Thursday, June 4, 2020



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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