Since
then, there has been a concern about the effect of SARS-CoV-2 infection on
pregnant ladies and neonates delivered by mothers who are positive at the time
of delivery. Perinatal SARS-CoV-2 transmission roots include transplacental,
through contact with infected secretions during delivery and respiratory
droplets after delivery, and breast milk [4]. Low rates of virus positivity in
relevant biological specimens (placenta, amniotic fluid, vaginal secretion, and
breast milk) suggest that perinatal transmission is uncommon [4-6].
COVID-19
research efforts have built on earlier research on severe acute respiratory
syndrome (SARS) and the Middle East respiratory syndrome (MERS), that both are
caused by coronaviruses. At the beginning of the disease, many experts tried to
compare it with similar coronaviruses such as SARS and MERS, as no known cases
of vertical transmission had been noted, although the number of cases reported
was small [7]. However, with the presence of angiotensin-converting enzyme 2
receptor in the placenta, which is considered the receptor for SARS-CoV-2, and
the presence of immunoglobulin M (IgM) antibodies for SARS-CoV-2 in the blood
of neonates which cannot cross the placenta, raise the possibility of vertical
transmission of COVID-19 [8].
Current knowledge about the effect of SARS-CoV-2infection in
pregnant women and neonates has been collected largely from case reports, case
series, and population surveillance systems in high-income countries and a few
studies from developing counties where the income and social situation have a
major impact on maternal and neonatal health outcome.
To the best of our knowledge, few large cohort studies have
addressed the vertical transmission of SARS-CoV-2 in pregnant women and
investigated the risk factors for transmission to neonates delivered by those
women. Given the low incidence of vertical transmission of SARS-COV-2,
identifying associated risk factors can be challenging, especially with the
small number of neonates involve in the studies. Our study was designed to
address this issue in a hospital considered to be one of the leading national
pandemic centers in a developing country.
METHOD
This is a prospective study conducted during the period from March
2020 to January 2022 in one of the major hospitals in Jordan–Queen Alia
Military Hospital, which selected to be a referral hospital for SARS-CoV-2 patients since the start of the pandemic, with a capacity of more than
400 beds. High-risk SARS-CoV-2- positive pregnant women were referred to
our hospital from all over the country, especially those needing intensive care
for respiratory support in the form of CPAP or ventilator support.
All neonates born to SARS-CoV-2-positive
mothers were included in the study. The inclusion criteria were 1- gestational age of 24-42 weeks, 2- Mother developed
Covid positive within 30 days before delivery. and
the exclusion criteria were 1- unknown maternal status for Covid 19 infection
2- death or early discharge before obtaining the PCR test. Nasopharyngeal swabs for SARS-CoV-2 by reverse
transcriptase-polymerase chain reaction RT-PCR testing were obtained from neonates
at the age of 48 hours, and if
specimens were positive, tests were repeated after 7 days. Neonates who did not
need to be admitted to the neonatal intensive care unit (NICU) were admitted to
the nursery unit and were separated from their mothers until discharge from the
hospital; visitors were forbidden from entering the unit and breastfeeding was
encouraged after discharge from the hospital with
proper precautions, including hand hygiene and a mask. Mothers were given a contact number to
call if symptoms developed.
Immediately after delivery, neonatal
isolation was performed without delayed cord clamping or skin-to-skin contact,
according to hospital policy. All neonates were given a bath after delivery to
reduce the contamination with amniotic fluid. Parents alone were able to visit
the neonatal intensive care unit if they were polymerase chain reaction (PCR)
negative for COVID-19, according to NICU protocol.
The following data were gathered for each
neonate: gestational age, birth weight, gender, age of the mother, mode of
delivery and the indication, need for
admission, clinical conditions of the mother, the intensity of pneumonia and
level of lung involvement, complete blood count (CBC) for the mothers, vaccination status of the
mother, presence of prolonged rupture of the membrane for more than 18 hours
and the result of the reverse transcriptase-polymerase chain reaction (RT-PCR) nasopharyngeal swabs of each neonate,
according to the protocol.
Electronic medical records were used to collect the maternal data.
