Clinical Features Pregnancy with COVID-19 at Sanglah General Hospital

Denpasar, Bali periode of April 2020 – September 2020

Jaya Kusuma, AAN1, Surya IGP1, Suwardewa, Tjokorda Gde Agung1, Sanjaya, I
Nyoman1, Negara, Ketut Surya1, Putra, I Wayan Artana1, Wiradnyana, AAG Putra1,
Widiyanti, Endang Sri1, Mulyana, Ryan Saktika1, Pangkahila, Evert Solomon1, Susanto,
Daniel Hadinata2, Sardeva, I N Rake Genatra2, Widnyana, I Gusti Made Kusuma2,
Darmawan, Ngakan Ketut2
1
Maternal Fetal Medicine Division, Obstetric and Gynecology Department, Medical Faculty of Udayana
University/ Sanglah General Hospital
2
Registrar of Obstetric and Gynecology Department, Medical Faculty of Udayana University/ Sanglah General
Hospital
Corresponding author : Jaya Kusuma,AAN

Abstract

Objective: The Corona Virus Disease 2019 (COVID-19) pandemic has made a wide impact
on health systems and communities around the world. The development of knowledge about
pathogenesis and the lack of research on COVID-19 in pregnancy led to the need for a study
of the characteristics of pregnancy with COVID-19 to find out clinical, serological and
pregnancy outcomes with COVID-19 at Sanglah Hospital Denpasar.

Methods: A retrospective descriptive study using secondary data from the medical records of
pregnant women with COVID-19 for the period April-September 2020 at Sanglah Hospital,
Denpasar.

Results: From April to September 2020 there were 41 confirmed case of pregnancies with
COVID-19 and 2 maternal deaths related to COVID-19 at Sanglah Hospital. In this study, the
most maternal age for pregnancies with COVID-19 were 26-30 years (19 cases / 46.34%) and
the most gestational age was in the third trimester (38 cases / 92.68%). Anti-SARS-CoV-2
rapid test results showed that IgG and IgM were reactive in 18 cases (43.90%), the sensitivity
and specificity of the rapid test as a screening tool for COVID-19 in pregnancy were 86.11%
and 89.34%, respectively. There were 27 asymptomatic cases and 4 cases with severe
symptoms. The mean Neutrophile Lymphocyte Ratio (NLR) in cases with severe symptoms
was 7.96. It was found that the most pregnancy complications were preeclampsia in 8 cases
(19.50%). 32 cases (84.21%) were delivered by cesarean section. The most birth weight was
≥ 2500 grams in 27 cases (69.23%), with 33 cases of vigorous babies (84.62%), there were 2
babies confirmed with COVID-19.

Conclusion: Pregnant women are a population vulnerable to COVID-19 due to changes in

the immunological and physiological systems during pregnancy. Most COVID-19 occurs in
the third trimester. There was preeclampsia complicating pregnancy and most of the
pregnancy outcome were vigorous babies. There were 2 cases of neonates confirmed by
COVID-19. Further research is needed to prove intrauterine vertical transmission of COVID-
19.
Keywords: pregnancy, COVID-19

Background

The outbreak of a new coronavirus infection which became known as Severe Acute

Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) which caused Corona Virus Disease

2019 (COVID-19) first appeared in Wuhan, China with a clinical presentation similar to

pneumonia caused by a virus. This virus is easily and quickly transmitted through respiratory

droplets, physical contact and aerosols. In subsequent developments, data was also obtained

that there was human-to-human transmission. This type of pneumonia caused by SARS-CoV-

2 quickly spread throughout the world and became a global pandemic, including in Indonesia

until now.1 Until September 13, 2020, cases in Indonesia have reached 218,382 confirmed

cases with a death rate of 3.99% (8,723 cases). 2 The most common clinical manifestations

found in patients with COVID-19 are fever, myalgia, headache and dry cough.3 Symptoms of

COVID-19 that develop to be severe are caused by an excessive immune response

characterized by increased plasma levels of IL-1β, IL-2, IL-6, IL-7, IL-10, granulocyte

colony-stimulating factor (G-CSF) and tumor necrosis factor (TNF), known as the Cytokine

