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\begin{document}

\title{CORONAVIRUS INFECTION (SARS-CoV-2) IN PREGNANT WOMEN: SYSTEMATIC REVIEW}



\author[1]{Paulino Vigil-De Gracia}%
\author[2]{Carlos Luo}%
\affil[1]{Caja de Seguro Social}%
\affil[2]{Affiliation not available}%


\vspace{-1em}



  
  \date{June 11, 2024}


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\selectlanguage{english}
\begin{abstract}
Objective: To review studies published with pregnant women infected with
SARS-CoV-2 and analyze the evolution of them and also of the newborn in
order to learn about this pathology in pregnant women. Search strategy:
Systematic review in the PUBMED and GOOGLE Scholar databases until March
30, 2020. This research was extended to the references of such articles.
Selection criteria: Observational studies that examined maternal and
perinatal outcomes of pregnant women with SARS-CoV-2 are published. Data
collection and analysis: Data about study characteristics, maternal y
perinatal outcomes variable extracted. Main results: We found 14
publications regarding a total of 83 pregnant women with SARS-CoV-2 and
results of 84 newborns. The average gestational age was 37 weeks. The
most common symptom was fever, and 30\% of the pregnant women had
lymphopenia on admission to hospital. Cesarean section was performed in
89\% of the patients; 70\% of them were indicated by SARS-CoV-2. The
most common obstetric complication was premature rupture of membranes in
9.6\% of them. The need for ventilation support was low. The use of
antivirals, corticosteroids, and drugs for the pathology management was
scarce, except for antibiotics. Preterm birth was 25\%, perinatal
mortality was low, and there was no maternal death. There was no
evidence of vertical transmission. Conclusion: Maternal and perinatal
morbidity-mortality is lower than in other known respiratory diseases.
Currently, it appears to be no benefit from antivirals and other drugs,
beyond the general support of the disease, and vertical transmission of
the virus has not been demonstrated.%
\end{abstract}%



\sloppy




\textbf{INTRODUCTION}

From the end of 2019, a viral infection caused by a new coronavirus has
emerged in Wuhan, China, and by March 11, 2020, the world health
organization declared this viral disease, now recognized as SARS-CoV-2,
as a pandemic disease.\textsuperscript{1--3}

In the few months that this infection has been observed, there has been
a fast and continuous knowledge contribution on epidemiology, genetics,
virology, diagnosis, and especially on the clinical aspect, highlighting
knowledge of lung disease. \textsuperscript{4,5}

During pregnancy, in theory, the risk of adverse outcomes for the mother
and her child increases if she contracts a viral respiratory infection.
Even maternal morbidity and lethality increases when compared to
nonpregnant women. \textsuperscript{6--9} In fact, this association has
been observed in mothers infected with other coronaviruses (SARS-CoV and
MERS-Cov). \textsuperscript{6,9} Adverse perinatal outcomes such as
prematurity, intrauterine death, and postnatal death have also been
reported with other coronavirus infections. \textsuperscript{10,11}

With the increasing number of cases worldwide, and countries reporting
more and more cases, it is obvious that there will be an increasing
number of pregnant women infected with SARS-CoV-2. \textsuperscript{12}

There are currently a variety of publications around SARS-CoV-2, ranging
from one case to a series of 16 cases. \textsuperscript{13--15} Most of
these publications report good maternal and neonatal evolution, unlike
reports in pregnant women with other coronavirus
infections.\textsuperscript{6--11}

The objective of this study is to show the medical and clinical findings
of pregnant women infected with SARS-CoV-2, and also the evolution of
the newborn, based on publications made available until March 30, 2020,
so that the physician can prepare for management and counseling of
pregnant women who may be diagnosed with SAR-CoV-2 infection.

\textbf{METHODOS}

We carried out a systematic analysis in the PUBMED and GOOGLE Scholar
databases until March 30, 2020, looking for published articles on
pregnant women infected with SARS-CoV-2, where the evolution in
pregnancy is reported after the infection diagnosis, birth, and the
results of it and evolution of the newborn. There was no language
restriction. This research was extended to the references of such
articles. Both researchers independently performed the study and
exported the relevant data to a data sheet, completed and endorsed by
both researchers. Also, doubts and discrepancies were resolved in a
consensual manner between both. The protocol was not registered due to
the time limit, the urgency, and the need for this report.

\textbf{RESULTS}

The initial research found 49 references. After the review, 14 articles
meet the inclusion criteria set out in this
review,\textsuperscript{13--25} figure 1.

In total, up to March 30, 2020, we found a total of 83 pregnant women
infected with SARS-CoV-2 who comply with information on pregnancy and
birth data, and in total 84 births were evaluated, table 1. All articles
are about patients in China.

