English Case Iufd+covid-19 Fuad Saddam

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ENGLISH CASE

INTRAUTERINE FETAL DEATH WITH


COVID-19 IN PREGNANCY

ANDALAS UNIVERSITY

Presented by:
dr. Fuad Saddam
Resident of Obstetrics and Gynecology

Guidance:
dr. Dedy Hendry. Sp.OG (K)

OBSTETRICS AND GYNECOLOGY DEPARTMENT


MEDICAL FACULTY OF ANDALAS UNIVERSITY /
DR. M. DJAMIL CENTRAL GENERAL HOSPITAL
PADANG
2020
TABLE OF CONTENT

TABLE OF CONTENT .............................................................................. i


TABLE OF FIGURE ................................................................................... ii
LIST OF TABLE ........................................................................................ iii
CHAPTER I. INTRODUCTION ............................................................. 1
CHAPTER II. CASE REPORT ................................................................ 3
CHAPTER III. LITERATURE REVIEW ............................................... 11
3.1. INTRAUTERINE FETAL DEATH/DEMISE (IUFD) OR
STILLBIRTH ............................................................................. 11
3.2. CORONAVIRUS DISEASE 2019 ..................................... 24
3.3. COVID-19 IN PREGNANCY ............................................ 32
3.4. COVID-19 EFFECT ON FETAL ....................................... 47
CHAPTER IV. DISCUSSION ................................................................... 49
CHAPTER V. CONCLUSION................................................................... 51
BIBLIOGRAPHY ....................................................................................... 52

i
LIST OF FIGURE

Figure 1.1 Pregnant women with COVID-19 by age, United States ............. 2
Figure 3.1 A macerated stillborn ................................................................... 11
Figure 3.2 Macerated stillbirth with peeling of skin ...................................... 15
Figure 3.3 Algorithm management IUFD ...................................................... 17
Figure 3.4 Ultrasound showing fetal stillbirth (Spalding’s sign) ................... 18
Figure 3.5 X-ray showing intrauterine fetal death ......................................... 19
Figure 3.6 Coronavirus strain HCoV-229E ................................................... 25
Figure 3.7 Phylogenetic relationships among members of the subfamily
Coronavirinae ................................................................................................. 26
Figure 3.8 Genome organization of representative human coronaviruses ..... 28
Figure 3.9 Coronavirus strain 229E in Huh-7 cells. ...................................... 28
Figure 3.10 Algoritm COVID-19 in pregnancy ............................................. 34
Figure 3.11 Algorythm pregnant with suspected or confirmed COVID-19 . 41
Figure 4.1 Fetus IUFD in these case .............................................................. 49

ii
LIST OF TABLE

Table 3.1 Cause of intrauterin fetal death ...................................................... 12


Table 3.2 Degree of fetal maceration ............................................................. 17
Table 3.3 Etiology of thyrotoxicosis in pregnancy ........................................ 22
Table 3.4 Clinical Features of Colds Produced by Experimental Infection With
Four Viruses ................................................................................................... 31

iii
CHAPTER I
INTRODUCTION

Intrauterine fetal deaths and stillbirths, defined as fetal demise after 20 weeks
of gestation, has profound emotional, psychiatric and social effects on both parents
and their families. Prevalence of IUFD and stillbirths is the direct indicator of the
quality of antenatal care in that society. Annual Report of the Confidential Enquiries
into Still Births and Death in Infancy (CESDI) identified suboptimal care as being
evident in half of such pregnancies. The share of developing countries is as much
as two thirds of the total perinatal mortality occurring in the world. Worldwide over
2.6 million of still births happen annually. Out of these, statistics reveal that 23.2%
(almost one fourth of IUFDs), were from India, the highest for any nation. In fact,
India is in the top half of the chart with 22 Stillbirths per 1000 live births. This
problem needs to be addressed, especially in our country, where inadequate
antenatal care is compounded by inaccessibility to healthcare facilities.1
Antepartum fetal deaths contribute to about seventy five percent of the
perinatal mortality. The fetal deaths are related to maternal (5-10%), placental (20-
35%) or fetal (25-40%) complications. Tulip, Extended Wigglesworth, Modified
Aberdeen are some classifications used for classifying the causes for fetal death.
Tulip classification uses maternal, fetal and placental causes whereas, Aberdeen
and Wigglesworth use maternal and fetal factors only. Irrespective of the method
of classification used, it is a well-established fact that adequate prenatal care is
associated with better pregnancy outcomes. Early booking, adequate antenatal care
early identification of the risk factors and timely intervention helps in preventing
perinatal morbidity and mortality. The main area of concern in our area of study
(western UP), is still inadequate access to healthcare facilities. Patients presented
in obstetric emergency, maximum being referred from outside, thus leaving us with
little time to act and salvage. Identification of the major contributory factors will
help us in imparting better patient care. We undertook this study to identify the most
common factors and etiology of IUFD at our centre.1
Data from the World Health Organization (2015) shows that the Infant
Mortality Rate (IMR) in ASEAN (Association of South East Asia Nations)

1
countries such as in Indonesia is 27/1000 live births. Furthermore, the results of the
2015 Interdental Population Survey (SUPAS) in Indonesia also showed that the
total IMR was 22.23/1000 live births, and this statistic had reached the 2015 MDGs
(Millennium Development Goals) target of 23/1000 live births (Depkes, 2015).
This statistic should be a concern for not only the government and health care
facilities but also the community to take necessary actions for preventions.2
Intrauterine Fetal Death (IUFD) can be caused by maternal causes in our
study were infections 16.7% and medical disorders 12.5%.1 most common
worldwide infection current infection was coronavirus infection (COVID-19).
Based on data on December 5, 2020, the global incidence of COVID-19 was
64,603,428 people confirmed positive for COVID-19 with 1,500,614 deaths. In
Indonesia, there were 563,680 cases, of which 17,479 people were confirmed dead
with COVID-19.3 Pregnant women with COVID-19, in United States [January 22-
November 30, 2020] total cases 42.268 which 55 cases death with confirm COVID-
19, with the distribution of data based on age as follows figure 1.1 below.4

Figure 1.1 Pregnant women with COVID-19 by age, United States 4

The lack of data related to COVID-19 on IUFD makes the author want to
discuss more deeply, especially in this case.

2
CHAPTER II
CASE REPORT
A. Identity
• Name : Mrs. J
• Age : 16 years old
• Medical Record : 01.08.96.15
• Admission date : September 25th 2020
B. Chief Complaint
A 16 years old woman was admitted to PONEK M Djamil Public Central
Hospital, referred from Sijunjung General Hospital, September 29th 2020 at
21.00, with diagnose G1P0A0L0 28-29 weeks of preterm of pregnancy +
suspek IUFD + confirmed COVID-19.

C. Present Illness History


• Previously patient came to Public Health Care with chief complaint fetal
movement was not felt since 2 days ago. At the same PHC patient get swab
a week ago (September 17th 2020) and the result was positive, then the
patient referred to Sijunjung General Hospital, then referred to Djamil
Central General Hospital Center for advanced management.
• Pelvic pain to the groin (-)
• Bloody show from the vagina (-)
• Fluid leakage from the vagina was absent
• Massive bleeding from the vagina was absent
• Amenorrhea since 8 months ago.
• First date of last menstrual on February 22nd, 2020
• Estimation date of delivery on November 29th, 2020
• Complain of nausea, vomiting, during early pregnancy and late pregnancy,
vaginal bleeding (-)
• Fever (-), cough (-), shortness of breath (-), flu (-)
• History of contact with a confirmed COVID-19 patient (+), history of contact
with people from outside the city in the last 2 weeks (-), history of travelling
out of town in the last 2 weeks (-)

3
• Prenatal care : prenatal care to midwife at 3rd, 4th, 5th, 7th, 8th month of
pregnancy, and never to obstetrician (-).
• Menstruation history: menarche at 13 years old, duration 5-6 days, regular
cycle once for every 28 days, 2-3 times pad changes / day without menstrual
pain
• History of previous illness : Diabetes, hypertension, heart, lung, kidney, liver
disease (-)
• History of family illness : There was no history of hereditary disease,
contagious and physicological illness in the family.

D. Obstetric History
• Marriage History : Once in 2019
• History of pregnancy/Abortus/Labour : 1/0/0
1. Current pregnancy

• History of Contraception : (-)


• History of immunization : (-)
• History of education : Senior high school

E. Physical Examination
General record
GA Cons BP HR RR Temp.
Moderate CMC 120/80 90 x/mnt 20 x /mnt 37,0oC
• Biometri
Body Weight before pregnancy : 47 kg
Body Weight Present : 55 kg
Body Height : 150 cm
BMI : 20,89 (normoweight)
Upper arm circumference : 25 cm
• Head : Normocephaly
• Eyes : Conjunctiva wasn’t anaemic, sclera wasn’t icteric,
exophthalmus (-)

4
• Neck : JVP 5 – 2 cmH2O, there is no enlargement in thyroid gland
• Chest : Heart and Lung : no abnormality was found
• Abdomen : Obstetrical record
• Genitalia : Obstetrical record
• Extremity : oedema -/-, Physiological reflex +/+, Pathological reflex -/-

Obstetric Record
Abdomen
• Inspection : Enlarge accordance to preterm pregnancy,
Striae gravidarum (+), midline hyperpigmentation (-), cicatrix (-)
• Palpation : L1 : Uterine fundal was palpated 4 fingers below xyphoid
procecus, a large nodular mass was palpated
L2 : a hard and resistance structure was felt on the left side,
Numerous small part of the baby was felt on the right side
L3 : a hard mass was palpable, not fixated
L4 : not performed
Uterine fundal height: 20 cm EFW : 1085 grams
Uterine contraction : (-)
• Percussion : Tympani
• Auscultation : Peristaltic sound was normal, FHR : (-)

Genitalia
• Inspection : V/U normal, vaginal bleeding (-),
VT : Dilatation of cervix (-), portio was thick, posterior,
hard consistency,
• Inlet pelvic size :
▪ Promontorium wasn’t palpable,
▪ Inominate line palpable one third part both side
▪ Pelvic side wall was stright
▪ Ischial spines wasn’t protrude
▪ Sacral bone was concave
▪ Sacrococcygeal bone was mobile