Storm phenomenon.4

The population of pregnant women has also not been spared from COVID-19 and the

number continues to increase. Pregnancy is a condition where there is a dysregulation of the

immune system that causes pregnant women to be susceptible to this infection, which is

reported to cause higher morbidity than common influenza. 5 The vulnerability of pregnant

women to Covid-19 is partly due to hormonal changes and a decrease in lung volume because

of an increase in uterine size during pregnancy. The patient can experience a more rapid

clinical deterioration. Moreover, other physiological changes such as an increase in the

transverse diameter of the thoracic cavity, decreased tolerance to hypoxia and vasodilation

can result in mucosal edema and increased secretions in the upper airways. 6 Pregnant women,
especially in the third trimester with COVID-19, are also reported to be at risk for premature

rupture of membranes, preterm birth, fetal tachycardia, fetal distress and the risk of vertical

transmission from mother to fetus.5

At the time of this report, there were 41 cases of pregnancy confirmed by COVID-19

through nasopharyngeal/oropharyngeal swab examination using the Reverse Transcription-

Polymerase Chain Reaction (RT-PCR) method handled at Sanglah Hospital Denpasar. Of

these cases, there were 14 cases with mild symptoms, 4 cases with severe symptoms, and 2

cases of maternal death related to COVID-19 were found. Data on the impact of COVID-19

on the clinical and pathological picture of pregnancy is still limited, there is no strong

evidence that pregnant women are more susceptible to infection with coronavirus and there is

very little evidence of vertical transmission, so there is still a lot to learn. The difference in

data regarding epidemiology, clinical symptoms, vertical transmission, treatment and

maternal mortality and morbidity in pregnant women with COVID-19 encourages the authors

to conduct further research on the clinical picture of pregnancy with COVID-19.

Method

This study involved all pregnant women with confirmed COVID-19 who underwent

conservative care and gave birth at Sanglah Hospital Denpasar in the period April 2020 -

September 2020. The diagnosis of COVID-19 was confirmed through RT-PCR examination

obtained from nasopharyngeal / oropharyngeal swab samples.

The data obtained were tabulated and analyzed descriptively including sample

characteristics and pregnancy management to obtain a clinical picture and outcome of

pregnancy with COVID-19.

Result

In the period of April 2020 to September 2020, there were 41 cases of pregnant women

with COVID-19 who were treated at Sanglah Hospital, and there were 2 maternal deaths

related to COVID-19 (4.88%).

Based on the maternal age group, it was found that the most pregnant women were in

the age range of 26-30 years with 19 cases (46.34%). Meanwhile, based on gestational age, it

was found that most cases occurred in the third trimester of pregnancy, namely 38 cases

(92.68%). Most of the pregnant women with COVID-19 came to Sanglah Hospital alone, as

many as 23 cases (56.11%) followed by referrals from network hospitals and private hospitals

in Bali (12.17% each), 4 cases of referrals from Puskesmas (9.77%), 2 cases of referrals from

the Health Office (4.88%), referrals from midwives and Udayana University Hospital

referrals as many as 1 patient each (2.45%). Reviewed from the results of the rapid test for

antibodies against SARS-CoV-2 which was carried out in 41 cases, the results showed the

most reactive IgG and IgM results, namely 18 cases (43.90%), 7 cases (17.07%) with reactive

IgG results, 6 cases (14.63%) with reactive IgM results, 5 cases with non-reactive results

(12.20%), and 5 cases (12.20%) did not undergo a rapid test. Of the 41 cases of pregnancy

confirmed with COVID-19 in this study, 27 cases (65.85%) were asymptomatic and 14 cases

(34.15%) with symptoms. From 27 asymptomatic cases, 1 case (3.70%) was found with non-

reactive rapid test results, 22 cases (81.48%) with reactive rapid test results, and in 4 cases

(14.82%) no rapid test was done. Whereas in 14 cases with symptoms, 4 cases (28.57%)

showed non-reactive rapid test results, 9 cases (64.29%) with reactive rapid tests, and 1 case

(7.14%) did not undergo rapid test. From the analysis of the sensitivity and specificity of the

Rapid test in this study, the sensitivity was 86.11% and the specificity was 89.34%. In this

study, most of the COVID-19 cases in pregnancy showed no symptoms, namely 27 cases
(65.85%), 8 cases (19.51%) experienced mild symptoms, 2 people (4.88%) with moderate

symptoms, and obtained 4 cases with severe symptoms (9.76%). There was one patient with

severe symptoms who had respiratory failure and received ventilator support for 10 days. In

this patient the termination of pregnancy was carried out at 25 weeks of gestation for 1 day

reduce the load on the mother's cardiorespiratory system, and save the fetus by estimated

baby weight 650 grams. After undergoing treatment, the patient's condition improved and

was declared cured of COVID-19 based on clinical improvement and negative RT-PCR

results. There was also one patient with a pregnancy of 30 weeks and 1 day with severe

symptoms who was given two bags of convalescent plasma therapy (200 ml) and found

improvement in her condition. In this patient, it was decided to do conservative treatment and

was able to continue the pregnancy after. The mean value of Neutrophyl to Lymphocyte