The maternal results show that the patients were, on average, 30 years
old and a gestational age of 37 weeks; table 2. The most common symptom
was fever, and 30\% of pregnant women had lymphopenia on hospital
admission. The diagnostic method used for pulmonary complication was
computed tomography in 88\% of patients, chest radiography was only used
in one patient. Vaginal delivery only occurred in 11\%, while the
indication for caesarean section in 70\% was caused by the presence of
pulmonary disease due to the coronavirus. The most common obstetric
complication was premature rupture of membranes, with 9.6\%; table 2.
The need for mechanical ventilatory support occurred in 3 patients
(3.6\%), and one of them was during pregnant. In pregnant women, the use
of antivirals, corticosteroids, and drugs for the management of maternal
pathology was little, except for antibiotics.

Preterm birth was observed in one out of 4 patients; table 3. Pneumonia
was diagnosed in 13\% of the newborns, possibly not associated with
SARS-CoV-2. Four newborns were to SARS-CoV-2 quantitative RT-PCR,
however, vertical transmission was not confirmed. There were two
perinatal deaths, one intrauterine and the other after 9 days
post-birth.

There were no maternal deaths among the 83 pregnant women diagnosed with
SARS-CoV-19, however the evolution of a very complicated patient is
unknown.

\textbf{Discussion}

\textbf{Main Findings}

This review of pregnant women with SARS-Cov-19 demonstrates that there
are 14 studies or reports with a total of 83 pregnant women showing that
the disease in pregnant women has the same or better prognosis than the
rest of the population.

\textbf{Strengths and limitations}

The main weakness of this review is that all the included studies are
case reports or series of low quality evidence, and therefore these
results should be taken with caution. And the strength comes out of
putting all the results of these patients together, and having them in a
single study, so that the treating physician is able to make better
decisions regarding the pregnant woman with coronavirus-2019 disease.

\textbf{Interpretation}

Studies of influenza, severe respiratory distress syndrome, and Middle
East respiratory syndrome due to coronaviruses show that these
pathologies increase maternal and perinatal morbidity and
mortality.\textsuperscript{6--11,27} Even the total number of pregnant
women with these diseases is less than that reported in this study, so
it seems unlikely that our findings will change significantly.

Some specific findings we can highlight from this review are that the
severity and mortality in pregnant women is less than in general
population but very similar with the age group.
\textsuperscript{28--30}The clinical findings are very similar to the
rest of the population,\textsuperscript{28,29,31} and, in addition, the
diagnosis of pulmonary pathology in pregnant woman is basically made
with computed tomography. Interestingly one third of this population had
lymphopenia. It was observed even in patients without symptoms of the
disease\textsuperscript{26}, this laboratory finding could be considered
when the infection by coronavirus-19 is observed in pregnant women.

It is noteworthy that the use of antivirals, chloroquine, and
Lopinavir-Ritonavir is very low in this pregnant population
(\textless{}5\%); however, the use of antivirals was more than 50\%
after birth. The need for mechanical ventilation was very low, which
suggests that pregnant patients, despite being a higher-risk population,
tend not to be complicated despite the disease; it is worthwhile to
continue investigating to determine if this is it true or not.

In the obstetric part, it is interesting that about 10\% are complicated
by premature rupture of the membranes, a percentage three times higher
when compared to the general population \textsuperscript{32}. Also, we
must highlight that one out of four pregnant women ended their pregnancy
prematurely; however, it was not a cause of perinatal mortality,
possibly because most of them were late preterm. Perinatal mortality is
low, and the evolution is very good, despite the presence of pneumonia
in one out of 10 newborns.

This review found no association or evidence of vertical transmission of
the coronavirus-2019 at birth. Four infants who had a positive test,
however those tests were made more than 36 hours after
birth\textsuperscript{16,22} and proving it with antibodies also raises
questions. \textsuperscript{33}

\textbf{Conclusions}

Despite the few publications of pregnant women with SARS-CoV-19, we can
point out that maternal and perinatal morbidity and mortality are lower
than in other known respiratory diseases as SARS-CoV and MERS-CoV
generated by coronavirus. Currently, there appears to be no benefit from
antivirals and other drugs beyond of the general disease support, and
vertical transmission of the virus has not been demonstrated and if it
exists, the possibility is very low and with little neonatal
repercussion.

\textbf{Disclosure of interests:~} We report no conflicts of
interest.\textbf{Author's contribution:} PV-D conceived the study. PV-D
and CL contributed to its design, PV-D and CL search, review and analyze
the papers, PV-D and CL interpret results. PV-D and CL revised the
manuscript. All authors approved the final manuscript as submitted.