5
▪ Pubic arch >90
• Outlet pelvic size :
Inter tuberous distance could accommodate an adult fist (>10.5 cm)
• Inlet & outlet : Normal Pelvic size

F. Laboratory Examination
- Haemoglobin : 11,4 gr/dl
- Leukocyte : 9,380 / mm3
- Haematocrit : 34 %
- Platelet : 250.000/mm3
- Diff count : 0/0/65/28/7
- PT/APTT : 10,6/29,4
- Total protein : 7,1 g/dl
- Albumin : 3,7 g/dl
- Globulin : 3,4 g/dl
- Total Bilirubin : 0,5 mg/dl
- Bil. direct/indirect : 0,2 / 0,3 mg/dl
- SGOT / SGPT : 26 / 16 mg/dl
- Ureum/creatinin : 16 / 0,6 mg/dl
- Na/K/Cl : 141 / 3,5 / 104

G. Diagnose
- G1P0A0L0 31 – 32 weeks of preterm pregnancy + confirmed COVID-
19 + IUFD
- Fetal death singleton intrauterine head presentation

H. Action
▪ Control general appearance, vital sign, uterine contraction, labor sign.
▪ Informed consent
▪ Consult Perinatology, Pulmology

I. Plan
Swab PCR September 27th, 2020

6
Daily Monitoring

September 26th, 2020 September 27th, 2020 September 28th, 2020 September 29th, 2020

Pelvic pain referred to the Pelvic pain referred to the Pelvic pain referred to the Pelvic pain referred to the
groin (-) groin (-) groin (-) groin (-)
Bloody show from the vagina Bloody show from the vagina Bloody show from the vagina Bloody show from the vagina
S (-) (-) (-) (-)
Fluid leakage from the vagina Fluid leakage from the vagina Fluid leakage from the vagina Fluid leakage from the vagina
(-) (-) (-) (-)
No massive bleeding from No massive bleeding from No massive bleeding from No massive bleeding from
vagina vagina vagina vagina

GA : Mdt GA : Mdt GA : Mdt GA : Mdt


Con : CMC Con : CMC Con : CMC Con : CMC
BP : 130/80 BP : 100/70 BP : 120/70 BP : 100/70
HR : 85 HR : 80 HR : 74 HR : 80
RR : 20 RR : 18 RR : 20 RR : 18
O
T : 37 T : 36,7 T : 36,9 T : 36,7

Abd : Uterine contraction (-) Abd : Uterine contraction (-) Abd : Uterine contraction (-) Abd : Uterine contraction (-)

Gen : V/U normal, VB (-) Gen : V/U normal, VB (-) Gen : V/U normal, VB (-) Gen : V/U normal, VB (-)

G1P0A0L0 31-32 weeks of G1P0A0L0 31-32 weeks of G1P0A0L0 31-32 weeks of G1P0A0L0 31-32 weeks of
preterm pregnancy + preterm pregnancy + preterm pregnancy + preterm pregnancy +
A
confirmed COVID-19 + confirmed COVID-19 + confirmed COVID-19 + confirmed COVID-19 +
IUFD, Day care-1 IUFD, Day care-2 IUFD, Day care-3 IUFD, Day care-4

• Control GA, VS, uterine


• Control GA, VS, uterine • Control GA, VS, uterine • Control GA, VS, uterine
contraction, labor sign
contraction, labor sign contraction, Control GA, contraction, Control GA,
VS, uterine contraction, VS, uterine contraction,
P • Same with pulmonology
• Same with pulmonology labor sign labor sign
therapy
therapy
• Same with pulmonology • Same with pulmonology
• Swab PCR : September
• Swab PCR : today therapy therapy
27th, 20

7
September 30th, 2020 September 30th, 2020 September 30th, 2020 September 30th, 2020
(07.00) (16.00) (20.00) (21.30)

Feeling pain from waist


Pelvic pain referred to the region to the groin (+) >>
groin (-)
Bloody show from the vagina Feeling pain from waist Bloody show (+)
S (-) region to the groin, and Patient feels want to bear
Fluid leakage from the vagina become worsened since 2 down
(-) hours ago, bloody show (+) Fluid leakage from the
No massive bleeding from vagina (+) since 1 hour ago
vagina

GA : Mdt GA : Mdt GA : Mdt GA : Mdt


Con : CMC Con : CMC Con : CMC Con : CMC
BP : 130/80 BP : 110/70 BP : 120/70 BP : 100/70
HR : 85 HR : 84 HR : 90 HR : 92
RR : 20 RR : 20 RR : 20 RR : 18
T : 37 T : 36,5 T : 36,9 T : 36,7

O
Abd : Uterine contraction (-) Abd : Uterine contraction 2- Abd : Uterine contraction 2- Abd : Uterine contraction 3-
3x/25”/moderate 3x/30”/moderate 4x/35-40”/strong

Gen : V/U normal, VB (-)


Gen : V/U normal, VB (-) Gen : V/U normal, VB (-) Gen : V/U normal, VB (-)
VT : Cervical opened 2-3 cm, VT : Cervical opened 5-6 cm, VT : : Cervical opened was
amniotic sac (+), portio amniotic sac (-) greenish complete, amniotic sac (-)
medial, effacement 100 %, residue, portio medial, greenish residue, portio
transverse lie of small effacement 100 %, left medial, effacement 100 %,
fontanel on H I-II anterior of small fontanel on anterior of small fontanel on
H II-III H IV

G1P0A0L0 31-32 weeks of G1P0A0L0 31-32 weeks of G1P0A0L0 31-32 weeks of G1P0A0L0 31-32 weeks of
preterm pregnancy + preterm pregnancy parturient preterm pregnancy parturient preterm pregnancy parturient
A confirmed COVID-19 + latent phase of first stage + active phase of first stage + of second stage + confirmed
IUFD, Day care-5 confirmed COVID-19 + confirmed COVID-19 + COVID-19 + IUFD, Day
IUFD, Day care-5 IUFD, Day care-5 care-5

• Control GA, VS, uterine


• Control GA, VS, uterine • Control GA, VS, uterine • Control GA, VS, uterine
contraction, labor sign
contraction, labor sign contraction, labor sign contraction, labor sign
P • Same with pulmonology
• Observe labor progression • Observe labor progression • Lead tobear down
therapy

• Plain : Vaginal delivery • Plain : Vaginal delivery • Plain : Vaginal delivery

8
September30th 2020 at 21.40 AM
A female baby was born by vaginal delivery with:
- BW : 1000 gr
- BH : 38 cm
- A/S : 0/0 (maceration grade II)
Placenta was born with active management of third stage, complete 1 piece, size
12x12x2 cm, weight 300 grams, and umbilical cord length was ± 45 cm, paracentral
insertion.
Bleeding during delivery was ± 80 cc

Diagnose
- P1A0L0 post IUFD vaginal delivery + confirmed COVID-19

Action:
– Post-delivery monitoring (Vital Sign, Vaginal bleeding, Uterine
contraction)
– IVFD RL drip Oxytocin 10 iu : metergin 0,2 mg → 1:1 → 28 d/m
– Cefixime 2x200mg peroral
– Azitromicin 1x500 mg peroral
– Paracetamol 3x500mg peroral
– Vit C 2x250mg peroral
– Zinc 2x20 mg peroral
– Bromocriptine 3x1 tab peroral
– Laboratory check post vaginal delivery

September 30th 2020 at 23.40 PM


S / VB (-), fever (-),
O /
GA Cons BP HR RR Temp.
Moderate CMC 120/80 89 x/mnt 20 x /mnt 36,7oC
• Abdomen : fundal height 3 fnger below umbilicus, good contraction
• Genitalia : V/U normal, VB (-)

9
A /
P1A0L0 post IUFD vaginal delivery + confirmed COVID-19

P/
– Post-delivery monitoring (Vital Sign, Vaginal bleeding, Uterine
contraction)
– IVFD RL drip Oxytocin 10 iu : metergin 0,2 mg → 1:1 → 28 d/m
– Cefixime 2x200mg peroral
– Azitromicin 1x500 mg peroral
– Paracetamol 3x500mg peroral
– Vit C 2x250mg peroral
– Zinc 2x20 mg peroral
– Bromocriptine 3x1 tab peroral
– Laboratory check post vaginal delivery

Follow up October 1st, 2020, at 07.00 AM


S / Fever (-), vaginal bleeding (-), miction (+)
O /
GA Cons BP HR RR Temp.
Moderate CMC 120/80 84 x/mnt 20 x /mnt 36,8oC
• Abdomen : fundal height 3 fnger below umbilicus, good contraction
• Genitalia : V/U normal, VB (-)
A /
P1A0L0 post IUFD vaginal delivery + confirmed COVID-19 + puerperium day1
P /
- Control (Vital Sign, Vaginal bleeding, Uterine contraction)
- Cefixime 2x200mg peroral
- Azitromicin 1x500 mg peroral
- Paracetamol 3x500mg peroral
- Vit C 2x250mg peroral
- Zinc 2x20 mg peroral
- Bromocriptine 3x1 tab peroral
- Reffered to Pulmonology

10
CHAPTER III
LITERATURE REVIEW

3.1 INTRAUTERINE FETAL DEATH/DEMISE (IUFD) OR STILLBIRTH

Intrauterine fetal death (IUFD) or intrauterine death (IUD) is one of the


greatest tragedies in obstetrics. IUFD embraces all fetal deaths occurring after the
24th week of gestation, both during pregnancy (antepartum death) and during labor
(intrapartum death). It is early fetal death if its weight is atleast 500 g or period of
gestation (POG) after 22 weeks with a crown rump length (CRL) of 25 cms or more.
Late fetal death is labeled when weight is 1000 gm or more, POG more than 28
weeks or CRL is 35 cms or more. When the fetus dies in utero in the antenatal
period, it is usually retained in the uterus for some days before it is expelled and
usually results in the delivery of a macerated stillbirth (Figure 3.1). Death during
labor ends in delivery of a fresh stillborn and does not pose a problem for
management. The fetal death rate is the number of fetal deaths per 1000 infants
born. 5,6,7
Incidence varies between 115 and 125 per 1000 births. Incidence in
Safdarjung hospital is 3.6%. It contributes significantly to perinatal mortality (an
important health indices). Roughly, 3 million IUFD occurs throughout the world
every year.