Ratio (NLR) in patients based on symptoms was 5.57 (1.73-14.73) in asymptomatic cases,

4.97 (1.70-12.50) in cases with mild symptoms, 2,58 (2.1-3.06) in cases with moderate

symptoms, and 7.96 (6.25-12.54) in cases with severe symptoms. In this study, 17 cases

(41.46%) had no complications in pregnancy. The most complications were preeclampsia

experienced by 8 patients (19.50%), followed by anemia in 4 cases (9.76%), post partum

hemorrhage experienced by 3 cases (7.32%), prematurity and peripartum cardiomyopathy

were obtained in 2 cases respectively (4.88%), and incomplete abortion, eclampsia,

premature rupture of membranes, thrombocytopenia, and fetal distress was found in

respectively 1 case (2.44%).

In 32 cases (84.21%), cesarean section was performed, in 6 cases (15.79%), vaginal

delivery was performed with the highest birth weight ≥ 2500 grams in 27 cases (69.23%),

1500-2500 grams birth weight was obtained in 11 cases (28.21%) and birth weight <1500

grams in 1 case (2.56%). The highest number of neonates outcome was vigorous babies,

namely 33 cases (84.62%), 4 neonates (10.26%) experienced severe asphyxia, moderate

asphyxia and fetal death in the uterus were experienced in 1 case (2.56%) each. 2 infants

(5.13%) were confirmed with COVID-19 with positive RT-PCR results for nasopharyngeal /

oropharyngeal swabs, 31 infants (79.49%) with negative RT-PCR swab NP / OP results, and

6 infants did not undergo RT-PCR NP / OP swab because they were post partum referral

cases. In the sample of this study, there were 1 case with Gemelli delivery and 2 cases of

pregnancy that had been successfully treated with conservative care and had not yet given

birth at the time of this study. The following table shows the characteristics of pregnant

women with COVID-19 during the study period:

Table 1. Characteristics Distribution of Pregnancy Cases with COVID-19

N %
Maternal age 15 – 20 3 7,32
(years) 21-25 8 19,51
26-30 19 46,34
31-35 7 17,07
36-40 4 9,76
Total 41 100
Gestational age 1 Trimester
st
1 2,44
2nd Trimester 2 4,88
3 Trimester
rd
38 92,68
Total 41 100
Referral origin Came on her own 23 56,11
General hospital
5 12,17
referral
Private hospital
5 12,17
referral
Udayana University
1 2,45
hospital referral
Midwife referral 1 2,45
Public health office
2 4,88
referral
Public health care
4 9,77
referral
Total 41 100
Rapid test results IgG reactive 7 17,07
IgM reactive 6 14,63
IgG dan IgM reactive 18 43,90
Non reactive 5 12,20
No rapid test 5 12,20
Total 41 100
Rapid test in Reactive 22 81,48
asymptomatic Non reactive 1 3,7
cases No rapid test 4 14,82
Total 27 100
Rapid test in Reactive 9 64,29
symptomatic cases Non reactive 4 28,57
No rapid test 1 7,14
Total 14 100
Symptoms Asymptomatic 27 65,85
Mild symptoms 8 19,51
Moderate symptoms 2 4,88
Severe symptoms 4 9,76
Total 41 100
Pregnancy
No complication 17 41,46
complication
Incomplete abortion 1 2,44
Prematurity 2 4,88
Preeclampsia 8 19,50
Eclampsia 1 2,44
Premature rupture of 1 2,44
the membrane
Anemia 4 9,76
Thrombocytopenia 1 2,44
PPCM 2 4,88
Postpartum
3 7,32
hemorrhage
Fetal distress 1 2,44
Total 41 100
Mode of delivery Vaginal delivery 6 15,79
Cesarean section 32 84,21
Total 38* 100
Neonates birth < 1500 gram 1 2,56
 weight
1500 – 2500 gram 11 28,21
≥ 2500 gram 27 69,23
Total 39** 100
Neonates outcome Vigorous baby 33 84,62
Mild asphyxia 1 2,56
Moderate asphyxia 4 10,26
Intrauterine fetal
1 2,56
death
Total 39** 100
Neonates RT-PCR Positive 2 5,13
results Negative 31 79,49
No RT-PCR 6 15,38
Total 39** 100
* Of the total 41 patients confirmed positive, there were 1 incomplete abortion, 2
conservative patients.
** Of the total 41 patients confirmed positive, 1 patient underwent curettage, 2
conservative patients, and 1 Gemelli patient.