\textbf{Details of ethics approval:} Not applicable

\textbf{Funding:} None

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Figure 1. Flow diagram - Summary of evidence search and analysis

Table 1:

Articles with inclusion criteria\selectlanguage{english}
\begin{longtable}[]{@{}lllllll@{}}
\toprule
Author & Journal & Hospital & City & Country & Pregnancies &
Births\tabularnewline
\midrule
\endhead
Wang X \textsuperscript{13} & Clin Infect Dis & Suzhou Municipal
Hospital & Suzhou & China & 1 & 1\tabularnewline
Chen H \textsuperscript{14} & Lancet & Zhongnan Hospital of Zhongnan
Hospital of Wuhan University & Wuhan & China & 9 & 9\tabularnewline
Zhang L \textsuperscript{15} & Cma J cn & Eastern Hospital of the
People's Hospital of Wuhan University & Wuhan & China & 16 &
16\tabularnewline
Dong L \textsuperscript{16} & JAMA & Renmin Hospital, Wuhan & Wuhan &
China & 1 & 1\tabularnewline
Liu W \textsuperscript{17} & Preprints & Tongji Hospital,Huazhong
University & Wuhan & China & 3 & 3\tabularnewline
Yangli L \textsuperscript{18} & J Infection & First Affiliated Hospita,
Sun Yat-sen University, Guangzhou, & Guangzhou & China & 10 &
10\tabularnewline
Chen Y \textsuperscript{19} & Front Pediatr & Union Hospital, Huazhong
University of Science \& Technology & Wuhan & China & 4 &
4\tabularnewline
Zhu H \textsuperscript{20} & Transl Pediatr & Maternal and Child Health
Hospital of Hubei Province. & Wuhan & China & 9 & 10\tabularnewline
Yu N \textsuperscript{21} & Lancet Infect Dis & Tongji Hospital, Tongji
Medical College, & Wuhan & China & 7 & 7\tabularnewline
Zeng L \textsuperscript{22} & JAMA Pediatr & Wuhan Children\selectlanguage{ngerman}´s hospital &
Wuhan & China & 3 & 3\tabularnewline
Chen S \textsuperscript{23} & Chin J Pathol & Union Hospital, Tongji
Medical College & Wuhan & China & 3 & 3\tabularnewline
Liu D \textsuperscript{24} & AJR Am J Roentgenol & Union Hospital,
Tongji Medical College & Wuhan & China & 11 & 11\tabularnewline
Li Y \textsuperscript{25} & Emerg Infect Dis & Hospital, College of
Medicine, Zhejiang University, Hangzhou & Hangzhou & China & 1 &
1\tabularnewline
Siyu C \textsuperscript{26} & Journal of medical virology & Maternal and
Child Hospital of Hubei Province & Wuhan & China & 5 & 5\tabularnewline
Total & 14 & 10 & 4 & 1 & 83 & 84\tabularnewline
\bottomrule
\end{longtable}

Table 2:

Clinical characteristics and outcome of mothers with COVID-19. *\selectlanguage{english}
\begin{longtable}[]{@{}ll@{}}
\toprule
Variable / Outcome &\tabularnewline
\midrule
\endhead
Weigh (SD), g & 3016 (243.3)\tabularnewline
Premature delivery N(\%) & 21(25.0)\tabularnewline
Apgar score 1 min & 8.39(0.6)\tabularnewline
Apgar score 5 min & 9.23(0.4)\tabularnewline
Neonatal pneumonia N(\%) & 10(13.0)\tabularnewline
Perinatal death N(\%) & 2(2.4)\tabularnewline
Positive neonatal SARS-CoV-2 quantitative RT-PCR & 4(5.1)\tabularnewline
Confirmed Vertical Transmission of SARS-CoV-2 & 0(0)\tabularnewline
\bottomrule
\end{longtable}

* Some results have different denominators; PROM = Premature rupture of
membranes, computed tomography = CT

Table 3:

Perinatal outcomes of pregnant women with COVID-19. *\selectlanguage{english}
\begin{longtable}[]{@{}ll@{}}
\toprule
Variable / Outcome &\tabularnewline
\midrule
\endhead
Weigh (SD), g & 3016 (243.3)\tabularnewline
Premature delivery N(\%) & 21(25.0)\tabularnewline
Apgar score 1 min & 8.39(0.6)\tabularnewline
Apgar score 5 min & 9.23(0.4)\tabularnewline
Neonatal pneumonia N(\%) & 10(13.0)\tabularnewline
Perinatal death N(\%) & 2(2.4)\tabularnewline
Positive neonatal SARS-CoV-2 quantitative RT-PCR & 4(5.1)\tabularnewline
Confirmed Vertical Transmission of SARS-CoV-2 & 0(0)\tabularnewline
\bottomrule
\end{longtable}

* Some results have different denominators\selectlanguage{english}
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\includegraphics[width=0.70\columnwidth]{figures/Figure-1/Figure-1}

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