Figure 3.1 A macerated stillborn5

11
3.1.1. Etiologi
Table 3.1 Cause of intrauterin fetal death6

a. Fetal Cause (25-40%) 5,6,7


- TSH enters the systemic circulation and interacts with specific
heptahelical, G-protein-coupled receptors on the surface of thyroid
follicular cells, which triggers a series of signal transduction cascades
culminating in the synthesis and release of thyroid hormones. Through
a classical endocrine negative feedback loop, decreased circulating
levels of thyroid hormones lead to an increase in TRH and TSH
secretion, which in turn leads to increased thyroid growth and activity.
- Congenital malformations : As a result of chromosomal and non-
chromosomal disorders of which neural tube defects, isolated
hydrocephalus and complex congenital heart diseases (CHD) (rubella)
are the most common. Hemoglobinopathies in fetus are also a cause.
Glycogen storage disease, X-linked congenital disorders or autosomal
dominant (skeletal dysplasias) are also causes etiology.
- Rh - incompatibility: In an Rh-negative mother with an Rh-positive
fetus, maternal red cell antibodies against Rh-antigen of IgG
(immunoglobulin G) type cross the placenta and cause fetal hemolytic
anemia and hydrops fetalis. Fetuses with hydrops may die in utero from
profound anemia and circulatory failure. Now, with administration of

12
anti-D immunoglobulin during and after pregnancy, antenatal
intrauterine transfusions and screening for Rh-sensitization in
pregnancy there has been a decrease in Rh-incompatibility as a cause of
fetal death.
- Infections: Congenital syphilis, cytomegalovirus, toxoplasmosis,
parvovirus B19, rubella, varicella infections and listeriosis.
- Male fetus.
b. Placental (25-35%) 5,6,7
Placental abruption and placenta previa are the leading causes of
obstetrical hemorrhage and can cause fetal death by producing acute
placental insufficiency. Placenta with two types of cell lines in a euploid
conception (placental mosaicism).
- Placental and cord abnormalities: Pregnancies with circumvallate
placenta, velamentous (vasa previa), membranous or marginal insertion
of cord to placenta, true knots in the cord, tight cord round the neck,
torsion, stricture and hematoma in the cord are rare causes of fetal death.
Prolapse of the umbilical cord is an important cause.
- Intrapartum asphyxia: Usually manifests itself by (a) signs of fetal
distress or (b) fetal death, according to its severity.
- Twin-to-twin transfusion syndrome: It is a common cause of fetal
death in monochorionic multifetal pregnancy.
- Chorioamnionitis frequently associated with prolonged membrane
rupture and long labors and if fetal infection ensues, fetal death can
occur.
c. Maternal (5-10%)5,6,7
Surprisingly, maternal disorders make only a small contribution to fetal
death. Common maternal causes for IUFD are:
- Hypertensive disorders: The combination of proteinuria and
hypertension markedly increases the risk of fetal death in utero. Fetal
death in these women is due to large placental infarcts, abruption
placentae and markedly small placental size.

13
- Diabetes mellitus: Stillbirths without identifiable cause unexplained
fetal demise are a phenomenon unique to pregnancies complicated by
overt and uncontrolled diabetes
- Thyroid disorders
- Obesity
- Cholestatic disease of pregnancy
- Multiple pregnancy
- No or inadequate antenatal care
- Severe anemia in mother
- Infections: Toxoplasmosis, other—rubella, cytomegalovirus and
herpes (TORCH) and other infections of the mother
- Trauma, sepsis, acidosis, shock and other medical disorders like heart
disease and renal disease can affect the general maternal condition
adversely enough to cause fetal death and sometimes, even cause
maternal mortality
- Abnormal labor, mismanaged labor, obstructed labor and uterine
rupture can also cause fetal death
- Post-term pregnancy: While unexpected death may occur during
pregnancy due to placental insufficiency, the risk is likely to be more in
labor
- Systemic lupus erythematosus (SLE) :
Antiphospholipid antibodies: The presence of lupus anticoagulant
(LA) and anticardiolipin antibodies (ACA) is associated with
decidual vasculopathy, placental infarction, fetal growth restriction
and fetal death.
Other coagulation disorders: Prothrombin, gene mutation, factor V
Leiden mutation, lll deficiency, etc.
- Hyperpyrexia due to any cause
- Adolescent or elderly gravidas
- The mother’s educational level less than the 10th standard
- Male fetus, low socioeconomic status, multiple gestation, drug abuse
are other associated causes

14
- Third trimester IUFD correlates significantly with thrombophilia
- Smoking
- Coffee: Drinking coffee during pregnancy increase stillbirth rate.
d. Unexplained (25–35%)
Usually one-fourth of fetal deaths are unexplained, but with careful
assessment of the clinical course, meticulous examination of fresh stillborn
and appropriate laboratory investigations including autopsy only about
10% of fetal deaths remain unclassified.

3.1.2. Pathology 5
When the fetus dies in the antenatal period, it is usually retained in the uterus
for some days before it is expelled, and it undergoes a process of maceration. The
epidermis becomes soft and sodden, bullae appear containing turbid fluid beneath
them and it peels off in patches exposing areas of dark red cutis. The entire fetus
becomes swollen and of a dusky red color. The articular ligaments are softened,
allowing free separation of bones to occur. The skull bones overlap, become loose
and the skull collapses. The solid viscera becomes soft and diffluent. The umbilical
cord is swollen and stained. The liquefaction of the tissues is due to a process of
aseptic autolysis as there is no bacterial decomposition. These changes vary in
degree with the length of retention in utero of the dead fetus. Peeling off of skin
becomes evident after 24 hours (Figure 3.2); the more advanced changes in solid
viscera and other parts require several days.

Figure 3.2 Macerated stillbirth with peeling of skin 5

15
3.1.3. Clinical Features5
Patient may present with abdominal pain and cessation of fetal movements,
which were previously experienced by the patient. This loss of fetal movements
must not be accepted as conclusive evidence of fetal demise unless confirmed by
other signs. There may be regression of symptoms of pregnancy like breast
tenderness, nausea, etc. Note her age and POG. Ask for history of bleeding, trauma,
any recent severe illness or fever, etc. Elicit any drug abuse history or any medical
disease. Try to find miscarriage, intrauterine growth restriction (IUGR), IUFD or
neonatal demise in previous pregnancy.
On examination, gradual retrogression of height of uterus occurs and it
becomes smaller than the period of amenorrhea. Dead fetus in utero feels quite
different from the living; because of loss of muscle tone, the limbs do not stand out
distinctly and the fetus feels like a homogenous mass. Fetal movements are not felt
during palpation. Egg-shell crackling feel of the fetal head, if elicited is almost
pathognomonic. Abnormal fetal posture and decreased liquor may be associated
findings. On auscultation, the fetal heart sound (FHS) is absent. Further
confirmation of the fetal heart on ultrasound examination is mandatory before
disclosing the diagnosis of fetal death.
3.1.4. Classification
Momentarily set aside the experiments of Shanklin and Babala, in 1971
Langley published a work on perinatal necropsy methodology. Speaking about
external examination, he pointed out that the start of skin breakdown could be
observed approximately 8 hours after death; then subdivided the phenomenon
evolution in degrees (I, II and III) of maceration. The same three-stage
thanatological evaluation system (known as “Langley Criteria”) was corrected by
Bain in 1974 because, according to his observations, at least 48 hours of intrauterine
retention after death were required to observe extensive peeling of the skin (Table
3.2).
A year later, in 1975, Craig and Potter dealt with the issue of fetal intrauterine
post-mortem maceration with a purely descriptive approach, without providing any
chronological indications, if not a single observation in addition to what has already
been stated previously from Langley and Bain: after a intrauterine retention of at

16
least 7-10 days the color of the fetus began to change from deep red to brownish-
olive.
Grade I : Epidermis white, loose, and absent over small areas. Appears
already a few hours after death. Grade II :Epidermis raised, forming blisters, and
easily detached in large pieces. Fetal death occurred 1 to 3 days earlier. Grade III :
Red-brown discolouring of the fetus caused by hemolysis and imbibition of the
tissues with blood pigment (fetus sanguinolentus). Loosely connected skeletal
joints. Skull soft and fluctuating. This stage is as a rule reached 3 t o 4 weeks after
death
Table 3.2 Degree of fetal maceration

3.1.5. Management

Figure 3.3 Algorithm management IUFD 5,6


a. Ultrasonograph 5,6
Failure to detect heart motion by real time ultrasound is reliable
evidence of fetal death. Other findings on sonography include scalp edema

17
and collapsed cranial bones which are overlapping (Spalding’s sign). USG
can also provide some clue to the cause of death in a few cases (congenital
abnormalities, retroplacental clot, etc).

Figure 3.4 Ultrasound showing fetal stillbirth (Spalding’s sign) 5

b. Straight X-ray Abdomen 5,6


Signs on the X-ray are seen, if fetal demise has occurred several days
previously. These following are the principal radiological signs of fetal death:
- Significant overlap of skull bones (Spalding’s sign) caused by liquefaction
of the brain, a process that requires several days to develop. There is also
abnormal increase of the cranial soft tissue as a result of maceration (the
Halo sign).
- Exaggerated curvature of the fetal spine. Because this sign depends on
maceration of the spinous ligaments, its development requires several
days. Moreover, mild degree of curvature of spine in the living fetus may
be misleading (Ball’s sign).
- Demonstration of gas [carbon dioxide (CO2) due to anerobic metabolism]
in the fetus is an uncommon but reliable sign of fetal death. Appearance of
gas shadow (Robert’s sign) in the chambers of the heart and great vessels
(e.g. aorta) may appear as early as 12 hours but is difficult to interpret.
- Crowding of ribs (concertina effect).

