporting information,
appendix S1, for further information).
Total SARS-CoV-2 antibodies in maternal and cord blood samples were
analysed using a qualitative (reactive/non-reactive) biochemical assay,
The VITROS Immunodiagnostic Product Anti-SARS-CoV-2 Total (CoV2T),
developed by Ortho-Clinical Diagnostics. The test result (S/C) = (signal
for test sample / signal at cutoff value) ≥ 1.00 is considered reactive
(i.e. positive for antibodies) and result < 1.00 is considered
non-reactive (i.e. negative for antibodies).
We obtained demographic and clinical data of participants as well as
non-participants in the “CareMum COVID-19 study” from the Danish
“COVID-19 in pregnancy” database, which contains information based on
medical records on all women diagnosed with COVID-19 during pregnancy in
Denmark as described elsewhere (12). Non-participants were women who
tested positive for SARS-CoV-2 and gave birth within the study period
but who for various reasons were not included in this study (e.g. women
did not understand and read Danish/English, did not want to participate
or were not asked due to busyness at the maternity ward). Case
completeness was secured by a retrospective registry linkage to national
databases covering information on results from SARS-CoV-2 pharyngeal
swabs. Furthermore, participants were asked to complete a questionnaire
about COVID-19 symptoms at the time of inclusion. Symptoms of
non-participants were not systematically reported.
Data was analysed using SPSS version 27 (SPSS Inc., Chicago, IL).
Categorical variables are presented as number with percentage and
continuous variables as mean with standard deviation (SD) or median with
interquartile range as appropriate. Analyses of differences between
means, medians and proportions were performed using Student’s T-test,
Mann-Whitney, or Fischer’s Exact test, respectively. The study was
approved by The Regional Committee on Health Research Ethics.