Table 2. Mean Value of Neutrophil to Lymphocyte Ratio (NLR) based on symptoms

NLR value range Mean NLR value

Asymptomatic 1.73 – 14.73 5.57
Mild symptoms 1.70 – 12.50 4.97
Moderate symptoms 2.1 – 3.06 2.58
Severe symptoms 6.25 – 12.54 7.96

Discussion

The continued development of knowledge about the pathogenesis of COVID-19,

especially pregnant women who are confirmed by COVID-19 and the lack of research on the

clinical and pathological features and outcomes of pregnancy with COVID-19 have led to

diverse management of pregnancy and childbirth in pregnant women infected with COVID-

19. This study is a preliminary study that aims to determine the magnitude and characteristics

of pregnancy cases with COVID-19. The most age distribution among pregnant women with
COVID-19 was in the age range of 26-30 years with 19 cases (46.34%). These results are

consistent with research conducted by Qiancheng et al., where the average age of pregnant

women with COVID-19 was 30 years, which was similar to non-pregnant women. 7 However,

this figure is different from the study conducted by Khalil et al., which was a meta-analysis,

where the highest number was found at the age of mothers > 35 years, namely 504 cases

(30.6%).8 Pregnancy cases with COVID-19 in the United States occurred mostly in the age

group 25-34 years, which was 48.10% of the total cases, and cases of pregnancy with

COVID-19 in the UK were most common in the 20-34 year age group, which was 58.07% of

the total cases.9,10

Based on gestational age, the distribution of pregnancy cases with COVID-19 was

mostly found in the 3rd trimester of pregnancy with 38 cases (92.68%). Similar results were

obtained in the study of Khalil et al., where 73.9% occurred in the third trimester of

pregnancy.8 The study of Qiancheng et al., also supports these findings where 85.7%

occurred in the third trimester of pregnancy.7 Pregnant women and their fetuses are thought to

be a high-risk population during infectious disease outbreaks because pregnancy

predominates the T-helper 2 (Th2) system, which protects the fetus, which makes the mother

vulnerable to viral infections. The attenuation of T-helper1 (Th1) cell-mediated immunity

occurs due to physiological changes to a Th2 dominant environment that contribute to overall

infectious morbidity by increasing the vulnerability of mother to intracellular pathogens such

as viruses. Moreover, during pregnancy, the upper respiratory tract tends to swell due to high

levels of estrogen and progesterone, and limited expansion of the lungs makes pregnant

women vulnerable to respiratory pathogens.11,12 Pregnancy is a unique immunological state, in

which the mother's immune system faces the major challenge of establishing and maintaining

tolerance to an allogeneic fetus while maintaining protective abilities against microbes. A

good pregnancy depends on adjusted immune adaptations both systemically and locally. The
immunological state of the mother actively adapts and changes to the growth and

development of the fetus at different stages of pregnancy, from a pro-inflammatory state

(useful for embryo implantation and placentation) in the first trimester to an anti-

inflammatory state (helps fetal growth) in the second trimester, and finally reaches a second

pro-inflammatory state (prepares for the onset of delivery process) in the third trimester.

Immunological status in pregnancy that is divided typically in each trimester is called the

immune clock theory which has an important role in the successful of pregnancy. 13 The pro-

inflammatory state in the first and third trimesters of pregnancy is characterized by an

increase in various kinds of proinflammatory cytokines. With the high infection rate in the

third trimester, we need to be aware that pregnant women in the first and third trimesters are

in a pro-inflammatory state, and the occurrence of cytokine storms caused by SARS-CoV-2

in the first and third trimesters of pregnancy can cause a more severe inflammatory state,

which can provide a more severe clinical picture. 13 Elevated levels of IL-6 (which is a

dominant Th1 response) were associated with an improved clinical picture and a significant

risk of death in COVID-19 patients.12,14

In this study, it was found that the majority of pregnant women with COVID-19 who

came to Sanglah Hospital alone were 23 patients (56.11%). Most of these cases were

identified during the initial screening of inpatients. Procedures at Sanglah Hospital require

screening and rapid test examinations for all inpatients because Denpasar was declared a red

zone for the spread of COVID-19. There were 11 referral patients from the hospital,

including 5 patients (12.17%) from public hospitals, 5 patients (12.17%) from private

hospital, and 1 patient (2.45%) from Udayana University Hospital. Other referrals came from