18
Figure 3.5 X-ray showing intrauterine fetal death 5

c. Routine and Special Investigation 5


They are done to find the cause of death. Hemoglobin level, ABO-Rh
typing, platlet count, venereal disease research laboratory (VDRL) of both
partners, fasting and postprandial blood sugar, thyroid function, renal
function tests (RFTs), liver function tests (LFTs) and bile salts, coagulation
profile, TORCH screening, urine complete examination and culture and
vaginal swab and in selected cases LA and ACA and thrombophilia
screening is done. Coagulation profile including bedside bleeding time
(BT) and clotting time (CT) is needed. Work-up for thrombophilia
includes prothrombin maturation, factor V Leiden mutation, antithrombin
II level. If available perform maternal anti-Ro, anti-La antibodies, and
antiplatelet antibodies. Do parental karyotyping.
- Examine the baby: Do a comprehensive assessment of all stillbirths. See
color of the liquor (meconium smeared or blood staining). Look for time
of death (fresh or macerated), any congenital abnormality. Note, weight of
the baby and color of its skin. A photograph of the stillborn baby or an
ultrasound should be preserved (if possible). Take consent and perform an
autopsy to know the cause. A negative consent is to be documented. If
consent is not given, perform limited autopsy [consists of physical
examination, biopsy from skin, heal and liver, a photograph, ultrasound

19
and if possible magnetic resonance imaging (MRI)] of the newborn.
Cytogenetic studies by karyotyping of the baby are helpful in the presence
of congenital malformation or IUGR. Try to find the maturity (palmar or
sole creases). Examination of umbilical cord for any knots, its length,
attachment and any abnormality is noted. Cord blood may be taken for
cytogenetic studies in fresh stillbirth.
- Examination of the placenta: Gross examination for any anatomical
abnormality is done. Note the weight, size, thickness any staining,
calcification, attachment of the cord, any retroplacental clot, etc. Do
macroscopic examination of the membranes. Microscopic examination
may be sent for bacteriological studies which are done if infection is
suspected. Send swab or part of placenta for microbiological tests.

3.1.6. Treatment 5,6


a. Pshycological Support 5,6
It is of paramount importance. The diagnosis is gently revealed to the
patient and relatives and consent for treatment taken. There are
symptoms like loss of sleep, anger, hostility, etc. but they often
regresses soon. The adaptation is easy, if the attending obstetrician is
considerate and substantial information is imparted (suggesting
probable cause, human behavior and counselor consultation).
The medical team and nursing staff should provide all support and
sympathy to the bereaved couple and their relatives. Long-term anxiety-
related symptoms in the mother are reduced if she sees her stillborn
baby and if she has an ultrasound or picture of the child or she has gone
through the ritual of burial of the child because in this way easing her
stress is helped.
- Expectant Management : The majority of women enter spontaneous
labor within 2 weeks of fetal death. In the absence of other complica-
tions, attempts to evacuate the uterus may be delayed for this interval.
The patient and her relatives are likely to be upset psychologically but
they should be assured of the safety of non-interference.

20
- Induction of Labor : Weekly assessment of fibrogen level is helpful.
Until fibrogen levels fall below 100 mg/mL clinically relevant
coagulopathy does not occur.
- Active intervention is required if the patient does not go into
spontaneous labor within 2 weeks of fetal death, signs of coagulopathy
are imminent or the patient is much depressed emotionally because of
carrying a dead fetus.
- Cervical assessment and Bishop scoring is done and if the Bishop score
is poor, the treatment is begun with cervical priming, which is done by
using prostaglandins. Prostaglandins used for cervical ripening are
prostaglandin E2,, i.e. cerviprime gel containing 0.5 mg of PGE2 which
is instilled intracervically and prostaglandin E1 (PGE1), i.e.
misoprostol which can be used orally and vaginally. Prostaglandins are
also used for induction of labor, along with cervical ripening, and they
are more effective, especially when the patient is remote from term.
- In near term, oxytocin administered intravenously (IV) is usually
effective in stimulating uterine activity. When the POG is remote from
term, oxytocin is less likely to prove effective unless given in higher
concentration.
- Surgical induction by artificial rupture of membranes is
contraindicated, as a dead fetus offers a greater opportunity for sepsis
to be established than a living one and also because of a chance of
failure of induction.
- Methods of delivery. The delivery should always be done by medical
induction:
1. A combination : of mifepristone and a prostaglandin preparation
is recommended as the first-line choice for induction of labor. A
single dose (200 mg) of oral mifepristone and misoprostol
(PGE1) intravaginal 25 %g 4 hourly are safe, effective and of low
cost. Induction delivery interval was 8 hours. Mifepristone (600
mg daily for 2 days) alone can be used for induction also.

21
2. Misoprostol (PGE1): 25–50 ug either vaginally or orally is also
found effective (see p. 579). Vaginal route use is more effective
compared to oral route. Misoprostol may be repeated at every 4
hours. Misoprostol is preferred to oxytocin or PGE2 as it is safe,
effective and cheap.
3. Prostaglandins (PGE2): Vaginal administration of prostaglandin
(PGE2) gel or lipid pessary high in the posterior fornix is very
effective for induction where the cervix is unfavorable. This may
have to be repeated after 6–8 hours. The procedure may be
supplemented with oxytocin infusion.
4. Oxytocin infusion: This is widely practised and effective in case
where the cervix is favorable. To begin with, 5–10 units of
oxytocin in 500 mL of Ringer’s solution is administered through
intravenous
b. Complication 5,6,7
- Blood coagulation disorders: If the fetus is retained in utero for
sometime before being expelled consumptive coagulopathy,
presumably mediated by thromboplastin from the dead products of
conception, becomes operational. Prospective studies indicate that
gross disruption of maternal coagulation mechanism rarely
developed earlier than one month after fetal death. If the dead fetus
is retained longer, however, about 25% of women develop
coagulopathy. Typically, the fibrinogen concentration falls
(hypofibrinogenemia) and in some cases, the decrease may reach
potentially dangerous concentrations of less than 100 mg/dL.
Simultaneously, fibrin degradation products are elevated and platelet
counts tends to decrease, but severe thrombocytopenia is
uncommon. Rarely disseminated intravascular coagulation (DIC)
and hemorrhage can be seen.
- Psychological upset: The psychological stress experienced by
carrying a dead fetus, needs special attention.

22
- Infection: Until the membranes are intact, infection is unlikely but
once the membranes rupture, infection especially by gas forming
organisms like Clostridium welchii may occur. The dead tissue
favors microbial growth with disastrous consequences causing
chorioamnionitis and septicemia.
- During labor: Uterine inertia, retained placenta and postpartum
hemorrhage (PPH) may occur.
- High doses of IV oxytocin may lead to hyponatremia and rupture
uterus.
c. Prevention 5,6,7
If she comes in preconceptional period after a previous IUFD
investigate on the line to find the etiology. Early start of a good
antenatal care and institutional delivery help. But prevention of
stillbirth is not always possible however in the following circumstances
a vigil can be kept.
1. Previous history of IUFD or growth restriction or neonatal death
(upto 10% chances of recurrence)
2. History of vaginal bleeding during this pregnancy especially
placental abruption
3. Hypertensive disorders of pregnancy
4. Pregnancy with diabetes mellitus
5. Other placental and fetal abnormalities seen
6. Postmaturity.
- Preconceptional period: Detail history of previous IUFD (of
mother’s antenatal course and dead child examination report). Try to
eliminate and correct as many causes as possible (illicit drugs,
smoking, obesity). Genetic disorders in parents are to be probed.
When she comes in antenatal period with above high risk history do
tests to find the cause (if any).
- Prediction of fetal compromise in present pregnancy may be done
by the following tests which may bring out high-risk patients. In first
trimester, pregnancy associated plasma protein-A (PAPP-A) is less

23
than 5th percentile it require special vigil. Similarly, in second
trimester screening, if a-fetoprotein and b-human chorionic
gonadotropin (b-hCG), levels are more than 95th percentile there are
more chances of fetal compromise. During each visit emphasise the
importance of reporting immediately if the fetal movements increase
or decrease. In cases of postmaturity, delivery should be monitored
under cardiotocography (CTG). While IUFD cannot be totally
prevented, regular antenatal care and screening of at risk mothers
and intensive fetal and maternal monitoring may help in achieving a
good outcome in pregnancy.
- Inhibition or Suppression of Lactation :In stillbirth, we advise the
patient to avoid nipple stimulation, and not to express milk by hand
or pump. The patient should be instructed not to massage or apply
heat to the breast. The patient should wear a supporting brassiere.
Analgesics are sometimes needed. Apply cold compresses to the
breast to reduce swelling and pain. Milk production by the breast
depends upon the suckling. As there is no suckling in the case of
stillbirth, no milk is produced. In about 2–3 days engorgement will
start receding. There is no indication of medical suppression of
lactation in this case.

3.2 CORONAVIRUS DISEASE 2019 (COVID-19) 8


The coronaviruses (CoVs) commonly cause mild but occasionally more
severe community-acquired acute respiratory infections in humans. CoVs also
infect a wide variety of animals, and several CoVs (e.g., severe acute respiratory
syndrome [SARS], Middle East respiratory syndrome [MERS]) have crossed the
species barrier, producing outbreaks of severe human respiratory disease. While
SARS-CoV was eradicated, MERS-CoV continues to circulate in human and camel
populations.
More recently, a related but different CoV producing severe respiratory
disease has emerged, the Middle East respiratory syndrome coronavirus (MERS-
CoV). MERS-CoV was grown in June 2012 from a sputum sample obtained from

24
a man in Saudi Arabia who died of overwhelming pneumonia. The virus was
quickly identified as a new CoV most closely related to several bat CoVs.
Human-to-human transmission has been documented but appears to be
inefficient except in hospital settings. The animal reservoir of MERS-CoV is
believed to be camels, although evidence suggests that bats may be infected with
related viruses. Infection of camels on the Arabian peninsula and throughout Africa
is widespread, and several cases of camel-to-human transmission have been
reported, generally from juvenile camels.
In 1965, Tyrrell and Bynoe cultured a virus obtained from the respiratory tract
of a boy with a common cold by passage in human embryonic tracheal organ
cultures. The media from these cultures consistently produced colds in volunteers.
The agent was ether sensitive but not related to any known human virus.
Subsequently, electron microscopy of fluids from infected organ cultures revealed
particles that resembled infectious bronchitis virus of chickens. At about the same
time, Hamre and Procknow recovered a cytopathic agent in tissue culture from
medical students with colds. The prototype virus was named 229E and was found
on electron microscopy to have a similar or identical morphology (Figure 3.6).

