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\begin{document}

\title{The role of shared risk factors for COVID-19 and preeclampsia: An
observational study}



\author[1]{Berta Serrano}%
\author[1]{Manel Mendoza}%
\author[1]{Paula Garcia-Aguilar}%
\author[1]{Erika Bonacina}%
\author[2]{Itziar Garcia-Ruiz}%
\author[1]{Pablo Garcia-Manau}%
\author[3]{Judit Gil}%
\author[1]{Mireia Armengol}%
\author[2]{Nuria Fernández-Hidalgo}%
\author[4]{Elena Sulleiro}%
\author[1]{Rosa Maria Lopez-Martinez}%
\author[5]{Marta Ricart}%
\author[6]{Lourdes Martin}%
\author[7]{Eva Lopez-Quesada}%
\author[8]{Angels Vives}%
\author[9]{Anna Maroto}%
\author[3]{Nerea Maiz}%
\author[2]{Anna Suy}%
\author[2]{Elena Carreras}%
\affil[1]{Vall d'Hebron Hospital}%
\affil[2]{Vall d'Hebron University Hospital}%
\affil[3]{Hospital Universitari Vall d'Hebron}%
\affil[4]{Vall d'Hebron Hospital Universitari}%
\affil[5]{University Hospital Germans Trias i Pujol}%
\affil[6]{Joan XXIII University Hospital in Tarragona}%
\affil[7]{Grup Mutua Terrassa}%
\affil[8]{Consorci Sanitari de Terrassa}%
\affil[9]{Doctor Josep Trueta University Hospital of Girona}%


\vspace{-1em}



  
  \date{May 18, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Objective: To examine baseline risk factors measured in the
first-trimester screening for preeclampsia (PE) in pregnant women with
COVID-19 versus the general population. To compare risk factors among
patients with mild and severe COVID-19. Design: Observational
retrospective study. Setting: Six maternities in Catalonia. Population:
Study patients were 231 pregnant women undergoing first-trimester
screening for PE and positive for SARS-CoV-2. Reference cohort were
13,033 pregnant women with first-trimester screening for PE from 6
maternities. Methods: Recording of maternal history, mean arterial blood
pressure (MAP), mean uterine artery pulsatility index (UtAPI), placental
growth factor (PlGF) and pregnancy-associated plasma protein-A at first
trimester. Confirmation of SARS-CoV-2 infection. Based on the need for
hospitalization, patients were classified into mild and severe COVID-19.
Main outcome measures: Comparison of proportion of cases at a high risk
for PE and of risk factors for PE among groups. Results: High risk for
PE was significantly higher amongst COVID-19 patients compared to the
general population, showing higher rates of obesity, chronic
hypertension, higher UtAPI, and lower rates of smokers. PlGF did not
differ significantly. In women with severe COVID-19, compared with mild
COVID-19, BMI and MAP were significantly higher, whereas PlGF and UtAPI
did not differ significantly. Conclusions: In patients with COVID-19
there was a higher proportion of women at a high risk for PE than in the
general population, mainly due to maternal risk factors, rather than
placental signs of a deficient trophoblastic invasion. Likewise,
according to COVID-19 severity, differences were due to maternal risk
factors only.%
\end{abstract}%



\sloppy


\textbf{INTRODUCTION}

The relationship of SARS-CoV-2 and pregnancy has been under study since
the outset of the coronavirus pandemic. Evidence shows that pregnant
women with COVID-19 are at an increased risk of severe pregnancy
complications, including preeclampsia (PE), admission at the intensive
care unit, preterm birth or maternal mortality\textsuperscript{1}.

One of the first studies about COVID-19 and pregnancy, published in
February 2020, suggested an increased PE incidence amongst pregnant
women with COVID-19\textsuperscript{2}. This was confirmed in a
systematic review published online in March 2020, where a PE incidence
of 14.6\% was observed in pregnant women with
COVID-19\textsuperscript{3}, as compared with 2-8\% in the general
population\textsuperscript{4}. INTERCOVID, a prospective comparative
study matching pregnant women with and without COVID-19, showed that the
risk of developing PE/eclampsia was almost 4 times greater in women with
COVID-19\textsuperscript{1}. Subsequent analysis of the same population
examining PE incidence showed a risk ratio of 1.95 (95\%CI:
1.38-2.75)\textsuperscript{5}. Recently, a large meta-analysis that
included 28 studies showed an increased PE incidence risk, with an odds
ratio of 1.62 (95\%CI: 1.45-1.82)\textsuperscript{6}.