Puskesmas as many as 4 patients (9.77%), 1 patient from midwife referral (2.45%), and 2

patients (4.88%) from the Health Office referral. Patients referred by the Health Office were

patients who came from tracing the contact history of other patients who were treated and had
positive RT-PCR swab results. The high number of referral cases is due to the position of

Sanglah Hospital as a Referral Hospital for patients of COVID-19.

The World Health Organization (WHO) does not recommend the use of a rapid test as

a diagnostic tool in patients with COVID-19 although research on the performance and

usefulness of diagnostics is very potential to be carried out. 15 According to Indonesian

Ministry of Health's Guidelines for the Prevention and Control of COVID-19, the use of rapid

tests is not used as a diagnostic tool. In conditions with limited RT-PCR testing capacity,

rapid tests can be used to screen specific populations and special situations. For pregnant

women, who are a specific population, the rapid test is the initial screening and the results

must still be confirmed by RT-PCR.16 The working principle of the antibody rapid test is to

detect the presence of antibodies produced by the body in response to an antigen through a

peripheral blood sample. Antibodies will be produced several days or weeks after the onset of

viral infection. In the majority of COVID-19 patients who were confirmed by molecular

testing (RT-PCR), the antibody response was reported to be weak, delayed, or not formed.

Research indicates that most patients respond to antibody responses in the second week after

the onset of symptoms. This means that the use of a rapid test to determine the antibody

response to COVID-19 may only be done in the recovery phase. 15 A Cochrane study in June

2020 explained that the percentage of rapid tests detecting the presence of antibodies in

COVID-19 patients was> 90% at the third week of infection, while at weeks 1 and 2 were

only 30% and 70%. It can be concluded that the rapid test cannot be used to detect COVID-

19 antibodies in the first two weeks of infection.17 The study in Brazil explained that the

sensitivity of the rapid test among those diagnosed with COVID-19 was 77.1% (64/83) and

the specificity was 98.0% in individuals with COVID-19. 18 This is consistent with our study

that the results of the rapid test were reactive IgG 7 (17.07%), reactive IgM 6 (14.63%), and

reactive IgG & IgM 18 (43.90%). Of the 41 cases of pregnancy confirmed by COVID-19 in
this study, 27 cases (65.85%) were asymptomatic and 14 cases (34.15%) with symptoms.

From 27 asymptomatic cases, 1 case (3.70%) was found with non-reactive rapid test results,

22 cases (81.48%) with reactive rapid test results, and in 4 cases (14.82%) no rapid test was

done. Whereas in 14 cases with symptoms, 4 cases (28.57%) showed non-reactive rapid test

results, 9 cases (64.29%) with reactive rapid tests, and 1 case (7.14%) did not undergo rapid

test.

In the period of April 2020 to September 2020 at Sanglah Hospital, it was obtained 31

cases with reactive rapid test results with positive RT-PCR swab NP/OP results (true

positive), 5 cases of non-reactive rapid test were confirmed positive from RT-PCR swab

NP/OP (false negative), 29 cases showed reactive rapid test results but negative RT-PCR

swab NP/OP results (false positive), and 243 cases with non-reactive rapid test results

showed negative RT-PCR swab NP/OP results (true negative). From these data, the

sensitivity of the rapid test in detecting COVID-19 in pregnancy was 86.11% and with a

specificity of 89.34%. Further research is needed with a larger number of samples to provide

a more accurate sensitivity and specificity analysis.