Figure 3.6 Coronavirus strain HCoV-229E, harvested from infected WI-38 cells

Using techniques similar to those used by Tyrrell and Bynoe, Mc Intosh and
colleagues reported the recovery of several infectious bronchitis–like agents from
the human respiratory tract, the prototype of which was named OC43 (OC for organ
culture). At much the same time, mouse hepatitis virus and transmissible
gastroenteritis virus of swine were shown to have the same morphology on electron

25
microscopy. Shortly thereafter, the name coronavirus (the prefix corona denoting
the crownlike appearance of the surface projections) was chosen to signify this new
genus.
The number of animal CoVs quickly grew, including viruses causing diseases
in rats, mice, chickens, turkeys, various other bird species, cattle, several wild
ruminants, beluga whales, dogs, cats, rabbits, and pigs, with manifestations in the
respiratory and gastrointestinal tracts, central nervous system, liver, reproductive
tract, and other locations. Through sequencing and antigenicity studies, the animal
CoVs and HCoVs initially were divided into three groups: group 1, which contained
HCoV-229E, as well as numerous animal viruses; group 2, which contained HCoV-
OC43 plus the closely related animal viruses, bovine CoV and mouse hepatitis
virus; and group 3, which included only avian viruses related to infectious
bronchitis virus (Figure 3.7). Current taxonomy divides the subfamily
Coronavirinae into four genera: Alphacoronavirus (which includes viruses
previously in group 1); Betacoronavirus (which includes viruses previously in
group 2, most notably SARS-CoV and MERS-CoV); Gammacoronavirus (which
includes viruses previously in group 3); and Deltacoronavirus (which includes
several newly described avian and swine viruses).

Figure 3.7 Phylogenetic relationships among members of the subfamily


Coronavirinae

26
The CoV nucleic acid is RNA, approximately 30 kb in length, of positive
sense, single stranded, polyadenylated, and infectious. The RNA, the largest known
viral RNA (Figure 3.8), codes for (in order from the 5′ end) a large polyprotein that
is cleaved by virus-encoded proteases to form several nonstructural proteins,
including an RNA-dependent RNA polymerase, methyltransferases, and a helicase,
followed by either four or five structural proteins intermingled with a variable
number of nonstructural and minor structural proteins. The first of the major
structural proteins is a surface hemagglutinin-esterase (HE) protein, present on
HCoVs OC43 and HKU1 and some animal betacoronaviruses, that may play some
role in the attachment or release of the particle, or both, at the cell surface. The gene
for the HE protein contains sequences similar to the hemagglutinin of influenza C
virus, likely evidence of an interfamily recombinational event that occurred many
years ago. Notably, the HE receptor binding activity of HCoV-OC43 and probably
also of HKU1 was progressively lost along with a decrease in HE-associated
esterase activity during evolution in humans. These changes most likely reflected
adaptation to the human sialic acid receptor after introduction into humans from
zoonotic sources. The next gene encodes the surface glycoprotein that forms the
petal-shaped surface projections and is responsible for attachment and the
stimulation of neutralizing antibody. This is followed by a small envelope (E)
protein, a membrane glycoprotein, and a nucleocapsid protein that is complexed
with the RNA. There are several other open reading frames, which are unique to
each strain of CoV. While their coding functions are not clear, many of them are
probably involved in immune evasion. The strategy of replication of CoVs is similar
to that of other nidoviruses, in that all messenger RNAs form a nested set with
common polyadenylated 3’ ends, with only the unique portion of the 5′ end being
translated. As in other RNA viruses, mutations are common in nature, although the
mutation rate is much lower, approximately 2 × 106 per site per replication cycle.
Unlike other RNA viruses, CoVs encode a 3′→5′ exonuclease that has proofreading
activities, playing a critical role in maintaining replication fidelity in cell cultures
and in animals. CoVs are also capable of genetic recombination if two viruses infect
the same cell at the same time.

27
Figure 3.8 Genome organization of representative human coronaviruses

All CoVs develop exclusively in the cytoplasm of infected cells (Figure 3.9).
They bud into cytoplasmic vesicles from membranes of the pre-Golgi endoplasmic
reticulum. These virus-filled vesicles are then extruded by the exocytic secretory
pathway with the small E protein critical for this process. The resultant virus
particles have a diameter of 70 to 80 nm on thin-section electron microscopy and
60 to 220 nm on negative staining. They are pleomorphic, with widely spaced,
petal-shaped projections 20 nm long (see Figure 3.6).

Figure 3.9 Coronavirus strain 229E in Huh-7 cells. (A) Double membrane
vesicles, which are sites of virus replication, are shown. (B) Sites of virus
assembly and budding (arrow) are shown.

28
The cellular receptor for 229E and most other alphacoronaviruses is
aminopeptidase N (APN). Interestingly, NL63, the other known human
alphacoronavirus, uses as its cellular receptor angiotensin-converting enzyme 2
(ACE2), the same receptor as is used by the SARS-CoV. Mouse hepatitis virus, a
betacoronavirus related to strain OC43, uses as its receptor a member of the
carcinoembryonic antigen family. HCoV-OC43 and bovine CoV, which is closely
related to HCoV-OC43, bind to 9-O-acetylated neuraminic acid as part of the entry
process. The host cell receptor for MERS-CoV is dipeptidyl peptidase 4, which,
like ACE2 and APN, is an ectopeptidase that is abundantly expressed in the
respiratory and enteric tracts. This preferential usage of large host ectopeptidases
for CoV entry is notable but not understood.
All the CAR HCoVs grow only with difficulty in tissue culture. Despite this,
both 229E and NL63 were discovered because they produced a detectable
cytopathic effect, the first in human embryonic kidney and the second in LLC-
MK2 cells. Both the SARS-CoV and the MERS-CoV were initially isolated and
grew readily in Vero cells. HCoVs OC43 and HKU1 have been grown in tissue
culture after laboratory adaptation or in primary ciliated human airway epithelial
cells. Detection of all these viruses in clinical specimens is most conveniently and
sensitively achieved using PCR.
The SARS epidemic began in Guangdong Province in the People’s Republic
of China in mid-November 2002. It came to worldwide attention in March 2003
when cases of severe, acute pneumonia were reported to WHO from Hong Kong,
Hanoi, and Singapore. Disease spread in hospitals to health care workers, visitors,
and patients; among family members; and, on occasion, in hotels, apartment
complexes, markets, and airplanes. Worldwide spread was rapid but focal. The
largest numbers of cases were reported from the People’s Republic of China, Hong
Kong, Taiwan, Singapore, and Toronto, Canada. The overall case-fatality rates in
these locations ranged from 7% to 17%, but persons with underlying medical
conditions and those older than 65 years of age had mortality rates as high as 50%.
There was no mortality in children or in adults younger than the age of 24 years.
In response to the global spread and associated severe disease, WHO
coordinated a rapid and effective control program that included isolation of cases,

29
careful attention to contact, droplet and airborne infection control procedures,
quarantine of exposed persons in some settings, and efforts to control spread
between countries through travel advisories and travel alerts. Presumably as a result
of these efforts, global transmission ceased by July 2003. A few subsequent cases
of SARS were detected, but all were either a result of laboratory spread or
individual cases related to presumed contact with civet cats or other intermediate
hosts. The last known case occurred in mid-2004.
Spread of SARS to humans is thought to have occurred primarily through
droplet or contact transmission, with a possible role for fomites. In most instances,
an individual case transmitted to very few others, although super-spreading events
were well documented, likely involving small-particle airborne transmission.
Spread in hospital settings appeared to be surprisingly efficient, but it could be
effectively suppressed with the enforcement of droplet and contact precautions and
airborne precautions during aerosol-generating procedures. Containment measures
were efficacious, in part, because patients were most contagious only after lower
respiratory disease developed. The chain of spread was finally broken in the
People’s Republic of China, the last country to experience epidemic spread, in July
2003.
It now seems almost certain that the human epidemic began with the spread
of a closely related bat virus first to palm civets or other animals sold in live wild
game markets and then to humans in Guangdong Province in the People’s Republic
of China, and that the virus adapted itself through mutation and possibly
recombination, until it transmitted readily among humans. The virus that spread
worldwide came largely from a single infected individual who traveled from
Guangdong Province to Hong Kong and infected a large number of individuals
before him self succumbing to the disease. In contrast, the virus that was epidemic
in the People’s Republic of China was more variable.
Administration of antigenically distinct CAR CoV to volunteers produced
illness with similar characteristics. A summary of these characteristics is given in
Table 3.4, in which a comparison is made with colds produced by rhinoviruses in
similarly inoculated volunteers. The incubation period of CoV colds was longer and
their duration somewhat shorter, but the symptoms were similar. Asymptomatic

30
infection was sometimes seen and, indeed, has been a feature of both serologic
surveys and PCR-based studies of natural infection of infants, children, and adults.
Table 3.4 Clinical Features of Colds Produced by Experimental Infection With
Four Viruses

More serious respiratory tract illness is probably also caused by all four
strains of CAR HCoV. The evidence for this is not conclusive, but it seems likely
that all strains can produce pneumonia and bronchiolitis in infants, otitis and
exacerbations of asthma in children and young adults, pneumonia in healthy adults,
exacerbations of asthma and chronic bronchitis in adults, influenza-like illness,
serious bronchitis and pneumonia in the elderly, and pneumonia in the
immunocompromised host. HCoVs are found in asymptomatic individuals of all
ages, and, when accompanied by illness, are also sometimes accompanied by
infections with other potential respiratory pathogens. Infection without disease and
coinfection during disease are features of many respiratory pathogens, including
rhinoviruses, adenoviruses, human metapneumovirus, human bocavirus, and
parainfluenza viruses, but also (although less frequently) respiratory syncytial virus
and influenza virus, making pathogenicity difficult to prove. Because infections
with CAR HCoVs are so common, however, it is possible that they are responsible
for a significant portion of these serious lower respiratory tract diseases, even
though the basic pathogenicity of HCoVs (judging from volunteer studies) is similar
to that of rhinoviruses, and clearly less than that of respiratory syncytial virus,
influenza viruses, and certain adenovirus types. There is some evidence that HCoV-

31
OC43 is more pathogenic in the elderly than HCoV-229E and that NL63 differs
from the other CAR HCoVs in preferentially causing childhood croup.