The primary study outcome was the newborn SARS-CoV-2 test results. Vertical
transmission was defined as positive SARS-CoV-2 test results on the initial
newborn swab, and postnatal transmission was defined as subsequent positive
SARS-CoV-2 test results after the first week of life, either during
hospitalization or after discharge, which was not the scope of this study.
Infection control protocol policy in our
hospital for the healthcare worker was strict temperature measurement and
symptom-reporting, followed by a reverse transcriptase-polymerase chain reaction (RT-PCR)test. Randomized nasopharyngeal swabs for health
care workers were obtained weekly. If a neonate tested positive for COVID-19,
we reviewed whether any healthcare worker in the unit was symptomatic or tested
positive during the previous 14 days.
We used Excel 2010 to analyze the data and the Fisher exact test to compare dichotomous variables. A two-tailed t-test was used to
compare the mean and standard deviation. Two-sided
P <0 .05 indicated significance.
The study was approved by the Human Research Ethics Committee of
the Royal Medical Services, Amman, Jordan. Waiver of Informed Consent was
obtained, and confidentiality was ensured at all levels.
RESULT
357 neonates were delivered to 344 women
diagnosed with COVID-19 infection within 14 days before the delivery. None of
the pregnant ladies were vaccinated for COVID-19. 110 neonates(30.8%)were
admitted to the neonatal intensive care unit (NICU). The vertical transmission
rate was 2.8%,with 10 neonates tested positive for COVID-19 by nasopharyngeal
swap by RT-PCR. None of the healthcare workers in the
neonatal unit were symptomatic or tested positive by PCR for COVID-19within 14
days before the neonates tested positive.
Table I shows the possible risk factors that we
investigate, could be associated with an increased risk of vertical
transmission of SARS-COV-2 before the delivery.
There was a significantly high percentage of cesarean delivery61% (210/344) among
the total number of women infected with SARS-COV-2 at the time of delivery. Eight out the ten of
the neonates (80%) who developed COVID-19 were delivered by cesarean section,
but was not statistically significant with respect to possibility of increase risk
of vertical transmission. Maternal age ranged from 19 to 43 years. The total
number of premature babies born to COVID-19-infected women was high 101/357
(28.1%). We found that the prematurity, severity of infection in the mothers,
duration of symptoms before delivery and lymphopenia during the infection of
the mothers were significant risk factors for vertical the transmission of
COVID 19. Chart 3: duration of symptoms of COVID 19 in the mothers before delivery
and its relation to COVID 19 in neonates.
DISCUSSION
The first reported case of COVID-19 in Jordan was in March 2020. Four
waves of the disease had followed. By the time of writing of this study, the
total number of cases in Jordan had reached 1,141,048 according to the
Jordanian Ministry of Health [9]. The vaccination program for the SARS-COV-2
vaccine started in January 2021 with priority for the elderly and those with
co-morbidities. This explained why none of the pregnant ladies in our study
were vaccinated against COVID-19. Further, the uncertainty about the safety of
the vaccine for pregnant women at the beginning of the vaccination program had
a major impact on the avoidance of vaccination by pregnant ladies.
Vertical transmission is defined as the transmission of the
infectious pathogen from the mother to the fetus during the antepartum and
intrapartum periods, or to the neonate during the postpartum period via the
placenta in utero, body fluid contact during childbirth, or through
direct contact owing to breastfeeding after birth [10]. Severe acute
respiratory syndrome coronavirus 2 viral RNA testing in
neonatal cord blood was positive in 2.9% of the samples (1/34), 7.7%
of the placenta samples (2/26), 0% of the amniotic
fluid (0/51), 0% of the urine samples (0/17), and 9.7% of the
fecal or rectal swabs (3/31) [10].
In our study, we investigate SARS-COV-2 transmission from the mother to neonate antepartum and intrapartum, but
not postpartum, as we separate the neonate from the mother after delivery, and
visitors were forbidden from entering the Unit except the parents if they have
PCR negative certification for SARS-COV-2. The neonates were given formula milk
during hospitalization, but the mothers were encouraged to breastfeed after
discharge, as most of the studies demonstrate the absence of SARS-CoV-2 in breast milk [11-13]. A strict infection
control policy was applied in the unit. We included in the study only neonates
positive for SARS-COV-2 infection during hospitalization and not
those who return to the hospital after discharge.