The World Health Organization (WHO) reports that there is no significant difference

in the risk of developing clinical symptoms in pregnant and nonpregnant patients who have

been infected with COVID-19. Patients most often came with mild symptoms of infection

including fever, cough, fatigue and shortness of breath. However, some were found with no

symptoms (asymptomatic).19 In this study, from a total of 41 patients, there were 27 patients

without symptoms (65.85%), 8 people with mild symptoms (19.51%), 2 people with

moderate symptoms (4.88%) and 4 people with severe symptoms ( 9.76%). Severe symptoms

experienced by patients in this study were respiratory distress and of 4 patients with severe

symptoms, 1 patient improved with convalescent plasma therapy and continued her

pregnancy, 2 patients died due to respiratory failure, and 1 patient experienced improvement
after receiving treatment. One severely symptomatic patient with severe pneumonia and

impending respiratory failure. On the ninth day of treatment, respiratory failure was found

and it was decided to do pregnancy termination by cesarean section at 25 weeks 1 day of

gestation to reduce the burden on the mother's cardiorespiratory system, and save the fetus

with an estimated baby weight of 650 grams. After undergoing postoperative care and

receiving ventilator support for 10 days, the patient's condition improved and was declared

cured of COVID-19 based on clinical improvement and negative RT-PCR results. There was

also one patient who was 30 weeks pregnant with severe symptoms who was given two bags

of convalescent plasma therapy (200 ml) and got an improvement in her condition. In this

patient, it was decided to undergo conservative treatment and was able to continue the

pregnancy after receiving treatment for 15 days.

In cases with severe symptoms, the mean value of Neutrophyl to Lymphocyte Ratio

(NLR) was higher than in cases of asymptomatic, mild symptoms, and moderate symptoms

(7.96 vs 5.57; 4.97; 2.58). This is consistent with the study conducted by Liu et al., which

concluded that NLR was the most significant factor in the incidence of disease severity and

had a significant predictive value.20 Based on a study by Liu et al., the incidence of disease

with severe symptoms was 50% at age ≥ 50 years and NLR ≥ 3.13, and 9.1% at age <50

years and NLR <3.13.20 Research by Yang et al., also obtained the same results that NLR is

an independent prognostic biomarker related to the progression of pneumonia in COVID-19.

The NLR threshold value of 3.3 indicates a superior prognostic likelihood of mild to severe

clinical symptoms, with the highest sensitivity and specificity. At the age of ≥ 49.5 years and

NLR ≥ 3.3, 46.1% of patients with mild symptoms developed severe symptoms. 21

Neutrophils are the main component of the leukocyte population in the human body which is

active and migrates from the venous system to the immune system or organ. Neutrophils

produce reactive oxygen species in large quantities which can induce DNA damage and
remove viruses from cells. Neutrophils interact with various cell populations and produce

cytokines. On the other hand, neutrophils can also be triggered by viral-related inflammatory

factors, including Interleukin-6 and Interleukin-8, Tumor Necrosis Factor-alpha and

granulocyte colony stimulating factor, and interferon-gamma produced by lymphocytes and

endothelial cells. Moreover, human immune response triggered by viral infection relies

mainly on lymphocytes, whereas systemic inflammation significantly suppresses cellular

immunity which significantly suppresses CD4 + T lymphocytes and increases CD8 + T

lymphocyte suppression. This results in an increase in NLR in viral induced inflammation.

The increase in NLR is related to disease severity, level of intensive care, need for

ventilators, and cure for COVID-19.21

Various studies abroad explain that there are no complications in mother, such as post

partum infection and preterm labor. However, there are also those who find that there are

complications for both mother and baby caused by COVID-19 infection. Research in Iran

found 9 women with severe COVID-19 infection experienced during the 2nd or 3rd trimester

where 7 out of 9 patients experienced death and 1 patient remained in critical condition and

needed a ventilator.19 In our study, 17 of 41 patients (41.46%) had no complications in

pregnancy, 8 patients (19.50%) had complications in the form of preeclampsia, and only 1

patient (2.44%) had complications in infants, namely fetal distress. Mascio et al., observed

16.2% incidence of preeclampsia in women with SARS-CoV-2 infection. This is more than

the 2-8% figure in the general population. There are several hypotheses about the occurrence

of preeclampsia in women with COVID-19, one of which is an increase in placental

dysfunction due to intravascular inflammation associated with infection that causes a

prothrombotic state in the blood to the placenta. Shanes et al., observed that placentas of

women infected with SARS-CoV-2 showed a higher rate of maternal vascular malperfusion.22
 In our study 32 of 38 deliveries (84.21%) were performed by caesarean section in the

operating room modified to negative pressure. The Indonesian Association of Obstetrics and

Gynecology (POGI) said that until now there was no strong clinical evidence to recommend

one way of delivery. The method of delivery is based on obstetric indications unless there is a

respiratory problem in the mother, it is necessary to have immediate delivery in the form of

cesarean section or vaginal surgery.23 Based on the book Handling Pregnancy with COVID-