3.3 COVID-19 IN PREGNANCY 9

The following advice is provided as a resource for UK Healthcare


Professionals based on a combination of available evidence, good practice and
expert advice. The priorities are (i) the reduction of transmission of COVID-19 to
pregnant women and (ii) the provision of safe care to women with
suspected/confirmed COVID-19.
Most cases of COVID-19 globally have evidence of human to human
transmission. This virus can be readily isolated from respiratory secretions, faeces
and fomites. Healthcare providers are recommended to employ strict infection
prevention and control (IPC) measures; guidance is available as per local Health
Protection guidance.
Pregnant women do not appear more likely to contract the infection than the
general population. Pregnancy itself alters the body’s immune system and response
to viral infections in general, which can occasionally be related to more severe
symptoms and this will be the same for COVID-19.
With regards to vertical transmission (transmission from mother to baby
antenatally or intrapartum), case reports from China have concluded that there is no
evidence for this. Expert opinion is that the fetus is unlikely to be exposed during
pregnancy. A case series published by Chen et al tested amniotic fluid, cord blood,
neonatal throat swabs and breastmilk samples from COVID-19 infected mothers
and all samples tested negative for the virus. Furthermore, in a different paper by
Chen et al, three placentas of infected mothers were swabbed and tested negative
for the virus, and in another case series by the same team, of three infants born to
symptomatic mothers tested for the coronavirus, none had positive tests. The
current evidence suggests that the virus is not present in genital fluid.

3.3.1. Clinical Features 9


The mean incubation period (from exposure to the appearance of
clinical features) is 5 to 7 days. Most people who are infected will show

32
features latest by 11 days of exposure. A history of travel abroad or contact
with someone who has travelled abroad should be included in the history
taking. The majority of people (pregnant and general population) present with
respiratory symptoms of COVID-19 infection. Pregnant women don't appear
to be more susceptible to consequences of infection of COVID-19 than
general population.
Most pregnant women will have mild to moderate flu-like symptoms of
cough, sore throat, and fever. Few may have difficulty in breathing or
shortness of breath. These have been classifed as features of severe acute
respiratory illness (SARI) by the WHO. Pregnant women, especially those
with associated medical diseases (diabetes, asthma, etc) may present with
pneumonia and marked hypoxia. Immunocompromised and elderly pregnant
women may present with atypical features such as fatigue, malaise, body ache
and/or gastrointestinal symptoms like nausea and diarrhea.
At the time of every patient contact, irrespective of the reason for the
clinical meeting with a pregnant woman, healthcare workers should enquire
about features of SARI, travel abroad and/or contact with a known or possible
COVID-19 infected person through household contact, visitors or attending
events where such a person was present.

3.3.2. Diagnose 9
The criteria for offering a laboratory test are the same for pregnant
women and the non-pregnant population. Currently, as per the guidance given
by the Indian Council for Medical Research (ICMR) pregnant women should
be tested in the following circumstances.
1. A pregnant woman who has acute respiratory illness with one of the
following criteria:
- a history of travel abroad in the last 14 days (6 March 2020
onwards). In addition to testing, these individuals (with or without
symptoms) and their household contacts should home quarantine
for 14 days.
- is a close contact of a laboratory proven positive patient or

33
- she is a healthcare worker herself or
- hospitalized with features of severe acute respiratory illness.
2. A pregnant woman who is presently asymptomatic should be tested
between 5 and 14 days of coming into direct and high risk contact
of an individual who has been tested positive for the infection.

Figure 3.10 Algoritm COVID-19 in pregnancy 9

As per the guidance from the Government of India, direct and high risk
contact is defined as those living in the same household, traveling together by
any conveyance, working together in close proximity (same room), or
healthcare workers providing direct care.
This testing strategy may evolve and recommendations may change.
Some countries such as South Korea and the experiences in Shanghai were
shaped by more widespread testing. In this approach, the rationale is to
identify as many infected individuals as possible and isolate or quarantine
them before they infect others. The counterpoint to this is that as community

34
spread occurs, over 50% of the population is likely to carry the virus and it
could mean a large outlay on testing which may not necessarily change the
general recommendations of social distancing and hygiene which are already
being propagated.
The CDC recommends collection of a nasopharyngeal swab specimen
to test for COVID-19. An oropharyngeal swab can be collected but is not
essential; if collected, it should be placed in the same container as the
nasopharyngeal specimen. Sputum should only be collected from patients
with productive cough; induction of sputum is not indicated. COVID-19 is
detected by reverse-transcription polymerase chain reaction (RT-PCR). The
test should be performed from a center which is authorized by the government
of India and state governments. There are 114 ICMR approved public
laboratories where the test can be done. The government has allowed testing
to be conducted at private laboratories from 22 March 2020. The detailed
guidelines on testing are available on the ICMR website. It highlights the
preference for home collection of samples, maintaining safety during
transport and disposal, guidance on disclosing results and fees. More rapid
molecular diagnostic tests which have been manufactured in India approved
by FDA and ICMR which can give results in 2-3 hours may be available soon.
At present, the RT-PCR test is recommended by the ICMR. However,
false negative tests are known to occur to the rate of 10-30% even with two
serial swabs tested by the RT-PCR technique. In the near future, testing may
be conducted by Nucleic Acid Amplification Test (NAAT) or by serological
testing. NAAT is a gold standard test. It is expensive and involves the risk of
multiplication of viral particles. Serological testing is faster and cheaper. At
a population level, serological testing may be more feasible to see the
prevalence. Also, after 3 weeks of infection, the RT-PCR would be negative,
but serology would give the diagnosis.
Other laboratory findings that have been seen with COVID-19 infection
are leucopenia, lymphocytopenia, mild thrombocytopenia, mild elevation of
liver enzymes and other acute infection markers. Co-infection with other
common respiratory pathogens and the common cold virus are often seen with

35
COVID-19. CT scan and other imaging modalities usually show patterns
consistent with atypical pneumonia. In cases where an X-Ray is taken or a
CT scan is needed for a pregnant woman, there should be provision of an
abdominal shield to protect the fetus from radiation exposure. An informed
consent for the imaging should be taken from the pregnant woman and her
relatives.
3.3.3. Treatment
Supportive therapy for COVID-19 infections should include rest,
oxygen supplementation, fluid management and nutritional care as needed.
The treatment of COVID-19 viral infection has been attempted by two
approaches. The first approach is the use of a combination of
Hydroxychloroquine and Azithromycin. These drugs are readily available
and cost-effective in India. The other approach has been to use antiviral drugs,
some of which are not yet available in India.
- Hydroxychloroquine in a dose of 600 mg (200 mg thrice a day
with meals) and Azithromycin (500 mg once a day) for 10 days
has been shown to give virological cure on day 6 of treatment in
100% of treated patients in one study. The study included 20
treated patients with upper and lower respiratory symptoms. In
this study, pregnancy was an exclusion criteria. However, as such,
both these drugs have been used in pregnancy and during
breastfeeding without significant effects on the mother or fetus.
Alternative dosage regimens for hydroxychloroquine are to give
400 mg twice a day on day 1 and then 400 mg once a day for the
next four days. Chloroquine can also be used as an alternative.
The dose is 500 mg twice a day for 7 days. Some authorities
recommend that azithromycin should be added only where there
is a clinical suspicion of superadded bacterial infection.
- Antiviral therapy : Lopinavir-ritonavir was the first antiviral
combination used in an attempt to treat COVID-19 infection. This
may be considered as a possible line of treatment for those who
have chronic disease, immunocompromise or uncontrolled

36
diabetes. However, there was no difference in time to clinical
improvement or mortality at 28 days in a randomized trial of 199
patients with severe COVID-19 given lopinavir-ritonavir
(400/100 mg) twice daily for 14 days in addition to standard care
versus those who received standard of care alone. Other agents
such as Remdesivir are being evaluated in a randomized trial.
In India, some health authorities have prescribed a regimen of
Oseltamavir 75 mg twice a day for five days in conjunction with
hydroxychloroquine. The recommendation is based on the
experience of the H1N1 (swine flu) experience. At present, data
on this regimen is limited. The regimen is simple, cost effective
and the drug is available easily.
- Vaccine; At present, a number of organizations in the public and
private sector are working towards the development of a vaccine.
Some safety trials have been initiated. However, it is estimated
that a vaccine would be available to use only after 6-12 months.
- NSAIDs: These are the drugs used most often in the care of
COVID-19 infected pregnant women for symptomatic relief of
fever and myalgia. Paracetamol is the preferred drug. If possible,
Ibuprofen and other NSAIDs may be avoided because there are
concerns about potentiating ACE receptors.
- Antenatal Steroids (fetal maturity): Steroids are recommended for
enhancing fetal lung maturity in situations where preterm delivery
is likely between 24 to 34 weeks of gestation. There is no
documented evidence of the use of steroids in COVID-19
infection. However, glucocorticoids have been associated with an
increased risk for mortality in patients with influenza and delayed
viral clearance in patients. Therefore, the use of steroids needs to
be individualized based on the woman's condition and should be
discussed with her and her family.
- Antihypertensives: There is controversy surrounding the use of
ACE (Angiotensin Converting Enzyme) inhibitors and ARBs

37
(Angiotensin Receptor Blockers) in the general population,
especially the elderly with hypertension. In pregnancy, these
drugs are not to be used due to their known deleterious effects on
the fetus. The point of using them in pregnant women, therefore,
does not arise.
- Antibiotics: If there is a suspicion of secondary bacterial
infection, appropriate antibiotics which are considered safe in
pregnancy should be added.
- Oxygen: If there is difficulty in breathing, oxygen
supplementation by nasal prongs or mask may be added. High
flow nasal oxygen at 4 to 6 liters per minute should be
immediately administered. Non invasive ventilation can also be
used. At this point, there should be a reevaluation of the patient's
status and consideration should be given to the need for
- Intensive Care Management; It is estimated that about 15% of
COVID-19 infected individuals will need care in hospital and 5%
will need intensive care. The outcome of such individuals is
largely determined by the underlying co-morbidities and the
availability of ICU facilities. In the public sector, India has a
hospital bed availability of about 5 per 1000 population and
intensive care bed availability of 1.3 per 100000 population. The
number of ventilators are about half of what is estimated to be
needed if there is a full-blown epidemic in the country. Western
countries are also facing similar shortages or space, beds,
personnel and infrastructure. This has resulted in a triage where
care is being accorded only to infected individuals with a good
prognosis of survival.
- If a woman is identified to need intensive care, it should be done
in conjunction with a team of ICU experts. Caring for critically
ill pregnant women patients with COVID -19 is based on
management of viral pneumonia with respiratory failure with