Different theories have been suggested regarding the association between
PE and COVID-19\textsuperscript{5--9}. One of them hypothesises that PE
and COVID-19 are associated due to sharing risk factors for endothelial
damage, such as obesity, hypertension, diabetes and maternal age. In
that case, PE in the preclinical stage could be an additional risk
factor for endothelial damage, thereby increasing the risk of developing
COVID-19, mostly in its severe forms. The question is whether
preexisting endothelial damage due to abnormal trophoblastic invasion
increases the risk of developing COVID-19 and its severity, or whether
the association between both conditions is driven by the fact that
COVID-19 and PE share risk factors increasing the risk of both
conditions. If preexisting endothelial damage due to abnormal
trophoblastic invasion\textsuperscript{10} makes patients more
vulnerable to COVID-19 (or more likely to develop a severe form of
COVID-19), women with COVID-19 would have lower placental growth factor
(PlGF) levels and increased mean uterine artery pulsatility index
(UtAPI) as compared to the reference population.

The primary aim of this study was to examine baseline risk factors, as
well as biochemical and biophysical markers measured in the
first-trimester combined screening for PE in pregnant women with
COVID-19 versus the general population. The secondary aim was to compare
these baseline characteristics and markers between women with mild and
severe COVID-19.

\textbf{METHODS}

This was an observational retrospective study conducted at Vall d'Hebron
Barcelona Hospital Campus, Barcelona, Spain. This study was approved by
the Vall d'Hebron Barcelona Hospital Campus Ethics Committee
(PR{[}AMI{]}556/2021) on 5\textsuperscript{th} November 2021. For the
study group, inclusion criteria were women (a) attending our site with
confirmed SARS-CoV-2 infection at any point during pregnancy and (b)
undergoing the first-trimester combined screening for PE. The
recruitment period for the SARS-CoV-2 group was from February 2020 to
September 2021. Our centre was a referral hospital for severe COVID-19
pneumonia, especially during pregnancy; therefore, cases were both
patients from our area and patients referred from all across Catalonia.
For the population group, data was obtained from general population
attending first-trimester screening for PE in 6 centres across Catalonia
(Vall d'Hebron Barcelona Hospital Campus, Hospital Universitari Germans
Trias i Pujol, Hospital Universitari de Tarragona Joan XXIII, Hospital
Universitari M\selectlanguage{ngerman}útua Terrassa, Consorci Sanitari de Terrassa, Hospital
Universitari de Girona Doctor Josep Trueta) between May 2019 and June
2021. A previous study assessing the screening performance of the
first-trimester screening for PE was approved (PR(AMI)147/2021), and,
therefore, data from general population was prospectively recorded.

SARS-CoV-2 infection was confirmed either by real-time polymerase chain
reaction (RT-PCR) or an antigen test. Several changes in screening
protocols have occurred during the study period, while scientific
evidence or assistance care needs were changing. Therefore, our study
population included both patients systematically screened at hospital
admission and patients screened because of symptomatology or close
contact. In the study group, severity of the symptoms was the criteria
used for classification: mild forms of COVID-19, including asymptomatic
and symptomatic women not requiring hospitalization, and severe forms of
COVID-19, including patients requiring hospitalization due to severe
pneumonia.

In Catalonia, the first-trimester screening for PE is routinely
performed during the first-trimester scan between 11+0 and 13+6 weeks of
gestation. Gestational age is confirmed by fetal crown-rump length
measurement during this scan\textsuperscript{11}. Demographic
characteristics, obstetric history, maternal history and biophysical and
biochemical markers are documented in the clinical records. Biophysical
markers, including transabdominal mean uterine artery pulsatility index
(UtAPI) and mean arterial blood pressure (MAP), are assessed during the
first-trimester scan. Biochemical markers, including serum
pregnancy-associated plasma protein-A (PAPP-A) and placental growth
factor (PlGF), are measured at the routine first-trimester blood test
(from 8+0 to 13+6 weeks of gestation). Maternal serum PAPP-A and PlGF
levels were determined by the fully automated Elecsys assays for PAPP-A
and PlGF on an immunoassay platform (cobas e analysers; Roche®
Diagnostics, Rotkreuz, Switzerland). First-trimester risk for PE was
then calculated\textsuperscript{4}. High risk for PE was defined as a
risk for early-onset PE \selectlanguage{english}[?] 1/170. This cut-off value provides a 90.9\%
detection rate for early-onset PE at a 12.7\% false-positive
rate\textsuperscript{12}.

