114 CMAAO CORONA FACTS and MYTH BUSTER:
VERTICAL Transmission
Dr K K Aggarwal
President CMAAO
With inputs from Dr Monica Vasudev
938: Vertical Transmission of Novel Coronavirus
Clinicians in Italy report two cases of
possible vertical transmission of SARS-CoV-2, the virus responsible for
COVID-19, from the mother to the baby in utero.
This is the first report of cases of
positive polymerase chain reaction (PCR) for SARS-CoV-2 in mother, neonate and
placental tissues," Dr. Luisa Patane and colleagues of ASST Papa Giovanni
XXIII in Bergamo write in the American Journal of Obstetrics and Gynecology -
Maternal Fetal Medicine.
Between March 5 and April 21, two of 22
babies born to women with COVID-19 were PCR positive for SARS-CoV-2 in
nasopharyngeal (NP) swab samples.
The first baby, a boy, was born vaginally
after spontaneous labor at around 37 weeks' gestation to a mother who was
experiencing fever and cough and had a positive SARS-CoV-2 NP swab. The mother
wore a surgical mask during labor and delivery, skin to skin contact was not
allowed, but rooming-in and breastfeeding with mask were allowed.
The baby had positive NP swabs immediately
at birth, after 24 hours, and after seven days. He remained asymptomatic,
except for mild initial feeding difficulties, and was discharged from the
hospital at 10 days of life.
The second baby, a girl, was delivered by
cesarean section at 35 weeks' gestation to a mother who had also had fever and
cough and positive COVID-19 NP swab. The baby was immediately separated from
the mother at birth and admitted to the neonatal intensive-care unit.
The baby had a negative NP swab at birth
and a positive NP swab at day seven, with no contact between mother and neonate
during that period. No neonatal complications were observed, only some feeding
difficulties were reported in the first days of life; she was discharged at 20
days life 20.
In both cases, SARS-CoV-2 RNA was found in
placental tissue.
The presence of SARS-CoV-2 RNA in the
syncytiothrophoblast - the epithelial covering of the embryonic placental
villi, which invades the wall of the uterus to establish nutrient circulation
between the embryo and the mother - signifies presence of the virus on the
fetal side, the clinicians point out.
Risk for congenital infection
Possible vertical transmission has been
reported in several cases of peripartum maternal infection in the third
trimester, suggesting congenital infection is possible but uncommon [1].
There are no accepted criteria for
definitive evidence of congenital infection. Most take criteria proposed by
Shah et al 2]. This system takes into account maternal symptoms and
epidemiologic exposure, results of maternal testing, clinical status of the
neonate at birth, and results of neonatal testing:
Symptomatic mothers are classified as
confirmed SARS-CoV-2 infection (positive test), possible infection (no test),
unlikely to be infected (negative test but no other cause for symptoms
identified), or not infected (negative test and another cause for symptoms
identified). Asymptomatic mothers with a positive contact history are
classified as confirmed infection (positive test), unlikely to be infected (a
single negative test), or not infected (two negative tests at different time
points).
Congenital infection with intrauterine
fetal death/stillbirth is confirmed if virus is detected by polymerase chain
reaction (PCR) from fetal or placental tissue or electron microscopic detection
of viral particles in tissue or viral growth in culture of fetal or placental
tissue. Detection of virus by PCR from a fetal surface or fetal side of the
placenta would be classified as possible infection. Infection would be unlikely
if virus is only detected by PCR in surface swab from maternal side of placenta
only and no testing done or no detection of the virus by PCR from fetal or
placental tissue. Absence of infection would be based on no detection of the
virus by PCR or by electron microscopy in fetal tissue(s) on autopsy.
Congenital infection in a live born infant
depends on presence or absence of clinical features of infection in a newborn
and mother with SARS-CoV-2 infection. In symptomatic cases, congenital infection
is confirmed if virus is detected by PCR in umbilical cord blood or neonatal
blood collected within first 12 hours of birth or amniotic fluid collected
prior to rupture of membranes. In asymptomatic cases, neonatal infection is
confirmed if virus is detected by PCR in cord blood or neonatal blood collected
within 12 hours of birth. Criteria for probable, possible, unlikely, or
noninfected also exist.
Neonatal infection may be acquired
intrapartum. For symptomatic newborns of infected mothers, intrapartum
infection is confirmed if SARS-CoV-2 PCR of a nasopharyngeal swab at birth
(after cleaning the infant) and at 24 to 48 hours of age are both positive and
an alternative explanation for symptoms is excluded. Criteria for probable,
possible, unlikely, or noninfected also exist.