38
additional precautions to reduce risk of transmission. The
principle evidence based guidelines for ARDS include:
1. Conservative Intravenous fluid strategies
2. Empirical early antibiotic for possible bacterial pneumonia
3. Early invasive ventilation may be needed
4. Lung protective ventilation strategies
5. Periodic prone positioning during mechanical ventilation
.There is little evidence on prone positioning in pregnant
women. Pregnant women may benefit from being placed in the
lateral decubitus position.
6. Extracorporeal membrane oxygenation where needed
Labour Triage for women with COVID-19 infection. A protocol should
be in place in every maternity unit to receive pregnant women in labour or
suspected labour with confirmed or suspected COVID-19 infection. The
outline of the arrangements for healthcare facilities has been mentioned in an
earlier section. The same principles should be followed. The following
aspects should be borne in mind in planning for this triage process.
- The woman should call in advance to alert the maternity unit about
her arrival whenever this is possible. This will give some time to the
healthcare workers to prepare in triage and don the PPE.
- The woman should use private transport or an ambulance when
possible to reach the maternity unit.
- She should be met with appropriately donned PPE at reception itself.
- Reception and triage in the same room as to be used for admission
in labour and delivery. This should be a room with negative pressure.
But it is not available everywhere.
- Keep the room free from any unnecessary items (decorations, extra
chairs, etc) which could act as infected fomites later.
- There should be a restriction on the number of attendants allowed
with the woman. There should be a restriction on the entry and exit
of non-essential staff into the room. The companion of the woman
should be treated as infected and all precautions should be taken.

39
In the future, if the number of COVID-19 infected patients rises, it is
expected that there would be some who would be recognized to have the
infection for the first time when they present in labour. Anticipating this, an
elaborate advisory to this effect has been issued by the Ministry of Health and
Family Welfare on hospital and institutional preparedness and the conduct of
mock drills and standard operating procedures.
Management of Labor and Delivery in women with COVID-19
infection. In all circumstances, maternity care providers should continue to
provide client-centred, respectful skilled care and support. Birth attendants
should be limited to one named contact. There should be adequate counselling
of the mother about the infection. Separate delivery room and operation
theatres are required for management of suspected or confirmed COVID-19
mothers. Both should have neonatal resuscitation corners located at least 2 m
away from the delivery table. Resources required include space, equipment,
supplies and trained healthcare providers for delivery, caesarean section and
neonatal resuscitation. The standards and facilities required for infection
control in these areas should be same as that for other adults with suspected
or confirmed COVID-19 infection.
Following the principles in earlier sections on recognition, offering
testing, PPE use and principles of isolation of COVID-19 infected women,
this section is restricted to the management of labour and delivery and the
modifications necessary in women with COVID-19 infection. Depending on
the clinical picture and severity of the condition, a multispeciality team may
be involved in caring for the pregnant woman in labour. The anaesthetist and
neonatologist should be informed of such a woman presenting in labour.
If a woman presents in preterm labour, tocolysis is contraindicated in
following the general principles of avoiding such an intervention with
systemic disease. This decision should be individualized depending on the
degree of clinical severity of the infection. If there is pulmonary involvement,
beta-mimetic agents should be avoided.

40
Figure 3.11 Algorythm pregnant with suspected or confirmed COVID-199

Persons under investigation or confirmed cases , from the obstetric


perspective, follow the same management pathwayas outlined; There is a
significant group of patients, who though infected, remain asymptomatic.
There should be good communication between the laboratory, the screening

41
unit, the obstetric unit and the entire multidisciplinary COVID team to
prepare a fast and quicktransfer from entry point to the isolation unit. A
COVID team should be formed at each unit with a senior obstetrician,
anaesthetist, neonatologist, critical care with infectious diseases expert to plan
the best response. Examination and tests are performed for assessment of
severity and further planning of care.
Timing of delivery should not be altered on the basis of COVID-19
infection. The presence of infection is not an indication to induce labour or
deliver the woman. At present, there is no evidence of transplacental vertical
transmission. There would be no rationale in doing so. The exception to this
would be the critically ill pregnant woman where delivery may be indicated
to relieve the extra metabolic and pulmonary load. However, the possible
benefits of this need to be weighed against the possible risks of worsening the
systemic status with a surgical intervention. Such a decision has to be guided
by individual circumstances including the degree of clinical stability,
gestational age, available infrastructure and the couple's wishes.
In labour, monitoring should include the periodic evaluation of the
respiratory status with a watch for symptoms of difficulty or shortness of
breath, respiratory rate, pulse rate and oxygen saturation on pulseoximetry. If
there is a deterioration of these features, intensive care measures would be
required including ventilation.
As such, the pregnant woman with COVID-19 infection can be allowed
to labour and indications for interventions should follow standard obstetric
practice. With every examination and contact, healthcare workers should be
mindful of adequate protective gear. An intravenous access should be
established and fluids should be restricted in labour. It may be prudent to offer
continuous electronic fetal monitoring in labour for women with COVID-19
infection wherever such facilities are available. The second stage of labour
should be cut short to prevent maternal exhaustion and reducing maternal
efforts, in case where there is respiratory involvement by the infection.
At present, pregnant women have almost universally been delivered by
caesarean section when they present in labour with COVID-19 infection.

42
There is no proven scientific rationale for this. It could reflect local preference
and practices.
The maternal profiles and neonatal outcome of labour has been
described in a study of 33 pregnant women who delivered with COVID-19
infection in Wuhan. The study describes the presentation of the women in
labour. Three of the 33 neonates were found to be infected in this study. They
had mild features of the infection. Excerpted data from this study is presented
below.
Some viral infections such as cytomegalovirus and HIV are transmitted
through breast milk. However, as present knowledge stands, there is no
evidence that COVID-19 is secreted in breast milk. The CDC states that “we
do not know whether mothers with COVID-19 can transmit the virus via
breast milk”. It is reassuring that in six Chinese cases tested, breastmilk was
negative for COVID-19; however, given the small number of cases, this
evidence should be interpreted with caution. The main risk for infants of
breastfeeding is the close contact with the mother, who is also likely to share
infective airborne droplets.
As breast milk is the best source of nutrition and immunity for the
infant, UNFPA encourages it. In the light of the current evidence, we advise
that the benefits of breastfeeding outweigh any potential risks of transmission
of the virus through breast milk. The risks and benefits of breastfeeding,
including the risk of holding the baby in close proximity to the mother, should
be discussed with her. This guidance may change as time goes on and more
studies and knowledge evolves. For women wishing to breastfeed, the
following precautions should be taken to limit spread to the baby:
- Pregnant woman should wash her hands before and after touching
her baby,
- Mother should practice respiratory hygiene by wearing a mask and
not sneezing in front of a baby during breast feeding;
- All surfaces should be kept clean and disinfect she has touched
- If a mother is confirmed with COVID-19 infection or who is a
symptomatic and wishes expressing breast milk with a manual or

43
electric breast pump, the mother should wash her hands before
touching any pump and bottle and should follow recommendations
for proper pump cleaning after each use.
- Consider asking someone who is well to feed expressed milk to the
baby
Where mothers are expressing breast milk in hospital, a dedicated breast
pump should be used. For women bottle feeding with formula or expressed
milk, strict adherence to sterilisation guidelines is recommended. If she is too
unwell to breastfeed her baby due to COVID-19 or its complications, she can
be supported to safely provide breast milk to her baby in a way possible, and
acceptable to her.
3.3.4. Prevention 9
All practitioners shall also get the self-declaration forms (enclosed) for
those who, within their knowledge, are having travel history of COVID-19
affected areas. In case the person has any such history in the last 14 days and
is symptomatic as per case definition of COVID-19, the person must be
isolated in the hospital and will be tested for COVID-19 as per protocol.
In addition to the above two measures, the Indian Council of Medical
Research (ICMR) also recommends the use of hydroxychloroquine as
prophylaxis for asymptomatic healthcare workers caring for suspected or
confirmed COVID-19 infected patients. The recommended regimen is to take
the tablet of 400 mg hydroxychloroquine twice a day on day 1 and then once
weekly for 7 weeks. The medicine should be taken with meals. It is
contraindicated in case of known sensitivity to the drug or if a healthcare
worker suffers from G6PD deficiency or retinopathy. The healthcare worker
should not fall into a false sense of security when pharmacoprophylaxis is
being used and the other preventive measures should be followed. In case of
accidental occupational exposure, the following protocol should be followed
in addition to pharmacoprohylaxis.
The term Quarantine is used to separate and restrict the movement of
well persons who are known to be exposed (directly or indirectly) or
suspected to be exposed to a communicable disease to see if they become ill.

44
These people may have been exposed to a disease and remain asymptomatic.
Quarantine may be at home or in a facility designated by the state which
includes hotels, hostels, guesthouses or hospitals. This has been shown to be
an effective measure against the spread of infection. On the other hand,
Isolation refers to the separation and restriction of movements of ill persons
who have a contagious disease in order to prevent its transmission to others.
It typically occurs in a hospital setting or a special facility. At present, in
India, all symptomatic patients who have a positive test for COVID19 are
being isolated. The criteria for quarantine are the same for pregnant women
and the general population. These criteria, duration and measures may be
changed with the passage of time as per advice of the Government of India.
A contact in the context of COVID-19 is:
- A person living in the same household as a COVID-19 case
- A person having had direct physical contact with a COVID-19 case
or his/her infectious secretions without recommended personal
protective equipment (PPE) or with a possible breach of PPE
- A person who was in a closed environment or had face to face
contact with a COVID-19 case at a distance of within 1 meter
including air travel.
The home quarantined person should:
- Stay in a well-ventilated single-room preferably with an
attached/separate toilet.
- If another family member needs to stay in the same room, it's
advisable to maintain a distance of at least 1 meter between the two.
- Needs to stay away from elderly people, pregnant women, children
and persons with co-morbidities within the household.
- Restrict his/her movement within the house.
- Under no circumstances attend any social/religious gathering e.g.
wedding, condolences, etc.
General health measures to be followed in quarantine include hand
washing, avoiding sharing fomites, wearing a surgical mask and changing it
every 6 to 8 hours with correct disposal in 1% hypochlorite solution. If