19: Practical Guidelines and Algorithms, the choice of delivery method must also consider

the availability of resources, facilities in hospitals, hospital care, availability of personal

protective equipment (PPE), executability, human resources, and the risk of exposure to

medical personnel and other patients. 24 A total of 6 cases in this study gave birth vaginally

with midwives and were referred to Sanglah Hospital for further treatment or the patient

came to Sanglah Hospital during the second stage of labor. All rescuers in this study wore

level 3 personal protective equipment (PPE) as recommended by POGI, the American

College of Obstetricians and Gynecologists (ACOG), and the Centers for Disease Control

and Prevention (CDC). According to research by Liu et al., 2020 in 77% of pregnant patients

with COVID-19 a cesarean section was performed, five of which were due to pregnancy

complications.25 ACOG, 2020 and Boelig et al., 2020 recommended that the mode of delivery

in pregnant patients with COVID-19 is according to obstetric indications and COVID-19

itself is not an indication for cesarean section.26,27 Berghella, 2020 stated the same thing that

COVID-19 is not an indication for cesarean section because it can increase the risk of

maternal morbidity and does not improve neonatal outcome.28

Most of the neonatal outcomes in this study were neonates, 27 cases (69.23%) had birth

weight ≥ 2500 grams, 33 neonates (84.62%) were vigorous babies. From a study conducted

by Qiancheng et al., 2020, it was stated that the mean birth weight of infants was 3130 grams

(2915 - 3390 grams) and only 1 baby was born weighing <2500 grams. 7 In that study, there
were also no neonatal mortality, fetal death, and neonatal asphyxia. All neonates were

subjected to RT-PCR examination twice at a gap of 24-48 hours and none of the neonates got

positive results. This result is also supported by research conducted by Chen et al., 2020

which found that the median APGAR score for the first 1 minute was 9 (8-9), and the first

minute APGAR score in mothers with severe symptoms was 8 (8 - 10). 29 The four infants

with severe asphyxia in this study were among others due to prematurity, very low birth

weight, and fetal distress.

A total of 31 neonates (79.49%) got negative results on the RT-PCR of

nasopharyngeal/oropharyngeal (NP/OP) swab examination. In this study, two neonates with

positive RT-PCR NP/OP swab results were found. According to the Royal College of

Obstetricians and Gynecologists (RCOG), vertical transmission from pregnant women to

their babies is possible as reported by several studies by measuring IgM levels in the baby's

blood.19 One study by Akhtar et al., 2020 reported COVID-19 infection in neonates 36 hours

after delivery, but follow-up tests to look for possible intrauterine transmission were negative

for SARS-CoV-2 nucleic acid on the placenta and umbilical cord. 19 A case report by Fenizia

et al., in Italy suggests the possibility of intrauterine SARS-CoV-2 vertical transmission. This

study found SARS-CoV-2 on vaginal swabs, placental tissue, and cord blood. In addition,

IgM and or IgG anti SARS-CoV-2 were also found in umbilical cord blood. 30 The presence of

anti IgM SARS-CoV-2 in the umbilical cord confirms the possibility of vertical transmission

because the IgM molecule is large and cannot cross the placental barrier. Thus, if it is found

in the umbilical cord blood, it is the result of the fetal response to the SARS-CoV-2 antigen.

Further research is needed to prove the occurrence of intra-uterine transmission by examining

the histopathology of the placental and umbilical cord tissue, detection of antibodies and/or

antigens in umbilical cord blood, and detection of antigens in amniotic fluid. Six neonates did
not undergo RT-PCR NP/OP swab examination because the mother was a post partum

referral case.

Conclusion

Pregnant women are a population vulnerable to COVID-19 due to various changes in

immunological and physiological systems in pregnancy. This study is a preliminary study

that aims to determine the magnitude and characteristic of pregnancy cases with COVID-19.

The impact of COVID-19 on maternal and neonatal outcomes in this study, sequentially, it

was found that the most pregnancy complications were preeclampsia and the most pregnancy

outcome was vigorous baby. It is not yet clear whether preeclampsia, prematurity, and

premature rupture of membranes are related to COVID-19 or are independent conditions.

Likewise, cases of maternal death related to COVID-19. Further research is needed to prove

the existence of intrauterine vertical transmission of COVID-19 in pregnancy.

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