All examiners were certified by the Fetal Medicine Foundation for PE
risk assessment and Doppler ultrasound assessment.

\textbf{Statistical Analysis}

Categorical data were reported as frequency and percentage, and
comparisons between groups were estimated by chi-square or Fisher tests,
as appropriate. Continuous variables were reported as the median and
interquartile range, and Mann-Whitney U test was used to assess
differences between groups. The statistical significance level was set
at p\textless{}0.05.

The statistical software package R (version 4.0.3) was used for data
analysis (R Foundation for Statistical Computing, Vienna,
Austria)\textsuperscript{13}.

\textbf{RESULTS}

For the study group (or COVID-19 group), 231 women fulfilled the
inclusion criteria. In the population group (or reference group), 13,033
women underwent the routine first-trimester screening for PE.

\emph{Comparison of the COVID-19 and reference groups}

In the COVID-19 group, 44 out of 231 (19.0\%) cases were identified to
be at a high risk for PE at the first-trimester screening, and this
incidence was significantly higher than the 1,719 out of 13,033 (13.2\%)
found in the general population (p=0.012). When PE risk factors were
examined individually, we found that women with COVID-19 had higher
UtAPI and body mass index (BMI), higher incidence of chronic
hypertension, and fewer were smokers. No significant differences were
found in MAP, PlGF, maternal age, black race, or history of PE or
diabetes mellitus between the COVID-19 group and the general population
(Table 1).

\emph{Comparison between mild and severe forms of COVID-19}

In the COVID-19 group, 160 (69.3\%) women developed mild COVID-19 and 71
(30.7\%) women developed severe COVID-19. Of the 160 women with mild
COVID-19, 25 (15.6\%) were at a high risk for PE in the first-trimester
screening. Likewise, of the 71 women with severe COVID-19, 19 (26.8\%)
were also at a high risk for PE in the first-trimester screening.
Nevertheless, this difference was not statistically significant
(p=0.071). In women with severe COVID-19 MAP in the first trimester was
higher, as well as BMI. No other significant differences were found in
other markers or risk factors for PE between the groups with mild and
severe forms of COVID-19 (Table 2).

\textbf{DISCUSSION}

\textbf{Main findings}

This study shows a higher prevalence of risk factors for PE during the
first trimester in women with COVID-19 as compared with the reference
population. In the COVID-19 group the proportion of high BMI and chronic
hypertension was higher, whereas the proportion of smokers was lower,
which are also risk factors for developing PE. Regarding biochemical and
biophysical markers, no differences were found in PlGF levels. However,
in the COVID-19 group there was a slight increase, although
statistically significant, in UtAPI (1.08 MoM versus 1.00 MoM).

When we examined the COVID-19 group according to severity (mild or
severe), no differences were observed in PlGF and UtAPI. However, women
with severe COVID-19 had significantly higher BMI and MAP at the
first-trimester screening.

The findings of this study support the hypothesis that women with
COVID-19 are at a higher risk for PE than the general population;
however, it seems that this was due mainly to shared maternal risk
factors (obesity and hypertension), as there was no significant
difference in PlGF levels, and the small difference in UtAPI is probably
not correlated with abnormal trophoblastic invasion, as first-trimester
multiple of the median (MoM) UtAPI values in our population ranges from
1.12 to 1.67 in women that subsequently develop PE, whereas MoM UtAPI
values are 1.03 in women without PE\textsuperscript{14}.

\textbf{Strengths and limitations}

The present study provides novel evidence that women with COVID-19 are
at a higher risk for PE at the first trimester mainly due to maternal
risk factors, which are shared by both conditions. In addition, there
does not seem to be an association between COVID-19 and risk factors for
placental insufficiency. One of the main strengths of this study is the
large number of subjects. Additionally, the first-trimester screening
for PE was routinely performed; therefore, despite this being a
retrospective study, maternal risk factors, PlGF and UtAPI were
prospectively recorded for all patients at the time of the routine
first-trimester scan.