45
symptoms appear during quarantine, the pregnant woman should contact a
health facility by telephone and follow the given advice.
Family members of the pregnant woman quarantined at home should
keep a distance from her at all times and avoid direct contact with her and her
fomites. Disposable gloves should be used in case soiled linen has to be
handled. Visitors should not be allowed. Clothes should be washed
separately.
The duration of home quarantine is 14 days from the time of exposure
to a confirmed case or earlier if a test is performed on a suspect case and it is
negative.
Some viral infections such as cytomegalovirus and HIV are transmitted
through breast milk. However, as present knowledge stands, there is no
evidence that COVID-19 is secreted in breast milk. The CDC states that “we
do not know whether mothers with COVID-19 can transmit the virus via
breast milk”. It is reassuring that in six Chinese cases tested, breastmilk was
negative for COVID-19; however, given the small number of cases, this
evidence should be interpreted with caution. The main risk for infants of
breastfeeding is the close contact with the mother, who is also likely to share
infective airborne droplets.
As breast milk is the best source of nutrition and immunity for the
infant, UNFPA encourages it. In the light of the current evidence, we advise
that the benefits of breastfeeding outweigh any potential risks of transmission
of the virus through breast milk. The risks and benefits of breastfeeding,
including the risk of holding the baby in close proximity to the mother, should
be discussed with her. This guidance may change as time goes on and more
studies and knowledge evolves. For women wishing to breastfeed, the
following precautions should be taken to limit spread to the baby:
- Pregnant woman should wash her hands before and after touching her
baby,
- Mother should practice respiratory hygiene by wearing a mask and not
sneezing in front of a baby during breast feeding;
- All surfaces should be kept clean and disinfect she has touched

46
- If a mother is con rmed with COVID-19 infection or who is a
symptomatic and wishes expressing breast milk with a manual or
electric breast pump, the mother should wash her hands before touching
any pump and bottle and should follow recommendations for proper
pump cleaning after each use.
- Consider asking someone who is well to feed expressed milk to the baby
Where mothers are expressing breast milk in hospital, a dedicated breast
pump should be used. For women bottle feeding with formula or expressed
milk, strict adherence to sterilisation guidelines is recommended. If she is too
unwell to breastfeed her baby due to COVID-19 or its complications, she can
be supported to safely provide breast milk to her baby in a way possible, and
acceptable to her.

3.4 COVID-19 EFFECT ON THE FETAL 10

There are currently no data suggesting an increased risk of miscarriage or


early pregnancy loss in relation to COVID-19. Case reports from early pregnancy
studies with SARS and MERS do not demonstrate a convincing relationship
between infection and increased risk of miscarriage or second trimester loss. 10
As there is no evidence of intrauterine fetal infection with COVID-19 it is
therefore currently considered unlikely that there will be congenital effects of the
virus on fetal development. There is no evidence currently that the virus is
teratogenic.10
There are case reports of preterm birth in women with COVID-19, but it is
unclear whether the preterm birth was always iatrogenic, or whether some were
spontaneous. Iatrogenic delivery was predominantly for maternal indications
related to the viral infection, although there was evidence of fetal compromise and
prelabour preterm rupture of the membranes, in at least one report. 10
With the limited number of deliveries to COVID-19 infected women, at
present, there is no evidence of any fetal effects of the infection in terms of fetal
abnormalities or other fetal parameters of growth, amniotic fluid or doppler indices.
There is no rationale for recommending amniocentesis to detect fetal infection at
this time. An ultrasound 14 days after the infection can be considered for the

47
pregnant woman who has recovered from infection. At present, there is no evidence
of higher risk of abortion with COVID-19 infection. At present, there is no evidence
of higher risk of preterm labour with COVID-19 infection. However, as with
systemic disease which can compromise maternal health, there is a possibility that
preterm labour may occur in these situations.9

48
CHAPTER IV
DISCUSSION

In this case, it was discussed about confirmed COVID-19 with IUFD. The
patient is known to have a history of contact with a family who is confirmed positive
for COVID-19, but no respiratory symptoms that lead to COVID-19 are found. The
patient then did not feel the movement of the fetus, so the patient decided to check
the pregnancy to Primary Health Care. The patient was tested for a swab PCR and
the result confirmed COVID-19.
On physical examination, there was no sign of respiratory problems from
COVID-19. Fetal heart rate examination was not found. On examination, the
absence of fetal activity and fetal heart rate (-). In this case the patient was
diagnosed as confirmed COVID-19 with IUFD in pregnancy. Determination of the
patient's diagnosis based on swab PCR and findings is a definite diagnosis, so that
the diagnosed in the patient is correct. On post mortem examination, the fetus shows
extensive peeling of the skin, and red. so that the fetus occurs grade II maceration
in IUFD. This condition is in accordance from the literature where second degree
maceration occurs about 3-7 days after the death of the fetus where the mother has
not felt the movement of the baby since 3 days ago.

Figure 4.1 Fetus IUFD in these case

49
Management of COVID-19 accompanied by IUFD in these case, patients is
given management from pulmonolgyst (COVID-19 team); azithromicin 1x500 mg,
vitamin C 2x250 mg, Zinc 2x20 mg. Based from literature, given azithromicin
antibiotics is considered appropriate because it provides a preventive effect in
worsening symptoms of COVID-19. 9
In this case of IUFD, the patient was observed. During follow-up, the patient
developed signs of spontaneous labor. This is in accordance with the literature in
which patients with IUFD will go into spontaneous labor in <2 weeks. So that the
decision to terminate through spontaneous labor is considered correct. 9
In this case, we want to prove whether the occurrence of IUFD is due to
COVID-19. In this case it has not been proven whether COVID-19 is the cause of
IUFD. Based on that literature “Almost all reports came from outcome of the 3rd
trimester pregnancy. Few abortions were noted in the1st and in the end of 2nd
trimester but whether there was any effect of SARS-CoV-2 it was not certainly
identified. Among 3rd trimester babies both mature and premature babies were born.
No adverse effect of SARS-CoV-2 was observed on babies. Many studies reported
on the basis of negative RT-PCR of maternal amniotic fluid, placental membrane,
umbilical cord, breast milk, vaginal fluid and fetal nasopharyngeal swab that there
is either no or very little possibilities of vertical transmission of virus from mother
to fetus”.9,11
In this case the gestation was 32-33 weeks. The chances of fetal death in this
case are not maternal, placental, fetal, or iatrogenic causes. Fetal death due to
COVID-19 suffered by mothers has not been proven. There is no strong evidence
to support the relation of IUFD in mothers with COVID-19. When a baby is
contracted infection during delivery there will be no serious effect of growth and
development of the baby but baby will be considered as a patient of COVID-19.
There was found in this study that Almost all samples of amniotic fluid, cord blood,
neonatal throat swab were collected immediately after delivery in the operating
room. It indicates that vertical transmission from mother to baby does not occur.
So, presence of IgM immediate after birth indicates intrauterine infection as it takes
3-7 days to appear IgM after any infection. Although neonatal nasopharyngeal swab
testing immediately after delivery was negative, it cannot exclude intrapartum

50
transmission as the virus may require a longer incubation period before these swabs
convert to positive. So it can be concluded that the incidence of IUFD in fetuses
with mothers confirmed with COVID-19 has not been proven. the possible
incidence of IUFD in this case was from idiopathic cause.11
Other study confirm that correlation cannot be neither confirmed nor rejected
between COVID-19 and stillbirth. 12
The most common complication that occurs in mothers with IUFD is
coagulation disorders. The complication in this case where the mother with
confirmed COVID-19 was hypercoagulopathy. Worsening the hypercoagulopathy
that occurred in this case, so that complications of this coagulation disorder being
DIC. However, in this case it is necessary to further examination and observation
in order to diagnose DIC. 11,12

51
CHAPTER V
CONCLUSION

1. Management of this case considered appropriate where the patient was vaginal
delivery with confirm COVID-19 and IUFD/Stillbirth Condition.
2. Further monitoring is needed that was diagnosed COVID-19 and more studies
to see correlation between the incidence IUFD due to confirmed COVID-19
case.

52
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1. Jamal Shehla, Agarwal Shelly. IUFD incidence, case, and complication :


retrodpective study done at a tertiary care centre in greater Noida, India.
International Journal of Reproduction, Contraception, Obstetrics and
Gynecology. 2320 (6). p:5483-87.
2. Sinaga Alma, Purwarini Justina, Anggraeni Dewi. The Experiences of
Mothers with Intrauterine Fetal Death/Demise (IUFD) in Indonesia. Nurse
MediaJournal of Nursing. 10(1). 2020. p:86-95.
3. Committee for COVID-19 and National Economic Recovery. Indonesia.
2020.
Accessed December 5th 2020 : https://covid19.go.id
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ncov/cases-updates/special-populations/pregnancy-data-on-covid-19.html
5. Goel Poonam, Salhan Sudha, Navneet. Textbook of Obstetrics Second
Edition. Chapter 21 Intrauterine fetal death. 2016. p:199-204.
6. DC Dutta’s. Textbook of Obstetrics Eight Edition. Chapter 22 Preterm
Labor, PROM, Posmaturity, IUFD. 2015. p:375-80.
7. Cunningham, Leveno, Bloom, Dashe, Hoffman et al. William Obstetrics
Twenty Fifth Edition. Chapter 35 Stillbirth. 2018.
8. Stanley Perlman, McIntosh Kenneth. Coronaviruses, Including Severe
Acute Respiratory Syndrome (SARS) and Middle East Respiratory
Syndrome (MERS). 2020. p:2073-80.
9. Federation of Obstetric and Gynecology Society of India. Good Clinical
Practice Recommendation on Pregnancy with COVID-19 Infection. 2020.
p:1-10.
10. Royal College of Obstetricians and Gynecologists. Coronavirus (COVID-
19) Infection in Pregnancy. 2020. p;1-35.
11. Begum, Nehsan, Mehsan, Absharif. Journal of Bangladesh College of
Physicians and Surgeon. Pregnancy and Childbirth in COVID-19 Positive
or Probable and Suspected Patients; A Comprehensive Review. 2020 (38).
p:91-108.
12. Jessie Darido, Chloe Dussour, Jade Lehrer, Julie Grevoul, Larissa et al.
Science Journal of Clinical Medicine. The Correlation Between COVID-19
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CHSF. 2020 9(4). p;94-97.

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