The vertical transmission of SARS-COV-2 infection was 2.8%, which is in line with most of the published studies
[14].In a large meta-analysis study, 936
tested neonates were included. It indicated a pooled proportion of 3.2% (95%
confidence interval) for vertical transmission [10]. Another meta-analysis study which included
405 neonates delivered to SARS-COV-2-positive women showed that the pooled
incidence of vertical transmission was 1.6% [15]. This can be explained by the finding that placental cells
co-expressing ACE2 and TMPRSS2 proteins, required for SARS-CoV-2 viral cell
entry, are rare [16].Data from the National Registry for Surveillance and
Epidemiology of Perinatal COVID-19 infection(NPC-19) showed that the rate was
1.9%, as they included 2287 neonates delivered to COVID-19-positive mothers, of
whom 44 neonates were positive for COVID-19 [17].
E. Mullins et al. [18] report the outcome of infected pregnancies
(4005 women) from a collaboration formed early during the pandemic between the
investigators of two registries: the UK and Global Pregnancy and Neonatal
Outcomes in COVID-19 (PAN-COVID) study and the American Academy of Pediatrics
(AAP) Section on Neonatal-Perinatal Medicine(SONPM) National Perinatal COVID-19
Registry. They found that cesarean delivery
occurred in 47.9%, and 38.3% of the cases, respectively. The high rate of cesarean section in our
study during the first wave of COVID-19 (from October to late December 2020)
was due to the policy of hospitals to perform PCR for COVID-19 for all patients
before entering the theater, so the patients found positive for COVID-19 were
transferred to our hospital for cesarean delivery. During the third and fourth
wave of COVID 19 infection, a high percentage of cesarean sections were mainly
indicated due to moderate to severe respiratory infection, based on the need
for oxygen and respiratory support and chest-computed tomography (CT) scan in
pregnant women, as the policy was to terminate the pregnancy to improve the
respiratory status of the mother. Despite an
increase in the rate of cesarean sections, the mode of delivery of pregnant
women infected with SARS-CoV-2 could not increase or decrease the risk of
infection for newborns [14].
The gender of the neonates and the presence of prolonged rupture of
the membrane did not affect the rate of vertical transmission. Preterm deliveries (<37 weeks of
gestational age) were 28.5% of the total deliveries in our study, which is
considered high, compared to other studies [18-22], who showed an increased
rate of premature deliveries; however, in our study, it is higher than
reported, as most of the mothers who were symptomatic and needed respiratory
support were transferred to our hospital for the benefit of the mother. In the
third and fourth COVID-19 waves, the most common cause of premature deliveries
was poor maternal respiratory status. We found that
prematurity is a risk factor for increase vertical transmission in our study
this is due to abundance
of angiotensin-converting protein 2 (ACE-2) receptors in the placenta in early
gestation which is associated with increase in rate of transmission in earlier
gestation and they diminish across gestational age [23].
There was no difference in the mean
maternal age of neonates positive for COVID-19 and those who were negative, but
we found positive relationship between the duration of infection in the mother
and the vertical transmission, where a duration of > 10 days was associated
with an increasing rate of vertical transmission.
The severity of the maternal disease and its relationship to the
vertical transmission of SARS-CoV-2 is a debatable issue. Some studies found no
correlation [24-25], but in our study the severity of the disease and the
duration of symptoms before the delivery were the most significant risk factors
for vertical transmission. This could be explained by the fact that mothers
presenting with severe COVID-19 symptoms may have higher SARS-CoV-2 viral loads
[26], which could make them more prone to transmit the infection to their
neonates.
The vertical transmission of COVID-19 in the third trimester of
pregnancy seems possible but occurs at a very low frequency (2.8%). The risk increased with prematurity,
severity of infection in the mothers, long duration of symptoms before delivery
and lymphopenia during the infection of the. further studies are needed
to establish the effect on neonates.
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