One of the main limitations of this study is its retrospective nature.
Additionally, this study may have a selection bias. On the one hand,
cases in the study group with severe disease might be over-represented,
as our site was a referral hospital for severe COVID-19 with pneumonia
in Catalonia. On the other hand, asymptomatic cases in the study cohort
might also be over-represented, since a RT-PCR was incorporated during
the pandemic as a routine test for all admitted patients.

Another limitation of the study is that the general population used as
the reference group cannot be considered purely a control group due to
the lack of specific information about SARS-CoV-2 infection. For this
reason, some asymptomatic and mild COVID-19 cases might be found in the
reference group. Nevertheless, this might have reduced the chances of
finding differences between groups making our findings even more
meaningful.

\textbf{Interpretation}

The association between PE and COVID-19 has been studied since the
beginning of the coronavirus pandemic. Some studies have hypothesized
that the association between PE and COVID-19 may be explained by the
fact that both conditions share common systemic risk factors, such as
obesity, advanced maternal age, diabetes, or hypertension, among
others\textsuperscript{5,9}. However, the potential association between
PE and COVID-19 due to specific placental risk factors has never been
examined.

Giorgione and Thilaganathan suggested that subclinical cardiovascular
dysfunction in general population may induce placental malperfusion and
ischemia, thus increasing PE risk. Therefore, subclinical cardiovascular
dysfunction due to COVID-19 may lead to acquired utero-placental
malperfusion, potentially causing PE. Although we agree that maternal
systemic risk factors may explain the association between COVID-19 and
PE, we believe that the association between both conditions is unlikely
to be due to an abnormal trophoblastic invasion\textsuperscript{9}.
Therefore, our results might partly support the findings of the
INTERCOVID study, which showed that the association between COVID-19 and
PE did not not decrease with aspirin treatment\textsuperscript{5}.

Other studies have demonstrated a clear association between diabetes,
increased BMI and the risk of developing COVID-19\textsuperscript{15}.
Additionally, these studies showed that severe COVID-19 was associated
with higher maternal age, higher BMI, hypertension and
diabetes\textsuperscript{16}. Our results support these findings.

Determining whether the association of PE and COVID-19 is due to shared
risk factors or whether it is driven by placental predisposition is
crucial to provide appropriate treatment and surveillance. Our data
provide evidence that PE and COVID-19 share systemic risk factors that
may account for the association between these two conditions. However,
our data suggest that placental insufficiency is unlikely to be involved
in the development of COVID-19 or its severity. Given that aspirin's
mechanism of action for PE prevention primarily involves the improvement
of trophoblastic invasion\textsuperscript{10}, aspirin treatment is
unlikely to be effective for reducing COVID-19 risk in pregnancies at a
high risk for PE in the first trimester; nevertheless, more research is
needed to ascertain the role of aspirin in pregnant women with COVID-19.

\textbf{CONCLUSION}

In patients with COVID-19, there was a higher proportion of women at a
high risk for PE at the first-trimester screening than in the general
population, mainly due to maternal risk factors, rather than placental
signs of a deficient trophoblastic invasion.

Likewise, when comparing according to COVID-19 severity, the proportion
of women with a high risk for PE tended to be greater amongst those with
severe forms of COVID-19 and it was due to maternal risk factors only.



\textbf{ACKNOWLEDGMENTS}

We thank Maria del Mar Jimenez Quesada for English language corrections
of the manuscript and all the physicians who provided healthcare to
pregnant women with COVID-19 during these uncertain times and under
unusual circumstances.

One of the authors is a member\textbf{~} of the~ European Reference
Network on Rare Congenital Malformations and Rare Intellectual
Disability ERN-ITHACA~ {[}EU Framework Partnership Agreement ID:
3HP-HP-FPA ERN-01-2016/739516{]}.

\textbf{DISCLOSURE OF INTEREST}

Manel Mendoza, Lourdes Martin and Itziar Garcia-Ruiz received lecture
fees from Roche Diagnostics. The other authors declare that they have no
conflicts of interest.