For asymptomatic newborns of infected
mothers, intrapartum infection is confirmed if SARS-CoV-2 PCR of a
nasopharyngeal swab at birth (after cleaning the infant) and at 24 to 48 hours
of age are both positive. Criteria for possible or noninfected also exist
Neonatal infection may be acquired
postpartum. This is defined by clinical features of COVID-19 at ≥48 hours of
age (regardless of parent/caregiver SARS-CoV-2) and confirmed if SARS-CoV-2 PCR
of a respiratory sample at birth is negative but SARS-CoV-2 PCR of a
nasopharyngeal/rectal swab is positive at 24 to 48 hours of age. Criteria for
probable or noninfected also exist.
In most women who test positive for
SARS-CoV-2 in the nasopharynx, vaginal and amniotic fluid specimens have been
negative to date [3,4], but one patient with a positive vaginal swab has been
reported [5].
Viremia rates in patients with COVID-19
appear to be low (1 percent in one study [6]) and transient, suggesting
placental seeding and vertical transmission would be not common.
Most placentas studied so far had no
evidence of infection, but the virus has been identified in a few cases [7-9].
In a patient with confirmed COVID-19 who
had second-trimester miscarriage, samples taken from a placental cotyledon and
submembrane were positive for SARS-CoV-2; all fetal, amniotic fluid, cord
blood, and maternal blood and vaginal samples were negative [7].
Another report described one positive
placental swab from the amniotic surface and two positive membrane swabs from
between the amnion and chorion after manual separation of the membranes in
women with severe or critical COVID-19 illness delivered by cesarean; none of
the infants were positive for SARS-CoV-2 [8].
A third report described two
SARS-CoV-2-positive mothers in whom the fetal side (syncytiotrophoblast) of
their placentas and their neonates were also positive [9].
The extent and clinical significance of
vertical transmission remain unclear.
The following findings support a diagnosis
of congenital: the neonate was not in contact with vaginal secretions
(documented as positive for SARS-CoV-2); membranes were intact before birth;
there was no skin-to-skin contact with the mother before collection of the
first neonatal nasopharyngeal swab.
1. Egloff
C, Vauloup-Fellous C, Picone O, et al. Evidence and possible mechanisms of rare
maternal-fetal transmission of SARS-CoV-2. J Clin Virol 2020; 128:104447.
2. Shah
PS, Diambomba Y, Acharya G, et al. Classification system and case definition
for SARS-CoV-2 infection in pregnant women, fetuses, and neonates. Acta Obstet
Gynecol Scand 2020; 99:565.
3. Qiu
L, Liu X, Xiao M, et al. SARS-CoV-2 is not detectable in the vaginal fluid of
women with severe COVID-19 infection. Clin Infect Dis 2020.
4. Chen
H, Guo J, Wang C, et al. Clinical characteristics and intrauterine vertical
transmission potential of COVID-19 infection in nine pregnant women: a
retrospective review of medical records. Lancet 2020; 395:809.
5. Kirtsman
M, Diambomba Y, Poutanen SM, et al. Probable congenital SARS-CoV-2 infection in
a neonate born to a woman with active SARS-CoV-2 infection. CMAJ 2020.
6. Wang
W, Xu Y, Gao R, et al. Detection of SARS-CoV-2 in Different Types of Clinical
Specimens. JAMA 2020.
7. Baud
D, Greub G, Favre G, et al. Second-Trimester Miscarriage in a Pregnant Woman
With SARS-CoV-2 Infection. JAMA 2020.
8. Penfield
CA, Brubaker SG, Limaye MA, et al. Detection of SARS-COV-2 in Placental and
Fetal Membrane Samples. Am J Obstet Gynecol MFM 2020; :100133.
9. Patanè
L, Morotti D, Giunta MR, et al. Vertical transmission of COVID-19: SARS-CoV-2
RNA on the fetal side of the placenta in pregnancies with COVID-19 positive
mothers and neonates at birth. Am J Obstet Gynecol MFM 2020; :100145.
10. Dong
L, Tian J, He S, et al. Possible Vertical Transmission of SARS-CoV-2 From an
Infected Mother to Her Newborn. JAMA 2020.
11. Zeng
L, Xia S, Yuan W, et al. Neonatal Early-Onset Infection With SARS-CoV-2 in 33
Neonates Born to Mothers With COVID-19 in Wuhan, China. JAMA Pediatr 2020.
12. Zeng
H, Xu C, Fan J, et al. Antibodies in Infants Born to Mothers With COVID-19
Pneumonia. JAMA 2020.
13. Alzamora
MC, Paredes T, Caceres D, et al. Severe COVID-19 during Pregnancy and Possible
Vertical Transmission. Am J Perinatol 2020.
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