\textbf{CONTRIBUTION TO AUTHORSHIP}

BS, MM and EC had full access to all of the data in the study and take
full responsibility for the integrity of the data and accuracy of the
data analysis. BS, MM and EC conceived and designed the study. BS, MM,
PGA, EB, IGR, PGM, NFH, ES, NM and AS contributed to literature
research. BS, MM, JG, MA, RMLM, MR, LM, ELQ, AV and AM contributed to
data collection and confirmation. BS and MM contributed to data analysis
and data interpretation. BS and MM were in charge of writing the
manuscript draft. EC made substantial revisions to the manuscript. All
authors read and approved the final manuscript.



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\textbf{Table 1. Comparison of preeclampsia risk factors between the
COVID-19 group and the general population}\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
\begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
\textbf{COVID-19} \textbf{N=231}\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
\textbf{General population} \textbf{N=13,033}\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
\textbf{p}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
High risk of preeclampsia\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
44 (19.0\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
11,719 (13.2\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.012\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Mean arterial pressure (MoM)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1.09 (1.01-1.18)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1.09 (1.01-1.17)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.906\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Uterine artery PI (MoM)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1.08 (0.88-1.31)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1.00 (0.82-1.20)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
PLGF (MoM)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.96 (0.77-1.89)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.97 (0.77-1.20)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.760\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
BMI (kg/m\textsuperscript{2})\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
25.2 (22.2-29.4)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
24.5 (21.8-28.3)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.041\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Maternal age (y)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
31.8 (26.8-36.2)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
32.6 (28.2-36.4)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.065\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Black race\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
7/230 (3.0\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
402 (3.1\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Chronic hypertension\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
6/218 (2.8\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
104/11698 (0.9\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.015\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
History of preeclampsia\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
9/218 (4.1\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
261/11917 (2.2\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.100\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Smoking\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
13/229 (5.7\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1494/12847 (11.6\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.007\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Nulliparous\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
66/219 (30.1\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
4249/11664 (36.4\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.065\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Assisted reproduction technique\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
8/231 (3.5\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
303/13033 (2.3\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.361\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Diabetes mellitus\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2/228 (0.9\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
158/12552 (1.3\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1.0\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

Continuous variables are shown as the median and interquartile range
(1st and 3rd quartiles). Categorical data are shown as absolute
frequency and percentage.

PLGF~= Placental growth factor; MoM~= multiples of the median; PI~=
pulsatility index; BMI~= body mass index

\textbf{Table 2. Comparison of preeclampsia risk factors between mild
and severe forms of COVID-19}\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
\begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
\textbf{Mild} \textbf{N=160}\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
\textbf{Severe} \textbf{N=71}\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
\textbf{p}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
High risk of preeclampsia\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
25 (15.6\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
19 (26.8\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.071\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Mean arterial pressure (MoM)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1.08 (1.00-1.16)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1.12 (1.05-1.22)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.008\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Uterine artery PI (MoM)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1.07 (0.85-1.33)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1.09 (0.94-1.26)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.756\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
PLGF (MoM)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.97 (0.77-1.22)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.96 (0.77-1.11)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.862\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
BMI (kg/m\textsuperscript{2})\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
23.7 (21.7-27.6)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
28.2 (24.6-30.8)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Maternal age (y)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
31.3 (26.3-36.0)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
34.1 (28.0-37.9)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.069\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Black race\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
5 (3.1\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2 (2.9\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1.0\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Chronic hypertension\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
3 (2.0\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
3 (4.6\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.366\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
History of preeclampsia\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
7 (4.6\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2 (3.1\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1.0\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Smoking\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
12 (7.6\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1 (1.4\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.069\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Nulliparous\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
49 (31.8\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
17 (26.2\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.426\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Assisted reproduction technique\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
5 (3.1\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
3 (4.2\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.704\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Diabetes mellitus\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1 (0.6\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1 (1.4\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.521\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

Continuous variables are shown as median and interquartile range (1st
and 3rd quartiles). Categorical data are shown as absolute frequency and
percentage.

PLGF~= Placental growth factor; MoM~= multiples of the median; PI~=
pulsatility index; BMI~= body mass index

\selectlanguage{english}
\FloatBarrier
\end{document}

